Dilated cardiomyopathy in the era of precision medicine: latest concepts and developments

Abstract

Dilated cardiomyopathy (DCM) is an umbrella term entailing a wide variety of genetic and non-genetic etiologies, leading to left ventricular systolic dysfunction and dilatation, not explained by abnormal loading conditions or coronary artery disease. The clinical presentation can vary from asymptomatic to heart failure symptoms or sudden cardiac death (SCD) even in previously asymptomatic individuals. In the last 2 decades, there has been striking progress in the understanding of the complex genetic basis of DCM, with the discovery of additional genes and genotype-phenotype correlation studies. Rigorous clinical work-up of DCM patients, meticulous family screening, and the implementation of advanced imaging techniques pave the way for a more efficient and earlier diagnosis as well as more precise indications for implantable cardioverter defibrillator implantation and prevention of SCD. In the era of precision medicine, genotype-directed therapies have started to emerge. In this review, we focus on updates of the genetic background of DCM, characteristic phenotypes caused by recently described pathogenic variants, specific indications for prevention of SCD in those individuals and genotype-directed treatments under development. Finally, the latest developments in distinguishing athletic heart syndrome from subclinical DCM are described.

Keywords: ARVC; Athletic heart syndrome; BAG3; Cardiomyopathies; DCM; DSP; Dilated cardiomyopathy; FLNC; Heart failure; Hypokinetic non-dilated cardiomyopathy; Inherited cardiac diseases; LMNA; Molecular cardiology; PLN; Precision medicine; TMEM43.

Fig. 1

Clinical spectrum of dilated cardiomyopathy. DCM, dilated cardiomyopathy; HNDC, hypokinetic non-dilated cardiomyopathy; CM, cardiomyopathy; AHA, anti-heart antibodies

Fig. 2

A clinical management algorithm for DCM. CMR, cardiac magnetic resonance; CRT, cardiac resynchronization therapy; DCM, dilated cardiomyopathy; EPS, electrophysiological study; hs-Tn, high-sensitivity troponin; ICD, implanted cardioverted defibrillator; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; NSVT, non-sustained ventricular tachycardia; SCD, sudden cardiac death. * A diagnosis of myocarditis or peripartum cardiomyopathy does not exclude the possibility of familial disease. # Genetic testing should be considered in all cases of DCM, including sporadic cases. An implanted cardioverted defibrillator may be still considered for patients not fulfilling established criteria of high risk of extensive myocardial fibrosis, ventricular arrhythmogenicity, elevated biomarkers

Fig. 3

Diagram for distinguishing between subclinical DCM and athletic heart syndrome. BNP, brain natriuretic peptide; DCM, dilated cardiomyopathy; ECG, electrocardiogram; EF, ejection fraction; NT-proBNP, N-terminal pro hormone BNP; SCD, sudden cardiac death; VO₂, oxygen consumption. # For a pathogenic or likely pathogenic variant in a gene associated with dilated cardiomyopathy, * excluding Troponin rise after strenuous exercise