DILATED CARDIOMYOPATHY

The 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: 846