Diagnosis and Evaluation of Dilated Cardiomyopathy

Japp AG, Gulati A, Cook SA, Cowie MR, Prasad SK.
The Diagnosis and Evaluation of Dilated Cardiomyopathy. J Am Coll Cardiol 2016;67:2996-3010.

The following are key points to remember from this review article about the diagnosis and evaluation of dilated cardiomyopathy (DCM), divided into four parts: 1) evaluation of etiology, 2) assessment of remodeling, 3) evaluation for an implantable cardioverter-defibrillator (ICD), and 4) detection of the pre-DCM phenotype.

  1. Evaluation of Etiology:
    • DCM predominantly affects younger adults and is the most frequent indication for cardiac transplantation. DCM is best regarded not as a single disease entity, but rather as a nonspecific phenotype, the final common response of myocardium to a number of genetic and environmental insults. Therefore, before diagnosing DCM, it is necessary to exclude conditions with phenotypic overlap.
    • Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) provides an alternative approach to coronary angiography and may identify prior myocardial infarction (subendocardial or transmural LGE) in as many as 13% of patients with suspected DCM and unobstructed coronary arteries.
    • CMR may aid etiologic evaluation through detection of myocardial edema (e.g., active myocarditis or sarcoidosis), and classification of LGE distribution (e.g., muscular dystrophy, previous myocarditis, sarcoidosis, or Chagas disease). Alongside CMR, 18F-fluorodeoxyglucose positron emission tomography is emerging as a valuable tool for diagnosing cardiac sarcoidosis and monitoring disease activity.
    • CMR enables noninvasive detection of myocarditis through three combined tissue characterization techniques (“Lake Louise criteria”). It offers high diagnostic accuracy in acute myocarditis, but is less sensitive in chronic inflammatory disease. Endomyocardial biopsy (EMBx) remains the gold standard investigation, but given the current diagnostic yield and procedural risks of EMBx, it would appear difficult to justify its universal inclusion in the diagnostic workup of DCM.
    • Routine genetic testing is only recommended in familial disease (≥2 affected family members), where its diagnostic yield is 30-35%. LMNA mutations are associated with high rates of conduction system disease, ventricular arrhythmias, and sudden cardiac death (SCD), and may consequently lower the threshold for prophylactic ICD implantation. DCM patients with a variant of the SCN5A gene exhibit a phenotype associated with significant arrhythmias and frequent premature ventricular complexes. Functional characterization of the mutation in vitro revealed an activating effect on the Nav1.5 sodium channel, predicted to cause rate-dependent ventricular ectopy. Although such patients responded poorly to conventional HF therapy, treatment with sodium channel blocking drugs produced a dramatic reduction in ectopy and normalization of left ventricular (LV) function.

  2. Assessment of Remodeling:
    • Although CMR is the gold standard for ventricular assessment, its routine use is limited by restricted availability, expense, and device incompatibility. Myocardial deformation imaging techniques (e.g., speckle-tracking echocardiography-derived strain or CMR myocardial tagging) offer greater sensitivity than LV ejection fraction (LVEF) for identifying subtle abnormalities of systolic function, and may assume a role in the early detection of disease.
    • Velocity-encoded CMR offers a useful alternative modality for evaluating functional mitral regurgitation, especially when echocardiography is equivocal, particularly in patients being assessed for percutaneous transcatheter mitral valve repair.
    • Replacement myocardial fibrosis occurs typically in the mid-wall in approximately one-third of patients with advanced DCM, and is detectable by LGE-CMR. It provides a substrate for ventricular re-entrant arrhythmia and is independently associated with an increased risk of mortality and HF morbidity in DCM. The presence of replacement fibrosis and extent in DCM hearts, as assessed by LGE-CMR, substantially determines the likelihood of LV reverse remodeling in response to pharmacological therapy and cardiac resynchronization therapy.
    • Dyssynchrony evaluation by echocardiography currently has no role in patients with left bundle branch block and QRS interval duration ≥150 ms or those with narrow QRS intervals.

  3. Evaluation for an ICD:
    • LGE-CMR could help to optimize ICD deployment, by identifying patients with high remodeling potential who may warrant lengthier periods of treatment before ICD decision making. The same principle extends to DCM patients with “reversible” causes such as alcohol-related, peripartum, or acute inflammatory cardiomyopathy. The risk of SCD during the deferment period could possibly be ameliorated by wearable cardioverter-defibrillators.
    • Myocardial fibrosis identified by LGE-CMR is an independent predictor of SCD risk and all-cause mortality, providing prognostic information that is incremental to LVEF. The absence of midwall LGE identifies a population of DCM patients at low risk of SCD, even when LVEF is ≤35%. The combination of LGE-CMR with biomarker analysis may offer even greater discriminatory power, identifying an “ultra-low” risk of arrhythmic outcomes (e.g., 1-3%/year) among DCM patients who meet current criteria for ICD implantation.

  4. Detection of the Pre-DCM Phenotype:
    • Genetic counseling in facilitating informed decisions regarding testing and supporting patients following results is important due to limitations of predictive genetic testing including the attendant psychological burden, the inability to predict time and severity of disease onset, and the lack of available therapies to avert disease development.
    • Myocardial deformation imaging may provide phenotypic markers of latent DCM earlier than LV enlargement. Among relatives of patients with DCM caused by sarcomeric gene mutation, mutation carriers exhibited substantially reduced strain and strain rate compared with noncarriers, despite all having normal LV size and LVEF.
    • In patients receiving potentially cardiotoxic cancer therapy, reductions in global longitudinal strain ≥10% consistently precede and predict the development of overt LV dysfunction. Subclinical detection in these patients is crucial because timely intervention (e.g., change in chemotherapy regimen) may prevent disease progression, whereas systolic dysfunction is often irreversible once LVEF declines.
    • LGE-CMR can detect myocardial replacement fibrosis prior to overt LV remodeling in patients with laminopathy or Becker’s muscular dystrophy. However, the assessment of diffuse interstitial fibrosis by emerging T1 mapping methods may allow differentiation of diseased from healthy myocardium, even in the absence of LGE, and holds considerable promise for early DCM diagnosis.
    • The introduction of T2* monitoring for thalassemia patients in the United Kingdom has contributed to a 70% decline in mortality from cardiac iron overload since 2000.
    • Serum protein biomarkers can deliver insights into multiple facets of cardiac remodeling, including myocyte death, extracellular matrix remodeling, ventricular stretch, and oxidative stress, and may therefore play an adjunctive role in uncovering latent disease. For example, high-sensitivity cardiac troponin assays provide a potential avenue for the detection of low-grade, subclinical myocardial injury—among cancer patients receiving cardiotoxic chemotherapy, elevations in serum troponin strongly predict subsequent LV dysfunction.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Cardio-Oncology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Heart Transplant, Interventions and Imaging, Interventions and Structural Heart Disease, Angiography, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging, Mitral Regurgitation

Keywords: Arrhythmias, Cardiac, Biological Markers, Cardiomyopathy, Dilated, Cardiotoxicity, Coronary Angiography, Death, Sudden, Cardiac, Defibrillators, Implantable, Echocardiography, Gadolinium, Genetic Testing, Heart Failure, Heart Transplantation, Magnetic Resonance Spectroscopy, Mitral Valve Insufficiency, Muscular Dystrophy, Duchenne, Myocardial Infarction, Myocarditis, Neoplasms, Phenotype, Positron-Emission Tomography, Sarcoidosis, Thalassemia, Troponin, Ventricular Function, Left

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