Lecture #103. W. Zaloga D.O. (PPT) PDF

CARDIOMYOPATHIES PART 2 – RESTRICTIVE CARDIOMYOPATHIES (RCM) AND MISCELLANEOUS CARDIOVASCULAR SYSTEM William Zaloga, D.O. Department of Clinical Medicine Wilson Hall Room #424F Arkansas State University Jonesboro, Arkansas Session Objectives 1. Discuss, describe, and explain the general...

CARDIOMYOPATHIES PART 2 – RESTRICTIVE CARDIOMYOPATHIES (RCM) AND MISCELLANEOUS CARDIOVASCULAR SYSTEM William Zaloga, D.O. Department of Clinical Medicine Wilson Hall Room #424F Arkansas State University Jonesboro, Arkansas Session Objectives 1. Discuss, describe, and explain the general characteristics and pathophysiology of restrictive cardiomyopathies 2. Discuss, describe, and explain the characteristics and pathophysiology of cardiac amyloidosis. 3. Briefly describe amyloid pathology. 4. Discuss and describe miscellaneous restrictive cardiomyopathies including endomyocardial fibrosis, Loeffler endomyocarditis, and endocardial fibroelastosis 5. Summarize and compare dilated, hypertrophic, and restrictive cardiomyopathies. Amyloidosis Amyloid Abnormal proteins deposits (amyloid fibrils) build up in tissue - nonbranching fibrils that form protein aggregates with beta-pleated sheet, conformation accounts for its staining properties Beta-sheet form of amyloid is proteolysis-resistant There are many different types of amyloid, each due to a specific protein misfolding - become irregular due to genetic effects, and/or acquired environmental factors Grouped into localized (primarily a single organ, caused by several different amyloids) and systemic forms, a few can identify as either Another classification, primary where there is no other disease that is causing the condition, usually affects heart, kidneys, liver, nerves; secondary usually triggered by inflammatory disease, like rheumatoid arthritis, most commonly affects kidneys, liver, spleen Four most common types of systemic amyloidosis - light chain (AL)- multiple myeloma, chronic inflammation (AA) – ex. rheumatoid arthritis, dialysis-related (Aβ2M), and hereditary and old age/senile (ATTR, wild- type transthyretin amyloid overproduction) Source: Robbins and Cotran, Pathologic Basis of Disease, 10th edition, 2020, Ch. 12 Amyloidosis Non-specific and vague signs and symptoms with varied presentations Fatigue Peripheral edema Shortness of breath Palpitations Orthostatic hypotension In AL amyloidosis, can include enlargement of the tongue and periorbital purpura In wild-type ATTR amyloidosis, include heart and tendons: Bbilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, small fiber neuropathy, and autonomic dysfunction Diagnosis may be suspected when protein found in urine, with organ enlargement, or unexplained problems with multiple peripheral nerves - diagnosis confirmed by tissue biopsy Source: Robbins and Cotran, Pathologic Basis of Disease, 10th edition, 2020, Ch. 12 Restrictive Cardiomyopathy Primary decrease in ventricular compliance Results in impaired ventricular filling during diastole Contractile (systolic) function of LV usually not affected Idiopathic or associated with diseases such as radiation fibrosis, amyloidosis, sarcoidosis, metastatic tumor, or products of inborn errors of metabolism Idiopathic - ventricle usually normal size or slightly enlarged, not dilated, myocardium is firm Abnormally rigid, NOT necessarily thickened Biatrial dilation – can cause arrhythmias Microscopy: Patchy or diffuse interstitial fibrosis varying from minimal to severe Endomyocardial biopsy can show disease specific findings in some cases Source: Robbins and Cotran, Pathologic Basis of Disease, 10th ed., 2020, Ch. 12 Idiopathic Restrictive Cardiomyopathy https://www.studyblue.com/notes/note/n/week-82-myocarditis-and- cardiomyopathies-/deck/9469649 Cardiac Amyloidosis Major organ involved in senile amyloidosis Amyloid deposits in atria and ventricles or atria alone; if subendocardial, conduction system may be disturbed Isolated atrial amyloidosis is 4X more common in African Americans > 60 years because of gene mutation in 4% of African American population producing mutant form of transthyretin Grossly may show no significant findings May be mildly enlarged and firm (typical restrictive cardiomyopathy), rubbery, non-compliant May see waxy semi-translucent nodules (subtle) especially on left atrial endocardium Histologically hyaline eosinophilic deposits of amyloid may be found in the interstitium, conduction tissue, valves, endocardium, pericardium, and small intramural coronary arteries With H&E stained tissue sections, amorphous, eosinophilic Congo Red stain shows salmon pink deposits with apple green birefringence upon polarization microscopy Source: Robbins and Cotran, Pathologic Basis of Disease, 10th edition, 2020, Ch. 12 Cardiac amyloidosis Amyloid deposits give the myocardium a pale, translucent, waxy appearance Rubbery, non-compliant http://www.wikidoc.org/index.p hp/File:Cardiac_amyloidosis_c ase_1.jpg Amorphous deposits of pale pink material between myocardial fibers, characteristic for amyloid, one cause for "infiltrative" or "restrictive" cardiomyopathy http://library.med.utah.edu/WebPath/CVHTML/CV072.html Congo red stain: Optical microscopy shows amyloid stains orange-red/salmon pink, but with polarized light, the amyloid has an "apple-green" birefringence http://library.med.utah.edu/WebPath/CVHTML/CV073.html Pathophysiology Lilly, Pathophysiology of Heart Disease, 5th edition, 2011, p. 258 Clinical presentation Signs and symptoms of CHF are common such as: Decreased cardiac output (fatigue and decreased exercise tolerance) Systemic congestion (often more prominent than pulmonary congestion) leads to JVD, peripheral edema, and ascites with a large, tender liver, pulmonary rales CXR: Normal-sized heart with signs of pulmonary congestion ECG: Nonspecific ST & T wave abnormalities; conduction disturbances such as AV block or BBB Restrictive cardiomyopathies share nearly identical symptoms, physical signs, and hemodynamic profiles with constrictive pericarditis - distinguish because constrictive pericarditis is often correctable Lilly, Pathophysiology of Heart Disease, 5th edition, 2011, p. 258 Other restrictive cardiomyopathies: Endomyocardial fibrosis AKA tropical endomyocardial fibrosis, usually a disease of children and young adults especially in Africa/tropics, rare in North America Fibrosis of ventricular endocardium and subendocardium extending from apex to AV valves (may involve valves) Volume and compliance of ventricles is decreased Ventricular mural thrombi may develop Unknown etiology and pathogenesis; however, because pathology resembles eosinophilic cardiomyopathy sometimes considered part of a single disease process that also includes Loeffler endocarditis (eosinophilic endomyocardial fibrosis) Endocardial fibrosis may result from thrombus organization Source: Robbins and Cotran, Pathologic Basis of Disease, 10th edition, 2020, Ch. 12 Loeffler endomyocarditis Rare restrictive cardiomyopathy with endomyocardial fibrosis and usually large mural thrombi Not restricted geographically Increased peripheral blood eosinophils and eosinophils in multiple organs including heart Abnormal eosinophils may release toxic products like major basic protein which cause endocardial damage  areas of necrosis with eosinophilic infiltrate  scarring  layering of endocardium by thrombus  formation of thrombus Associated with chronic myeloproliferative disorder’s PDGFR alpha/beta genes Poor prognosis Source: Robbins and Cotran, Pathologic Basis of Disease, 10th edition, 2020, Ch. 12 Eosinophils and mild myocardial necrosis – Loeffler’s endomyocarditis Reiko Ito, Takuma Sakon, Kiyoshi Yasui, Mari Iwamoto and Yukoh Aihara Allergology International 2003; 52: 219-224 Endocardial fibroelastosis Uncommon, obscure etiology Focal or diffuse fibroelastic thickening usually of mural LV endocardium Usually in the first 2 years of life In a third of cases, accompanied by aortic valve obstruction or a congenital cardiac anomaly Might be common morphologic endpoint of several different insults including viral infections (e.g., intrauterine exposure to mumps) or mutations in the gene for tafazzin, which affects mitochondrial inner membrane integrity Source: Robbins and Cotran, Pathologic Basis of Disease, 10th edition, 2020, Ch. 12 Left ventricle of an infant with endocardial fibroelastosis who died of cardiac failure The endocardium is thick and opaque due to proliferation of collagen and elastic fibers Etiology unknown http://zavantag.com/docs/2110/index-46183.html Restrictive cardiomyopathy summary Dilated Hypertrophic Restrictive Ventricular Dilated LV with Marked hypertrophy Fibrotic or infiltrated morphology possibly some often asymmetric myocardium myocardial thickening Symptoms Fatigue, weakness, Dyspnea, angina, Dyspnea, fatigue dyspnea, orthopnea, syncope PND Physical Exam Pulmonary rales, S3; S4; if outflow Signs of RV failure: if RV failure present, obstruction present, JVD, hepatomegaly, JVD, hepatomegaly, systolic murmur peripheral edema peripheral edema loudest at left sternal border, may be accompanied by mitral regurgitation Pathophysiology Impaired systolic Impaired diastolic “Stiff” LV with contraction relaxation; LV impaired diastolic systolic function relaxation but vigorous, often with normal systolic dynamic obstruction function Question A 72-year-old male with bilateral atrial dilation undergoes a heart biopsy to evaluate fatigue, jugular vein distension, hepatomegaly, peripheral edema, and indications of a “stiff ventricle”. The H&E stained biopsy shows eosinophilic, homogenous material between the myocytes which stains salmon pink with Congo Red special stain and then shows apple green birefringence upon polarization. What is the most likely diagnosis? A. Endomyocardial fibrosis B. Loeffler endomyocarditis C. Endocardial fibroelastosis D. Cardiac amyloidosis E. Arrhythmogenic right ventricular cardiomyopathy Summary slide Restrictive cardiomyopathy – definition, overview Example – cardiac amyloidosis Restrictive cardiomyopathy – pathophysiology Endomyocardial fibrosis Loeffler endomyocarditis – eosinophils, myeloproliferative disorders association Endocardial fibroelastosis Comparison chart: HCM, DCM, RCM References Kumar, V. (2014). The Heart. In Robbins basic pathology (9th ed, ch. 12). Philadelphia, PA: Saunders/Elsevier Lilly, L. (2011). Cardiomyopathies. In Pathophysiology of heart disease: A collaborative project of medical students and faculty (5th ed.). Baltimore, MD: Wolters Kluwer/Lippincott Williams & Wilkins. First Aid for the USMLE Step 1, 2016 USMLERx Question Bank Robbins and Cotran, Pathologic Basis of Disease, 10th ed., 2020, Ch. 12 Lecture feedback form https://comresearchdata.nyit.edu/redcap/surveys/?s=HRCY448FWYXREL4R