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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
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.
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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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