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
Martin S. Maron, Ahmad Masri, Lubna Choudhury, Iacopo Olivotto, Sara Saberi, Andrew Wang, Pablo Garcia-Pavia, Neal K. Lakdawala, Sherif F. Nagueh, Florian Rader, Albree Tower-Rader, Aslan T. Turer, Caroline Coats, Michael A. Fifer, Anjali Owens, Scott D. Solomon, Hugh Watkins, Roberto Barriales-Villa, Christopher M. Kramer, Timothy C. Wong, Sharon L. Paige, Stephen B. Heitner, Stuart Kupfer, Fady I. Malik, Lisa Meng, Amy Wohltman, Theodore Abraham
Summary: This study evaluated the safety and efficacy of aficamten in patients with obstructive hypertrophic cardiomyopathy (oHCM). The results showed that aficamten significantly reduced left ventricular outflow tract gradients and improved clinical symptoms.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
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
Cardiac & Cardiovascular Systems
Hao Cui, Hartzell Schaff, Juliano Lentz Carvalho, Rick A. Nishimura, Jeffrey B. Geske, Joseph A. Dearani, Brian D. Lahr, Alexander T. Lee, J. Martijn Bos, Michael J. Ackerman, Steve R. Ommen, Joseph J. Maleszewski
Summary: This study analyzed the myocardial histopathology of 1,836 patients with obstructive HCM undergoing septal myectomy, finding associations between myocyte hypertrophy, myocyte disarray, and interstitial fibrosis with severity of heart disease. Older age, lower degree of myocyte hypertrophy, and lower degree of endocardial thickening were independently associated with worse post-myectomy survival.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Michael Butzner, Douglas L. Leslie, Yendelela Cuffee, Christopher S. Hollenbeak, Christopher Sciamanna, Theodore Abraham
Summary: This study estimated the annual prevalence of obstructive hypertrophic cardiomyopathy (oHCM) in the US from 2016 to 2018 and found that the majority of privately insured patients with oHCM are undiagnosed. The prevalence of oHCM remained stable over the three-year period, with higher rates in males and patients aged 55-64 years.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Dennis Lawin, Thorsten Lawrenz, Kristin Marx, Nils Benedikt Danielsmeier, Madan Raj Poudel, Christoph Stellbrink
Summary: The impact of gender on outcomes after alcohol septal ablation (ASA) was investigated in a large retrospective analysis. The study found that female patients with hypertrophic obstructive cardiomyopathy (HOCM) were older and had more advanced disease at the time of ASA. Short-term hemodynamic response to ASA was better in women, but they were more likely to develop atrioventricular block.
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)
Article
Cardiac & Cardiovascular Systems
Quanfei Hou, Wenqian Wu, Lingyun Fang, Xin Zhang, Chenchen Sun, Li Ji, Ming Yang, Ziqiao Lei, Fan Gao, Jing Wang, Mingxing Xie, Shu Chen
Summary: This study developed a patient-specific hemodynamics assessment using cardiac computed tomography angiography (CCTA) based computational fluid dynamics (CFD) for hypertrophic obstructive cardiomyopathy (HOCM) patients. The assessment accurately evaluated the morphology and hemodynamics of HOCM patients and predicted the volume of resected myocardium for septal myectomy when combined with virtual myectomy.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Josef Veselka, Lothar Faber, Max Liebregts, Robert Cooper, Jaroslav Januska, Maksim Kashtanov, Maciej Dabrowski, Peter Riis Hansen, Hubert Seggewiss, Jiri Bonaventura, Eva Polakova, Eva Hansvenclova, Henning Bundgaard, Jurrien ten Berg, Rodney Hilton Stables, Jiri Jarkovsky, Morten Kvistholm Jensen
Summary: The study evaluated short- and long-term outcomes related to dose of alcohol administered during alcohol septal ablation (ASA) in HOCM patients. Results showed that patients receiving low-dose or high-dose of alcohol had similar short- and long-term outcomes, with the low-dose group undergoing more subsequent septal reduction procedures.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2021)
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
Emanuele Monda, Michele Lioncino, Giuseppe Palmiero, Francesco Franco, Marta Rubino, Annapaola Cirillo, Federica Verrillo, Adelaide Fusco, Martina Caiazza, Marialuisa Mazzella, Elisabetta Moscarella, Francesca Dongiglio, Joseph Sepe, Giuseppe Pacileo, Paolo Calabro, Giuseppe Limongelli
Summary: Bisoprolol is effective and well-tolerated in controlling symptoms and left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2022)
Article
Cell Biology
Maike Schuldt, Beau van Driel, Sila Alguel, Rahana Y. Parbhudayal, Daniela Q. C. M. Barge-Schaapveld, Ahmet Gueclue, Mark Jansen, Michelle Michels, Annette F. Baas, Mark A. van de Wiel, Max Nieuwdorp, Evgeni Levin, Tjeerd Germans, Judith J. M. Jans, Jolanda van der Velden
Summary: This study identified unique metabolic signatures in the serum of preclinical carriers and patients with hypertrophic cardiomyopathy, which could potentially be used for risk stratification and precision therapeutics for the disease.
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)