The Pathology of Myocardial Diseases

1. The Pathology of Myocardial Diseases

2. (1) Cardiomyopathy Defined as “heart muscle disease of unknown cause,” generally referred to as primary or idiopathic cardiomyopathy, (2) Specific heart muscle disease defined as “heart muscle disease of known cause or associated with disorders of other systems. Myocardium

3. The clinical picture is largely determined by one of the following three clinical, functional, pathologic patterns, each of which can have either a known or an unknown cause: Dilated Cardiomyopathy(90%) Hypertrophic Cardiomyopathy Restrictive Cardiomyopathy Cardiomyopathies Myocardium

4. Etiology of the DCM : 1. Primary (Idiopathic) (30%) DCM 2. Secondary DCM Dilated Cardiomyopathy (DCM) Myocardium

5. 1. Primary (Idiopathic) dilated cardiomyopathy Characterized by the gradual development of cardiac failure associated with four-chamber hypertrophy and dilatation of the heart of unknown cause. Familial occurrence (approximately 20% of cases) autosomal dominant, autosomal recessive, and X-linked inheritance Genetic syndromes: Friedreich's ataxia Duchenne's-Becker's muscular dystrophy Myocardium

6. Pathophysiology Apoptosis, or programmed cell death, has been reported in clinical and experimental dilated cardiomyopathy, which is characterized by depressed systolic function or systolic pump failure cardiomegaly ventricular dilatation Reduced left ventricular contractile force leads to decreased cardiac output, resulting in increased residual volumes in end-systole and end-diastole. Myocardium

7. Usually affects those 20 to 60 years old Slowly develops Fifty percent of patients die within 2 years only 25% of patients survive longer than 5 years Death is usually attributable to progressive cardiac failure and/or arrhythmia Embolism from dislodgement of an intracardiac thrombus may occur Myocardium

8. Secondary dilated cardiomyopathies Alcoholism Chemicals&Drugs Heavy metals Emetine Doxorubicin Cocaine Methamphetamine Cobalt High output states Anemia Thyrotoxicosis Pregnancy HIV and other infections Viral endocarditis/myocarditis Parasites Protozoa Chagas disease (most common cause in parts of South America) Collagen vascular disease Glycogen storage disease Thiamine deficiency and zinc deficiency Hypophosphatemia Amyloidosis Neuromuscular disorders Myocardium

9. Pathology The heart is usually heavy Weighing two to three times normal, Flabby (usually with dilatation of all chambers) Nevertheless, because of the wall thinning that accompanies dilatation, the ventricular wall thickness may be less than, equal to, or more than normal. Mural thrombi are common particularly near the apex of the left and right ventricles and in the atria thromboembolism Mitral regurgitation, when present, is primarily a result of left ventricular chamber dilatation (functional mitral regurgitation). Myocardium

10. The left ventricle often has patchy myocardial (mostly subendocardial) fibrous scars The sizes of individual muscle cells vary; The nuclei are usually enlarged throughout, indicating hypertrophy. Myocardium

11. Complications Heart failure Volume overload Pulmonary edema Hypoxia Cardiogenic shock Death Myocardium

12. Arrhythmogenic Right VentricularCardiomyopathy (Right ventricular Dysplasia) Familial disorder Progressive nature of the lesion with apoptosis Sudden death in vigorous good health right-sided and sometimes left-sided heart failure rhythm disturbances (particularly ventricular tachycardia) Morphology the right ventricular wall is severely thinned, extensive fatty infiltration loss of myocytes interstitial fibrosis Myocardium

13. Hypertrophic Cardiomyopathy(HCM) Hypertrophic cardiomyopathy is also known by such terms as Synonyms: idiopathic septal hypertrophy asymmetric septal hypertrophy Les Aspin's disease Reggie Lewis's disease muscle-bound heart A genetic basis in many cases Myocardium

14. It is characterized by a heavy muscular hypercontracting heart, in striking contrast to the flabby, hypocontracting heart of dilated CM. In contrast to the hypertrophy induced by the increased workload of valvular, hypertensive, ischemic, and congenital heart diseases, that observed in Hypertrophic CM develops progressively in the absence of an identifiable extrinsic inciting stress. Myocardium

15. End-stage heart failure can be accompanied by dilatation. The major problems in HCM are: atrial fibrillation with mural thrombus formation, embolization from the mural thrombi, infective endocarditis on the mitral valve, intractable cardiac failure, sudden death (most common cause of death and particularly likely in young males with familial HCM or with a family history of sudden death). Myocardium

16. Morphological findings The essential anatomic feature of HCM is massivemyocardial hypertrophy. The classic pattern is said to be disproportionate thickening of the ventricular septum as compared with the free wall of the left ventricle (with a ratio greater than 1.3), frequently termed asymmetric septal hypertrophy. Myocardium

17. Restrictive cardiomyopathy can be idiopathic or secondary to a heart muscle disease that manifests as restrictive physiology. The common hemodynamic disturbance is impairment of ventricular filling due to the thickening and increased rigidity of the endocardium and myocardium secondary to infiltration by amyloid or by fibrosis. Restrictive Cardiomyopathy(RCM) Myocardium

18. Systolic function remains normal or near normal until late stages. Most older people get some amyloid in their atria and aortas. If amyloid involves the myocardium extensively, the muscles cannot contract. This is the usual cause of "restrictive cardiomyopathy". Myocardium

19. Etiology: Idiopathic restrictive cardiomyopathy Loeffler eosinophilic endomyocardial disease Secondary restrictive cardiomyopathy Hemochromatosis Amyloidosis Sarcoidosis Progressive systemic sclerosis (scleroderma) Carcinoid heart disease Glycogen storage disease of the heart Myocardium

20. MORPHOLOGY: the ventricles are of approximately normal size or slightly enlarged the cavities are not dilated the myocardium is firm biatrial dilatation (common) Microscopically there is patchy or diffuse interstitial fibrosis/amyloid. Myocardium

21. Specific Heart Muscle Disease

22. Cardiac infections Viruses coxsackievirus ECHO influenza HIV CMV Chlamydia (C.psitacci) Rickettsia Bacteria Corynebacterium Neisseria Borrelia Fungi (Candida) Protozoa Trypanosoma Toxoplasma Helminth (Trichinosis) Myocardium

23. Toxic substances Alcohol Cobalt Cathecolamines CO Lithium Hydrocarbons Arsenic Cancer chemotherapy Myocardium

24. Metabolic causes Hyperthyroidism Hypothyroidism Hypokalemia Hyperkalemia Hypoproteniamia, Hypovitaminosis(thiamine) Hemochromatosis Myocardium

25. Neuromuscular disease Stroge disorders Friedreichs ataxia Muscular dystrophia Congenital atrophies Hunter-Hurler syndrome Glycogen storage disease Amyloidosis Myocardium

26. Infiltrative diseases Immun-mediated reactions Leukemia Carcinomatosis Sarcoidosis Radiation-induced fibrosis Myocarditis Post-transplant rejection Myocardium

27. Myocarditis Myocarditis is an uncommon disease that is characterized by inflammation of the heart; leukocytic infiltrate resultant nonischemic necrosis degeneration of myocytes Subsequent myocardial destruction often leads to a dilated cardiomyopathy. Most cases of well-documented myocarditis are viral in origin. Myocardium

28. Infectious agents Viruses(Coxsackievirus(B), Advenovirus, Echovirus, EBV, Hepatitis C, HHV, HIV, CMV, Influenza, Measles, Mumps, Rubella, Varicella) Chlamydia(C.psitacci) Rickettsia (R. rickettsii, R. tsutsugamushi) Bacteria (Corynebacterium, Neisseria, Borrelia, Klebsiella, Leprospira, Cocci, Clostridia, Treponema, Brucella, Salmonella) Fungi (Candida, Actinomycosis, Coccidioidomycosis, Histoplasmosis) Protozoa (Trypanosoma cruzi, toxoplasma, amebiasis) Other parasites (Toxocara canis, Schistosomiasis, Heterophyiasis, Cysticercosis, Echinococci, Visceral larva migrans. Etiology of Myocarditis Myocardium

29. Immun-mediated reactions Drugs Hypersensitivity myocarditis is observed with a variety of medications (eosinophilic infiltrate of the myocardium) A direct cytotoxic effect on the myocardium Post-transplant rejection Medications penicillin, ampicillin, hydrochlorothiazide, methyldopa, sulfonamide lithium, doxorubicin, cocaine, numerous catecholamines, acetaminophen, cyclophosphamide, tetracycline, isoniazid, phenytoin, ect. Myocardium

30. Chemicals Systemic diseases Radiation therapy (dilated cardiomyopathy) Lead Arsenic Carbon monoxide Scorpion envenomations Autoimmune diseases ( SLE, Scleroderma, Rhematoid arthritis) Sarcoidosis Giant cell myocarditis SLE Giant cell arteritis Dermatomyositis Ulcerative colitis Myocardium

31. It may occur at any age The vulnerable ones... infants immunosuppressed individuals pregnant women Myocardium

32. A Specific type of Myocarditis:Chagas’ disease Caused by a protozoa: Trypanosoma cruzi Although uncommon in the northern hemisphere, Chagas’ disease affects up to one-half of the population in endemic areas of South America. Myocardial involvement is found in approximately 80% of infected individuals. Myocardium

33. Trichinosis The most common helminthic disease with associated cardiac involvement. Corynebacterium diphtheriae Traditionally considered a myocarditis, injury to the myocardium by the potent exotoxin of the bacterium Corynebacterium diphtheriae is characterized by patchy myocyte necrosis with only a sparse lymphocytic infiltrate. Myocardium

34. HIV myocarditis Myocarditis occurs in many patients with acquired immunodeficiency syndrome (AIDS). Two types have been identified: (1) inflammation and myocyte damage without a clear etiologic agent (2) myocarditis caused directly by HIV or by an opportunistic pathogen Myocardium

35. Morphology During the active phase of myocarditis, the heart may appear normal or enlarged with dilatation of either ventricle or all chambers. The lesions may be diffuse or patchy. The ventricular myocardium is typically flabby and often mottled by either pale foci or minute hemorrhagic lesions. The endocardium and valves are unaffected except that mural thrombi may be present in any chamber. Myocardium

36. Microscopic classification: Nonmyocarditis Active myocarditis Characterized by abundant inflammatory cells and myocardial necrosis Borderline myocarditis Characterized by an inflammatory response that is too sparse for this type to be labeled as active myocarditis; degeneration of myocytes not demonstrated with light microscopy. Myocardium

37. Histology During Active myocarditis Interstitial mononuclear, predominantly lymphocytic inflammatory infiltrate (focal or patchy) + Focal necrosis necrosis and disarrangement of the myocytes are typical and often are seen with coxsackievirus infection occasionally with a necrotic myocyte (often with contraction bands) Myocardium

38. The histologic pattern of reaction to bacterial or fungalinvasiondepends on the specific causative organism, if present. Hypersensitivity reactions that involve the myocardium induce interstitial infiltrates that are principally perivascular, composed of lymphocytes, macrophages, and a high proportion of eosinophils. In the chronic and healing stages, myocytes are replaced by fibroblasts (scar tissue). Myocardium

39. In giant cell myocarditis, giant cells are present in the myocardium with or without granulomas. Tuberculosis, syphilis, rheumatoid arthritis, rheumatic heart disease, or with fungal or parasitic infections. The characteristic cell probably is histiocytic in origin and usually is found in nonviral myocarditis. Similar cells have been noted in patients with myocarditis associated with drugs such as phenylbutazone. Myocardium

40. Systemic lupus erythematosus (SLE) may demonstrate myocardialfibrinoid lesions found in the connective tissue with an accompanying cellular reaction. This reaction also may affect the valves, most notably, the mitral and aortic valves. Libman and Sacks describe this latter type of endocarditis. Although the predominant cardiac manifestation of SLE is pericarditis, myocardial involvement with CHF can occur Myocardium

41. Viral Myocarditis Myocardium

42. Aspergillus Myocarditis Myocardium

43. Pyemic Myocarditis Myocardium

44. Complications: Congestive heart failure Pulmonary edema Cardiogenic shock Cardiac failure Recurrent myositis Dysrhythmia/Arrhythmia Thromboembolism. Myocardium

45. Secondary cardiomyopathies Alcohol Chemotherapy (doxo- and daunorubicin; Adriamycin) Cathecolamines and Pheochromocytoma("catecholamine heart", with single-fiber necrosis as in cocaine heart) Peripartum cardiomyopathy Amyloidosis Hemochromatosis Hyper-/hypo- thyroidism Pompe's glycogenosis Duchenne's & Friedreich's Disease End-stage HIV infection Myocardium

46. Alcohol Alcohol or its metabolites (especially acetaldehyde) has a direct toxic effect on the myocardium Chronic alcoholism may be associated with thiamine deficiency, introducing an element of beriberi heart disease Adriamycin and Other Drugs Some of the chemotherapeutic agents doxorubicin (adriamycin) and daunorubicin are well recognized causes of toxic myocardial injury Many other agents, such as lithium, phenothiazines, and cocaine, have been implicated in myocardial injury Cocaine also causes catecholamine-induced cell damage Myocardium

47. Peripartum cardiomyopathy Pregnancy invokes the possibilities of hypertension volume overload nutritional deficiency other metabolic derangement immunologic reaction Myocardium

48. Amyloidosis Cardiac amyloidosis may appear along with systemic amyloidosis or may affect only the heart, particularly in the aged (senile isolated cardiac amyloidosis) Clinically important amyloid deposits can occur in the hearts of patients with multiple myeloma Myocardium

49. Hereditary hemochromatosis and hemosiderosis Most commonly with a dilated pattern Iron deposition is more prominent in ventricles than atria and in the working myocardium than in the conduction system Microscopy marked accumulation of hemosiderin within cardiac myocytes (intracellular) Varying degrees of cellular degeneration and fibrosis Myocardium

50. THANK YOU Myocardium