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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1112759/full |
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| author | Francesco Cava Caterina Micolonghi Caterina Micolonghi Maria Beatrice Musumeci Simona Petrucci Camilla Savio Marco Fabiani Giacomo Tini Aldo Germani Fabio Libi Carla Rossi Vincenzo Visco Antonio Pizzuti Antonio Pizzuti Massimo Volpe Massimo Volpe Camillo Autore Speranza Rubattu Speranza Rubattu Maria Piane Maria Piane |
| author_facet | Francesco Cava Caterina Micolonghi Caterina Micolonghi Maria Beatrice Musumeci Simona Petrucci Camilla Savio Marco Fabiani Giacomo Tini Aldo Germani Fabio Libi Carla Rossi Vincenzo Visco Antonio Pizzuti Antonio Pizzuti Massimo Volpe Massimo Volpe Camillo Autore Speranza Rubattu Speranza Rubattu Maria Piane Maria Piane |
| author_sort | Francesco Cava |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T19:30:00Z |
| format | Article |
| id | doaj.art-6ed17b1f6031429e95495c699b8134e3 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-09T19:30:00Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-6ed17b1f6031429e95495c699b8134e32023-04-05T04:39:52ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-04-011010.3389/fcvm.2023.11127591112759Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease?Francesco Cava0Caterina Micolonghi1Caterina Micolonghi2Maria Beatrice Musumeci3Simona Petrucci4Camilla Savio5Marco Fabiani6Giacomo Tini7Aldo Germani8Fabio Libi9Carla Rossi10Vincenzo Visco11Antonio Pizzuti12Antonio Pizzuti13Massimo Volpe14Massimo Volpe15Camillo Autore16Speranza Rubattu17Speranza Rubattu18Maria Piane19Maria Piane20Department of Clinical and Molecular Medicine, Sapienza University, Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Rome, ItalySant'Andrea University Hospital, Rome, ItalyDepartment of Clinical and Molecular Medicine, Sapienza University, Rome, ItalyDepartment of Clinical and Molecular Medicine, Sapienza University, Rome, ItalySant'Andrea University Hospital, Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Rome, ItalyDepartment of Clinical and Molecular Medicine, Sapienza University, Rome, ItalyDepartment of Clinical and Molecular Medicine, Sapienza University, Rome, ItalySant'Andrea University Hospital, Rome, ItalySant'Andrea University Hospital, Rome, ItalyDepartment of Clinical and Molecular Medicine, Sapienza University, Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Rome, ItalyCasa Sollievo Della Sofferenza Foundation, San Giovanni Rotondo, ItalyDepartment of Clinical and Molecular Medicine, Sapienza University, Rome, ItalyIRCCS S.Raffaele, Rome, ItalyIRCCS S.Raffaele, Cassino, ItalyDepartment of Clinical and Molecular Medicine, Sapienza University, Rome, ItalyIRCCS Neuromed, Pozzilli, ItalyDepartment of Clinical and Molecular Medicine, Sapienza University, Rome, ItalySant'Andrea University Hospital, Rome, ItalyHypertrophic 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.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1112759/fullhypertrophic cardiomyopathyQTcLQTSgene muatationQTc abnormalities |
| spellingShingle | Francesco Cava Caterina Micolonghi Caterina Micolonghi Maria Beatrice Musumeci Simona Petrucci Camilla Savio Marco Fabiani Giacomo Tini Aldo Germani Fabio Libi Carla Rossi Vincenzo Visco Antonio Pizzuti Antonio Pizzuti Massimo Volpe Massimo Volpe Camillo Autore Speranza Rubattu Speranza Rubattu Maria Piane Maria Piane Long QTc in hypertrophic cardiomyopathy: A consequence of structural myocardial damage or a distinct genetic disease? Frontiers in Cardiovascular Medicine hypertrophic cardiomyopathy QTc LQTS gene muatation QTc abnormalities |
| 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 | hypertrophic cardiomyopathy QTc LQTS gene muatation QTc abnormalities |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1112759/full |
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