Differences between familial and sporadic dilated cardiomyopathy: ESC EORP Cardiomyopathy & Myocarditis registry

Abstract

Aims Dilated cardiomyopathy (DCM) is a complex disease where genetics interplay with extrinsic factors. This study aims to compare the phenotype, management, and outcome of familial DCM (FDCM) and non‐familial (sporadic) DCM (SDCM) across Europe. Methods and results Patients with DCM that were enrolled in the prospective ESC EORP Cardiomyopathy & Myocarditis Registry were included. Baseline characteristics, genetic testing, genetic yield, and outcome were analysed comparing FDCM and SDCM; 1260 adult patients were studied (238 FDCM, 707 SDCM, and 315 not disclosed). Patients with FDCM were younger (P < 0.01), had less severe disease phenotype at presentation (P < 0.02), more favourable baseline cardiovascular risk profiles (P ≤ 0.007), and less medication use (P ≤ 0.042). Outcome at 1 year was similar and predicted by NYHA class (HR 0.45; 95% CI [0.25–0.81]) and LVEF per % decrease (HR 1.05; 95% CI [1.02–1.08]. Throughout Europe, patients with FDCM received more genetic testing (47% vs. 8%, P < 0.01) and had higher genetic yield (55% vs. 22%, P < 0.01). Conclusions We observed that FDCM and SDCM have significant differences at baseline but similar short‐term prognosis. Whether modification of associated cardiovascular risk factors provide opportunities for treatment remains to be investigated. Our results also show a prevalent role of genetics in FDCM and a non‐marginal yield in SDCM although genetic testing is largely neglected in SDCM. Limited genetic testing and heterogeneity in panels provides a scaffold for improvement of guideline adherence.

European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases

“…In the pre‐molecular era, systematic cardiac screening of the relatives of patients with DCM identified probable familial disease in about 20–35% of cases 353–355 . Subsequently, identification of DCM‐related genes and development of high‐throughput sequencing technologies led to the identification of pathogenic variants in up to 50% of DCM patients 340,355 including a non‐marginal yield in sporadic DCM 356 . Moreover, there are more and more situations in which genetic predisposition interacts with extrinsic or environmental factors resulting in mixed genetic/environmental causes, such as myocarditis, as well as peripartum, alcoholic, or chemotherapy‐related cardiomyopathies 341,342,357,358 …”

Diagnosis and Risk Prediction of Dilated Cardiomyopathy in the Era of Big Data and Genomics

“…However, even with first-rate variant curation, genetic variation only explains up to 40% of DCM cases. In patients without a family history of DCM (i.e., sporadic DCM), this yield can decrease to 10%, suggesting a bigger role for non-genetic causes including cardiotoxic medication (anthracycline), alcohol, and inflammation ( Figure 2 ) [ 3 , 4 , 5 , 37 , 38 , 39 ].…”

“…The Seattle Heart Failure Model (SHFM) [ 71 ], MAGGIC risk score [ 72 ], and the Barcelona bio-HF calculator [ 73 ] are three models with comparable risk prediction performance [ 74 ]. The performance of these models in DCM may, however, be suboptimal because their derivation also included patients with ischemic aetiology who are known to have a higher mortality risk than DCM patients (3-year mortality between 24–40%) [ 37 , 74 ]. Indeed, a recent comparison of these prediction models in an external DCM cohort produced an area under the curve (AUC) of ≥0.6, with the more sophisticated risk models (BCN Bio-HF and SHFM) yielding the highest accuracies [ 71 , 73 , 74 ].…”

“…Interestingly, the risk models typically overestimated mortality risk in DCM patients. This may be caused by a difference in age (DCM patients tend to be younger (±15 years) than other heart failure aetiologies), which is one of the strongest variables affecting mortality [ 37 , 74 ]. Moreover, there is a distinct subgroup of DCM patients who experience LV function recovery and have a subsequent mild clinical course during follow-up [ 75 ].…”

Genetic variants in Chinese patients with sporadic dilated cardiomyopathy: a cross-sectional study

“…So far, compared to the information obtained from a large number of studies on FDCM cases, much less information is available regarding the role of genetic factors, such as rare genetic variations, on the pathogenesis of SDCM. Previously, a few studies on mutations of several individual genes implicated the role of genetic factors in the development of SDCM (3)(4)(5)(6). Several cohorts, mainly containing Caucasian patients with FDCM or a combination of FDCM and SDCM, were also investigated for mutations in a relatively small number of selected candidate genes, including MYH7, TNNT2, SCN5A, CSRP3, and LBD (7)(8)(9).The consideration of genetic variants is important when evaluating the pathogenicity of a genomic variant.…”