Nonischemic dilated cardiomyopathy (DCM) often has a genetic pathogenesis. Because of the large number of genes and alleles attributed to DCM, comprehensive genetic testing encompasses ever-increasing gene panels. Genetic diagnosis can help predict prognosis, especially with regard to arrhythmia risk for certain subtypes. Moreover, cascade genetic testing in family members can identify those who are at risk or with early stage disease, offering the opportunity for early intervention. This review will address diagnosis and management of DCM, including the role of genetic evaluation. We will also overview distinct genetic pathways linked to DCM and their pathogenetic mechanisms. Historically, cardiac morphology has been used to classify cardiomyopathy subtypes. Determining genetic variants is emerging as an additional adjunct to help further refine subtypes of DCM, especially where arrhythmia risk is increased, and ultimately contribute to clinical management.

Dilated Cardiomyopathy: Genetic Determinants and Mechanisms

Background— Late gadolinium enhancement (LGE) by cardiac MR (CMR) is a predictor of adverse cardiovascular outcomes in patients with nonischemic cardiomyopathy (NICM). However, these findings are limited by single-center studies, small sample sizes, and low event rates. We performed a meta-analysis to evaluate the prognostic role of LGE by CMR (LGE-CMR) imaging in patients with NICM.

Methods and Results— PubMed, Cochrane CENTRAL, and EMBASE were searched for studies looking at the prognostic value of LGE-CMR in patients with NICM. The primary end points included all-cause mortality, heart failure hospitalization, and a composite end point of sudden cardiac death (SCD) or aborted SCD. Pooling of odds ratios was performed using a random-effect model, and annualized event rates were assessed. Data were included from 9 studies with a total of 1488 patients and a mean follow-up of 30 months. Patients had a mean age of 52 years, 67% were men, and the average left ventricular ejection fraction was 37% on CMR. LGE was present in 38% of patients. Patients with LGE had increased overall mortality (odds ratio, 3.27; P <0.00001), heart failure hospitalization (odds ratio, 2.91; P =0.02), and SCD/aborted SCD (odds ratio, 5.32; P <0.00001) compared with those without LGE. The annualized event rates for mortality were 4.7% for LGE+ subjects versus 1.7% for LGE− subjects ( P =0.01), 5.03% versus 1.8% for heart failure hospitalization ( P =0.002), and 6.0% versus 1.2% for SCD/aborted SCD ( P <0.001).

Conclusions— LGE in patients with NICM is associated with increased risk of all-cause mortality, heart failure hospitalization, and SCD. Detection of LGE by CMR has excellent prognostic characteristics and may help guide risk stratification and management in patients with NICM.

Late gadolinium enhancement on cardiac magnetic resonance predicts adverse cardiovascular outcomes in nonischemic cardiomyopathy: a systematic review and meta-analysis.

Objectives The aim of this study was to evaluate the association between late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging and ventricular arrhythmias or sudden cardiac death (SCD) in patients with dilated cardiomyopathy (DCM). Background Risk stratification for SCD in DCM needs to be improved. Methods A systematic review and meta-analysis were conducted. A systematic search of PubMed and Ovid was performed, and observational studies that analyzed the arrhythmic endpoint (sustained ventricular arrhythmia, appropriate implantable cardioverter-defibrillator [ICD] therapy, or SCD) in patients with DCM, stratified by the presence or absence of LGE, were included. Results Twenty-nine studies were included, accounting for 2,948 patients. The studies covered a wide spectrum of DCM, with a mean left ventricular ejection fraction between 20% and 43%. LGE was significantly associated with the arrhythmic endpoint both in the overall population (odds ratio: 4.3; p  35% (odds ratio: 5.2; p  Conclusions Across a wide spectrum of patients with DCM, LGE is strongly and independently associated with ventricular arrhythmia or SCD. LGE could be a powerful tool to improve risk stratification for SCD in patients with DCM. These results raise 2 major questions to be addressed in future studies: whether patients with LGE could benefit from primary prevention ICDs irrespective of their left ventricular ejection fractions, while patients without LGE might not need preventive ICDs despite having severe left ventricular dysfunction.

Late Gadolinium Enhancement and the Risk for Ventricular Arrhythmias or Sudden Death in Dilated Cardiomyopathy: Systematic Review and Meta-Analysis.

Background:Current guidelines only recommend the use of an implantable cardioverter defibrillator in patients with dilated cardiomyopathy for the primary prevention of sudden cardiac death (SCD) in...

Association Between Midwall Late Gadolinium Enhancement and Sudden Cardiac Death in Patients With Dilated Cardiomyopathy and Mild and Moderate Left Ventricular Systolic Dysfunction

Prognostic Significance of LGE by CMR in Aortic Stenosis Patients Undergoing Valve Replacement

Background— Scar signal quantification using late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) identifies patients at higher risk of future events, both in ischemic cardiomyopathy (ICM) and nonischemic dilated cardiomyopathy (DCM). However, the ability of scar signal burden to predict events in such patient groups at the time of referral for implantable cardioverter-defibrillator (ICD) has not been well explored. This study evaluates the predictive use of multiple scar quantification measures in ICM and DCM patients being referred for ICD.

Methods and Results— One hundred twenty-four consecutive patients referred for ICD therapy (59 with ICM and 65 with DCM) underwent a standardized LGE-CMR protocol with blinded, multithreshold scar signal quantification and, for those with ICM, peri-infarct signal quantification. Patients were followed prospectively for the primary combined outcome of appropriate ICD therapy, survived cardiac arrest, or sudden cardiac death. At a mean follow-up of 632 ± 262 days, 18 patients (15%) had suffered the primary outcome. Total scar was significantly higher among those suffering a primary outcome, a relationship maintained within each cardiomyopathy cohort ( P <0.01 for all comparisons). Total scar was the strongest independent predictor of the primary outcome and demonstrated a negative predictive value of 86%. In the ICM subcohort, peri-infarct signal showed only a nonsignificant trend toward elevation among those having a primary end point.

Conclusions— Myocardial scar quantification by LGE-CMR predicts arrhythmic events in patients being evaluated for ICD eligibility irrespective of cardiomyopathy etiology.

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Prediction of arrhythmic events in ischemic and dilated cardiomyopathy patients referred for implantable cardiac defibrillator: evaluation of multiple scar quantification measures for late gadolinium enhancement magnetic resonance imaging.

Luljeta Pallaveshi

Papers

Prediction of arrhythmic events in ischemic and dilated cardiomyopathy patients referred for implantable cardiac defibrillator: evaluation of multiple scar quantification measures for late gadolinium enhancement magnetic resonance imaging.