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DILATED CARDIOMYOPATHYThe term dilated cardiomyopathy (DCM) is applied to a form of cardiomyopathy characterized by progressive cardiac dilation and contractile (systolic) dysfunction, usually with concomitant hypertrophy. It is sometimes called congestive cardiomyopathy. Figure 12-31Graphic representation of the three distinctive and predominant clinical-pathologic-functional forms of myocardial disease. TABLE 12-10-- Cardiomyopathy and Indirect Myocardial Dysfunction: Functional Patterns and Causes Functional Pattern Left Ventricular Ejection Fraction * Mechanisms of Heart Failure Causes Indirect Myocardial Dysfunction (Not Cardiomyopathy) Dilated <40% Impairment of contractility (systolic dysfunction) Idiopathic; alcohol; peripartum; genetic; myocarditis; hemochromatosis; chronic anemia; doxorubicin (Adriamycin); sarcoidosis Ischemic heart disease; valvular heart disease; hypertensive heart disease; congenital heart disease Hypertrophic 50–80% Impairment of compliance (diastolic dysfunction) Genetic; Friedreich ataxia; storage diseases; infants of diabetic mothers Hypertensive heart disease; aortic stenosis Restrictive 45–90% Impairment of compliance (diastolic dysfunction) Idiopathic; amyloidosis; radiation-induced fibrosis Pericardial constriction *Normal, approximately 50–65%. TABLE 12-11-- Conditions Associated with Heart Muscle Diseases Cardiac Infections Viruses Chlamydia Rickettsia Bacteria Fungi Protozoa Toxins Alcohol Cobalt Catecholamines Carbon monoxide Lithium Hydrocarbons Arsenic Cyclophosphamide Doxorubicin (Adriamycin) and daunorubicin Metabolic Hyperthroidism Hypothyroidism Hyperkalemia Hypokalemia Nutritional deficiency (protein, thiamine, other avitaminoses) Hemochromatosis Neuromuscular Disease Friedreich ataxia Muscular dystrophy Congenital atrophies Storage Disorders and Other Depositions Hunter-Hurler syndrome Glycogen storage disease Fabry disease Amyloidosis Infiltrative Leukemia Carcinomatosis Sarcoidosis Radiation-induced fibrosis Immunologic Myocarditis (several forms) Post-transplant rejection Although it is recognized that approximately 25% to 35% of individuals with DCM have a familial (genetic) form, DCM can result from a number of acquired myocardial insults that ultimately yield a similar clinicopathologic pattern. These include toxicities (including chronic alcoholism, a history of which can be elicited in 10% to 20% of patients), myocarditis (an inflammatory disorder that precedes the development of cardiomyopathy in at least some cases, as documented by endomyocardial biopsy), and pregnancy-associated nutritional deficiency or immunologic reaction. In some patients, the cause of DCM is unknown; such cases are appropriately designated as idiopathic dilated cardiomyopathy. Morphology. In DCM, the heart is usually heavy, often weighing two to three times normal, and large and flabby, with dilation of all chambers ( Fig. 12-32 ). Nevertheless, because of the wall thinning that accompanies dilation, the ventricular thickness may be less than, equal to, or greater than normal. Mural thrombi are common and may be a source of thromboemboli. There are no primary valvular alterations, and mitral or tricuspid regurgitation, when present, results from left ventricular chamber dilation (functional regurgitation). The coronary arteries are usually free of significant narrowing, but any coronary artery obstructions present are insufficient to explain the degree of cardiac dysfunction. The histologic abnormalities in idiopathic DCM also are nonspecific and usually do not reflect a specific etiologic agent.Moreover, their severity does not necessarily reflect the degree of dysfunction or the patient's prognosis. Most muscle cells are hypertrophied with enlarged nuclei, but many are attenuated, stretched, and irregular. Interstitial and endocardial fibrosis of variable degree is present, and small subendocardial scars may replace individual cells or groups of cells, probably reflecting healing of previous secondary myocyte ischemic necrosis caused by hypertrophy-induced imbalance between perfusion, supply and demand. Pathogenesis. Historically, the etiologic associations in dilated cardiomyopathy have included myocardial inflammatory Figure 12-32Dilated cardiomyopathy. A, Gross photograph. Four-chamber dilatation and hypertrophy are evident. There is granular mural thrombus at the apex of the left ventricle (on the right in this apical four-chamber view). The coronary arteries were unobstructed. B, Histology demonstrating variable myocyte hypertrophy and interstitial fibrosis (collagen is highlighted as blue in this Masson trichrome stain). Figure 12-33Arrythmogenic right ventricular cardiomyopathy. A, Gross photograph, showing dilation of the right ventricle and near transmural replacement of the right ventricular freewall myocardium by fat and fibrosis. The left ventricle has a virtually normal configuration. B, Histologic section of the right ventricular free wall, demonstrating replacement of myocardium (red) by fibrosis (blue, arrow) and fat (collagen is blue in this Masson trichrome stain). Figure 12-34Hypertrophic cardiomyopathy with asymmetric septal hypertrophy. A, The septal muscle bulges into the left ventricular outflow tract, and the left atrium is enlarged. The anterior mitral leaflet has been moved away from the septum to reveal a fibrous endocardial plaque (arrow) (see text). B, Histologic appearance demonstrating disarray, extreme hypertrophy, and characteristic branching of myocytes as well as the interstitial fibrosis characteristic of hypertrophic cardiomyopathy (collagen is blue in this Masson trichrome stain). C, Schematic structure of the sarcomere of cardiac muscle, highlighting proteins in which mutations cause defective contraction, hypertrophy, and myocyte disarray in hypertrophic cardiomyopathy. The frequency of a particular gene mutation is indicated as a percentage of all cases of HCM; most common are mutations in b-myosin heavy chain. Normal contraction of the sarcomere involves myosin-actin interaction initiated by calcium binding to troponin C, I, and T and a-tropomyosin. Actin stimulates ATPase activity in the myosin head and produces force along the actin filaments. Myocyte-binding protein C modulates contraction. (A, reproduced by permission from Schoen FJ: Interventional and Surgical Cardiovascular Pathology: Clinical Correlations and Basic Principles. Philadelphia, W.B. Saunders, 1989. C, from Spirito P, et al: The management of hypertrophic cardiomyopathy. N Engl J Med 336:775, 1997.) Figure 12-35Pathways of dilated and hypertrophic cardiomyopathy, emphasizing several important concepts. Some forms of dilated cardiomyopathy (others are caused by myocarditis, alcohol, and other toxic injury or the peripartum state) and virtually all forms of hypertrophic cardiomyopathy are genetic in origin. The genetic causes of dilated cardiomyopathy involve mutations in any of a wide variety of proteins, predominantly of the cytoskeleton, but also the sarcomere, mitochondria, and nuclear envelope. In contrast, the mutated genes that cause hypertrophic cardiomyopathy encode proteins of the sarcomere. Although these two forms of cardiomyopathy differ greatly in subcellular basis and morphologic phenotypes, they share a common pathway of clinical complications. TABLE 12-12-- Major Causes of Myocarditis Infections Viruses (e.g., coxsackievirus, ECHO, influenza, HIV, cytomegalovirus) Chlamydiae (e.g., C. psittaci) Rickettsiae (e.g., R. typhi, typhus fever) Bacteria (e.g., Corynebacterium diphtheriae, Neisseria meningococcus, Borrelia (Lyme disease) Fungi (e.g., Candida) Protozoa (e.g., Trypanosoma Chagas disease, toxoplasmosis) Helminths (e.g., trichinosis) Date: 2016-04-22; view: 948
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