Arunima Misra, MD, FACC, Shawn T. Ragbir, MD and Biykem Bozkurt, MD, FACC

1. What is the definition of dilated cardiomyopathy?

    Dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders characterized by ventricular dilation and depressed myocardial contractility in the absence of abnormal loading conditions (e.g., hypertension or valvular heart disease) or ischemic heart disease sufficient to cause global systolic impairment. Thus, DCM can be envisioned as the final common pathway for myriad cardiac disorders that either damage the heart muscle or, alternatively, disrupt the ability of the myocardium to generate force and subsequently cause chamber dilation.

    In practice and clinical trials, DCM is used interchangeably with nonischemic cardiomyopathy (NICM), although the latter includes systolic heart failure (heart failure) related to hypertension or valvular disease.

2. How prevalent is DCM?

    The incidence of DCM is 5 to 8 per 100,000 persons, whereas the prevalence is 36 per 100,000. DCM accounts for 10,000 deaths annually and represents approximately 30% to 40% of heart failure cases (as defined by NICM). African Americans are three times more likely to develop DCM than whites, and more likely to die from DCM compared with age-matched whites.

3. How does DCM present?

    The presenting features of DCM are typical of heart failure and include symptoms of left ventricular (LV) failure, including progressive exertional dyspnea, fatigue, weakness, diminished exercise capacity, orthopnea, paroxysmal nocturnal dyspnea, and nocturnal cough. Abdominal distension, right upper quadrant abdominal pain, early satiety, postprandial fullness, and nausea are seen with the development of right-sided heart failure. In advanced heart failure, cardiac cachexia may develop. Approximately 4% to 13% of the patients with DCM will present with asymptomatic LV dysfunction and LV dilation.

4. What kind of diagnostic studies should be carried out for DCM?

    The diagnostic evaluation is similar to those with ischemic heart failure and should include routine assessment of serum electrolytes, liver function tests, complete blood cell count, cardiac enzymes, serum natriuretic peptide levels (B-type natriuretic peptide [BNP] or N-terminal prohormone of BNP [NT-proBNP]), chest radiograph, electrocardiogram, and assessment of LV function by echocardiography or radionuclide imaging.

    Echocardiography typically shows four-chamber dilation, wall thinning, global hypokinesis, and left ventricular ejection fraction (LVEF) less than 35% to 40%. LV apical thrombi can be identified in up to 40% of patients with DCM. Tricuspid and mitral regurgitation may be present as a result of annular dilation and altered LV geometry. Doppler mitral inflow patterns may reveal elevated filling pressures.

    Multigated radionuclide angiocardiography (MUGA) may be used to assess LV systolic function in those with poor echocardiographic windows. Compared with echo assessment of LVEF, MUGA may have less interobserver and intertest variability. Thallium-201 myocardial scintigraphy is not a reliable technique for differentiating patients with ischemic cardiomyopathy (ICM) from those with DCM, as patients with DCM may have both reversible and fixed perfusion abnormalities related to the presence of myocardial fibrosis, although a completely normal scan (without reversible or fixed defects) would favor the diagnosis of NICM.

    Cardiac catheterization may be performed if symptoms suggestive of ischemia are present or if coronary artery disease is strongly suspected. Catheterization in DCM generally shows normal coronary arteries or mild, nonobstructive, isolated atherosclerotic lesions that are insufficient to explain the extent of cardiomyopathy.

    Endomyocardial biopsy may be performed if and only if a specific diagnosis is suspected in which specific therapy may be efficacious upon establishment of diagnosis (see Chapter 23 on endomyocardial biopsy).

5. What is the natural history of DCM?

    The natural history of DCM depends on the underlying cause. Generally, symptomatic patients have a 25% mortality at 1 year and 50% mortality at 5 years. The prognosis in those with asymptomatic LV dysfunction is less clear. Pump failure accounts for approximately 70% of deaths, whereas sudden cardiac death accounts for approximately 30%.

    Approximately 25% of symptomatic DCM patients will improve spontaneously. Idiopathic DCM has a lower total mortality compared with ischemic cardiomyopathy, although the risk of sudden death may be higher.

6. What are the prognostic features of DCM?

    Many of the prognostic features are similar to those in ischemic cardiomyopathy, including age, LVEF, New York Heart Association (NYHA) class, lack of heart rate variability, elevated levels of neurohormones, and elevated markers of myocardial cell death. However, certain causes of DCM carry a more favorable prognosis and are potentially reversible—for example, cardiomyopathy associated with alcohol, peripartum, trastuzumab, or tachycardia. Other causes, such as anthracyclines or human immunodeficiency virus (HIV), have a worse prognosis.

7. What are the common causes of DCM?

    The term nonischemic cardiomyopathy may include cardiomyopathies commonly caused by hypertension or valvular heart disease, which are not conventionally accepted under the definition of DCM. Causes for DCM include genetic causes (familial cardiomyopathies), toxins (alcohol, cocaine, chemotherapy such as anthracycline), infection (such as Coxsackie virus, HIV, Trypanosoma cruzi), inflammatory disorders (such as collagen vascular disease, hypersensitivity myocarditis), nutritional causes (such as thiamine deficiency), pregnancy, endocrine causes (such as diabetes, hyperthyroidism), tachycardia, and stress-induced (tako-tsubo) cardiomyopathy.

8. What are the features of alcohol-induced cardiomyopathy?

    Alcohol-induced cardiomyopathy is said to occur when cardiomyopathy is noted in a heavy drinker in the absence of other causes (i.e., by exclusion). Alcoholic patients consuming more than 90 g of alcohol a day (approximately 7 to 8 standard drinks per day) for more than 5 years are at risk for this entity. Symptoms may develop with continued drinking. Approximately 20% of subjects with excessive drinking may demonstrate clinical heart failure. The typical patient is a man 30 to 55 years old who has been a heavy alcohol consumer for 10 years. Women may be more susceptible to the cardiodepressive effects of alcohol. Death rates are higher in African Americans (compared with whites). Abstinence may partially or completely reverse the cardiomyopathy. Overall prognosis remains poor, with a mortality of 40% to 50% at 3 to 6 years without abstinence.

9. What are the features of cocaine-induced cardiomyopathy?

    Approximately 4% to 18% of cocaine users have depressed LV function. Cardiac catheterization reveals normal or mildly diseased coronary arteries, insufficient to explain the extent of myocardial dysfunction. Abstinence may lead to reversal.

10. What are the features of chemotherapy-induced cardiomyopathy?

    Anthracyclines and trastuzumab are among the more prominent chemotherapeutic agents associated with cardiomyopathy. Three major types of anthracycline cardiotoxicity are distinguished: acute, chronic, and late onset, which differ considerably in clinical picture and prognosis. Cardiac failure is rare with acute toxicity. Chronic cardiotoxicity is observed in 0.4% to 23%, several weeks or months after chemotherapy. Such anthracycline-induced cardiomyopathy carries a 27% to 61% mortality rate despite aggressive medical treatment. Late cardiotoxicity occurs years after chemotherapy, at 5% at 10 years, and presents as heart failure, arrhythmia, or conduction abnormalities. The primary risk factor for cardiomyopathy is cumulative dose administered. Toxicity is rare (less than 3%) with cumulative doses below 400 mg/m². Other risk factors include extremes of age and coexisting cardiac disease. Elevated cardiac troponin and BNP after chemotherapy may allow identification of patients who may develop cardiac toxicity. Anthracyclines should not be administered to patients with a baseline LVEF of 30% or less. LV function should be assessed repeatedly before each subsequent dose (or if the initial ejection fraction [EF] is more than 50%, after a cumulative dose of 350 to 500 mg/m²), and treatment stopped if EF declines by 10% or more, or to a value less than 30% (or less than 50% if EF was normal at baseline). Reversibility has been documented anecdotally. The most effective protection is dexrazoxane (an iron chelator), with a two- to threefold decrease in the risk of cardiomyopathy.

    Trastuzumab is a monoclonal antibody that selectively binds human epidermal growth factor receptor 2 (HER2), which is expressed in 25% of cases of breast cancer. In earlier trials in advanced breast cancer, trastuzumab was associated with the development of heart failure in up to 27% of patients. The majority of these patients, however, had received significant cumulative doses of anthracyclines or had preexisting cardiac disease. Risk factors for development of trastuzumab-associated heart failure include increasing age, lower LVEF, and higher anthracycline dose. Trastuzumab-associated heart failure responds better to standard therapy than does anthracycline-induced heart failure, with complete recovery usually seen within 6 months of discontinuing trastuzumab.

11. What are the features of HIV-related cardiomyopathy?

    HIV-related cardiomyopathy accounts for up to 4% of DCM. The incidence is higher among patients with a CD4 count less than 400 cells/mm³. HIV-related cardiomyopathy is discussed in detail in Chapter 46 on cardiac manifestations of HIV and acquired immunodeficiency syndrome (AIDS).

12. What are the associations between collagen vascular disease and DCMs?

    In systemic lupus erythematosus (SLE), global LV dysfunction has been reported in 5% of patients, segmental LV wall motion abnormalities in 4% of patients, and right ventricular enlargement in 4% of patients, but DCM is rare. In rheumatoid arthritis, symptomatic cardiac disease, including myocarditis, develops in 8% of patients. Progressive systemic sclerosis can rarely lead to heart failure through myocardial fibrosis, arrhythmia, or intermittent vascular spasm. Dermatomyositis may be associated with cardiomyopathy in some patients. For further discussion, see Chapter 47 on cardiac manifestations of connective tissue disorders and vasculitides.

13. What is peripartum cardiomyopathy?

    Peripartum cardiomyopathy (PPCM) is the development of symptomatic heart failure in the last trimester of pregnancy or within 6 months of parturition. Other causes of DCM must be excluded in such patients before making the PPCM diagnosis. PPCM occurs in 1 per 2289 to 4000 live births. Risk factors may include older age, multiparity, African American ancestry, multiple gestation, toxemia, chronic hypertension, and use of tocolytics. In recent case series, up to 50% of PPCM developed with the first two pregnancies. Fifty percent of women recover baseline cardiac function within 6 months. Even though the prognosis in subsequent pregnancies is better if cardiac function recovers, 21% of these patients will develop heart failure symptoms. The prognosis in subsequent pregnancies is poorer if cardiac function remains abnormal—37% deliver prematurely and 19% die.

14. What are the features of tachycardia-induced cardiomyopathy?

    Sustained elevated ventricular rates have been shown to cause changes in LV geometry and dilation. This entity should be considered in patients with no other explanation for LV dysfunction and a concomitant tachyarrhythmia. Hyperthyroid-induced sinus tachycardia or atrial fibrillation should be excluded in such patients. Treatment involves restoration of normal sinus rhythm or control of ventricular rate, with which there is typically resolution as quickly as 4 to 6 weeks.

15. What are the features of nutritional causes of DCM?

    Thiamine deficiency causes cardiovascular beriberi, in which the circulation is hyperkinetic and DCM results. Treatment for beriberi should consist of administration of thiamine, along with standard heart failure therapy. DCM may occur with chronic alcoholism and with anorexia nervosa.

16. What are the features of cardiomyopathy caused by iron overload?

    Iron-overload cardiomyopathy occurs as a result of increased cardiac iron deposition, commonly in disorders such as hereditary hemochromatosis and β-thalassemia major. Extracardiac manifestations typically precede symptomatic heart failure. Initially, the hemodynamic profile represents a restrictive pattern. As cardiomyopathy advances, DCM ensues. The diagnosis of iron overload is suggested by elevated serum ferritin and a ratio of iron to total iron-binding capacity greater than 50%. The most definitive test for calculation of iron stores is measurement of iron concentration by liver biopsy.

    The mainstays of therapy are phlebotomy (in hereditary hemochromatosis) and chelation therapy (in secondary iron overload related to blood transfusions, prophylactically after transfusion of 20 to 30 units of red blood cells [RBCs] or when serum ferritin is more than 2500 ng/mL). Early diagnosis and treatment before tissue damage has occurred is essential, because life span seems to be normal in treated patients but markedly shortened in those who are not.

17. What are the pharmacologic treatments to be used in DCM?

    Similar to therapy for chronic stable heart failure, standard medical therapy with β-blockers and angiotensin-converting enzyme (ACE) inhibitors (or angiotensin-receptor blockers) is indicated per current guidelines from the American College of Cardiology/American Heart Association (ACC/AHA). Intake of salt should be restricted. Depending on the circumstances, spironolactone, or a combination of isosorbide dinitrate and hydralazine, may be added in symptomatic heart failure, and in some patients digoxin may be considered. Use of spironolactone should entail judicious adjustment of potassium supplements and close laboratory follow-up. Diuretics should be used to manage volume overload symptoms.

    Antiarrhythmic therapy is reserved for individualized treatment of symptomatic arrhythmias, especially for suppression of ventricular arrhythmias after an implantable cardioverter-defibrillator (ICD). Recent data suggest that use of such agents for maintaining sinus rhythm in heart failure patients with atrial fibrillation may not be better than rate control.

18. What are the device treatments to be used in DCM?

    Defibrillators are indicated for secondary prevention in survivors of ventricular fibrillation (VF) or hemodynamically significant ventricular tachycardia (VT); in patients with structural heart disease or unexplained syncope with hemodynamically significant VF or VT on electrophysiologic study; and in patients with NICM who have an LVEF 35% or lower.

    Recent trials of cardiac resynchronization therapy (with or without concomitant defibrillator) have shown a 50% decrease in all-cause mortality versus placebo among subjects with NICM or DCM. In addition to the mortality benefit, resynchronization improves quality of life. Thus, resynchronization therapy, with or without defibrillator, should be offered to patients who have an LVEF 35% or less, a QRS duration 0.12 seconds or more, and sinus rhythm who continue to be categorized as NYHA functional class III or IV despite optimal recommended medical therapy. Recent studies in patients with mild heart failure symptoms (NYHA class II) also demonstrated survival benefit, especially in patients with left bundle branch block (LBBB) and QRS greater than 150 ms. According to the 2009 heart failure guidelines, symptomatic patients with atrial fibrillation may also be considered for resynchronization therapy, a class IIa indication.

19. Should DCM patients be anticoagulated?

    Patients with DCM have multiple risk factors that predispose to thromboembolic events—with the incidence ranging from 0.8 to 2.5 per 100 patient-years. Pooled data from small, randomized, controlled clinical trials and current guidelines do not support routine anticoagulation in heart failure with sinus rhythm. The results of the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial showed that in a large randomized comparison of aspirin versus warfarin in patients with heart failure and reduced ejection fraction (not in atrial fibrillation) there was no overall difference in the combined primary outcome of death, ischemic stroke, or intracranial hemorrhage between treatment groups. Available data do support the use of anticoagulants in the presence of atrial fibrillation, previous stroke or other thromboembolic events, or visible protruding or mobile thrombus on echocardiography.

20. What is the role of exercise therapy?

    Exercise training should be considered in stable patients. Training has been shown to decrease symptoms, improve exercise tolerance, and improve quality of life beyond that provided by pharmacologic treatment. Long-term outcomes, however, are not entirely known, although small studies have shown reduction in mortality or readmission for heart failure. The Heart Failure and a Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial failed to demonstrate a reduction in all-cause mortality or all-cause hospitalization in patients randomized to a structured exercise program when compared to “usual care,” although secondary analysis did suggest some benefit.

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