Introduction: Cardiac Pathology I, II, & III PDF

Introduction: Cardiac Pathology I, II, & III Gurjit Nagra M.D., Ph.D.  Analogy ▪ A car engine keeps the car running ▪ Overtime if you don’t do an oil change and keep the engine at its best performance, the car drive is not smooth ▪ Body has heart as a vascular supply ‘engine’ to a...

Introduction: Cardiac Pathology I, II, & III Gurjit Nagra M.D., Ph.D.  Analogy ▪ A car engine keeps the car running ▪ Overtime if you don’t do an oil change and keep the engine at its best performance, the car drive is not smooth ▪ Body has heart as a vascular supply ‘engine’ to all the organs ▪ It is always on ▪ With the proper diet and exercise i.e. diets with low atherosclerosis risks that would not lead to infraction, heart’s functionality is at its best  Epicardium Layers of Heart: ▪ synonymous the visceral pericardium, functions as a protective layer. ▪ This membrane consists of connective tissue covered by epithelium. ▪ Its deeper portion (close to the myocardium) often contains adipose tissue, particularly along the paths of the larger blood vessels. Myocardium ▪ is relatively thick ▪ consists largely of the cardiac muscle tissue responsible for forcing the blood out of the heart chambers. ▪ Muscle fibers are arranged in planes, separated by connective tissues, which are richly supplied with blood capillaries, lymph capillaries, and nerve fibers, nourishing and controlling the heart. Endocardium ▪ consists of epithelium and connective tissue, which contains many elastic and collagenous fibers. ▪ Connective tissue also contains some specialized cardiac muscle fibers, called Purkinje fibers part of specialized conduction network of the heart Layers of Heart: Histology  CHF = Congestive Heart Failure/ just Heart Failure LHF =Left Heart Failure RHF=Right Heart Failure Heart Diseases LH = Left Heart RH = Right Heart Inflm = Inflammation Layer Specific Valvular Congenital HF Cardiomyopathy Ischemic Cancer (-Cardium) R →L L→R Stable Myxoma Shunt Shunt Endo Myo Peri LHF RHF LH RH Rhabdomyoma Infllm Dilated Hypertrophic Restrictive Unstable Prinzmetal Metastatic Endocarditis Tetralogy of Atrial septal Fallot (TOF) defect (ASD) Transposition of great Ventricular Rheumatic Carditis vessels septal defect Truncus (VSD) arteriosus Tricuspid Patent Ductus arteriosus Obstructive: Pericarditis atresia Total (PDA) Coarctation of anomalous Aorta pulmonary Atrio- Aortic stenosis Infection venous ventricular Pulmonary Non-infection connection septal defect stenosis Cardiomyopathy ▪ Definition: ▪ primary myocardial disease producing myocardial dysfunction ▪ Diagnosis: ▪ made after ruling out coronary artery disease (CHD), Valvular heart disease & congenital heart disease ▪ Types: ▪ Dilated : Most common (90% of all cases) ▪ Hypertrophic : Sudden death in young athlete ▪ Restrictive : Least common Cardiomyopathy: Different types Systolic dysfunction: difficulty with pushing out the blood Diastolic dysfunction: difficulty relaxing Dilated cardiomyopathy: ▪Most common cardiomyopathy (90% of cases). Systolic dysfunction ▪Etiology: ▪Idiopathic ▪Familial: due to mutation of TTN gene encoding the sarcomeric protein titin ▪Associated with Duchenne Muscular Dystrophy: X-linked - Dystrophin gene ▪Drugs: alcohol, cocaine, doxorubicin ▪Infection: coxsackie B virus, Chagas disease ▪Ischemia: CAD ▪Systemic conditions: hemochromatosis, sarcoidosis, thyrotoxicosis, wet beriberi ▪Peripartum cardiomyopathy ▪Clinical Findings: ▪Presents between 20-50 yrs ▪Heart Failure: Progressive CHF – left & right, S3 ▪Systolic regurgitant murmur: Mitral regurgitation ▪dilated heart on echocardiogram EF 70%) Ejection fraction or at high end level (i.e 67-70%) (Normal: ~50-70%) ▪ May see mitral regurgitation due to impaired mitral valve closure ▪ Treatment: cessation of high-intensity athletics, use of β-blocker or non- dihydropyridine Ca2+ channel blockers (i.e. verapamil). Implantable cardiovascular defibrillator ICD if syncope occurs.  Concentrate on the Disc Hypertrophic cardiomyopathy Con’td.. Con = Concentric hypertrophy Di = Diastolic dysfunction Pathology Features: ▪ Diastolic dysfunction ensues. Marked ventricular concentric hypertrophy (sarcomeres added in parallel),often septal predominance. ▪ Myofibrillar disarray and fibrosis. Physiology of HOCM: ▪ asymmetric septal hypertrophy and systolic anterior motion of mitral valve leads to outflow obstruction resulting in dyspnea, possible syncope. NOTE: Other causes of concentric LV hypertrophy: ▪ Chronic HTN ▪ Friedreich ataxia Pathology: Hypertrophic cardiomyopathy Gross Microscopy: ▪ Massive myocardial hypertrophy without ▪ Myofiber hypertrophy Interstitial fibrosis ventricular dilation Myofiber disarray ▪ Asymmetrical septal hypertrophy- subaortic region ▪ Compressed LV cavity- Banana-like  Normal ejection fraction ~50-75% Restrictive cardiomyopathy: Restrictive Cardiomyopathy Causes: Puppy LEASH Rarest form of cardiomyopathy; EF=normal or mildly reduced ▪ Pathophysiology: Post-radiation fibrosis ▪ Diastolic dysfunction Löffler endocarditis: associated with ▪ Primary decrease in ventricular compliance hypereosinophilic syndrome; histology ▪ Impaired ventricular filling during diastole shows eosinophilic infiltrates in ▪ Morphology: myocardium. ▪ Ventricles are normal or slightly dilated ▪ Both atrias are dilated Endocardial fibroelastosis (thick ▪ Clinical features : Congestive cardiac failure fibroelastic tissue in endocardium of ▪ Progressive and chronic (months to years i.e. post young children) radiation) heart failure ▪ Peripheral edema Amyloidosis ▪ Jugulovenous distension ▪ Kussmaul sign Sarcoidosis ▪ Paradoxic Inspiratory rise in Jugular venous pressure on inspiration Hemochromatosis: although dilated ▪ Decreased ECG voltage cardiomyopathy is more common Kussmaul sign: https://creativemeddoses.com/topics-list/kussmaul-sign-and-inspiration/ Restrictive cardiomyopathy: Amyloidosis ▪ Senile systemic amyloidosis : ▪ Transthyretin Amyloid deposition – atria & ventricles ▪ Isolated atrial amyloidosis : Atrial natriuretic peptide – amyloid only in atria ▪ Sites : ▪ Interstitial ▪ blood vessels ▪ valves ▪ endocardium ▪ Amyloid deposition can be ▪ pericardium demonstrated by polarized light (left) or Congo red stain (right). ▪ Confirmation by: ▪ It can cause a restrictive ▪ Congo red staining & apple green birefringence cardiomyopathy involving the under polarized light myocardial layer or can involve the ▪ Clinical Features: conduction system with resultant bradyarrhythmias (if involving the ▪ Diastolic dysfunction & Congestive Heart Failure endocardial layer). (CHF) ▪ Listed on Slide 16 Type of CMP Findings Dilated ▪ All four chambers dilated, (Congestive) ▪ hypertrophy. ▪ most common cause is chronic alcoholism ▪ some may be the end-stage of remote viral myocarditis ▪ Eccentric (in series) hypertrophy Hypertrophic ▪ Most common form, idiopathic hypertrophic subaortic stenosis (IHSS) ▪ Asymmetric interventricular septal hypertrophy, ▪ Concentric LV hypertrophy ▪ left ventricular outflow obstruction Restrictive ▪ Myocardium infiltrated with a material that results in impaired ventricular filling. ▪ most common causes are amyloidosis and hemochromatosis. With restrictive cardiomyopathy secondary to amyloidosis need to do bx, for sarcoidosis and hemochromatosis do MRI Note Eccentric vs Concentric hypertrophy Hypertrophic cardiomyopathy Dilated cardiomyopathy  CHF = Congestive Heart Failure LHF =Left Heart Failure RHF=Right Heart Failure Heart Diseases LH = Left Heart RH = Right Heart Inflm = Inflammation Layer Specific Valvular Congenital HF Cardiomyopathy Ischemic Cancer (-Cardium) R →L L→R Stable Myxoma Shunt Shunt Endo Myo Peri LHF RHF LH RH Rhabdomyoma Infllm Dilated Hypertrophic Restrictive Unstable Prinzmetal Metastatic Endocarditis Tetralogy of Atrial septal Fallot (TOF) defect (ASD) Transposition of great Ventricular Rheumatic Carditis vessels septal defect Truncus (VSD) arteriosus Tricuspid Patent Ductus arteriosus Obstructive: Pericarditis atresia Total (PDA) Coarctation of anomalous Aorta pulmonary Atrio- Aortic stenosis Infection venous ventricular Pulmonary Non-infection connection septal defect stenosis Tumors of heart: ▪ Primary: rare ▪ Myxoma ▪ Fibroma ▪ Lipoma ▪ Papillary fibroelastoma ▪ Rhabdomyomas ▪ Angiosarcomas & other sarcomas ▪ Secondary ▪ Most common heart tumor is a metastasis i.e. melanoma Myxoma: ▪ Most common 1° cardiac tumor in adults ▪ 90% occur in the atria (mostly left atrium). ▪ Myxomas are usually described as a “ball valve” obstruction in the left atrium (associated with multiple syncopal episodes). ▪ Clinical: ▪ IL-6 production by tumor lead to constitutional symptoms i.e. fever, weight loss ▪ Syncope, left heart failure & mitral valve damage ▪ Embolization : stroke 1-10 cm sessile (flat ▪ May auscultate early diastolic “tumor plop” sound or dome shaped or ▪ Histology: pedunculated (like Brown sugar boba ▪ gelatinous material, myxoma cells immersed in mushroom) glycosaminoglycans ▪ Diagnostic: Echocardiogram Characteristic Acid- Mucopolysaccharide ▪ Complications: *Arterial thromboembolism Matrix and ▪ Treatment: Surgery Embedded Polygonal Stellate (quiet Cells (Hematoxylin fibroblasts) shaped and Eosin, ×100 cells in a myxomatous background Cardiac Rhabdomyoma ▪ Benign hamartoma ▪ Most common primary heart tumor in children ▪ Located in the ventricles ▪ Associated with tuberous sclerosis ASIDE: What is Tuberous sclerosis: Rhabdomyoma- Grossly a white ▪ Autosomal Dominate with nodule in the myocardium. ▪ cortical tubers ▪ subependymal giant cell astrocytomas ▪ retinal glial hamartoma ▪ cardiac rhabdomyoma ▪ pulmonary hamartomas ▪ renal angiomyolipoma ▪ subungual fibroma Cardiac Rhabdomyoma: Magnified: Circumscribed benign tumor with no definite capsule and composed of cells called spider cells (left side of the image)- which are polygonal cells having large clear cytoplasm compared with the normal myocardium Metastatic tumor: More common than primary cancer of heart Most frequent cause Lung cancer Breast cancer Esophageal cancer  CHF = Congestive Heart Failure LHF =Left Heart Failure RHF=Right Heart Failure Heart Diseases LH = Left Heart RH = Right Heart Inflm = Inflammation Layer Specific Valvular Congenital HF Cardiomyopathy Ischemic Cancer (-Cardium) R →L L→R Stable Myxoma Shunt Shunt Endo Myo Peri LHF RHF LH RH Rhabdomyoma Infllm Dilated Hypertrophic Restrictive Unstable Prinzmetal Metastatic Endocarditis Tetralogy of Atrial septal Fallot (TOF) defect (ASD) Transposition of great Ventricular Rheumatic Carditis vessels septal defect Truncus (VSD) arteriosus Tricuspid Patent Ductus arteriosus Obstructive: Pericarditis atresia Total (PDA) Coarctation of anomalous Aorta pulmonary Atrio- Aortic stenosis Infection venous ventricular Pulmonary Non-infection connection septal defect stenosis Ischemic Heart Disease: ▪ Pathophysiology of atherosclerotic plaque and MI ▪ Coronary artery atherosclerotic plaque results from a complex process ▪ Driven by multiple factors within the intimal layer of the coronary artery wall. ▪ Factors include: ▪ Endothelial cell dysfunction ▪ Oxidized serum lipids ▪ Inflammation ▪ Thrombosis: secondary effects of angiogenesis and calcification. Atherosclerotic plaque and MI intimal plaque, with a luminal layer of foamy macrophages necrotic core with foam cell macrophages necrotic core (NC), with thinning of the fibrous cap free cholesterol from cell membranes forming crystals healing infarct, with fibroblasts, early dense scar (blue area) from the endocardium (above) to collagen strands, and abundant the epicardium (below) hemosiderin macrophages some viable entrapped cardiac muscle near the endocardium acute MI, transmural, with rupture. The rupture track is toward the left. The dark blue areas are degenerative neutrophils hemosiderin macrophages (arrows) higher magnification of the blue areas in e that are fragmenting neutrophils healed transmural infarct Ischemic Heart Disease: Chest pain due to ischemic myocardium 2° to coronary artery narrowing or spasm; no myocyte necrosis. ▪ Stable: ▪ usually 2° to atherosclerosis ▪ exertional chest pain in classic distribution ▪ resolving with rest or nitroglycerin. ▪ Vasospastic: also called Prinzmetal or Variant: ▪ occurs at rest 2° to coronary artery spasm; ▪ transient ST elevation on ECG. ▪ Smoking is a risk factor ▪ hypertension and hypercholesterolemia are not risk factors ▪ Triggers include cocaine, alcohol, and triptans. ▪ Treat with Ca2+ channel blockers, nitrates, and smoking cessation (if applicable). ▪ Unstable: ▪ thrombosis with incomplete coronary artery occlusion; ▪ no cardiac biomarker elevation ▪ Increase in frequency or intensity of chest pain or any chest pain at rest. Post Myocardial Infarction Changes: Time Gross changes in the heart Microscopic changes Complications 0-4hrs wavy fibers ▪ Arrythmia (wavy fibers), ▪ Heart Failure ▪ Cardiogenic shock Early cog nec 4-24hrs Coagulative necrosis (dark mottling cell content released into blood; edema, hemorrhage or Reperfusion injury → free radicals and ↑ Ca2+ influx → discoloration) hypercontraction of myofibrils (dark eosinophilic stripes) Note: No neutrophils 1-3days Hyperemia Coagulative necrosis + Neutrophilic infiltration Postinfarction fibrinous pericarditis Yellow and soft necrotic center & mottling 3-14days Hyperemic or red tan margins surrounding the Removal of necrotic tissue by macrophages Free wall rupture → tamponade yellow tan pallor → gray white scar, progresses granulation tissue, fibroblasts collagen deposition, papillary muscle rupture → mitral regurgitation from the border towards the core of the Angiogensis interventricular septal rupture due to infaract macrophage-mediated structural degradation → left- to-right shunt LV pseudoaneurysm (risk of rupture) 2 weeks to Gray White, non contractile fibrous scar Granulation tissue leading to Dense Fibrous tissue ▪ Cardiac ventricular aneurysm several ▪ Dressler’s months ▪ Immunological pericarditis ▪ Thromboembolism  CHF = Congestive Heart Failure LHF =Left Heart Failure RHF=Right Heart Failure Heart Diseases LH = Left Heart RH = Right Heart Inflm = Inflammation Layer Specific Valvular Congenital HF Cardiomyopathy Ischemic Cancer (-Cardium) R →L L→R Stable Myxoma Shunt Shunt Endo Myo Peri LHF RHF LH RH Rhabdomyoma Infllm Dilated Hypertrophic Restrictive Unstable Prinzmetal Metastatic Endocarditis Tetralogy of Atrial septal Fallot (TOF) defect (ASD) Transposition of great Ventricular Rheumatic Carditis vessels septal defect Truncus (VSD) arteriosus Tricuspid Patent Ductus arteriosus Obstructive: Pericarditis atresia Total (PDA) Coarctation of anomalous Aorta pulmonary Atrio- Aortic stenosis Infection venous ventricular Pulmonary Non-infection connection septal defect stenosis Heart Failure: ▪ Clinical syndrome of cardiac pump dysfunction leads to congestion and low perfusion. ▪ Symptoms: ▪ dyspnea, orthopnea, fatigue ▪ Signs: ▪ include S3 heart sound, rales, jugular venous distention (JVD), pitting edema ▪ Systolic dysfunction: ▪ reduced Ejection Fraction EF, ↑End diastolic Volume EDV; ↓contractility often 2° to ischemia/MI or dilated cardiomyopathy. ▪ Diastolic dysfunction: ▪ preserved EF, normal EDV;↓compliance (↑ End Diastolic Pressure EDP) often 2° to myocardial hypertrophy. ▪ Right HF most often results from left HF. ▪ Cor pulmonale refers to isolated right HF due to pulmonary cause. ▪ Treatment: ▪ ACE inhibitors or angiotensin II receptor blockers, β-blockers (except in acute decompensated HF), and spironolactone ↓ mortality. Loop and thiazide diuretics are used mainly for symptomatic relief. Hydralazine with nitrate therapy improves both symptoms and mortality in select patients. Left Heart Failure: ▪ Orthopnea: ▪ Shortness of breath when supine: Increased venous return from redistribution of blood (immediate gravity effect) exacerbates pulmonary vascular congestion. ▪ Paroxysmal nocturnal dyspnea: ▪ Breathless awakening from sleep: Increased venous return from redistribution of blood, reabsorption of peripheral edema, etc. ▪ Pulmonary edema: ▪ Increased pulmonary venous pressure leads to pulmonary venous distention and transudation of fluid. Presence of hemosiderin-laden macrophages (“HF” cells) in lungs. ▪ Complications: ▪ Pulmonary edema predisposing to Pneumonias ▪ Acute renal failure ▪ Global cerebral ischemia - Coma Left Heart Failure: Lung findings in patient with Left heart failure : Wet heavy, Edematous, congested, brown induration Left Heart Failure: Lung Microscopy ▪ Septal congestion, edema ▪ Alveolar edema, hemorrhage & hemosiderin-laden macrophages ( heart failure cells) C/F: Dyspnea, Orthopnea, Paroxysmal nocturnal dyspnea Left heart failure: X-ray findings Peri-hilar congestion Kerley’s B lines – Patchy interstitial and increased lymphatic flow alveolar infiltrates and fluid in interstitium. Right Heart Failure: ▪ Hepatomegaly: Nutmeg liver ▪ ↑central venous pressure leads to resistance to portal flow. Rarely, leads to “cardiac cirrhosis.” ▪ Jugular venous distention: ▪ ↑ venous pressure. ▪ Peripheral edema: ▪ ↑ venous pressure leads to fluid transudation. Right Heart Failure: Liver ▪ Left: low magnification ▪ Middle: Higher magnification – ▪ Trichrome highlights fibrosis around central vein [yellow Centrilobular congestion – arrowhead] (called cardiac cirrhosis) nutmeg liver ( gross) ▪ Beginning scar formation [green arrowheads]. ▪ Note residual atrophic hepatocytes [blue arrowheads] Side by Side: LHF Vs. RHF  CHF = Congestive Heart Failure/ Heart Failure LHF =Left Heart Failure RHF=Right Heart Failure Heart Diseases LH = Left Heart RH = Right Heart Inflm = Inflammation Layer Specific Valvular Congenital HF Cardiomyopathy Ischemic Cancer (-Cardium) R →L L → R Endo Restri Stable Myxoma Myo Peri LHF RHF LH RH Infllm Dilated Hypertr Unstable Rhabdomyoma Shunt Shunt ophic ctive Prinzmetal Metastatic Endocarditis Tetralogy of Atrial septal Fallot (TOF) defect (ASD) Transposition of great Ventricular Rheumatic Carditis vessels septal defect Truncus (VSD) arteriosus Tricuspid Patent Ductus arteriosus Obstructive: Pericarditis atresia Total (PDA) Coarctation of anomalous Aorta pulmonary Atrio- Aortic stenosis Infection venous ventricular Pulmonary Non-infection connection septal defect stenosis Endocarditis Pathogenesis: Circulating bacteria are lodged on previously damaged valves (sub-acute) Hemodynamic stress Damage to endothelium Formation of platelet thrombi from circulating bacteria IV drug abusers Staphylococcus aureus Valves affected- Tricuspid most frequent Bacterial endocarditis Pathogenesis: Pathogenesis of infective endocarditis (IE) and its complications. (A,B) Mitral valve vegetations in infectious endocarditis. (C) Bacteria in the bloodstream adhere to damaged or inflamed valves and cause invasive infection. (D) Bacterial persistence and proliferation lead to valve colonization and biofilm formation (especially Staphylococcus aureus). (E) The valvular lesion progresses further, followed by vegetation maturation. (F) Severe valvular damage and disseminated vegetation particles result in clinical symptoms and various complications Source: Research Gate Clinical Features: Bacterial endocarditis FROM JANE with : Fever Roth spots Osler nodes Murmur Janeway lesions Roth spots Osler nodes (Ouchy) Janeway lesions Nail-bed hemorrhage (painless) Anemia Nail-bed hemorrhage Emboli Acute Infective endocarditis :large friable vegetations Sub-acute bacterial endocarditis :smaller vegetations Valve Destruction in IE  Infective Endocarditis Acute (25%) Sub-acute (75%) Caused by highly virulent Caused by organisms of low organism (i.e. staphylococcus virulence (i.e. streptococcus aureus) viridans, staphylococcus epidermidis) Affects previously normal heart Previously damaged valves are valves affected Large destructive vegetations Relatively smaller vegetations High mortality - 50 % patients Most recover with treatment  CHF = Congestive Heart Failure / Heart Failure LHF =Left Heart Failure RHF=Right Heart Failure Heart Diseases LH = Left Heart RH = Right Heart Inflm = Inflammation Layer Specific Valvular Congenital HF Cardiomyopathy Ischemic Cancer (-Cardium) R →L L → R Endo Restri Stable Myxoma Myo Peri LHF RHF LH RH Infllm Dilated Hypertr Unstable Rhabdomyoma Shunt Shunt ophic ctive Prinzmetal Metastatic Endocarditis Tetralogy of Atrial septal Fallot (TOF) defect (ASD) Transposition of great Ventricular Rheumatic Carditis vessels septal defect Truncus (VSD) arteriosus Tricuspid Patent Ductus arteriosus Obstructive: Pericarditis atresia Total (PDA) Coarctation of anomalous Aorta pulmonary Atrio- Aortic stenosis Infection venous ventricular Pulmonary Non-infection connection septal defect stenosis  ACUTE RHEUMATIC FEVER: ▪ Systemic, post-streptococcal (group A ß-hemolytic streptococci) non-suppurative inflammatory disease ▪ Childhood disease – 5 to 15 years ▪ Common in developing countries ▪ Rare in the US (1:50,000) ▪ Pathogenesis: ▪ Immunologically mediated -type 2 hypersensitivity - multisystem disease ▪ NOT a direct effect of bacteria ▪ Occurs 1- 5 weeks after an episode of group A (beta hemolytic) streptococcus pharyngitis (in 3% of patients) ▪ Inciting antigen Group A streptococcal -M protein ▪ Antibodies to M protein cross-react with self antigens, often myosin (molecular mimicry). ▪ Often involves the heart JONES CRITERIA OF RHEUMATIC FEVER (RF) Major Minor Joint – Migratory Fever J NES (major criteria): Polyarthritis Joint (migratory polyarthritis) (carditis) Carditis Arthralgia Nodules in skin (subcutaneous) Erythema marginatum (evanescent rash Nodules (Subcutaneous) Lab findings : Increased with ring margin) CRP, ESR Sydenham chorea Erythema marginatum Leukocytosis Must for diagnosis : Sydenham chorea EKG – prolonged PR ▪ 2 major or 1 major + 2 minor with interval evidence of preceding streptococcal sore throat Previous history of RF Extra cardiac manifestation in Rheumatic fever Polyarthritis (migratory) Most common initial presentation Erythema marginatum In large joints (knee) and small joints (wrist) Subcutaneous nodules 0.5-2cm, ovoid, painless Extensor surface of wrist, elbow, ankles, knees Reversible rapid, involuntary movements affecting all muscles Late manifestation of acute rheumatic fever Evidence of preceding streptococcal infection : elevated Anti Streptolysin O (ASO) & anti DNAse Erythema marginatum Circular ring of erythema around normal skin Trunk & proximal extremities Subcutaneous nodules Rheumatic fever Pericarditis: Fibrinous (“bread and butter”) Precordial chest pain & Pericardial friction rub Fibrinous Pericarditis : (“bread and butter”) Rheumatic Fever Myocarditis: ▪ Pathognomonic lesion in the myocardium is called Aschoff Body Aschoff giant cell ▪ Found in all the layers of the heart fibrinoid necrosis ▪ Aschoff bodies: granuloma with ▪ Aschoff giant cells ▪ Anitschkow cells: enlarged Anitschkow cells (caterpillar cells) macrophages with ovoid, -enlarged macrophages with ovoid, wavy, rod- wavy, rod-like nucleus like nucleus ▪ Fibrinoid necrosis ▪ T lymphocytes, & occasional plasma cells Aschoff Body: granuloma Rheumatic Fever endocarditis: ▪ Recurrent inflammation of mitral & aortic valves – stenosis ▪ MR & AR can occur leading to Left Sterile vegetations along the line heart failure of closure ▪ Vegetations ▪ Sterile, non-embolic warty (verrucous) vegetations along lines of closure (edge) ▪ Site Involved ▪ Mitral valve (most common), Mitral & aortic valves; Tricuspid and pulmonary (rare) Affects heart valves (MAT)—mitral > aortic >> tricuspid (high- pressure valves affected most). Early lesion is mitral valve regurgitation; late lesion is mitral stenosis. Mitral Stenosis: Aortic Stenosis: Rheumatic Fever Complications: Mitral stenosis Congestive Heart Failure: CHF Infective endocarditis Valvular insufficiency Mitral / aortic insufficiency Constrictive pericarditis Embolization  CHF = Congestive Heart Failure/ Heart Failure LHF =Left Heart Failure RHF=Right Heart Failure Heart Diseases LH = Left Heart RH = Right Heart Inflm = Inflammation Layer Specific Valvular Congenital HF Cardiomyopathy Ischemic Cancer (-Cardium) R →L L→R Stable Myxoma Shunt Shunt Endo Myo Peri LHF RHF LH RH Rhabdomyoma Infllm Dilated Hypertrophic Restrictive Unstable Prinzmetal Metastatic Endocarditis Tetralogy of Atrial septal Fallot (TOF) defect (ASD) Transposition of great Ventricular Rheumatic Carditis vessels septal defect Truncus (VSD) arteriosus Tricuspid Patent Ductus arteriosus Obstructive: Pericarditis atresia Total (PDA) Coarctation of anomalous Aorta pulmonary Atrio- Aortic stenosis Infection venous ventricular Pulmonary Non-infection connection septal defect stenosis Myocarditis: Infection causes ▪ Inflammation and consequent degeneration and necrosis of myocardial fibers ▪ Myocarditis suspected when there is a sudden heart failure without preexisting atherosclerosis ▪ Most common causes in North America ▪ Viruses – Enteroviruses like Coxsackie, Echo, Influenza, CMV & HIV ▪ Most important cause in South America ▪ Flabby heart ▪ Chagas' disease (Trypanosoma cruzi) ▪ 4-chamber dilation ▪ Patch hemorrhagic ▪ Other infection : mottling ▪ Mural thrombi may ▪ Bacterial: Corynebacterium diphtheria, form borrelia ▪ Helminth: Trichinosis Myocarditis: Infection causes Cont’d… ▪ Lymphocytic myocarditis: ▪ Mononuclear & inflammatory cell infiltrate (all over) ▪ associated myocyte injury Viral myocarditis Myocarditis: Infection causes Cont’d… ▪ Myocarditis of Chagas disease ▪ A myofiber is distended with trypanosomes (arrow). ▪ There is a surrounding inflammatory reaction ▪ individual myofiber necrosis. Immune-mediated reactions Myocarditis: non-infectious causes ▪ Systemic Lupus Erythematous (SLE) ▪ Rheumatoid Arthritis ▪ Drug Hypersensitivity: Eosinophilic myocarditis ▪ methyldopa Hypersensitivity myocarditis: ▪ infiltrate of eosinophils and mononuclear ▪ sulfonamides inflammatory cells in perivascular and large ▪ tricyclic antidepressants interstitial spaces. ▪ Seen with drug hypersensitivity ▪ Transplant rejection Causes of eosinophilia (PA2CMAN Eats): Parasites Asthma Aspergillosis Chronic adrenal insufficiency Myeloproliferative disorders Allergic processes Neoplasia (eg, Hodgkin lymphoma) Eosinophilic granulomatosis with polyangiitis Myocarditis: Unknown causes Recall: Typical granuloma ▪ Granulomatous myocarditis : ▪ Giant cell myocarditis : Myocyte sarcoidosis necrosis with lymphocytes, ▪ (non-caseating granuloma) macrophages & many giant cells ▪ Poor prognosis Myocarditis: Clinical Features & consequences ▪ Fever, palpitation, precordial pain, dyspnea ▪ Functional Mitral regurgitation ▪ Congestive Heart failure ▪ Arrhythmias ▪ sudden cardiac death  CHF = Congestive Heart Failure/ Heart Failure LHF =Left Heart Failure RHF=Right Heart Failure Heart Diseases LH = Left Heart RH = Right Heart Inflm = Inflammation Layer Specific Valvular Congenital HF Cardiomyopathy Ischemic Cancer (-Cardium) R →L L→R Stable Myxoma Shunt Shunt Endo Myo Peri LHF RHF LH RH Rhabdomyoma Infllm Dilated Hypertrophic Restrictive Unstable Prinzmetal Metastatic Endocarditis Tetralogy of Atrial septal Fallot (TOF) defect (ASD) Transposition of great Ventricular Rheumatic Carditis vessels septal defect Truncus (VSD) arteriosus Tricuspid Patent Ductus arteriosus Obstructive: Pericarditis atresia Total (PDA) Coarctation of anomalous Aorta pulmonary Atrio- Aortic stenosis Infection venous ventricular Pulmonary Non-infection connection septal defect stenosis  Pericarditis: ▪ Acute: ▪ chest pain ▪ Pericardial friction rub ▪ Pericardial effusion: faint heart sound ▪ Low intermittent fever, tachycardia, dry cough ▪ Chronic: inflammation of the pericardium that lasts > 3 months ▪ Constrictive pericarditis: compromised cardiac function caused by a thickened, rigid, and fibrous pericardium secondary to acute pericarditis ▪ Kussmaul’s sign: Neck vein distension on inspiration ▪ JVD ▪ Tachycardia ▪ Pericardial knock or calcification ▪ Drop in systolic pressure greater than 10mm of Hg during inspiration (pulsus paradoxus) ▪ Effusive-constrictive pericarditis (Special): Pericardial effusion occurs in addition to a thickened pericardium, which can lead to tamponade ▪ characterized by symptoms of chronic constrictive pericarditis, pericardial effusion (acute), or a mixture of both. ▪ Smaller or slow-growing effusions: Patients may be asymptomatic. ▪ Large effusions or rapidly growing effusions: symptoms of cardiac tamponade (acute: trauma) pulsus paradoxus ▪ Beck triad: hypotension, muffled heart sounds, and distended neck veins ▪ Dullness at the left base of the lung due to compression Before continuing: confusion here… Pericarditis: Types ▪ Serous pericarditis: Coxsackie virus most common - viruses (self limited; corticosteroids) and non-infectious causes i.e. SLE, NOTE: Caseous lesions consist Scleroderma, Rheumatic fever of necrotic cellular debris surrounded by a zone of ▪ Caseous pericarditis: – unless proved otherwise, it is tuberculous in suppurative inflammation origin ▪ Fibrinous: Bread and butter pericarditis ▪ Causes: ▪ Rheumatic fever, SLE ▪ Acute MI – Inflammatory response to necrosis involving epicardium ▪ Uremia – chemical irritation ▪ Radiation, metastasis ▪ Suppurative or Purulent pericarditis: ▪ Due to direct spread from lung infection ▪ S. aureus, Streptococcus pneumoniae, gram-negative bacilli ▪ Pus accumulates in the pericardial sac infected with pyrogenic bacteria. Pericarditis: Types Cont’d…. Hemorrhagic Pericarditis: Exudate of blood mixed with fibrinous-to suppurative effusion Causes: Following cardiac surgery Malignancy Constrictive Pericarditis: Fibrosis with TB obliteration/destruction of pericardial cavity – pericardium is thickened Tuberculosis (most important) Idiopathic (common) Radiation Post Surgery Outcome : Diastolic filling defect Pericardial knock - an early diastolic sound caused by loss of pericardial elasticity accompanying fibrosis that limits ventricular filling. Pericardial Effusion: Serous (clear)- viral; can be part of anasarca (generalized edema) Chylous (milky)- obstruction of thoracic duct (tumors) Sero-sanguinous (blood+liquid) - trauma Hemopericardium (blood) rupture of M.I. aortic dissection bleeding disorder Cardiac tamponade: grave condition that happens after sudden and/or excessive accumulation of fluid in the pericardial space Beck triad (hypotension, distended neck veins, distant heart sounds) Increased HR, pulsus paradoxus ECG shows low-voltage QRS and electrical alternans  CHF = Congestive Heart Failure / Heart Failure LHF =Left Heart Failure RHF=Right Heart Failure Heart Diseases LH = Left Heart RH = Right Heart Inflm = Inflammation Layer Specific Valvular Congenital HF Cardiomyopathy Ischemic Cancer (-Cardium) R →L L→R Stable Myxoma Shunt Shunt Endo Myo Peri LHF RHF LH RH Rhabdomyoma Infllm Dilated Hypertrophic Restrictive Unstable Prinzmetal Metastatic Endocarditis Tetralogy of Atrial septal Fallot (TOF) defect (ASD) Transposition of great Ventricular Rheumatic Carditis vessels septal defect Truncus (VSD) arteriosus Tricuspid Patent Ductus arteriosus Obstructive: Pericarditis atresia Total (PDA) Coarctation of anomalous Aorta pulmonary Atrio- Aortic stenosis Infection venous ventricular Pulmonary Non-infection connection septal defect stenosis Valvular diseases: Left Heart Aortic Stenosis Etiology: ▪ Most frequently due to calcified congenital bicuspid valve (>50% cases) ▪ Age-related sclerosis of aortic valve ▪ Chronic rheumatic fever Pathophysiology: ▪ Calcific aortic stenosis in a 3-cuspid aortic ▪ Obstruction to LV outflow during systole-LV contracts & it is encountering valve in an elderly person ▪ As there is a forced push of blood against the resistant, there is a peak to ▪ Leaflets are heavily calcified, but there is no commissural fusion the murmur, and this is diamond shape configuration-i.e. why it is called ejection murmur (a crescendo-decrescendo) ▪ Reduction in aortic valve orifice --- concentric Left Ventricular Hypertrophy LVH Clinical: ▪ Systolic ejection murmur: Crescendo decrescendo ▪ Syncope and angina with exercise ▪ the murmur intensity decreases with the decrease in the preload & ▪ Calcific aortic stenosis of a congenitally increases with the increase in the preload in the ventricle bicuspid aortic valve ▪ The 2 leaflets are heavily calcified, but there is no commissural fusion Aortic Regurgitation: Found In: ▪ Infective endocarditis (most common cause) ▪ Long standing systemic hypertension ▪ Chronic Rheumatic heart disease ▪ Syphilitic aortic aneurysms ▪ Dissecting aortic aneurysms ▪ Coarctation of aorta ▪ Marfan’s syndrome Clinical: Cardiac auscultation : Early diastolic murmur Valvular diseases: Right Heart Tricuspid Insufficiency/Regurgitation & Pulmonary Stenosis **TIPS ▪ Carcinoid tumor metastases in the liver – Release serotonin (5 HT) ▪ Symptoms: ▪ Flushing of skin (vasodilatation) ▪ Diarrhea (increased gut motility) ▪ Tricuspid regurgitation & pulmonary stenosis due to increased collagen production in the valves ▪ Investigation : Increased urinary 5HIAA NOTE: 1. Carcinoid syndrome occurs when the tumor produces excessive amounts of serotonin in an individual with liver metastases Carcinoid tumor Symptoms 2. Carcinoid tumors are a type of slow-growing cancer that can arise in several places throughout your body. Carcinoid tumors, which are one subset of tumors called neuroendocrine tumors, usually begin in the digestive tract (stomach, appendix, small intestine, colon, rectum) or in the lungs.  CHF = Congestive Heart Failure/ Heart Failure LHF =Left Heart Failure RHF=Right Heart Failure Heart Diseases LH = Left Heart RH = Right Heart Inflm = Inflammation Layer Specific Valvular Congenital HF Cardiomyopathy Ischemic Cancer (-Cardium) R →L L→R Myxoma Endo Myo Peri Stable Shunt Shunt LHF RHF LH RH Infllm Hypertrophic Restrictive Rhabdomyoma Dilated Unstable Metastatic Prinzmetal Endocarditis Tetralogy of Atrial septal Fallot (TOF) defect (ASD) Transposition of great Ventricular Rheumatic Carditis vessels septal defect Truncus (VSD) arteriosus Tricuspid Patent Ductus arteriosus Obstructive: Pericarditis atresia Total (PDA) Coarctation of anomalous Aorta pulmonary Atrio- Aortic stenosis Infection venous ventricular Pulmonary Non-infection connection septal defect stenosis Congenital Heart Diseases: Etiology ▪ Idiopathic (90%) ▪ Genetic association ▪ Increased incidence in siblings ▪ Chromosomal abnormalities (5%) ▪ Trisomy 21( Downs) – endocardial cushion defect ▪ Trisomy 18, 13, Cri du Chat- VSD ▪ Turners syndrome – Coarctation of Aorta ▪ Di-Georges – Truncus Arteriosus ▪ Environmental (>>R shunt--- Pulmonary hypertension ▪ Associated conditions: ▪ Prematurity, acidosis, hypoxemia; Congenital rubella infections; 90% isolated; remainder in association with VSD, coarctation ▪ No functional difficulties at birth ▪ Detected by the presence of continuous harsh machinery murmur heard throughout the cardiac Treatment: cycle– systolic & diastolic b/w shoulder blades To close PDA - Indomethacin (inhibits PGE2) & hyperbaric oxygen (PGE2 kEEp it open) Obstructive anomalies: ▪ Coarctation of aorta ▪ Aortic stenosis & atresia ▪ Pulmonary stenosis & atresia Coarctation of Aorta: ▪ Localized constriction of Aorta ▪ Two forms – ▪ Infantile/ preductal coarctation: 70% ▪ Coarctation between subclavian artery & ductus (with patent ductus) ▪ Note: Clinical manifestation depends on 1. Severity of narrowing & ▪ 2. Patency of ductus – cyanosis of lower extremities Associated with turners syndrome **Congenital Cardiac Defects Association: