Abstract
Abstract Background Recent-onset dilated cardiomyopathy (RODCM) is a disease of heterogeneous aetiology including genetic, inflammatory, toxic and metabolic causes. Recognition of the genetic component could improve diagnostic management and risk stratification. Left ventricular reverse remodelling (LVRR) has been identified as a marker of favourable prognosis in RODCM. Purpose In this pilot study, we are first to assess the genetic background of RODCM in the Czech Republic by whole-exome sequencing and correlate genotype with LV reverse remodelling. Methods In this multi-centre prospective observational study, we enrolled 83 patients with RODCM and a history of symptoms of less than 6 months, for whole-exome sequencing. All patients underwent 12-month clinical and echocardiographic follow-up. LVRR was defined as an absolute increase in left ventricular ejec-tion fraction >10% accompanied by a relative decrease of left ventricular end-diastolic diameter >10% at 12 months. Results Whole-exome sequencing identified at least one disease-related variant in 45 patients (54%). As expected, the gene spectrum of identified variants in RODCM was quite wide comprising a total of 28 different genes, with the majority of truncating variants in titin gene which was found in 10 (12%) patients. LVRR occurred in 28 patients (34%), most often in carriers of isolated titin truncating variants, followed by individuals with a negative, or inconclusive results and carriers of other disease-related variants (56% vs. 42% vs. 19%, P 0.041). Genotype and LVRR Exom negative or non conclusive Isolated titin truncating variant Other variant or combination P-value (n=38) (n=9) (n=36) 12 months ΔLVEF absolute (%) 16 (6–23) 15 (9–34) 6 (3–15) 0.036* 12 months ΔLVEF >10% (n=44; 53%) 24 (63%) 7 (78%) 13 (36%) 0.019* 12 months ΔLVEDD <−10% (n=34; 41%) 18 (47%) 6 (67%) 10 (28%) 0.058 LVRR – 12 months, ΔLVEF >10% and ΔLVEDD <−10% (n=28; 34%) 16 (42%) 5 (56%) 7 (19%) 0.041* n, number; ΔLVEF, change of left ventricular ejection fraction; ΔLVEDD, change of left ventricular end-diastolic diameter; LVRR, left ventricular reverse remodelling. *Statistically significant result. Gene distribution in RODCM Conclusion A substantial proportion of RODCM cases has genetic background. Carriers of titin truncating variants are more likely to reach LVRR at 12 months, which could be seen as a positive prognostic marker of disease development. Genetic testing could contribute to better prognosis prediction and individualised treatment of patients with RODCM. Acknowledgement/Funding This study was supported by the research grant of the Ministry of Health, Czech Republic: MZ 15-27682A. All rights reserved.
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