Review
Cardiac & Cardiovascular Systems
Ilias K. Gartzonikas, Katerina K. Naka, Aris Anastasakis
Summary: Hypertrophic cardiomyopathy (HCM) is a genetically inherited cardiomyopathy with common mutations in the genes MYBPC3 and MYH7. Diagnosis requires ruling out secondary causes of left ventricular hypertrophy. HCM is characterized by various clinical manifestations, with diastolic dysfunction and increased ventricular arrhythmogenesis being commonly observed. Current therapies focus on symptom management and prevention of sudden cardiac death, but there is a need for improved treatments targeting heart failure and atrial fibrillation. With advancements in understanding the genetic and molecular basis of HCM, novel treatments are expected in the near future.
HELLENIC JOURNAL OF CARDIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
A. J. Marian
Summary: Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by left ventricular hypertrophy and may lead to heart failure or sudden cardiac death. Pathogenic variants in genes encoding myocardial protein constituents, especially MYH7 and MYBPC3 genes, are the main causes of HCM. Advances in genetic testing and drug development have improved the therapeutic prospects for HCM.
CIRCULATION RESEARCH
(2021)
Article
Multidisciplinary Sciences
Ke Gong, Kai Yang, Ting Xie, Yong Luo, Hui Guo, Zhiping Tan, Jinlan Chen, Qin Wu, Yibo Gong, Luyao Wei, Jinwen Luo, Yao Yao, Yifeng Yang, Li Xie
Summary: By analyzing gene expression files in the GEO database, this study identified differentially expressed circRNAs, miRNAs, and mRNAs in HCM, and predicted the target molecules of circRNAs and miRNAs. A ceRNA network was constructed by calculating the intersection of these differentially expressed RNA molecules and their expected targets. Functional enrichment analysis revealed the potential etiology of HCM, which is associated with calcium channel release. The qPCR results showed differential expression levels of circRNA, miRNA, and mRNA, suggesting their potential as noninvasive indicators for early screening and prognostic prediction of HCM.
Review
Medical Laboratory Technology
Mireia Alcalde, Rocio Toro, Fernando Bonet, Jose Cordoba-Caballero, Estefania Martinez-Barrios, Juan Antonio Ranea, Marta Vallverdu-Prats, Ramon Brugada, Viviana Meraviglia, Milena Bellin, Georgia Sarquella-Brugada, Oscar Campuzano
Summary: Arrhythmogenic cardiomyopathy is a rare inherited disease characterized by fibro-fatty replacement of the myocardium, leading to malignant arrhythmias and a high risk of sudden cardiac death. Early identification of at-risk individuals is crucial to prevent lethal episodes. Genetic analysis can identify deleterious rare variants in genes encoding desmosome proteins, but other factors like microRNAs may also modulate disease onset and outcome. Understanding the role of microRNAs may have clinical implications as potential biomarkers in arrhythmogenic cardiomyopathy.
TRANSLATIONAL RESEARCH
(2023)
Review
Health Care Sciences & Services
Paloma Jorda, Rocio Toro, Carles Diez, Joel Salazar-Mendiguchia, Anna Fernandez-Falgueras, Alexandra Perez-Serra, Monica Coll, Marta Puigmule, Elena Arbelo, Ana Garcia-Alvarez, Georgia Sarquella-Brugada, Sergi Cesar, Coloma Tiron, Anna Iglesias, Josep Brugada, Ramon Brugada, Oscar Campuzano
Summary: Rare variants in the RBM20 gene are associated with malignant arrhythmias, early recognition of arrhythmic genotypes is crucial for avoiding lethal episodes, and personalized medicine may impact the adoption of preventive measures.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Health Care Sciences & Services
Marta Vallverdu-Prats, Mireia Alcalde, Georgia Sarquella-Brugada, Sergi Cesar, Elena Arbelo, Anna Fernandez-Falgueras, Monica Coll, Alexandra Perez-Serra, Marta Puigmule, Anna Iglesias, Victoria Fiol, Carles Ferrer-Costa, Bernat del Olmo, Ferran Pico, Laura Lopez, Paloma Jorda, Ana Garcia-Alvarez, Coloma Tiron de Llano, Rocio Toro, Simone Grassi, Antonio Oliva, Josep Brugada, Ramon Brugada, Oscar Campuzano
Summary: Genetic reclassification of rare variants associated with arrhythmogenic cardiomyopathy is crucial for obtaining accurate diagnoses. In a study reevaluating 39 rare ACM-related variants, it was found that 30.77% of these variants had their classification changed primarily due to updated global frequencies.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Medicine, General & Internal
Claire M. Lawley, Juan Pablo Kaski
Summary: Hypertrophic cardiomyopathy (HCM) is a significant cause of illness and death in children. Most cases are caused by gene variants in the cardiac sarcomere components, inherited as an autosomal dominant trait. Recent studies have shown that phenotypic expression of HCM can occur in young children, highlighting the need for clinical screening and genetic testing in pediatric relatives. The multidisciplinary care of HCM-affected children and families relies on genomics.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Emergency Medicine
Leen Alblaihed, Christine Kositz, William J. Brady, Tareq Al -Salamah, Amal Mattu
Summary: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder of the myocardium that can cause ventricular arrhythmia and sudden cardiac death. Early recognition of the disease by emergency clinicians is crucial to prevent subsequent death, as it is a significant cause of arrhythmic death among young people and athletes. This publication reviews the pathophysiology, classification, clinical presentations, and appropriate approach to diagnosis and management of ARVC.
AMERICAN JOURNAL OF EMERGENCY MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Michael P. Gannon, Mark S. Link
Summary: Hypertrophic cardiomyopathy (HCM) presents with variable clinical manifestations due to diverse genetic mutations. Animal models help study genotypic expression, protein function, and potential targeted therapies for the disease. Understanding the cascade of mutations and their functional significance can lead to the development of effective treatments.
TRENDS IN CARDIOVASCULAR MEDICINE
(2021)
Review
Medicine, General & Internal
Estefania Martinez-Barrios, Simone Grassi, Maria Brion, Rocio Toro, Sergi Cesar, Jose Cruzalegui, Monica Coll, Mireia Alcalde, Ramon Brugada, Andrea Greco, Maria Luisa Ortega-Sanchez, Eneko Barberia, Antonio Oliva, Georgia Sarquella-Brugada, Oscar Campuzano
Summary: In the field of forensic medicine, molecular autopsy is a genetic analysis performed after a comprehensive forensic autopsy to uncover the cause of death in cases that remain unexplained. This typically occurs in young individuals and is suspected to originate from an underlying inherited arrhythmogenic syndrome. Next-generation sequencing can identify potentially pathogenic rare genetic variants in up to 25% of sudden death cases in young individuals. Early identification of these pathogenic genetic alterations can help prevent malignant arrhythmias and sudden death in at-risk relatives. However, there are challenges in interpreting and translating genetic findings into clinical practice.
FRONTIERS IN MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Monica Coll, Anna Fernandez-Falgueras, Anna Iglesias, Bernat del Olmo, Laia Nogue-Navarro, Adria Simon, Alexandra Perez Serra, Marta Puigmule, Laura Lopez, Ferran Pico, Monica Corona, Marta Vallverdu-Prats, Coloma Tiron, Oscar Campuzano, Josep Castella, Ramon Brugada, Mireia Alcalde
Summary: This study examined rare intronic variants in SCD cases to determine their effect on splicing. The results showed that variants affecting canonical splice sites almost always caused aberrant splicing, but a small percentage of cases still showed normal splicing. In contrast, in silico predictions failed to accurately predict the effects, with unexpected aberrant splicing occurring in some cases. These findings suggest that deep intronic variants may have a greater impact than previously thought, highlighting the importance of accurate classification and follow-up for family members.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Juha H. Vaehaetalo, Lauri T. A. Holmstroem, Katri Pylkaes, Sini Skarp, Katja Porvari, Lasse Pakanen, Kari S. Kaikkonen, Juha S. Perkioemaeki, Risto Kerkelae, Heikki V. Huikuri, Robert J. Myerburg, M. Juhani Junttila
Summary: This study aims to investigate the genetic background of cardiac hypertrophy in sudden cardiac death (SCD) victims with single vessel coronary artery disease (CAD). The study found that rare variants associated with cardiomyopathies were common among SCD victims with single vessel disease and myocardial hypertrophy, suggesting that these variants may increase the risk for fatal arrhythmias and SCD.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Hamza El Hadi, Anne Freund, Steffen Desch, Holger Thiele, Nicolas Majunke
Summary: Cardiomyopathies are a diverse group of heart muscle disorders with potentially fatal consequences such as arrhythmias and heart failure. They are a leading cause of heart transplantation worldwide. Recent advancements in understanding the molecular basis and diagnostic evaluation have paved the way for targeted therapies. However, further research is needed to improve risk assessment and prevention strategies for sudden cardiac death.
Article
Genetics & Heredity
Alexandre Janin, Louis Januel, Cecile Cazeneuve, Antoine Deliniere, Philippe Chevalier, Gilles Millat
Summary: With a detailed molecular investigation of 4185 patients with inherited cardiac diseases, the study identified (likely) pathogenic variations in approximately 30% of the cohort, including pathogenic copy number variations in 3.1% of patients and in 21.1% of patients who died from sudden cardiac death. Unexpected variants were present in 28 cases, highlighting the clinical utility of genetic testing in guiding clinical management in inherited cardiac diseases.
MOLECULAR DIAGNOSIS & THERAPY
(2021)
Article
Cardiac & Cardiovascular Systems
C. Anwar A. Chahal, David J. Tester, Ahmed U. Fayyaz, Keerthi Jaliparthy, Nadeem A. Khan, Dongmei Lu, Mariha Khan, Aradhana Sahoo, Aiswarya Rajendran, Jennifer A. Knight, Michael A. Simpson, Elijah R. Behr, Elson L. So, Erik K. St Louis, R. Ross Reichard, William D. Edwards, Michael J. Ackerman, Virend K. Somers
Summary: This study examined a large cohort of SUDEP cases in a single-center in the United States, identifying several cases reclassified as SUDEP, with 15% having an ECG when alive and 11 (11.4%) undergoing whole exome sequencing analysis. The most frequent antemortem genetic finding was pathogenic variants in the SCN1A gene, while postmortem whole exome sequencing identified 18 ultra-rare variants.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Cardiac & Cardiovascular Systems
E. RosalieWitjas-Paalberends, Ahmet Guclu, Tjeerd Germans, Paul Knaapen, Hendrik J. Harms, Alexa M. C. Vermeer, Imke Christiaans, Arthur A. M. Wilde, Cris Dos Remedios, Adriaan A. Lammertsma, Albert C. van Rossum, Ger J. M. Stienen, Marjon van Slegtenhorst, Arend F. Schinkel, Michelle Michels, Carolyn Y. Ho, Corrado Poggesi, Jolanda van der Velden
CARDIOVASCULAR RESEARCH
(2014)
Article
Cardiac & Cardiovascular Systems
Gabriella Captur, Luis R. Lopes, Timothy J. Mohun, Vimal Patel, Chunming Li, Paul Bassett, Gherardo Finocchiaro, Vanessa M. Ferreira, Maite Tome Esteban, Vivek Muthurangu, Mark V. Sherrid, Sharlene M. Day, Charles E. Canter, William J. McKenna, Christine E. Seidman, David A. Bluemke, Perry M. Elliott, Carolyn Y. Ho, James C. Moon
CIRCULATION-CARDIOVASCULAR IMAGING
(2014)
Review
Cell Biology
Corrado Poggesi, Carolyn Y. Ho
JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY
(2014)
Article
Neurosciences
E. Rosalie Witjas-Paalberends, Claudia Ferrara, Beatrice Scellini, Nicoletta Piroddi, Judith Montag, Chiara Tesi, Ger J. M. Stienen, Michelle Michels, Carolyn Y. Ho, Theresia Kraft, Corrado Poggesi, Jolanda van der Velden
JOURNAL OF PHYSIOLOGY-LONDON
(2014)
Article
Medicine, Research & Experimental
Jason L. Vassy, Denise M. Lautenbach, Heather M. McLaughlin, Sek Won Kong, Kurt D. Christensen, Joel Krier, Isaac S. Kohane, Lindsay Z. Feuerman, Jennifer Blumenthal-Barby, J. Scott Roberts, Lisa Soleymani Lehmann, Carolyn Y. Ho, Peter A. Ubel, Calum A. MacRae, Christine E. Seidman, Michael F. Murray, Amy L. McGuire, Heidi L. Rehm, Robert C. Green
Editorial Material
Cardiac & Cardiovascular Systems
Christopher Semsarian, Carolyn Y. Ho
EUROPEAN HEART JOURNAL
(2019)
Article
Cardiac & Cardiovascular Systems
Carolyn Y. Ho, Iacopo Olivotto, Daniel Jacoby, Steven J. Lester, Matthew Roe, Andrew Wang, Cynthia Burstein Waldman, David Zhang, Amy J. Sehnert, Stephen B. Heitner
CIRCULATION-HEART FAILURE
(2020)
Editorial Material
Cardiac & Cardiovascular Systems
Carolyn Y. Ho
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
Biochemistry & Molecular Biology
Carolyn Y. Ho, Sharlene M. Day, Anna Axelsson, Mark W. Russell, Kenneth Zahka, Harry M. Lever, Alexandre C. Pereira, Steven D. Colan, Renee Margossian, Anne M. Murphy, Charles Canter, Richard G. Bach, Matthew T. Wheeler, Joseph W. Rossano, Anjali T. Owens, Henning Bundgaard, Lee Benson, Luisa Mestroni, Matthew R. G. Taylor, Amit R. Patel, Ivan Wilmot, Philip Thrush, Jose D. Vargas, Jonathan H. Soslow, Jason R. Becker, Christine E. Seidman, Neal K. Lakdawala, Allison L. Cirino, Kristin M. Burns, John J. V. McMurray, Calum A. MacRae, Scott D. Solomon, E. John Orav, Eugene Braunwald
Summary: In a randomized phase 2 clinical trial, the angiotensin receptor blocker valsartan showed promising results in improving cardiac structure and function in patients with early-stage hypertrophic cardiomyopathy, suggesting a potential safe and accessible treatment option to attenuate disease progression.
Review
Cardiac & Cardiovascular Systems
Alessia Argiro, Carolyn Ho, Sharlene M. Day, Jolanda van der Velden, Elisabetta Cerbai, Sara Saberi, Jil C. Tardiff, Neal K. Lakdawala, Iacopo Olivotto
Summary: Cardiomyopathies are diseases characterized by primary functional and structural abnormalities of the heart muscle. The most effective classification is based on the presenting phenotype. Sex modulates the prevalence, clinical manifestations, and course of cardiomyopathies. Differences in ion channel expression and left ventricular remodeling exist between male and female patients. Societal and environmental factors may also contribute to clinical differences between sexes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Cardiac & Cardiovascular Systems
Nay Aung, Luis R. Lopes, Stefan van Duijvenboden, Andrew R. Harper, Anuj Goel, Christopher Grace, Carolyn Y. Ho, William S. Weintraub, Christopher M. Kramer, Stefan Neubauer, Hugh C. Watkins, Steffen E. Petersen, Patricia B. Munroe
Summary: This study discovered 21 genetic loci associated with left ventricular maximum wall thickness (LVMWT), a biomarker for left ventricular hypertrophy. These loci have known functional roles in myocardial growth and sarcomere organization. The study also found that the genetic risk score for LVMWT is predictive of hypertrophic cardiomyopathy (HCM).
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Carmen C. Sucharov, Bonnie Neltner, Ashley E. Pietra, Anis Karimpour-Fard, Joshen Patel, Carolyn Y. Ho, Shelley D. Miyamoto
Summary: In this study, the researchers investigated whether circulating miRNAs could stratify the disease stage in sarcomeric HCM. The results showed that circulating miRNAs can differentiate healthy controls from HCM patients and differentiate clinical HCM from subclinical HCM. These findings have implications for improving the diagnosis of HCM and understanding the mechanisms underlying disease progression.
CIRCULATION-HEART FAILURE
(2023)
Review
Cardiac & Cardiovascular Systems
Wendy K. Chung, Carolyn Ho, Teresa Lee, Christine E. Seidman, Stephanie M. Ware
PROGRESS IN PEDIATRIC CARDIOLOGY
(2018)
Article
Cardiac & Cardiovascular Systems
Carolyn Y. Ho, John J. V. McMurray, Allison L. Cirino, Steven D. Colan, Sharlene M. Day, Akshay S. Desai, Steven E. Lipshultz, Callum A. MacRae, Ling Shi, Scott D. Solomon, E. John Orav, Eugene Braunwald
AMERICAN HEART JOURNAL
(2017)
