Nejm 1994;331:1564

Cause: Dilated cardiomyopathy characterized by dilatation and impaired contraction of LV or both ventricles; may be idiopathic, familial/genetic, viral, immune, alcoholic, or toxic

A familial cause is identified in ˜35% of cases; 16 chromosomal loci with altered cytoskeletal and nuclear transfer proteins have been implicated (J Am Coll Cardiol 2005;45:969; Lancet 2001;358:1627).

Ischemic cardiomyopathy: Dilated cardiomyopathy with impaired LV function not explained by extent of CAD or ischemic damage.

Valvular cardiomyopathy: LV dysfunction out of proportion to abnormal loading conditions.

Inflammatory cardiomyopathy: Myocarditis with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms known include Chagas’s disease and HIV, enterovirus, adenovirus, and cytomegalovirus infections.

Metabolic cardiomyopathy is associated with thyrotoxicosis, hypothyroidism, adrenal cortical insufficiency, pheochromocytoma, acromegaly, DM, hemochromatosis, glycogen storage disease, Hurler’s syndrome, Refsum’s syndrome, Niemann-Pick disease, Hand-Schüller-Christian disease, Fabry-Anderson disease, Morquio-Ullrich disease, disturbances of potassium
metabolism, magnesium deficiency, kwashiorkor, anemia, beriberi, selenium deficiency, and familial Mediterranean fever.

Toxic cardiomyopathy may be produced by phenothiazines, reserpine, chloroquine, cobalt, lead, lithium, mercury, CO, EtOH, cocaine, snake venom, and cancer rx. Anthracyclines (doxorubicin, danorubicin) and imatinab are associated with the highest frequency of CHF, but CHF is also seen with mitoxantrone, cisplatin, cyclophosphamide, fosfamide, mitomycin, paclitaxel, bevacizumab, retinoic acid, and pentostatin (Circ 2001;109:3122).

Peripartum cardiomyopathy: Heterogeneous syndrome manifesting in last 6 wk of pregnancy or 5 mon thereafter. It is more common in women with multiple births or pre-eclampsia. Its incidence is 1 per 3000-4000 live births (Jama 2000;283:1183).

Epidem: Annual incidence: 5-8 cases/100,000 population. Blacks and males have a 2.5-fold increase in risk. Associated with HT, β-adrenergic agonist use, and alcohol consumption. Usually presents between ages 20 and 50. 75-85% ofpts present with CHF, and 90% of these are already NYHA functional class III or IV.

20% ofpts have a first-degree relative with decreased EF or cardiomegaly. Inheritance is usually autosomal dominant, although autosomal recessive, X-linked recessive, and mitochondrial inheritance have been reported (Nejm 1992;326:77).

Pathophys: 4-chamber cardiac enlargement with dilation frequently out of proportion to hypertrophy; histology in dilated cardiomyopathy is nonspecific and shows interstitial and perivascular fibrosis

Sx: Fatigue, diminished exercise capacity and exertional dyspnea (86% ofpts), orthopnea, PND, palpitations (30%), peripheral edema (29%); asymptomatic cardiomegaly is detected in 4-13% ofpts; abdominal distention, right-upper-quadrant pain, nausea, anorexia (with right-sided CHF). Exertional chest pain is the initial symptom in 8-20% and is present in ˜35% ofpts overall.

Si: JVD with prominent V wave, brisk Y descent; diffuse, laterally displaced apical impulse, S₄ (inpts in NSR); S₃; systolic murmur
(AV regurgitation). Syncope, S₃ gallop, and right-sided CHF indicate a poor prognosis.

Crs: Presentation is usually with CHF, often progressive. CHF is the cause of death in ˜75% ofpts. Arrhythmias, thromboembolism, and sudden death may occur at any stage. Reported mortality rates are 25-30% at 1 yr and 35-62% at 5 yr.

Predictors of poor outcome include male gender, age > 55 yr at diagnosis, class IV sx, syncope or h/o VT, cardiac arrest, EF < 20%, right-sided failure, and pulmonary HT. Pts with peripartum cardiomyopathy appear in general to have the best prognosis, whilepts with HIV disease or h/o doxorubicin rx have a poor prognosis (Nejm 2000;342:1077).

Cmplc: Afib is seen in < 25% of cases.

Clinically apparent systemic and/or pulmonary emboli are the initial manifestations in 1.5-4% of cases; their overall incidence is 1-12%. Pts with severe LV ventricular dysfunction andpts with Afib, h/o thromboembolism, or echocardiographic evidence of thrombus or prothrombotic states of pregnancy are at greatest risk.

Lab: CBC, UA, glucose, creatinine, Ca⁺⁺, albumin, TSH level indicated

EKG: First-degree AV block, LBBB, left anterior fascicular block, and intraventricular conduction delays occur in > 80% of cases: first- or second-degree AV block RBBB is rare, but LBBB is a predictor of poor prognosis.

Echocardiogram: 4-chamber enlargement; global LV hypokinesis. Monitoring EF, fractional shortening, LV diastolic function, and abnormal response to iv dobutamine may be helpful in followingpts receiving chemotherapy (Circ 2004;109:2122).

Stress test: Forpts with chest pain, prior MI, or high probability of occult CAD

X-ray: CXR: Cardiomegaly; pulmonary venous redistribution; pulmonary edema

Rx: Treatment is that for CHF (see Chapter 6). Vasodilator rx is the standard initial rx (or hydralazine/isosorbide dinitrate) plus diuretics.

Digitalis is effective in controlling sx inpts in NSR. Its long-term benefits include improved EF and exercise capacity.

β-blockers (carvedilol or metoprolol) may also be of benefit.

Anticoagulation with warfarin is appropriate forpts with mural thrombi or h/o embolic phenomena; it is also frequently recommended forpts with EF < 0.30, even though evidence of efficacy from controlled clinical trials is lacking.

Antiarrhythmic drugs have not been shown to decrease mortality. AICD may be of benefit inpts with symptomatic VT or cardiac syncope (Jama 2004;292:2879).

Cardiac transplantation survival rates: 79% at 1 yr, 74% at 5 yr, 72% at 10 yr. Maximal O₂ uptake > 12 mL/kg/min characterizes thosepts most likely to have improved survival after transplantation.

Doxorubicin-induced cardiomyopathy: Cardiotoxicity can be reduced by limiting the peak plasma concentration and overall cumulative dose. Echocardiography is recommended before every additional course up to a total dose of 300 mg/m². Radionuclide angiocardiography should also be performed if the pt is receiving > 400 mg/m² in one course. Echo should be repeated 3, 6, and 12 mon after completion of rx and q 2 yr thereafter, and radionuclide angiocardiography should be done after 12 mon and then q 5 yr (Nejm 1998;339:900).

In peripartum cardiomyopathy, persistence of LV dysfunction beyond 6-12 mon post-dx is a contraindication to subsequent pregnancy (Nejm 2001;344:1629).

Lancet 2004;363:1881; J Am Coll Cardiol 2003;42:1687; Jama 2002;287:1308