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
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
Cardiac & Cardiovascular Systems
Elizabeth Jordan, Laiken Peterson, Tomohiko Ai, Babken Asatryan, Lucas Bronicki, Emily Brown, Rudy Celeghin, Matthew Edwards, Judy Fan, Jodie Ingles, Cynthia A. James, Olga Jarinova, Renee Johnson, Daniel P. Judge, Najim Lahrouchi, Ronald H. Lekanne Deprez, R. Thomas Lumbers, Francesco Mazzarotto, Argelia Medeiros Domingo, Rebecca L. Miller, Ana Morales, Brittney Murray, Stacey Peters, Kalliopi Pilichou, Alexandros Protonotarios, Christopher Semsarian, Palak Shah, Petros Syrris, Courtney Thaxton, J. Peter van Tintelen, Roddy Walsh, Jessica Wang, James Ware, Ray E. Hershberger
Summary: A systematic curation of 51 genes related to DCM revealed that 19 genes have high evidence (12 definitive/strong, 7 moderate), but these genes only explain a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed.
Review
Medicine, General & Internal
Enrica Chiti, Marco Paolo, Emanuela Turillazzi, Anna Rocchi
Summary: MiRNAs are small non-coding RNAs involved in regulating biochemical pathways in the human body; their levels can be altered due to pathophysiological mechanisms, making them potential biomarkers for cardiac diseases and other pathological conditions. This review summarizes findings of miRNA biomarkers in the three most common structural cardiomyopathies.
Article
Cardiac & Cardiovascular Systems
Fernando de Frutos, Juan Pablo Ochoa, Marina Navarro-Penalver, Annette Baas, Jesper Vandborg Bjerre, Esther Zorio, Irene Mendez, Rebeca Lorca, Job A. J. Verdonschot, Pablo Elpidio Garcia-Granja, Zofia Bilinska, Diane Fatkin, M. Eugenia Fuentes-Canamero, Jose M. Garcia-Pinilla, Maria I. Garcia-Alvarez, Francesca Girolami, Roberto Barriales-Villa, Carles Diez-Lopez, Luis R. Lopes, Karim Wahbi, Ana Garcia-Alvarez, Ibon Rodriguez-Sanchez, Javier Rekondo-Olaetxea, Jose F. Rodriguez-Palomares, Maria Gallego-Delgado, Benjamin Meder, Milos Kubanek, Frederikke G. Hansen, Maria Alejandra Restrepo-Cordoba, Julian Palomino-Doza, Luis Ruiz-Guerrero, Georgia Sarquella-Brugada, Alberto Jose Perez-Perez, Francisco Jose Bermudez-Jimenez, Tomas Ripoll-Vera, Torsten Bloch Rasmussen, Mark Jansen, Maria Sabater-Molina, Perry M. Elliot, Pablo Garcia-Pavia
Summary: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to end-stage heart failure (ESHF). Heart failure complications predominate over ventricular arrhythmias, which are rare.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Mark Hofmeyer, Garrie J. Haas, Elizabeth Jordan, Jinwen Cao, Evan Kransdorf, Gregory A. Ewald, Alanna A. Morris, Anjali Owens, Brian Lowes, Douglas Stoller, W. H. Wilson Tang, Sonia Garg, Barry H. Trachtenberg, Palak Shah, Salpy V. Pamboukian, Nancy K. Sweitzer, Matthew T. Wheeler, Jane E. Wilcox, Stuart Katz, Stephen Pan, Javier Jimenez, Frank Smart, Jessica Wang, Stephen S. Gottlieb, Daniel P. Judge, Charles K. Moore, Gordon S. Huggins, Daniel D. Kinnamon, Hanyu Ni, Ray E. Hershberger
Summary: Advanced dilated cardiomyopathy (DCM) is associated with a higher probability of pathogenic or likely pathogenic rare variants in DCM genes, which can help assess the risk of outcomes in managing DCM patients and their at-risk family members.
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
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)
Review
Cardiac & Cardiovascular Systems
Upasana Tayal, James S. Ware, Neal K. Lakdawala, Stephane Heymans, Sanjay K. Prasad
Summary: This review provides a practical primer for clinicians on the genetic basis of dilated cardiomyopathy, including the clinical relevance, key genetic concepts, which patients may benefit from genetic testing, common genetic tests performed, how to interpret genetic results, and the clinical applications. Areas for future research in this dynamic field are also discussed.
EUROPEAN HEART JOURNAL
(2021)
Review
Cardiac & Cardiovascular Systems
Upasana Tayal, James S. Ware, Neal K. Lakdawala, Stephane Heymans, Sanjay K. Prasad
Summary: This review provides a practical primer for clinicians on the genetic basis of dilated cardiomyopathy, introducing key concepts, explaining genetic testing, interpretation of results, and clinical applications, as well as highlighting areas for future research in this field.
EUROPEAN HEART JOURNAL
(2021)
Review
Biology
Paulina Langa, Sanam Shafaattalab, Paul H. Goldspink, Beata M. Wolska, Aurelia A. Fernandes, Glen F. Tibbits, R. John Solaro
Summary: We discussed the role of Notch signaling in inherited heart failure, focusing on hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) linked to mutant sarcomere proteins. Recent findings showed an upregulation of elements in the Notch signaling pathway in cardiomyocytes derived from human induced pluripotent stem cells expressing a TNNT2 variant. These findings highlight the importance of considering Notch signaling in familial cardiomyopathies.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(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
Cardiac & Cardiovascular Systems
Megan J. Puckelwartz, Lorenzo L. Pesce, Lisa M. Dellefave-Castillo, Matthew T. Wheeler, Tess D. Pottinger, Avery C. Robinson, Samuel D. Kearns, Anthony M. Gacita, Zachary J. Schoppen, Wenyu Pan, Gene Kim, Jane E. Wilcox, Allen S. Anderson, Euan A. Ashley, Sharlene M. Day, Thomas Cappola, Gerald W. Dorn, Elizabeth M. McNally
Summary: By comparing protein coding variations in the genomes of familial cases of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), it was found that individuals with DCM had more nonsynonymous single-nucleotide variants (nsSNVs) in cardiomyopathy genes. These variants were significantly associated with reduced left ventricular ejection fraction and increased left ventricular diameter in individuals with DCM, but not in those with HCM. This suggests that increased variation in cardiomyopathy genes predisposes individuals to DCM and worsens disease severity.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Medicine, General & Internal
Maurits A. Sikking, Sophie L. V. M. Stroeks, Michiel T. H. M. Henkens, Max F. G. H. M. Venner, Xiaofei Li, Stephane R. B. Heymans, Mark R. Hazebroek, Job A. J. Verdonschot
Summary: Dilated cardiomyopathy (DCM) has a genetic cause in up to 40% of cases, and the presence of cardiac inflammation is associated with a younger disease onset in genetic DCM patients. However, cardiac inflammation does not increase the risk of mortality, heart failure hospitalization, or life-threatening arrhythmias. This suggests that myocarditis may be an exogeneous trigger for DCM in patients with a genetic susceptibility or that cardiac inflammation represents an early phase of the disease.
JOURNAL OF CLINICAL MEDICINE
(2023)
