Article
Multidisciplinary Sciences
Giuliana G. Repetti, Yuri Kim, Alexandre C. Pereira, Jodie Ingles, Mark W. Russell, Neal K. Lakdawala, Carolyn Y. Ho, Sharlene Day, Christopher Semsarian, Barbara McDonough, Steven R. DePalma, Daniel Quiat, Eric M. Green, Christine E. Seidman, J. G. Seidman
Summary: The clinical expression of hypertrophic cardiomyopathy (HCM) is influenced by background genetic variation and environmental factors. A study of 11 pairs of monozygotic HCM twins showed discordant cardiac morphology even among twins with the same pathogenic variant, indicating a significant role for epigenetics and environment in HCM disease progression. Whole genome sequencing analysis did not reveal notable somatic genetic variants to explain the clinical differences in the twins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cardiac & Cardiovascular Systems
Luis R. Lopes, Soledad Garcia-Hernandez, Massimiliano Lorenzini, Marta Futema, Olga Chumakova, Dmitry Zateyshchikov, Maria Isidoro-Garcia, Eduardo Villacorta, Luis Escobar-Lopez, Pablo Garcia-Pavia, Raquel Bilbao, David Dobarro, Maria Sandin-Fuentes, Claudio Catalli, Blanca Gener Querol, Ainhoa Mezcua, Jose Garcia Pinilla, Torsten Bloch Rasmussen, Ana Ferreira-Aguar, Pablo Revilla-Marti, Maria Teresa Basurte Elorz, Alicia Bautista Paves, Juan Ramon Gimeno, Ana Virginia Figueroa, Raul Franco-Gutierrez, Maria Eugenia Fuentes-Canamero, Marina Martinez Moreno, Martin Ortiz-Genga, Jesus Piqueras-Flores, Karina Analia Ramos, Ainars Rudzitis, Luis Ruiz-Guerrero, Ricardo Stein, Mayte Triguero-Bocharan, Luis de la Higuera, Juan Pablo Ochoa, Dad Abu-Bonsrah, Cecilia Y. T. Kwok, Jacob B. Smith, Enzo R. Porrello, Mohammed M. Akhtar, Joanna Jager, Michael Ashworth, Petros Syrris, David A. Elliott, Lorenzo Monserrat, Perry M. Elliott
Summary: The study identified a low but pathogenic frequency of heterozygous ALPK3tv in patients with HCM, which was confirmed through family co segregation studies. ALPK3tv carriers exhibited a characteristic HCM phenotype, showing different clinical and imaging features compared to patients with sarcomere gene variants.
EUROPEAN HEART JOURNAL
(2021)
Article
Cardiac & Cardiovascular Systems
Luis R. Lopes, Soledad Garcia-Hernandez, Massimiliano Lorenzini, Marta Futema, Olga Chumakova, Dmitry Zateyshchikov, Maria Isidoro-Garcia, Eduardo Villacorta, Luis Escobar-Lopez, Pablo Garcia-Pavia, Raquel Bilbao, David Dobarro, Maria Sandin-Fuentes, Claudio Catalli, Blanca Gener Querol, Ainhoa Mezcua, Jose Garcia Pinilla, Torsten Bloch Rasmussen, Ana Ferreira-Aguar, Pablo Revilla-Marti, Maria Teresa Basurte Elorz, Alicia Bautista Paves, Juan Ramon Gimeno, Ana Virginia Figueroa, Raul Franco-Gutierrez, Maria Eugenia Fuentes-Canamero, Marina Martinez Moreno, Martin Ortiz-Genga, Jesus Piqueras-Flores, Karina Analia Ramos, Ainars Rudzitis, Luis Ruiz-Guerrero, Ricardo Stein, Mayte Triguero-Bocharan, Luis de la Higuera, Juan Pablo Ochoa, Dad Abu-Bonsrah, Cecilia Y. T. Kwok, Jacob B. Smith, Enzo R. Porrello, Mohammed M. Akhtar, Joanna Jager, Michael Ashworth, Petros Syrris, David A. Elliott, Lorenzo Monserrat, Perry M. Elliott
Summary: The study aimed to determine the frequency of heterozygous truncating ALPK3 variants in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity through burden testing. The results showed that ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy and a short PR interval, indicating a characteristic HCM phenotype. Patients with ALPK3tv also had higher rates of heart failure or cardiac transplantation, with imaging and histopathology revealing extensive myocardial fibrosis and myocyte vacuolation.
EUROPEAN HEART JOURNAL
(2021)
Article
Genetics & Heredity
Adam Waring, Andrew Harper, Silvia Salatino, Christopher Kramer, Stefan Neubauer, Kate Thomson, Hugh Watkins, Martin Farrall
Summary: This study introduces methods for gene association and variant interpretation that detect clustering of rare missense variants in Mendelian disease genes, which can enhance disease-gene discovery. The statistical methods presented in this study are more powerful and computationally faster than alternative methods, and can effectively integrate ACMG criteria to provide strong evidence of pathogenicity for variants of uncertain significance.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Medicine, General & Internal
Sophie Urtado, Helene Hergault, Stephen Binsse, Vincent Aidan, Mounir Ouadahi, Catherine Szymanski, Sophie Mallet, Marie Hauguel-Moreau, Robert Yves Carlier, Olivier Dubourg, Nicolas Mansencal
Summary: This study assessed the usefulness of a longitudinal strain adjusted to regional thickness in hypertrophic cardiomyopathy (HCM). The results demonstrated that this adjusted method can provide a better evaluation of myocardial deformation.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Cardiac & Cardiovascular Systems
Seitaro Nomura, Minoru Ono
Summary: Cardiomyopathy develops through a combination of genetic and environmental factors. Genetic testing can identify causative genes in about half of the cases and predict clinical prognosis. Genome-wide genetic research is crucial for accurate disease risk assessment, as cardiomyopathy is caused by both single rare variants and combinations of multiple common variants. Single-cell analysis research is advancing rapidly, and the combination of genomic analysis and single-cell molecular profiling is expected to contribute to more detailed stratification of cardiomyopathy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Review
Cardiac & Cardiovascular Systems
William E. Moody, Perry M. Elliott
Summary: The recognition and improved diagnostic techniques for hypertrophic cardiomyopathy (HCM) have led to earlier and more effective management, resulting in improved life expectancy and quality of life for patients. Advances in molecular genetics and novel therapies offer exciting prospects for the future treatment of HCM.
Article
Cardiac & Cardiovascular Systems
Nicholas A. Marston, Larry Han, Iacopo Olivotto, Sharlene M. Day, Euan A. Ashley, Michelle Michels, Alexandre C. Pereira, Jodie Ingles, Christopher Semsarian, Daniel Jacoby, Steven D. Colan, Joseph W. Rossano, Samuel G. Wittekind, James S. Ware, Sara Saberi, Adam S. Helms, Carolyn Y. Ho
Summary: Patients with childhood-onset hypertrophic cardiomyopathy are more likely to have sarcomeric disease, have a higher risk of life-threatening ventricular arrhythmias, and have a greater need for advanced heart failure therapies.
EUROPEAN HEART JOURNAL
(2021)
Review
Cardiac & Cardiovascular Systems
Minh B. Nguyen, Seema Mital, Luc Mertens, Aamir Jeewa, Mark K. Friedberg, Julien Aguet, Arnon Adler, Christopher Z. Lam, Andreea Dragulescu, Harry Rakowski, Olivier Villemain
Summary: This review examines the association between genetic variations and outcomes in pediatric hypertrophic cardiomyopathy (HCM), discussing current approaches to phenotyping cardiovascular characteristics and exploring potential avenues for improving risk assessment of sudden cardiac death in children with HCM.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Cardiac & Cardiovascular Systems
Yishay Wasserstrum, Jose M. Larranaga-Moreira, Cristina Martinez-Veira, Edward Itelman, Dor Lotan, Avi Sabbag, Rafael Kuperstein, Yael Peled, Dov Freimark, Roberto Barriales-Villa, Michael Arad
Summary: Hypertrophic cardiomyopathy with reduced ejection fraction (HCMr) is associated with heart failure and poor outcome. Factors associated with the development of HCMr include younger age of diagnosis, poor functional class, and ventricular arrhythmia. Predictors of future HCMr development include atrial fibrillation, pacemaker implantation, and decreased left ventricular ejection fraction. Genetic factors play a significant role in the development of HCMr.
Review
Biochemistry & Molecular Biology
Anna Burban, Szymon Pucylo, Aleksandra Sikora, Grzegorz Opolski, Marcin Grabowski, Agnieszka Kolodzinska
Summary: This article discusses the main cause of heart failure, which is cardiomyopathies. Among them, the most common is hypertrophic cardiomyopathy (HCM). The article also describes other cardiomyopathies with myocardial hypertrophy, including Fabry disease, Pompe disease, and Danon disease. It provides information on the genetics and pathogenesis of these diseases, as well as current and experimental treatment options such as pharmacological intervention and gene therapies. Further research is needed to evaluate the efficacy and safety of genetic approaches in treating these diseases. The article provides current knowledge and advances in the treatment of cardiomyopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Sarah Abou Alaiwi, Thomas M. Roston, Peter Marstrand, Brian Lee Claggett, Victoria N. Parikh, Adam S. Helms, Jodie Ingles, Rachel Lampert, Neal K. Lakdawala, Michelle Michels, Anjali T. Owens, Joseph W. Rossano, Sara Saberi, Dominic J. Abrams, Euan A. Ashley, Christopher Semsarian, John C. Stendahl, James S. Ware, Erin Miller, Thomas D. Ryan, Mark W. Russell, Sharlene M. Day, Iacopo Olivotto, Christoffer R. Vissing, Carolyn Y. Y. Ho
Summary: A study on children diagnosed with hypertrophic cardiomyopathy (HCM) found that they have a higher risk of developing left ventricular systolic dysfunction (LVSD) compared to adult patients. This study highlights the importance of careful surveillance for LVSD in children with HCM, especially during their transition to adult care.
Review
Medicine, General & Internal
Andrea Ottaviani, Davide Mansour, Lorenzo V. Molinari, Kristian Galanti, Cesare Mantini, Mohammed Y. Khanji, Anwar A. Chahal, Marco Zimarino, Giulia Renda, Luigi Sciarra, Francesco Pelliccia, Sabina Gallina, Fabrizio Ricci
Summary: This narrative review provides a comprehensive overview of current clinical practice and emerging therapeutic strategies for sarcomeric HCM, with a focus on cardiac myosin inhibitors. It highlights the limitations of conventional management and discusses recent advances in molecular genetics and emerging therapies, including gene editing, RNA-based therapies, and targeted small molecules. It emphasizes the importance of multidisciplinary care and patient-centered approaches, as well as the need for further research and collaboration in the field of HCM.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Antonio de Marvao, Kathryn A. McGurk, Sean L. Zheng, Marjola Thanaj, Wenjia Bai, Jinming Duan, Carlo Biffi, Francesco Mazzarotto, Ben Statton, Timothy J. W. Dawes, Nicolo Savioli, Brian P. Halliday, Xiao Xu, Rachel J. Buchan, A. John Baksi, Marina Quinlan, Pawel Tokarczuk, Upasana Tayal, Catherine Francis, Nicola Whiffin, Pantazis Theotokis, Xiaolei Zhang, Mikyung Jang, Alaine Berry, Antonis Pantazis, Paul J. R. Barton, Daniel Rueckert, Sanjay K. Prasad, Roddy Walsh, Carolyn Y. Ho, Stuart A. Cook, James S. Ware, Declan P. O'Regan
Summary: Rare variants in sarcomere-encoding genes have low penetrance for overt HCM in middle-aged adults, but are associated with an increased risk of heart failure and a weakened cardiomyopathic phenotype.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Le Qin, Siqi Zhu, Peng Liu, Lan Zhu, Chihua Chen, Shengjia Gu, Wenjie Yang, Mi Zhou, Fuhua Yan
Summary: This study aimed to evaluate the additional prognostic values of myocardial strain/strain rate (SR) beyond late gadolinium enhancement (LGE) for risk stratification in hypertrophic cardiomyopathy (HCM) patients. The results showed that peak systolic (PS)-global longitudinal strain rate (GLSR) was independently associated with major adverse cardiovascular events (MACEs) and had stronger predictive ability. It also improved sensitivity and specificity compared to LGE/left ventricular (LV) mass.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2023)