10-44: Dilated Cardiomyopathy

Heart failure definitions have changed over the years and patients with a dilated cardiomyopathy are generally placed into the category of heart failure with reduced ejection fraction where the LVEF is defined as less than or equal to 40%. In about half of the patients in this category, there is LV enlargement and it is this group that defines dilated cardiomyopathy. This is a large group of heterogeneous myocardial disorders characterized by reduced myocardial contractility in the absence of abnormal loading conditions such as with hypertension or valvular disease. The prevalence averages 36 cases/100,000 in the United States and accounts for approximately 10,000 deaths annually. Blacks are afflicted three times as often as whites. The prognosis is poor with 50% mortality at 5 years once symptoms emerge.

The causes are multiple and diverse. Up to 20–35% have a familial etiology. A large proportion is idiopathic. Endocrine, inflammatory, and metabolic causes include obesity, diabetes, thyroid disease, celiac disease, systemic lupus erythematosus, acromegaly, and growth hormone deficiency. Toxic, drug-induced, and inflammatory causes are listed in the prior section. Nutritional diseases such as deficiency of thiamine, selenium, and carnitine have also been documented. Dilated cardiomyopathy may also be caused by prolonged tachycardia either from supraventricular arrhythmias, from very frequent PVCs (more than 15% of heart beats), or from frequent RV pacing. Dilated cardiomyopathy is also associated with HIV, Chagas disease, rheumatologic disorders, iron overload, sleep apnea, amyloidosis, sarcoidosis, chronic alcohol usage, end-stage kidney disease, or cobalt exposure (“Quebec beer-drinkers cardiomyopathy”). Peripartum cardiomyopathy and stress-induced disease (tako-tsubo) are discussed separately.

A. Symptoms and Signs

In most patients, symptoms of heart failure develop gradually. It is important to seek out a history of familial dilated cardiomyopathy and to identify behaviors that might predispose patients to the disease. The physical examination reveals rales, an elevated JVP, cardiomegaly, S₃ gallop rhythm, often the murmurs of functional mitral or tricuspid regurgitation, peripheral edema, or ascites. In severe heart failure, Cheyne-Stokes breathing, pulsus alternans, pallor, and cyanosis may be present.

B. ECG and Chest Radiography

The major findings are listed in Table 10–16. Sinus tachycardia is common. Other common abnormalities include left bundle branch block and ventricular or atrial arrhythmias. The chest radiograph reveals cardiomegaly, evidence for left and/or right heart failure, and pleural effusions (right more frequently than left).

C. Diagnostic Studies

In the 2017 AHA/ACCF heart failure guideline focused update, patients with dyspnea should have a BNP or NT-proBNP measured to help establish prognosis and disease severity (class I, level of evidence [LOE] A). Other biomarkers, such as troponin I or T and measures that reflect inflammation, oxidative stress, neurohormonal disarray and myocardial or matrix remodeling are under investigation for their ability to guide therapy.

An echocardiogram is indicated to exclude unsuspected valvular or other lesions and confirm the presence of ventricular dilatation, reduced LV systolic function and associated RV systolic dysfunction, or pulmonary hypertension. Mitral Doppler inflow patterns also help in the diagnosis of concomitant diastolic dysfunction. Color flow Doppler can reveal tricuspid or mitral regurgitation, and continuous Doppler can estimate PA pressures. Intracavitary thrombosis is occasionally seen. Exercise or pharmacologic stress myocardial perfusion imaging may uncover underlying coronary disease. Radionuclide ventriculography provides a noninvasive measure of the EF and both RV and LV wall motion, though its use has been supplanted by cardiac MRI in most institutions. Cardiac MRI is particularly helpful in inflammatory or infiltrative processes, such as sarcoidosis or hemochromatosis, and is the diagnostic study of choice for RV dysplasia. MRI can also help define an ischemic etiology by noting gadolinium hyperenhancement consistent with myocardial scar from infarction or prior myocarditis. Cardiac catheterization is seldom of specific value unless myocardial ischemia is suspected, although right heart catheterization should be considered to help guide therapy when the clinical syndrome is not clear cut (class I indication, LOE C). Myocardial biopsy is rarely useful in establishing the diagnosis, although occasionally the underlying cause (eg, sarcoidosis, hemochromatosis) can be discerned. Its use is considered a class IIa indication with LOE of C. It should not be used routinely. Biopsy is most useful in transplant rejection.

The management of heart failure is outlined in the section on heart failure. Standard therapy includes control of BP and of contributing factors such as obesity, smoking, diabetes or potentially cardiotoxic agents. All patients with a remote history of MI or acute coronary syndrome and reduced LVEF should be given ACE inhibitors, ARBs, or sacubatril/valsartan. Beta-blockers should be included in this population as well. All patients with dilated cardiomyopathy regardless of etiology should be treated with beta-blockers and ACE inhibitors. If still symptomatic, aldosterone antagonists should be added, and ARNI used instead of an ACE inhibitor or ARB. The use of the combination of all three of ACE inhibition, ARB, and aldosterone antagonists can create harm, though, and is discouraged due to concerns for hyperkalemia. Calcium channel blockers should be avoided except as necessary to control ventricular response in atrial fibrillation or flutter. If congestive symptoms are present, diuretics and an aldosterone antagonist should be added. In patients with class II–IV heart failure symptoms, an aldosterone receptor antagonist should be added when the LVEF is less than 35% (unless contraindicated). Care in the use of mineralocorticoid receptor antagonists is warranted when the glomerular filtration rate is less than 30 mL/min/1.73 m² or when the potassium is elevated. All patients with diabetes should be taking mineralocorticoid antagonists if the LVEF is less than or equal to 40%. Systemic BP control is extremely important. Use of the angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, has been approved for NYHA Heart Failure of Functional class II–IV. If the resting heart rate is greater than 70 beats per minute, the LVEF is less than 35%, and the patient has chronic stable heart failure, the use of ivabradine to slow the heart rate has also been approved. Ivabradine should not replace other beta-blockers, however. Digoxin is a second-line medication but remains favored as an adjunct by some clinicians; digoxin may be beneficial to reduce recurrent hospitalizations and to control the ventricular response in atrial fibrillation in sedentary patients. Given the question of abnormal nitric oxide utilization in blacks, the use of hydralazine-nitrate combination therapy is recommended in this population. Sodium restriction is helpful, especially in acute heart failure. Continuous positive airway pressure can improve LV function in patients with sleep apnea.

When atrial fibrillation is present, heart rate control is important if sinus rhythm cannot be established or maintained. There are few data, however, to suggest an advantage of sinus rhythm over atrial fibrillation on long-term outcomes. Many patients may be candidates for cardiac synchronization therapy with biventricular pacing if there is significant mitral regurgitation and the QRS width is greater than 150 msec.

To help prevent sudden death, an ICD is reasonable (class IIa, LOE B) in asymptomatic ischemic cardiomyopathy patients with an LVEF of less than 30% on appropriate medical therapy (at least 40 days post-MI). Upgrading a cardiac resynchronization pacemaker with a debrillator appears to be useful much more often in ischemic than nonischemic cardiomyopathy patients. Cardiac rehabilitation and exercise training have consistently been found to improve clinical status.

Few cases of cardiomyopathy are amenable to specific therapy for the underlying cause. Alcohol use should be discontinued, since there is often marked recovery of cardiac function following a period of abstinence in alcoholic cardiomyopathy. Endocrine causes (hyperthyroidism or hypothyroidism, acromegaly, and pheochromocytoma) should be treated. Immunosuppressive therapy is not indicated in chronic dilated cardiomyopathy. There are some patients who may benefit from implantable LV assist devices either as a bridge to transplantation or as a temporary measure until cardiac function returns. LV assist devices can be considered as destination therapy in patients who are not candidates for cardiac transplantation. Arterial and pulmonary emboli are more common in dilated cardiomyopathy than in ischemic cardiomyopathy and suitable candidates may benefit from long-term anticoagulation. All patients with atrial fibrillation should be so treated. DOACs are preferred over warfarin unless there is associated mitral stenosis. Either warfarin or a DOAC should be considered when a mobile LV thrombus is observed on the echocardiogram.

The prognosis of dilated cardiomyopathy without clinical heart failure is variable, with some patients remaining stable, some deteriorating gradually, and others declining rapidly. Once heart failure is manifest, the natural history is similar to that of other causes of heart failure, with an annual mortality rate of around 11–13%. The underlying cause of heart failure has prognostic value in patients with unexplained cardiomyopathy. Patients with peripartum cardiomyopathy or stress-induced cardiomyopathy appear to have a better prognosis than those with other forms of cardiomyopathy. Patients with cardiomyopathy due to infiltrative myocardial diseases, HIV infection, or doxorubicin therapy have an especially poor prognosis.

Patients with new or worsening symptoms of heart failure with dilated cardiomyopathy should be referred to a cardiologist. Patients with continued symptoms of heart failure and reduced LVEF (35% or less) should be referred for consideration of placement of an ICD or cardiac resynchronization therapy (if QRS duration is 150 msec or more, especially with a left bundle branch block pattern). Patients with advanced refractory symptoms should be referred for consideration of heart transplant or LV assist device therapy.

Patients with hypoxia, fluid overload, or pulmonary edema not readily resolved in an outpatient setting should be admitted.