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Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease?

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease, characterized by the presence of unexplained left ventricular hypertrophy. This condition is often associated with electrocardiographic abnormalities including QTc prolongation occurring in 13% of patients. The main explanation for...

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Autores principales: Cava, Francesco, Micolonghi, Caterina, Musumeci, Maria Beatrice, Petrucci, Simona, Savio, Camilla, Fabiani, Marco, Tini, Giacomo, Germani, Aldo, Libi, Fabio, Rossi, Carla, Visco, Vincenzo, Pizzuti, Antonio, Volpe, Massimo, Autore, Camillo, Rubattu, Speranza, Piane, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113437/
https://www.ncbi.nlm.nih.gov/pubmed/37089884
http://dx.doi.org/10.3389/fcvm.2023.1112759
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author Cava, Francesco
Micolonghi, Caterina
Musumeci, Maria Beatrice
Petrucci, Simona
Savio, Camilla
Fabiani, Marco
Tini, Giacomo
Germani, Aldo
Libi, Fabio
Rossi, Carla
Visco, Vincenzo
Pizzuti, Antonio
Volpe, Massimo
Autore, Camillo
Rubattu, Speranza
Piane, Maria
author_facet Cava, Francesco
Micolonghi, Caterina
Musumeci, Maria Beatrice
Petrucci, Simona
Savio, Camilla
Fabiani, Marco
Tini, Giacomo
Germani, Aldo
Libi, Fabio
Rossi, Carla
Visco, Vincenzo
Pizzuti, Antonio
Volpe, Massimo
Autore, Camillo
Rubattu, Speranza
Piane, Maria
author_sort Cava, Francesco
collection PubMed
description Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease, characterized by the presence of unexplained left ventricular hypertrophy. This condition is often associated with electrocardiographic abnormalities including QTc prolongation occurring in 13% of patients. The main explanation for prolonged QTc in HCM is myocardial hypertrophy and the related structural damage. However, other mechanisms, including long QT syndrome (LQTS) genes mutations, may be involved. In the present study we explored the hypothesis of a distinct genetic basis underlying QTc prolongation in HCM by investigating the potential co-inheritance of pathogenic gene variants associated with LQTS and HCM. For this purpose, starting from a cohort of 150 HCM patients carrying pathogenic variants in sarcomere genes, we selected 25 patients carrying a QTc prolongation unexplained by any other cause. The QTc was considered prolonged if greater than 450 ms in males and greater than 470 ms in females. The NGS analysis was performed with Illumina TrueSight Cardio panel genes on Illumina MiniSeq platform. We identified pathogenic/likely pathogenic variants in the KCNQ1 in two patients (c.1781G > A, p. Arg594Gln; c.532G > A, p. Ala178Thr) (8%). Variants of uncertain significance were identified in SCN5A, KCNJ5, AKAP9 and ANK2 in four patients (16%). Although the results are limited by the small number of patients included in the study, they highlight a minor contribution of LQTS genes for QTc prolongation in HCM patients. The screening for ion channel genes mutations may be considered in HCM patients with prolonged QTc unexplained by any other cause. This in-depth molecular diagnosis may contribute to improve risk stratification and treatment planning.
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spelling pubmed-101134372023-04-20 Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease? Cava, Francesco Micolonghi, Caterina Musumeci, Maria Beatrice Petrucci, Simona Savio, Camilla Fabiani, Marco Tini, Giacomo Germani, Aldo Libi, Fabio Rossi, Carla Visco, Vincenzo Pizzuti, Antonio Volpe, Massimo Autore, Camillo Rubattu, Speranza Piane, Maria Front Cardiovasc Med Cardiovascular Medicine Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease, characterized by the presence of unexplained left ventricular hypertrophy. This condition is often associated with electrocardiographic abnormalities including QTc prolongation occurring in 13% of patients. The main explanation for prolonged QTc in HCM is myocardial hypertrophy and the related structural damage. However, other mechanisms, including long QT syndrome (LQTS) genes mutations, may be involved. In the present study we explored the hypothesis of a distinct genetic basis underlying QTc prolongation in HCM by investigating the potential co-inheritance of pathogenic gene variants associated with LQTS and HCM. For this purpose, starting from a cohort of 150 HCM patients carrying pathogenic variants in sarcomere genes, we selected 25 patients carrying a QTc prolongation unexplained by any other cause. The QTc was considered prolonged if greater than 450 ms in males and greater than 470 ms in females. The NGS analysis was performed with Illumina TrueSight Cardio panel genes on Illumina MiniSeq platform. We identified pathogenic/likely pathogenic variants in the KCNQ1 in two patients (c.1781G > A, p. Arg594Gln; c.532G > A, p. Ala178Thr) (8%). Variants of uncertain significance were identified in SCN5A, KCNJ5, AKAP9 and ANK2 in four patients (16%). Although the results are limited by the small number of patients included in the study, they highlight a minor contribution of LQTS genes for QTc prolongation in HCM patients. The screening for ion channel genes mutations may be considered in HCM patients with prolonged QTc unexplained by any other cause. This in-depth molecular diagnosis may contribute to improve risk stratification and treatment planning. Frontiers Media S.A. 2023-04-05 /pmc/articles/PMC10113437/ /pubmed/37089884 http://dx.doi.org/10.3389/fcvm.2023.1112759 Text en © 2023 Cava, Micolonghi, Musumeci, Petrucci, Savio, Fabiani, Tini, Germani, Libi, Rossi, Visco, Pizzuti, Volpe, Autore, Rubattu and Piane. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Cava, Francesco
Micolonghi, Caterina
Musumeci, Maria Beatrice
Petrucci, Simona
Savio, Camilla
Fabiani, Marco
Tini, Giacomo
Germani, Aldo
Libi, Fabio
Rossi, Carla
Visco, Vincenzo
Pizzuti, Antonio
Volpe, Massimo
Autore, Camillo
Rubattu, Speranza
Piane, Maria
Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease?
title Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease?
title_full Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease?
title_fullStr Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease?
title_full_unstemmed Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease?
title_short Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease?
title_sort long qtc in hypertrophic cardiomyopathy: a consequence of structural myocardial damage or a distinct genetic disease?
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113437/
https://www.ncbi.nlm.nih.gov/pubmed/37089884
http://dx.doi.org/10.3389/fcvm.2023.1112759
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