Cardiac Pathology

USMLE

Cardiac Pathology

Cardiac Pathology (Outline Notes)

Normal Heart   

hypertrophy dilation cardiomegaly

Myocardium 1) cardiac myocytes 2) five major components i) cell membrane (sarcolemma) and T tubules ii) sarcoplasmic reticulum iii) the sarcomere iv) mitochondria v) the nucleus 3) sarcomere - functional intracellular contractile unit of cardiac muscle i) thick filaments - myosin and thin filaments - actin ii) roponin and tropomyosin iii) Z-line - thin filaments anchored iv) Frank-Starling mechanism v) heart failure - pathophysiology 4) atrial myocytes are smaller and less structured than ventricular counterparts i) atrial granules - ANP ii) ANP released under conditions of atrial pressure elevation and distension iii) physiologic effects of ANP; vasodilation, natriuresis, suppression of renin-angiotensinaldosterone axis and fall in arterial pressure 5) Functional integration mediated by intercalated discs join individual cells permitting both mechanical and ionic coupling i) gap junctions provide electrical coupling with unrestricted passage on ions ii) abnormalities in distribution of gap junctions in IHD and myocardial heart disease responsible for development of arrhythmia 6) Cardiac conduction system i) Sinoatrial Node - pacemaker of the heart ii) Atrioventricular Node iii) Bundle of His iv) Right and left bundle branches

Blood Supply 1) 3 epicardial arteries and intramural arteries i) Left Anterior Descending Artery (LAD) (1) bifurcation of left coronary artery (2) diagonals and septal perforators (3) supplies apex of the heart, the anterior wall of LV and anterior two thirds of ventricular septum (4) occasionally perfuse the posterior third of the ventricular septum called left dominant circulation ii) Left Circumflex Artery (LCX) (1) bifurcation of left coronary artery (2) obtuse marginals (3) perfuses lateral wall of the LV iii) Right Coronary Artery (RCA) (1) perfuses the entire RV, the posterobasal wall of the LV and posterior third of the ventricular septum

Valves 1) Semilunar Valves i) aortic and pulmonary valves ii) normal valve cusps appear thin and transluscent

2) Atrioventricular Valves i) mitral and tricuspid valves have chordae tendinae attached to papillary muscles ii) normal mitral valve competency depends on coordinated actions of annulus, leaflets, cords, papillary muscles and associated LV wall (mitral apparatus)

Principles of Cardiac Dysfunction Mechanisms 1) Failure of the pump itself i) contracts weakly ii) cannot relax sufficiently 2) Obstruction to Flow i) lesion preventing valve opening causing increased ventricular pressure which overworks the chambers behind the obstruction ii) e.g. aortic valvular stenosis 3) Regurgitant Flow i) mitral or aortic valve regurgitation ii) adds a volume workload on the ventricle 4) Disorders of Cardiac Conduction or Arrhythmias i) lead to nonuniform and therefore inefficient contraction of the muscular walls 5) Disruption of the continuity of circulatory system i) permits blood to escape ii) e.g. gunshot wound

Heart Failure 1) heart unable to pump blood to meet requirements of the body and can do so only from an elevated filling pressure 2) Congestive Heart Failure (CHF) - poor prognosis 3) Cardiovascular response to excessive hemodynamic burden or disturbance on myocardial contractility i) Frank - Starling Mechanism (1) increased preload of dilation enhances contractility ii) Myocardial Hypertrophy (1) mass of contractile tissue augmented iii) Activation of neurohumoral systems (1) Norepinephrine (2) renin-angiotensin-aldosterone system (RAS) (3) atrial natriuretic peptide (ANP) 4) Systolic dysfunction i) deterioration of myocardial function ii) ischemic injury, pressure or volume overload or dilated cardiomyopathy 5) Diastolic dysfunction i) inability of the heart chamber to relax, expand and fill sufficiently ii) massive LVH, myocardial fibrosis, amyloid deposition or constrictive pericarditis

Cardiac Hypertrophy 1) 2) 3) 4)

compensatory response to increased mechanical work or trophic signals pressure-overloaded ventricles → pressure or concentric hypertrophy volume-overloaded ventricles → hypertrophy with dilation of ventricle sustained evolves to cardiac failure

Left Heart Failure 1) most often caused by i) Ischemic Heart Disease ii) Hypertension iii) Aortic and Mitral Valvular Disease iv) Non-ischemic Myocardial Disease 2) Heart i) Left ventricle often hypertrophied and dilated ii) Left atrium - secondarily enlarged with atrial fibrillation and possible thrombus formation iii) embolic stroke 3) Lungs i) Pulmonary congestion and edema ii) Pulmonary changes in sequence iii) perivascular interstitial transudate in the interlobular septa - Kerley B lines iv) edematous widening of alveolar septa v) edema fluid in the alveolar spaces

vi) Siderophages or Heart Failure Cells vii) Clinical Manifestations (1) Cough (2) Dyspnea - earliest (3) Orthopnea (4) Paroxysmal Nocturnal Dyspnea 4) Kidneys i) decreased cardiac output → reduction in renal perfusion → renin-angiotensin-aldosterone system → retention of salt and water → expansion of interstitial fluid and blood volumes → pulmonary edema ii) salt retention counteracted by atrial natriuretic peptide iii) prerenal azotemia - impaired excretion of nitrogenous products 5) Brain i) hypoxic encephalopathy ii) irritability, loss of attention span and restlessness iii) stupor and coma

Right Heart Failure 1) left-sided failure most common cause 2) Cor Pulmonale - right heart failure due to pulmonary hypertension i) right ventricle is burdened by increased resistance ii) bulging of ventricular septum to the left can cause left ventricular dysfunction 3) Liver and Portal System i) congestive hepatomegaly (1) chronic passive congestion – “nutmeg liver” (2) with left-sided failure too, severe central hypoxia produces centrilobular necrosis (3) cardiac sclerosis or cirrhosis ii) elevated portal pressure leading to (1) congestive splenomegaly (2) chronic edema of bowel interfere with absorption of nutrients (3) ascitis 4) Kidneys i) more marked than with left-sided failure 5) Brain i) hypoxia of CNS 6) Pleural and Pericardial Space i) Pleural (particularly right) and pericardial effusions ii) Pleural effusions range from 100 ml to 1 liter (1) large effusions cause partial atelectasis 7) Subcutaneous Tissue i) peripheral edema esp. pedal and tibial ii) bedridden patient - presacral iii) anasarca

Ischemic Heart Disease 1) myocardial ischemia - imbalance between supply and demand for oxygenated blood a) insufficiency of oxygen and reduced availability of nutrient substrate and inadequate removal of metabolite 2) atherosclerotic obstruction

Epidemiology 1) leading cause of death for both men and women in the US 2) has fallen over one-third i) prevention by modification of risk determinant ii) therapeutic advances

Pathophysiology 1) Fixed Coronary obstruction i) 90% - fixed obstruction with one or more lesion causing at least 75% reduction in area of at least one of the major epicardial artery (1) compensatory vasodilation not sufficient to meet increased demand ii) stenosing plaques within first several cm. of LAD and LCX and entire length of RCA. 2) B. Acute Plaque Change i) precipitate acute coronary syndrome ii) disruption of partially stenosing plaques

(1) Hemorrhage into atheroma (2) Rupture or fissuring (3) Erosion or ulceration 3) Coronary Thrombus i) acute transmural MI, thrombus superimposed on previously stenosing plaque ii) unstable angina, acute subendocardial infarction or sudden cardiac death, obstruction is incomplete iii) Factors that augment thrombotic potential (1) Platelets and generation of TxA2 (2) elevated blood fibrinogen (3) low plasminogen activator inhibitor (4) high Lipoprotein a (5) embolize (6) potent activator of growth signal to smooth muscle cells 4) Vasoconstriction i) compromise lumen size and contribute to plaque fracture ii) stimulated by: (1) circulating adrenergic agonists (2) released platelet products (3) impaired secretion of nitric oxide relative to endothelin due to endothelial dysfunction (4) mediators released by inflammatory cells

Angina Pectoris  paroxysmal and recurrent attacks of substernal or precordial chest discomfort caused by transient myocardial ischemia that falls short of infarction 1) Stable Angina i) most common form ii) pain precipitated by exertion and relieved by rest or by vasodilators iii) severe narrowing of atherosclerotic coronary vessels 2) Unstable Angina i) crescendo angina and preinfarction angina ii) pain occurs with increasing frequency and precipitated with less effort even at rest iii) impending infarction 3) Prinzmetal Angina i) intermittent chest pain at rest ii) vasospasm iii) unrelated to physical activity, heart rate or blood pressure iv) vasodilators, nitroglycerin and calcium channel blockers

Myocardial Infarction Serum Markers

A. Serum Markers in Acute MI Time of Elevation Peak

CK-MB

4 - 8 hrs

Troponin I and T AST LDH

3 – 6 hrs 12 – 16 hrs 24 hrs

18 hrs 16 hrs 2 days 3 – 6 days

Returns to normal 2 – 3 days 7 – 10 days 3 days 8 – 14 days

1) General Characteristics i) i most important cause of morbidity and leading cause of death in Western World ii) myocardial coagulative necrosis caused by coronary artery occlusion iii) series of progressive changes of the heart with release of myocardial enzymes and proteins iv) cells involved include neutrophils, macrophages and fibroblasts. v) Two distinct pattern (1) Transmural infarction (2) Subendocardial infarction 2) Cardiac Enzymes and Proteins i) Creatine Kinase (CK).

(1) CK-MB from myocardium primarily (2) rise - 4-8 hours (3) peak - 18 hours faster if reperfused (4) normal - 48-72 hours (5) normal CK and CK-MB during first 2 days of chest pain excludes MI ii) Lactate Dehydrogenase (LDH)

iii) Troponins (Tn) (1) ideal marker because (a) abundant cardiac-specific protein (b) released in serum following injury proportional to extent of injury (c) persistent (d) inexpensively, rapidly and easily assayed (2) troponin-T (TnT) and troponin I (TnI) regulate contraction of cardiac and skeletal muscles (3) in early stages like CK but persists for 7 to 10 days 3) Clinical Features i) rapid, weak pulse and often diaphoretic ii) dyspnea with pulmonary congestion and edema iii) Silent MI 4) Complications i) Arrhythmia - most common cause of death in first several hours ii) Myocardial pump failure - lead to CHF or shock iii) Myocardial rupture - within first 4-7 days and death due to cardiac tamponade iv) Rupture of papillary muscle v) Mural thrombosis vi) Ventricular aneurysm l vii) Pericarditis viii) Infarct extension ix) Infarct expansion B. Morphologic Changes in Acute Myocardial Infarction Time Gross Changes Microscopic Changes Clinical Correlation Vascular congestion at Arrhythmia most common 0 – 6 hours None perimeter of lesion cause of death 12 hours None Neutrophils appear Start of coagulative necrosis Slight swelling and change of with cytoplasmic 12- 24 hours color eosinophilia, disappearance of nuclei Well-developed coagulative Pale or reddish brown infarct 24 hours necrosis with neutrophil with surrounding hyperemia infiltration Macrophage replaces Increasingly yellow color of 3rd day neutrophils, phagocytosis of infarct debris Yellow infarcted area Angiogenesis begins with Risk of myocardial rupture 7th day surrounded by congested red growth of young fibroblasts greatest at 4 to 7 days border and new vessels Red, newly formed vascular Phagocytosis of debris connective tissue encircles almost complete, with th 10 day and gradually replaces yellow continued fibrovascular necrotic tissue growth 2nd to Synthesis of collagen and 4th week other intracellular matrix Increasing pallor of infarct 5th week Progressive fibrosis due to progressive fibrosis Well-developed gray white Ventricular aneurysm may 3 - 6 months Mature fibrous tissue scar occur in scarred area ► Special Note ■ Enzyme marker appearance: Troponin, Creatine Kinase -> AST -> LDH

Chronic Ischemic Heart Disease 1) progressive heart failure as a consequence of ischemic myocardial damage 2) prior myocardial infarction and even aortocoronary bypass surgery.

3) exhaustion of compensatory hypertrophy of non-infarcted viable myocardium now in danger of ischemic injury 4) left ventricular hypertrophy and dilation 5) myocardial hypertrophy, diffuse subendocardial vacuolization and scars of healed infarcts

Sudden Cardiac Death 1) unexpected death from cardiac causes within 1 hour after or without the onset of symptoms.

2) in vast majority of cases, first clinical manifestations of IHD

3) lethal arrhythmia (asystole, ventricular fibrillation) 4) other probable causes include i) congenital structural or coronary arterial abnormalities ii) aortic valve stenosis iii) mitral valve prolapse iv) myocarditis v) dilated or hypertrophic cardiomyopathy vi) pulmonary hypertension vii) hereditary or acquired abnormalities of the cardiac conduction system viii) isolated hypertrophy, either hypertensive or unexplained

Hypertensive Heart Disease Systemic Hypertensive Heart Disease 1) criteria for diagnosis i) LVH (usually concentric) in the absence of other cardiovascular pathology ii) a history or pathologic evidence of HPN 2) hypertrophy of the heart is an adaptive response to pressure overload

Pulmonary Hypertensive Heart Disease 1) Cor Pulmonale with RVH, dilation and potentially failure secondary to pulmonary HPN 2) RV failure due to congenital heart disease or LV failure is not Cor Pulmonale 3) Causes: i) Diseases of the Pulmonary Parenchyma e.g. COPD, etc. ii) Diseases of Pulmonary Vessels e.g. Primary Pulmonary Hypertension, etc. iii) Diseases affecting Chest Movement e.g Kyphoscoliosis, etc. iv) Disorders inducting Pulmonary Arterial Constriction e.g. Hypoxemia, etc.

4) Acute Cor Pulmonale i) follow massive pulmonary embolism 5) Chronic Cor Pulmonale i) follows prolonged pressure overload

Rheumatic Fever and Heart Disease ďƒ˜ ďƒ˜

Rheumatic Fever - acute immunologically mediated multi-system inflammatory disease after group A beta hemolytic streptococcal pharyngitis Acute rheumatic carditis - may progress to chronic valvular deformities

Characteristic 1) most important consequence is chronic RHD with deforming fibrotic vascular disease (primarily mitral stenosis) which can produce permanent dysfunction that can be severe and fatal decades later 2) Jones Criteria i) migratory polyarthritis of the large joints ii) carditis iii) subcutaneous nodules iv) erythema marginatum v) Sydenham chorea - neurologic disorder with involuntary purposeless, rapid movements

Etiology 1) immunologic origin 2) streptococcal antigens elicit an antibody reactive to M proteins of streptococcal organisms that crossreacts with tissue glycoproteins in the heart, joints and other tissues 3) genetic susceptibility

Pathology 1) Aschoff Body i) classic lesion of rheumatic fever ii) interstitial myocardial inflammation iii) fragmented collagen and fibrinoid material, surrounded by T-lymphocytes, occasional plasma cells and Anitschkow cells and occasional Aschoff cells 2) Pancarditis i) Pericarditis ii) Myocarditis (1) most common cause of death during early stages of acute rheumatic fever

iii) Endocarditis (1) areas of highest hemodynamic stress (a) points of valve closure and the posterior wall of left atrium (b) MacCallum plaque (2) In early stages, valve leaflets are red and swollen and vegetations (verrucae) form along the lines of closure of valve leaflets (a) nonfriable and do not embolize (3) Rheumatic heart disease (a) late sequelae due to fibrotic healing - valves become thickened, fibrotic and deformed (b) fusion of valve cusps, thickening of chordae tendinae and calcification (i) Mitral Valve 1. frequently involved 2. only valve affected in 50% of cases 3. stenosis with fish-mouth buttonhole deformity, insufficiency or both 4. Mitral stenosis has diastolic pressure higher in left atrium than left ventricle (ii) Aortic Valve 1. affected most with mitral valve 2. stenotic or insufficiency (iii) Tricuspid Valve 1. affected along with mitral and aortic valve in 5% of cases (iv) Pulmonary Valve (4) Noncardiac Manifestations (a) Fever, malaise and increased ESR (b) Joint involvement (i) Arthralgia (ii) Arthritis 1. larger joints of knees, ankle, wrists and elbows (iii) Migratory polyarthritis (c) Skin Lesions (i) subcutaneous nodules (ii) erythema marginatum (d) Central nervous system (i) sydenham chorea

Clinical Features 1) Acute Rheumatic fever (ARF) i) occurs 10 days to 6 weeks after group A beta-hemolytic streptococcal pharyngitis ii) affect children although 20% occurs in middle to later life iii) antibodies to streptolysin O and DNAse B even if pharyngeal cultures negative iv) arthritis and carditis (1) migratory polyarthritis with fever (2) acute carditis - heart failure 2) Chronic Rheumatic Carditis i) increased vulnerability to reactivation ii) Carditis worsens and damage is cumulative iii) manifests after years or decades of recurrent attacks iv) signs and symptoms depend on which valve involved

Other Endocarditis Infective Endocarditis (IE) 1) 2) 3) 4)

bacterial or fungal infection of the endocardium large, soft, friable, easily detached vegetations complicated by ulceration, with perforation of valve cusps or rupture of chordae tendinae Classification i) Acute endocarditis (1) caused by S. aureus, 50% of cases (2) secondary to infection elsewhere ii) Subacute bacterial endocarditis (1) less virulent organisms (eg. S. viridans, 50% of cases) (2) patient with congenital heart disease or pre-existing valvular disease often of rheumatic origin 5) Clinical Features i) Valvular involvement (1) mitral valve most frequent (2) mitral valve with aortic valve in 40% of cases

ii)

(3) tricuspid valve involved in 50% of case of endocarditis in intravenous drug users usually staphylococcus Complications (1) Distal embolization (2) septic infarct in brain and elsewhere (3) focal necrotizing glomerulitis caused by immune complex disease or septic emboli

Non-bacterial Thrombotic Endocarditis 1) debilitating disorders, e.g. metastatic cancer 2) small, sterile fibrin deposits along line of closure of valve leaflets 3) sterile peripheral embolization

Libman-Sacks Endocarditis 1) SLE 2) small vegetations on either or both surfaces of the valve leaflets

Endocarditis of Carcinoid Syndrome 1) 2) 3) 4)

carcinoid syndrome - vasoactive peptides and amines esp. serotonin thickened plaques involving the mural endocardium or valvular cusps of right side of heart rarely involves left heart - serotonin detoxified in lungs elevated urinary 5-hydroxyindoleacetic acid and chromogramin A

1) 2) 3) 4)

late result of rheumatic fever secondary to various other inflammatory process congenital prosthetic cardiac valves due to physical deterioration, thrombus formation or infectious endocarditis

Valvular Heart Disease

Mitral Valve 1) Prolapse (MVP) i) most frequent valvular lesion, often in young women ii) myxoid degeneration of the ground substance of the valve iii) "floppy" cusp with prolapse into the atrium during systole.

(1) systolic murmur with a midsystolic click iv) benign and asymptomatic but can result in mitral insufficiency v) associated with arrhythmias vi) predisposes to IE 2) Stenosis i) almost always RHD 3) Insufficiency i) usually RHD ii) result from MVP, IE or damage to a papillary muscle from MI iii) LV dilation with stretching of mitral valve ring

Aortic Valve 1) frequently involved in RHD and IE with mitral valve 2) Stenosis i) calcific aortic stenosis due to calcification of: (1) otherwise normal valve due - degenerative calcific aortic stenosis > 60 y.o.

(2) a congenital bicuspid aortic valve (3) valve affected by RHD, with fusion of valve commisssures 3) Insufficiency i) caused by (1) Nondissecting aortic aneurysm due to cystic medial necrosis (2) RHD - with associated mitral valve disease (3) Syphilitic aortitis (Luetic) with dilation of the aortic valve ring

Tricuspid Valve 1) involved with mitral and aortic valves i) trivalvular involvement accounts for 5% of RHD 2) in carcinoid syndrome

Pulmonary Valve

1) most commonly by congenital malformation i) occurs either alone or part of congenital defects, e.g. tetralogy of fallot 2) rarely in RHD 3) in carcinoid syndrome

Myocardial Heart Disease 

Cardiomyopathy - noninflammatory and are not associated with hypertension, congenital heart disease, valvular disease or coronary artery disease

Dilated or Congestive Cardiomyopathy 1) 2) 3) 4)

most common form four-chamber hypertrophy and dilation and by right and left-sided intractable failure unknown etiology related to alcoholism, thiamine deficiency or prior myocarditis

Hypertrophic Cardiomyopathy 1) 2) 3) 4)

hypertrophy of all chamber walls, especially the ventricular septum (asymmetric septal hypertrophy) disoriented, tangled and hypertrophied myocardial fibers autosomal dominant characteristic LV outflow obstruction, danger of syncope and even sudden death in young athletes

Restrictive Cardiomyopathy 1) infiltrative processes within myocardium, result in stiffening of the heart muscle, which interferes with pumping action 2) cardiac amyloidosis - result in both right and left heart failure

Myocarditis 1) 2) 3) 4)

biventricular heart failure in young persons diffuse myocardial degeneration and necrosis usually viral with coxsackie most common South America - part of Chagas disease caused by Trypanosoma Cruzi

Pericardial Heart Disease Non-inflammatory 1) Hydropericardium i) serous transudate in pericardial space ii) any condition causing systemic edema iii) most often - CHF, nephrotic syndrome or chronic liver disease 2) Hemopericardium i) blood in the pericardial sac ii) traumatic perforation of the heart or aorta or myocardial rupture after AMI

Acute Pericarditis 1) Serous Pericarditis i) SLE, ARF and viral infections ii) clear straw-colored, protein rich exudate with inflammatory cells 2) Fibrinous or serofibrinous pericarditis i) uremia, MI or ARF ii) fibrin-rich exudate 3) Purulent or suppurative pericarditis i) bacterial infection ii) grossly cloudy or frankly purulent inflammatory exudate 4) Hemorrhagic pericarditis i) tumor invasion of pericardium ii) tuberculosis and bacterial infection iii) bloody inflammatory exudate

Chronic (Constrictive) Pericarditis 1) tuberculous or pyogenic staphylococci 2) thickening and scarring of the pericardium with r loss of elasticity i) interferes with cardiac motion and venous return ii) mimics signs of right heart failure

3) proliferation of fibrous tissue with calcification

Cardiac Neoplasm Primary Tumors 1) Myxoma of left atrium i) most frequently occurring cardiac tumor ii) often in adults iii) pedunculated form cause obstruction of AV valves during systole iv) "wrecking ball" effect can damage valves 2) Rhabdomyoma i) infants and young children ii) with tuberous sclerosis

Metastatic Tumors 1) more common than primary tumors

Congenital Heart Disease (CHD) Causes and Association 1) etiology usually undetermined 2) chromosomal anomalies such as Down syndrome and Turner syndrome often complicated by CHD i) Turner syndrome - coarctation of the aorta ii) endocardial cushion defects associated with Down syndrome 3) increase in PDA in patients living at high altitudes 4) Rubella (German measles) infection cause CHD i) Congenital Rubella Syndrome (1) maternal rubella in first trimester and constellation of fetal defect (2) cardiovascular defects, microcephaly with mental retardation, deafness, cataracts and growth retardation ii) Cardiac Malformations (1) PDA (2) AS (3) VSD (4) pulmonary infundibular or valvular stenosis sometimes occurring as part of tetralogy of Fallot iii) Maternal Immune Status to Rubella (1) determined before and during pregnancy (2) IgM - primary infection (3) IgG - either recent primary infection, past infection or reinfection 5) Genetic Predispostion i) tetralogy of Fallot can cluster among families

Classification 1) Noncyanotic diseases (1) those with no shunt (2) left to right shunt (3) in ASD, both pressure and oxygen saturation equalized between 2 atria 2) Cyanotic diseases (1) transposition of great vessels (2) malformations with right to left shunts (3) Eisenmengerization

Left to Right Shunts - Late Cyanosis 1) Atrial Septal Defect (ASD) i) an abnormal opening in the atrial septum ii) foramen ovale is present in one third of normal individual and does not permit mixing of blood unless right atrial pressures are elevated iii) asymptomatic until adulthood (1) Secundum (a) 90% of all ASD (b) defect located near the mid-septum (2) Primum (a) 5% of ASD (b) adjacent to AV valves with a cleft anterior mitral leaflet (3) Sinus Venosus (a) near entrance of superior vena cava

2) Ventricular Septal Defect (VSD) i) most common congenital cardiac anomaly ii) incomplete closure of ventricular septum iii) most are the size of the aortic valve orifice iv) membranous VSD v) infundibular VSD vi) muscular VSD vii) small muscular VSD close spontaneously while large membranous or infundibular VSD remain patent and need to be surgically closed viii) large, uncorrected VSD may result in shunt reversal, cyanosis and death.

3) Patent Ductus Arteriosus (PDA) i) persistence after birth of normal communication between the pulmonary arterial system and aorta of the fetus ii) occur as isolated anomaly iii) often PDA does not produce functional difficulties except for presence of a machine-murmur iv) closed early in life as is feasible, except in the survival of infants with other forms of CHD with obstructed pulmonary or systemic flow, e.g. aortic valve atresia 4) Atrioventricular Septal Defect (AVSD) i) abnormal development of embryologic AV canal when both superior and inferior endocardial cushions fail to fuse adequately with incomplete closure of AV septum and inadequate formation of AV valves ii) > 1/3 of patient with complete AVSD have Down Syndrome

Right to Left Shunts - Early Cyanosis 1) Tetralogy of Fallot (TOF) i) most common form of cyanotic congenital heart disease ii) anterosuperior displacement of infundibular septum iii) Four features: (1) VSD (2) subpulmonary stenosis accompanied by pulmonary valvular stenosis (3) aorta overrides the VSD (4) RVH- results in boot-shaped heart iv) clinical consequence depend on severity of obstruction (1) mild, resemble isolated VSD - pink tetralogy (2) increasing severity, pulmonary arteries become hypoplastic and right to left shunting predominates - classic tetralogy 2) Tricuspid Atresia i) complete occlusion of the tricuspid valve orifice ii) unequal division of the AV canal iii) almost always with hypoplasia of the right ventricle 3) Transposition of the great arteries i) ventriculoarterial discordance - aorta arises from the right ventricle and the pulmonary artery emanates from the left ventricle ii) aorta lies anterior and to the right of the pulmonary artery iii) incompatible with postnatal life, unless a shunt access iv) Transposition with VSD is considered stable v) Transposition with patent foramen ovale or PDA are unstable since they can close - require immediate intervention (balloon atrial septostomy) vi) without surgery will die within first months 4) Total anomalous pulmonary venous connection i) no pulmonary veins directly join the left atrium ii) pulmonary veins drains to left innominate vein or cornary sinus iii) volume and pressure hypertrophy of right atrium and ventricle 5) Truncus Arteriosus i) failure of embryologic truncus arteriosus to divide ii) single great artery - receives blood from both ventricles

Obstructive Congenital Anomalies 1) Coarctation of the Aorta i) affects males 2x females ii) increased incidence with Turner syndrome iii) infantile form (preductal) with tubular hypoplasia of aortic arch proximal to a PDA and symptomatic in childhood iv) adult form (postductal or juxtaductal) with discrete infolding of the aorta just opposite the closed ductus arteriosus (ligamentum arteriosum) v) clinical manifestation depends on severity

vi) bicuspid valve on 50% of cases vii) aortic stenosis, ASD, VSD, mitral regurgitation and berry aneurysms viii) adult form (postductal or juxtaductal) results in hypertension in upper extremities with notching of ribs on x-ray 2) Pulmonary Stenosis or Atresia i) obstruction of pulmonary valve ii) occurs with tetralogy of Fallot or transposition iii) RVH 3) Aortic Stenosis or Atresia i) narrowing of aortic valve from birth (1) valvular stenosis (2) subaortic stenosis (3) suparvalvular stenosis

Cardiac Transplantation 1) frequently performed 2) Success due to i) careful selection of candidate ii) improved maintenance immunosuppression iii) early diagnosis of acute rejection by sequential endomyocardial biopsy 3) graft arteriosclerosis - stenosing intimal thickening of coronary arteries i) major limitation to long term success ii) lead to silent MI, denervated hearts do not have chest pains