Dilated Cardiomyopathy: Etiology, Pathophysiology, and Echocardiographic Evaluation

Cause

DCM has a spectrum of causes ( Table 66.1 ). Genetic abnormalities encompass defects in genes encoding a variety of subcellular structures and processes, which ultimately disrupt cellular force generation and transmission, structural integrity, ion transportation, nuclear functions, and intracellular signaling ( Table 66.2 ). ^, Infectious causes can span viral, bacterial, fungal, parasitic, spirochetal, and protozoal disease. Cardiac dysfunction can ensue from direct effects of infection or may result from secondary effects of the immune-mediated response to infection. Autoimmune disorders, including autoimmune myocarditis, can also result in DCM. Giant cell myocarditis represents a particularly aggressive disease that can lead to rapidly declining left ventricular (LV) systolic function. Toxin-mediated DCM can result from prescription drugs, recreational drugs, or environmental exposures. Alcohol abuse is an important cause of DCM. Alcohol accounts for between one-fifth and one-third of all cases of DCM in developed countries. Although the initial phase of infiltrative diseases such as sarcoidosis and hemochromatosis present with normal LV cavity size, as these diseases progress, they can transform into a DCM phenotype. Endocrinopathies, nutritional deficiency, electrolyte disturbance, and uremia are other systemic causes of DCM (see Table 66.1 ). DCM can also be seen in neuromuscular disease, pregnancy, and tachycardia. There can be challenges in identifying the cause when DCM phenotypes may overlap with features of other cardiomyopathies. Advanced hypertrophic cardiomyopathy, arrhythmogenic right ventricular (RV) cardiomyopathy (with LV involvement), LV noncompaction, athlete’s heart, and cirrhotic cardiomyopathy can share features of DCM.

Pathophysiology

Regardless of the cause, the underlying pathophysiology of DCM follows a final common pathway of contractile dysfunction and LV dilatation. Reduction in contractility leads to both “forward” and “backward” heart failure states. Whereas the forward failure state results in low-output physiology, the backward failure state results in elevation of LV diastolic pressure, resulting in elevation in pulmonary venous and pulmonary arterial pressure (thereby causing pulmonary edema and elevated RV afterload). Disturbances in neurohumoral response, myocardial remodeling, peripheral vascular resistance, and cardiorenal balance can exacerbate the disease and lead to vicious cycles of declining cardiovascular function. ^, Dilatation of the left ventricle occurs to maintain adequate stroke volume in the presence of impaired myocardial contractility, by the Frank-Starling mechanism. As the left ventricle dilates, the papillary muscles are apically displaced, impairing the closing mechanism of the mitral valve. In combination with mitral annular dilatation, this leads to secondary mitral regurgitation, which further volume loads the left ventricle and impairs forward cardiac output. ^, Development of ventricular fibrosis leads to ventricular arrhythmic risk. Systemic volume overload and mitral regurgitation result in left atrial dilatation and can lead to atrial fibrillation. Atrial fibrillation can further exacerbate impairment of cardiovascular performance by eliminating a key mechanism of preload (atrial systole, or “atrial kick”) in the setting of LV systolic impairment. Additionally, atrial fibrillation can exacerbate mitral annular dilatation and result in worsening of mitral regurgitation (atrial functional mitral regurgitation). ^,

Most causes of DCM create biventricular systolic impairment, but even those with a predominance of LV systolic dysfunction can create RV systolic impairment because of secondary effects on the pulmonary circulation. Additionally, in the setting of a dilated left ventricle, with walls stretched, LV compliance is reduced. Hence, markers of diastolic dysfunction are commonly seen. The cascade of effects described above lead to considerable morbidity, with symptomatic fluid overload and recurrent hospitalization, multiorgan dysfunction, arrhythmias, and premature mortality. Adequate recognition of the DCM phenotype and assessment of progress over time is crucial for optimal surveillance of the efficacy of medical and device therapy and the timing of advanced interventions.

Echocardiographic Features