Dilated Cardiomyopathy
Reema Hasan
Taylor Alexander Lebeis
Supriya Shore
Monica Mechele Colvin
INTRODUCTION
Cardiomyopathy is a disease of the heart muscle, which can include dilatation and impaired contraction of one or both ventricles as well as infiltrative diseases of the myocardium. Due to the dilatation and hypertrophy that develops after myocardial injury, patients may develop impaired systolic function, resulting in dilated cardiomyopathy (DCM).1 DCM has many causes and all of them affect ventricular function to a varying degree. While most patients with DCM have symptoms, some may be asymptomatic because of compensatory mechanisms. Continued enlargement of the ventricles leads to a decline in ventricular function followed by conduction system abnormalities, ventricular arrhythmias, thromboembolism, and heart failure.
The earlier patients are identified and treated, the better the prognosis.
Without medical therapy, DCM is progressive, leading to heart failure and death. Once end-stage heart failure develops, survival rates are poor without heart transplants. In this chapter, we discuss the various etiologies of DCM, its pathogenesis, diagnosis, and management.
Definition and Classifications
The classification of DCM has evolved over time with advances in genetics and disease recognition. Currently, DCM refers to a spectrum of heterogeneous myocardial disorders that are characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease. In clinical practice, the etiology of heart failure (HF) has been categorized as ischemic or nonischemic cardiomyopathy, with the latter interchangeably used with DCM. However, this fails to recognize that nonischemic cardiomyopathy can include cardiomyopathies caused by volume or pressure overload (such as hypertension or valvular heart disease) that are not conventionally accepted under the definition of DCM.
Classification schemes, such as the one proposed by the American Heart Association (AHA), divide cardiomyopathies into two major groups based on predominant organ involvement: primary cardiomyopathies (ie, genetic, nongenetic, and acquired) are those solely or predominantly confined to heart muscle, whereas secondary cardiomyopathies have myocardial involvement as part of a generalized systemic (multiorgan) disorder (ie, amyloidosis, hemochromatosis, sarcoidosis, autoimmune/collagen vascular diseases, toxins, cancer therapy, and endocrine disorders such as diabetes mellitus).
The European Society of Cardiology (ESC) Working Group on Myocardial and Pericardial Diseases takes a different approach based on a clinically oriented classification in which heart muscle disorders are grouped into specific morphologic and functional phenotypes, including hypertrophic cardiomyopathies, DCM, arrhythmogenic right ventricular dysplasia, restrictive cardiomyopathies, and unclassified cardiomyopathies. Each phenotype is then subclassified into familial and nonfamilial forms.
Most recently, the MOGE(S) nosology system was developed, which incorporates the morphofunctional phenotype (M), organ(s) involvement (O), genetic inheritance pattern (G), etiologic annotation (E) including genetic defect or underlying disease/substrate, and the functional status (S) of the disease using both the American College of Cardiology (ACC)/AHA HF stages and New York Heart Association (NYHA) functional class. This nomenclature is endorsed by the World Heart Federation and is supported by an internet-assisted application. It also assists in the description of cardiomyopathy in symptomatic and asymptomatic patients, as well as family members in the context of genetic testing.
Epidemiology
The reported incidence and prevalence of dilated cardiomyopathies worldwide are affected by geographic differences, evolving diagnostic criteria, and socioeconomic factors. In the United States, the age-adjusted prevalence of DCM is reported to be approximately equal to 36 cases per 100,000 population or 1:2500 individuals.2 Approximately, 30% to 40% of patients diagnosed with DCM have a nonischemic origin.3 DCM is more commonly seen in men than women. While DCM typically occurs in the third or fourth decade of life, it can be seen in children and the elderly. Age is an independent risk factor for mortality in DCM.
PATHOGENESIS
Enlargement of the left ventricle (LV) or both the right and left ventricles occurs in DCM due to LV failure or a secondary myopathic process that is causing biventricular failure. Reduced systolic function is thought to be due to myocardial remodeling that causes an increase in both end-systolic and end-diastolic volumes (Figure 70.1). Dilatation of the ventricles can lead to
tricuspid or mitral insufficiency. Over time, this will lead to a reduced ejection fraction and increased ventricular wall stress. To compensate, heart rate and peripheral vascular tone increase, resulting in additional myocardial injury. Neurohormonal activation of the renin-angiotensin-aldosterone system and an increase in catecholamines are compensatory mechanisms that occur. Natriuretic peptides levels also increase. Ultimately, the compensatory mechanisms become injurious creating myocardial ischemia. Eventually, the heart becomes overwhelmed and fails. Histologic examination of the myocardium typically shows nonspecific changes of fibrosis and hypertrophy, although myocardial injury with an infiltrate of inflammatory cells is also seen.
tricuspid or mitral insufficiency. Over time, this will lead to a reduced ejection fraction and increased ventricular wall stress. To compensate, heart rate and peripheral vascular tone increase, resulting in additional myocardial injury. Neurohormonal activation of the renin-angiotensin-aldosterone system and an increase in catecholamines are compensatory mechanisms that occur. Natriuretic peptides levels also increase. Ultimately, the compensatory mechanisms become injurious creating myocardial ischemia. Eventually, the heart becomes overwhelmed and fails. Histologic examination of the myocardium typically shows nonspecific changes of fibrosis and hypertrophy, although myocardial injury with an infiltrate of inflammatory cells is also seen.
 FIGURE 70.1 Pathogenesis of cardiomyopathy. (Reprinted by permission from Springer: Tham YK, Bernardo BC, Ooi JY, et al. Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets. Arch Toxicol. 2015;89(9):1401-1438. Copyright © 2015 Springer Nature.) |
CLINICAL PRESENTATION AND EVALUATION
History and Physical
DCM can be asymptomatic for many years. If untreated, most patients will develop the syndrome of HF. Symptoms of HF include paroxysmal nocturnal dyspnea, orthopnea, leg swelling, and shortness of breath with exertion or at rest. Nonspecific symptoms include fatigue, malaise, and weakness. More advanced cases can include thromboembolic complications, conduction disturbances, arrhythmias, or sudden cardiac death. Since symptoms can be nonspecific, it is not uncommon for the diagnosis to be missed or confused with asthma.
Physical exam findings include crackles in the lungs, elevated jugular venous pressures, peripheral edema, and a S3 gallop. The point of maximum impulse, or PMI, may be displaced laterally. Tricuspid or mitral regurgitation murmurs can be present because of ventricular enlargement and annular dilation. Neck examination can reveal jugular venous distention, large V-waves, brisk Y descent, and a positive hepatojugular reflux. The murmur of mitral regurgitation may not be holosystolic, and the usual inspiratory increase in the murmur of tricuspid regurgitation (Carvallo’s sign) is frequently absent.
The initial diagnostic approach should exclude all potentially reversible causes of LV dysfunction (Algorithm 70.1). Laboratory testing should include thyroid function tests, HIV serology, electrolytes, hemoglobin A1c, hematocrit, and iron studies. Urine toxicology screen and alcohol level can be checked when substance abuse is suspected. Excess alcohol consumption has been reported in up to 40% of patients with idiopathic DCM. A history of alcohol consumption is important since abstinence may result in a dramatic increase in ejection fraction. A recent viral illness, particularly one accompanied by myalgias or pericarditis, may suggest a role for myocarditis. Ischemic heart disease should be considered whenever coronary risk factors or chest pain on exertion is present. If a complete family history suggests a familial cardiomyopathy, echocardiography may need to be performed in close relatives to rule out asymptomatic abnormalities.
Hypothyroidism, hyperthyroidism, and anemia should be excluded before diagnosing DCM. A chest x-ray may show cardiomegaly and evidence of pulmonary effusions and venous
congestion. Electrocardiogram (ECG) may show nonspecific ST-segment and T-wave abnormalities or even atrial fibrillation. Oxygen consumption of less than 14 mL/kg/min on a metabolic stress test indicates a poor prognosis.
congestion. Electrocardiogram (ECG) may show nonspecific ST-segment and T-wave abnormalities or even atrial fibrillation. Oxygen consumption of less than 14 mL/kg/min on a metabolic stress test indicates a poor prognosis.
 ALGORITHM 70.1 Diagnostic approach to dilated cardiomyopathy. CMRI, cardiac magnetic resonance imaging; CXR, chest radiograph; Hgb, hemoglobin; HIV, human immunodeficiency virus; TSH, thyroid-stimulating hormone; TTE, transthoracic echocardiogram. (Data from Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA Guideline for the management of heart failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70(6):776-803.) |
DIAGNOSIS
Dilated cardiomyopathy describes a heterogeneous collection of disorders causing myocardial dysfunction without significant valvular, ischemic, congenital, or hypertensive disease.1 The general diagnostic workup for dilated cardiomyopathy is described in this section; refer to Algorithm 70.1 regarding the approach. The initial evaluation of dilated cardiomyopathy begins with a thorough clinical history and physical examination. Special attention needs to be made for clinical risk factors and comorbid conditions that predispose the patient for HF and warrant additional investigation. Additionally, a detailed family history of HF, heart disease, sudden cardiac death, exercise intolerance, or other unexplained dyspnea needs to be obtained.
After completing the general clinical examination, an ischemic evaluation should be performed to determine whether coronary artery disease is the cause of the reduced ejection fraction. Not all patients require an ischemic evaluation. Generally, those under the age of 35 years do not require an ischemic evaluation unless risk factors for such exist or there is a high clinical suspicion.9 For those who warrant an investigation, the type of ischemic evaluation is dependent upon the patient characteristics and risk factors. Common methods of evaluating for ischemia include left heart catheterization, coronary computed tomography angiography, or stress testing (nuclear medicine, cardiac magnetic resonance imaging [CMRI], or echocardiography). After establishing that the origin of the patient’s cardiomyopathy is nonischemic, it is important to determine whether there is a reversible etiology.
The 2016 AHA Scientific Statement on Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies describes the general approach to the workup of DCM.1 The path of evaluation is determined by clinical suspicion of disease states based on the presentation of the specific patient and whether there is high-enough pretest probability to indicate specific testing. A list of disease states and specific testing is found in Table 70.1.
Diagnostic Testing
Echocardiography
Transthoracic echocardiography (TTE) is the backbone of the imaging evaluation of cardiomyopathy. It is able to provide information about the structure and function of the heart at a low cost in real time. TTE allows for evaluation of wall motion and has the ability to survey for structural changes that may be the cause of the cardiomyopathy including congenital abnormalities and valvular dysfunction. Contrast echocardiography can help enhance images for estimation of the ejection fraction and identification of LV thrombi. If there is a question about the presence of thrombus, CMRI can be used to more accurately assess.
TABLE 70.1 Imaging Findings and Specialized Testing for Specific Cardiomyopathies | |||||||||||||||||||||||||||||||||||||||||||
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Three-dimensional (3D) echocardiography has been used with increasing frequency due to improved accuracy and reproducibility. As opposed to TTE, 3D echocardiography allows for better spatial resolution between structures, and estimation of both RV and LV ejection fractions is not affected by geometric assumptions, although it is limited by lower temporal resolution, image quality, and less published data.4
Speckle tracking echocardiography is another echocardiographic feature that involves tracking the displacement of speckles in the myocardium and represents myocardial deformation (ie, strain). It can be used to detect cardiomyopathy and is independent of the beam angle, which can be limiting in other echocardiographic measurements. Speckle tracking can be used to identify specific patterns consistent with specific disease states. Global longitudinal strain is an independent predictor of all-cause mortality in patients with heart failure due to reduced ejection fraction (HFrEF). The overall assessment of cardiomyopathy by TTE involves the incorporation of all available data to have a complete evaluation.
Cardiac Magnetic Resonance Imaging
CMRI is a useful tool in the evaluation of DCM. CMRI is often more accurate than echocardiography in determining the left and right ventricular volumes and function, especially in those with suboptimal imaging windows. CMRI can further characterize the severity of valvular disease and its contribution to cardiomyopathy. Additionally, CMRI has the ability to evaluate for myocardial inflammation, edema, fibrosis, and ischemia. In T2-weighted images, myocardial edema can be identified in active myocarditis.3 In ischemic disease, there is often regional subendocardial late gadolinium enhancement (LGE)—which represents expansion of the extracellular space and delayed contrast washout, most commonly due to fibrosis—whereas there are multiple patterns of LGE in patients with DCM (ie, midwall striae or patches, subepicardial, or subendocardial enhancement). Nevertheless, the presence of LGE portends a poor prognosis.3
CMRI is particularly helpful in certain cardiomyopathies. In cardiac hemochromatosis, CMRI is able to quantitatively assess iron load in the myocardium with changes in signal time and shorter relaxation time. Global subendocardial LGE is typically seen in cardiac amyloidosis. Lesions in cardiac sarcoidosis typically present in the mid-myocardial basal segments of the septal and lateral walls, and early enhancement of granulomas is suggestive of inflammation and edema. CMRI is limited by the cost, availability, and incompatibility with some implanted cardiac devices.
Cardiac Computed Tomography
Typically used as part of the ischemic evaluation and for congenital disease, cardiac computed tomography (CT) can be used when CMRI cannot be safely performed such as with a ventricular assist device or when the images are otherwise disrupted by the body habitus or cardiac implants. Cardiac CT is noninvasive and has a high sensitivity for coronary artery disease. It is able to accurately measure LV wall thickness, mass, and volume, and can also provide a functional assessment of the heart, but some assessments require administration of a contrast agent and a stable rhythm for ECG gating. Cardiac CT is a reasonable option when there are limitations to echocardiography and CMRI.
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