Cardiovascular System

MALFORMATIONS OF VENTRICULAR OUTFLOW TRACTS

Tetralogy of Fallot (TOF)

●● Infundibular pulmonic stenosis, VSD, aortic valve dextroposition, right ventricular hypertrophy

Aortic valvular stenosis

intervention ●● Endocardial fibroelastosis and subendocar-

dial ischemic damage ●● Complications: Bacterial endocarditis,

arrhythmias, ischemic myocardial damage, sudden cardiac death

●● Treated with balloon valvotomy, valve replacement

Hypoplastic left heart syndrome

enlarged ●● Obstruction of PA/patent ductus arteriosus

(for adequate systemic blood flow) ●● Endocardial fibroelastosis and myocardial

hypertrophy ●● Associated coarctation of aorta ●● Incompatible with life unless staged surgi-

cal repair (Norwood repair)/cardiac transplantation in neonatal life

Multistage Norwood repair

Stage I (Blalock-Taussig shunt)

supply ●● Pulmonary blood flow and pressure is

regularized

Stage II (Bi-directional Glenn procedure)

Stage III (Fontan variant procedure)

and systemic venous blood ●● Tunnel anastomosis between IVC and

right PA

MALFORMATIONS OF AORTIC ARCH SYSTEM

Ductus arteriosus

●● Normally, ductus is patent in utero (due to low oxygen levels and increased prostaglandin levels)

●● Normally, ductus closes within 15 hours after birth (term normal weight neonates)

●● In PDA, remains patent beyond 2-3 weeks of life

internal elastic cushion ●● Complicated by left-to-right shunt and con-

gestive heart failure

Coarctation of aorta

●● Area of narrowing in upper thoracic aorta, juxtaductal

●● Composed of fibroelastic tissue and smooth muscle

lower extremity

Aortic arch branching abnormalities

●● Left aortic arch with aberrant right subclavian artery

arch structures that encircle and compress trachea and esophagus

MALFORMATIONS OF CORONARY ARTERIES

●● Anomalous origin of left coronary artery from pulmonary trunk

●● Inadequate blood supply to left ventricle by anomalous coronary artery (pulmonary trunk is low pressure vessel)

●● Anterolateral myocardial infarction, early death

●● Clinical course determined by collateral vessels

MALFORMATIONS OF VENOUS SYSTEM

Persistent left superior vena cava

Interruption of inferior vena cava with azygous continuation

●● Infrahepatic interruption of IVC by azygous continuation

Partial anomalous pulmonary venous return

●● Blood from one to three pulmonary veins drains into right atrium or SVC

●❑ Anomalous pulmonary venous drainage to IVC

●❑ Associated multiple anomalies: Right lung hypoplasia, dextrocardia, systemic arterial supply to lung, defective bronchial anatomy

●❑ On plain chest x-ray; anomalous vein seen as a tubular structure parallel to right heart border as a Turkish sword (“scimitar”)

Total anomalous pulmonary venous return

●● All four pulmonary veins drain into systemic circulation

●● Associated with pulmonary venous obstruction and severe pulmonary hypertension

●● Medial hypertrophy of pulmonary arteries and veins, intimal proliferation and arterialization of pulmonary veins

Cor triatriatum

●● Left atrium partitioned by fibromuscular shelf

●● Pulmonary venous compartment separated from atrial appendage and mitral valve orifice

MALFORMATIONS OF POSITION AND SITUS

Dextrocardia

●● Heart located in right side of chest with apex pointing to right

Dextroposition

●● Heart displaced to right side of chest with apex pointing to left

Ectopia cordis

Situs ambiguous (heterotaxia)

●● Heart sidedness determined by morphology of atrial appendage

Asplenia

Polysplenia

MYOCARDIAL DISEASE

●● Cardiomyopathy (CMP) is disease of myocardium associated with cardiac dysfunction

Primary CMP

HCMP (hypertrophic)

●● Massive cardiomegaly with increased weight, thickened left ventricular free wall/ interventricular septum

myocyte disarray ●● In infants, restriction of both right and left

ventricular outflow ●● AD disorder ●● Mutated myosin binding protein C

(MYBPC3) and cardiac beta-myosin heavy chain (MYH7)

Arrhythmogenic right ventricular dysplasia (ARVD)

●● Partial or massive transmural replacement of right ventricular myocardium by fibrofatty tissue

●● Myocardial disarray leading to ventricular arrhythmias

Non-compaction of ventricular myocardium

●● Persistence of spongy myocardium (more common in LV)

●● Similar pattern seen in early embryonic stages of heart development

●● Fine trabecular meshwork of ventricular myocardium with intervening endocardium lined sinusoids

some Xq28

Dilated cardiomyopathy (DCMP)

●● Common endpoint of multiple underlying conditions

●● Heart enlarged and heavy, biventricular/ all four chambers, dilatation and poor contraction

Restrictive CMP

●● Stiff heart wall due to fibrotic/infiltrative disorders

Endocardial fibroelastosis

tissue, opaque endocardium ●● Association with mumps/adenovirus infec-

tion in utero

Myocarditis (inflammatory cardiomyopathy)

●● Inflammatory infiltrate composed of neutrophils, lymphocytes, plasma cells, macrophages, giant cells, eosinophils

●● Associated myocardial damage (vacuolization, necrosis, debris, frayed edges)

B virus, detected by polymerase chain reaction, serology)

●● Bacterial (streptococci, staphylococci, Neisseria)

●● Protozoal (Trypanosoma cruzi, Chagas disease; Toxoplasma gondii, toxoplasmosis)

Giant cell myocarditis

●● Rapidly progressive, death or cardiac transplant

inflammatory bowel disease ●● Infiltrate of giant cells, mixed inflammatory

cells (no granulomas)

Secondary CMP

Glycogen storage disease (GSD)

tion of glycogen ●● Type II (Pompe disease)

●❑ Lysosomal-Bound glycogen in heart and skeletal muscle

●❑ Myocyte distension with vacuolated and lacy cytoplasm due to accumulation of glycogen (PAS positive)

Danon disease

failure, mental retardation ●● Myocytes have PAS and acid phosphatase

positive membrane bound inclusions

Mucopolysaccharidoses

acid mucopolysaccharides ●● Type I (Hurler syndrome): Valves and endo-

cardium of all four chambers thickened, mitral valve nodules

Hereditary hemochromatosis

●● Juvenile form: Mutation of genes hemojuvelin or hepcidin

DCMP

Mitochondrial electron transport chain disorders

●● Mitochondrial enzyme deficiencies caused by mtDNA or nDNA mutations

●● Cardiac myofiber filled with pools of mitochondria

●● EM: Closely packed stacks of mitochondrial cristae

NEUROMUSCULAR DISORDERS

Muscular dystrophies

Myotonic dystrophy

●● DCMP, interstitial/epicardial fibrosis, conduction defects

Congenital myopathies

●● Myofibrillar myopathy (abnormal desmin), DCMP, central core disease

Friedreich ataxia

●● GAA trinucleotide repeat expansion in frataxin gene

Barth syndrome

paction of left ventricle, neutropenia, skeletal myopathy, prepubertal growth delay, facial dysmorphism (infants/toddlers)

INFANT OF DIABETIC MOTHER CARDIOMYOPATHY

fatal

ISCHEMIC MYOCARDIAL NECROSIS

●● Myocyte necrosis (cytoplasmic eosinophilia and nuclear pyknosis), marginal neutrophilic infiltrate, dystrophic calcification

●● Ischemia damages papillary muscles/ventricular subendocardium

SYSTEMIC ARTERY DISEASE

Arteriopathy

Idiopathic infantile arterial calcifications

●● Deposition of calcium hydroxyapatite in and around internal elastic lamina

●● Intimal fibrous proliferation, reactive inflammatory response in arteries

immune hydrops

Fibromuscular dysplasia

●● Non-inflammatory disorganization and fibrosis of large muscular arteries

●● Duplication and fragmentation of internal and external elastic lamina

ANEURYSMS

Marfan syndrome

●● Dilatation and dissection of ascending aorta in Marfan syndrome

●● Cystic medial degeneration with accumulation of mucopolysaccharides

Ehlers-Danlos syndrome

●● Thin-walled vessels with decreased elastic/ collagen tissue

Menkes steely hair syndrome

●● Defective intestinal absorption of copper and reduced activity of copper-dependent enzymes (lysyl oxidase)

Atherosclerosis

lipoprotein ●● Aorta, coronary arteries, and cardiac valves

involved ●● Deposition of foam cells, fibrosis, and cho-

lesterol clefts ●● Valve stenosis/insufficiency

Vasculitis

Kawasaki disease

ness, cervical lymphadenopathy, bilateral conjunctivitis

Takayasu arteritis

vessel wall, fibrosis, thrombosis, vessel occlusion, aneurysm formation

●● Endocarditis; inflammatory cells within endocardium

NON-INFECTIVE ENDOCARDITIS

lent blood flow → nidus for platelet aggregation and thrombus formation

●● Warty, nodular vegetations (fibrin, entrapped platelets, erythrocytes, and few leukocytes)

●● Etiology: Intracardiac catheters, hypercoagulable states, malignancy, burns, DIC

INFECTIVE ENDOCARDITIS

●● Congenital heart defects, prosthetic valves, shunts; nidus for infection

●● Fever, malaise, new/changing heart murmur, positive blood culture, demonstration of vegetations on echocardiogram

●● Streptococcus viridans, Staphylococcus aureus, fungal organisms

●● Vegetations on atrial surface of AV valves and ventricular surface of outflow valves

●● Vegetations composed of fibrin, polymorphonuclear cells, bacterial colonies/fungal organisms, necrotic material, platelets, and calcification

INFLAMMATORY/ AUTOIMMUNE DISORDERS

Systemic lupus erythematosus (SLE)

●● Pericardial effusion/thickening, mesothelial proliferation, necrosis, fibrinous exudates, inflammation, granulation tissue

endocarditis

Neonatal SLE

antibodies ●● Diagnosed in utero

Rheumatic fever

●● Delayed autoimmune reaction to Group A, beta-hemolytic streptococcal pharyngitis

●● Major criteria: Carditis, migratory polyarthritis, erythema marginatum, subcutaneous nodules, Sydenham chorea

●● Minor criteria: Fever, polyarthralgia, elevated acute phase reactants

inflammatory cells including lymphocytes, plasma cells, and Anitschkow cells

●❑ Anitschkow cells: Histiocytic cell with ragged borders, vesicular nucleus containing central speculated bar of chromatin

(mitral stenosis) ●● Pericarditis (fibrinous)

PERICARDITIS

Serous effusion

fibrinous exudates

Purulent pericarditis

ema, pneumonia, mediastinum

pnea

Tuberculous pericarditis

●● Hemorrhagic fluid with caseating granulomas

Obliterative or constrictive pericarditis

OTHER ANOMALIES

●● Pericardial cysts; mesothelial lined and filled with clear fluid

●● Congenital aplasia of parietal pericardium; myocardial herniation

●● Cardiac conduction system composed of SA node, AV node, bundle of HIS, and bundle branches

SUPRAVENTRICULAR TACHYCARDIA

●● Mostly benign except Wolff-ParkinsonWhite (WPW) syndrome

WPW syndrome

●● Persistent cardiac muscle strands connecting atrial and ventricular muscle (bypassing AV node)

●● ECG-short PR interval, broad QRS complex, delta waves

AV CONDUCTION DISORDERS (AV BLOCK)

●● Interruption of impulse conduction from atrium to ventricle

●● Etiology; congenital heart disease, maternal autoimmune disease with circulating antiSSA/Ro and anti-SSB/La antibodies

VENTRICULAR TACHYCARDIAS

●● Long QT syndrome (prolonged QT polarization and slow repolarization)

●● Disorders affecting cardiac muscle K+, Ca2+, NA+ (channelopathies)

●● Catecholaminergic polymorphic ventricular tachycardia

●● Mean resting pulmonary artery pressure more than 25 mm Hg

●● Pulmonary vasculature includes pre-acinar and intra-acinar arteries

●● Pre-acinar pulmonary arteries develop with the pulmonary airways, completing development by 16-17 weeks of intrauterine life

●● Intra-acinar arterial development starts in utero but medial muscle development lags behind, completing by 8-10 years of age

●● Pulmonary vascular resistance diminished after birth (compared to fetal life); due to release of nitrous oxide/prostacyclin by endothelial cells and dilatation of vessels

●● Histological features; medial muscular hypertrophy, intimal fibroplasia, intimal cellular thickening, plexiform lesions, dilation lesion

PERSISTENT PULMONARY HYPERTENSION OF NEWBORN

●● Pulmonary vascular resistance fails to drop at birth → right-to-left shunt with cyanosis

●● Pulmonary malformation/hypoxia-related maladaptation

●● Abnormal muscle thickening in media of peripherally located intra-acinar arteries

CHD WITH LEFT-TO-RIGHT SHUNT

intimal thickening (cellular/fibroid), decreased number of peripheral arteries

cyanosis

FAMILIAL AND IDIOPATHIC PULMONARY ARTERY HYPERTENSION

LEFT HEART OBSTRUCTIVE DISEASE

●● Hypertensive changes in pulmonary arteries/veins

The type of primary cardiac tumor varies with age

RHABDOMYOMA

●● First 2 years of life (including fetus and neonates)

cause sudden death ●● May regress spontaneously ●● Fetal diagnosis: Non-immune hydrops, car-

diac mass on routine ultrasound, arrhythmias, family history of TS

●● Well-circumscribed, yellowish masses, ventricular myocardium, microscopic to larger size

●● Composed of large myocardial cells with accumulation of glycogen in cytoplasm (spider cells)

CARDIAC FIBROMA

●● Second-most common cardiac tumor of childhood

plant

TERATOMA

sion ●● Non-immune hydrops, cardiac tamponade

MYXOMAS

tutional symptoms ●● Sporadic or syndromic ●● Associated with Carney complex (AD dis-

order, PRKAR1A gene, skin lesions, myxomas, endocrine abnormalities)

●● Located in endocardium near fossa ovalis, left atrium

ride-rich myxoid matrix ●● Immunohistochemistry: Vimentin, cal-

retinin, CD31, CD34, CK (glandular elements)

HISTIOCYTOID CARDIOMYOPATHY

diac death ●● Small, flat to nodular collections of large

pale myocardial cells with foamy cytoplasm, rich in glycogen and lipid