European heart journal · 2026
Genotype and arrhythmic risk in dilated cardiomyopathy.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Padalia Kishan, Fornaro Alessandra, Claggett Brian, Jason Max, Moritz Sarah, Medo Kristen, Graw Sharon, Hespe Sophie, Ingles Jodie, Ho Carolyn Y, Helms Adam S, Shore Supriya, Sinagra Gianfranco, Merlo Marco, Khan Sadiya S, Lin Kim, Olivotto Iacopo, Owens Anjali, Wheeler Matthew, Stevenson Lynne, Reza Nosheen, Rossano Joseph, Paldino Alessia, Verdonschot Job A J, Taylor Matthew R G, Tayal Upasana, Heymans Stephane R B, Prasad Sanjay, Lakdawala Neal K, Parikh Victoria N, Mestroni Luisa, Wilsbacher Lisa D, DCM-SHaRe Investigators
Аннотация
BACKGROUND AND AIMS: Dilated cardiomyopathy (DCM) presents with variable risk of life-threatening arrhythmias. Genetic diagnosis guides sudden death prevention strategies, but risk magnitude for arrhythmogenic genes remains unknown. This study leveraged the international Sarcomeric Human Cardiomyopathy Registry (SHaRe) to address this gap and improve risk stratification.
METHODS: Effects of pathogenic/likely pathogenic (P/LP) variants in genes associated with DCM and ventricular arrhythmia on clinical events were analysed in DCM-SHaRe patients. Patients were stratified by presence of a P/LP variant in a high-arrhythmogenic risk gene (LMNA, DSP, FLNC, RBM20, PLN, SCN5A, DES, TMEM43), a low-arrhythmogenic risk gene (TTN, TNNT2, MYH7, others), or gene-elusive. Outcomes included age-, sex-, and baseline left ventricular ejection fraction (LVEF)-adjusted risk of major ventricular arrhythmia (MVA), atrial fibrillation (AF), heart failure (HF), death, and their composite.
RESULTS: Among 2660 genotyped adults with DCM (mean diagnosis age 47 ± 15 years, 39.8% female), 434 (16%) had P/LP variants in high-arrhythmogenic genes, 451 (17%) in low-arrhythmogenic genes, and 1775 (67%) were gene-elusive. Compared with gene-elusive patients, patients with high-arrhythmogenic P/LP variants showed increased MVA [hazard ratio (HR) 3.25, 95% confidence interval (CI) 2.63-4.01], AF (HR 2.42, 95% CI 1.96-2.98), HF (HR 2.46, 95% CI 1.89-3.19), and composite (HR 1.97, 95% CI 1.69-2.29) risk, which remained significant after adjusting for age, sex, and LVEF. Patients with high-arrhythmogenic P/LP variants and LVEF ≥ 50% maintained increased MVA (HR 2.36, 95% CI 1.59-3.51) and composite (HR 1.63, 95% CI 1.25-2.12) risk.
CONCLUSIONS: Genetic testing enables powerful risk stratification for arrhythmias and HF in DCM independent of age, sex, or LVEF.
METHODS: Effects of pathogenic/likely pathogenic (P/LP) variants in genes associated with DCM and ventricular arrhythmia on clinical events were analysed in DCM-SHaRe patients. Patients were stratified by presence of a P/LP variant in a high-arrhythmogenic risk gene (LMNA, DSP, FLNC, RBM20, PLN, SCN5A, DES, TMEM43), a low-arrhythmogenic risk gene (TTN, TNNT2, MYH7, others), or gene-elusive. Outcomes included age-, sex-, and baseline left ventricular ejection fraction (LVEF)-adjusted risk of major ventricular arrhythmia (MVA), atrial fibrillation (AF), heart failure (HF), death, and their composite.
RESULTS: Among 2660 genotyped adults with DCM (mean diagnosis age 47 ± 15 years, 39.8% female), 434 (16%) had P/LP variants in high-arrhythmogenic genes, 451 (17%) in low-arrhythmogenic genes, and 1775 (67%) were gene-elusive. Compared with gene-elusive patients, patients with high-arrhythmogenic P/LP variants showed increased MVA [hazard ratio (HR) 3.25, 95% confidence interval (CI) 2.63-4.01], AF (HR 2.42, 95% CI 1.96-2.98), HF (HR 2.46, 95% CI 1.89-3.19), and composite (HR 1.97, 95% CI 1.69-2.29) risk, which remained significant after adjusting for age, sex, and LVEF. Patients with high-arrhythmogenic P/LP variants and LVEF ≥ 50% maintained increased MVA (HR 2.36, 95% CI 1.59-3.51) and composite (HR 1.63, 95% CI 1.25-2.12) risk.
CONCLUSIONS: Genetic testing enables powerful risk stratification for arrhythmias and HF in DCM independent of age, sex, or LVEF.