Dilated Cardiomyopathy

Phenotypically, dilated cardiomyopathy (DCM) is characterized by ventricular dilatation and systolic dysfunction, frequently accompanied by compensatory eccentric hypertrophy, atrial dilation, and functional mitral regurgitation and/or tricuspid regurgitation. Both ventricles are frequently involved (1). Ventricular dilation and reduced contractility predispose to intracardiac thrombus formation due to stasis of blood. Atrial fibrillation frequently develops in the setting of left atrial enlargement (2), and ventricular arrhythmias may occur, particularly in the context of acute myocarditis or in the presence of myocardial fibrosis (3, 4, 5, 6).

Etiologies of dilated cardiomyopathy (DCM) include both genetic (primary) and acquired (secondary) causes (see Table Causes of Dilated Cardiomyopathy), and DCM is best regarded as a phenotypic response to diverse myocardial insults rather than a single disease entity.

Familial disease is present in approximately 30 to 40% of cases, with monogenic variants identified in a substantial proportion (25 to 40%) of these patients (1). TTN and LMNA are the most commonly implicated genes in DCM.

Acquired etiologies include infections (eg, coxsackievirus B, Trypanosoma cruzi in endemic regions), toxins (eg, alcohol, cardiotoxic chemotherapeutic agents), tachycardia-mediated cardiomyopathy, and systemic disorders, including autoimmune, endocrine (eg, thyrotoxicosis), nutritional (eg, thiamine deficiency), and neuromuscular diseases (see table Causes of Dilated Cardiomyopathy). Persistent tachyarrhythmias, frequent ventricular ectopy, or chronic right ventricular pacing may result in potentially reversible left ventricular systolic dysfunction. Similarly, hyperadrenergic states can precipitate acute LV systolic dysfunction (eg, stress [Takotsubo] cardiomyopathy) that is typically reversible.

Some conditions, including pregnancy, can also act as modifiers, aggravating cardiomyopathy without being directly causal, and leading to the clinical manifestation of previously asymptomatic DCM. (Note that the exacerbation of a pre-existing clinical or subclinical cardiomyopathy by pregnancy is distinct from peripartum cardiomyopathy.)

The clinical onset of dilated cardiomyopathy (DCM) is typically insidious, with gradual progression of symptoms; however, more abrupt presentations may occur in patients with acute myocarditis, stress (Takotsubo) cardiomyopathy, or tachycardia-mediated cardiomyopathy.

Clinical manifestations reflect the predominant ventricular involvement. Left ventricular systolic dysfunction most commonly leads to exertional dyspnea, orthopnea, and fatigue, which is attributable to elevated left-sided filling pressures and/or reduced cardiac output. Right ventricular involvement results in systemic venous congestion, manifesting as peripheral edema, hepatomegaly, abdominal distension, and elevated jugular venous pressure.

Other cardiac findings on examination may include an S3 or S4 gallop, a mitral or tricuspid regurgitation murmur, a displaced point of maximal impulse, and, in severe cases, pulsus alternans.

Patients may also present with atrial and ventricular arrhythmias or sudden cardiac death due to malignant ventricular tachyarrhythmias. Acute fulminant myocarditis may present with cardiogenic shock and multiorgan failure.

• History and physical examination, including family history

• ECG

• Chest radiography

• Echocardiography

• Cardiac MRI

• Endomyocardial biopsy (select cases)

• Testing for cause as indicated

The diagnosis of dilated cardiomyopathy (DCM) is established through comprehensive clinical evaluation and the exclusion of other common causes of LV systolic dysfunction (eg, systemic hypertension, primary valvular disorders, significant coronary artery disease—see table Diagnosis and Treatment of Cardiomyopathies). A detailed family history should be taken to identify family members with possible early-onset heart disease, heart failure, or sudden death and to guide consideration of genetic testing (1). Initial evaluation includes electrocardiography, chest radiography, transthoracic echocardiography, and cardiac MRI.

Laboratory testing includes natriuretic peptides, which are typically elevated and provide both diagnostic and prognostic information (2, 3). Additional testing should be guided by clinical context and may include assessment for reversible or contributory conditions (eg, iron studies, thyroid function tests, viral serology, nucleic acid testing). Troponin concentrations may be elevated, particularly in patients with myocarditis or ongoing myocardial injury; however, in the absence of the characteristic dynamic rise and fall, troponin elevation is not specific for acute myocardial ischemia. Other laboratory testing should be performed to evaluate for end-organ dysfunction (eg, liver, kidney).

Given the high prevalence of coronary artery disease, an ischemia evaluation should be performed to exclude obstructive coronary artery disease as the cause of LV systolic dysfunction.

ECG or ambulatory rhythm monitoring may be normal or show abnormalities, including T-wave changes, left bundle branch block, conduction abnormalities including prolongation of atrioventricular conduction (4), or atrial fibrillation. Atrial and ventricular ectopy, including nonsustained ventricular tachycardia, is common.

Chest radiograph may reveal an enlarged cardiac silhouette, splaying of the carina, interstitial edema, and pleural effusions.

Dilated Cardiomyopathy (Chest Radiograph)

Image

This radiograph shows severe cardiomegaly in a patient with dilated cardiomyopathy.

© Springer Science+Business Media

Transthoracic echocardiography characteristically demonstrates left ventricular dilation with global hypokinesis and atrial enlargement and excludes primary valvular disorders. Functional mitral and tricuspid regurgitation may result from annular dilation and papillary muscle displacement (4). Although the typical pattern is one of diffuse hypokinesis, regional wall motion abnormalities may occur, reflecting the heterogeneous or patchy nature of myocardial involvement in DCM. In selected cases, use of contrast echocardiography may be required to improve endocardial border definition and to exclude the presence of a left ventricular thrombus.

Cardiac MRI provides detailed structural and tissue characterization. Patterns of inflammation and late gadolinium enhancement assist in identifying specific etiologies (eg, myocarditis or infiltrative cardiomyopathies) and contribute to risk stratification, particularly with respect to future risk of ventricular arrhythmias and lack of reverse (ie, favorable) remodeling (4, 5, 6, 7, 8).The presence of late gadolinium enhancement in a ring-like pattern ("ring sign") is one such unfavorable prognostic marker.

MRI Findings of Cardiac Sarcoidosis

Image

This cardiac MRI shows a late gadolinium enhancement in a patchy pattern (arrow) characteristic of sarcoidosis.

© 2017 Elliot K. Fishman, MD.

Positron-emission tomography (PET) is a valuable tool for the diagnosis of cardiac sarcoidosis and monitoring disease activity (6).

Endomyocardial biopsy should be considered in selected patients with rapidly progressive heart failure despite appropriate medical therapy when there is a probability of a specific and potentially treatable diagnosis (eg, giant cell myocarditis, eosinophilic myocarditis) that requires histopathologic confirmation (2, 3).

• Treat the cause (if a reversible etiology has been identified)

• Guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF)

• Implantable cardioverter-defibrillator or cardiac resynchronization therapy (CRT) for symptomatic patients with left ventricular ejection fraction (LVEF) ≤ 35% despite optimal medical therapy

• Consideration of durable left ventricular assist device or cardiac transplantation for patients with advanced disease

Reversible causes (eg, tachyarrhythmias, infections, metabolic or nutritional disorders) should be identified and treated (1). Immunosuppressive therapy should be reserved for patients with inflammatory causes (eg, giant cell myocarditis, eosinophilic myocarditis, sarcoidosis) and certain patients with autoimmune disorders (eg, systemic lupus erythematosus).

Patients with dilated cardiomyopathy (DCM) should be treated with guideline-directed medical therapy for HFrEF because these agents reduce morbidity and mortality (2). The cornerstones of treatment include beta blockers, angiotensin receptor/neprilysin inhibitor (ARNi) (or angiotensin-converting enzyme [ACE] inhibitor or angiotensin II receptor blocker (ARB) if ARNi not feasible), mineralocorticoid receptor antagonists (MRA), and sodium glucose cotransporter-2 protein inhibitors (SGLT2i), with diuretics for volume management (3, 4).

Anticoagulation may be considered in patients with documented intracardiac thrombus, and atrial fibrillation (3, 5, 6).

Special considerations apply in peripartum cardiomyopathy. Many standard heart failure treatments are potentially teratogenic (eg, ACE inhibitors, ARB, ARNi, MRA, SGLT2i, some anticoagulants). Anticoagulation may be considered in patients with severe left ventricular dysfunction due to heightened thrombotic risk (7, 8).

Implantable cardioverter-defibrillator therapy is recommended for primary prevention in patients with symptoms and persistent LVEF ≤ 35% despite chronic guideline-directed medical therapy, and cardiac resynchronization therapy (CRT) is indicated in patients with symptoms with LVEF ≤ 35% and QRS prolongation, particularly in the presence of a left bundle branch block (3, 4). Percutaneous edge-to-edge mitral valve repair can be considered in carefully selected patients with severe secondary mitral regurgitation despite optimal medical therapy and/or CRT. Advanced heart failure refractory to medical therapy may require durable left ventricular assist device support or cardiac transplantation in appropriate candidates (3, 4).

The management of acute heart failure and chronic heart failure is discussed in more detail elsewhere.

Outcomes in dilated cardiomyopathy (DCM) have significantly improved over recent decades, although they remain variable, depending on etiology, disease severity, and response to treatment (1, 2, 3, 4). Contemporary 5-year mortality rates range from 20 to 30%, compared with historical rates of approximately 50% (5, 6, 7, 8). The principal causes of death are pump failure and sudden cardiac death (9, 10). Survival differs by demographic factors, with generally worse outcomes observed in men compared with women. Population-based studies also demonstrate higher age-adjusted mortality rates among Black patients compared with White patients (1, 9).