Genetic architecture of recent-onset dilated cardiomyopathy in Moravian region assessed by whole-exome sequencing and its clinical correlates
Abstrakt
Aims. Recent-onset dilated cardiomyopathy (RODCM) is a disease of heterogeneous aetiology and clinical outcome.
In this pilot study, we aimed to assess its genetic architecture and correlate genotype with left ventricular reverse remodelling (LVRR). Patients and Methods.
In this multi-centre prospective observational study, we enrolled 83 Moravian patients with RODCM and a history of symptoms of less than 6 months, for whole-exome sequencing (WES). All patients underwent 12-month clinical and echocardiographic follow-up.
LVRR was defined as an absolute increase in left ventricular ejection fraction > 10% accompanied by a relative decrease of left ventricular end-diastolic diameter > 10% at 12 months. Results.
WES identified at least one disease-related variant in 45 patients (54%). LVRR occurred in 28 patients (34%), most often in carriers of isolated titin truncated variants, followed by individuals with a negative, or inconclusive WES and carriers of other disease-related variants (56% vs. 42% vs. 19%, P=0.041).
Conclusion. A substantial proportion of RODCM cases have a monogenic or oligogenic genetic background.
Carriers of non-titin disease-related variants are less likely to reach LVRR at 12-months than other individuals. Genetic testing could contribute to better prognosis prediction and individualized treatment of RODCM.