Abstract
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). 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. 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). 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.
Highlights
Dilated cardiomyopathy (DCM) is a prevalent disease leading to chronic heart failure (CHF)
Clinical and genetic screening for familial DCM In our well-defined cohort of 83 consecutive patients with recent-onset DCM (RODCM) we found a positive family history of DCM in 14 patients (17%), while 69 patients (83%) appeared to be sporadic cases
This pilot study is a first whole-exome sequencing study describing the genetic architecture of recent-onset dilated cardiomyopathy in the Moravian region
Summary
Dilated cardiomyopathy (DCM) is a prevalent disease leading to chronic heart failure (CHF). It has a heterogeneous aetiology including genetic, inflammatory, toxic and metabolic causes. The clinical diagnosis of DCM is based on the presence of left ventricular (LV) systolic dysfunction in the absence of abnormal loading conditions or significant coronary artery disease sufficient to cause global systolic impairment. An ultimate diagnostic and prognostic challenge are patients with recent-onset DCM (RODCM) who may have variable clinical outcomes ranging from complete recovery of LV systolic dysfunction to rapid progression to end-stage CHF or sudden cardiac death. Due to the permanent character of myocardial damage, LVRR should be less prevalent in genetic forms of DCM (ref.7,11)
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