Table of contents :

Epidemiology : in 2002 62 million Americans (32 million females and 30 million males > 20%) - had a cardiovascular disease (including hypertension). The prevalence rises progressively with age from 5% at age 20 to 75% at age > 75 years. 8% or 22 million adults in the US have heart disease. In the US, the prevalence rate for those who have angina pectoris is 17.5 per 1000 people
Cardiovascular diseases (CVD) represent the first leading cause of death in Westernized countries, accounting for 45-50% of all deaths: 35% are coronary artery diseases (CAD). Contradicting conventional wisdom, the largest-ever worldwide collaborative study of heart disease has found that women are slightly more likely to die from CVD than men and that heart attacks and stroke kill twice as many women as all cancers combined. Out of the total 16.5 million CVD deaths annually, 8.6 million are of women. Although > 80% of the global burden of cardiovascular disease occurs in low-income and middle-income countries, knowledge of the importance of risk factors is largely derived from developed countries. Therefore, the effect of such factors on risk of coronary heart disease in most regions of the world is unknown.
Risk factors significantly related to acute myocardial infarction (p<0.0001 for all risk factors and p=0.03 for alcohol) include :

• smoking (odds ratio 2.87 for current vs never, PAR 35.7% for current and former vs never)
• raised ApoB/ApoA1 ratio (3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile)
• history of hypertension (1.91, PAR 17.9%)
• diabetes mellitus (2.37, PAR 9.9%)
• abdominal obesity (1.12 for top vs lowest tertile and 1.62 for middle vs lowest tertile, PAR 20.1% for top 2 tertiles vs lowest tertile)
• psychosocial factors (2.67, PAR 32.5%)
• daily consumption of fruits and vegetables (0.70, PAR 13.7% for lack of daily consumption)
• regular alcohol consumption (0.91, PAR 6.7%)
• regular physical activity (0.86, PAR 12.2%)

• family history of cardiovascular accident in ancestor females before age 40 and males before age 50

Heart diseases

• Web resources :
• Heart disease at CDC
• Journals
• Texas Heart Institute Journal [free at PubMed Central (PMC); archive starts with Vol. 27(1); 2000]

• congenital heart diseases / cardiopathies

Epidemiology : prevalence = 0.8% of all (alive) newborns (1 per 200).
Aetiology :
• unknown (85%)
• intrinsic aetiology
• chromosome alterations (6%)
• single gene mutations (4%)
• Holt-Oram syndrome (HOS) / heart-hand syndrome : autosomal heart disease of varying severity, usually an atrial or ventricular septal defect, associated with skeletal malformation (hypoplastic thumb and short forearm)
• Noonan syndrome
• Kartagener syndrome
• malformations of the septum, outflow tract and aortic arch are the most common congenital cardiovascular defects and occur in mice lacking Cited2, a transcriptional coactivator of TFAP2. Cited2^-/- mice also develop laterality defects, including right isomerism, abnormal cardiac looping and hyposplenia, which are suppressed on a mixed genetic background. Cited2^-/- mice lack expression of the Nodal target genes Pitx2c, Nodal and Ebafin the left lateral plate mesoderm, where they are required for establishing laterality and cardiovascular development. CITED2 and TFAP2 were detected at the Pitx2c promoter in embryonic hearts, and they activate Pitx2c transcription in transient transfection assays. An abnormal Nodal-Pitx2c pathway represents a unifying mechanism for the cardiovascular malformations observed in Cited2^-/- mice, and that such malformations may be the sole manifestation of a laterality defect^ref.
• extrinsic aetiology (< 5%)
• rubella virus (vaccine for women not infected yet)
• thalidomide(once used to treat gravidic emesis)
• ethanol
• Li
• diabetes mellitus
Perloff's classification according to the following criteria :
• presence or absence of cyanosis
• normal, increased or decreased pulmonary blood flow
• normal, increased or decreased pulmonary blood pressure
• right or left anomaly
• right or left dominant ventricle
• general cardiopathies
• innocent murmurs
• double-inlet ventricle : a congenital anomaly in which both atrioventricular valves or a single common atrioventricular valve open into a single ventricle, which usually resembles the left ventricle morphologically (double inlet left v.) but may resemble the right (double inlet right v.) or neither or both ventricles.
• double-outlet left ventricle : a rare anomaly in which both great arteries arise from the left ventricle; it is often associated with a hypoplastic right ventricle, ventricular septal defect, valvular or subvalvular pulmonic stenosis, and a variety of associated malformations.
• double-outlet right ventricle : incomplete transposition of the great vessels in which both the aorta and the pulmonary artery arise from the right ventricle, associated with a ventricular septal defect. The defect may be remote from or close to either or both semilunar valves; it may be related to the aorta (subaortic), to the pulmonary trunk (subpulmonic), to both vessels (doubly committed), or to neither (uncommitted); and it may be associated with pulmonary stenosis.
• congenital complete heart block (CHB)
• corrected transposition of great vessels / congenitally or physiologically corrected transposition of the great arteries / mixed levocardia (0.5% of congenital cardiopathies) : a developmental cardiac anomaly characterized by transposition of the great vessels with inversion of the ventricles and atrioventricular valves; termed “corrected” because the inverted ventricles compensate for the transposition, producing a mirror-image blood flow in the heart, ensuring that blood flow continues in its usual physiologic pathway. However, because in > 99% of cases this condition usually is associated with other abnormalities, many have commented that it should not be called "corrected" .The most common anatomic associations include a ventricular septal defect (VSD) (80%) and the presence of pulmonary valve stenosis (50%), and tricuspid valve anomalies (including dysplasia, straddling, or Ebstein-like malformation (with or without regurgitation), 14-56%). The presence of a VSD causes a systemic-to-pulmonary shunt; however, this usually is balanced because of the "protective" effect of coexisting pulmonic stenosis.
• Taussig-Bing syndrome : a rare congenital malformation of the heart characterized by transposition of the great vessels and a ventricular septal defect straddled by a large pulmonary artery; hemodynamically it is characterized by pulmonary hypertension, pulmonary plethora, cyanosis, and greater O₂ saturation of blood in the pulmonary artery than in the aorta.
• microcardia : smallness of the heart
• cardiac or heart malposition / ectocardia : congenital displacement of the heart, either inside or outside the thorax.
• dextrocardia : location of the heart in the right hemithorax, with the apex pointing to the right, occurring with transposition (situs inversus) of the abdominal viscera, or without such transposition (other organs are normally placed).
• isolated dextrocardia : mirror-image transposition of the heart without accompanying alteration of the abdominal viscera.
• mirror-image dextrocardia : location of the heart in the right side of the chest, the atria being transposed and the right ventricle lying anteriorly and to the left of the left ventricle, usually associated with complete situs inversus.
• secondary dextrocardia : displacement of the heart to the right as a result of disease of the pleura, diaphragm, or lungs
• levocardia : a term denoting the normal position of the heart, used when other viscera are transposed
• isolated levocardia : levocardia associated with transposition (situs inversus) of the abdominal viscera, congenital structural anomaly of the heart, and sometimes with absence of the spleen.
• mixed levocardia / corrected transposition of the great vessels
• situs inversus viscerum / situs transversus : lateral transposition of the viscera of the thorax and abdomen; a familial pattern and consanguineous parents have been reported. Complete transposition of the viscera in the absence of other defects is structurally sound

Aetiology : Klinefelter's syndrome
• dextroversion : location of the heart in the right hemithorax, the left ventricle remaining on the left as in the normal position, but lying anterior to the right ventricle.
• ectopia cordis : congenital displacement of the heart outside the thoracic cavity because of maldevelopment of the pericardium and sternum
• pectoral ectopia cordis : location of the heart outside the thoracic wall, through a cleft in the lower sternum
• ectopia cordis abdominalis : a rare anomaly in which the heart is located in the abdominal cavity.
• acyanotic cardiopathies without a shunt
• right cardiopathies
• pulmonic valve stenosis
• congenital pulmonic valve failure
• idiopathic dilatation of the pulmonary trunk
• PPH
• acyanotic Ebstein anomaly of the tricuspid valve
• right ventricle hypoplasia
• arrhythmogenic right ventricular dysplasia (ARVD) or cardiomyopathy (ARVC) : a congenital right-sided cardiomyopathy

Epidemiology : predominantly in young males
Aetiology :
• hereditary (30%; autosomal dominant) : heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome^ref
• sporadic (70%)
Pathogenesis : replacement of cardiomyocytes by fibrous or adipose tissue (transmural in right ventricle and subepicardiac in left ventricle) resulting in weakness, dilatation of the right ventricle, and pseudoaneurysmal bulging of the infundibulum, apex, and posterior basilar region of the right ventricle during systole. Cardiomyocytes entrapped within fatty tissue are electrically unstable and can occasionally lead to palpitations, syncope, and sometimes ventricular tachycardia arising in the right ventricle =>
• sudden arrhythmic cardiac death
• dangerous tachyarrhythmias
• contractile failure
Symptoms & signs : ARVD patients present between the second and fifth decades of life either with symptoms of palpitations and syncope associated with ventricular tachycardia or with SCD. There is a wide variation in presentation and course of ARVD patients, which can likely be explained by the genetic heterogeneity of the disease^ref
Laboratory examinations : white tissue at cardio-MRI. Diagnosis is often delayed
Therapy : once diagnosed and treated with an implanted cardioverter/defibrillator (ICD), mortality is low
• left cardiopathies
• aortic valve stenosis
• aortic valve failure
• congenital obstruction to left atrial inflow
• pulmonary vein stenosis
• mitral stenosis
• intraatrial septum in left atrium due to (cor triatriatum)

Treatment : perforation.
• mitral valve failure
• congenitally corrected trasnposition of the great arteries
• anomalous origin of the left coronary artery from the pulmonary trunk
• miscellaneous
• double-orifice mitral valve
• congenital perforations
• accessory commissures with anomalous chordal insertion
• congenitally short or absent chordae
• cleft posterior leaflet
• parachute mitral valve
• unicuspid aortic valve : occurs rarely and is typically diagnosed in early childhood in association with aortic stenosis^ref
• bicuspid aortic valve : a congenital anomaly of the aortic valve, caused by incomplete separation of 2 of the 3 cusps; it is generally asymptomatic early in life but is predisposed to calcification and stenosis later on.^ref This condition, which narrows the passage through which blood exits the heart, can require surgery at birth. In severe cases the heart does not develop properly in the fetus and the child is born with an illness called hypoplastic left heart syndrome

Aetiology : calcification of the aortic valve is the third leading cause of heart disease in adults. The incidence increases with age, and it is often associated with a bicuspid aortic valve present in 1-2% of the population. Despite the frequency, neither the mechanisms of valve calcification nor the developmental origin of a 2, rather than 3, leaflet aortic valve is known. Mutations in the signalling and transcriptional regulator NOTCH1 cause a spectrum of developmental aortic valve anomalies and severe valve calcification in non-syndromic autosomal-dominant human pedigrees. Consistent with the valve calcification phenotype, Notch1 transcripts were most abundant in the developing aortic valve of mice, and Notch1 repressed the activity of Runx2, a central transcriptional regulator of osteoblast cell fate. The hairy-related family of transcriptional repressors (Hrt), which are activated by Notch1 signalling, physically interacted with Runx2 and repressed Runx2 transcriptional activity independent of histone deacetylase activity. These results suggest that NOTCH1 mutations cause an early developmental defect in the aortic valve and a later de-repression of calcium deposition that causes progressive aortic valve disease^ref.
Complications :
• infectious endocarditis
• aortic dissection
• aortic stenosis
• aortic failure
• quadricuspid aortic valve is a rare cause of pure aortic regurgitation and can be associated with displacement of the coronary ostium, indicating a developmental defect^ref
• endocardial fibroelastosis : diffuse patchy thickening of the mural endocardium, particularly in the left ventricle, due to proliferation of collagenous and elastic tissue. It usually occurs in infants without other cardiac defects, but may occur in adolescents and adults, usually in association with congenital cardiac malformations. Thickening and incompetence of mitral and aortic valves is often associated. It is usually classified as dilated if the left ventricle is enlarged and hypertrophied or contracted if the left ventricle is of normal or reduced size.
• primary endocrine endocardial fibroelastosis : a congenital form of endocardial fibroelastosis, manifest in infancy and occurring unassociated with other cardiac defects.
• coarctation of aorta, infantile type : a form usually seen in infants, characterized by cyanosis and diffuse involvement of the aortic isthmus, associated with other anomalies such as a patent ductus, due to dysharmonic body development (robust trunk and weak lower limbs) : hyposphigmia of femoral artery (compared to radial artery), upper arterial hypertension, costal incisions.
• pseudocoarctation of the aorta : an uncommon congenital anomaly of the arch of the aorta that simulates coarctation radiographically but does not produce occlusion of the vessel.
• cervical aortic arch : a rare, usually asymptomatic, congenital anomaly in which the aortic arch has an abnormally superior location, occasionally extending to the thoracic inlet or into the neck
• double aortic arch : a congenital anomaly in which the aorta divides into 3 branches which embrace the trachea and esophagus and reunite to form the descending aorta
• right aortic arch : a congenital anomaly in which the aorta is displaced to the right and passes behind the esophagus, thus forming a vascular ring that may cause compression of the trachea and esophagus
• acyanotic cardiopathies with left-to-right shunt => pulmonary arterial hypertension (PAH)
• endocardial cushion defects : a spectrum of septal defects resulting from imperfect fusion of the endocardial cushions :
• persistent ostium primum : an endocardial cushion defect characterized by a cleft in the basal portion of the atrial septum, usually associated with cleft mitral valve.
• persistent complete common atrioventricular canal
• septal defect : a defect in one of the cardiac septa, resulting in an abnormal communication between the opposite chambers of the heart
• atrioseptal or atrial septal defect (ASD) (8-13%) : congenital cardiac anomalies in which there is persistent patency of the atrial septum due to failure of fusion between either the septum secundum or the septum primum and the endocardial cushions
• isolated septal defect
• in septum primum
• atrioventricularis communis / persistent common atrioventricular canal : a congenital cardiac anomaly in which the endocardial cushions fail to fuse, the ostium primum persists (producing a low-lying atrial septal defect), sometimes a single atrioventricular valve occurs which has anterior and posterior cusps, and there is commonly a defect of the membranous interventricular septum
• ostium primum defect (severe) is a incomplete form of atrioventricularis communis, there is no septum at the base of the defect, between the mitral and tricuspid valves; it is usually associated with a cleft mitral cusp and occasionally with a cleft tricuspid valve or a ventricular septal defect.
• ostium secundum defect : there is a rim of septum all around the defect
• complete absence : common atrium or trilobated heart
• premature closure of foramen ovale => left atrium hypoplasia => death at birth
• patent foramen ovale (PFO)
• probe patency of foramen ovale : incomplete physical closure of the foramen ovale postnatally, although functional closure occurs, so that a probe may be passed between the atria in the adult. It occurs in 20 to 25% of all hearts.
Epidemiology : prevalence = 26%, but reduces with advancing age (34.3% until third decade (3.3 mm), 20.2% at ninth decade); commonly associated with
Aetiology : by maintaining an embryonic right atrial flow pattern into adult life and directing the blood from the inferior vena cava preferentially toward the interatrial septum, Chiari's network (found in 1.3% to 4% of autopsy studies and 2% at TEE) may favor persistence of a patent foramen ovale (associated in 83% of cases) and formation of an atrial septal aneurysm and facilitate paradoxic embolism^ref
Pathogenesis : interatrial right-to-left shunting during those periods of time when right atrial pressure exceeds left atrial pressure (Valsalva maneuver, occurring physiologically during defecation, weight lifting or pulling, strong repeated cough) =>
• embolism
• thromboembolism
• paradoxical embolism
• direct arterial embolism at the level of foramen ovale
• occult AF paroxysms => atrial thrombosis => cardioembolism
• gaseous or fatty embolism
• refractory hypoxemia in patients with right ventricular infarction or severe pulmonary disease
• orthostatic desaturation in the setting of the rare platypnea-orthodeoxia syndrome
• neurological decompression illness in divers
• migraine headache with aura^{ref1, ref2}
• transient global amnesia
• OSAS
• COPD
Therapy : despite the growing recognition of the PFO, particularly when associated with an atrial septal aneurysm (ASA), as risk factor for paradoxical embolism, the optimal treatment strategy for symptomatic patients remains undefined.
• surgical closure with prosthetic device
• anticoagulant drugs
Laboratory examinations :
• contrast-enhanced transesophageal echocardiography (TEE) + Valsalva maneuver
• contrast-enhanced transcranial echocolordoppler (TCD) (supine patients with horizontal arms, antecubital access, 9 ml NS + 1 ml air mixed just before injection => monitor 5 seconds after injection for 10 seconds; transit > 1 microbubble within 40") + Valsalva maneuver. It doesn't allow differential diagnosis with shunt at other level. Higher sensitivity with femoral vein access. Repeat if negative : the shunt may be permanent or latent (unmasked after Valsalva maneuver)^ref
• mild shunt : 1-10 microbubbles
• moderate shunt : 11-20 microbubbles
• severe shunt : > 20 microbubbles (tent effect)
Prognosis : if not treated, the likelihood of a relapse of ischemic stroke increases by 3%/yr
• septal defect associated with ...
• ... pulmonic valve stenosis
• Fallot trilogy
• Fallot pentalogy
• ... transposition of pulmonary veins
• total transposition : the 4 pulmonary veins join into a single trunk which drains into ...
• supracardiac variety
• ... azygos vein
• ... brachiocephalic trunk
• ... upper cava vein
• ... left pulmonary vein, which then drains into upper cava vein
• cardiac variety :
• ... right atrium
• ... coronary sinus
• subcardiac variety :
• ... lower cava vein
• ... suprahepatic veins
• mixed variety : 2 of the abovementioned varieties.
• partial transposition
• venous sinus-type partial transposition : the 2 right pulmonary veins drain into upper cava vein
• ... mitral valve stenosis (Lutembacher disease)
Epidemiology : 30% of congenital lesions in adults
Symptoms & signs :
• doubling of S₁ sound
• fixed doubling of 2^nd tone
• opening click
• filling or mesodiastolic or delayed diastolic murmur
Therapy :
• antithrombotic drugs
• percutaneous transcatheter closure
• surgical closure
• baffle fenestration or adjustable atrial septal defect in a modified Fontan operation. Hemodynamic benefits include increased cardiac index and systemic oxygen transport, as well as lower systemic venous pressure. The incidence and duration of pleural effusions is also reduced by this approach. Potential complications include those associated with the closure mechanism (snare or umbrella) as well as the possibility of paradoxical embolism.
• partial anomalous pulmonary venous connection
• ventricular septal defects (VSD) (25% of all congenital cardiopathies) : congenital cardiac anomaly in which there is persistent patency of the ventricular septum in either the muscular or fibrous (membranous) portions, most often due to failure of the bulbar septum to completely close the interventricular foramen.
• isolated septal defect (Eisenmenger disease)
• inlet septum
• pars perimembranosa
• over the crista supraventricularis (less frequent).
• below the crista supraventricularis (more frequent).
• pars muscularis / septum inferius (Roger disease / maladie de Roger) : single or multiple => Roger murmur
• infundibular septum
• cushions
• complete asbsence : univentricular heart
• septal defect associated with ...
• aortic regurgitation
• left ventricular to right atrial shunt
• ...
• Fallot tetralogy
• Fallot pentalogy
Symptoms & signs :
• systolic regurgitation murmur
• 3^rd tone
• aortic root to right heart shunt
• ruptured sinus of Valsalva aneurysm
• coronary arterovenous fistula
• anomalous origin of the left coronary artery from the pulmonary trunk
• aortopulmonary level shunt
• patent Botallo ductus arterious (PDA) : while in foetus blood flows from left pulmonary artery into aortic arc, in adult (when it doesn't undergo obliteration to create the arterial ligament) it flows from aorta into left pulmonary artery. Signs :
• differential cyanosis
• continuos murmur
• aortic or aorticopulmonary septal defect / aorticopulmonary fenestration or window : a congenital anomaly in which there is abnormal communication between the ascending aorta and pulmonary artery just above the semilunar valves
• multiple level shunts
• complete common atrioventricular canal
• ventricular septal defect (VSD) with atrial septal defect (ASD)
• ventricular septal defect (VSD) with patent ductus arteriosus (PDA)
• Fallot pentalogy / pentalogy of Fallot : the 4 defects of the Fallot tetralogy of Fallot + patent foramen ovale (PFO) or atrial septal defect (ASD)
• Cantrell's pentalogy / pentalogy of Cantrell : a cleft in the inferior part of the sternum associated with midline abdominal defects such as omphalocele, defective pericardium and diaphragm with communication between the pericardial and peritoneal cavities, and cardiac anomalies such as ventricular septal defect or less often atrial septal defect, tetralogy of Fallot, or left ventricular diverticulum.
• cyanotic cardiopathies with right-to-left (RLS) shunt
• normal or decreased pulmonary blood flow
• overriding aorta : a congenital anomaly occurring in tetralogy of Fallot and Eisenmenger disease, in which the aorta is displaced to the right so that it appears to arise from both ventricles and straddles the ventricular septal defect.
• normal or decreased pulmonary blood pressure
• dominant right ventricle : Fallot tetralogy / "blue disease"

Pathogenesis : first described in 1888, it consists of an anomaly of truncoconic septum => pulmonic valve stenosis & ventricular septal defect (VSD) => aorta communicating with both ventricles (overriding aorta, "knight aorta") & hypertrophy of right ventricle
• pseudotruncus arteriosus : the most severe form of tetralogy of Fallot with associated pulmonary atresia in which outflow is through a single major vessel, the aorta, accompanied by the remnant of the atretic pulmonary artery.
• Corvisart's disease : tetralogy of Fallot associated with right aortic arch
Symptoms & signs : early cyanosis, squatting (decreases blood return from lower limbs and increases pulmonary arterial hypertension (PAH) which limits left-to-right shunt), bronchitis (due to pulmonary hyperemia), doubling of 2^nd tone.ventricular septal defect, overriding aorta, obstruction of the right ventricular outflow tract, and right ventricular hypertrophy.
Without surgical repair, survival past the fifth decade of life is rare but has been reported : an extreme case survived at age 81^ref. The mechanisms for prolonged survival may be initially mild pulmonary stenosis that progresses^ref or adaptations that ameliorate the right-to-left shunting, such as the formation of systemic–pulmonary collaterals^ref, persistent patent ductus arteriosus^ref, or systemic hypertension^ref. Surgery for uncorrected tetralogy of Fallot in elderly patients is associated with increased mortality and is indicated only in symptomatic patients^ref.
• dominant left ventricle
• Ebstein anomaly : congenital low dysplacement of tricuspid valve with right-to-left atrial shunt
• tricuspid valve atresia + ASD or VSD
• complete transposition of the great arteries with pulmonic valve stenosis
• double-outlet right ventricle with pulmonic valve stenosis
• single ventricle with pulmonic valve stenosis
• pulmonary arteriovenous fistula
• vena caval to left atrial communication
• normal ventricles
• increased pulmonary blood pressure
• Eisenmenger syndrome : ventricular septal defect with pulmonary hypertension and cyanosis due to right-to-left (reversed) shunt of blood. Sometimes defined as pulmonary arterial hypertension (pulmonary vascular disease) and cyanosis with the shunt being at the atrial, ventricular, or great vessel area. It occurs in patients with large ...
• ... congenital cardiac ...
• Eisenmenger disease : ventricular septal defect (VSD) (=> hypertrophy of right ventricle) and aorta communicating with both ventricles (overriding aorta, "knight aorta"). Therapy : heart transplantation.
• aortopulmonary window
• patent ductus arteriosus (PDA)
• ... surgically created extracardiac ...
• 10% of Blalock-Taussig anastomosis (subclavian artery to pulmonary artery)
• 30% of Waterston anastomosis (ascending aorta to pulmonary artery)
• 30% of Potts anastomosis (descending aorta to pulmonary artery)
... left-to-right shunts. These shunts initially cause increased pulmonary blood flow. Subsequently, usually before puberty, pulmonary vascular disease causes pulmonary arterial hypertension, ultimately resulting in reversed (right-to-left) or bidirectional shunt flow with variable degrees of cyanosis.
Symptoms & signs : hypoxia => cyanosis, dyspnea, syncope
• increased pulmonary blood flow
• complete transposition of great arteries or vessels (5-7% of all congenital cardiopathies, the commonest) : a congenital cardiovascular malformation in which the aorta arises entirely from the morphologic right ventricle and the pulmonary artery from the morphologic left ventricle, so that the venous return from the peripheral circulation is recirculated by the right ventricle via the aorta to the systemic circulation without being oxygenated in the lungs. It is incompatible with prolonged life unless mixing of oxygenated and deoxygenated blood occurs at some anatomic level (atrial septal defect, ventricular septal defect, patent ductus arteriosus (PAD))

Treatment : surgical atrial septectomy => balloon atrial septostomy (Blalock-Hanlon operation : a palliative operation for transposition of the great vessels, consisting of the creation of an interatrial septal defect) => atrial switch (Senning operation : surgical creation of two interatrial channels for crossing the systemic and pulmonary venous circulations in transposition of the great vessels) => arterial switch operation / Mustard operation : correction of transposition of great vessels by construction of an intra-atrial baffle, composed of pericardial tissue or synthetic material, to direct the systemic and pulmonary venous blood into the left and right ventricles, respectively (survival rate > 90%)
• double-outlet right ventricle of the Taussig-Bing type
• truncus arteriosus
• total anomalous pulmonary venous connection
• single ventricle wthout pulmonic stenosis
• common atrium
• tetralogy of Fallot with pulmonary atresia and increased collateral arterial flow
• tricuspid atresia with large ventricular septal defect and no pulmonic stenosis
• hypoplastic left heart syndrome (HLHS) : any of a group of congenital anomalies consisting of hypoplasia or atresia of the left ventricle and of the aortic or mitral valve or both and hypoplasia of the ascending aorta; it is characterized by respiratory distress and extreme cyanosis, with cardiac failure and death in early infancy. It accounts for nearly 25% of deaths among neonates with congenital heart disease. A hypertrophic frenulum separating the alveolar portion of the maxillary palatine suture is a marker^ref. A hypothesis is proposed implicating an immune mechanism involving maternal antibodies produced in response to pharyngitis caused by group A b-hemolytic streptococci (GABHS) (“strep throat”). After crossing the placenta, the antibodies injure the developing fetal heart, leading to HLHS either because of direct injury to the LV or secondary to reduced blood flow through affected aortic and mitral valves. Analogy is drawn to rheumatic heart disease (RHD), a known sequela of strep throat^ref.
Complications : hyperuricemia, cholelithiasis, renal failure, impaired hemostasis
Aetiology : SNPs in BMP4 can lead to atrioventricular canal defects (AVCD)
• cardioptosis : downward displacement of the heart.
• cardiocoele : protrusion of the heart through a fissure of the diaphragm or through a wound.
• cardioplegia : arrest of contraction of the myocardium, as may be induced by the use of
• chemical compounds
• cold (cryocardioplegia)
... in the performance of surgery upon the heart.
• carditis : inflammation of the heart.
• Lyme carditis : cardiac involvement, generally transient, in Lyme disease; it usually manifests as some degree of atrioventricular block but ventricular tachycardia and left ventricular dysfunction (LVD) may occur.
• rheumatic carditis / rheumatic heart disease (RHD) : cardiac involvement in rheumatic fever, which when severe may be manifested by congestive heart failure, progressive cardiac enlargement, pericarditis, and significant murmurs due to valvular dysfunction.
• streptococcal carditis : carditis occurring as a result of streptococcal sore throat.
• diseases of endocardium
• endocarditis : exudative and proliferative inflammatory alterations of the endocardium, usually characterized by the presence of vegetations or verrucae on the surface of the endocardium (vegetative or verrucous endocarditis) or in the endocardium itself. It may occur as a primary disorder or as a complication of or in association with another disease.

Localizations :
• valvular endocarditis (most commonly) : endocarditis affecting the membrane over the valves of the heart, rather than the mural, chordal, trabecular, or papillary tissue
• native valve endocarditis : infective endocarditis involving one or more of the natural heart valves. The most affected is the mitral valve.
• prosthetic valve endocarditis : infective endocarditis as a complication of implantation of a prosthetic valve in the heart; the vegetations usually occur along the line of suture
• ulcerative endocarditis : infective endocarditis characterized by rapid ulceration of the valvular lesions.
• mural or parietal endocarditis : a form affecting the lining of the walls of the heart chambers, rather than the valvular, chordal, trabecular, or papillary tissue
• endocarditis chordalis : endocarditis affecting particularly the chordae tendineae.
• right-side endocarditis : primary acute endocarditis of the right side of the heart.
Aetiology :
• infectious or infective endocarditis (IE) / malignant or septic endocarditis : endocarditis caused by infection with microorganisms. It has been classified according to course. Because underlying causes and available therapies have changed, this division has little current clinical validity and has been largely replaced by classification on the basis of etiology or underlying anatomy.

Epidemiology : incidence = 1.6÷6 cases / 100,000 / yr; male-to-female ratio 1:5; average onset at age 60; mortality has declined since half of 1970's
Localizations : as for rheumatic endocarditis, but right endocarditis is more common in intravenous drug addicted
• acute bacterial endocarditis (ABE) involves a normal heart valve, and has a short history and rapid course (incubation : 2-5 weeks). RF in 25-50%.
• Staphylococcus aureus (staphylococcal endocarditis : infective endocarditis caused by staphylococcal invasion of the heart valves; lasting 1-2 weeks, expecially in immunocompromised hosts)
• Neisseria gonorrhoeae
• Streptococcus pneumoniae
• subacute endocarditis / endocarditis lenta (affects damaged heart valves, and lasting 3-4 weeks or months)
• subacute bacterial endocarditis (SBE) :
• streptococcal endocarditis : infective endocarditis caused by streptococcal invasion of the heart valves
• fecal streptococci (in feces of both children and adults; nowadays renamed Enterococcus spp.)
• Enterococcus avium (feces of children)
• Enterococcus faecalis
• Enterococcus faecium
• viridans endocarditis : a subacute form of infective endocarditis due to infection with viridans streptococci.
• Streptococcus bovis (feces of children)
• Streptococcus intermedius (feces of adults)
• Streptococcus milleri
• Streptococcus mitis (feces of adults)
• Streptococcus mutans
• Streptococcus salivarius (feces of adults)
• Streptococcus sanguinis
• fungal or mycotic endocarditis : infectious endocarditis, usually subacute, due to various fungi, most commonly
• Candida spp. (Candida endocarditis / endocardial candidiasis)
• Aspergillus spp.
• Ajellomyces capsulatus
• HACEK group :
• Haemophilus spp.
• Actinobacillus actinomycetemcomitans
• Cardiobacterium hominis
• Eikenella spp.
• Kingella kingae
• Brucella melitensis
• Yersinia spp.
• Listeria monocytogenes
• Coxiella burnetii (rickettsial endocarditis : endocarditis caused by invasion of the heart valves with Coxiella burnetii; it is a sequela of Q fever, usually occurring in persons who have had rheumatic fever)
• anaerobic bacteria^ref :
• anaerobic cocci
• Propionibacterium acnes
• Bacteroides fragilis group
• Veillonella spp.
• Acinetobacter spp.
• Chlamydia spp.
• Mycoplasma spp.
• Treponema pallidum subsp. pallidum (syphilitic endocarditis : endocarditis resulting from extension of syphilitic infection from the aorta)
• Mycobacterium tuberculosis (tuberculous endocarditis : a rare form of endocarditis in which the endocardium is involved by extension of a tuberculous perimyocarditis or of miliary tuberculosis)
• Suttonella indologenes
• Tropheryma whippelii
Predisposing conditions :
• local conditions increasing pressures and slowing blood flow => deposition of microorganisms and platelets
• high risk
• aortic valve stenosis
• calcification of mitral valve ring
• valve prostheses (prosthetic valve endocarditis)
• ventricular septal defect (VSD)
• patent ductus arteriosus (PAD)
• coarctation of aorta
• Marfan's syndrome
• intermediate risk
• prolapse of mitral valve
• mitral valve stenosis
• right heart valvulopathies
• previous fibroplastic endocarditis
• asymmetric septal hypertrophy
• calcified aortic sclerosis
• vascular catheters
• low risk
• atrial septal defect (ASD)
• AMI
• atherosclerosis
• immunodepression
Source of infectious organisms :
• direct implantation during diagnostic or therapeutic invasive techniques
• hematogenous route
• endovenous drug addiction (=> endocarditis on tricuspid valve => tricuspid valve failure)
• tooth extraction
• abdominal or urinary surgery
• respiratory infections
• skin infections
Symptoms & signs :
• due to systemic infection
• long-lasting, remitting or intermittent fever with chills, diaphoresis
• malaise, lethargy
• myoarthralgia and tenosynovitis => focal embolic glomerulonephritis => proteinuria and hematuria
• delirium, headache
• pallor
• weight loss
• splenomegaly
• anemia
• leukocytosis
• Litten's sign
• splinter hemorrhages
• Janeway's lesions
• due to local infection
• dyspnea, chest pain, abdominal and limb pain
Morphology : few large polypoid thrombotic vegetations consisting of fibrin, platelets, and granulocytes) : that can embolize in early stages, ulcerations => cuspid perforation, and colonies of microorganisms, Bracht-Wächter bodies (nonspecific inflammatory foci of lymphocytic and mononuclear cells in the myocardium) (differential diagnosis with nonbacterial thrombotic endocarditis (NBTE))
Definition of infective endocarditis according to
• Duke criteria, 1994, proposed by Durack et al.^ref. These criteria have been validated by the authors of reports of numerous studies during the past 4 years in a wide spectrum of patients, including children, adults, the elderly, prosthetic valve recipients, injection drug users, nondrug users, patients in tertiary care settings, patients in primary hospitals, and patients treated outside of the United States. When pathologically confirmed cases were considered to be the gold standard for assessing the Duke criteria, the collective sensitivity of the Duke criteria in numerous studies was >80%^ref. In addition, the high specificity^ref and negative predictive value^ref of the Duke criteria have been confirmed. Despite these data, the Duke criteria have shortcomings. An often-heard criticism of the Duke criteria is the overly broad categorization of the group "possible IE." For example, in the original Duke criteria, an individual patient could be classified as having "possible IE" if only 1 minor criterion was present and if the patient did not meet requirements for "rejected IE." To "reduce the size of this possible group and to amplify the size of the rejected group," Bayer^ref recently called for a "diagnostic floor" for the group of patients listed as "possible IE." Other critics have suggested the modification of current^ref or the inclusion of additional minor criteria^ref to increase the sensitivity of the Duke criteria. Finally, issues such as the relative risk of IE in cases of Staphylococcus aureus bacteremia^{ref1, ref2}, the poor diagnostic sensitivity in suspected cases of Q-fever IE^ref, and the relative role of transesophageal echocardiography (TEE) in the diagnosis of IE^{ref1, ref2, ref3} remain unresolved.
• modified Duke criteria, 2000, with modifications shown in Italics^ref :
• definite infective endocarditis
• pathologic criteria
• microorganisms demonstrated by culture or histologic examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen; or
• pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis
• clinical criteria
• 2 major criteria; or
• 1 major criterion and 3 minor criteria; or
• 5 minor criteria
• possible infective endocarditis
• 1 major criterion and 1 minor criterion; or
• 3 minor criteria
• rejected :
• firm alternate diagnosis explaining evidence of infective endocarditis; or
• resolution of infective endocarditis syndrome with antibiotic therapy for 4 days; or
• no pathologic evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for 4 days; or
•  does not meet criteria for possible infective endocarditis, as above
Major criteria :
• blood culture positive for IE (time for PCR introduction ?^ref)
• typical microorganisms consistent with IE from 2 separate blood cultures:
• viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or
• community-acquired enterococci, in the absence of a primary focus; or
• microorganisms consistent with IE from persistently positive blood cultures, defined as follows:
• at least 2 positive cultures of blood samples drawn >12 h apart; or
• all of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn at least 1 h apart)
• single positive blood culture for Coxiella burnetii or antiphase I IgG antibody titer >1 : 800
• evidence of endocardial involvement
• echocardiogram positive for IE (transesophageal echocardiography recommended in patients with prosthetic valves, rated at least "possible IE" by clinical criteria, or complicated IE [paravalvular abscess]; transthoracic echocardiography as first test in other patients), defined as follows :
• oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or
• abscess; or
• new partial dehiscence of prosthetic valve
• new valvular regurgitation (worsening or changing of pre-existing murmur not sufficient)
Minor criteria :
• predisposition, predisposing heart condition or injection drug use
• fever, temperature >38°C
• vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway's lesions
• immunologic phenomena: glomerulonephritis, Osler's nodes, Roth's spots, and rheumatoid factor
• microbiological evidence: positive blood culture but does not meet a major criterion as noted above (excludes single positive cultures for coagulase-negative staphylococci and organisms that do not cause endocarditis) or serological evidence of active infection with organism consistent with IE
• echocardiographic minor criteria eliminated
Complications :
• septic embolism => Osler's nodes, multiple cerebral and renal infarction or abscess
• perforation => acute valvular failure => acute heart failure
• myocardial abscess
• cardiac aneurysm
• focal membranous glomerulonephritis
• diffuse proliferative glomerulonephritis
Therapy & prophylaxis before minor and major surgery : antibacterial drugs.
Prognosis :
• lethality : 40%.
• recovery when treated
• organization of thrombi => joining of edges => nastriform calcified masses on edges after years
• rheumatic endocarditis : endocarditis associated with rheumatic fever. Involvement may be mural but is usually valvular and involves the entire valve; it is then more accurately termed rheumatic valvulitis, characterized by valvular edema, numerous small, erosions and translucent vegetations (1-3 mm "warts" or protrusions of connective tissue covered by fibrin and platelets) located as a rosary chain on the edges of the valve cusps along the lines of closure and chordae tendinae. As vegetations are well-anchored, they don't embolize

Localizations : mitral valve (alone or with aortic valve) (90%) > isolated aortic valve > mitral, aortic and tricuspid valves > mitral and tricuspid > tetravalvulitis
Pathogenesis : after 1 year => retracting fibrosis (fibroplastic endocarditis) => stiffening and joining of commissurae
• nonbacterial thrombotic endocarditis (NBTE) / marantic endocarditis : endocarditis characterized by noninfected vegetations composed of fibrin and other blood elements, generally located on the line of closure of the mitral and aortic valves and susceptible to embolization.

Aetiology : chronic debilitating disease
• cancers
• Libman-Sacks disease or endocarditis / atypical or nonbacterial verrucous endocarditis or carditis / endocarditis benigna : NBTE associated with systemic lupus erythematosus and occasionally in scleroderma, thrombotic purpura, and other collagen diseases; the vegetations (whose size is intermediate between that of rheumatic and infectious endocarditis) consist of necrotic nuclear debris (hematoxylinophilic bodies), fibrinoid degeneration, and trapped, disintegrating, fibroblastic and inflammatory cells and are located on the edges of the valve cusps along the lines of closure, on chamber walls and chordae tendinae

Localizations : tricuspid valve > tricuspid + mitral valves > tricuspid + pulmonary valves
Pathogenesis : => fibrosis (as for rheumatic endocarditis)
• thromboendocarditis : a term formerly used for nonbacterial thrombotic endocarditis or sometimes incorrectly for nonbacterial verrucous endocarditis.
• Löffler's parietal fibroplastic endocarditis / constrictive endocarditis / eosinophilic endomyocardial disease : endocarditis associated with eosinophilia, marked by fibroplastic thickening of the endocardium, and resulting in congestive heart failure, persistent tachycardia, hepatomegaly, splenomegaly, serous effusions into the pleural cavity, edema of the legs, and edema and ascites of the arms
Laboratory examinations :
• transesophageal echocardiography (TEE) => polypoid endocardial vegetations on valve edges or chamber walls (and rarely on endothelium of large arteries)
• hemoculture
• variation of preexisting cardiac murmurs
• increased ESR
• sometimes alterated CSF
• diseases of heart valves / valvulopathies
• cardiovalvulitis : inflammation of the valves of the heart.
• failure
• stenosis
• restenosis : recurrent stenosis, especially of a valve of the heart, after surgical correction of the primary condition.
• false restenosis : stenosis recurring after failure to divide either commissure of the cardiac valve beyond the area of incision of the papillary muscles.
• true restenosis : restenosis occurring after complete opening of one or both of the commissures of the cardiac valve involved.
• diseases of atrioventricular valves
• diseases of mitral valve^ref
• mitral stenosis (MS)
• buttonhole or fishmouth mitral stenosis / mitral buttonhole : an advanced state of mitral stenosis in which adhesion and shortening of the mitral cusps produces a diaphragmatic slit resembling a buttonhole
Epidemiology : female:male ratio 3:1.
Aetiology :
• rheumatic fever : complete calcification of a rheumatic left atrium was first described in 1898, in association with chronic rheumatic mitral disease, and is more common in women, most of whom have symptoms for > 20 years. The condition is assumed to be the end result of extensive rheumatic pancarditis. The calcification may be confined to the left atrial appendage or, rarely, to the posterior left atrial wall — owing to a regurgitant mitral jet — in which case the calcified patch is called the MacCallum's patch. Massive calcification usually spares the interatrial septum, but when the septum is affected, any further surgery near the mitral valve is hazardous. Radiography of the left lateral side of the chest is recommended to assess long-standing rheumatic mitral-valve disease. Complete calcification has been described as a "coconut atrium" or "porcelain atrium"^ref
• thromboembolism
• atrial myxoma
• bronchial carcinoid
Pathogenesis => symptoms : fusion of valve commissures, fibrotic and calcified cuspids, shortened chordae tendinea =>
• A normally 4 cm²
• A = 2-4 cm² (mild stenosis)
• A = 1.3-2 cm² (moderate stenosis)
• A < 1.3 cm² (severe stenosis) => surgery
symptomatic if A < 1 cm² => decreased AV flow => atrial hypertension => left heart failure (exercise intolerance (tachycardia), AT and AF => arterial thromboembolism, bitonal voice due to compression of left lower laryngeal / recurrent nerve, cyanotic mitralic facies; rarely myocardium ischemia) => pulmonary arterial hypertension (PAH) (=> hemoptysis, dyspnea, acute pulmonary edema if A < 0.7 cm²).
Signs :
• heart auscultation
• opening click of mitral valve
• filling or mesodiastolic or delayed diastolic murmur
• presystolic or atriosystolic murmur
• increased intensity of S₁ sound
• normal or increased intensity of S₂ sound
• hyposphygmic radial pulse
• EKG
• camel-shaped P wave
• atrial tachycardia and atrial fibrillation
• chest X-ray
• enlarged left atrium auriculae
• increased lung vascularization
• if age < 50 : transesophageal echocardiography (TEE) (doming opening and atriomegaly)
• if age > 50 : cardiac catheterism + coronarography to exclude CAD
Therapy:
• asymptomatic (NYHA dyspnea class I or II) : echocardiography every year and medical therapy
• symptomatic (NYHA dyspnea class III or IV, thromboembolism, AF, A < 1.2 cm², tachycardia) :
• diuretics for heart failure; digoxin, b-blockers, and rate-limiting calcium antagonists for rate control in AF
• conservative surgery (divulsion, commissurotomy or ballooned valvuloplasty) or valve replacement
Secondary prevention : penicillin prophylaxis against recurrent episodes of rheumatic fever; anticoagulants to prevent systemic thromboembolism
• mitral failure or regurgitation (MR)

Aetiology :
• acute => atrial compliance doesn't increase
• acute myocardial infarction (AMI)
• trauma
• infectious endocarditis(vegetations, fissuration)
• left atrial myxoma
• left ventricle aneurysm
• myocardium abscess
• chronic => increased atrial compliance
• congenital : fenestrated mitral valve
• inflammatory
• rheumatic fever
• systemic lupus eryhtematosus (SLE)
• systemic scleroderma (SSc)
• rheumatoid arthritis (RA)
• ankylosing spondylitis (AS)
• Takayasu arteritis
• degeneration
• myxomatous degeneration (mitral valve prolapse)
• Marfan's syndrome
• Ehlers-Danlos disease
• valvular ring calcifications
• infections : bacterial endocarditis in carriers of valve prostheses or after cardiosurgery in elderlies
• structural impairment
• dilatation of left ventricle
• dyskinesia of papillary muscles and chordae tendinea
• thromboembolism
• annular dilatation
• thickened leaflets
• flail mitral valve : a mitral valve having a cusp that has lost its normal support (as in ruptured chordae tendineae) and flutters in the blood stream
• redundant leaflets with abnormal coaptation
• papillary muscle rupture
• papillary muscle dysfunction
• annular calcification
• paraprosthetic leak
Symptoms are those due to AF, pulmonary arterial hypertension (PAH), dyspnea, acute pulmonary edema, and right ventricle failure
Signs :
• acute
• protomesosystolic regurgitation murmur
• chronic
• pansystolic regurgitation murmur
• large doubling of 2^nd tone
• 3^rd tone
Carpenter classification :
• type I (fig.a) : normal leaflet, normal chordal motion; annular dilatation due to dilatated cardiomyopathy
• type II (fig. b) : leaflet prolapse, excessive chordal motion = mitral valve prolapse (MVP) syndrome / Barlow's disease or syndrome / floppy mitral valve syndrome / midsystolic click–late systolic murmur syndrome / systolic click–murmur syndrome

Epidemiology : prevalence = 5% of population (females > males)
Pathogenesis : myxomatous proliferation of the leaflets of the mitral valve
• too large leaflets
• too long chordae tendinea
• ischemia of papillary muscles
Symptoms : often asymptomatic. Palpitations and chest discomfort may occur
Signs on auscultation :
• mesotelesystolic regurgitation murmur
• midsystolic clicks
Treatment : in some cases progressive mitral regurgitation necessitates valve replacement (redundancy or hooding of mitral valve leaflets so that they prolapse into the left atrium, often causing mitral regurgitation), conservative (asportation of part of the strip(s) and suture of the remaining part, shortening of chordae tendinea by inserting them back into papillary muscles, solid ring) or prosthetic surgery.
• type III (fìg. c) : restricted leaflet or restricted chordal motion

Therapy :

	0	1	2
symptoms (NYHA class)	absent	I/II	III/IV
EF%	> 60	50-60	< 50
ESD [mm]	< 40	40-45	> 45
factibility	absent	possible	sure

Overall score :
• 0-1 : dilatation, clinical follow-up, echocardiography every 12 months
• 2 : borderline, clinical follow-up, echocardiography every 6 months
• 3-6 : surgery
• asymptomatic (NYHA dyspnea class I or II) :
• normal heart => echocardiography every 6-8 months
• dilated or hypokinetic heart => cardiac catheterism and coronarography if age > 40
• EF > 25-30% => conservative (valvuloplastic with insertion of solid ring or suture) or prosthetic surgery.
• EF < 25-30% => medical therapy (diuretics and vasodilators (usually ACEIs) for heart failure; nitrates and b-blockers for angina), valve replacement, or heart transplantation
• symptomatic (NYHA dyspnea class III, tachyarrhythmia, AF) => transesophageal echocardiography (TEE) (echocolordoppler may be expecially useful)
Secondary prevention : no proven treatment
• mitral valve stenofailure

Aetiology :
• rheumatic fever
• senile degeneration
• diseases of tricuspid valve
• tricuspid stenosis (TS)

Signs :
• doubling of S₁ sound
• filling or mesodiastolic or delayed diastolic murmur
• tricuspid failure or regurgitation (TR)

If mild it can be considere paraphysiological.
Aetiology : gastrointestinal carcinoid
Signs :
• systolic regurgitation murmur
Treatment : cardiac catheterism + right ventriculography =>
• functional failure =>
• mild => no need for surgery
• severe =>
• organic failure => conservative surgery or valve replacement
• combined disease
• diseases of semilunar valves
• diseases of aortic valve^ref
• aortic stenosis (AS)

Aetiology :
• malformative : bicuspid aortic valve
• calcific or calcifying aortic stenosis : atherosclerosis
• post-inflammatory : rheumatic fever
• rarely bacterial endocarditis
• Heyde's syndrome : association between calcific aortic-valve stenosis and gastrointestinal bleeding due to submucosal angiodysplasi. It  is a form of type IIA von Willebrand's syndrome, an acquired deficiency of high-molecular-weight von Willebrand factor multimers. Aortic-valve replacement leads to cessation of gastrointestinal bleedin. von Willebrand factor is essential for the well-known role of platelets in maintaining vascular integrity independent of their essential function in hemostasis^ref
Grading :
• normal transvalvular pressure gradient < 4 mmHg
• 50-60 mmHg : moderate stenosis
• > 80 mmHg : severe stenosis
Varieties  :
• valvular aortic stenosis : congenital, bicuspid aortic valve, rheumatic fever, senile fibrocalcification
• supravalvular aortic stenosis : a rare form of aortic stenosis occurring above the aortic valve, usually caused by a complete circumferential fibrous ring of constricting tissue at the level of the sinus of Valsalva => Williams-Beuren syndrome / elfin facies syndrome
• subaortic or subvalvular aortic stenosis : aortic stenosis due to an obstructive lesion in the left ventricle below the aortic valve, causing a pressure gradient across the obstruction within the ventricle
• membranous
• nodular
• due to hypertrophic cardiomyopathy
Sudden onset.
Symptoms & signs :
• effort symptoms : fatigue, dyspnea, lipothymia, angina, resting arrhthmias (increased afterpotential QT dispersion)
• edemas
• diamond-shaped systolic ejection murmur irradiated to carotid arteries
• paradoxical doubling of S₂ sound
• S₃ sound
• S₄ sounds
Laboratory examinations : widespread use of catheterisation to assess the extent of aortic-valve stenosis could increase the risk of cerebral blood clotting and brain damage
Therapy :
• A < 0.75 cm² / m²_BSA => DP_{transvalvular} > 50 mmHg : aortography, coronarography if age > 40 years
• A > 0.75 cm² / m²_BSA => DP_{transvalvular} < 50 mmHg
• asymptomatic => echocardiography
• symptomatic => diuretics for heart failure, nitrates and b-blockers for angina
=> conservative (divulsion, commissurotomy or ballooned valvuloplasty) or valve replacement (indicated also for women planning a pregnancy) + ventriculoplasty (if post-ischemic) to prevent aCHF
Complications : type 2 acquired von Willebrand's disease / von Willebrand's syndrome => slatentization of intestinal angiodysplasia (IA) (Heyde's syndrome)
Secondary prevention : no proven treatment but lipid-lowering therapy may slow progression of calcific aortic stenosis
• aortic failure, insufficiency or regurgitation (AR)

Aetiology :
• alterations of cuspids
• rheumatic fever
• rheumatoid arthritis (RA)
• infectious endocarditis
• trauma
• annuloaortic ectasia : dilatation of the proximal aorta and the fibrous ring of the heart at the aortic orifice, marked by aortic regurgitation and, when severe, by dissecting aneurysm
• Marfan's syndrome
• Turner syndrome
• Ehlers-Danlos disease
• ascending aorta aneurysm
• ankylosing spondylitis (AS)
• aortitis
• Treponema pallidum subsp. pallidum
• Reiter syndrome
• ulcerative colitis
• loss of support : subaortic ventricular septal defect (VSD)
• quadricuspid aortic valve
Pathogenesis : myocardial hypertrophy compensatory of left ventricular volume overload
Symptoms & signs :
• diastolic regurgitation murmur
• presystolic or atriosystolic murmur
• Traube's sign / pistol-shot sound : a loud sound like a pistol shot heard in auscultation over the femoral arteries in aortic regurgitation
• Hill's sign : disproportionate femoral systolic hypertension, seen in aortic regurgitation and certain other conditions involving increased stroke volume.
• results of markedly increased stroke volume :
• Quincke's pulse :
• Müller's sign : a sign of aortic insufficiency consisting of pulsation, or bobbing, of the uvula and redness of the tonsils and velum palati during systole, infrequently seen with severe or sudden-onset aortic regurgitation. In some patients, the pulsation extended to the soft palate and posterior oropharynx^ref
• Musset's sign : rhythmical jerking movement of the head; seen in cases of aortic aneurysm and aortic insufficiency.
Treatment : carotideal doppler if age > 65 =>
• normal heart, asymptomatic, intermediate failure => control every 6-8 months
• enlarged heart, severe failure =>
• asymptomatic
• normal EF => control every 3 months
• decreased EF =>
• symptomatic => aortography, cardiac catheterism, coronarography =>
• EF > 25 % => surgery
• EF < 25 % => echocardiography with dobutamine
• negative => diuretics and vasodilators (usually ACEIs) for heart failure; valve replacement and eventually heart reduction or transplantation
• positive => surgery
Secondary prevention : vasodilators (nifedipine or ACEIs) to protect the left ventricular myocardium and delay the need for surgery
• combined disease
• diseases of pulmonic valve
• pulmonary stenosis
• subinfundibular
• infundibular stenosis : stenosis below the pulmonary valve, within the infundibulum (conus arteriosus) of the right ventricle of the heart.
• valvular
• supravalvolar (stenosis of pulmonary artery and its branches))
Aetiology : gastrointestinal carcinoid
Signs :
• systolic ejection murmur
• large doubling of 2^nd tone
• paradoxical doubling of 2^nd tone
• pulmonary failure

If mild it can be considere paraphysiological.
Symptoms & signs : diastolic regurgitation murmur
• combined disease
• multiple valvulopathies
• diseases of myocardium / cardiomyopathies : a general diagnostic term designating primary noninflammatory disease of the heart muscle, often of obscure or unknown etiology and not the result of ischemic, hypertensive, congenital, valvular, or pericardial disease.

Diagnosis : EKG.
Aetiology and pathogenesis
• myocardial contusion : contusion of the heart, most frequently due to impact against an automobile steering wheel or other blunt object; the trauma may cause arrhythmias, conduction disturbances, or clinical signs of acute myocardial infarction such as electrocardiographic abnormalities.
• idiopathic or primary cardiomyopathies : those disorders in which the pathological process involves solely the myocardium and in which the cause is unknown and not part of a disease affecting other organs
• idiopathic
• familial or intrinsic aetiology (20-50%; 68% between age 1 and 19)
• mutations in cardiomyocyte-expressed genes (=> direct damage)
• sarcomere proteins
• cytoskeleton proteins
• energy metabolism proteins
• mutations in modifier genes
• ACE
• altered expression of normal genes
• secondary cardiomyopathies : any form that is due to another cardiovascular disorder (e.g., systemic arterial hypertension) or is a manifestation of systemic disease (e.g., sarcoidosis).
• sporadic
• arrhythmias

HR varies physiologically during respiration (up to 5% during normal respiration, up to 30% during deep respiration).
If HR < 60 bpm in an adult : bradycardia
• central bradycardia : bradycardia dependent on disease of the CNS
• fetal bradycardia : a fetal heart rate (FHR) < 120 beats per minute, generally associated with hypoxia; it is usually due to placental insufficiency; it may also result from placental transfer of local anesthetics or beta-adrenergic blocking agents, and rarely from heart block associated with congenital heart disease or maternal collagen vascular disease.
• nodal bradycardia : bradycardia in which the stimulus of the heart's contraction arises in the atrioventricular node or common bundle.
• postinfective bradycardia : bradycardia occurring after infectious disease.
• essential bradycardia : bradycardia occurring without discoverable cause.
• Branham's bradycardia or sign : bradycardia produced by digital closure of an artery proximal to an arteriovenous fistula.
If HR > 100 bpm in an adult : tachycardia
• atrioventricular reciprocating tachycardia (AVRT) : a reentrant tachycardia in which the reentrant circuit contains both the normal atrioventricular nodal to His bundle pathway and an accessory pathway as integral parts
• antidromic atrioventricular (AV) reciprocating tachycardia : a reentrant tachycardia in which the reentrant circuit involves anterograde conduction over the accessory pathway and retrograde conduction over the normal AV node to His bundle pathway
• orthodromic atrioventricular (AV) reciprocating tachycardia : a nodal reentrant tachycardia in which the reentrant circuit involves anterograde conduction over the usual AV node to His bundle pathway and retrograde conduction over an accessory pathway
• double tachycardia : the occurrence of 2 types of ectopic tachycardia, e.g., nodal and ventricular tachycardia, at the same time.
• ectopic tachycardia : abnormally rapid heart action in response to impulses arising outside the sinoatrial node.
• orthostatic tachycardia : disproportionate rapidity of the heart rate on rising from a reclining to a standing position.
• pacemaker-mediated tachycardia / endless loop tachycardia : in patients with dual chamber pacemakers, tachycardia caused by retrograde conduction of ventricular impulses, either premature ventricular complexes or impulses triggered by ventricular pacing which are sensed by the atria and trigger a subsequent ventricular impulse; an endless loop may develop
• paroxysmal tachycardia : a condition marked by attacks of rapid action of the heart having sudden onset and cessation. It is usually qualified by the locus of impulse origin as either ventricular or supraventricular; some classifications subdivide the latter into atrial and junctional tachycardias.
• reciprocating tachycardia : a tachycardia due to a reentrant mechanism and characterized by a reciprocating rhythm
• reentrant tachycardia / circus movement tachycardia : any tachycardia characterized by a reentrant circuit.
• reflex tachycardia : rapid action of the heart initiated through a reflex neural arc by an event occurring elsewhere in the body.
• sinus reentrant tachycardia : tachycardia arising from a reentrant circuit that encompasses the sinus node.
• sinus beat : a natural pulsation of the heart, originating in the sinus node
• ectopic beat : a heart beat originating at some point other than the sinus node.
• postectopic beat : the normal beat following an ectopic beat.
• forced beat : an extrasystole produced by artificial stimulation of the heart.
• capture beats : in atrioventricular dissociation, occasional ventricular responses to a sinus impulse that reaches the atrioventricular node in a nonrefractory phase.
• dropped beat : absence of a single ventricular contraction.
• fusion beat : in electrocardiography, the complex resulting when an ectopic ventricular beat coincides with normal conduction to the ventricle; the complex has features of both the normal and the ectopic beat.
• interpolated beat : a contraction occurring exactly between 2 normal beats without altering the sinus rhythm.
• pseudofusion beat : an ineffective pacing stimulus delivered during the absolute refractory period following a spontaneous depolarization but before sufficient charge accumulates to prevent pacemaker discharge; on the electrocardiogram the pacemaker impulse spike is superimposed on the QRS complex of the spontaneous complex.
• echo or reciprocal beat : a cardiac impulse that in one cycle causes ventricular contraction, travels back toward the atria, then reexcites the ventricles; a series of such beats constitutes a reciprocal rhythm.
• reentrant beat : any of the characteristic beats of a reentrant circuit.
• retrograde beat : a beat occurring as a result of impulse conduction backward relative to the normal atrioventricular direction.
• anomalous complex : in EKG, an abnormal atrial or ventricular complex resulting from aberrant impulse conduction occurring over accessory conduction pathways : retrograde atrial depolarization => P wave is over QRS complex.
QS distance :
• narrow (normal) QRS complex (90 < lasting < 120 ms) marks supraventricular arrhythmias
• wide QRS complex (lasting > 120 ms) is due to slower conduction through ventricular work cells instead of specialized conduction cells. It may be ventricular or supraventricular (e.g. atrioventricular block).
GISEA classification :
• hyperkinetic arrhythmias => hyperkinetic heart syndrome : increased CO of unknown cause associated with slightly elevated SBP and pulse pressures, normal MAP, and low SVR

Aetiology :
• active formation of ectopic impulses in working cells

Aetiology :
• enhanced automaticity : some circumstances can increase phase 4 slope and so accelerate reaching of relative refractory period in ectopic pacemaker area(s)
• myocardium ischemia
• calcifications
• drugs
• nicotine
• caffeine
• cardiac catheterism
• ethanol
• holiday heart syndrome : paroxysms of arrhythmias, most commonly AF, in patients without overt cardiomyopathy after a weekend bout of alcoholic consumption, especially during the year-end holiday season.
• fatigue
• anger : busts of anger precede the most dangerous flutters of the heart in both healthy hearts and patients with ICDs. In 100% of cases where people reported anger levels above 2 out of 5, the arrhythmias were initiated by a series of rapid, premature heart contractions. This type of contraction is known to put an individual at greater risk of sudden arrest. In contrast, only 68% of arrhythmias not preceded by angry feeling had this characteristic. The emotional distress brought on by earthquakes^ref, missile attacks and even the loss of key football matches can trigger heart attacks : it had been presumed that this results from an increased likelihood of clot formation, but strong emotions such as anger can also disrupt the electrical rhythms of the heart because the adrenaline surge associated with a burst of anger might be the trigger.
• mechanical stretch of cardiac muscle cells
• b₁-AR stimulation
• emotions => orthosympathetic hyperactivity (it can be broken by inducing vagal reflexes, just as pressure over ocular bulbs or carotideal sinuses)
• thyrocardiac or thyrotoxic heart disease : heart disease associated with hyperthyroidism, marked by atrial fibrillation, cardiac enlargement, and congestive heart failure.
• reentry : reexcitation of a myocardium area which is no longer refractory by a single impulse, continuing for one or more cycles and sometimes resulting in ectopic beats or tachyarrhythmias. It can exist over either an anatomical or a functional area of slowed impulse conduction and requires also refractoriness of tissue to stimulation and an area of unidirectional block to conduction.

Aetiology :
• atrial or intra-atrial reentry : reentry in which the entire reentrant circuit lies within one or both atria, excluding the sinus node
• sinus nodal reentry : reentry in which impulses traverse a reentrant circuit within or near the sinus node before being conducted to the rest of the heart
• reflection / reflected reentry : a special form of reentry in which an impulse crosses a narrow area of diminished responsiveness to excite distal tissue, pauses long enough for repolarization of proximal tissue, and returns, retracing its pathway and reexciting the same fibers in reverse rather than traversing a circuit. If the returning impulse is strong enough, a seesaw movement of current can result, causing tachyarrhythmias
• anatomical reentry : reentry in which the block to conduction is an anatomical obstacle; it is usually described by the ring model
• preexcitation syndrome : any syndrome characterized by EKG evidence of preexcitation due to an accessory atrioventricular pathway whose conduction rate is faster than that in the normal pathway => short P–R interval
• Wolff-Parkinson-White (WPW) syndrome : the association of paroxysmal tachycardia (or atrial fibrillation) and preexcitation

Pathogenesis : atria and ventricles are connected also through Kent's bundle. As the AV node can be bypassed, atrial fibrillations can evolve rapidly into ventricular fibrillations. It also allows reentry (tachycardias when resting).
Laboratory examinations : wide QRS complex which characteristically shows an early QRS vector (delta wave)
• Lown-Ganon-Levine syndrome

Pathogenesis : reentry through James fibers
Laboratory examinations : normal QRS complex, accompanied by atrial tachycardia
• enlenghtment of conduction way : cardiomegaly
• functional reentry : reentry in which the block to conduction is due to functional heterogeneity of the electrophysiological properties of regions of cardiac tissue; it is usually described by the leading circle model
• anisotropic reentry : reentry that is functional in not occurring around an anatomical obstacle but whose functional properties are conferred by the inherent structural anisotropy of the cardiac muscle fibers; thus it has qualities of both functional and anatomical reentry
• decrease of conduction rate :
• incomplete block of Purkinje's system : when there are at least 2 parallel conduction ways, one with lower resistance (although conduction is slowed down) and the other with...
• unidirectional anterograde block
• longer lasting of the refractory period
In both cases retrograde conduction allows reentry.
• AMI
• hyperkalemia
• shortening of refractory period :
• adrenalin / epinephrine
• electrical pacing
Models : reentrant mechanism : the mechanism by which a locus of unidirectional block to conduction in cardiac muscle can result in ectopic beats or tachyarrhythmias. In addition to the block, also required are at least areas of slow conduction and refractoriness of the tissue to stimulation. Conduction of a normally initiated impulse is delayed by the block long enough for normal surrounding tissue to repolarize and to be reexcited by the delayed impulse; this may begin a self-perpetuating series of abnormal conduction cycles
• leading circle model : a multidimensional model of reentry that describes the cycle of alternating tissue activation and refractoriness in terms of a functional, rather than anatomical, intertissue interface acting as a barrier around which the wavefronts circle. In the model, their pathway is the smallest circuit in which the head of each wavefront is just within the tail of that preceding and thus is able to excite tissue still in its relative refractory period
• figure-of-eight model : a variation of the leading circle model of reentry in which the interface of refractory tissue is a curved barrier, with the result that the wavefronts split, proceed around each edge of the arc, and return centrally to describe a figure 8 configuration
• ring model : a model describing the mechanism of anatomical reentry, based on a circuit that is formed around an impenetrable barrier to propagation and contains a locus of slow conduction. The locus blocks the initial normal impulse but is traversed by later impulses from the opposite direction that reexcite normal cardiac fibers, which can occur repetitively. There must exist either a segment of slow conduction or overall slow conduction with a locus of unidirectional block, and total conduction time in the circuit must exceed the refractory period of the fibers so that an excitable gap exists between a wavefront head and the tail of that preceding
Reentrant circuit : the circuit formed by the circulating impulse in reentry
• macroreentrant circuit : a reentry pathway involving the bundle branches of the conduction system of the heart.
• microreentrant circuit : a reentry pathway involving only a few myocardial cells.
• afterdepolarizations and triggered automaticity
• early afterdepolarization (EAD) if it interrupts phase 3 repolarization. It can be caused by :
• slow underlying HR
• hypokalemia
• class III antiarrhythmic drugs that prolong action potential duration
• delayed afterdepolarization (DAD) if it occurs after full repolarization. It can be caused by :
• high [Ca²⁺]_cytosol
• myocardium ischemia
• adrenergic stress
• Digitalis intoxication
Single impulse from 1 area => extrasystole / premature beat, followed by a compensatory pause (the pause in impulse generation occurring after an extrasystole, designated as :
• full if the sinus node is not reset and the total length of the aberrant plus the following cycle is equivalent to that of 2 normal cycles
• incomplete, less than full, or noncompensatory if the sinus node is reset and the normal cycle length disrupted)
Due to low EDV the sphygmic wave doesn't reach peripheral pulses. Extrasystole can be classified according to their ...
• shape
• monomorphic : single focus
• polymorphic : more foci
• frequency (Lown grading) :
• grade I extrasystole : < 30 monomorphic extrasystoles / hour
• grade II extrasystole : > 30 monomorphic extrasystoles / hour
• grade III extrasystole : polymorphic extrasystoles
• grade IV extrasystole
• grade IVa extrasystole : coupled extrasystoles
• grade IVb extrasystole : sequential extrasystoles
• grade V extrasystole : R on T (R/T) phenomenon (the occurrence of a PVC near the peak of the T wave in electrocardiography; it may lead to ventricular tachycardia or ventricular fibrillation)
• rhythm :
• irregular extrasystoles
• regular extrasystoles : allorhythmia
• bigeminism : an extrasystole every 2 normal beats
• trigeminism : an extrasystole every 3 normal beats
• quadrigeminism : an extrasystole every 4 normal beats
If > 3 sequential extrasystoles with HR > 100 bpm (usually HR = 140-250 bpm) occur => heterotopic tachycardia
• not sustained tachycardia (lasting < 30")
• sustained tachycardia (lasting > 30" or stopped by therapy within 30")
• permanent tachycardia
• iterative tachycardia
• paroxysmal tachycardia (sudden beginning and ending)
Multiple areas of tachycardia => many different small contraction waves diffusing contemporaneously in different directions => they can't nullify each other => chain reaction : subdivision of impulses around each refractory area => fibrillation. Vulnerable period = the end of contraction.
Classification according to origin :
• supraventricular active formation of ectopic impulses in working cells => normal conduction ways => narrow (normal) QRS
• supraventricular tachycardia (SVT) : any regular tachycardia in which the point of stimulation is located above the bundle branches, either in the sinus node, atria, or atrioventricular junction; it may also include those arising from large reentrant circuits encompassing both atrial and ventricular sites

Laboratory examinations : when associated with a BBB, SVT may be confused with VT
Therapy : adenosine => amiodarone
• atrial active formation of ectopic impulses in working cells
• atrial extrasystole / premature atrial complex (PAC) / atrial premature beat (APB) / atrial premature complex (APC) : a single ectopic atrial beat arising prematurely, manifest electrocardiographically as an abnormally shaped premature P wave, usually with a slightly increased PR interval. It occurs in normal hearts, sometimes associated with the use of stimulants, but may be associated with structural heart disease.

‡
• atrial tachycardia : a rapid cardiac rate, usually 160-190 bpm originating from an atrial locus; it may result from enhanced automaticity or impulse reentry.
• nonparoxysmal atrial tachycardia due to Digitalis glycosides
• chaotic or multifocal atrial tachycardia (MAT) : tachycardia characterized by atrial rates of 100 to 130 beats per minute, markedly variable P wave morphology, and irregular P–P intervals; it occurs predominantly in patients with chronic obstructive pulmonary disease, diabetics, and the elderly, and may lead to atrial fibrillation
Therapy : self-carotid sinus massage
• atrial flutter : more impulses from a reentry area => sinus rate : 200-350 bpm, F waves (for flutter; "saw tooth"-shaped). AV block is stable (but varies day by day !) => ventricular heart rate (VHR) is a submultiple of atrial rate => stable R-R distance.
• 1:1
• 2:1 block
• 3:1 block
• 4:1 block
3D illustrations of the electrical pathways in patients with atrial flutter document multiple patterns of abnormal contractions through the heart, contractions that could be missed by more conventional diagnostic methods.
• atrial fibrillation (AF) (a.k.a. "afib")^ref : single unidirectional reentry way around discharges of cava veins in right atrium.

Epidemiology : AF is the most common persistent arrhythmia encountered in clinical practice. The incidence of AF has been shown to increase from 0.1% a year in people aged < 40 years to > 1.5% a year in women > 80 and > 2% a year in men > 80^ref. AF is the most common clinically significant cardiac arrhythmia. In one series, AF accounted for 34.5% of patients hospitalized with a cardiac rhythm disturbance. It has been estimated that 2.2 million Americans have paroxysmal or persistent AF^ref. The prevalence of AF is estimated at 0.4% of the general population, increasing with age^ref. AF is uncommon in childhood except after cardiac surgery. It occurs in < 1% of those under 60 years of age but in > 6% of those over 80 years of age^{ref1, ref2, ref3} . The age-adjusted prevalence is higher in men^{ref1, ref2}. Blacks have less than half the age-adjusted risk of developing AF that is seen in whites^ref. The frequency of lone AF was less than 12% of all cases of AF in some series^{ref1, ref2, ref3} but over 30% in others^{ref1, ref2}. The prevalence of AF increases with the severity of congestive heart failure (HF) or valvular heart disease.
Aetiology : associated to OSAS (obesity + hypertension)
Sinus rate = 400-700 bpm => random AV block => variable R-R distance, i.e. :
• tachyarrhythmic AF (HR = 125-180 bpm)
• normorhythmic AF
• bradyarrhythmic AF
• grade 3 or complete AV block (HR < 60 bpm)
Timing : episodes of AF that last > 30 seconds and that are unrelated to a reversible cause are classified as ...
• first detected AF =>
• paroxysmal (self terminating) AF : episodes that generally last =< to 7 days (most < 24 h)
• persistent (not self-terminating) AF : usually > 7 days. Persistent AF includes cases of long-standing AF (eg, greater than 1 year), in which cardioversion has not been indicated or attempted, usually leading to permanent AF
• permanent or chronic AF : cardioversion failed or not attempted
When a patient has had 2 or more episodes, AF is considered recurrent.
AF secondary to a precipitating condition such as acute myocardial infarction, cardiac surgery, myocarditis, hyperthyroidism, or acute pulmonary disease is considered separately. In these settings, treatment of the underlying disorder concurrently with management of the episode of AF usually eliminates the arrhythmia
Pathogenesis : telediastole is not effective but EDV decreases only of 20-30%, so untreated patients can live up to years. The contribution of atrial systole to ventricular filling is only 15-25% (higher if ventricular dysfunctions occurs).
• atrial factors
• pathology of the atrium in patients with AF : the atria of patients with persistent AF display structural abnormalities beyond those caused by underlying heart disease. Patchy fibrosis with juxtaposition of normal and diseased atrial fibers may account for nonhomogeneity of atrial refractoriness^ref. Fibrosis or fatty infiltration can also affect the sinus node and might be a reaction to inflammatory or degenerative processes that are difficult to detect. The role of inflammation in the pathogenesis of AF has not yet been evaluated, but histological changes consistent with myocarditis were reported in 66% of biopsy specimens from patients with lone AF^ref. Infiltration of the atrial myocardium can occur in amyloidosis, sarcoidosis, and hemochromatosis. Atrial fiber hypertrophy has been described as a major and sometimes the sole histological feature. Progressive atrial dilatation has been demonstrated echocardiographically in patients with AF^ref and, like hypertrophy, can be either a cause or a consequence of persistent AF.
• mechanisms of AF : theories of the mechanism of AF involve 2 main processes: enhanced automaticity in 1 or several rapidly depolarizing foci and reentry involving 1 or more circuits^ref. Rapidly firing atrial foci, located in 1 or several of the superior pulmonary veins, can initiate AF in susceptible patients^{ref1, ref2}. Foci also occur in the RA and infrequently in the superior vena cava or coronary sinus^{ref1, ref2,ref3}. The focal origin appears to be more important in paroxysmal AF than in persistent AF. Ablation of such foci can be curative^ref. The multiple-wavelet hypothesis as the mechanism of reentrant AF was advanced by Moe and colleagues, who proposed that fractionation of the wave fronts as they propagate through the atria results in self-perpetuating "daughter wavelets." The number of wavelets present at any time depends on the refractory period, mass, and conduction velocity in different parts of the atria. Although the patterns of activation underlying the irregular atrial electrical activity of AF have traditionally been described as disorganized or random, recent evidence has emerged that AF is spatially organized. Based on mapping studies of patients undergoing surgery for the Wolff-Parkinson-White (WPW) syndrome, 3 patterns of induced AF have been identified. Type I AF involves single wave fronts propagating across the RA. Type II AF involves 1 or 2 wave fronts, and type III AF is characterized by multiple activation wavelets propagating in different directions. Ultimately, a better understanding of electrophysiological mechanisms will lead to the development of effective preventive measures^ref.
• AV conduction
• general aspects : the AV node is ordinarily the factor that limits conduction during AF. The compact AV node is located anteriorly in the triangle of Koch^ref, surrounded by transitional cells. There appear to be 2 distinct atrial inputs to the AV node, posteriorly via the crista terminalis and anteriorly via the interatrial septum. Studies on rabbit AV nodal preparations show that during AF, propagation of impulses through the AV node to the His bundle depends in part on the relative timing of the anterior and posterior septal activation inputs to the AV node^ref (39). Other factors that affect conduction through the AV node are its intrinsic conduction and refractoriness, concealed conduction, and autonomic tone.
• AV conduction in the WPW syndrome : accessory pathways are muscle connections between the atrium and ventricle that have the capacity to conduct rapidly. Conduction over an accessory pathway during AF can result in a very rapid ventricular response that can be fatal^ref. Drugs such as digitalis, calcium channel antagonists, and beta-blockers, which are usually given to slow conduction across the AV node during AF, do not block conduction over the accessory pathway and can even enhance conduction, resulting in hypotension or cardiac arrest^ref. Patients who develop AF with a rapid ventricular response associated with hemodynamic instability that results from conduction over an accessory pathway should undergo immediate electrical cardioversion. In the absence of hemodynamic instability or a preexcited ventricular response, intravenous procainamide and ibutilide are drugs of choice to achieve pharmacological cardioversion or to block conduction over the accessory pathway.
• myocardial and hemodynamic consequences of AF : during AF, 3 factors can affect hemodynamic function: loss of synchronous atrial mechanical activity, irregularity of ventricular response, and inappropriately rapid heart rate. A marked decrease in cardiac output can occur with the loss of atrial contraction, especially in patients with impaired diastolic ventricular filling, hypertension, mitral stenosis, hypertrophic cardiomyopathy (HCM), or restrictive cardiomyopathies. The variation in RR intervals during AF can also result in hemodynamic impairment. A persistently rapid atrial rate can adversely affect atrial mechanical function (tachycardia-induced atrial cardiomyopathy)^ref. Such changes in atrial tissue might explain the delayed recovery of atrial contractility in patients after cardioversion to sinus rhythm. A persistently elevated ventricular rate during AF (130 bpm or faster in one study)^ref can produce dilated ventricular cardiomyopathy^{ref1, ref2, ref3}. It is critically important to recognize tachycardia-induced cardiomyopathy, because control of the ventricular rate can lead to partial or even complete reversal of the myopathic process. In fact, HF can be the initial manifestation of AF. A variety of hypotheses have been proposed to explain tachycardia-mediated cardiomyopathy that involve myocardial energy depletion, ischemia, abnormalities of calcium regulation, and remodeling, but the actual mechanisms responsible for this disorder are still unclear^ref.
• thromboembolism : although ischemic stroke and systemic arterial occlusion in AF are generally attributed to embolism from the left atrium (LA), the pathogenesis of thromboembolism is complex^ref. Up to 25% of AF-associated strokes can be due to intrinsic cerebrovascular diseases, other cardiac sources of embolism, or atheromatous pathology in the proximal aorta^{ref1, ref2}. About half of elderly AF patients have chronic hypertension (a major risk factor for cerebrovascular disease), and approximately 12% harbor cervical carotid artery stenosis. Carotid atherosclerosis is not substantially more prevalent in AF patients with stroke than in patients without AF, however, and is probably a relatively minor contributing factor^ref.
• pathophysiology of thrombus formation : thrombus associated with AF arises most frequently in the LA appendage (LAA). This cannot be examined reliably by precordial (transthoracic) echocardiography^ref, whereas transesophageal Doppler echocardiography provides a sensitive and specific method to assess LAA function^ref and to detect thrombotic material. LAA flow velocities are reduced because of loss of organized mechanical contraction during AF^{ref1, ref2}. This substrate of decreased flow within the LA/LAA has been associated with spontaneous echo contrast, thrombus formation, and embolic events^{ref1, ref2, ref3, ref4, ref5, ref6, ref7}. LAA flow velocities are lower in patients with atrial flutter than what is usually seen with normal sinus rhythm but are higher than with AF. Whether this accounts for the slightly lower prevalence of LAA thrombus and perhaps a lower rate of thromboembolism associated with atrial flutter is uncertain. In patients with AF, independent predictors of spontaneous echo contrast include LA size, LAA flow velocity^ref, left ventricular (LV) dysfunction, fibrinogen level^ref, hematocrit^{ref1, ref2}, and aortic atherosclerosis ^{ref1, ref2, ref3, ref4}. This phenomenon might be an echocardiographic surrogate for regional coagulopathy and, when dense, is of clinical value to identify AF patients at high risk for thromboembolism^ref, but its utility for prospective risk stratification for thromboembolism beyond that achieved by clinical assessment has not been established. Although conventional clinical management is based on the presumption that thrombus formation requires continuation of AF for approximately 48 h, thrombi have been identified by transesophageal echocardiography (TEE) within shorter intervals^{ref1, ref2}. Contrary to the prevalent view that systemic anticoagulation for 4 weeks results in endocardial adherence and organization of LAA thrombus, TEE studies have verified resolution of thrombus in the majority of patients^ref. Similar observations have defined the transient nature of LA/LAA dysfunction on conversion of AF, which provides a mechanistic rationale for anticoagulation for several weeks before and after successful cardioversion.
• clinical implications : because the pathophysiology of thromboembolism in patients with AF is uncertain, the mechanisms that link risk factors to ischemic stroke in AF are also incompletely defined. The strong association between hypertension and stroke in AF is probably mediated primarily by embolism that originates in the LAA^ref, but hypertension also increases the risk of noncardioembolic strokes in AF^{ref1, ref2}. Hypertension in AF patients is associated with reduced LAA flow velocity and spontaneous echo contrast, which predisposes the patient to thrombus formation^{ref1, ref2}. Ventricular diastolic dysfunction might underlie the effect of hypertension on LA dynamics^{ref1, ref2}. The effect of advancing age to increase stroke risk in AF is multifactorial. In patients with AF, aging is associated with LA enlargement, reduced LAA flow velocity, and spontaneous echo contrast, each of which predisposes to LA thrombus formation^{ref1, ref2}. Additionally, age is a risk factor for atherosclerosis, including complex aortic arch plaque, and is associated with stroke independently of AF^ref. LV systolic dysfunction predicts ischemic stroke in AF patients receiving no antithrombotic therapy^{ref1, ref2, ref3}.
Symptoms & signs : AF has a heterogeneous clinical presentation, occurring in the presence or absence of detectable heart disease or related symptoms. For example, the term "lone AF (LAF)" has been variously defined. The prognosis in terms of thromboembolism and mortality is most benign when applied to young individuals (aged < 60 years) without clinical or echocardiographic evidence of cardiopulmonary disease^ref. These patients have a favorable prognosis with respect to thromboembolism and mortality. By virtue of aging or the development of cardiac abnormalities, however, patients move out of the lone AF category over time, and the risks of thromboembolism and mortality rise. Lone AF is distinguished from idiopathic AF, which implies uncertainty about its origin without reference to the age of the patient or associated cardiovascular pathology. By convention, the term nonvalvular AF is restricted to cases in which the rhythm disturbance occurs in the absence of rheumatic mitral stenosis or a prosthetic heart valve.
• causes and associated conditions
• acute causes of AF : AF can be related to acute, temporary causes, including alcohol intake, surgery, electrocution, myocarditis, pulmonary embolism, other pulmonary diseases, and hyperthyroidism. Successful treatment of the underlying condition can eliminate AF. AF is a common early postoperative complication of myocardial infarction and of cardiac or thoracic surgery.
• AF without associated cardiovascular disease : in younger patients, approximately 30% to 45% of paroxysmal cases and 20% to 25% of persistent cases of AF occur as lone AF^{ref1, ref2}.
• AF with associated cardiovascular disease : specific cardiovascular conditions associated with AF include valvular heart disease (most often mitral), coronary artery disease (CAD), and hypertension, particularly when LV hypertrophy (LVH) is present.
• neurogenic AF : the autonomic nervous system can trigger AF in susceptible patients through heightened vagal or adrenergic tone. Many patients experience onset of AF during periods of enhanced parasympathetic or sympathetic tone. Coumel described a group of patients that he characterized in terms of a vagal or adrenergic form of AF. Patients with pure vagal or adrenergic AF are uncommon, but if the history reveals a pattern of onset of AF with features of one of these syndromes, the clinician can select agents more likely to prevent recurrent episodes.
• clinical manifestations : AF can be symptomatic or asymptomatic, even in the same patient. Symptoms vary with the ventricular rate, underlying functional status, duration of AF, and individual patient perceptions. The dysrhythmia can present for the first time with an embolic complication or exacerbation of HF. Most patients with AF complain of palpitations, chest pain, dyspnea, fatigue, or lightheadedness. Release of atrial natriuretic peptide can be associated with polyuria. AF can lead to tachycardia-mediated cardiomyopathy, especially in patients who are unaware of the arrhythmia. Syncope is an uncommon but serious complication that usually indicates sinus node dysfunction, valvular aortic stenosis, HCM, cerebrovascular disease, or an accessory AV pathway.
• quality of life : although strokes certainly account for much of the functional impairment associated with AF, the rhythm disturbance also decreases quality of life. In the Stroke Prevention in Atrial Fibrillation (SPAF) study cohort, the New York Heart Association functional classification, developed for HF, was an insensitive index of quality of life in patients with AF^ref. In another study^ref, 47 (68%) of 69 patients with paroxysmal AF considered the dysrhythmia disruptive of their lives. This perception was not associated with either the frequency or duration of symptoms. The AFFIRM trial (Atrial Fibrillation Follow-up Investigation of Rhythm Management), which is still in progress, is comparing maintenance of sinus rhythm with rate control in patients with AF, addressing many facets of quality of life, as did the smaller PIAF (Pharmacological Intervention in Atrial Fibrillation) study^ref. In selected patients, radiofrequency catheter ablation of the AV node and pacemaker insertion improved quality-of-life scores compared with medical therapy^{ref1, ref2, ref3, ref4, ref5, ref6}. Long-term oral anticoagulant therapy, which involves frequent blood testing and multiple drug interactions, is another factor with important implications for the quality of life of AF patients. Decision analysis found that only 61% of 97 patients preferred anticoagulation therapy to no treatment^ref, a considerably smaller proportion than that for whom treatment has been recommended according to published guidelines.
Complications :
• if HR < 180 bpm => decreased CO => anterograde manifestations
• if underlying IHD => retrograde manifestations
• AF is associated with a 2-fold increase in mortality and considerable morbidity related to heart failure, pulmonary thromboembolism in patients with mitral valve stenosis or cardiomegaly, or poor rate control
• acute thrombosis => systemic arterial thromboembolism (RR = 6)

Risk factors for ischemic stroke and systemic embolism in patients with nonvalvular AF
• previous stroke or TIA (RR = 2.5)
• history of hypertension (RR = 1.6)
• congestive heart failure (RR = 1.4)
• advanced age (continuous, per decade) (RR = 1.4)
• diabetes mellitus (RR = 1.7)
• coronary artery disease (RR = 1.5)
• rheumatic heart disease
• TEE characteristics : spontaneous echo contrast in left atrium; left atrial appendage velocity < 20 cm/s; complex aortic atheroma
Published risk-stratification schemes for primary prevention of thromboembolism in patients with nonvalvular AF (patients with AF and prior thromboembolism are at high risk of stroke, and anticoagulation is indicated for secondary prevention in such cases) :

sourceref	high risk	intermediate risk	low risk
Atrial Fibrillation Investigators ref	age >= 65 years history of hypertension coronary artery disease diabetes mellitus		age < 65 years  no high-risk features
American College of Chest Physiciansref	age > 75 years history of hypertension left ventricular dysfunction (left ventricular dysfunction refers to moderate to severe wall motion abnormality assessed globally by 2-dimensional echocardiography, reduced ejection fraction, fractional shortening < 0.25 by M-mode echocardiography, or clinical heart failure) > 1 intermediate risk factor	age 65-75 years diabetes mellitus coronary artery disease thyrotoxicosis	age < 65 years no risk factors
Stroke Prevention in Atrial Fibrillationref	women greater than 75 years systolic BP > 160 mmHg left ventricular dysfunction (did not distinguish high-risk from intermediate-risk patients)	history of hypertension no high-risk features	no high-risk features no history of hypertension

Laboratory examinations : minimum and additional clinical evaluation of patients with atrial fibrillation :
• minimum evaluation
• history and physical examination, to define
• the presence and nature of symptoms associated with AF
• the clinical type of AF (first episode, paroxysmal, persistent, or permanent)
• the onset of the first symptomatic attack or date of discovery of AF
• the frequency, duration, precipitating factors, and modes of termination of AF
• the response to any pharmacological agents that have been administered
• the presence of any underlying heart disease or other reversible conditions (eg, hyperthyroidism or alcohol consumption) : evaluate thyroid function for both aetiology and therapy with amiodarone
• electrocardiogram, to identify
• rhythm (verify AF)
• LV hypertrophy
• P-wave duration and morphology or fibrillatory waves
• preexcitation
• bundle-branch block
• prior MI
• other atrial arrhythmias
• to measure and follow the RR, QRS, and QT intervals in conjunction with antiarrhythmic drug therapy
On the electrocardiogram (ECG), AF is described by the replacement of consistent P waves by rapid oscillations or fibrillatory waves that vary in size, shape, and timing, associated with an irregular, frequently rapid ventricular response when atrioventricular (AV) conduction is intact. The ventricular response to AF depends on electrophysiological properties of the AV node, the level of vagal and sympathetic tone, and the action of drugs. Regular RR intervals are possible in the presence of AV block or interference by ventricular or junctional tachycardia. A rapid, irregular, sustained, wide-QRS-complex tachycardia strongly suggests AF with conduction over an accessory pathway or AF with underlying bundle-branch block. Extremely rapid rates (over 200 bpm) suggest the presence of an accessory pathway. P wave is replaced by fibrillation waves (f waves), best viewed in V₁. QQ distance = 0.35-0.95 s.
AF can be isolated or associated with other arrhythmias, often atrial flutter or atrial tachycardia. Atrial flutter can arise during treatment with antiarrhythmic agents prescribed to prevent recurrent AF. Atrial flutter is more organized than AF, with a saw-tooth pattern of regular atrial activation called flutter (f) waves on the ECG, particularly visible in leads II, III, and aVF. Untreated, the atrial rate typically ranges from 240 to 320 bpm, with f waves inverted in ECG leads II, III, and aVF and upright in lead V₁. The wave of activation in the right atrium (RA) may be reversed, resulting in f waves that are upright in leads II, III, and aVF and inverted in lead V1. 2-to-1 AV block is common, producing a ventricular rate of 120 to 160 bpm. Atrial flutter can degenerate into AF, AF can initiate atrial flutter, or the ECG pattern can alternate between atrial flutter and AF, reflecting changing atrial activation. Other atrial tachycardias, as well as AV reentrant tachycardias and AV nodal reentrant tachycardias, can also trigger AF. In other atrial tachycardias, P waves are readily identified and are separated by an isoelectric baseline in 1 or more ECG leads. The morphology of the P waves can help localize the origin of atrial tachycardias. A unique type of atrial tachycardia originates in the pulmonary veins^ref, is typically more rapid than 250 bpm, and often degenerates into AF. Intracardiac mapping can help differentiate the various atrial arrhythmias.

• chest radiograph, to evaluate
• the lung parenchyma, when clinical findings suggest an abnormality
• the pulmonary vasculature, when clinical findings suggest an abnormality
• echocardiogram, to identify
• valvular heart disease
• left and right atrial size
• LV size and function
• peak RV pressure (pulmonary hypertension)
• LV hypertrophy
• LA thrombus (low sensitivity)
• pericardial disease
• blood tests of thyroid function
• for a first episode of AF, when the ventricular rate is difficult to control, or when AF recurs unexpectedly after cardioversion
• additional testing : one or several tests may be necessary
• exercise testing
• if the adequacy of rate control is in question (permanent AF)
• to reproduce exercise-induced AF
• to exclude ischemia before treatment of selected patients with a type IC antiarrhythmic drug
• Holter monitoring or event recording
• if diagnosis of the type of arrhythmia is in question
• as a means of evaluating rate control
• transesophageal echocardiography
• to identify LA thrombus (in the LA appendage)
• to guide cardioversion
• electrophysiological study
• to clarify the mechanism of wide-QRS-complex tachycardia
• to identify a predisposing arrhythmia such as atrial flutter or paroxysmal supraventricular tachycardia
• seeking sites for curative ablation or AV conduction block/modification
Therapy :
• paroxysmal AF : no therapy needed unless severe symptoms (e.g. hypotension, heart failure, angina pectoris) => anticoagulation as needed
• recurrent paroxysmal AF =>
• minimal or no symptoms => anticoagulation and rate control as needed => no drug for prevention of AF
• disabling symptoms in AF => anticoagulation and rate control as needed => antiarrhythmic drug therapy
• persistent AF :
• accept permanent AF => anticoagulation and rate control as needed
• rate control and anticoagulation as needed => consider antiarrhythmic drug therapy => cardioversion => long-term antiarrhythmic drug therapy unnecessary
• recurrent persistent AF =>
• minimal or no symptoms => anticoagulation and rate control as needed
• disabling symptoms in AF => anticoagulation and rate control => antiarrhythmic drug therapy => electrical cardioversion as needed => continue anticoagulation as needed and therapy to maintain sinus rhythm
Initiate drug therapy before cardioversion to reduce the likelihood of early recurrence of AF. Pharmacological treatment before cardioversion in patients with persistent atrial fibrillation: effects of various antiarrhythmic drugs on acute and subacute outcome of transthoracic direct current shock (drugs are listed alphabetically within each class of recommendation) :

	enhanced conversion by direct current (DC) shock and prevent immediate recurrence of atrial fibrillation (IRAF)	suppress subacute recurrence of atrial fibrillation (SRAF) and maintenance therapy class	recommendation class	level of evidence
effective	amiodarone	all drugs in recommendation class I (except ibutilide) plus b-blockers	I	B
	flecainide
	ibutilide
	propafenone
	propafenone + verapamil
	quinidine
	sotalol
uncertain/unknown	b-blockers	diltiazem	IIb	B
	disopyramide	dofetilide
	diltiazem	verapamil
	dofetilide
	procainamide
	verapamil

All drugs (except b-blockers and amiodarone) should be initiated in hospital.
Recommended doses of drugs proven effective for pharmacological cardioversion of atrial fibrillation :

drug	route of administration	dosage (Dosages given in the table may differ from those recommended by the manufacturers. Insufficient data are available on which to base specific recommendations for the use of one loading regimen over another for patients with ischemic heart disease or impaired left ventricular function, and these drugs should be used cautiously or not at all in such patients)	potential adverse effects
amiodarone	oral	inpatient: 1.2–1.8 g per day in divided dose until 10 g total, then 200–400 mg per day maintenance or 30 mg/kg as single dose	hypotension, bradycardia, QT prolongation, torsade de pointes (rare), GI upset, constipation, phlebitis (IV)
		outpatient: 600–800 mg per day divided dose until 10 g total, then 200–400 mg per day maintenance
	intravenous/oral	5–7 mg/kg over 30–60 min, then 1.2–1.8 g per day continuous IV or in divided oral doses until 10 g total, then 200–400 mg per day maintenance
dofetilide	oral	creatinine clearance (mL/min) => Dose (mcg BID) > 60 => 500 40-60 => 250 20-40 => 125 < 20 => contraindicated	QT prolongation, torsade de pointes; adjust dose for renal function, body size, and age
flecainide (insufficient data are available on which to base specific recommendations for the use of one loading regimen over another for patients with ischemic heart disease or impaired left ventricular function, and these drugs should be used cautiously or not at all in such patients)	oral	200–300 mg	hypotension, rapidly conducting atrial flutter
	intravenous	1.5–3.0 mg per kg over 10–20 min
ibutilide	intravenous	1 mg over 10 min; repeat 1 mg when necessary	QT prolongation, torsade de pointes
propafenone	oral	450–600 mg
	intravenous	1.5–2.0 mg per kg over 10–20 min
quinidine (the use of quinidine loading to achieve pharmacological conversion of atrial fibrillation is controversial, and safer methods are available with the alternative agents listed in the table. Quinidine should be used with caution)	oral	0.75–1.5 g in divided doses over 6–12 h, usually with a rate-slowing drug	QT prolongation, torsade de pointes, GI upset, hypotension

Antiarrhythmic drug therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation. Drugs are listed alphabetically and not in order of suggested use.
• heart disease ? =>
• no (or minimal : For adrenergic atrial fibrillation, beta-blockers or sotalol are the initial drugs of choice. Consider nonpharmacological options to maintain sinus rhythm if drug failure occurs) => flecainide, propafenone, sotalol => amiodarone, dofetilide => disopyramide, procainamide, quinidine => consider nonpharmacological options
• yes (consider nonpharmacological options to maintain sinus rhythm if drug failure occurs) =>
• HF => amiodarone, dofetilide
• CAD => sotalol => amiodarone, dofetilide => disopyramide, procainamide, quinidine
• hypertension => LVH >= 4 cm =>
• yes => amiodarone
• no => flecainide, propafenone => amiodarone, dofetilide, sotalol => disopyramide, procainamide, quinidine
Typical doses of drugs used to maintain sinus rhythm in patients with atrial fibrillation :

drug (listed alphabetically)	daily dosage	potential adverse effect
amiodarone	100–400 mg	photosensitivity, pulmonary toxicity, polyneuropathy, GI upset, bradycardia, torsade de pointes (rare), hepatic toxicity, thyroid dysfunction
disopyramide	400–750 mg	torsade de pointes, HF, glaucoma, urinary retention, dry mouth
dofetilide	500–1000 mg (a loading dose of 600 mg per day is usually given for one month or 1000 mg per day over 1 week)	torsade de pointes
flecainide	200–300 mg	ventricular tachycardia, congestive HF, enhanced AV nodal conduction (conversion to atrial flutter)
procainamide	1000–4000 mg	torsade de pointes, lupus-like syndrome, GI symptoms
propafenone	450–900 mg	ventricular tachycardia, congestive HF, enhanced AV nodal conduction (conversion to atrial flutter)
quinidine	600–1500 mg	torsade de pointes, GI upset, enhanced AV nodal conduction
sotalol	240–320 mg (dose should be adjusted for renal function and QT-interval response during in-hospital initiation phase)	torsade de pointes, congestive HF, bradycardia, exacerbation of chronic obstructive or bronchospastic lung disease

Recommendations for use of orally administered pharmacological agents for heart rate control in patients with atrial fibrillation :

drug (listed alphabetically within each class of recommendation)	loading dose	onset	usual maintenance dose (the usual ones necessary, but higher doses may be appropriate in some patients)	major side effects	recommendation
digoxin	0.25 mg PO each 2 h; up to 1.5 mg	2 h	0.125–0.375 mg daily	Digitalis toxicity, heart block, bradycardia	I
diltiazem	NA	2-4 h	120–360 mg daily in divided doses; slow release available	hypotension, heart block, HF	I
metoprolol (the table includes representative members of the type of beta-blocker drugs, but other, similar agents could be used for this indication in appropriate doses.)	NA	4-6 h	25–100 mg BID	hypotension, heart block, bradycardia, asthma, HF	I
propanolol	NA	60-90 min	80–240 mg daily in divided doses	hypotension, heart block, bradycardia, asthma, HF	I
verapamil	NA	1-2 h	120–360 mg daily in divided doses; slow release available	hypotension, heart block, HF, digoxin interaction	I
amiodarone	800 mg daily for 1 wk 600 mg daily for 1 wk 400 mg daily for 4–6 wk	1-3 wk	200 mg daily	pulmonary toxicity, skin discoloration, hypothyroidism, corneal deposits, optic neuropathy, warfarin interaction, proarrhythmia	Ib

Intravenous pharmacological agents for heart rate control in patients with atrial fibrillation :

drug	loading dose	onset	maintenance dose	major side effects	class recommendation
diltiazem	0.25 mg/kg IV over 2 min	2-7 mm	5-15 mg per hour infusion	hypotension, heart block, HF	I (type IIb in congestive HF)
esmolol (only representative members of the type of b-adrenergic antagonist drugs are included in the table, but other, similar agents could be used for this indication in appropriate doses)	0.5 mg/kg over 1 min	5 min	0.05–0.2 mg·kg-1·min-1	hypotension, heart block, bradycardia, asthma, HF	I
metoprolol	2.5–5 mg IV bolus over 2 min; up to 3 doses	5 min	NA	hypotension, heart block, bradycardia, asthma, HF	I (type IIb in congestive HF)
propanolol	0.15 mg/kg IV	5 min	NA	hypotension, heart block, bradycardia, asthma, HF	I (type IIb in congestive HF)
verapamil	0.075–0.15 mg/kg IV over 2 min	3-5 min	NA	hypotension, heart block, HF	I (type IIb in congestive HF)
digoxin	0.25 mg IV each 2 h, up to 1.5 mg	2 hr	0.125–0.25 mg daily	Digitalis toxicity, heart block, bradycardia	IIb (type I in congestive HF)

Recommendations for pharmacological cardioversion of AF <= 7 days duration (the doses of medications used in these studies may not be the same as those recommended by the manufacturers) :

	drug	route of administration	type of recommendation	level of evidence
agents with proven efficacy	dofetilide	oral	I	A
	flecainide	oral or intravenous	I	A
	ibutilide	intravenous	I	A
	propafenone	oral or intravenous	I	A
	amiodarone	oral or intravenous	IIa	A
	quinidine	oral	IIb	B
less effective or incompletely studied	procainamide	intravenous	IIb	C
	digoxin	oral or intravenous	III	A
	sotalol	oral or intravenous	III	A

Types of proarrhythmia during treatment with various antiarrhythmic drugs for atrial fibrillation or atrial flutter according to the Vaughan Williams classification
• ventricular proarrhythmia
• torsade de pointes (VW type IA and type III drugs)
• sustained monomorphic ventricular tachycardia (usually VW type IC drugs)
• sustained polymorphic ventricular tachycardia/VF without long QT (VW types IA, IC, and III drugs)
• atrial proarrhythmia
• provocation of recurrence (probably VW types IA, IC, and III drugs)
• conversion of AF to flutter usually VW type IC drugs)
• increase of defibrillation threshold (a potential problem with VW type IC drugs)
• abnormalities of conduction or impulse formation
• acceleration of ventricular rate during AF (VW type IA and type IC drugs)
• accelerate conduction over accessory pathway (digoxin, intravenous verapamil or diltiazem)
• sinus node dysfunction and atrioventricular block (almost all drugs)
Recommendations for use of pharmacological agents to control the rate of ventricular responses to atrial fibrillation

drug (the doses of medications used in these studies may not be the same as those recommended by the manufacturers)	route of administration	type of recommendation	level of evidence
diltiazem	intravenous	I	A
esmolol	intravenous	I	A
verapamil	intravenous or oral	I	A
other b-blockers	intravenous or oral	I	B
digoxin	intravenous or oral	IIa	B

restore sinus rhythm by ...
• pharmacological cardioversion : in-hospital administration of flecainide and propafenone in a single oral loading dose has been shown to be effective and superior to placebo in terminating atrial fibrillation. In a selected, risk-stratified population of patients with recurrent atrial fibrillation, pill-in-the-pocket treatment is feasible and safe, with a high rate of compliance by patients, a low rate of adverse events, and a marked reduction in emergency room visits and hospital admissions^ref
• electrical cardioversion (electroversion)
• partial myocardial ablation :
• surgical ablation :
• Cox maze operation : based on mapping studies of animal and human AF, Cox et al^{ref1, ref2, ref3, ref4} developed a surgical procedure that controls AF in > 90% of selected patients. The exact mechanism has not been established conclusively, but the creation of barriers to conduction within the RA and LA limits the amount of myocardium available to propagate reentrant wave fronts, thereby inhibiting sustained AF. Incisions encircling the pulmonary veins can prevent initiation of AF by isolating potentially arrhythmogenic foci near the pulmonary veins from the remainder of the atria or by isolating atrial regions with the shortest refractory periods
• modifications of the Cox maze operation involve encircling the pulmonary veins by surgical incisions within the LA and radial incisions in both atria that join the mitral and tricuspid valve annuli^{ref1, ref2, ref3}. Circumferential pulmonary-vein ablation is reported to be effective for paroxysmal and chronic atrial fibrillation^{ref1, ref2, ref3, ref4, ref5}. Sinus rhythm can be maintained long term in the majority of patients with chronic atrial fibrillation by means of circumferential pulmonary-vein ablation independently of the effects of antiarrhythmic-drug therapy, cardioversion, or both. The maintenance of sinus rhythm is associated with a significant decrease in both the severity of symptoms and the left atrial diameter^ref.
Surgical operations for AF have been successfully combined with operative correction of a variety of structural cardiac conditions. In patients with highly symptomatic AF who require open heart operations for valvular, ischemic, or congenital heart disease, consideration should be given to concomitant maze operation for AF or flutter, although this entails additional risk. The mortality rate of an isolated maze operation is < 1%, but mortality is higher when the procedure is combined with other types of operative repair. The morbidity associated with the maze operation includes consequences common to median sternotomy and cardiopulmonary bypass, as well as a risk of short-term fluid retention (owing to reduced release of ANP), transient reduction in LA and RA transport function, and early postoperative atrial tachyarrhythmias. In addition, when the blood supply to the sinus node is disrupted, sinus node dysfunction might require permanent pacemaker implantation. Progressive iterations of these operations have reduced the risk of this complication to < 10%.
• catheter-induced ablation
• electrical ablation
• chemical ablation
• suppression of AF by pacing : although atrium-based pacing is associated with a lower risk of AF and stroke than ventricle-based pacing for patients requiring pacemakers for bradyarrhythmias, the use of pacing as a primary therapy for prevention of recurrent AF has not been validated.
• internal atrial cardioverter/defibrillators : there has been an interest in internal cardioversion of AF for the past 10 years. Attempts have been made to find shock waveforms that reduce the energy requirements for cardioversion, making the shock tolerable to awake patients. One cardioverter capable of atrial sensing and cardioversion as well as ventricular sensing and pacing was evaluated in 290 AF patients. The conversion rate to sinus rhythm was 93%. Another device, with dual-chamber sensing, pacing, and cardioversion/defibrillation capabilities and a maximum output of 27 J, is a ventricular defibrillator with atrial cardioversion capabilities. It was designed to treat both atrial and ventricular arrhythmias with pacing modalities before delivering low-energy shocks. Potential candidates for atrial cardioverter/defibrillators, mainly those with infrequent episodes of poorly tolerated AF, are often suitable for catheter ablation.
Cardioversion should be preceeded for 4-6 weeks and followed by 2 weeks by anticoagulant prophylaxis as restoration of normal contractility pushes previously formed thrombi into arteries (expecially in new onset AF) : prophylaxis may be avoided if onset < 48 hrs ago, no atriomegaly (< 50 mm) and no left ventricular dysfunction, while is required with severe heart or thyroid disease.
Prophylaxis : not after a single paroxysmal episode as the effectiveness cannot be assessed. They prevent ventricular tachycardia but do not improve overall survival^ref
• of arrhythmia :
• if there is no structural heart disease, first choice therapy are type Ic antiarrhythmics (encainide, propafenone), second-line is amiodarone, and third-line is type Ia (defetilide)
• if LVEF < 40% +/- CHF => class III (amiodarone, dofetilide)
• CAD, normal LVEF, no CHF => 1st choice : class III (sotalol, amiodarone) antiarrhythmics => 2nd choice : class III (amiodarone, dofetilide) => 3rd choice : type Ia (disopyramide, procainamide, quinidine)
• if systemic arterial hypertension : 1st choice : class Ic (encainide, flecainide) antiarrhythmics => 2nd choice : class III (sotalol, amiodarone) => 3rd choice : type Ia (disopyramide, procainamide, quinidine) or III (dofetilide) antiarrythmics
• of thrombosis :
• age < 65 years
• no risk factors : ASA
• risk factors : oral anticoagulants (target INR = 2.5; range = 2-3)
• age 65-75 years
• no risk factors : ASA/oral anticoagulants
• risk factors : oral anticoagulants (target INR = 2.5; range = 2-3)
• age > 75 years : oral anticoagulants (target INR = 2.5; range = 2.5-3)
Recommendations for antithrombotic therapy in patients with atrial fibrillation based on thromboembolic risk stratification :

patient features	antithrombotic therapy	grade of recommendation
age < 60 years; no heart disease (lone AF)	aspirin (325 mg daily) or no therapy	I
age < 60 years; heart disease but no risk factors (risk factors for thromboembolism include HF, LVEF < 0.35, and history of hypertension)	aspirin (325 mg daily)	I
age >= 60 years; no risk factors (risk factors for thromboembolism include HF, LVEF < 0.35, and history of hypertension)	aspirin (325 mg daily)	I
age >= 60 years; with diabetes mellitus or CAD	oral anticoagulation (INR 2.0–3.0)	I
addition of aspirin, 81–162 mg daily is optional		IIb
age >= 75 years especially women	oral anticoagulation (INR 2.0)	I
HF; LVEF <= 0.35; thyrotoxicosis; hypertension	oral anticoagulation (INR 2.0–3.0)	I
rheumatic heart disease (mitral stenosis); prosthetic heart valves; prior thromboembolism; persistent atrial thrombus on TEE	oral anticoagulation (INR 2.5–3.5 or higher may be appropriate)	I

Prognosis : the rate of ischemic stroke among patients with nonrheumatic AF averages 5% per year, which is 2 to 7 times the rate for people without AF^{ref1, ref2, ref3, ref4, ref5}. One of every 6 strokes occurs in patients with AF^ref. Including transient ischemic attacks and clinically silent strokes detected radiographically, the rate of brain ischemia accompanying nonvalvular AF exceeds 7% per year ^{ref1, ref2, ref3, ref4, ref5}. In the Framingham Heart Study, patients with rheumatic heart disease and AF had a 17-fold increased risk of stroke compared with age-matched controls^ref, and the attributable risk was 5 times greater than in those with nonrheumatic AF^ref. Among AF patients from general practices in France, the ALFA Study (Etude en Activité Liberale sur le Fibrillation Auriculaire) found a 2.4% incidence of thromboembolism over a mean of 8.6 months of follow-up^ref. The annual risk of stroke attributable to AF increased from 1.5% in Framingham Study participants aged 50 to 59 years to 23.5% for those aged 80 to 89 years^ref. The total mortality rate is approximately doubled in patients with AF compared with patients in normal sinus rhythm and is linked with the severity of underlying heart disease^{ref1, ref2, ref3}.
Web resources : Resource Centre for AF and lone AF by Hans Larsen
• atrial dissociation :  independent beating of the left and right atria, each with normal rhythm or with various combinations of normal rhythm, atrial flutter, or atrial fibrillation.
• junctional active formation of ectopic impulses in working cells
• junctional extrasystole / premature junctional complex (PJC) / junctional premature beat / nodal or atrioventricular (AV) junctional premature beat or complex : an ectopic beat arising prematurely in the atrioventricular junction and traveling toward both the atria and ventricles if unimpeded, causing the P wave to be premature and abnormal or absent and the QRS complex to be premature.

‡
• (atrioventricular (AV)) junctional or nodal tachycardia : that arising in response to impulses originating in the atrioventricular junction, with a HR > 75 bpm
• paroxysmal
• due to enhanced automaticity.
• due to reentry
• atrioventricular nodal reentrant tachycardia : that resulting from reentry in or around the atrioventricular node, characterized by a QRS complex of supraventricular origin, sudden onset and termination, and a regular HR = 150-250 bpm
• paroxysmal supraventricular tachycardia (PSVT) : SVT occurring in attacks of rapid onset and cessation (lasting from few seconds up to many hours)

Aetiology : usually is due to a reentrant circuit..
• Wolff-Parkinson-White syndrome
• Lown-Ganon-Levine syndrome
Therapy : verapamil
• accelerated or nonparoxysmal junctional tachycardia : a junctional tachycardia of slow onset, with a HR = 70-130 bpm. It is due to enhanced automaticity of the atrioventricular junctional tissue

Aetiology :
• digitalis toxicity
• acute myocardial infarction
• acute carditis
• surgical trauma.
=> multiple impulses from more areas = junctional fibrillation
• permanent junctional reciprocating tachycardia (PJRT) : a chronic orthodromic atrioventricular nodal reciprocating tachycardia in which retrograde conduction on a posteroseptal accessory pathway is much slower than anterograde conduction along the normal conduction pathway.
Therapy : self-carotid sinus massage
• ventricular active formation of ectopic impulses in working cells => abnormal conduction ways => wide QRS
• ventricular extrasystole / premature ventricular complex (PVC) / ventricular premature beat (VPB) / ventricular premature complex (VPC) : an ectopic beat arising in the ventricles and stimulating the myocardium prematurely. It is characterized by an early, wide, oddly shaped high voltage QRS complex due to asynchronous ventricular depolarization with an ST segment and T wave directed opposite to the QRS complex, usually without resetting of the sinus node, and with occasional fusion beats
• ventricular trigeminy : an arrhythmia consisting of the repetitive sequence of 1 VPC followed by 2 normal beats
• interpolated ventricular premature beat or complex : a VPC that does not block conduction of the next sinus beat and thus is not associated with a compensatory pause.
Aetiology :
• may occur in normal hearts (stress)
• organic heart disease.
• hypertension with neurovegetative activation
• GERD
• peptic ulcer
• cholecystopathy
• hyperthyroidism
Symptoms & signs : palpitation / cardiopalsm (a subjective sensation of an unduly rapid or irregular heart beat); Braunwald sign : occurrence of a weak pulse instead of a strong one immediately after a PVC
Laboratory examinations : PVCs with RBBB-like morphology arise in left ventricle
‡
• ventricular tachycardia (VT) : an abnormally rapid ventricular rhythm with aberrant ventricular excitation (wide QRS complexes), usually in excess of 150 per minute, which is generated within the ventricle and is most commonly associated with atrioventricular dissociation. Minor irregularities of rate may also occur (ventricular pause : a momentary delay in rhythmicity in VT). Evidence implicates a reentrant pathway as the usual cause => atrioventricular (AV) dissociation : control of the atria by one pacemaker and of the ventricles by another, independent pacemaker; it may be due to heart block, to severe slowing of the sinus rhythm with activation of an ectopic pacemaker, to acceleration of an ectopic pacemaker that usurps control of the ventricles, or to a combination of factors. Marked by U wave at EKG.
• capture beat : in atrioventricular dissociation, occasional ventricular responses to a sinus impulse that reaches the atrioventricular node in a nonrefractory phase.
• fusion beat : in electrocardiography, the complex resulting when an ectopic ventricular beat coincides with normal conduction to the ventricle; the complex has features of both the normal and the ectopic beat.
• pseudofusion beat : an ineffective pacing stimulus delivered during the absolute refractory period following a spontaneous depolarization but before sufficient charge accumulates to prevent pacemaker discharge; on the electrocardiogram the pacemaker impulse spike is superimposed on the QRS complex of the spontaneous complex
• interference atrioventricular dissociation : a form of atrioventricular dissociation in which an accelerated junctional or ventricular pacemaker usurps control of the ventricles and rapidly bombards the atrioventricular node from below, rendering the node refractory to supraventricular impulses.
• isorhythmic atrioventricular dissociation : a form of atrioventricular dissociation in which the atria and ventricles beat at similar rates, although independently; it usually results from severe sinus bradycardia in which the sinus node discharge rate drops just below that of the atrioventricular junctional tissue
• primary electrical disease : a condition characterized by serious ventricular tachycardia, and sometimes ventricular fibrillation, in the absence of recognizable structural heart disease
• torsades de pointes syndrome / long-QT (LQT) syndrome (LQTS)

Aetiology :
• acquired :
• certain medications (class IA antiarrhythmic drugs, diethylpropion, bendrofluazide, ...)
• hypokalemia
• congenital :
• LQT1 / Jervell and Lange-Nielsen syndrome (JLNS) / surdo-cardiac syndrome : an autosomal recessive form of the long QT syndrome, characterized by neural deafness and syncope, and sometimes ventricular fibrillation and sudden death, due to mutations in LQT1 / mutation in the KQT-like voltage-gated potassium channel-1 gene (KCNQ1)
• Romano-Ward syndrome (RWS) : an autosomal dominant form of the long QT syndrome, characterized by syncope and sometimes ventricular fibrillation and sudden death, due to mutations in KQT-like voltage-gated potassium channel-1 gene (KCNQ1).
• LQT2 : mutations in human ether-a-go-go-related gene (HERG)
• LQT3 : mutations in a polypeptide of voltage-gated sodium channel type V (SCN5A)
• LQT4 / LQT syndrome with sinus bradycardia : syndromes arising from mutations in ankyrin-B (whose protein coordinates ion channels and transporters and thus regulates the flow of ions in and out of heart muscle cells, which in turn controls the beating of the heart) had in the past been grouped with the LQTS class of arrhythmias, but prolonged QT intervals are not a consistent feature, indicating that this is a distinct arrhythmia. Ankyrin-B is not only found in muscle cells of the atria and ventricles, but also in nerve cells within the heart, leading researchers to believe that the gene could play important role in different aspects of heart function. Also, ankyrin-B is expressed by cells in different organ systems, including the insulin-producing cells of the pancreas, certain nervous system cells, the linings of the lungs and kidneys, and the retina
• LQT5 : mutations in KCNE1 / minimal potassium ion channel (MINK)
• LQT6 : mutations in KCNE2
Pathogenesis : prolongation of the Q–T interval (cardiac repolarization is markedly prolonged) combined with torsades de pointes and manifest as several different forms, EADs cause polymorphic ventricular tachycardia with a long QT interval and sudden cardiac death
Laboratory examinations : Bazett's formula : QTc = QT/sqrt(RR)

ref	adult males	adult females
normal	< 430	< 450
borderline	430-450	450-470
pathological	> 450	> 470

If HR > 120 bpm => embryocardiac rhythm.
Laboratory examinations :
• nonsustained VT :


• sustained VT :


ECG criteria that favor VT :
• AV dissociation
• QRS width > 0.14 s with RBBB configuration; > 0.16 s with LBBB configuration
• QRS axis :
• left axis deviation with RBBB morphology; extreme left axis deviation (northwest axis) with LBBB morphology
• concordance of QRS in precordial leads
• morphologic patterns of the QRS complex :
• RBBB :
• mono- or biphasic complex in V₁
• RS (only with left axis deviation) or QS in V₆
• LBBB :
• broad R wave in V₁ or V₂ >= 0.04 s
• onset of QRS to nadir of S wave in V₁ or V₂ of >= 0.07 s
• notched downslope of S wave in V₁ or V₂
• Q wave in V₆
Differential diagnosis : SVT + BBB
Therapy :
• pulseless VT should be treated as VF
• pulseful VT should be treated with carotid sinus massage and lidocaine
• monomorphic : amiodarone
• polymorphic :
• normal QT (also amiodarone)
• long QT : correct electrolyte disorders
‡
• ventricular fibrillation (VF) => circulatory standstill.
• high voltage VF : 0.5 mV, normal QRS complexes

‡  (20-30")
• low voltage VF : 0.2-0.3 mV, no QRS complex => 10' : 0.1 mV
Aetiology :
• AMI
• electrical shock
Therapy : defibrillation within 1'. Before a defibrillator is available, cardiopulmonary resuscitation (CPR) may be useful for > 90'. Unconscious adult patients successfully resuscitated from cardiac arrest due to VF should undergo therapeutic hypothermia
• tachydysrhythmia : an abnormal heart rhythm with tahycardia in an adult; the term tachyarrhythmia is usually used instead
• completely desynchronized electrical activity
• AF
• VF
• partially desynchronized electrical activity
• VT with torsades de pointes syndrome
• parasystolia : ectopic pacemaker (usually in ventricle) competes with SA node.
• synchronized electrical activity
• normotopic or sinus tachycardia (ST) : tachycardia originating in the sinus node (100 < HR < 160-170 bpm) is a physiological compensation mechanism due to increased automatism in reaching potential threshold during relative refractory period.

Aetiology : b₁-AR orthosympathetic hyperactivity
• normal during exercise or anxiety
• shock, hypotension
• hypoxia
• congestive heart failure
• fever (cellular hypermetabolism : + 18 bpm / °C up to 40.5°C)
• various high output states.
• Roemheld-Tecklenburg-Ceconi syndrome
• SVT
• atrial flutter
• VT
• hypokinetic arrhythmias / bradydysrhythmia : an abnormal heart rhythm with bradycardia in an adult; the term bradyarrhythmia is usually used instead.
• sinusal hypokinetic arrhythmias
• sinoatrial or sinus bradycardia (SB) : a slow sinus rhythm, with a HR < 45 bpm in an adult

Aetiology :
• common in young adults and in athletes
• parasympathetic hyperactivity
• vagal bradycardia : bradycardia due to vagal hypertone
• carotid sinus syndrome or syncope / Charcot-Weiss-Baker syndrome
• sinoatrial (SA) block

Grading :
• grade I SA block : no signs at EKG (?)
• grade II SA block : Wenckebach phenomenon
• grade III SA block : no P wave, HR < 40 bpm
• sinus arrest : a halt, usually transient, in the normal cardiac (sinus) rhythm due to a slowing or cessation of impulse initiation by the sinus node, lasting for an interval that is not an exact multiple of the normal cardiac cycle; either ectopic pacemakers assume control of the rhythm or periods of ventricular asystole occur
• sinus pause : a transient interruption in the sinus rhythm, of a duration that is not an exact multiple of the normal cardiac cycle.
• sick sinus syndrome (SSS) : a benign syndrome of atrial and ventricular bradycardia, generally intermittent and sometimes mixed with episodes of rapid regular or irregular atrial or ventricular tachyarrhythmias (bradycardia-tachycardia syndrome / brady-tachy syndrome) or periods of sinus arrest, due to malfunction originating in the supraventricular portion of the cardiac conduction system. It usually affects elderlies and is unmasked by antiarrhythmic drugs

Laboratory examinations : Holter monitor every 6-12 months, pacemaker even if asymptomatic (syncope, fatigue, adynamia due to atrioventricular block, sinoatrial block or trifascicular arrest)
=> passive formation of ectopic pacemaker => escape or escaped beat : an ectopic beat that follows an abnormally long pause between impulses propagated by the sinoatrial node; name for the escape of impulse propagation from normal control.
• atrial escape beat : an ectopic beat originating within the atria; it occurs when the sinus node does not fire or fires ineffectively.
• atrioventricular (AV) junctional escape beat or complex : a depolarization initiated in the atrioventricular junction when one or more impulses from the sinus node are nonexistent or ineffective => tawarian or hissian escape rhythm (40 < HR < 60 bpm) : narrow QRS complex.
• if junctional failure => ventricular escape beat : an ectopic beat of ventricular origin occurring in the absence of supraventricular impulse generation or conduction; it is characterized by a bizarre, usually wide QRS complex and lack of an ectopic P wave.
• conduction disorders
• atrioventricular (AV) block in the conduction of impulse between sinoatrial node and His bundle branches : PP distance is normal but PR (PQ) tract = 200-500 ms = 5-12 small squares in EKG (when HR is normal).

Aetiology :
• damage of AV node and/or His-Purkinje system (calcifications, fibrosis, necrosis, myocarditis, parasympathetic hyperactivity, ...)
• enleghtnenment of the refractory period of part of the conduction ways (Digitalis glycosides)
• increase of sinusal rate (atrial flutter, atrial fibrillation)
Grading :
• grade 1 AV block : 200 > PR segment < 250 ms (5-6 squares in EKG). Conduction is slowed down but never stopped, so each P wave is followed by a QRS complex. Usually block occurs at AV node.
• grade 2 AV block : 250 < PR segment < 450 ms (6-11 squares in EKG). Some P waves are not followed by a QRS complex
• Mobitz 1 : P-R distance undergoes progressive enlenghtnment at every heart beat until the 3^rd (2:1 conduction), 4^th (3:1 conduction) or 5^th (4:3 conduction) cycle lacks a QRS complex and so on (Luciani-Wenckebach periodism). It is due to functional defects in vagal tone. Usually block occurs at AV node.
• Mobitz 2 : cycles with normal or augmented P-R distance are separated by cycles lacking the QRS complex. It is due to organic injuries below the AV node (usually a bundle branch is damaged and conduction through the other one is intermitting).
• grade 3 AV block => overdrive suppression => atrioventricular dissociation : no P wave is followed by a QRS complex
=> preautomatic pause => passive formation of ectopic pacemaker : according to the level of the block, it may result in a
• junctional escape rhythm
• if junctional failure occurs, a ventricular escape beat => if > 6 beats : idioventricular or sub-hissian escape rhythm (15 < HR < 40 bpm) : wide QRS complex.
• accelerated idioventricular rhythm (AIVR)
Symptoms : Morgagni-Adams-Stokes syndrome
Laboratory examinations : atrioventricular conduction evaluation
• atrial activation times : measurement of intraatrial conductiontimes. Prolonged activation times may be associated with atrial flutter or fibrillation.
• measurement of AH and HV intervals : prolongation of AH interval (> 125 ms) or prolongation of the HV interval (> 55 ms) may help localize the site of delay
• intremental atrial pacing : to determine the cycle length at which block occurs in the AV node and/or His-Purkinje system. Block below the His bundle at rates of < 150 bpm portends the development of infra-His block
Site of 2:1 atrioventricular block :
• QRS width :
• BBB : anywhere
• normal QRS : in AV node or His bundle
• PR interval of conducted P wave :
• > 0.30 s : in AV node
• <= 0.16 s : in His-Purkinje system or His bundle
• atropine or exercise
• improve conduction : in AV node
• worsen conduction : in His-Purkinje system or His bundle
• carotid sinus pressure
• improve conduction : in His-Purkinje system or His bundle
• worsen conduction : in AV node
• retrograde conduction
• present : in His-Purkinje system or His bundle
• absent : maybe anywhere
Therapy : transcutaneous pacing => subcutaneous pacemaker with electrodes on right ventricle.
• intraventricular blocks : QRS duration > 0.10 s > 2.5 small squares)
• incomplete bundle branch block (IBBB) (electrical alternation) (100 < QRS lasting < 120 ms (2.5-3 small squares in EKG))
• complete bundle branch block (CBBB) (QRS lasting > 120 ms (> 3 small squares in EKG))
• left bundle branch block (LBBB) : block of the proximal part of the left bundle branch or alternatively block of both the left anterior and superior fasciculi of the left bundle branch (they cannot be distinguished at EKG), causing delayed depolarization of the left ventricle free wall and reversed depolarization of interventricular septum, so thjat all leads usually beginning with r wave now show a q wave and viceversa

Aetiology :
• cardiopathy : ischemic heart disease, systemic arterial hypertension, aortic stenosis, fibrous degeneration of conduction tissue, hypertrophic cardiomyopathy, rheumatic fever, syphilis, cardiac tumors, after heart surgery or congenital cardiopathies
• intermittent LBBB : ischemic heart disease; rarely functional block
Laboratory examinations : excessive late negativity on rightward leads and excessive late positivity on leftward leads, with very wide QRS. Assuming supraventricular rhythm and no preexcitation syndrome :
• lack of the normal q (septal) wave in V₅, V₆ or more leftward leads (DI and aV_L in patients with horizontal hert). As the q wave can be normally absent in V₆, you have to assess the lack of secondary R wave in V₁ (which could diagnoses RBBB)
• secondary but common findings :
• in some leads QRS complexes may have incisures
• in V₅, V₆, DI and aV_L,
• QRS complexes tend to be of rsR' type or M-shaped and R waves tend to be wide and monophasic. In clockwise heart rotation, V₅, V₆, DI and aV_L tend to show RS complexes
• the ST segments tend to be depressed
• the T waves tend to be reversed
• in right precordial leads,
• the ST segments tend to be elevated
• the T waves are abnormally wide
• the S waves are abnormally wide
• the initial r waves may be very small or lacking (in the latter case, QRS complexes will have wide Q waves)
• in precordial leads the main direction of T waves and ST segments tend to be ooposed to the main direction of QRS complexes in any lead
• in limb leads there is an abnormal angle between the mean QRS and T axes on the frontal plan OR the QRS axis is determined while the T axis cannot be
• the QRS axis is usually normal or rarely left deviated
Once established a diagnosis of LBBB the criteria for normality of QRS complexes, ST segments and T waves are no longer valid

• left anterior hemiblock (LAHB) / intraventricular left superior block (more common) : depolarization of anterosuperior left ventricle starts from the posteroinferior left ventricle

Aetiology :
• intermittent LAHB is found in unstable diseases
• chronic LAHB
• in elderlies without other signs of cardiopathy, due to fibrous degeneration of the left anterior bundle branch
• ischemic heart disease (chronic stable angina or acute coronary syndromes (expecially AMI affecting the left bundle branch))
• systemic arterial hypertension
• congestive cardiomyopathy
• calcific aortic stenosis (calcium depots may extend into the conduction tissue)
• myocarditis
• surgical trauma (e.g. after replacement f aortic valve)
Laboratory examinations :
• QRS duration = 0.09-0.1 s
• left axial deviation (< -30°) excluding other causes
• initial r waves in downward leads (DII, DIII, and aV_F)
• left posterior hemiblock (LPHB) / intraventricular left inferior block (less common)

Aetiology : ?
Laboratory examinations : diagnosis is always by exclusion
• QRS duration = 0.09-0.1 s
• right axial deviation (+90-120°) excluding other causes
• right bundle branch block (RBBB) : delayed depolarization of right ventricle free wall => late positivity on rightward leads and late negativity on leftward leads

Aetiology :
• incomplete RBBB is found in 2-3% of healthy subjects and in atrial septal defect
• complete RBBB is found congenitally (atrial septal defect or Fallot's tetralogy), or in ischemic cardiomyopathy, systemic arterial hypertension, pulmonary embolism, rheumatic cardiomyopathy, pericarditis, Chagas myocarditis
• intermittent RBBB is found after ischemic heart disease, pulmonary embolism, or functional in supraventricular tachycardias
Laboratory examinations : if the rhythm is supraventricular
• a secondary R wave appears in V₁ (so that the QRS complex can be rsr', rSr', RSr', RSR', or M-shaped) and a secondary S wave appears in V₆
• secondary but frequent findings
• in left precordial leads (V₄, V₅, and V₆), high voltage and long duration S waves are observed (also in V₃ and V₂ in counterclockwise heart rotation, or in V₆ only in clockwise rotation)
• high voltage and long duration S waves are observed also in D₁ and aVL
• in right precordial leads (typically in V₁-V₃; in V₁ only in counterclockwise rotation and eventually from V₁to V₅ in clockwise rotation) a depression of ST segment and an inversion of T wave are observed
• important but not determinant findings
• QRS axis normal or rarely deviated to right by 15-30°; often undeterminable; if very deviated consider bifascicular block (i.e. RBBB+LAHB  if there is left axial deviation or RBBB+LPHB if there is right axial deviation)
• the initial part of the QRS complex is normal in all leads, the voltage, R and Q progresion criteria can be assessed (e.g. LVH and AMI can still be diagnosed)
• Brugada syndrome : missense mutation in SCN5A that affects the voltage dependence of sodium-channel inactivation (also ST segment elevation and sudden death)
• functional of frequency-dependent bundle branch blocks / aberrant intraventricular conduction accompanying supraventricular (usually atrial) tachycardias and sometimes atrial fibrillation (intermittent) are normally right-sided (pathological when left-sided)
• bifascicular blocks
• RBBB + LAHB (more common)

Aetiology :
• elderlies with fibrotic degeneration of conduction tissue (rare progression towards complete AV block)
• other conditions in which progression to complete AV block = 5-15%
• atherosclerotic heart disease
• calcific aortic stenosis
• hypertrophic cardiomyopathy
• congenital endocardial cushion defect
• acute myocardial infarction (progression to complete AV blok in 25-50%)
• RBBB + LPHB (less common)

Aetiology : as above (progression to complete AV block in 60-70%)
• LAHB + LPHB
• trifascicular blocks : RBBB + LAHB + LPHB
• diffuse intraventricular block :

Aetiology :
• myocarditis
• severe cardiomyopathies
• infiltrative cardiomyopathy
• severe rheumatic fever
• ischemic heart disease (expecially with ventricular aneurysm)
• hyperkalemia
• severe hypoxia
• hypothermia
• quinidine or procainamide overdose
Laboratory examinations : QRS > 0.11 s and normal QRS axis in the frontal plan
• ventricular asystolia (cardiac standstill / sudden cardiac arrest (SCA)) => circulatory standstill
• Lenègre's disease : acquired complete heart block due to primary degeneration of the conduction system.
• Lev's disease : acquired complete heart block due to sclerosis of the cardiac skeleton.
Therapy :
• pace-maker
• cardiac massage
• atropine
Sauders' classification is based on a topographic criterion.
Symptoms :
• none
• palpitation (palpitation
• fatigue
• syncope
• sudden cardiac death
Laboratory examinations :
• EKG at rest and under effort
• ambulatory ECG monitor : a portable continuous electrocardiographic recorder, typically monitoring 2 channels for 24 hours; it is used to detect the frequency and duration of cardiac rhythm disturbances and to assess pacemaker programming. The term is sometimes used synonymously with Holter monitor [Norman Jefferis Holter, American biophysicist, 1914–1983]. Normally there are 1,000-4,000 PVCs/day and should be treated only when > 5,000 a day (low incidence when < 520/day). According to Lowry classification (post-AMI arrhythmias in CICUs) multifocality is unfavorable, but not in the general population. Holter monitor is used to follow-up aryrhthmic patients after therapy and to document resting or unstable angina (together with clinical log for 48 hrs)
Therapy :
• none required : not hemodynamically significative, sporadic PVCs.
• required : hemodynamically significative (symptoms, evolution, impaired CO or fibrillation (malignant arrhythmias), underlying cardiac (eg. AVB IIb or III) or extracardiac (e.g. caffeine, nicotine, hyperthyroidism, pheochromocytoma, stress) disease, sustained
• aetiological
• antiarrhytmic
• antiarrhythmic drugs
• electroversion
Web resources : Heart Rhythm Society
• myocarditis : inflammation of the muscular walls of the heart.
• endomyocarditis / myoendocarditis : combined myocarditis and endocarditis
Aetiology :
• infectious myocarditis (infectious agents may damage the myocardium by direct invasion, production of toxins, or mediation of an immunological response)
• myolysis cardiotoxica : degeneration of the heart muscle occurring in systemic infection.
• viruses (viral myocarditis : primary or secondary (usually to URTI/LRTI) myocarditis within 2-3 months from viral infection, due to CPE or immune-mediated damage; it most often occurs in infants, pregnant women, and immunosuppressed patients)
• Coxsackie viruses A
• Coxsackie viruses B2, B3 , B4 and B5
• echoviruses 9, 11 and 22
• polioviruses
• adenoviruses
• mumps virus
• influenzavirus A
• influenzavirus B
• congenital rubella virus
• HHV-3 / VZV
• HHV-4 / EBV
• HHV-5 / CMV
• HBV
• HCV
• HIV-1
• rabies virus
• LCMV
• YFV
• Chikungunya virus
• dengue virus
• Junin virus
• Machupo virus
• Bacteria => bacterial myocarditis (it may be caused either by the presence of the organisms in the myocardium or by toxins released from a distant infection)
• Corynebacterium diphteriae (diphtheritic myocarditis : that due to bacterial toxin production in diphtheria; primary lesions are degenerative and necrotic, with a secondary inflammatory response. It is usually subclinical but can cause permanent cardiac damage.)
• Clostridium perfringens
• Streptococcus pneumoniae
• Staphylococcus spp.
• Neisseria meningitidis
• Neisseria gonorrhoeae
• Haemophilus influenzae
• Listeria monocytogenes
• Legionella pneumophila
• Salmonella spp.
• Brucella melitensis
• Mycobacterium tuberculosis (tuberculous myocarditis : granulomatous inflammation of the myocardium in tuberculosis, usually resulting from infection elsewhere in the body)
• Actinomyces israelii
• Nocardia spp.
• Mycoplasma pneumoniae
• Chlamydophila psittaci
• Chlamydophila pneumoniae
• Treponema pallidum
• Leptospira spp.
• Borrelia burgdorferi
• rickettsial myocarditis : primary myocarditis associated with infection by rickettsiae; it is frequently subclinical
• Rickettsia prowazekii
• Rickettsia rickettsii
• Orientia tsutsugamushi
• Coxiella burnetii
• Fungi (in immunocompromised patient)
• Aspergillus spp.
• Candida spp.
• Ajellomyces capsulatus
• Coccidioides immitis
• Ajellomyces dermatitidis
• Sporothrix schenckii
• Filobasidiella spp.
• Protozoa (protozoal myocarditis)
• Trypanosoma cruzi
• Toxoplasma gondii
• Trypanosoma brucei gambiense
• Trypanosoma brucei rhodesiense
• Leishmania spp.
• Balantidium coli
• Plasmodium spp.
• Entamoeba hystolytica
• Metazoa
• Echinococcus granulosus
• Trichinella spiralis
• Schistosoma haematobium
• Strongyloides stercoralis
• Paragonimus westermani
• Loa loa
• Ascaris lumbricoides (larvae)
• Toxocara canis
• Toxocara cati
• Taenia solium (cysts)
• toxic myocarditis or cardiomyopathy : degeneration and focal myocytolysis of heart (a miliary lesion characterized by loss of muscular syncytium, preservation of stroma, absence of inflammatory reaction, and eventual necrosis) caused by agents or situations causing trauma to the myocardium.
• drugs
• catecholamines (also in patients with pheochromocytoma)
• anthracyclines when total dose > 500 mg/m² (lipid peroxidation of myocyte sarcolemma => cytoplasmic vacuolization and lysis of myofibrils)
• cyclophosphamide (not always dose dependent ; myocardial hemorrhage)
• psychostimulants
• phenothiazine
• chemicals
• ethanol
• cocaine
• animal or insect toxins
• snake venom
• metals
• arsenic
• phosphorus
• carbon monoxide (CO)
Laboratory examinations : contraction band necrosis / coagulative myocytolysis : a cardiac lesion seen in patients with neurologically induced cardiographic changes, in myocardial biopsy specimens, and in cocaine or epinephrine toxicity, characterized by hypercontracted myofibrils with contraction bands and mitochondrial damage; it is caused by calcium ion influx into dying cells, which results in the arrest of cells in the contracted state, following severe ischemia and subsequent reperfusion)
• radiation myocarditis due to radiotherapy for mediastinic neoplasms
• autoimmune or granulomatous myocarditis
• rheumatic myocarditis : a common sequela of rheumatic fever due to Streptococcus pyogenes) characterized histologically by perivascular granulomata known as Aschoff bodies or nodules
• cardiac sarcoidosis(CS) : primary or secondary localization; noncaseating granulomas with sclerotic evolution and areas of cardiomyocyte necrosis
• acute isolated myocarditis / Fiedler's myocarditis / idiopathic giant cell myocarditis (IGCM) : acute interstitial myocarditis of unknown etiology, marked by sudden onset, absence of endocarditis or pericarditis
• giant cell myocarditis : a subtype of acute isolated myocarditis characterized by the presence of multinucleate giant cells and other inflammatory cells including lymphocytes, plasma cells, and macrophages, and by ventricular dilatation, mural thrombi, and widespread areas of necrosis. The term is sometimes used synonymously with granulomatous myocarditis or may be distinguished from it as not including granuloma formation.
Laboratory examinations : dilated, flaccid heart; gray-to-yellow areas of serpiginous necrosis; characterized by eosinophils, myocyte damage, and foci of lymphocytic myocarditis
Prognosis : frequent fatal outcome
• hypersensitivity myocarditis : that due to allergic reactions caused by hypersensitivity to various agents. It is characterized by interstitial infiltration, principally perivascular, by lymphocytes, plasma cells, macrophages, and eosinophils.
• sulfonamides
• penicillins
• methyldopa
• smallpox vaccination (severe mixed eosinophilic-lymphocytic myocarditis)
Morphology : only microscopic features are peculiar (regressive phenomena and infiltrates)
• interstitial myocarditis : myocarditis affecting chiefly the interstitial fibrous tissue
• parenchymatous myocarditis : myocarditis affecting chiefly the muscle substance itself.
• Corvisart's disease : formerly, chronic hypertrophic myocarditis.
• localization :
• diffuse
• focal
• confluent
• grading :
• mild
• moderate
• severe
Laboratory examinations : only 16% are confirmed histologically on endomyocardial biopsy (lymphocytes in viral and radiation myocarditis; neutrophils in bacterial and toxic myocarditis; eosinophils in hypersensitivity and parasitary myocarditis; granulomata in rheumatic myocarditis and cardiac sarcoidosis, and IGCM), with ISH or PCR
Prognosis :
• restitutio ad integrum
• granulomata => regional myocardiosclerosis / fibrous myocarditis : a term formerly used frequently to describe focal or diffuse fibrosis of the myocardium caused by chronic inflammation.
• ischaemic heart disease (IHD)

Epidemiology : they cause 45% of worldwide mortality.
Aetiology :
• hypoxia
• coronary arterydisease (CAD) / coronary heart disease (CHD)

Pathogenesis : as for Hagen-Poiseuille law coronary flow = (P_{right atrium} - P_{left ventricle}) / (R_intrinsic + R_{autoregulable}), coronary reserve (i.e. the difference between maximal and basal coronary flows thanks to modulation of R_{autoregulable}) may decrease due to :
• increase of basal coronary flow
• tachycardia due to :
• hyperthyroidism
• compensation to stress, represented by
• mechanical work
• mental work (10-15%)
• excitation
• anger
• exposure at cold
• abundant meals
• women who averaged < 5 hours of sleep a night are 39% more likely to develop heart disease than women who got 8 hours. Those sleeping 6 hours a night had an 18% higher risk of developing blocked arteries than the 8-hour sleepers. Short-term sleep deprivation can raise blood pressure and levels of the stress hormone cortisol, lower glucose tolerance and lead to variations in heart rate.
• hypertrophic cardiomyopathy
• decrease of maximal coronary flow
• increase of R_{autoregulable}
• prolonged coronary spams (2-3%) due to [TxB₂] >> [PGI₂]
• young patients
• voluntary hyperventilation test (HVT)-provoked hyperpnea for 6' => respiratory alkalosis
• first 2-3 hours after awakening, when orthosympathetic system overwhelms parasympathetic one
• late evening, due to fatigue
• Monday morning
• higher levels of serum ACE due to insertion/deletion polymorphism in intron 16
• A=>C 1166 transversion in AT₁receptor gene
• increase of R_intrinsic of coronary arteries
• coronary stenosis (critical if Ø < 75%; coronary blood flow-limiting at rest only if stenosis > 90%, under effort only if > 50%)
• arteriosclerotic heart disease (ASHD) / coronary arteriosclerosis : arteriosclerosis or atherosclerosis of the coronary arteries : MMPs released during inflammation (endocarditis) allow the fissuration of an unstable atherosclerotic plaque in a coronary artery => exposure of thrombogenic material => coronary thrombosis : development of an obstructive red thrombus in a coronary artery (95% of AMIs; in UA only 20% of thrombi are occlusive and only 25% are red thrombi). On the other hand atherosclerosis may induce endothelial dysfunction, which in turn leads to vasospasm : the latter causes arterial stasis favouring once again coronary thrombosis
• a single base pair insertion/deletion variant, which results in a run of either 5 or 6 thymidines 1608 bp from the transcription start site, alters transcription factor binding and influences levels of MMP3 mRNA and protein. The polymorphism contributes to variation in arterial traits and to the risk of CHD and its progression. There is evidence for the action of positive selection, beginning approximately 24,000 years ago, increasing the frequency of the high-expression allele in Europe but not elsewhere. Europeans have greater arterial elasticity and suffer dramatically fewer CHD events than they would have had this positive selection not occurred : British middle-aged men would have suffered 43% more heart attacks^ref.
• total pathogen burden based on multiple infections (HAV, Chlamydiophila pneumoniae, Helicobacter pylori, HHV-5 / CMV, influenzavirus A and  influenzavirus B)^{ref1, ref2}
Risk for vascular injury in atherogenic dyslipidemias : combined familial hypercholesterolemia > polygenic hypercholesterolemia > hypoalphalipoproteinemia
• extension of dissecting type A thoracic aortic aneurysm
• iatrogenous procedures
• atrial myxoma
• congenital anomalies of coronary arteries :
• anomalous origin from pulmonary artery
• fistulae along route
• infectious or inflammatory coronary arteritis : inflammation of the coronary arteries
• thoracic (coronary artery or heart) trauma
• coronary embolism : are embolism of one of the coronary arteries due to endocarditis of aortic valve.
• dysmetabolic diseases :
• Fabry disease
• amyloidosis
• cocaine
• decrease of (P_{right atrium} - P_{left ventricle}) (coronary flow occurs only during diastole)
• decreased capillary bed
It is a dysequilibrium between O₂ need and O₂ contribution.
• O₂ need depends on contractile status, wall tension (which in turns depends on intramural pressure, ventricular pressure, and ventricle volume), and heart rate (depending on parasympathetic stimulation).
• O₂ contribution depends on percentage of extraction from blood (which in turns depends on P_{O2 in arterial blood} and coronary vasomotor tone; normally 70%) and coronary flow (which in turns depends on extravascular compression - related to wall tension, heart rate and diastolic pressure - and perfusion pressure - related to resistance of blood vessels)
=> anaerobic glycolysis => lactate as a byproduct
As there is a range of physiological compensation, not all atherosclerotic patients develop symptoms or are recognized under instrumental examinations evaluating coronary flow.
Epidemiology : both the prevalence and the incidence of CHD increase with increasing age. In the age range 65-75, there is a 50% prevalence, and a 60% prevalence in those over 75. > 11 million people in the USA suffer from CAD. Many patients receive medications to increase blood flow but nearly 500,000 PTCA and CABG procedures are performed each year in those patients who do not benefit from medication.
Risk factors :
• low stature
• single living : in Western populations, such high risk groups will constitute comparatively limited parts of the population, and in Denmark they are easily identifiable in routine population registers^ref.
• on average, adults who had a coronary event had been small at birth and thin at 2 years of age and thereafter put on weight rapidly. This pattern of growth during childhood was associated with insulin resistance in later life. The risk of coronary events was more strongly related to the tempo of childhood gain in BMI than to the BMI attained at any particular age^ref
• 23% of men with erectile dysfunction (ED) have asymptomatic CAD confirmed by angiography vs. 4% in the general population. The prevalence of ED is high (66%) among those with chronic angina and multivessel disease and low (18%) among those who have had an AMI with only one vessel affected. Furthermore, men who had had an AMI and who also have ED are 6 times more likely to have multivessel disease than men who had normal erectile function. 40% of men who had erectile dysfunction smoked heavily, compared with 4% in the control group. An estimated 30-40% of diabetic and aged patients with ED do not benefit from currently available drugs, including PDE-5 inhibitors partly due to the accumulation of AGEs in the corpus cavernosum. Erectile dysfunction should be considered a 'cardiovascular equivalent'^ref.
• in humans, the strong statistical association between fitness and survival suggests a link between impaired oxygen metabolism and disease. After 11 generations, rats with low aerobic capacity scored high on cardiovascular risk factors that constitute the metabolic syndrome. Large-scale epidemiological studies of subjects with and without cardiovascular disease demonstrate that low aerobic exercise capacity is a stronger predictor of mortality than other established risk factors^{ref1, ref2, ref3, ref4}. In patients with type 2 diabetes mellitus, low aerobic capacity is associated with reduced expression of genes involved in oxidative phosphorylation^ref. In insulin-resistant elders, there is a 40% reduction in mitochondrial oxidative and phosphorylation activity, largely attributable to impaired skeletal muscle glucose metabolism^ref. These observations are consistent with impaired regulation of mitochondrial function as an important mechanism for low aerobic capacity and cardiovascular risk factors linked to the metabolic syndrome. These risk factors include weight gain, high blood pressure, reduced endothelial function, hyperinsulinemia, and increased triglyceride concentration in blood. The working hypothesis of the present study was that rats selected on the basis of low versus high intrinsic exercise performance would also differ in maximal oxygen uptake, mitochondrial oxidative pathways, and cardiovascular risk factors linked to the metabolic syndrome. In previous work, they began large-scale artificial selection for low and high aerobic treadmill-running capacity with the genetically heterogeneous N:NIH stock of rats as the founder population^ref. 11 generations of selection produced low-capacity runners (LCRs) and high-capacity runners (HCRs) that differed in running capacity by 347%. The founder population had a capacity to run for 355 ± 144 m (23.1 min) until exhausted. On average, the treadmill-running capacity decreased 16 m per generation in LCRs and increased 41 m per generation in HCRs in response to selection. At generation 11, the LCRs averaged 191 ± 70 m (14.3 min), and the HCRs ran for 853 ± 315 m (41.6 min). For this study, they used young adult rats (ages 16 to 24 weeks) derived from generations 10 and 11 to test their hypothesis that risk factors for common diseases segregate with variation in intrinsic aerobic capacity. High blood pressure is associated with increased risk for stroke and ischemic heart disease^ref. Endothelial dysfunction is an independent predictor of long-term cardiovascular disease progression and cardiovascular event rates^ref. Because individuals with cardiovascular disease often show diminished capacity for adaptation to exercise training^ref, they measured 12 variables to assess the general exercise capacity and left ventricular function both in sedentary control (C) and in exercise-trained (T) LCR and HCR rats. Each rat was trained for 6 weeks on a treadmill at an intensity relative to its own individual maximal oxygen consumption (VO_2max)^ref. Consistent with a low tolerance for exercise, the C-LCR rats had a 58% lower VO_2max, a 17% lower economy of running (i.e., higher oxygen cost of running), 23% less left ventricular weight, and a trend (P = 0.07) toward shorter left ventricular cell length compared with the C-HCR rats. Isolated left ventricular cells from C-HCR rats had better systolic and diastolic function relative to the C-LCR rats. The decrease in aerobic capacity was associated with decreases in the amounts of transcription factors required for mitochondrial biogenesis and in the amounts of oxidative enzymes in skeletal muscle. Impairment of mitochondrial function may link reduced fitness to cardiovascular and metabolic disease^ref
Prevention (IHD is considered a CHD risk equivalent) : Polypill and Polymeal
Symptoms & signs (differential diagnosis with other causes of acute chest pain) :
• diaphoresis
• tachycardia
• dyspnea
• nausea and vomiting
• syncope
Comorbidities : 57% of patients who had acute coronary syndrome had abnormal glucose metabolism; 66% of those who met criteria for new diabetes mellitus were not diagnosed or treated as such by the physicians who managed them^ref.
Laboratory examinations :
• echocardiography or myocardial perfusion scintigraphy under pharmacological stress (vasodilators)
• vasodilators : direct or indirect adenosine agonists cause flow maldistribution (the coronary circulation downstream of an eventual stenotic artery is more vasodilated than that downstream of the normal vessel : the drugs vasodilate the circulation downstream of the healthy artery causing stealing from ischemic area) and show coronary reserve
• adenosine
• dipyridamole (0.56 mg/kg in 4 minutes, 0.28 mg/kg between 8 and 10 minutes, then at minute 12, 13, 14 and 15. Finally atropine 0.25 mg/kg for 4 times) : false positives.
• exercise-simulating drugs : b-AR agonists increase oxygen requirement, cause coronary stealing and reduce subendocardiac perfusion
• dobutamine : 5 mg/kg at minute 3, 10 mg/kg at minute 6, 9 mg/kg at minute 20, 12 mg/kg at minute 30, 15 mg/kg at minute 40, then atropine 0.25 mg/kg at minute 18 and b-blocker at minute 21.
• orbutamine
Examination is positive if regional dysynergy (hypokinesia => akinesia => dyskinesia / aneurysm) appears : alterations persist even when EKG is returned to normality.
• exercise EKG test (EET) : any of various tests that assess cardiovascular health and function after application of a stress to the heart, usually exercise but sometimes others such as atrial pacing, the cold pressor test, or specific drugs.

Subjects are monitored electrocardiographically, symptomatically, by blood pressure and heart rate (via a modified V₅ load), and often by recordings of ventilation and tidal volume recordings as well as other applicable noninvasive or invasive methods
• atrial pacing stress test : a stress test in which temporary immediately reversible atrial pacing (via cardiac electrocatheterization) is used to stress coronary reserve; used for patients incapable of exercise or in whom an exercise stress test is contraindicated. This stress test is not physiological : in physical exercise there is significative peripheral vasodilation, increasd cardiac output and systolic volume, while in atrial pacing cardiac output mildly increases and the systolic volume decreases by increasing heart rate. This is an invasive procedure
• exercise stress tests : any of various stress tests in which exercise is used in the electrocardiographic assessment of cardiovascular health and function, particularly in the diagnosis of myocardial ischemia. They are usually graded exercise test (GXT), consisting of a series of incrementally increasing work loads sustained for defined intervals.
• submaximal exercise test : an exercise test halted at a predetermined point that is less than the maximal exercise capability of the subject, usually at a particular percentage of the maximal heart rate or after a set time interval.
• nongraded tests :
• Master “2-step” exercise test : an early exercise test in which a patient stepped on and off a set of two stairs for a number of trips standardized for age, weight, and sex, with electrocardiograms recorded immediately after test cessation. It has been supplanted by graded exercise tests that can induce higher levels of stress.
• Hines and Brown cold pressor test (CPT) : immersion of one hand in ice water for several minutes, causing vasoconstriction, tachycardia, and transient hypertension; it is used as an alternative stress test for detection of coronary artery disease in patients incapable of undergoing an exercise stress test and as a test of vasomotor function.
• graded tests :
• treadmill exercise test (TET) / treadmill stress test (TMST) : any of various graded exercise tests in which the patient walks on an inclined treadmill, which is generally increased in speed and incline through the test
• Balke-Ware protocol : the treadmill speed is held constant and its slope increased, with the incremental increases in work so closely spaced as to approach continuity
• Bruce protocol : each interval is at a specific load level for 3 minutes and is followed by another at a prescribed incremental increase in treadmill speed and slope
• Ellestad protocol : over 6 stages the treadmill speed is incrementally raised five times and its slope is raised once.
• modified Bruce protocol : an alteration in the Bruce protocol so that the treadmill is initially horizontal rather than uphill, with the first few intervals increasing the treadmill slope only
• Naughton protocol : the selected treadmill speed remains constant through the test but the treadmill slope is raised at the end of each 2-minute increment.
Manchester Royal Infirmary protocol : patients should have discontinued b-blockers (which prevent reaching maximal heart rate) and digitalis (which alters EKG tracing), should be fasting. Patients with CHF, severe systemic arterial hypertension, AMI in the previous 2-3 months, history of new onset angina pectoris since a few weeks or with variations in severity suggesting subentrant of unstable angina cannot undergo testing. Large breasts should be supported to minimize artifacts, and hirsute chests should undergo trichotomy.
The initial load should be equivalent to a daily activity, while the final load should allow reaching the limit heart rate established :

stage	duration (min)	total time (min)	velocity	slope (%)	workload (METS)	equivalent recreational activity
1	1	1	3 km/h (1.9 mph)	0	2	walking
2	3	4	3 km/h (1.9 mph)	10	5	riding
3	3	7	4 km/h (2.5 mph)	12	6-7	slow running
4	3	10	5.5 km/h (3.4 mph)	14	8-9	running
5	3	13	7 km/h (4.4 mph)	16	16	squash

After each stage the patient is placed supine and a 3-channel ECG is recorded from the following leads : V₄, V₅, V₆ (the most sensitive : as the hemodynamic rapidly changes after discontinuation of the effort it is important they are tested first)=> DI, DII, DIII => aV_R, aV_L, aV_F => V₁, V₂, V₃. A complete 12-lead ECG is recorded again after 2, 4, and 6 minutes (in these cases the order has no longer importance).
Criteria for test arrest :
• onset of clinical-ECG anomalies :
• clinical indications
• the patient asks cessation of the test
• excessive fatigue
• excessive dyspnea
• vertigo
• pallor, cold skin, fatigue
• pressure and heart rate drop despite increasing workload
• dangerous arrhythmias
• frequent PVCs
• multifocal PVCs
• VT
• atrial flutter
• atrial fibrillation
• onset of ischemia
• increasing angina
• ST depression or elevation > 1 mm
• device dysfunction :
• defect in monitoring
• defect in defibrillator or treadmill
• achievement of established limit heart rate, usually lower than 85-90% of maximal heart rate calculated from healthy patients with the same age
• < 40 yrs : 175 bpm => 170 bpm
• 40-50 yrs : 170 bpm => 160 bpm
• 50-60 yrs : 165 bpm => 155 bpm
• 60-70 yrs : 160 bpm => 150 bpm
The test is considered positive if there are ST elevations (1-2% : severe proximal stenosis in a main coronary branch) or depressions (98%) > 1 mm and lasting > 0.08 s : they appear only during exercise in 10% (usually missed as intra-exercise recording requires expensive devices), only after exercise in 5%, while remain after exercise in 85%. Suggestive findings include :
• pseudonormalization of reversed T waves at rest
• onset of terminal inversion of T wave or inversion of U wave
• onset of ventricular tachycardia or multiple PVCs
• increased voltage in precordial R waves
• onset of systemic arterial hypotension
Meaningless findings :
• onset of atrial or nodal arrhythmias
• onset of grade I AV block
• onset of intraventricular block
• flattening or inversion of T wave
• increased voltage of U wave
• curvilinear depression of ST segment < 1 mm and < 0.08 ms
• alterations of P wave morphology
Factors causing false positives :
• defective intraventricular conduction
• ventricular preexcitation
• manifest ventricular hypertrophy
• valvulopathies causing ventricular hypertrophy not detected at rest ECG
• systemic arterial hypertension causing ventricular hypertrophy not detected at rest ECG
• pulmonary arterial hypertension causing ventricular hypertrophy not detected at rest ECG
• congestive or hypetrophic cardiomyopathy and myocarditis
• electrolyte alterations, expecially hypokalemia
• hypothyroidism
• drugs (digitalis, quinidine, procainamide, diuretics, antidepressants, sedatives)
• pericarditis
• mitral valve prolapse
• postprandial modifications
• hyperventilation
• previous nonspecific alterations of ST segment and T wave
• pectus excavatum
Factors causing false negatives :
• b-blockers or other drugs impairing heart rate rise
• inadequate workload
• physical training (higher limit heart rate)
• bicycle ergometer exercise test : an exercise test in which the patient pedals a stationary bicycle ergometer; the test is usually graded, with incremental or continuous increases in power produced by increases in pedal resistance at a given pedal speed. Most patients find easier to walk then to ride.
• arm ergometry exercise test : a variant of the bicycle ergometer stress test in which the patient uses his arms to pedal the bicycle.
... whose modality can be :
• ramping (increasing load)
• duration (constant load)
• rectangular (constant load and defined duration)
• triangular (the most used ; + 25 W every 2')
• scalar
• intemitting with resting interval and
• constant load
• increasing load
HR relates with difficulties in doing work.
Power has to be evaluated together with myocardial oxygen consumption = 0.14 x 6.3 x HR x P_{artery systolic} / 100.
Aims :
• diagnosis of ischemic heart disease when basal ECG is negative but there are clinical signs (false negatives = 10-30% according tothe maximal load)
• evaluation of functional capacity :
Mortality = 0.01% in ICU-provided offices; morbidity = 0.02%.
• myocardial scintigraphy / SPECT
• thallium stress test : stress is placed on the cardiovascular system by exercising the patient on a treadmill or bicycle ergometer and thallous chloride Tl-201 is injected intravenously when stress is maximal, just prior to exercise cessation. Immediate (stress) and delayed (redistribution) images are obtained with a gamma camera; then abnormalities of radionuclide distribution and redistribution are assessed, compared with electrocardiograms obtained during exercise, and used to diagnose areas of ischemia and coronary artery disease. In patients incapable of exercise, stress is induced by injection of dipyridamole or adenosine
• PET
• cardio-MRI
• coronarography is indicated in :
• patients with chronic stable angina pectoris who are severely symptomatic despite medical therapy and who are being considered for revascularization, i.e., a PCI or CABG
• patients with troublesome symptoms that present diagnostic difficulties in whom there is need to confirm or rule out the diagnosis of IHD
• patients with known or possible angina pectoris who have survived cardiac arrest
• patients with angina or evidence of ischemia on noninvasive testing with clinical or laboratory evidence of ventricular dysfunction

patients judged to be at high risk of sustaining coronary events based on signs of severe ischemia on noninvasive testing, regardless of the presence or severity of symptoms
patients with chest discomfort suggestive of angina pectoris but a negative or nondiagnostic stress test who require a definitive diagnosis for guiding medical management, alleviating psychological stress, career or family planning, or insurance purposes.
• patients who have been admitted repeatedly to the hospital for suspected acute coronary syndromes (acute myocardial infarction or unstable angina) but in whom this diagnosis has not been established and in whom the presence or absence of CAD should be determined.
• patients with careers that involve the safety of others (e.g., pilots, fire fighters, police) who have questionable symptoms, suspicious or positive noninvasive tests, and in whom there are reasonable doubts about the state of the coronary arteries.
• patients with aortic stenosis or hypertrophic cardiomyopathy and angina in whom the chest pain could be due to IHD.
• male patients >45 and females >55 years who are to undergo a cardiac operation, such as valve replacement or repair, and who may or may not have clinical evidence of myocardial ischemia.
• patients who are at high risk after myocardial infarction because of the recurrence of angina or the presence of heart failure, frequent ventricular premature contractions, or signs of ischemia on the stress test.
• patients with angina pectoris, regardless of severity, in whom noninvasive testing indicates a high risk of coronary events.
• patients in whom coronary spasm or another nonatherosclerotic cause of myocardial ischemia (e.g., coronary artery anomaly, Kawasaki's disease) is suspected.
Comparative advantages of stress echocardiography and stress radionuclide perfusion imaging in diagnosis of CAD :
• advantages of stress echocardiography
• higher specificity
• versatility—more extensive evaluation of cardiac anatomy and function
• greater convenience/efficacy/availability
• lower cost
• advantages of stress perfusion imaging
• higher technical success rate
• higher sensitivity—especially for single vessel coronary disease involving the left circumflex
• better accuracy in evaluating possible ischemia when multiple resting LV wall motion abnormalities are present
• more extensive published data base—especially in evaluation of prognosis
 Grading :
• angina pectoris or cordis / angor pectoris / Rougnon-Heberden disease : a paroxysmal thoracic pain, often radiating to the arms, particularly the left, sometimes accompanied by a feeling of suffocation and impending death; it is most often due to ischemia of the myocardium and precipitated by effort or excitement
• chronic stable angina pectoris : angina pectoris occurring in attacks of predictable frequency and duration after provocation by circumstances that increase myocardial oxygen demands, such as exercise, emotional stress, or excitement, the precipitating circumstances tending to remain constant across episodes. If not treated, the quantity of fatigue needed to cause angina is always the same under the same initial conditions.
• syndrome X : a relatively benign syndrome of angina pectoris or angina-like chest pain associated with normal arteriographic appearance of the coronary arteries.
Pathogenesis : myocardial hibernation : chronic but potentially reversible cardiac dysfunction caused by chronic myocardial ischemia, persisting at least until blood flow is restored
Laboratory examinations :
• Holter monitor for resting angina
• echo-dipyridamole for effort angina
Therapy : guidelines for the treatment of chronic stable angina
• treatment of symptoms
• class I (therapies supported by evidence of efficacy)
• aspirin
• b-blockers—particularly with a prior history of MI
• calcium antagonists as initial therapy ... :
• if b-blockers are contraindicated
• with b-blockers to control symptom
• when b-blockers are stopped due to side effects
• sublingual nitroglycerin (tablets or spray) for relief of symptoms
• lipid lowering; LDL <2.6 mmol/L (100 mg/dL)
• health-promoting behaviors including smoking cessation, treatment of obesity, low-fat diet, supervised exercise program
• class IIa (weight of evidence in favor of a therapy)
• clopidogrel when aspirin is contraindicated
• long-acting nondihydropyridine calcium antagonists (not short-acting) instead of -blockers as initial therapy
• add long-acting nitrates and -blockers or calcium antagonists for symptoms as needed
• class III (therapies that are not useful and can be harmful)
• dypiridamole
• chelation therapy
• treatment of risk factors to improve outcomes
• class I
• smoking cessation
• treatment of dyslipidemia; LDL 2.6 mmol/L (100 mg/dL)
• ACEIs
• treatment of hypertension
• ideal weight and supervised exercise program
• low-fat diet
• treatment of diabetes using ADA National Guidelines
• class IIb (evidence of efficacy less well established)
• folate therapy for elevated homocysteine
• interventions directed at psychosocial stress
• class III
• hormone replacement therapy in postmenopausal women
• vitamins E and C
• treatment of depression
• chelation therapy
• herbal remedies and acupuncture
• treatment using revascularization
• class I
• CABG for significant left main disease
• CABG for 3-vessel coronary disease and reduced (50%) left ventricular function
• CABG for 2-vessel CAD including LAD disease and reduced LV function
• CABG for 3-vessel CAD plus high risk for PCI, abnormal (high risk) stress test, or diabetes
• CABG in patients with prior CABG or PCI, recurrent restenosis, and high risk on noninvasive testing
• PCI for 1- to 3-vessel CAD, normal LV function, no diabetes, lesions suitable (low risk) for PCI
• PCIor CABG for failed medical therapy and acceptable risk with either modality
• class IIa
• repeat CABG for multiple vein graft stenoses, particularly including the LAD
• PCI for simple focal vein graft stenosis
• PCI or CABG for 1- or 2-vessel disease and moderate ischemia on noninvasive testing, including disease of the LAD
• class IIb
• PCI instead of CABG in 2- or 3-vessel CAD (including the LAD) with controlled diabetes and lesions suitable (low risk) for PCI
• PCIfor technically suitable left main disease when CABG is not possible
• PCI instead of CABG in 1- to 3-vessel CAD when each lesion is suitable (low risk) but the patient exhibits reduced LV function, treated diabetes, history of malignant arrhythmia, survived sudden death
• class III
• PCI in left main disease or 3-vessel CAD with diabetes mellitus or poor LV function in patients who are candidates for CABG surgery
• PCI or CABG in patients with mild symptoms, no evidence of ischemia in noninvasive testing, and not yet given an adequate trial of medical therapy
• baseline coronary stenoses ( 60%) and no signs of ischemia on noninvasive testing
• follow-up—monitoring disease, testing, and therapies
• class I
• chest x-ray with new evidence of congestive heart failure (CHF)
• LV function testing for new evidence of CHF or MI
• echocardiogram for worsening of valvular disease
• treadmill testing for any change in clinical state
• stress imaging for any change in clinical state if the ECG cannot be interpreted or patient cannot exercise
• stress imaging for patients with prior revascularization and any change in clinical state
• coronary angiography in patients with obvious change in clinical state and limitations in daily activity despite medical therapy
• class IIb : repeat annual treadmill exercise testing in patients with no change in clinical state, who can exercise, have no ECG abnormalities at rest, with an estimated morality of  1% per year
• class III
• echo or nuclear stress imaging for LV function and ischemia with no change in symptoms, normal ECG, no MI, and no CHF
• repeat treadmill stress test in  3 years in stable patients with estimated annual mortality 1% on an initial evaluation shown by:
• low-risk Duke treadmill score
• negative imaging study
• normal LV function and no obstructive CAD
•  stress imaging if stable, can exercise, normal resting ECG
•  repeat coronary arteriogram with no change in clinical state, exercise testing, or stress imaging or insignificant CAD on initial examination
• nitrate therapy is an absolute contraindication to the use of PDE-5 inhibitors, however, since oral nitrates confer little benefit when added to optimum doses of b-blockers and/or CCBs, it followed that stable patients may be able to have their nitrate therapy discontinued or exchanged for a drug that does not react with a PDE-5 inhibitor, such as a CCB or b-blocker. Stable coronary patients with erectile dysfunction (ED) could have their oral nitrates discontinued to allow for safe use of a PDE-5 inhibitor. > 50% of the men on oral nitrates who were clinically stable with good ability to exercise had their nitrates discontinued in the presence of continuing b-blockers or CCB therapy and close follow-up. > 90% of the men no longer taking nitrates were treated with a PDE-5 inhibitor which was effective in restoring sexual function in 85%. Importantly, there have been no adverse cardiac events in the group^ref.
•  acute coronary syndromes (ACS)
• preinfarction or unstable angina (UA) pectoris (UAP) / crescendo angina: angina pectoris occurring unpredictably or suddenly increasing in severity or frequency; attacks may occur without provocation, such as during sleep or rest, may not respond to nitroglycerin, and may be of unusually long duration. Prinzmetal's (variant) angina is often included in this category

It can be classified :
• clinically
• Braunwald classification
• severity
• class I : new-onset angina under effort (may evolve to AMI !)
• class II : rest pain, but not within 48 hours (subacute)
• class III : rest pain within 48 hours (acute)
• clinical circumstances
• class A : noncardiac cause of increased angina identified ("secondary" UA)
• class B : no secondary cause identified ("primary" UA)
• class C : UA within 14 days after AMI
• medical treatment intensity
• class A : no treatment, just aspirin
• class B : typical oral (including sublingual) anginal therapy
• class C : intensive anginal therapy, including parenteral agents (e.g. heparin, intravenous nitroglycerin)
• previously diagnosed progressive or increasing angina : the quantity of fatigue needed to cause angina is not always the same under the same initial conditions

Canadian Cardiovascular Society (CCS) grading :
• grade I : ordinary physical activity does not cause angina, such as walking or climbing stairs. Angina occurs with strenuous, rapid, or prolonged exertion at work or recreation
• grade II : slight limitation of ordinary activity (angina occurs on walking or climbing stairs rapidly, walking uphill, walking or stair climbind after meas; in cold, in winf, or under emotional stress; or only during the few hours after awakening. Angina occurs on walking > 2 blocks on the level and climbing > 1 flight of ordinary stair at a normal pace and under normal conditions
• grade III : marked limitation of ordinary activity (angina occurs with walking 1-2 blocks on the level and climbing 1 flight of stairs at a normal pace)
• grade IV : inability to carry on any physical activity without discomfort (anginal syndrome may be present at rest)
• physiopathologically, as
• primary angina (also when resting ; due to decreased O₂ contribution)
• nonocclusive thrombus over a fissurated atherosclerotic plaque in coronary artery
• vasoconstriction of ...
• epicardial coronary artery due to fixed stenosis within 1 cm from spasm site (Prinzmetal's variant angina pectoris / angina inversa : a variant of angina pectoris, often considered a form of UA, in which the attacks occur during rest, exercise capacity is often well preserved, and attacks are associated with EKG elevation of the ST segment)
• microvascular (microvascular angina) (metabolic syndrome)
• organic coronary artery stenosis
• post-PTCA restenosis
• hypertrophic obstructive cardiomyopathy (HOCM)
• coronary arteritis => coronary thrombosis
• secondary angina (only under stress, due to increased O₂ need in presence of severe, stable coronary obstruction)
• mixed angina : organic stenosis => functional stenosis
Symptoms & signs (differential diagnosis with other causes of acute chest pain) :
• gravative low retrosternal pain (70-80%) irradiating to inner face of left arm, flexory surfaces of forearm and hand (eventually to neck, mandible angle, teeth, epigastrium (described as indigestion), interscapular region and right shoulder => limb). Pain is partly visceral, partly somatic and partly psychological (angor animi) in origin
• patient makes fist and holds it up to his chest, to describe the pain (Levine's sign)
• silent angina / angina sine dolore : an episode of coronary insufficiency in which no pain is experienced
Laboratory examinations :
• echocardiography : dyskinesia
• EKG : 50-75% have no alteration; 12% have ST elevation (> 1mm) or Q wave not known to be old; 4% have ischemia or strain on EKG not known to be old (ST depression > 1 mm or ischemic T waves); 51% have none of the preceding but prior angina; 14% have myocardial infarction (heart attack or nitroglycerin use) and no prior angina; Holter monitor
Possible interpretation of QT elevation with septal asynergia but normal angiography :
• post-infarction aneurysm :
• acute anginal attack ?
• noncardiac chest pain
• AMI (deep negative T waves = subendocardiac maldistribution)
• spontaneous reperfusion (e.g. after prolonged vasospasm)
• false negative of contrast echo
• variant angina
Therapy :
• it usually disappears within 1-5' (max 15') after removing stress. In the meanwhile sublingual nitrovasodilators, oxygen, Ca²⁺ channel blockers (CCB) and b-blockers can be administered (also used for ex juvantibus diagnosis)
• revascularization for class III patients
Risk stratification :
• acute risk : 10-40% evolve to AMI
• [cTnI]_plasma
• ST segment alterations
• recurrent ischemia
• chronic risk
• ejection fraction (EF)
• age
• previous ischemia
• previous ACBP
• diabetes mellitus
Prognosis : 15-50% mortality after 1 year since diagnosis
‡ (preinfarction angina : angina pectoris preceding a myocardial infarction)
• acute myocardial infarction (AMI) / heart attack

Epidemiology :
• incidence : 120,000 in Italy, 800,000 in USA (40% are relapses)
• first manifestation of CAD in 17-50% of cases
• lethality = 20-34%
• > 60% before intervention of a physician
• 50% within 1 hour
• 34% when at hospital =coronary ICUs=> 25-30% =thrombolysis within 6 hrs=> 6-7%.
• 25% of all mortality in Westernized countries
Aetiology :
• a 4-marker SNP haplotype in chromosome 13q12–13 spanning the gene ALOX5AP encoding 5-lipoxygenase activating protein (FLAP) is carried by 12% of people in Iceland and 29% of heart attack patients (RR = 2; deCode Genetics Inc. study). This haplotype also confers almost 2 times greater risk of stroke. Variants are found in 10% of people in USA. Another ALOX5AP haplotype carried by 8% of people in UK is associated with myocardial infarction. Stimulated neutrophils from individuals with myocardial infarction produce more LTB₄, a key product in the 5-lipoxygenase pathway, than do neutrophils from controls, and this difference is largely attributed to cells from males who carry the at-risk haplotype^ref.
• after accounting for other risk factors, such as high cholesterol, hypertension, obesity, cigarette smoking and diabetes, risk of heart attack or stroke in siblings who had at least one parent with early onset cardiovascular disease (younger than 55 in the father and younger than 65 in the mother) is increased by 100% in men and 70% in women
Localization : in 99% of cases the necrotic area corresponds to the field of distribution of the occluded arterial branch, while in 1% of cases the atherosclerotic artery induces a spasm in a near artery causing paradoxical AMIs.
• right ventricle (1%)
• left ventricle (99%)
• left coronary artery (75%)
• anterior descending artery (40-50%)
• before first diagonal branch : anterolateral infarction (also anterolateral wall of right ventricle)
• after first diagonal branch : anteroseptal infarction (anterior 2/3 of septum, apex, small part of anterior wall of left ventricle)
• circumflexed branch (15-25%) => posterolateral infarction : lateral and posterior segments of left ventricle
• right coronary artery (30-40%) : common trunk (33%) => inferoseptal infarction
• posterior 1/3 of septum
• lower wall of left ventricle
• posterior wall of left ventricle
• small part of
Pathogenesis : block of contraction within 1' => reversible megamitochondria => apoptosis of subendocardial layers => apoptosis of subepicardiac layers within 3-6 hours; myocardial stunning : temporarily impaired myocardial metabolic and contractile function, resulting from a brief episode of ischemia, that persists for a few days after reperfusion if this occurs within 2-3 hours from infarction (stunned myocardium). It is complete at 90% within 6 hours but can last for up to 48 hours.
Symptoms & signs (differential diagnosis with other causes of acute chest pain) :
• fatigue but psychomotory agitation due to decreased brain perfusion
• lavish perspiration
• dyspnea due to acute pulmonary edema (interstitial => alveolar)
• nausea and vomiting
• feeling of sudden death
• painful or painless (25%, expecially in elderlies, cachectics, and in patients affected by diabetes mellitus due to contemporaneous neuropathy)
• dilatation of annulus => mitral valve failure => : appearance of both 3^rd (and 4^th) tone leads to gallop rhythm
• Killip's staging
• 1 : neither coarse crackle nor 3^rd tone (30-40% prevalence => 8% lethality)
• 2 : coarse crackle on < 50% of auscultatory field or 3^rd tone (30-50% prevalence => 30% lethality)
• 3 : coarse crakles on > 50% of auscultatory field (= acute pulmonary edema) (5-10% prevalence => 44% lethality)
• 4 : cardiogenous shock (systemic blood pressure < 90 mmHg) and coarse crackles on all lung fields (10% prevalence => 80-100% lethality)
• compensatory tachycardia (bradycardia in lower IMAs) => 40% increase of systemic arterial pressure
Laboratory examinations :
• echocardiography : ischemic (pre-existing or new ?) non-contracting area (hypokinesia => akinesia => dyskinesia / aneurysm)
• EKG grading : please note some AMIs occur without EKG alterations ! Otherwise they can mark the 3 "I"s (ischemia, injury and infarction). Bundle branch blocks (BBB) can mask ischemia signs; 79% have ST elevation (> 1mm) or Q wave on EKG not known to be old; 20% have ischemia or strain on EKG not known to be old (ST depression > 1 mm or ischemic T waves); 4% have none of the preceding but prior angina; 2% have myocardial infarction (heart attack or nitroglycerin use) and no prior angina.
• minimal AMI / microinfarction / non-ST elevation myocardial infarction (NSTEMI) : diagnosed only with cTnI alterations, no EKG sign.

‡
• depression (> 1 mm) of ST segment and/or alterations of T wave marking ischemia (< 20')
• peaked T waves
• inverted T waves
Differential diagnosis of ST segment depression : accentuated Ta wave(both before and after QRS complex)
‡
• monophasic Pardee's wave / current of injury (elevation (> 1 mm) of ST segment beginning in the descending branch of the R wave and forming a dome-shaped wave that masks the T wave). It marks injury (20 < t < 40'). It is better seen in those leads which are parallel to the depolarization vector. E.g. in the stenosis of left or anterior descending branch Pardee's wave is seen in D₁, aV_L, V₃, V₄, V₅ and V₆.

Dislevellings are measured as follows :
• X-axis : point J (at the apex of S wave) + 0.04 s (= 1 mm = 1 square)
• baseline :
• PR baseline : the line joining
• PT baseline : the line joining the beginning of P wave and the ending of T wave
Aetiology : diffuse, multiple coronary stenosis (hypoperfusion due to shock, tachycardia or increased metabolic requirements) => infarction of inner third of myocardium
Pathogenesis : the percentage of circulating T_reg cells is significantly reduced in patients with STEMI, suggesting that this immunosuppressive T-cell subset is compartmentalized within the acutely ischemic myocardium to limit the ongoing inflammation associated with this condition, and that coronary revascularization is associated with partial reconstitution of peripheral T_reg pool^ref
Prognosis : fibrosis is more rapid than in transmural AMI
Differential diagnosis of ST segment elevation :
• ischemia/myocardial infarction :
• noninfarction, transmural ischemia (Prinzmetal's angina pattern)
• acute myocardial infarction
• postmyocardial infarction (ventricular aneurysm pattern)
• acute pericarditis :


• normal variant ("early repolarization" pattern)
• left ventricular hypertrophy (LVH)/LBBB (usually localized to V₁-V₂ or V₃)
• other (rarer)
• Brugada syndrome (RBBB-like pattern with ST elevations in right precordial leads) (usually localized to V₁-V₂ or V₃)
• class IC antiarrhythmic drugs (usually localized to V₁-V₂ or V₃)
• DC cardioversion
• hypercalcemia
• hyperkalemia
• hypothermia (J wave/Osborn wave)
• myocardial injury
• myocarditis
• tumor invading left ventricle
• trauma to ventricles
Complications : endocardiac thrombosis
This ST elevation myocardial infarction (STEMI) / nontransmural AMI / non-Q necrosis wave myocardial infarction (NQMI) (previously termed subendocardial AMI) can evolve to ...
‡
• Q necrosis wave myocardial infarction (QMI / QwMI) (previously termed transmural AMI) (> 2-3 hours).
• QRS alterations : the following criteria are not valid in presence of LBBB or preexcitation
• reduction of r wave voltage as compared to EKG tracing before AMI or interpolating precordial leads (not limb leads)
• abnormal, life-lasting QS complexes (necrosis "Q waves") in V₃, V₄, V₅, V₆, I, II, aV_F (QS complexes are always normal in DIII and aV_R; they can also appear during extreme clockwise rotation in V₁ and occasionally in V₂, and in vertical heart in aV_L)

It marks infarction (> 1-2 hours).
• anomalous q waves in  V₃, V₄, V₅, V₆, I, II, aV_F (QS complexes are always normal aV_R; they can also appear during extreme clockwise rotation in V₁ and occasionally in V₂, and in vertical heart in aV_L; DIII may have deep Q wave in horizontal heart or when the positive deflession in aV_L is greater than in aV_F)
• duration > 0.04 s
• voltage > 25% of the following R wave
• depression of ST segment
• negative T wave
Q waves in D₃ and aV_F may be due to "horizontal heart" (differential diagnosis after inspiration or with echocardiography)
Histology : necroptic findings "x" time after occlusion (timing is required both for legal purposes and to assess the timeliness of first-aid)
• 0-2 hours : 20% dies due to arrhythmias of pump failure
• none at macroscopic and light microscopy examinations
• TEM on biopsy of areas vascularized by the occluded artery (not trackable if AMI was due to vasospasm !) detects vacuolar degeneration of endoplasmic reticulum, megamitochondria, and irreversible rupture of sarcolemma
• the infarcted area is ill defined as it contains vital cardiomyocytes
• the threshold between ...
• completely reversible damage (< 20') : depletion of glycogen granules due to anaerobic metabolism => accumulation of lactate, inorganic phosphate and protons => binding of calcium to TnC is prevented.
• irreversible damage (> 20') : interruption of sarcolemma => alteration of DV_m => loss of Mg²⁺, hydropic degeneration, accumulation of lipids and calcium phosphate in mitochondrial matrix; contractile structures are the most resistant.
• 2-6 hours : visible infarction at macroscopic examination; IHC marks the healthy area as succinate dehydrogenase⁺ (tetrazolium salt precipitates only in the enzyme-rich areas) while infarcted areas doesn't stain due to mitochondrial degeneration
• 6-12 hours : at the periphery of infarcted area myocardiocytes contain streaming (more eosinophilic, parallel, waved fibers due to lack of contraction, passively made nearer by contraction of surrounding healthy myocardium)
• 12-24 hours : pale infarcted area at macroscopic examination; coagulative necrosis (marginated chromatin => pyknosis, homogeneous sarcoplasm) => colliquative myocytolysis => hydropic degeneration => peripheral myofibrils, central nucleus surrounded by empty halo
• day 2-3 : opaque look, increased consistence, dentellated red halo due to surrounding hyperemia, and microhemorrhages surrounding an ochre infarcted area (color is due to fatty degeneration of intravascular granulocytes); cardiomyocytes have lost nuclei and striae and appears as hyalinous masses; neutrophils in interstitium if patient died during bacterial infection
• day 4-5 : yellow infarcted area; many granulocytes and lymphocytes in interstitium
• day 7-10 : soft (myomalacia) with pus surrounding hemorrhage; granulation tissue (neutrophils are replaced by macrophages) with neocapillaries
• week 3-5 : pink cicatricial tissue => complications or maturation to fibrous white tissue
• month 3 : stabilized scar. No dating can be practiced after 3 months (old myocardial infarction (OMI))
Differential diagnosis of Q waves :
• physiologic or positional factors :
• normal variant "septal" q waves
• normal variant Q waves in V₁ to V₂, aV_L, III, and aV_F
• left pneumothorax or dextrocardia : loss of lateral R-wave progression
• myocardial injury or infiltration
• acute processes : myocardial ischemia or acute myocardial infarction, myocarditis, hyperkalemia
• chronic processes : acute myocardial infarction, idiopathic cardiomyopathy, myocarditis, amyloid, tumor, sarcoid, scleroderma, Chagas' disease, echinococcus cyst
• ventricular hypertrophy/enlargement :
• left ventricular (poor R-wave progression (small or absent R waves in the right to midprecordial leads)
• right ventricular (reversed R-wave progression (progressive decrease in R-wave amplitude from V1 to the mid- or lateral precordial leads) or poor R-wave progression (small or absent R waves in the right to midprecordial leads), particularly with chronic obstructive lung disease)
• hypertrophic cardiomyopathy (may simulate anterior, inferior, posterior, or lateral infarcts)
• conduction abnormalities :
• LBBB (poor R-wave progression (small or absent R waves in the right to midprecordial leads)
• Wolff-Parkinson-White patterns
Mechanical complications (1-2%) :
• early remodeling => heart aneurysm (expecially in left ventricle) : necrotic myocardium expands during systole. Usually a late complication.

‡
• heart rupture (causing 25% of deaths; usually in first 2-3 days and at the beginning of week 2) due to ischemia of...
• ... free wall => continuous murmur due to blood flowing into pericardium (hemopericardium or intramural dissecating hematoma)
• ... interventricular septum => blood flows from left ventricle to right ventricle => (new) pansystolic regurgitation murmur
• ... papillary muscle(s) => acute AV valve failure ("sail valve") => (new onset) pansystolic regurgitation murmur
• mitral valve => acute pulmonary postcapillary arterial hypertension
Anterior AMI :

• occlusion of the proximal left anterior descending coronary artery (LAD) : instead of the signature ST-segment elevation, the ST segment shows in 2% of patients a 1- to 3-mm upsloping ST-segment depression at the J point in leads V1 to V6 that continued into tall, positive symmetrical T waves. The QRS complexes were usually not widened or were only slightly widened, and in some there was a loss of precordial R-wave progression. In most patients there was a 1- to 2-mm ST-elevation in lead aVR^ref
Anterolateral AMI :

Inferior AMI :

Inferior AMI + LBBB :

AMI + RBBB + LAHB :

• laboratory blood examinations (myocardial enzymes and structural proteins : modern therapies modify analyte washout and cause faster clearance)
• examinations marking flogosis
• CRP
• SAA
• total Sia
• fibrinogen
• examinations marking thrombosis
• thrombus precursor protein (TpP™) : thrombin cleaves fibrinopeptide A from the fibrinogen molecule exposing polymerization sites on the newly formed desAA fibrin monomer units. Fibrin monomers can complex with intact fibrinogen, degradation products of fibrinogen and fibrin, and polymerize with other desAAfibrin monomers. This milieu of fibrin complexes, also known as soluble fibrin, is an indicator of the level of thrombin activity in the circulation. As the polymerization of desAAfibrin proceeds, thrombin removes another set of peptides, (fibrinopeptide B), from the fibrinogen molecule resulting in the formation of a species known as desAABBfibrin. These soluble polymers are the immediate precursor to insoluble fibrin and are thus referred to as Thrombus Precursor Protein (TpP™). As polymerization proceeds, the soluble fibrin polymeric entities, TpP™ become incorporated into the thrombus as insoluble fibrin polymers.
• selectin P
• examinations marking ischemia
• glycogen phosphorylase BB (GPBB)
• examinations marking necrosis : they allow estimation of timing and width of the necrotic area unless downstream vasoconstriction causes slow washout
• myoglobin (Mb) (M_r = 17.8 kDa => released in blood vessels after 2 hours, 30x peak after 4 hours, normal after 18 hours)
• total CPK (M_r = 80 kDa => released in lymphatic vessels after 4 hours, 37x peak after 8 hours, normal after 2-3 days)
• total CPK-MB : CPK-MB₂ / CPK-MB₁ rate increases after 90'. Mass assay has better sensitivity than catalytic activity determination.
• total CPK-MM: CPK-MM₃ / CPK-MM₁ rate increases after 3 hours
False positives : i.m. injection, trauma, effort, ...
• cTnI (after 2-4 hours > 0.5 mg/dL (96% sensitivity and 94% specificity), 75x peak after 12 hours, normal after 5-9 days) : 3-6% free in cytosol, 94-97% myofiber-associated; detected with 2 mAbs directed against the stabile conformation epitope of cTnI (ie. aa. 30-110). In plasma ternary cTnI-C-T complexes > binary cTnI-C complexes > free cTnI. 50% is phosphorylated in Ser²³ and/or Ser²⁴, unknown % has Cys⁸⁰-Cys⁹⁷ disulfide bond : electrostatic interaction with heparin may interfere with assays. On the contrary of cTnI, cTnT can be overexpressed in skeletal muscles of patients with DMD, polymyositis, and severe renal failure
• SGOT1 / AST1 (after 8-12 hours, 5x peak after 36 hours, normal after 4-7 days)
• total LDH (after 12-24 hours, peak after 36 hours, normal after 7-10 days)
• LDH₁ / aKBDH (82% increase)
• LDH₂ (minor increase)
• fatty acid binding protein 3 (FABP3)
• the level of the inactive N-terminal fragment of pro–BNP (NT-pro-BNP) is a strong predictor of mortality among patients with ACS and is a marker of long-term mortality in patients with stable coronary disease, providing prognostic information above and beyond that provided by conventional cardiovascular risk factors and the degree of left ventricular systolic dysfunction^ref.
Prophylaxis : antibacterial chemoprophylaxis before minor and major surgery in valvulopathic patients to prevent bacterial infective endocarditis.
Therapy :
• "MONA"
• morphine (it decreases preload, inotropy, and chronotropy, thus favorably altering determinants of myocardial oxygen consumption) (no in right ventricle AMIs !)
• oxygen
• nitrovasodilatators (no in right ventricle AMIs as they decrease preload ! Also antiplatelet action)
• aspirin / acetylsalicylic acid (ASA) (150 to 325 mg of aspirin in a nonenteric formulation orally or 500 mg intravenously unless they had received at least 325 mg of aspirin within the prior 24 hours. After the first 24 hours, maintenance therapy with 75 to 325 mg of aspirin once daily was to be administered orally for at least 30 days)
• reperfusion within 3-6 hours (6-12 hours only if pain and ST elevation persist)
• thrombolytic drugs (practice within 1 hour; useless if practiced after 12 hours), reduces mortality from 13% to 8%. Anyway 30-40% experience failure to open, expecially when white thrombi are involved (drugs don't act on platelets) or functional stenosis coexist. Rescue PCI should be considered for patients in whom reperfusion fails to occur (< 50% ST-segment resolution) within 90 minutes after thrombolytic treatment^ref.
• anti-platelet drugs such as clopidogrel could be used in patients with an allergy to aspirin, or they could be added to aspirin at the investigator's discretion, as part of the patient's treatment regimen^{ref1, ref2, ref3}
• anticoagulant^ref : fondaparinux (2.5 mg daily) is similar to enoxaparin (1 mg/kg of body weight twice daily) for a mean of 6 days in reducing the risk of ischemic events at 9 days, but it substantially reduces major bleeding and improves mortality and morbidity at 180 days^ref. Although low-molecular-weight heparins are generally indicated in myocardial infarction without ST-segment elevation or unstable angina, the limited evidence regarding their use in myocardial infarction with ST-segment elevation is conflicting. Prehospital administration of enoxaparin, as compared with unfractionated heparin, caused an increase in intracranial hemorrhage among elderly patients^ref. In patients receiving fibrinolysis for ST-elevation myocardial infarction, treatment with enoxaparin (for patients < 75 years of age, 30-mg intravenous bolus followed 15 minutes later by a s.c. injection of 1.0 m/kg, with injections administered every 12 hours. For patients >75 years of age, the i.v. bolus was eliminated and the s.c. dose was reduced to 0.75 mg/kg every 12 hours. For the first 2 subcutaneous injections, a maximum of 100 mg (for patients < 75 years old) or 75 mg (for those > 75 years old) was to be administered) throughout the index hospitalization is superior to treatment with unfractionated heparin (beginning with an intravenous bolus of 60 U/kg (maximum, 4000 U) followed within 15 minutes by an infusion of 12 U/kg/h (initial maximum, 1000 U/h)) for 48 hours but is associated with an increase in major bleeding episodes^ref. Prolonged i.v. infusions of unfractionated heparin have not been shown to prevent reocclusion after angiographically proven successful fibrinolysis, leading to the current recommendation to limit the duration of infusion to 48 hours^{ref1, ref2}. The use of unfractionated heparin requires frequent monitoring to adjust the infusion rate to maintain a therapeutic range of anticoagulation^ref

• surgical reperfusion
• (cardiac catheterism => coronarography =>) percutaneous transluminal coronary angioplasty (PTCA) / percutaneous coronary intervention (PCI) / percutaneous coronary revascularization within 60' reduces mortality only from 8% to 4%, but 1 case out of 3-4 undergoes in-stent restenosis with 20% of patients (associated with higher levels of serum ACE due to insertion/deletion polymorphism in intron 16) need a new revascularization procedure within 6 months. Aspirin and ticlopidine are used together for 1 month after PTCA, then only aspirin is left. The incidence of in-stent restenosis after percutaneous coronary intervention ranges from 5 to 35% after the implantation of an uncoated stent and is somewhat lower after the implantation of a drug-eluting stent in patients who are at moderate risk^ref. Treatment of in-stent restenosis with a balloon catheter for coronary angioplasty is limited by high rates of restenosis (39 to 67%)^{ref1, ref2, ref3, ref4, ref5}. Other approaches, such as the implantation of a second, uncoated stent or mechanical debulking (e.g., rotablation), have not been associated with a significant reduction in recurrent in-stent restenosis^ref. Intracoronary irradiation (brachytherapy) has been found to be effective in this setting, with recurrence rates of 16 to 23%^{ref1, ref2}. The implantation of drug-eluting stents in restenotic stented lesions has had similar results. Rates of restenosis of 13 to 20% with the Cypher stent and of 15 to 22% with the Taxus stent have been reported^{ref1, ref2, ref3, ref4, ref5, ref6}. However, these stent-in-stent approaches involve two or more layers of metal in a native coronary artery. Furthermore, a restenosis rate of 43% has been reported after treatment of a restenotic drug-eluting stent with a second drug-eluting stent^ref. Restenosis that is caused by neointimal hyperplasia is a slow process, suggesting that the local administration of a drug would need to be prolonged in order to be beneficial. Stent-based local drug delivery provides sustained drug release with the use of stents that have special features for drug release, such as a polymer coating^{ref1, ref2}. However, cell-culture experiments indicate that even brief contact between vascular smooth-muscle cells and lipophilic taxane compounds can inhibit the proliferation of such cells for a long period^{ref1, ref2, ref3}. In experiments in swine, intracoronary delivery of paclitaxel by means of contrast medium or a drug-coated balloon catheter resulted in concentrations of the drug in vascular tissue that were high enough to have antiproliferative effects, thus leading to a significant reduction in neointimal proliferation^{ref1, ref2, ref3, ref4}. In these studies in animals, the most pronounced reduction of neointimal formation was seen with paclitaxel-coated balloon catheters^{ref1, ref2}. The Treatment of In-Stent Restenosis by Paclitaxel-Coated Balloon Catheters (PACCOCATH ISR), was to investigate the use of angioplasty balloon catheters coated with paclitaxel for the treatment of coronary in-stent restenosis : treatment of coronary in-stent restenosis with paclitaxel-coated balloon catheters significantly reduced the incidence of restenosis. These data suggest that the inhibition of restenosis by local drug delivery may not require stent implantation and sustained drug release at the site of injury^ref
• aorto-coronary by-pass (ACBP) / coronary artery bypass grafting (CABG) reduces mortality more than PTCA
Compared with minimally invasive direct coronary artery bypass (MIDCAB) grafting, left anterior descending (LAD) artery stenting offers similar outcomes with shorter hospital stays : the results are better in patients with diabetes who had MIDCAB than in those diabetic patients who had stents^ref.
Comparison of revascularization procedures in multivessel disease
• percutaneous coronary intervention (PCI)
• advantages :
• less invasive
• shorter hospital stay
• lower initial cost
• easily repeated
• effective in relieving symptoms
• disadvantages :
• restenosis
• high incidence of incomplete revascularization
• unknown effect on outcomes in patients with severe left ventricular dysfunction
• limited to specific anatomic subsets
• poor outcome in diabetics with 2- or 3-vessel coronary disease
• coronary artery bypass grafting (CABG)
• advantages :
• effective in relieving symptoms
• improved survival in certain subsets
• ability to achieve complete revascularization
• disadvantages :
• cost
• increased risk of a repeat procedure due to late graft closure
• morbidity and mortality of major surgery
Restenosis (experimental animal model : rat carotid balloon damage) can be prevented by
• coating the stent (drug-eluting stent (DES)) with ...
• rapamycin (Cypher; source : Cordis). Complication : fibrosis.
• sirolimus
• paclitaxel
• gene therapy
• photoangioplasty by photodynamic therapy (PDT)
Evaluation of reperfusion : thrombolysis in myocardial infarction (TIMI) criteria :
• grade 0 : no anterograde perfusion. No-reflow phenomenon : when blood flow is restored to a part following prolonged ischemia, there is initial hyperemia followed by a gradual decline in perfusion until there is almost no blood flow. It may be caused by :
• distal thromboembolism
• high microvascular resistance : damage may be due to
• ischemia reperfusion injury (IRI)
• tissue oedema
• leukocyte embolism
• grade 1 flow : minimal penetration of contrast
• grade 2 flow : delayed flow of contrast
• grade 3 flow : brisk flow of contrast
Vessels with TIMI grade 0 or 1 are considered occluded and those with grade 2 or 3 are considered patent
• diuretics to treat acute pulmonary edema in left ventricle AMI
• plasma expanders to increase preload in right ventricle AMI
• defibrillation to treat of ventricular fibrillation: it reduces mortality from 25% to 13%.
• b₁-AR antagonists (atenolol 5 mg i.v. => maintenance p.o.) have negative inotropic and chronotropic effects, decreasing O₂ requests, but are contraindicated in left ventricular dysfunction
• ACEIs : they should be associated to b-blockers ony if there is left ventricular dysfunction !
• antiarrhythmic drugsto reduce risk of VF but they cause increased risk of complete intraventricular block or ventricular asystolia (cardiac standstill).
• L-type selective Ca²⁺ channel blockers (CCB)
• Mg₃(SO₄)₂ to prevent VF
• lidocaine i.v.
Salvage therapy : therapy or arrhythmias, left ventricular dysfunction acute pulmonary edema and shock, ventricular unloading, residual ischemia, tendineal chord and septal surgery
Prognosis according to % of necrotic left ventricle myocardium :
• < 10% : normokinesis
• > 10% : decrease of ejection fraction
• > 15% : left ventricle change in shape from a rotation ellypsoid into a sphere with decreased contractile effectiveness
• > 25% : acute or chronic symptomatic CHF
• > 40% (during AMIs involving the common trunk or the left / anterior interventricular descending branch of left coronary artery, which feeds 70% of whole myocardium) : cardiogenous shock
Timing :
• acute (< 24 hrs)
• subacute / recent (3 months)
• pregress (> 3 months)
Cardiac stress = t / myocardial thickness = (P ^. r) / myocardial thickness.
Complications (in 80% of AMIs) :
• early
• acute left (and sometimes even right) ventricle failure => increased P_EDV => decreased ejection fraction => cardiogenous shock (7.5 %, only if > 40% left ventricle is involved)
• shoulder-hand syndrome : reflex sympathetic dystrophy limited to the upper extremity, marked by pallor or rubor, pain, diaphoresis, edema, or osteoporosis, following injury to nerves or blood vessels
• arrhythmic complications
• sinusal bradycardia (33%) due to compensatory vagal hypertone after low heart AMIs (20%)
• atrial fibrillation (10-15%) and/or atrial flutter => thromboembolism => stroke
• if the AV node-vascularizing branch of left coronary artery is involved => transient AV block (20%), treated with transient pace-maker and atropine.
• life-threatening or malignant arrhythmias : premature ventricular complexes (the commonest complication) : if > 6/minute,  polymorphic, R/T => ventricular tachycardia => primary ventricular fibrillation => PEA (expecially during first 4 hours; only 4% when at hospital)
• Laubry-Soulle syndrome
• late
• ischemic complications due to thrombotic reocclusion, spasm, or low coronary output
• post-AMI angina pectoris
• early
• late : within 2 weeks
• extension within 24 hrs
• relapse after 24 hrs
• chronic left (and sometimes even right) ventricle failure =>
• relapsing AMIs
• small blood vessels diseases
• pericarditis
• epistenocardiac pericarditis within 4-7 days from a transmural AMIs => cardiac tamponade
• Dressler syndrome
• secondary ventricular fibrillation within some weeks
• heart aneurysm
• chronic reparative heart aneurysm
• LV scar tissue > 40% => dilated cardiomyopathy (if scar tissue < 40% compensatory muscular hypertrophy is effective)
• thrombosis
• over damaged endocardium (nowadays prevented by thrombolytic drugs) or transmural => arterial thromboembolism (=> embolic stroke, splenic, renal, or intestinal embolism)
• pulmonary thrombembolism due to :
• deep vein thrombosis in patients forced to lye in bed after AMI => venous thrombembolism
• right heart thrombosis
• paradoxical embolism
• chronic mitral valve failure due to scarring or dilatation of annulus
• acute renal failure (ARF)
Prevention of recurrences : treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested. Such treatment should therefore not be recommended. The mean total homocysteine level was lowered by 27% among patients given folic acid plus vitamin B₁₂, but such treatment had no significant effect on the primary end point (risk ratio, 1.08). Also, treatment with vitamin B₆ was not associated with any significant benefit with regard to the primary end point (relative risk of the primary end point, 1.14). In the group given folic acid, vitamin B₁₂, and vitamin B₆, there was a trend toward an increased risk (relative risk, 1.22)^ref. Supplements combining folic acid and vitamins B₆ and B₁₂ did not reduce the risk of major cardiovascular events in patients with vascular disease^ref
Web resources : Heart attack warning signs at AHA
Pathogenetics outputs => symptoms & signs
• cardiomegaly = myocardium hypertrophy + dilatation of chamber(s)
• congestive or dilated cardiomyopathy (DCM) / Abramov's "primary myocarditis" : a syndrome of left and/or right ventricular dilatation, systolic contractile dysfunction (dilatation of chamber(s) + myocardium eccentric hypertrophy/normothrophy => EDV > 117% of the normal => hypocontractility due to Maestrini-Starling law), and often congestive heart failure; the course is usually progressive with a poor prognosis

Epidemiology : 0.2 % prevalence (males > females); incidence = 5-8 new cases per 100,000 people/year
Aetiology (eccentric shape : RWT < 0.45)
• intrinsic aetiology (20%)
• 1 : autosomic dominant (56%)
• cardiomyopathy, dilated 1A (autosomal dominant)
• lamin A/C
• cardiomyopathy, dilated 1B (autosomal dominant)
• cardiomyopathy, dilated 1C (autosomal dominant)
• cardiomyopathy, dilated 1D (autosomal dominant)
• cardiomyopathy, dilated 1E (autosomal dominant)
• cardiomyopathy, dilated 1F (autosomal dominant)
• cardiomyopathy, dilated 1G (autosomal dominant)
• cardiomyopathy, dilated 1H (autosomal dominant)
• cardiomyopathy, dilated 1I / desmin
• cardiomyopathy, dilated 1J (autosomal dominant)
• cardiomyopathy, dilated 1K (autosomal dominant)
• cardiomyopathy, dilated 1L / sarcoglycan, delta (35kDa dystrophin-associated glycoprotein)
• cardiomyopathy, dilated 1M (autosomal dominant)
• desmoplakin => dilated cardiomyopathy with woolly hair and keratoderma
• myosin binding protein C, cardiac
• myosin, heavy polypeptide 7, cardiac muscle, beta
• titin
• 2 : autosomic recessive (16%) :
• cardiac a-actin
• cardiomyopathy, dilated 2A (autosomal recessive)
• 3 : X-linked recessive (5-10%)
• dystrophin
• cardiomyopathy, dilated 3A / tafazzin (Barth syndrome)
• autoimmunity :
• autoimmune myocarditis
• infectious cardiomyopathy : chronic myocardial disease following infection.
• peripartum or postpartum cardiomyopathy : cardiac enlargement and CHF of unknown cause beginning in the last month of pregnancyor the first few months after delivery.
• acute myocardial infarction (AMI) (limited to infarctioned area)
• systemic arterial hypertension
• toxic
• alcoholic cardiomyopathy : dilated cardiomyopathy occurring in patients with a history of chronic ethanol abuse; it is believed to be due to a direct toxic effect of alcohol or its metabolites
• beer-drinkers' cardiomyopathy: cardiac dilatation and hypertrophy due to excessive beer consumption; in at least some cases it has been caused by addition of cobalt to the beer during manufacturing
• type 2 glycogen storage disease (GSD)
• hypothyroidism (myxedema heart disease)
Symptoms : dyspnea, tachycardia
Signs :
• jugular vein distension (JVD) in right cardiomegaly
• anterior displacement of ventricle during protosystole causes the "ictus of the point" at the apex beat (the most inferolateral point of visible or palpable pulsation of the chest wall due to movement of the apex of the heart, normally medial and superior to the intersection of the left midclavicular line and the 5th left intercostal space. Generally it corresponds roughly to the position of the apex of the heart and is often the point of maximal impulse) : the pericardium lifts the thoracic wall in intercostal spaces. Normally sized 2 cm² :
• larger in anterior and left body displacement, during physical exercise or emotions, or pathological conditions such as left ventricular hypertrophy, fever, retraction of anterior lung border
• smaller in pericardial effusion, pulmonary emphysema and CHF
Strenght is directly related to size.
• left ictus of the point : the pericardium lifts the 5^th intercostal space 1 cm internal to left hemiclavear line (displacements : lower and more internal in longitype, higher and more lateral in brachytypes; higher in expiration, lower in inspiration; 2 cm more lateral in left decubitus; left displacement in left ventricular hypertrophy, right pleural effusion or pneumothorax, left fibrothorax, right hemidiaphragm lifting, atelectasis; right displacement in left pleural effusion or pneumothorax, right atelectasis or pneumothorax or paralysis of left hemidiaphragm, dextrocardia). Varieties :
• lifting or shaking ictus (only in protosystole) involving most precordial area, due to ..
• mitral valve failure
• aortic valve failure (cupuliform ictus)
• left ventricle aneurysm
• hyperdynamic circulation
• protracted or sustained ictus (also during mesosystole), due to aortic valve stenosis
• reentrying ictus, due to constrictive pericarditis
• fragmented ictus, corresponding to 3^rd tone and 4^th tone
The ictus cannot be seen when behind a rib or large breast (assess the patient during deep inspiration), obese patients, CHF, pulmonary emphysema, large pericardial effusion.
• right ictus due to hypertrophy of right ventricle : the pericardium lifts the centrum cordis (on left or rarely right parasternal line, 4th-5th intercostal space) or the epigastrium. It is physiological in thin patients, while it can arise from one of the following diseases :
• congestive heart failure
• cor pulmonale
If right ventricular hypertrophy is severe during systole you can observe a reentry of the thoracic wall due to reduced right ventricular volume. Harzer's sign : palpation of right ictus with the thumb over xiphoid process
• ictus of the 2nd right intercostal space occurs in ascending aortic aneurysm
• ictus of the 2nd left intercostal space occurs in uplmonary artery ectasia or rarely due to left atrial dilation or hypertrophy
• jugular ictus occurs in aortic arch aneurysm or ectasis
The reentry of the thoracic wall during systole (as sensed at peripheral pulses) may be due to adhesions between parietal pericardium and chest wall.
• heart palpation : examiner at patient's right uses third phalanx of second and third right fingers to sense prominences and dolorability at the end of expiration (when interposed air is minimal). Palpation and grading of size and strength of ictus of the point is facilitated by left lateral decubitus or, if seated, left anterior displacement, or displacing eventual large left breast with left hand.
• thrill : a sensation of vibration felt by the examiner on palpation of the body, such as over the heart during loud, harsh cardiac murmurs
• aneurysmal thrill : a thrill felt on palpation of an aneurysm.
• Oliver's or Porter's sign / tracheal tugging : a pulling sensation in the trachea, due to aneurysm of the arch of the aorta; it is most apparent when the head is extended and a finger is placed on the thyroid cartilage
• Cardarelli's sign : palpation of rhytmic laryngeal palpation during its lateral rotation suggests aortic arch aneurysm
• aortic thrill : one felt over the aortic orifice in disease of its valves.
• diastolic thrill : a vibratory sensation felt over the precordium during ventricular diastole, as in advanced aortic insufficiency.
• presystolic thrill : a thrill felt just before the systole by the hand placed over the apex of the heart.
• systolic thrill : a thrill felt on systole over the precordium, as in aortic stenosis, pulmonary stenosis, and ventricular septal defect.
• fat thrill : a peculiar thrill sometimes felt in abdominal examinations due to excessive fatness of the parietes.
• hydatid fremitus or thrill : a tremulous impulse sometimes felt on palpation of the body surface over a hydatid cyst
• purring thrill : a thrill of a quality suggesting the purring of a cat.
• fremitus : a vibration perceptible on palpation
• (friction) rub : an auscultatory sound caused by the rubbing together of two serous surfaces, as in a pericardial rub or pleural friction rub
• pericardial (friction) rub : a scraping or grating noise heard with the heart beat, usually a to-and-fro sound, associated with pericarditis or other pathological condition of the pericardium. They persist when the patient stops breathing
• pleural or pleuritc friction rub : a rub produced by friction between the visceral and costal pleurae. They disappear when the patients stops breathing
• pleuropericardal rub : a rub produced by friction between the parietal pleura and parietal pericardium. They disappear when the patients stops breathing
• pericardial fremitus : a thrill of the chest wall due to the friction of the surfaces of the pericardium over each other.
• pleural fremitus : a palpable vibration of the wall of the thorax due to a friction rub between the opposing surfaces of the pleura.
• bronchial or rhonchal fremitus : palpable vibrations produced by the passage of air through a large bronchial tube filled with mucus
• subjective fremitus : one felt by the patient on humming with the mouth closed
• tactile fremitus : a strong vocal fremitus that can be felt by a hand on the thorax
• tussive fremitus : one felt on the chest when the patient coughs
• pectoral or vocal fremitus (VF) : a thrill caused by speaking, perceived by the ear of the auscultator applied to the chest
Laboratory examinations :
• chest X-ray: moderate to marked cardiac silhouette enlargement with cardiothoracic ratio (CTR) : the ratio of the transverse diameter of the heart to the internal diameter of the chest at its widest point just above the level of the dome of the diaphragm, a rough guide to cardiac enlargement, being normally < 0.5. (distance between right-atrium incision in right lung and sagittal layer + distance between left-ventricle incision in left lung and sagittal layer) / (maximal thorax diameter) > 0.45; pulmonary venous hypertension
• EKG :
• QRS amplitude in V₁ + V₆ > 3.5 mV = 35 mm on paper.
• ST segment and T wave abnormalities
• the lead with the highest potential is D₁ (left axial deviation in left cardiomegaly) or D₃ (right axial deviation in right cardiomegaly) instead of D₂. In pneumopathics posterior axial deviation occurs, simulating right bundle branch block (RBBB).
• echocardiography : left ventricular dilatation and dysfunction (diffuse hypokinesia)
• CPK-MB concentration
• radionuclide ventriculogram : left venricular dilatation and dysfunction
• cardiac catheterization : left ventricular dilatation and dysfunction, elevated left- and often right-sided pressures, diminished cardiac output
• endomyocardial biopsy. Miscroscopic anatomy : hypertrophic, stirred or degenerated (perinuclear vacuolization and colliquative myocytolysis) cardiomyocytes, endomyocardial fibrosis (EMF), and inflammatory infiltrates
• genome loci
Therapy : heart transplantation
Experimental animal models : mice deficient in PD-1 immunoinhibitory coreceptor develop autoimmune dilated cardiomyopathy (DCM), with production of high-titer autoantibodies against cardiac troponin I (cTnI) (encoded by a gene in which mutations can cause familial hypertrophic cardiomyopathy) and induce heart dysfunction and dilatation by chronic stimulation of voltage-dependent L-type Ca²⁺ influx in cardiomyocytes.
• hypertrophic cardiomyopathy (HCM) : a cardiomyopathy, possibly of autosomal dominant inheritance, marked by ventricular hypertrophy, particularly of the left ventricle and often involving the interventricular septum more than free wall, with or without and interventricular systolic pressure gradient, with diastolic dysfunction (hypercontractility) manifest as impaired ventricular filling; usually of a nondilated left ventricular cavity

Epidemiology : HCM is the leading cause of sudden death in people under the age of 30. About 0.1% to 0.2% of the world's population has HCM; each year, about 1% of these die^ref
Aetiology :
• primitive / inherited (autosomal dominant : 40% in 2 successive generations) : 200 or so mutations in 12 genes, all of which code for the sarcomeric proteins in heart muscle have, to date, been linked with HCM^ref.

Aetiology :
• cardiac a-actin
• type 1 : myosin, heavy polypeptide 6, cardiac muscle, a
• type 1 : myosin, heavy polypeptide 7, cardiac muscle, b
• cardiomyopathy, hypertrophic 2
• cardiomyopathy, hypertrophic 3
• tropomyosin 1 (a)
• type 4 : myosin binding protein C, cardiac
• cardiomyopathy, hypertrophic 6
• myosin, light polypeptide 2, regulatory, cardiac, slow
• myosin, light polypeptide 3, alkali; ventricular, skeletal, slow
• myosin light chain kinase 2, skeletal muscle
• PK-Ag₂ (with WPW syndrome)
• cardiac troponin I (cTnI)
• cardiac troponin T2
• titin
• A=>C 1166 transversion in AT₁receptor gene
• secondary to increased afterload...
• right atrial hypertrophy (RAH)

Aetiology :
• right atrial ischemia or infarction
• as for RVH
Laboratory examinations : EKG : P wave in DII, DIII, or aV_F > 3 mm. Other findings : the positive component of P wave in V₁ > 1.5 mm; usually associated to signs of RVH. Frequently accentuation of atrial repolarization wave.
• left atrial hypertrophy (LAH)

Aetiology :
• as for LVH
• mitral stenosis
Laboratory examinations : EKG : differential diagnosis from right atrial ischemia or infarction with PMH
• bifid P wave in DI, DII, aV_F or aV_L or > 0.12 s
• main negative component (completely negative deflession or greater underlying area) of P wave in V₁
• usually associated to signs of LVH; if pure mitral stenosis associated with RVH
• biatrial hypertrophy

Aetiology : as for biventricular hypertrophy
Laboratory examinations : EKG : satisfies criteria for both right atrial hypertrophy and LAH
• right ventricular hypertrophy (RVH)

Aetiology :
• pressure or systolic overload
• pulmonary arterial hypertension (PAH)
• left heart failure
• cor pulmonale : enlargement of common trunk of pulmonary artery => right ventricle => right atrium, due to pulmonary arterial hypertension (PAH) secondary to a pulmonary disease (not secondary to congenital or acquired left heart failure !)
• acute cor pulmonale due to acute pulmonary arterial hypertension

Symptoms & signs : McGinn-White sign : a Q wave and late inversion of the T wave in lead III, low ST intervals and T waves in lead II, and inverted T waves in chest leads V2 and V3, the electrocardiographic evidence of right ventricular dilatation due to massive pulmonary embolism, plus the clinical signs of acute cor pulmonale.
• chronic cor pulmonaledue to chronic pulmonary arterial hypertension (rarely a cause of RVH !)
Laboratory examinations : chest X-ray (common trunk of pulmonary artery corresponds to the second left arc)
Prognosis : survival after 5 years from diagnosis = 60-70% (deaths are due to arrhythmias or evolution to CHF).
• pulmonic valve stenosis
• Fallot's tetralogy
• volume or diastolic overload
• atrial septal defect
• tricuspid valve failure
• anomalous pulmonary blood flow return
• ventricular septal defect (VSD)
• patent ductus arteriosus (PDA)
Laboratory examinations : EKG :
• right axial deviation of QRS on frontal plan excluding other causes
• dominant R wave (Rs, R, RR', or qR complex) in V₁(differential diagnosis)
• no signs of anterolateral AMI (which has right axial deviation and dominant R wave in V₁, too)
• QRS duration < 0.12 s (otherwise the presence of a dominant R wave in V₁ would suggest RBBB, a condition that, when present, impairs diagnosis of RVH)
• secondary findings :
• ST segment depression and T wave inversion in some leads between V₁ and V₄
• deep S wave in V₅, V₆ and also in DI and aVL
• signs of right atrial hypertrophy
• left ventricular hypertrophy

Aetiology :
• pressure or systolic overload
• systemic arterial hypertension(cor bovinum if weight > 1 kg)
• aortic valve stenosis
• aortic coartaction
Pathogenesis :  parietal stress => inhibition of cardiac performance => humoral factors (catecholamines, AT-II, ET) and genetic background => compensatory hypertrophy =>
• reduced diastolic compliance => remodeling
• reduced systodiastolic performance => congestive heart failure (CHF)
• decreased EDV => hypertrophy and dilatation of left atrium => supraventricular arrhytmias (atrial flutter, AF)
• increased pulmonary artery pressure at rest => orthopnea
• increased pulmonary pressure under effort => reduced effort tolerance
• ischemic heart disease (IHD) due to :
• reduction of coronary reserve => vascular rarefaction (not proportional), increased extracoronary resistance (also in diastole), increased basal coronary flow,
• increased oxygen demand
Laboratory examinations : EKG : modifications of ST segment and T wave are relatively predominant over QRS complex modifications
• volume or diastolic overload
• malformative hyperafflux
• aortic valve failure
• mitral valve failure
• patent ductus arteriosus
• physical exercise (concentrical shape : RWT > 0.45)
Laboratory examinations : EKG : modifications of QRS complex are relatively predominant over ST segment and T wave modifications
Laboratory examinations :
• EKG : QRS voltage and duration are suggestive but not diagnostic in absence of left ventricular hypertrophy (they depend on subcutaneos chest wall thickness = obesity)
• high sensitivity, poor specificity (only suggestive if not associated with morphologic alterations : high voltage are common in individuals with thin chest wal and trained to physical exercise)
• R wave in V₄, V₅, and/or V₆ > 27 mm
• R_{V5 or V6 (the higher)} + S_{V1, V2 or V3 (the higher)} > 40 mm
• S wave V₁, V₂ and/or V₃ > 30 mm
• R wave in aV_L > 13 mm
• R wave in aV_F > 20 mm
• ventricular activation time > 0.04 s (high specificity, poor sensitivity)
• abnormal ST segment depression in left leads (ie. V₄, V₅, or V₆, and DI and aV_L if horizontal heart (usual in LVH of the adult) or in DIII and aV_F if vertical heart (usual in LVH of child)
• T wave inversion in left leads (as above)
• Cornell voltage-duration index : (Cornell voltage index) x (duration of QRS complex) > 2440 mm x s^{ref1, ref2}, an approximation of the area under the QRS^ref, appears to further enhance sensitivity (37-51%) of the ECG for LVH while maintaining high specificity
• Cornell voltage index : R_aVL + S_V3 > 20 mm in females or 28 mm in males^{ref1, ref2} (sensitivity = 28-36%; specificity = 87%)
• Sokolow-Lyon index : R_{V5 or V6 (the higher)} + S_V1 > 35 (38 ?) mm (Sokolow M, Lyon TP. The ventricular complex in left ventricular hypertrophy as obtained by unipolar precordial and limb leads. Am Heart J. 1949;37:161–186) (sensitivity = 22%; specificity = 79%)
• QRS duration (sensitivity = 27%)
• Romhilt-Estes point score > 4 (sensitivity = 12-20%; specificity = 87%)
• Rodriguez Padial score (sensitivity = 82%; specifity = 8%)
• 12-lead product (sensitivity = 45-50%)
• 12-lead sum of voltage (sensitivity = 31-43%)
• other findings :
• as precordial leads explore a larger region of left ventricular myocardium (ie there is counterclockwise heart rotation), qR complexes are seen also in right precordial leads (no longer exclusively in V₄, V₅ and V₆)
• usually associated with signs of left atrial hypertrophy
• high voltage U wave in right and intermediate precordial leads
• mild left axial deviation of the QRS electric axis on the frontal plan : if < -30° suspect concomitant LAHB
• M-mode (1D) echocardiography (after B-mode (2D) localization) :
• concentric left ventricular hypertrophy (LVH) : thickening of the walls with a reduced cavity size, (e.g., aortic stenosis). RWT > 0.45 and LVIDd < 3.1 cm / m²_BSA
• eccentric dilated LVH : RWT < 0.45 and LVIDd > 3.1 cm / m²_BSA
• eccentric nondilated LVH : RWT < 0.45 and LVIDd < 3.1 cm / m²_BSA
• mixed LVH : RWT > 0.45 and LVIDd > 3.1 cm / m²_BSA
• left ventricular mass index (LVMI) (Framingham study)
• > 125 g/m²_BSA or > 134 in males+females
• > 125 g/m²_BSA or > 120 in males only
• > 110 g/m²_BSA or > 105 in females only
• > 51 g/m_height^2.7 in males+females
• IVSd / LVEED > 0.45
• 2 SPP - D / LVEED > 0.44
RWT > 0.45 and LVMI < 125 g/m²_BSA : concentric remodeling (9.5-25%)

	pressure overload	left ventricular hypertrophy	left ventricle dilatation
parietal stress	increased	no	increased : increased fiber section reentry automatism increased afterload decreased voltage threshold subendocardiac ischemia => ventricular arrhythmias => sudden death
ejection fraction	decreased	no	very decreased

RWT < 0.45 and LVMI < 125 g/m²_BSA : normal
RWT > 0.45 and LVMI > 125 g/m²_BSA : concentric hypertrophy (3.6-45%)
RWT > 0.45 and LVMI > 125 g/m²_BSA : eccentric hypertrophy (10.4-46%)
• biventricular hypertrophy

Aetiology :
• severe rheumatic valvulopathies (aortic valvulopathy with pulmonary hypertension or mitral failure with pulmonary hypertension
• cardiomyopathy
• congenital cardiopathies (occasionally)
Laboratory examinations :
• EKG : QRS < 0.11 s; T wave inversion in precordial leads; both right axial deviation and signs of LVH; more rarely signs of RVH and QRS axis < -30°. When LVH and RVH are similar in extent no EKG sign is found !
Pathogenesis : accumulation of an abnormal protein inside sarcomeres causes the cells to grow too large and in a shambolic fashion, particularly around the left ventricle
• increased peripheral resistances => pressure or systolic overload => isometric hypercontractility => concentric hypertrophy
• increased diastolic flow => volume or diastolic overload => isotonic hypercontractility =>eccentric hypertrophy (not always macroscopic)
=> hypertrophy of cardiomyocytes (transverse diameter > 25 mm; increased %sarcoplasmic area occupied by myofibrils and nuclei), heart mass > 350 g; LV thickness > 15 mm; RV thickness > 4 mm; LV_mass > 125 g / m²_BSA) => dilatation => myocardiocyte disarray (intersecating, stellate, vorticous) and interstitial fibrosis => CHF (due to myocardial ischemia, insufficiency of mitochondrial proliferation, and reestablishment of a fetal pattern of gene expression) and arrhythmias => high risk of sudden cardiac death.
Symptoms & signs : ictus or point for all duration of systole. The association of left ventricular hypertrophy with cerebrovascular disease is due to association between coronary and cerebral afferent vascular atherosclerosis, subcutaneous microangiopathy and atrial fibrillation.
Macroscopic anatomy : ventricular septal asymmetry (rarely symmetric heart)
Variants :
• hypertrophic dilated cardiomyopathy (HDCM) (wall thinning => CHF)
• hypertrophic obstructive cardiomyopathy (HOCM) : a form of hypertrophic cardiomyopathy in which the location of the septal hypertrophy causes obstructive interference to left ventricular outflow
• medioventricular hypertrophy => idiopathic hypertrophic subaortic stenosis / muscular subaortic stenosis : the left ventricle is hypertrophied (commonly with disproportionate involvement of the interventricular septum) and the cavity is small; it is marked by obstruction to left ventricular outflow (aortic valve stenosis)

Symptoms & signs : Brockenbrough's sign : occurrence of a weak pulse instead of a strong one immediately after a premature ventricular contraction; indicative of idiopathic hypertrophic subaortic stenosis.
• septal hypertrophy =>
• mitral valve stenosis
• Bernheim's syndrome : right heart failure due to left ventricular hypertrophy with bulging of the interventricular septum that causes obstruction to flow from the right atrium to ventricle, altering ventricular filling and capacity.
• restrictive variant (reduced compliance, no evident hypertrophy, atrial dilatation)
• apical hypertrophy => decreased EDV
Laboratory examinations :
• heart auscultation : 2-3 Levine grades mitral or aortic systolic ejection murmur varying time by time.
• chest X-ray : mild to moderate cardiac silhouette enlargement
• EKG :
• P wave > 0.12 s, bimodal and biphasic (2 separated drops < 0.04 s)
• overload :
• ST depression in absence of therapy with digitalis glucosides has worst prognosis
• asymmetric T wave
• abnormal Q waves ?
• M-mode (1D) echocardiography (after B-mode (2D) localization) :
• asymmetric septal hypertrophy (ASH)
• systolic anterior motion (SAM) of the mitral valve
• eccentric dilatation (rarely concentric misinterpretation)
• cardiac catheterization : vigorous systolic function, dynamic left ventricular outflow obstruction, elevated left- and right-sided filling pressures
• radionuclide ventriculography : vigorous systolic function
• ²⁰¹Tl myocardial perfusion scintigraphy : perfusion defect
• contrast-enhanced MRI is better than dual-radionuclide SPECT using ^99mTc-sestamibi and ¹²³I 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) in detecting heart damage in patients with HCM^ref
• genetic testing is now gaining a foothold in studies of HCM, and holds the promise of sorting out those who have a high risk of suffering sudden death from those with a low risk. So far, genetic testing for HCM in Europe and the United States has been available only to individuals with a high risk of having HCM, and then only under the auspices of research programmes. But the first commercial test went on sale on May 2004 in the United States. Designed by Jonathan and Christine Seidman of the genetics department at Harvard Medical School in Boston, Massachusetts, the test is based on detecting mutations in 8 genes that the couple think account for 75% of cases of HCM. This genetic test misses not only 25% of the genes already linked to the condition, but also the many other genetic mutations that are probably involved but have not yet been discovered. Yet it remains unclear how these genetic mutations affect risk^ref.
Therapy :
• drugs
• surgery
• ICD to kick-start the heart back into action should there be a major problem
Prognosis : apart from patients with previous heart failure or severe restrictive physiology, most women with hypertrophic cardiomyopathy tolerate pregnancy well. Symptoms worsen during pregnancy in < 10% : general and epidural anesthesia cause no complications. See also HCM as a contraindication for sports.
Web resources : HCM at Medline Plus
• obliterative or restrictive cardiomyopathy : a form in which there is endomyocardial scarring or myocardial infiltration resulting in excessively rigid ventricular walls, impeding left and/or right ventricular filling; it is marked by abnormal diastolic function sometimes with normal or nearly normal systolic function.

Aetiology :
• intrinsic
• cardiomyopathy, restrictive 1A (autosomal dominant) => familial restrictive cardiomyopathy
• cardiomyopathy, restrictive 2A (autosomal recessive)
• cardiomyopathy, restrictive 3A (X-linked)
• desmin-related myopathy
• extrinsic
• African endomyocardial fibrosis / Loffler's heart disease : idiopathic myocardiopathy occurring endemically in various regions of Africa and rarely in other areas, characterized by cardiomegaly, marked thickening of the endocardium with dense, white fibrous tissue that frequently extends to involve the inner third or half of the myocardium, and congestive heart failure.
• parasitosis (Filarioidea, Loa loa) => hypereosinophilia
• noninfiltrative
• scleroderma
• infiltrative cardiomyopathy : restrictive cardiomyopathy characterized by deposition in the heart tissue of abnormal substances
• hemochromatosis
• amyloidosis
• thesaurismoses :
• mucopolysaccharidoses
• glycogenoses
• sarcoidosis
• systemic sclerosis
• endomyocardial
Pathogenesis : normal caliper and thickness of ventricula but loss of elasticity => decreased compliance => decreased EDV => right ventricle failure => atriomegaly
Symptoms & signs : stiff heart syndrome : any cardiac disease characterized by restrictive hemodynamics; it may result from any pathologic process that renders the myocardial fibers abnormally rigid or that externally applies a constricting pressure and as a consequence impedes flow of blood into the ventricular cavities.
Laboratory examinations :
• chest X-ray : mild cardiac silhouette enlargement
• EKG : low voltage, conduction defects
• echocardiography : polished glass-like image, increased left ventricular wall thickess, noral or mildly reduced systolic function
• delayed contrast-enhanced cardiac MRI^ref appears to be superior to other techniques in the detection of myocardial involvement in a wide range of systemic diseases affecting the heart, such as amyloidosis^ref,  sarcoidosis^{ref1, ref2}, and scleroderma^ref because of its noninvasive nature, high spatial resolution, and lack of nephrotoxicity. Early and accurate diagnosis of fibrosis is important, especially when treatment is considered to prevent the potentially lethal consequences
• radionuclide ventriculography : normal or mildly reduced systolic function
• cardiac catheterization : normal or mildly reduced systolic function, elevated left- and right-sided filling pressures (decrease of DP), "dip-and-plateau" diastolic pressure pattern in both left and right ventricle. "W" shape diastolic pressure pattern in right atrium
Differential diagnosis from constrictive pericarditis with fibrosis at right ventricle endomyocardial biopsy.
• arrhythmogenic right ventricular dysplasia (ARVD) or cardiomyopathy
• Keshan disease : a fatal, congestive cardiomyopathy caused by deficiency of essential trace elements in the diet; it primarily affects children and women of childbearing age, and occurs in areas with low soil trace elements, such as parts of China, New Zealand, and Finland.
• stress cardiomyopathy / 'broken-heart syndrome' / transient left-ventricular apical-ballooning syndrome / takotsubo cardiomyopathy (after an octopus trap with a round bottom that resembles the appearance of a stunned heart) : reversible left ventricular dysfunction precipitated by emotional stress

Aetiology : sudden emotional stress can release catecholamines (particularly adrenaline) that stun the heart into submission, resulting in symptoms that mimic a typical heart attack : they have chest pain, fluid in the lungs, shortness of breath and heart failure. But although the ability of the heart to pump is significantly reduced and the heart muscle is weakened, it is not killed, or infarcted, as in a classic attack. The tissue is alive : it's just not moving. Initial levels of catecholamines (particularly adrenaline) in the patients with broken heart syndrome were 2 to 3 times greater than those in classic heart-attack patients, and between 7 and 34 times greater than in healthy people. By spotting broken-heart sufferers, unnecessary procedures (such as defibrillator implant) could be averted
Epidemiology : known since 1995 in Japan, while it has so far gone relatively unrecognized in the West^{ref1, ref2}. Postmenopausal women seem to be more vulnerable. The patients have unique electrocardiogram and ultrasound patterns, lacked coronary artery disease and recovered quickly. The median age of patients with stress-induced cardiomyopathy was 63 years, and 95% were women.
Symptoms & signs : chest pain, pulmonary edema, and cardiogenic shock
Laboratory examinations : diffuse T-wave inversion and a prolonged QT interval occurred in most patients. Most patients have mildly elevated serum troponin I levels, but there is no angiographic evidence of clinically significant CAD. Severe left ventricular dysfunction was present on admission (median ejection fraction, 0.20; interquartile range, 0.15 to 0.30) and rapidly resolved in all patients (ejection fraction at two to four weeks, 0.60; interquartile range, 0.55 to 0.65; P<0.001). Endomyocardial biopsy showed mononuclear infiltrates and contraction-band necrosis. Plasma catecholamine levels at presentation were markedly higher among patients with stress-induced cardiomyopathy than among those with Killip class III myocardial infarction (median epinephrine level, 1264 pg/ml [interquartile range, 916 to 1374] vs. 376 pg/ml [interquartile range, 275 to 476]; norepinephrine level, 2284 pg/ml [interquartile range, 1709 to 2910] vs. 1100 pg/ml [interquartile range, 914 to 1320]; and dopamine level, 111 pg/ml [interquartile range, 106 to 146] vs. 61 pg/ml [interquartile range, 46 to 77]; P<0.005 for all comparisons)
• infarctoid cardiopathy : a heart condition with symptoms resembling those of myocardial infarction
• cardiomyoliposis : fatty degeneration of the heart muscle
• cardiomelanosis : melanosis of the heart.
• cardiomalacia : morbid softening of the muscular substance of the heart
• cardiodynia : pain in the heart
A genomic/post-genomic classification of inherited cardiomyopathies^ref :
• cytoskeletal cardiomyopathy ("cytoskeletalopathy") : dilated cardiomyopathy, arrhthmogenic right ventricular cardiomyopathy, cardiocutaneous syndromes
• sarcomeric cardiomyopathy ("sarcomyopathy") : hypertrophic and restrictive cardiomyopathy
• ion channel cardiomyopathy ("channelopathy") : long and short QT syndromes, Brugada syndrome, catecholaminergic polymorphic VT
•  diseases of the pericardium
• partial left pericardial defects : the main pulmonary artery and left atrium may bulge through the defect; very rarely, herniation and subsequent strangulation of the left atrium may cause sudden death
• pericarditis : inflammation of the pericardium
• external pericarditis : that which chiefly affects the outer surface of the pericardium.
• acute pericarditis (2-6%, 1 every 10,000 hospital admissions) : lasting < 6 weeks
• fibrinous or fibrous pericarditis : pericarditis characterized by a fibrinous exudate, sometimes accompanied by a small amount of serous effusion; it is usually manifest as a pericardial friction rub
• early phase : opaque serosal membrane => little fibrin, desquamating mesothelium => inflammatory infiltrates, subserosal connective tissue
• late phase : gray-yellowish serosal membrane => liftings that can be ...
• ... irregular : bread-and-butter pericarditis : fibrinous pericarditis in which the fibrinous exudate forms a thick shaggy coat over the pericardium, with adhesions between the layers (bread-and-butter pericardium : a pericardium having a thick fibrinous deposit on its surfaces)
• ... regular : pettinated
• ... papillary : cor villosum
... due to mechanical friction rubs.
• pericarditis sicca : acute fibrinous pericarditis without effusion
Evolutions :
• dissolution of the exudate => recovery
• chronicization => adhesive pericarditis
• purulent or suppurative pericarditis / pyopericardium / empyema of pericardium : a form characterized by pus formation, usually due to pyogenic bacterial infection, and less often to fungal or viral infection, which may be spread from neighboring tissues, through the blood or lymphatic systems, or via direct implantation in wounds. It is characterized by fibrinopurulent or purulent exudates with neutrophils in subserosal connective tissue, myocardium, and mediastinum. Resolution is infrequent and it often results in constrictive pericarditis and cardiac tamponade.
• serofibrinous pericarditis : pericarditis characterized by a fibrinous exudate accompanied by substantial serous effusion, otherwise resembling fibrinous pericarditis.
• idiopathic pericarditis / acute benign pericarditis : an acute serofibrinous pericarditis of unknown cause; recurrent attacks are not unusual
• effusive pericarditis
• serous pericarditis : pericarditis characterized by serous effusion (< 200 mL), usually produced by a nonbacterial inflammation. Pericardial fluid is torbid > clear.
• hemorrhagic pericarditis : that in which the exudate is bloody as well as serous, serofibrinous, or purulent (differential diagnosis with hemopericardium)

Aetiology :
• pericardial tumors, expecially metastases from carcinoma
• Mycobacterium tuberculosis
• other bacterial infections
• uremia
• severe acute infections
• cholesterol pericarditis: pericarditis characterized by cholesterol-laden golden exudate, resulting from deposition of cholesterol crystals and subsequent inflammatory response including infiltration of the pericardium by lymphocytes, plasma cells, lipophagic macrophages, and giant cells.

Aetiology : evolution of tubercular hemorrhagic pericarditis due to necrosis of RBC
• granulomatous pericarditis

Aetiology :
• Treponema pallidum subsp. pallidum
• rheumatoid arthritis
• Mycobacterium tuberculosis
Aetiology :
• epistenocardiac pericarditis (limited to the area over infarcter myocardium)
• traumatic pericarditis : pericarditis caused by penetrating or nonpenetrating trauma to the pericardium, such as that due to
• bullet wounds
• improper catheter placement
It is characterized by pericardial pain and friction and may lead to hemopericardium or cardiac tamponade
• infectious pericarditis
• viruses (70%; viral pericarditis characterized by pericardial friction rub, serous effusion, and fibrin deposition; it appears to be the cause of at least some cases of idiopathic pericarditis, usually in Spring and Autumn, self-limiting within 2-3 weeks)
• coxsackieviruses B1, B2, B3, B4 and B5
• coxsackieviruses A4 and A16
• echoviruses 9 and 22
• influenzavirus A
• influenzavirus B
• adenoviruses
• mumps virus
• HHV-1 / HSV-1
• HHV-2 / HSV-2
• HHV-4 / EBV
• HHV-5 / CMV
• HBV
• Bacteria (severe bacterial pericarditis) : serofibrinous or serohemorrhagic => purulent
• contiguity (endocarditis, myocarditis, pneumonia, pleuritis, subdiaphragmatic abscesses)
• hematogenous spread
• trauma (pericardiotomy)
• Corynebacterium diphteriae
• Clostridium perfringens
• Staphylococcus spp.
• Legionella pneumophila
• Neisseria meningitidis
• Neisseria gonorrhoeae
• Haemophilus influenzae
• Listeria monocytogenes
• Nocardia spp.
• Borrelia burgdorferi
• Streptococcus spp.
• Salmonella spp.
• MAC
• Campylobacter spp.
• Chlamydia spp.
• Rickettsia spp.
• Mycoplasma spp.
• Actinomyces spp.
• Fungi (severe fungal pericarditis)
• Ajellomyces capsulatus
• Coccidioides immitis
• Ajellomyces dermatitidis
• Filobasidiella spp.
• Candida spp.
• Aspergillus spp.
• Protozoa
• Entamoeba hystolytica (amebic pericarditis : pericarditis occurring as a result of rupture of an amebic abscess of the liver through the diaphragm.)
• Toxoplasma gondii
• Metazoa
• Echinococcus granulosus
• Trichinella spiralis
• Taenia solium (larvae)
• Schistosoma spp.
• metastasis from breast or lung cancers
Adhesions between visceral and peritoneal layers due to fibrinous angioflogosis.
Symptoms :
• dyspnea or tachypnea.
• angina pectoris accentuated during inspiration, pain on neck and anterior border of trapezius muscle
Signs :
• Mohameddan pray position : not to decrease venous return as in squatting of patients with Fallot's tetralogy, but to move exudate foreward reducing the sensible pericardial area
• systolic hypotension with Kussmaul's paradoxical pulse => metabolic acidosis => cardiogenous shock
• Evart's sign : bronchial murmur and egophony at the angle of left scapula
• pericardial rubbing at auscultation due to fibrin clots
Laboratory examinations
• electrical alterations at EKG
• volume alterations at echocardiography
Complications :
• contiguity infectious myocarditis
• dry pericarditis (pericarditis not associated with effusion) => exudative pericarditis / pericarditis with effusion (pericarditis associated with the collection of a serous or purulent pericardial effusion : 15%) (shaggy pericardium : a pericardium coated with a roughened layer of fibrinous exudate)

‡
• cardiac tamponade
• relapses (20-30%)
• pericardiomediastinitis : pericarditis with mediastinitis; inflammation of the pericardium and mediastinum.

‡
• subacute pericarditis (6 weeks to 6 months)
• effusive-constrictive
• constrictive pericarditis
• chronic pericarditis
• localized pericarditis : a term usually denoting chronic pericarditis with thickened white or milky epicardial areas
Aetiology :
• idiopathic (45%)
• Mycobacterium tuberculosis (15%; tuberculous pericarditis : serofibrinous sometimes with caseous debris (caseous pericarditis), thick shaggy deposits of fibrin, pericardial friction rub, and adhesion of the pericardial layers; it often results in hemorrhagic pericarditis ("meat washing" look) and chronic constrictive pericarditis)
• Hutinel's disease : tuberculous pericarditis with cirrhosis of the liver in children.
• uremia (uremic pericarditis : pericarditis occurring as a complication of uremia; it is characterized by shaggy, vascular, fibrinous exudate on the visceral and parietal pericardial surfaces.)
• post-irradiation or radiation pericarditis : from high dose radiotherapy, often beginning as exudative effusion with fibrin deposits and sometimes progressing to chronic pericardial effusion or constrictive pericarditis. It may present decades after radiation exposure
• autoimmune pericarditis
• rheumatic fever (rheumatic pericarditis : fibrinous, serofibrinous, dry or purulent exudate, sparse to densely shaggy fibrin deposits, chest pain, and pericardial friction rub)
• systemic lupus erythematosus
• 1-3 weeks after necrosis
• postcommissurotomy
• postpericardiotomy pericarditis : a form occurring as a complication following cardiac surgery, characterized by effusion and rarely by constriction
• Dressler's syndrome (autoimmune)
• hypothyroidism
• neoplastic pericarditis : pericarditis associated with primary or secondary neoplastic infiltration of the pericardium, often characterized by serous or bloody pericardial effusion, constriction, arrhythmia, or tamponade
• carcinomatous pericarditis : that which is associated with malignant disease of the pericardium.
Types :
• effusive pericarditis
• adhesive (nonconstrictive) pericarditis : a condition resulting from the presence of dense fibrous tissue between the parietal and visceral layers of the pericardium (adherent pericardium : a pericardium that is abnormally connected with the heart by dense fibrous tissue). There may be complete obliteration of the pericardial cavity (pericarditis obliterans / obliterating pericarditis) from partial or diffuse (sero)fibrinous pericarditis, or there may be adhesions extending from the pericardium to the mediastinum (mediastinopericarditis), diaphragm, and chest wall (accretio cordis or pericardii) from tubercular or suppurative pericarditis.
• chronic calcific pericarditis ("el corazòn espinado")^ref
Symptoms & signs :
• Broadbent's sign : a retraction seen on the left side of the back, near the eleventh and twelfth ribs, related to pericardial adhesion.
• Cegka's sign : invariability of the cardiac dullness during the different phases of respiration; a sign of adherent pericardium.
• Friedreich's sign : diastolic collapse of the cervical veins due to adherent pericardium.
• Heim-Kreysig sign : a depression of the intercostal spaces occurring along with the cardiac systole in adherent pericarditis.
• constrictive pericarditis : a chronic form in which a fibrotic, thickened, adherent pericardium restricts diastolic filling and cardiac output. It is usually a consequence of a series of events beginning with an acute episode in which fibrin and sometimes calcium are deposited on the pericardial surface, followed by fibrotic scarring and thickening of the pericardium and obliteration of the pericardial space.
• effusive constrictive pericarditis : a form characterized by pericardial effusion in the presence of visceral pericardial constriction, manifest as continued elevation of right atrial pressure after pericardiocentesis; it often leads to chronic constrictive pericarditis.
Pathogenesis : sclerosis or calcifications.
Symptoms & signs : as for right heart failure
• Broadbent's sign : retraction of left lower scapular angle during cardiac systole
• Kussmaul's venous sign : distention of the jugular veins also during inspiration, seen in constrictive pericarditis and mediastinal tumor
Laboratory examinations :
• square root sign : in constrictive pericarditis, the diastolic level of the right ventricular pressure curve is initially normal but rapidly rises abnormally
• hemodynamics : "dip-and-plateau" diastolic pressure pattern in both left and right ventricle
Differential diagnosis with similar clinical disorders :

characteristic		cardiac tamponade	constrictive pericarditis	restrictive cardiomyopathy	right ventricular myocardial infarction
clinical	pulsus paradoxus	common	usually absent	rare	rare
	jugular vein : prominent y descent	absent	usually present	rare	rare
	jugular vein : prominent x descent	present	usually present	present	rare
	Kussmaul's sign	absent	present	absent	absent
	S3 sound	absent	absent	rare	may be present
	pericardial knock	absent	often present	absent	absent
EKG	low EKG voltage	may be present	may be present	may be present	absent
	electrical alternans	may be present	absent	absent	absent
echocardiography	thickened pericardium	absent	present	absent	absent
	pericardial calcification	absent	often present	absent	absent
	pericardial effusion	present	absent	absent	absent
	RV size	usually small	usually normal	usually normal	enlarged
	myocardial thickness	normal	normal	usually increased	normal
	right atrial collapse and right ventricular diastolic collapse	present	absent	absent	absent
	increased early filling, increased mitral flow velocity	absent	present	present	may be present
	exaggerated respiratory variation in flow velocity	present	present	absent	absent
CT/MRI	thickened/calcific pericardium	absent	present	absent	absent
cardiac catheterization	equalization of diastolic pressures	usually present	usually present	usually absent	absent or present
cardiac biopsy	helpful ?	no	no	sometimes	no

Treatment : pericardial decortication.
• hydropericarditis : pericarditis associated with hydropericardium
• calcified pericardium : a pericardium containing deposits of lime salts.
• pericardial effusions
• trasudate : hydropericardium : abnormal accumulation of serous fluid (> 100 mL) in the pericardial cavity.

Aetiology :
• anasarca
• local hurdle to mediastinic lymph and blood vessels
• cardiac tumors
Symptoms & signs : Duchenne's sign : the sinking in of the epigastrium on inspiration in paralysis of the diaphragm or in certain cases of hydropericardium
Autoptic findings : fluctuating and distended pericardium, smooth and bright inner surface
• exudate : exudative pericarditis
• chylous fluids => chylotamponade
• chylopericardium :
• primary idiopathic chylopericardium : rare entity first reported in 1886 by Hasebrock. The term primary chylopericardium was first used by Groves and Effler (1954), who described a case of isolated accumulation of chyle in the pericardium, with no obvious cause. In a review of the literature, 57 cases of true isolated chylopericardium (no obstructive lesions or history or cardiac surgery) had been documented by 2002. Idiopathic chylopericardium occurs in all age groups and affects both sexes equallly, with most cases presenting in children or young adults. Up to 40% of cases are asymptomatic, and tamponade is rare (6%). Diagnosis is confimed by the creamy white appearance of pericardial fluid, the presence of fat droplets microscopically, and the confirmation of a high level of triglycerides in the fluid. The nature of the effusion is usually revealed by pericardiocentesis. However, the diagnosis of chylopericardium may be established noninvasively by precordal imaging, using technetium-99m-labeled red blood cells and oral administration of 131I-triolein. Lymphangiography may in certain instances establish the fistulous connections and is also useful for delineating the anatomy of the thoracic duct. On the other hand, radionuclide imaging using 131I-triolein or pedal administration of technetium-99m-sulfur colloid may show a communication between the lymphatic system and the pericardial sac. In contrast to the success with conservative treatment of post-traumatic chylopericardium, such treatment of idiopathic chylopericardium is rarely successful. Surgery is usually required, although occasional cases of successful nonsurgical treatment have been reported. The surgical procedure consists of ligation and excision of the thoracic duct just above the diaphragm, combined with partial pericardiectomy. Pericardiectomy is performed to ensure complete drainage and to prenvent later constrictive pericarditis.
• secondary chylopericardium :
• thoracic and cardiac surgery
• chest trauma
• mediastinal neoplasms
• mediastinal tuberculosis
• mediastinal radiotherapy
• thrombosis of the subclavian vein
• pseudochylopericadium : accumulation of fatty total parenteral nutrition formulations after perforation of the heart due to central venous catheters with tip in right atrium or ventricle
• blood (differential diagnosis with hemorrhagic pericarditis)
• epicardiac hemorrhages

Aetiology :
• asphyxia (hemorrhagic petechiae)
• hemorrhagic diathesis (larger areas)
• anticoagulant drugs
• hemopericardium
• acute (> 200-300 mL) => cardiac tamponade
• chronic stillicide => pericardial distension
Aetiology :
• heart rupture during AMI
• dissection of De Bakey's type I aorta aneurysm
• rupture of intrapericardial artery
• ascending aorta
• coronary artery rupture
• trauma
• accidents or penetrated firearm bullets
• cardiac catheterism
• angioplasty
• bleeding at site of previous iatrogenic scars
• pericardial hemorrhages
• cardiac tumors
• post-AMI granuloma
Pathogenesis :
• acute pericardial effusion => cardiac tamponade if P_{pericardial cavity} > P_{right atrium}.

Aetiology : acute hemopericardium
Pathogenesis : prevention of ventricular diastole
Symptoms & signs : Beck's triad : 3 symptoms characteristic of cardiac compression: (1) a high venous pressure, (2) a low arterial pressure, and (3) a small quiet heart.
Treatment : pericardiocentesis (to decrease P_{pericardial fluid}) at 4^th intercostal space along left marginosternal line or below xiphoid.
• chronic pericardial effusion => caval hypertension
• P < 100/150 mmHg
• P > 100/150 mmHg => decreased cardiac output => increased heart rate => heart failure
Symptoms & signs :
• Auenbrugger's sign : a bulging of the epigastrium, due to extensive pericardial effusion
• Bamberger's sign : presence of signs of consolidation at the angle of the scapula in the left intercostal region (Bamberger's area), which disappear when the patient leans forward; a sign of pericardial effusion.
• Ewart's sign : bronchial breathing and dullness on percussion at the lower angle of the left scapula in pericardial effusion
• Rotch's sign : dullness on percussion of the right fifth intercostal space, a sign of pericardial effusion.
• Sansom's sign : marked increase of the area of dullness in the second and third intercostal spaces, due to pericardial effusion
• pneumopericardium : the presence of air or gas in the cavity of the pericardium
• hemopneumopericardium : hemopericardium + pneumopericardium
• hydropneumopericardium : hydropericardium + pneumopericardium
• cardiac or ventricular aneurysm : an aneurysmal dilatation of a portion of the wall of a ventricle, usually the left, or, rarely, a saccular protrusion through it (false aneurysm of the heart). It is usually consequent to myocardial infarction but other causes, such as bacterial endocarditis or trauma, have been described
• cardiocutaneous fistula after resection of left ventricular aneurysms
• atrial septal aneurysm (ASA)

Epidemiology : prevalence = 2-4%, associated to patent foramen ovale in 70%
• lipomatous hypertrophy of the atrium : this condition is not a true tumour, but rather a focal collection of mature fetal fat tissue forming a mass that may bulge into the right atrium. It is mainly found in obese, female, and elderly patients. There may be an association with cardiac arrhythmias.
• cardiac tumors
• primary benign tumors (58-72%). Approximately 90% of benign tumours occur in children younger than 12 years. Of these, 75% are in children younger than 2 years.
• myxoma (33.2-50%) : a benign gelatinous growth usually pedunculated and usually arising from the interatrial septum of the heart in the region of the fossa ovalis (75-86% in left atrium; rarely in right atrium (20%; 1 out of 1,000,000) and ventricles (5%); 90% are solitary; 10% have autosomal dominant inheritance; 1-5 cm with a weight between 15 to 180 g)
• villous or friable (35%)
• smooth (65%)
Symmptoms & signs : disrupts cardiac filling and emptying and cause obstruction and MR murmurs => mitral valve stenosis, embolism, arrhythmias, pericardial effusion, cardiac tamponade, effort dyspnea, weight loss, dizziness/syncope, fatigue, low-grade fever, polyneuritis, nausea, hemoptysis, and palpitations, and sometimes sudden syncopal attacks related to obstruction, eventually leading to sudden death
Therapy : semi-urgent excision
• cardiac lipoma(0.6-19%)
• papillary fibroelastoma (17%) : the most common heart valve tumor, commonly seen post mortem, composed of a characteristic cluster of hairlike projections consisting of collagen surrounded by elastic fibers and connective tissue and covered by endothelium, attached to a valve or to the papillary muscles, chordae tendineae, or endocardium. 2-28 mm in size, usually single and 40% mobile, commonly pedunculated, frequently located on the aortic or other cardiac valves, not associated with valvular dysfunction, source of emboli
• cardiac rhabdomyoma (5.8-20%) : most common cardiac tumors of infants and children, approximately 90% occur in patients younger than 1 year; they occur with equal frequency in the right and left ventricular outflow tracts and septal myocardium; nearly all are multiple; associated with tuberous sclerosis (TS) in 50% of patients. Can be diagnosed with fetal echocardiography.
• cardiac fibroma (5.8%) : occur predominantly in children and constitute the second most common type of primary cardiac tumor occurring in the pediatric group. Almost all occur within the ventricular myocardium, most frequently within the anterior free wall of the left ventricle or the interventricular septum and much less often in the posterior left ventricle wall or right ventricle. <10% of reported cases have atrial or great vessel involvement. Unlike myxomas, tumour embolisation is uncommon.
• cardiac teratoma
• cardiac hemangioma (5%)
• atrioventricular nodal cancer (2.9%)
• granular cell cancer (1.2%)
• paraganglioma (0.6%)
• myocytic hamartoma (0.6%)
• histiocytoid cardiomyopathy (0.6%)
• inflammatory pseudotumor (0.6%)
• others (1.2%)
• primary malignant tumors (25-42%; non-encapsulated and infiltrate surrounding tissue)
• cardiac sarcomas (39.9%)
• cardiac angiosarcoma(the most common primary cardiac malignancy) : arise most often in right heart, particulary the right atrium and involve the pericardium; may be associated with right heart obstruction, hemorrhagic pericardial effusion (areas of increased signal intensity with T1-weighted sequences), or obliteration of the pericardial space by tumor cells or thrombus.

Therapy : successful treatment with combined radiotherapy and chemotherapy followed by transplantation has been reported.
Prognosis : survival is under 1 year after diagnosis
• cardiac rhabdomyosarcoma: mostly found in adults (despite it is the most common primary cardiac malignancy in children) and is more likely than other primary cardiac sarcomas to involve the valves; can be in either chamber or pericardial extension, myocardial involvement is more common; as with other primary sarcomas, the prognosis is poor
• primary cardiac osteogenic sarcomaalmost always occurs in the left atrium and frequently demonstrates calcification. Certain features (eg, broad base of attachment, origin at a site other than the atrial septum) help differentiate this tumor from left atrial myxoma
• cardiac leiomyosarcomafavors the left atrium and tends to invade the pulmonary veins and mitral valve. Fibrosarcoma also tends to occur in the left atrium and is often necrotic
• cardiac liposarcomais very rare and usually manifests as a large, infiltrating mass. Foci of macroscopic fat are occasionally seen
• undifferentiated cardiac sarcomastypically occur in the left atrium and have variable epidemiologic and radiologic features.
• primary cardiac lymphoma(1-2.1% of the primary cardiac tumors)
• pericardial mesothelioma : diffuse, pericardial tumors involving both the visceral and parietal pericardial layers, but extend only superficially into the myocardium, and rarely involving cardiac chambers
• multiple or diffuse form with growth encasing the heart (common)
• solitary or localized form (uncommon)
Epidemiology : incidence of 0.0022%. Altogether there are about 150 cases reported in the literature. In most cases the diagnosis is made at autopsy or postoperatively.
Symptoms & signs : cardiac tamponade
Laboratory examinations : echocardiography, pathologic examination of pericardial fluid and pericardial biopsy, ⁶⁷Ga scintigraphy, Ber-EP4 antibody, and immunohistochemical procedures can be used
Differential diagnosis includes solitary fibrous tumor, synovial sarcoma, epithelioid angiosarcoma, and adenomatoid tumor of the pericardium.
Therapy :  surgical resection remains the main treatment modality. When the disease is localized and completely resected, long-term survival can result. Most often the tumor invades the myocardium or the great vessels and therefore is at best palliative in relieving pericardial tamponade or constriction. Addition of chemotherapy or radiation has been disappointing.
Prognosis is poor
• subserosal lymphatic metastases : most often involve the pericardium and epicardium (75%), presenting as a pericardial effusion, with or without a tamponade physiology. Myocardial involvement is less common than pericardial metastatic involvement, but does occur, particularly with lymphoma (expecially when associated with AIDS) or melanoma
• lung carcinoma (20-30%)
• leukemias and lymphomas
• breast carcinoma (20-30%)
• soft tissue sarcomas
• renal carcinoma (20-30%)
• colon carcinoma
• thyroid carcinoma (20-30%)
• esophageal adenocarcinoma (20-30%)
• malignant melanoma(the highest rate of pericardial metastases)
Differential diagnosis with :
• thrombus : usually discrete and somewhat spherical in shape or laminated against LV apex or LA wall
• endocarditis vegetations : usually valvular, occasionally on ventricular wall or Chiari network; irregular shape, attached to the proximal (up-stream) side of the valve with motion independent from the valve
‡
• cardiac or heart failure : inability of the heart to pump blood at an adequate rate to fill tissue metabolic requirements or the ability to do so only at an elevated filling pressure. It can be defined clinically as a syndrome of ventricular dysfunction accompanied by reduced exercise capacity and other characteristic hemodynamic, renal, neural, and hormonal responses.

Epidemiology : an estimated 4.7 million Americans suffer from the condition, with 400,000 new cases reported each year. It is an age-associated syndrome in that 75% of the patients are aged > 60 years (prevalence = 1-10% after age 65) and 80% of patients admitted to hospital are aged > 65 years.
Aetiology :
• congenital :
• defects in genes coding for
• a₂-AR
• b₁-AR
• phospholamban Arg⁹Cys
• PPAR-I7 is associated with reduced function of the left ventricle.
• few endothelial progenitor cells in blood
• acquired :
• CAD (75%)
• nonischemic
• known aetiology
• systemic arterial hypertension
• valvulopathies (aortic stenosis > aortic failure > mitral failure)
• viral myocarditis
• toxic myocarditis
• peripartum cardiomyopathy
• neuromuscular disease
• unknown aetiology
• dilated cardiomyopathy (25%)
• hypertrophic obstructive cardiomyopathy (HOCM)
Pathogenesis : ventricular dysfunction :
• decreased heart inotropism
• increased preload (therapy : vasodilatators, not positive inotropic drugs as they lead to an increase in afterload, too, due to the pre-existing compensatory peripheral vasoconstriction)
• increased afterload, defined as :
• cardiologic definition : heart wall thickness / ejection fraction = 1 / contractility
• clinical definition : aortic impedance
=> peripheral O₂ requests are not satisfied by CO => extrinsic (neuroendocrine) compensation mechanisms compensate the falsely sensed hypovolemia :
• orthosympathetic hyperactivity => down-regulation of b₁-AR(from 80% to 60% of cardiac b-ARs) and relative increase of b₂-AR (from 20% to 40% of all cardiac b-ARs)
• renin-angiotensin-aldosterone (RAAS) system
• atrial natriuretic peptide (ANP)
• nitric oxide (NO^.)
• antidiuretic hormone (ADH) / vasopressin (VP)
 => fluid retention (vicious circle !)
Congestive symptoms and signs occurs only when EF < 35 % : they depend on both myocardium deficiency and compensation mechanisms (on whose saturation level prognosis depends).
Classification : CO (index of anterograde function) and LVEDP (index of retrograde function) can be assessed clinically (by measuring sytemic ABP and temperature of extremities, and with chest auscultation and insepction of jugular vein distension, respectively) or with echography
• high-output heart failure : heart failure in which the cardiac output remains high enough to maintain a brisk circulation with warm extremities but is inadequate to meet demand; it is most often associated with hyperthyroidism, anemia, arteriovenous fistulas, beriberi, osteitis deformans, or sepsis.
• low-output heart failure : heart failure in which cardiac output is decreased, as in most forms of heart disease, leading to clinical manifestations of impaired peripheral circulation and peripheral vasoconstriction (cold, pale extremities, cyanosis, narrowed pulse pressure)
• diastolic heart failure (33%): heart failure due to a defect in ventricular filling caused by an abnormality in diastolic function

Aetiology :
• systemic arterial hypertension : decreased compliance of left ventricle (concentric left ventricular hypertrophy, myocardial fibrosis)
• ischemic heart disease (IHD) : reduced relaxation, reduced left ventricular compliance, left ventricular dilatation
• restrictive cardiomyopathy : reduced left ventricular compliance
• myocardial constriction : cardiac tamponade, constrictive pericarditis, mitral valve stenosis
• reduced diastolic filling time
• volume overload
Pathogenesis :
• abnormal relaxation
• pericardial restraint
• increased chamber stiffness
• chamber dilation
=> increased intraventricular diastolic pressure =>
• increased pulmonary pressure => pulmonary congestion => dyspnea
• decreased ventricular filling => decreased cardiac output (but EF > 50%) => fatigability
Laboratory examinations : E/A flow rate < 1 (it doesn't need assessment in patients with AF but normal mitral valve); EF > 50%
• systolic heart failure (33%) : heart failure due to a defect in expulsion of blood caused by an abnormality in systolic function^{ref1, ref2}

Aetiology :
• ischemic heart disease (IHD) (75%)
• nonischemic
• known aetiology
• systemic arterial hypertension
• valvulopathies (aortic stenosis > aortic failure > mitral failure)
• viral myocarditis
• toxic myocarditis
• peripartum cardiomyopathy
• neuromuscular disease
• arrhythmias
• unknown aetiology
• dilated cardiomyopathy
• hypertrophic obstructive cardiomyopathy (HOCM)
Pathogenesis :
• decreased contractile mass
• ischemic heart disease (IHD) (50-70%), necrosis, apoptosis
• decreased inotropism :
• dilated cardiomyopathy
• viral myocarditis
• increased afterload : systemic arterial hypertension and pulmonary arterial hypertension
Laboratory examinations : EF < 50% (CI < 3   [L / min / m²]) at echocardiography or radionuclide angiocardioraphy
• systodiastolic heart failure (33%)
Grading :
• NYHA CHF staging : subjective grading of dyspnea under effort. Alternative heart failure classification :
• asymptomatic (NYHA class I)
• symptomatic (NYHA class II and class III)
• symptomatic with recent dyspnea at rest (class IIIb)
• symptomatic with dyspnea at rest (class IV)
• AHA-ACC CHF staging :
• compensated heart failure
• stage A : at high risk for heart failure but without structural heart disease or symptoms of HF. Patients with hypertension, coronary artery disease, diabetes mellitus, using cardiotoxins or with family history of cardiomyopathy
• stage B : structural heart disease (akinesia, valvulopathies, reduced EF) but without symptoms of HF. Patients with : previous MI, LV systolic dysfunction, asymptomatic valvular disease
• uncompensated heart failure
• stage C : structural heart disease with prior or current symptoms of HF (dyspnea). Patients with : known structural heart disease, shortness of breath and fatigue, reduced exercise tolerance
• stage D : drug-refractory CHF requiring specialized interventions => need for hospital admission. Patients who have : marked symptoms at rest despite maximal medical therapy (e.g. those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized intervention)
Evolution :
• left-sided heart failure / left ventricular failure (LVF) : failure of adequate output by the left ventricle despite an increase in distending pressure and in end-diastolic volume (ischemic cardiomyopathy is heart failure with left ventricular dilatation resulting from ischemic heart disease; it does not meet the strict definition of a cardiomyopathy) : decrease of mean pressure in systemic arterial circulation => hypoxia in ...
• forward heart failure : a concept of heart failure that emphasizes the inadequacy of cardiac output relative to body needs; edema is attributed primarily to renal retention of sodium and water, and venous distention is considered a secondary feature.
• muscles : fatigue
• brain : anxiety, confusion, Cheyne-Stokes breathing due to ischemia of respiratory centre
• kidney : ischemia of juxtaglomerular apparatus and tubular necrosis
• increase of mid-diastolic pressure and volume in left ventricle
• appearance of the S₃ sound (and S₄ sound) (usually associated with tachycardia creating a S₃ gallop)
• increase of end-diastolic pressure and volume in left ventricle
• functional dilatation of mitral valve annulus => appearance of S₄ sound, variable intensity of S₁ sound and systolic regurgitation murmur (mitral valve failure or tricuspid valve failure)
• cardiomyocyte stirring => increase of cardiomyocyte contractility
• compensatory tachycardia (> 120 bpm) or bradycardia in patients with hypothyroidism
• secondary dilated cardiomyopathy
‡
• increase of left atrium end-diastolic pressure (LAEDP) => atriomegaly

Symptoms & signs : Broadbent's inverted sign : pulsations synchronizing with ventricular systole on the posterior lateral wall of the chest in gross dilatation of the left atrium.
‡
• increase of hydrostatic pressure in lung capillaries (pulmonary arterial hypertension / congestive pneumopathy)
• backward heart failure : a concept of heart failure stating that imbalance of performance of the ventricles due to dysfunction of one results in a rise in pressure behind that ventricle, with backward transmission of the increased pressure and consequent rise in venous pressure and distention
• hemoptysis due to rupture of a bronchial vein
• orthopnea : cardiac asthma / Rostan's asthma due to reduced strength and duration and hypoxemia and respiratory muscles, reduced pulmonary compliance due to congestion, obstruction of respiratory tract, hyperventilation (mechanoceptors, hypoxemia, hypercapnia). Under the same stress conditions a cardiopathic first undergoes anaerobiotic work => increase in P_CO2 => compensatory hyperventilation (polypnea) => increase of TV => ventilatory reserve = (IC - TV) / IC < 70% => activation of intrathoracic receptors and somatic sensory nerves => unpleasant sensation.

‡
• acute pulmonary cardiogenic edema => dyspnea
• CHF patients spent a significantly smaller percentage of their sleep time in the left lateral decubitus (LLD) position than in the right lateral decubitus (RLD) position, directly relating to the left ventricular end diastolic diameter (LVEDD) value and pulmonary capillary wedge pressure (PCWP) and inversely relating to cardiac output (CO). None of these factors affects the amount of time spent sleeping in RLD or supine positions. This may be a source of sleep disruption, related to the presence of cardiomegaly and/or pulmonary edema and probably one of the factors contributing to the predominance of right-sided pleural effusions in patients with heart failure. Anyway neither the left nor right sleeping positions are associated with significant differences in HR, mean arterial oxygen saturation, apnea/hypopnea index, or frequency of arousals, so there is no compelling reason to advise them to avoid the LLD position.
‡
• right-sided heart failure / right ventricular failure (RVF) : failure of proper functioning of the right ventricle, with increase of mean pressure in right ventricle; it is often combined with left-sided heart failure
• functional dilatation of tricuspid valve annulus => tricuspid valve failure => variable intensity of the S₁ soundand systolic regurgitation murmur
‡
• increase of mean right atrium pressure => hypokinetic circulation (circulation time > 25")
• Gärtner's phenomenon : the degree of fullness of the veins of the arm as it is raised above the level of the heart and the point at which the veins collapse indicate the degree of pressure in the right atrium
‡
• increase of mean pressure in systemic venous circulation (> 16 mmH₂O)
• hepatomegaly (liver is a.k.a. the 3^rd ventricle !) and jaundice
• cardiac cirrhosis => ascitis and dyspepsia => cachexia
• jugular vein distension (JVD) : arteriolization of jugular venous pulse in tricuspidal failure and hepatojugular reflux
• cyanosis of lips
• lower extremity edema due to orthopnoic position : pretibial subcutaneous edema
• congestion of intestinal mucosa => reduced calorie intake and absorption => cardiac cachexia
• cold hands and engorged forearm veins
• bilateral hydrothorax (or only right-sided : if only left-sided suspect pulmonary embolism or pleuritis)
• venous hypertension > 16 mmH₂O
If heart failure occurs in both heart halves it is a.k.a. congestive heart failure (CHF) : a clinical syndrome due to heart disease, characterized by breathlessness and abnormal sodium and water retention, often resulting in edema. The congestion may occur in the lungs or peripheral circulation or both, depending on whether the heart failure is right-sided or general.
• acute congestive heart failure (aCHF) : rapidly occurring deficiency in cardiac output marked

Aetiology :
• sudden increase in preload : rupture of tendon chords
• sudden decrease in afterload : hypertensive crises, pulmonary embolism
Symptoms & signs : venocapillary congestion, hypertension, and edema, usually pulmonary edema.
Robertson's sign : fibrillary contraction of the pectoralis muscle over the cardiac area in approaching death from heart disease
Framingham criteria for diagnosis of CHF : atleast one major and 2 minor criteria are required to establish a clinical diagnosis of CHF
• major criteria :
• paroxysmal nocturnal dyspnea
• jugular vein distention (JVD)
• small bronchi coarse crackles or rales
• cardiomegaly
• acute pulmonary edema
• S₃ gallop
• increased venous pressure (> 16 cmH₂O)
• positive hepatojugular reflux
• minor criteria
• extremity edema
• night cough
• dyspnea on exertion
• hepatomegaly
• pleural effusion
• vital capacity reduced by one-third from normal
• tachycardia (>= 120 bpm)
• major or minor : weight loss >= 4.5 kg over 5 days of treatment
Comorbidities : as many as 25-60% of heart failure patients have anemia, defined as hemoglobin < 12 g/dL in women and < 13g/dL in men. Studies have shown that if you have anemia and heart failure, your risk of death and complications are increased appreciably -- with as much as 30-60% additional risk of death and hospitalization from heart failure. the quartile of patients with the largest average decreases in Hgb over 12 months (defined as an average decrease of 1.6 g/dL, from 14.2 to 12.6 g/dL) experienced 47% more hospitalizations and 60% more deaths, compared to those in the quartile that exhibited an insignificant (0.10 g/dL) change in hemoglobin during 12 months. The researchers report that an increase in Hgb was associated with a 22% lower death rate in patients with anemia, compared to 21 percent without anemia, at the start of the study^ref.
Laboratory examinations :
• basal EKG : IHD, left ventricular hypertrophy with overload, reduced voltages (in tachycardia) or conduction disturbances (bradycardia of hypothyroidism), tachyarrhythmias or bradyarrhythmias
• the ECG strain pattern of ST depression and T-wave inversion is strongly associated with left ventricular hypertrophy (LVH) independently of coronary heart disease and with an increased risk of cardiovascular morbidity and mortality in hypertensive patients. ECG strain identifies hypertensive patients at increased risk of developing CHF and dying as a result of CHF, even in the setting of aggressive blood pressure lowering^ref.
• chest X-ray :
• size of cardiac shadow (CI > 0.5 in deep inspiration, in laterolateral projection the left ventricle superates the azygos line, reaches the vertebral column and superates its border)
• blood flow reversion in the pulmonary circulation (low at bases, higher at apices, where pulmonary veins (>16 mmHg) become visible, interstitial edema (> 25 mmHg : Palla sign, Kerley's lines), alveolar edema (parenchymal butterfly opacities)
• => echocardiography (EF%) with transmitral fluximetry (E/A ratio) allows differentiation between systolic and distolic failure, detection of ischemic heart disease, diameter and wall thickness of heart chambers and heart valves (stenosis if transvalvular velocity > 4 m/s)
• => radionuclide angiocardioraphy : overall and segmental function
• optional :
• cardiac catheterism and coronarography => PTCA/CABG
• endomyocardial biopsy
• tests for amyloidosis and hemochromatosis
• oxygen consumption (effort tolerance tests)
• tests for RAS and pheochromocytoma in patients with hypertension and pulmonary edema and normal heart function
• renal function test (creatininemia, urinalysis), CBC, hyponatremia, hypokalemia, chloridemia, magnesemia, glycemia, TSH, liver function tests
• ANA, RF
• lipid profile
• [metanephrine and catecholamines]_urine
• [norepinephrine]_plasma increases by 30%
• [renin]_plasma doubles every 2 mmHg drop in P_O2 from 100 to 80 mmHg
• heart-disease, heart-failure or heart-lesion cells (macrophages containing granules of iron, found in the pulmonary alveoli and sputum in CHF)
• [BNP or N-terminal pro-brain natriuretic peptide (NT-proBNP)]_plasma> 400 pg/ml : it is used for diagnosis, screening for asymptomatic left ventricular dysfunction, risk stratification and prognostication (see below), and treatment monitoring and has an higher accuracy than Framingham criteria in predicting the risk of mortality to sudden death and hospitalization. The suggested decision cut-point for the detection of heart failure for the BNP point-of-care assay is 100pg/ml in those aged more than 55 years. For NT-proBNP the recommended decision cut points are 100 pg/ml for men and 150 pg/ml for women in Europe, but 125 pg/ml for both genders in the USA. At present, there are two natriuretic peptide assays commercially available in both the USA and Europe that can be used in routine clinical and laboratory practice. The first is a rapid fluorescence immunoassay for BNP, which provides results within 15 min on a point-of-care patient testing device (Biosite Diagnostics, San Diego)^ref. Results on this device generally correlate well with results from radioimmunoassay^ref. This method may be particularly attractive in clinical situations where access to a laboratory is difficult or when a rapid result is required. The second is an electrochemiluminescent assay available for measuring NT-proBNP with a processing time of only 18 min (Roche Diagnostics GmbH, Basel)^ref. A further laboratory-based assay for BNP is available currently in Europe only and is manufactured by Bayer. The decision cut-point for the diagnosis of heart failure is identical to that of the Biosite assay—100pg/ml. Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea^{ref1, ref2}
Miscroscopic anatomy : nuclei appear large in transverse sections as cardiomyocytes are stirred; increased mitochondrialuncoupling proteins (UCPs)and depleted glucose transporter protein. Treatment should lower plasma free fatty acids and provide an alternative energy source. The results should be treated with caution because they do not prove a causative role for UCPs in heart failure, and the function of UCPs in the heart is still being investigated^ref.
Mechanisms of heart remodeling :
• neurohumoral : SNS, RAAS, and endothelin increase preload and afterload => negative hemodynamic and cellular effects
• myocyte biology alterations :
• eccitation/contraction decoupling
• cytoskeletal proteins
• myocytolysis
• hypertrophy
• modification of myocardial structure :
• necrosis/apoptosis
• fibrosis and collagene degradation
• alteration of geometry :
• dilatation
• spherical shape
• thinning of walls
• mitral valve failure
Therapy :
• prevention (most important!) :
• stage A : reduce ABP, treat cholesterolemia, glycemia, encourage cessation of cigarette smoking and drug abuse (cocaine, ethanol), ACEIs
• stage B : all measures under stage A, ACEIs in appropriate patients, b₁-blockers, peripheral vasodilators (?)
• correction of cause :
• IHD relapse, PTCA/CABG if hibernated myocardium is detected at echo-dobutamine
• left ventriculoplasty
• surgery
• heart transplantation
• ventricular assist device (VAD)
• total artificial heart (TAH)
• cardiomyoplasty
• dynamic cardiomyoplasty
• cellular cardiomyoplasty / cell therapy :
• stem cell cardiomyoplasty
•  haemopoietic stem cells
• cardiac stem cells
• autologous skeletal myoblasts
• gene therapy for induction of neoangiogenesis
• absolute rest in the first phase, then only in weekends, in a seated position
• short-acting benzodiazepines
• gradual restart of dynamic physical activity
• diet : avoid abundant meals, low-salt, low-calorie in overweight/obese patients
• reduce water intake in patients with hyponatremia
• precipitating cause : PTCA reduce symptoms but has the same prognosis of medical therapy on overall survival; CABG with arterial segment (immediate restenosis or permanent patency)
• reduce cardiac work (reduce pre and afterload)
• control hydrosaline retention
• increase contractility
• acting CHF (stage C and stage D) :
• symptomatic therapy
• symptoms due to hydrosaline retention : reduced water intake, diuretics, bed rest (decreased cardiac work => reduced aldosteronemia => increased sodiuria)
• improvement of pump function : anti-CHF drugs (ex adiuvantibus criterion : loss of > 5 L in 5 days of treatment with diuretics)
• reduce afterload with ACEIs, AT₁-antagonists, non inotropic peripheral vasodilators
• increase of inotropism : digitalis glucosides (in systolic heart failure), b₁-agonists, PDEI while waiting for heart transplantation
• in diastolic heart failure (benign prognosis) :
• level of evidence I : antihypertensive drugs, cardioversion in patients with AF, diuretics to control pulmonary congestion and peripheral edemas
• level of evidence IIa : CABG/PTCA
• level of evidence IIb : cardioversion or Na⁺ / K⁺ ATPase inhibitors in patients with AF, b₁-blockers, ACEIs, AT₁-antagonists, and CCBs in patients with already controlled hypertension
• reduction of mortality :
• ACEIs (captopril, enalapril, lisinopril, ranipril, trandopril) inhibit RAAS and SNS and reduce mortality by 18%
• AT₁-antagonists (valsartan and candesartan) reduce mortality by 20-33%
• b₁-blockers (metoprolol, bisoprolol, carvedilol, also associated to ACEIs) act as antiarrhythmics, reduce remodeling and prevent ischemia, reducing mortality by 34%
• MR antagonists inihibit sodium retention (not affected by ACEIs and AT₁-antagonists), hypokalemia and endocardial fibrosis and hyperplasia, reducing mortality by 16%(eplerenone) to 30%(spironolactone)
• useless drugs : ET₁ antagonists, etanercept; omapatrilat gives the same benefits of ACEIs but has more side effects in African-Americans)
• other : BNP, ICD to prevent VF, HMG-CoA reductase inhibitors, anticogulant drug, vasopressin antagonists
• recovery of structure and function (CHD, HTX)
• surgery
• heart transplantation
• ventricular assist device (VAD)
• total artificial heart (TAH)
• cardiomyoplasty
• dynamic cardiomyoplasty
• cellular cardiomyoplasty / cell therapy :
• stem cell cardiomyoplasty
•  haemopoietic stem cells
• cardiac stem cells
• autologous skeletal myoblasts
• gene therapy for induction of neoangiogenesis
• inhibition of biohumoral mechanisms responsible for left ventricular remodeling : AT₂ receptor agonists ?
• acute CHF : reduce preload and afterload with peripheral vasodilators => low doses of MR antagonists
• untreatable CHF : ultrafiltration and isotonic fluids (diuretics are useless as the renal perfusion pressure is too low !)
Prognosis : 50% die within 5 years of the diagnosis (overall mortality = 5-10%/yr) due to sudden cardiac death (50%) or cachexia (50%). Factors that have been shown to be predictors of mortality are increasing age, a history of diabetes mellitus or renal dysfunction, higher functional disability measures such as NYHA class (5-10%/yr in class II, 10-20%/yr in class II, 20-50%/yr in class IV), LVEF < 25%, hyponatremia and hypokalemia due to RAAS activation, lower BMI, lower ABP, the presence of ankle oedema, lower quality of life scores, high BNP and catecholamines, arrhythmias, and renal failure
• [BNP]_plasma : each 100 pg/ml increase in BNP is associated with a 35% increase in the relative risk of death. In asymptomatic patients, BNP > 20 pg/ml is associated with a doubled risk of death^ref
‡
• cardiogenous shock
• myogenic
• mechanical
• arrhythmic
Pathogenesis => symptoms & signs : EF ~ 10-15% => severe systemic arterial hypotension => compensatory tachycardia with pulseless electrical activity (PEA) / electromechanical dissociation (EMD) (normal EKG but no peripheral arterial pulses due to decreased CO), hemometakinesis => anaerobic metabolism of respiratory muscles => metabolic acidosis=> myasthenia, acute renal failure (ARF), sea-like skin (alterated cyanotic and ischemic areas due to vein and artery vasocontriction, respectively), abdominal silence, lipothymia => syncope. In a vicious positive feedback compensatory peripheral vasoconstriction increases heart work worsening heart failure.
Treatable causes :
• hypovolemia/hemorrhage
• tension pneumothorax
• cardiac tamponade
• pulmonary embolism (PE)
• hyperkalemia
• anaphylaxis
Laboratory examinations : echocardiography
Therapy : positive inotropic drugs, vasodilators, and counterpulsation
‡
• sudden cardiac death (SCD) : unexpected natural death due to cardiac causes that occur rapidly after the onset of acute symptoms in a patient with or without known preexisting heart disease, in whom cardiac dysfunction produces abrupt loss of cerebral blood flow. The interval between the onset of symptoms and death is given variably as ranging from < 1 hour to < 24 hours.

Epidemiology : nearly 50% of all deaths attributable to cardiovascular disease are sudden in nature, accounting for the loss of 300,000-400,000 lives annually in the USA^ref.
Aetiology : malignant arrhythmia (sudden arrhythmic death syndrome (SADS)) : 4.1% of sudden cardiac deaths in the 16-64 age-group are unexplained (cardiac pathological findings are normal and toxicological tests are negative). 80-90% of such deaths are due to ventricular tachyarrhythmias (ventricular fibrillation), while the remainder may result from bradyarrhythmias, complete intraventricular block or ventricular asystole (cardiac standstill), or pulseless electrical activity^ref
• coronary artery disease (myocardial infarction/ischemia) (80%^ref : the roles of myocardial ischemia or prior myocardial infarction (MI) in this regard are well established^ref
• nonischemic dilated cardiomyopathy
• hypertrophic cardiomyopathy (10-15% of arrhythmic deaths^ref)
• < 5% of malignant arrhythmias^ref.
• inherited cardiac disease (22%)
• arrhythmogenic right ventricular dysplasia
• Brugada syndrome
• long QT syndrome
• short QT syndrome
• Wolff-Parkinson-White syndrome
• complex congenital heart disease
• valvular heart disease
• cardiac sarcoidosis
• myocarditis
• non-structural cardiac electrophysiological disease
• drug induced
• electrolyte/metabolic disturbances
• aortic dissection
• pulmonary embolism
• pulmonary hypertension
Conventional, modifiable cardiovascular risk factors such as cigarette smoking, hypertension, diabetes mellitus, and dyslipidemia serve as easily identifiable markers of an increased risk of sudden cardiac death. However, their primary significance lies in their link to coronary artery disease, the predominant disease predisposing to sudden cardiac death, rather than as specific markers for immediate fatal arrhythmia^ref. Clinically, the degree of functional impairment, as categorized by the New York Heart Association classification, and the degree of left ventricular systolic dysfunction, as assessed by echocardiography, radionuclide scintigraphy, or radiocontrast ventriculography, are powerful predictors of the risk of death, whether it is arrhythmic or non-arrhythmic in nature^{ref1, ref2}. Invariably, an episode of aborted sudden cardiac death due to hemodynamically unstable sustained ventricular tachycardia or ventricular fibrillation unassociated with a reversible cause engenders the highest risk of sudden cardiac death^{ref1, ref2}.
Pathogenesis : circulatory arrest or standstill
Prognosis : evidence from community-based studies indicate that only 4-33% of people with out-of-hospital cardiac arrest survive to admission^{ref1, ref2}. Consequently, implantable cardioverter-defibrillator (ICD) therapy has become an important option in both primary and secondary prevention of sudden cardiac death due to ventricular tachyarrhythmias.
Laboratory examinations : standard 12-lead electrocardiography may reflect underlying structural heart disease or even help specify diseases of electrophysiological concern, including long QT syndrome^ref, short QT syndrome^ref, arrhythmogenic right ventricular dysplasia^ref, Brugada syndrome^ref and hypertrophic cardiomyopathy^ref. Additional noninvasive testing, such as 24-hour Holter monitoring, can be useful in ascertaining the risk of sudden cardiac death, especially if nonsustained or sustained ventricular tachycardia is documented in certain highrisk subgroups, such as those with left ventricular systolic dysfunction and CAD^ref. Further methods of noninvasive testing have been evaluated. After MI, signal-averaged electrocardiography demonstrates high negative predictive value, but clinical utilization remains limited by its low positive predictive value^{ref1, ref2, ref3}. Studies of noninvasive tests focusing on the role of the autonomic nervous system, such as heart rate variability (HRV)^ref and baroreflex sensitivity^ref, have indicated relatively low accuracy as predictors of arrhythmic events. To date, other noninvasive tests evaluating electrocardiographic repolarization abnormalities, including QT-interval dispersion and T-wave alternans, have proven either inconsistent or lacking in applicability beyond specific high-risk groups^ref. Electrophysiological testing continues to occupy a role in risk stratification for sudden cardiac death. Induced sustained ventricular tachyarrhythmia by programmed electrical stimulation is a well-established marker of increased risk of ventricular tachyarrhythmias^{ref1, ref2}. However, electrophysiological testing remains limited by the significant proportion of false negative results that occur^ref. Nevertheless, it remains a useful tool for evaluating patients with impaired left ventricular function and syncope^ref or nonsustained ventricular tachycardia^{ref1, ref2}.
Secondary prevention : in 1997, the Antiarrhythmics Versus Implantable Defibrillators (AVID) study provided definitive proof of the superiority of ICD therapy over drug therapy for those patients at highest risk of sudden cardiac death-those who had already experienced an aborted cardiac arrest^ref. This landmark multi-center, unblinded, randomized controlled trial enrolled 1,016 patients resuscitated from near-fatal ventricular fibrillation or ventricular tachycardia (not due to reversible causes) with left ventricular ejection fraction (LVEF) < 40%, and assigned them to either ICD therapy or antiarrhythmic drug therapy (empirically administered amiodarone in 95.8% of cases). The trial was stopped prematurely when ICD therapy was shown to result in a significant survival advantage in comparison to antiarrhythmic drug therapy. The mortality rate in the ICD group was 24.6% vs. 35.9% in the antiarrhythmic group after 3 years of follow-up, yielding a relative risk reduction of 31%. The resulting average length of additional life associated with ICD therapy at 3 years was 2.7 months. However, one area of concern in the AVID study was the significant difference in bAR therapy between the ICD group (47.6%) and the antiarrhythmic group (18.9%), probably yielding some degree of survival advantage to the former. Similar results were reported in 2 smaller randomized trials, the Canadian Implantable Defibrillator Study (CIDS)^ref and the Cardiac Arrest Study Hamburg (CASH)^ref
Primary prevention : unfortunately, only a small percentage of patients who suffer a cardiac arrest in the U.S. each year survive to benefit from an ICD for secondary prevention. Hence, ICD therapy for primary prevention of sudden cardiac death has become the focus of intense clinical investigation in recent years. The first major study in this regard was the Multicenter Automatic Defibrillator Implantation Trial (MADIT), which included 196 patients with prior MI, LVEF ? 35%, nonsustained ventricular tachycardia (NSVT), and inducible sustained ventricular tachycardia upon electrophysiologic study not suppressible by intravenous procainamide^ref. Followup over 5 years demonstrated a dramatic 41% relative risk reduction in mortality in the group randomized to ICD therapy as compared to the group given conventional therapy (including amiodarone). The Multicenter Unsustained Tachycardia Trial (MUSTT) included patients with CAD, LVEF ? 40%, NSVT, and inducible sustained ventricular tachycardia on electrophysiologic study^ref. At 5 years, patients receiving ICD therapy experienced a mortality rate of 24% as compared to 55% for patients receiving antiarrhythmic therapy guided by electrophysiologic testing, and 48% for those patients treated with conventional therapy. More recently, the MADIT II study^ref compared 1232 patients with prior MI and LVEF ? 30%, without requiring documented NSVT or electrophysiologic testing, randomized either to ICD therapy or conventional medical therapy (including bAR blockers and angiotensin-converting-enzyme inhibitors). After 20 months of follow-up, the mortality rates were 19.8% in the conventional therapy group and 14.2% in the defibrillator group. In essence, one life was saved among every 11 implants.  Accordingly, the United States Food and Drug Administration further expanded its list of approved indications for ICD therapy. Not all studies have shown clinical benefit with ICD therapy. The Coronary Artery Bypass Graft (CABG) Patch Trial randomized 1,055 patients with LVEF ? 35%, no prior ventricular tachycardia/ventricular fibrillation, and abnormal signal-averaged electrocardiogram scheduled for CABG surgery to either concomitant epicardial ICD implantation or only conventional medical management-excluding antiarrhythmic agents^ref. ICD therapy did not improve survival, probably reflecting the important benefit provided by definitive surgical revascularization in reducing myocardial ischemia and improving left ventricular systolic function. Primary prevention trials have also been undertaken to study patients with non-ischemic cardiomyopathy. Recently, the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) study was released^ref. In it, 458 patients with non-ischemic cardiomyopathy, LVEF < 36%, NYHA I-III, and ventricular ectopy on Holter monitoring, were randomized to either conventional medical therapy or a single chamber ICD. After 29 months of follow-up, the DEFINITE study showed a significant 78.6% relative risk reduction in sudden cardiac death, but only a non-significant 30% relative risk reduction in overall mortality with ICD therapy (p=0.08). Previously, 2 smaller randomized trials, the Amiodarone versus Implantable Defibrillator in Patients with Non-ischemic Cardiomyopathy and Asymptomatic Non-sustained Ventricular Tachycardia (AMIOVIRT) study^ref, and the Cardiomyopathy Trial (CAT)^ref, had failed to show a mortality benefit with ICD therapy in the context of non-ischemic dilated cardiomyopathy. The relative lack of efficacy with ICD therapy in this group of patients may be due to the fact that the initiation of ventricular tachyarrhythmias in non-ischemic cardiomyopathy is often due to a focal autonomic mechanism rather than a reentrant mechanism^ref. Hence, patients with non-ischemic cardiomyopathy may be more amenable to prophylaxis against sudden cardiac death with effective neurohormonal modulation alone (utilizing appropriate medical therapy). Data from the as-yet-unpublished Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) may help to further elucidate the role of prophylactic ICD therapy in patients with non-ischemic cardiomyopathy^ref. The results of the recently published Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial may provide the key to optimizing the efficacy of ICD therapy^ref. In this trial, 1,520 patients with non-ischemic or ischemic (55%) cardiomyopathy, NYHA III-IV, LVEF ? 35%, and QRS ? 120 milliseconds, were randomized to optimal pharmacologic therapy alone or with cardiac resynchronization therapy (CRT+biventricular pacing) with either a pacemaker or ICD. After one year, CRT improved exercise tolerance and quality of life, and reduced mortality risk by 24%. More impressively, it reduced the relative risk of death by 36% (19.2% vs. 12.2%) when coupled with ICD therapy (Table 4). Therefore, it is likely that the benefits of CRT and ICD therapy are additive in patients with advanced heart failure and a prolonged QRS duration. ICD Therapy: Implantation and Follow-up ICD surgery in the 1980s and early 1990s required general anesthesia and prolonged hospital stays, and entailed a significant perioperative mortality rate^ref. In that era, open thoracotomy was required for placement of epicardial patches tunneled to attach to the generator, the large size of which (> 200 cc) necessitated abdominal implantation. In the 1990s, utilization of biphasic shock waveforms allowed for the development of active canisters (generators), which are smaller in size and do not require epicardial patches^{ref1, ref2}. These smaller devices (~ 40 cc) can be implanted in the subcutaneous pectoral region, and the cephalic, axillary, or subclavian routes can be utilized^ref for transvenous right ventricular endocardial lead placement. Accordingly, only local anesthesia and conscious sedation are required for device testing, hospital stays are short, and perioperative mortality rates are low^{ref1, ref2, ref3, ref4}. The cardioverter-defibrillator lead is capable of bipolar sensing and pacing. It has at least one metal coil and is connected to the generator. A large charge of electricity, for shocking, can flow between this coil and the generator. The bulk of the generator consists of the battery (lithium silver vanadium oxide) that allows rapid discharge into a capacitor for shocks. Battery longevity ranges from 4-10 years, depending upon usage. Longterm elective follow-up usually consists of office visits approximately every 3 months. Routine visits include a focused history, measurement of vital signs, physical examination and recording of the patient's current medical regimen. In addition, a manufacturer-specific computer programmer is used to analyze the device, to check battery, capacitor and lead status, and retrieve data pertaining to tachycardia episodes and therapies (including intracardiac electrograms).
Tiered Therapy and Inappropriate Shocks The present generation of programmable ICDs feature "tiered therapy", including anti-tachycardia pacing (ATP) for termination of monomorphic ventricular tachycardia, synchronized low-energy cardioversion, unsynchronized high-energy defibrillation and back-up bradycardia pacing. ATP therapies usually consist of "burst" or "ramp" pacing targeted to terminate ventricular tachycardia, usually due to a reentrant mechanism. If the tachycardia is not successfully terminated after attempts at overdrive pacing, then a low-energy biphasic cardioversion
(2-10 Joules) can be delivered. Ultimately, the ICD can deliver a high-energy biphasic shock (30-40 Joules) for the purpose of terminating ventricular
tachycardia or ventricular fibrillation. It is has become standard to forgo further ICD shocks following at least 5-6 sequential shocks for
a refractory ventricular tachyarrhythmia. One unique problem is that of preprogrammed ICD therapy delivery for benign or non-life-threatening tachyarrhythmias. Most commonly, sinus tachycardia or atrial tachyarrhythmia may result in a heart rate high enough to trigger detection and subsequent
ICD therapy delivery resulting in a painful, inappropriate shock (Fig. 5). Strategies to combat such undesirable scenarios include concomitant drug therapy (such as b-AR blockers or sotalol), software reprogramming (enabling automatic mode switch for atrial fibrillation or atrial flutter), upgrading
of the device's hardware (single to dual chamber sensing), and radiofrequency catheter ablation.
Hybrid therapy : since reducing the risk of sudden cardiac death is the ultimate goal, adjunctive antiarrhythmic therapy may be beneficial. In particular, sotalol has been shown to reduce mortality and both appropriate and inappropriate shocks following ICD implantation, as compared to placebo^ref. It may be necessary to reevaluate ATP therapies or defibrillation thresholds following the introduction of new antiarrhythmic agents, especially amiodarone^ref. Contemporary software allows for sophisticated, noninvasive electrophysiologic testing designed to induce, pace terminate, and cardiovert or defibrillate tachyarrhythmias. As well, scar-related (reentrant) ventricular tachycardia mapping and ablation is becoming increasingly practical and efficacious^ref. Such interventional electrophysiologic techniques can be helpful to patients experiencing multiple ICD shocks due to recurrent monomorphic ventricular tachycardia or to those prone to a slow, incessant monomorphic ventricular tachycardia unamenable to device detection and therapy delivery.
The role of the ICD in the epidemiologic period of delayed degenerative diseases will inevitably continue to grow and bring with it a number of medical, economic and social consequences. For appropriately selected patients, ICD therapy can prolong life for months or even years, but it does little to actually improve a patient's quality of life. The evolving role of concomitant biventricular pacing for patients with symptomatic left ventricular systolic dysfunction and intraventricular conduction delay has the potential to both improve functional status and lower mortality^ref. As the number of patients receiving ICD treatment continues to rise, so does the daunting prospect of more ICD patients presenting with "electrical storms". An electrical storm, defined as > 3 shocks within a 24-hour period, can be difficult even for an experienced cardiac electrophysiologist to manage, and will pose an increasing challenge to our emergency rooms and coronary care units. Finally, the cost of the ICD remains expensive (approximately $30,000 per device). In 2005, ICD therapy is projected to account for approximately $6.9 billion dollars, 0.4% of the U.S. national health care expenditure. This is a large sum for a nation already grappling with a sizable annual deficit and total debt. It has yet to be seen if our public institutions and private industry are capable of finding a solution that will be deemed affordable, practical, and fair to society as a whole.
Web resources : American Heart Association on sudden cardiac death
• post–cardiac injury syndrome (PCIS) : fever, chest pain, pleuritis, and pericarditis occurring several weeks to months after injury to the heart
• postpericardiotomy syndrome (PPS) : pericardial or pleural reaction occurring more than one week after opening of the pericardium, characterized by fever, chest pain, and signs of pleural and/or pericardial inflammation.
• CABG
Symptoms & signs : fever, pleural effusion pericardial effusions => cardiac tamponade
Laboratory examinations : high ESR/CRP, anti-cardiolipin and anti-myocardium antibodies
Treatment : NSAIDs, corticosteroids / IVIg for refractory cases
• post–myocardial infarction syndrome / Dressler's syndrome
• an unusual complication after percutaneous procedures such as coronary stent implantation,2 after implantation of epicardial pacemaker leads3  and transvenous pacemaker leads,4,5,6,7,8 and following blunt trauma,9 stab wounds,10 and heart puncture.11
• Signs :
• inspection when lying on back and during left lying with left arm over head.
• palpation : open-handed. In right cardiomegaly jugular veins are turgid.
• Laboratory examinations :
• echocardiography / ultrasonic cardiography (UCG) : a method of graphically recording the position and motion of the heart walls or the internal structures of the heart and neighboring tissue by the echo obtained from beams of ultrasonic waves directed through the chest wall. The mitral valve (whose movements are faster and wider than any other valve) and the usually larger right ventricle serve as a marking point for orientation.
• contrast echocardiography : that in which the ultrasonic beam detects tiny intravascular bubbles produced by intravascular injection of a liquid, such as the patient's blood, saline, or dextrose in water, or of small amounts of carbon dioxide gas; bubble movement can demonstrate abnormalities of blood flow.
Clinical uses of echocardiography :
• transthoracic echocardiography (TTE)
• M-mode echocardiography
• 2D echocardiography
• cardiac chambers :
• chamber size
• left ventricular hypertrophy
• regional wall motion abnormalities
• valve : morphology and motion
• pericardium :
• effusion
• tamponade
• masses
• great vessels
• stress echocardiography
• 2D
• myocardial ischemia
• viable myocardium
• Doppler : valve disease
• Doppler echocardiography
• valve stenosis
• gradient
• valve area
• valve regurgitation : semiquantitation
• intracardiac pressures
• volumetric flow
• diastolic filling
• intracardiac shunts
• transesophageal echocardiography (TEE)
• inadequate transthoracic images
• aortic disease
• infective endocarditis
• source of embolism
• valve prosthesis
• intraoperative
• cardio-CT
• cardio-MRI
• nuclear cardiology
• evaluation of ventricular function
• first pass radionuclide angiocardiography
• gated equilibrium radionuclide angiocardiography
• evaluation of perfusion
• myocardial perfusion scintigraphy
• gated SPECT (GSPECT)
• evaluation of necrosis
• ^99mTc-pyrophosphate scintigraphy
• ¹¹¹In-anti-myosin mAb (not routinely used in clinical practice)
• Bibliography
• American Heart Association : Advanced Cardiac Life Support

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