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Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing?
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507268/ https://www.ncbi.nlm.nih.gov/pubmed/31179125 http://dx.doi.org/10.1155/2019/2743650 |
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author | Sousa, Alexandra Canedo, Paulo Campelo, Manuel Moura, Brenda Leite, Sérgio Baixia, Márcia Belo, Adriana Rocha-Gonçalves, Francisco Machado, José Carlos Silva-Cardoso, José Martins, Elisabete FATIMA Investigators, |
author_facet | Sousa, Alexandra Canedo, Paulo Campelo, Manuel Moura, Brenda Leite, Sérgio Baixia, Márcia Belo, Adriana Rocha-Gonçalves, Francisco Machado, José Carlos Silva-Cardoso, José Martins, Elisabete FATIMA Investigators, |
author_sort | Sousa, Alexandra |
collection | PubMed |
description | 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 ± 2 years, and mean age at ICD implantation was 50 ± 12 years. LVEF was 27 ± 9%, and LV end-diastolic diameter was 65 ± 7 mm. 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. |
format | Online Article Text |
id | pubmed-6507268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-65072682019-06-09 Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing? Sousa, Alexandra Canedo, Paulo Campelo, Manuel Moura, Brenda Leite, Sérgio Baixia, Márcia Belo, Adriana Rocha-Gonçalves, Francisco Machado, José Carlos Silva-Cardoso, José Martins, Elisabete FATIMA Investigators, Cardiol Res Pract Research Article 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 ± 2 years, and mean age at ICD implantation was 50 ± 12 years. LVEF was 27 ± 9%, and LV end-diastolic diameter was 65 ± 7 mm. 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. Hindawi 2019-04-24 /pmc/articles/PMC6507268/ /pubmed/31179125 http://dx.doi.org/10.1155/2019/2743650 Text en Copyright © 2019 Alexandra Sousa et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Sousa, Alexandra Canedo, Paulo Campelo, Manuel Moura, Brenda Leite, Sérgio Baixia, Márcia Belo, Adriana Rocha-Gonçalves, Francisco Machado, José Carlos Silva-Cardoso, José Martins, Elisabete FATIMA Investigators, Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing? |
title | Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing? |
title_full | Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing? |
title_fullStr | Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing? |
title_full_unstemmed | Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing? |
title_short | Genetic Variants Are Not Rare in ICD Candidates with Dilated Cardiomyopathy: Time for Next-Generation Sequencing? |
title_sort | genetic variants are not rare in icd candidates with dilated cardiomyopathy: time for next-generation sequencing? |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507268/ https://www.ncbi.nlm.nih.gov/pubmed/31179125 http://dx.doi.org/10.1155/2019/2743650 |
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