Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing?

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Sousa, A (Author) FMUP; Canedo, P (Author) Other; Campelo, M (Author) FMUP; Moura, B (Author) Other; Leite, S (Author) Other; Baixia, M (Author) Other; Belo, A (Author) Other; Rocha Goncalves, F (Author) Other; Machado JC (Author) FMUP; Silva Cardoso, J (Author) FMUP; Martins, E (Author) FMUP; Oliveira, AC (Author) Other; Lebreiro, A (Author) Other; Almeida, AR (Author) Other; António Madureira (Author) FMUP; Andrade, A (Author) Other; Gavina C (Author) FMUP; Brito, D (Author) Other; Correia, E (Author) Other; Goncalves, L (Author) Other; Lopes, L (Author) Other; Faria, MT (Author) Other; Azevedo, O (Author) Other; Baptista, R (Author) Other; Pinho, T (Author) Other

Journal

Title: Cardiology Research and Practice

Vol. 2019

Pages: 1-9

ISSN: 2090-8016

Publisher: Hindawi

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 2 Citations

Other information

Authenticus ID: P-00Q-JP6

DOI: 10.1155/2019/2743650

Abstract (EN): Background. Sudden cardiac death (SCD) risk stratification in dilated cardiomyopathy (DCM) has been based on left ventricular ejection fraction (LVEF), even though SCD may occur with LVEF>35%. Family history of unexplained SCD, especially in the young, raises concern about potential inheritable risk factors. It remains largely unknown how genetic tests can be integrated into clinical practice, particularly in the selection of implantable cardioverter defibrillator (ICD) candidates. We aimed to assess the diagnostic yield of genetic testing in DCM patients with a class I recommendation for ICD implantation, based on current guidelines. Methods. We included ambulatory stable adult patients with idiopathic or familial DCM with previously implanted ICD. Molecular analysis included 15 genes (LMNA, MYH7, MYBPC3, TNNT2, ACTC1, TPM1, CSRP3, TCAP, SGCD, PLN, MYL2, MYL3, TNNI3, TAZ, and LDB3) using next-generation sequencing. Results. We evaluated 21 patients, 12 (57%) males and 9 (43%) with familial DCM, including 3 (14%) with a family history of premature unexplained SCD. Mean age at DCM diagnosis was 40 +/- 2years, and mean age at ICD implantation was 50 +/- 12years. LVEF was 27 +/- 9%, and LV end-diastolic diameter was 65 +/- 7mm. Genetic variants were found in six (29%) patients, occurring in 5 genes: TPM1, TNNT2, MYH7, PLN, and MYBPC3. The majority were classified as variants of uncertain significance. Family history of SCD was present in both patients with PLN variants. Conclusion. In patients with DCM and ICD, genetic variants could be identified in a significant proportion of patients in several genes, highlighting the potential role of genetics in DCM SCD risk stratification.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9