Review
Biochemistry & Molecular Biology
Jiri Bonaventura, Eva Polakova, Veronika Vejtasova, Josef Veselka
Summary: Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with complex genetic basis involving mutations in multiple genes. Patients without pathogenic variants are now believed to have non-Mendelian HCM and may have a better prognosis. Identifying the genetic basis of HCM provides opportunities for understanding disease development and potential interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Francesca Girolami, Alessia Gozzini, Eszter Dalma Palinkas, Adelaide Ballerini, Alessia Tomberli, Katia Baldini, Alberto Marchi, Mattia Zampieri, Silvia Passantino, Giulio Porcedda, Giovanni Battista Calabri, Elena Bennati, Gaia Spaziani, Lia Crotti, Franco Cecchi, Silvia Favilli, Iacopo Olivotto
Summary: Genetic counselling and testing are crucial in diagnosing and managing hypertrophic cardiomyopathy (HCM), enabling personalized treatment strategies and family cascade testing. The complexity of interpreting genetic data, especially with Next Generation Sequencing technologies, necessitates collaboration between cardiologists and geneticists to accurately evaluate the pathogenicity of identified genetic alterations. Effective communication between the team and families is essential for delivering the full potential of genetic testing in HCM patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Cardiac & Cardiovascular Systems
Katherine Chiswell, Louisa Zaininger, Christopher Semsarian
Summary: Studies in the past 30 years have revealed the genetic basis of hypertrophic cardiomyopathy (HCM), leading to advancements in precision medicine through genetic testing and therapy. These advancements have improved diagnosis, risk stratification, and prognosis. Recent research has also provided insights into non-Mendelian inheritance and the development of polygenic risk scores, paving the way for future gene therapy research.
PROGRESS IN CARDIOVASCULAR DISEASES
(2023)
Review
Cardiac & Cardiovascular Systems
Fergus Stafford, Kate Thomson, Alexandra Butters, Jodie Ingles
Summary: Our understanding of the genetic basis and molecular pathogenesis of hypertrophic cardiomyopathy (HCM) is continuously evolving, with recent advances in genetic testing showing the presence of important HCM sub-groups. Genetic testing has emerged as a valuable tool for cascade genetic testing and may play a significant role in prognosis and patient management in the future. Genotype may potentially enhance risk stratification, management, treatment, and prognosis in HCM, leading to improved outcomes for patients and their families.
CURRENT CARDIOLOGY REPORTS
(2021)
Article
Cardiac & Cardiovascular Systems
Julie Hathaway, Krista Helio, Inka Saarinen, Jonna Tallila, Eija H. Seppala, Sari Tuupanen, Hannu Turpeinen, Tiia Kangas-Kontio, Jennifer Schleit, Johanna Tommiska, Ville Kytola, Miko Valori, Mikko Muona, Johanna Sistonen, Massimiliano Gentile, Pertteli Salmenpera, Samuel Myllykangas, Jussi Paananen, Tero-Pekka Alastalo, Tiina Helio, Juha Koskenvuo
Summary: The diagnostic yield of genetic testing in a heterogeneous cohort of patients with a clinical suspicion of HCM is lower than what has been reported in well-characterized patient cohorts. High diagnostic variants in the RASopathy genes were identified in this study.
BMC CARDIOVASCULAR DISORDERS
(2021)
Article
Biochemistry & Molecular Biology
Giovanna Gallo, Vittoria Mastromarino, Giuseppe Limongelli, Giulio Calcagni, Antonello Maruotti, Luca Ragni, Fabio Valente, Maria Beatrice Musumeci, Rachele Adorisio, Marta Rubino, Camillo Autore, Damiano Magri
Summary: The CPET assessment in pediatric HCM patients provides a true estimation of functional capacity and may be helpful in early identification of high-risk patients. Patients with worse CPET profiles were more likely to experience composite endpoint events, with peak oxygen uptake being strongly associated with adverse events during follow-up.
Review
Clinical Neurology
Gian Pal, Lola Cook, Jeanine Schulze, Jennifer Verbrugge, Roy N. Alcalay, Marcelo Merello, Carolyn M. Sue, Soraya Bardien, Vincenzo Bonifati, Sun Ju Chung, Tatiana Foroud, Emilia Gatto, Anne Hall, Nobutaka Hattori, Tim Lynch, Karen Marder, Deborah Mascalzoni, Ivana Novakovic, Avner Thaler, Deborah Raymond, Mehri Salari, Ali Shalash, Oksana Suchowersky, Niccolo E. Mencacci, Tanya Simuni, Rachel Saunders-Pullman, Christine Klein
Summary: Testing for genetic markers in Parkinson's disease is increasingly common, and although there are no proven gene-targeted therapies, clinical trials are underway. However, there is a lack of consensus and guidelines in genetic testing practices, and various gaps and controversies need to be addressed, including appropriateness of testing, variation based on ethnicity, long-term outcomes, and resource needs.
MOVEMENT DISORDERS
(2023)
Article
Genetics & Heredity
Andrew R. Harper, Anuj Goel, Christopher Grace, Kate L. Thomson, Steffen E. Petersen, Xiao Xu, Adam Waring, Elizabeth Ormondroyd, Christopher M. Kramer, Carolyn Y. Ho, Stefan Neubauer, Rafik Tadros, James S. Ware, Connie R. Bezzina, Martin Farrall, Hugh Watkins
Summary: The study identified 12 genome-wide significant susceptibility loci for HCM, showing a strong polygenic influence, especially for sarcomere-negative HCM. A genetic risk score influenced the odds of HCM and phenotypic severity in carriers of sarcomere variants. Mendelian randomization identified diastolic blood pressure as a key modifiable risk factor for sarcomere-negative HCM.
Article
Oncology
Jiaqi Dai, Tao Wang, Ke Xu, Yang Sun, Zongzhe Li, Peng Chen, Hong Wang, Dongyang Wu, Yanghui Chen, Lei Xiao, Hao Liu, Haoran Wei, Rui Li, Liyuan Peng, Ting Yu, Yan Wang, Zhongsheng Sun, Dao Wen Wang
Summary: Previous studies have identified differences in symptom severity and prognosis among patients with hypertrophic cardiomyopathy (HCM), suggesting the presence of potential HCM subtypes. In this study, consensus clustering was performed on echocardiography features of 793 HCM patients to identify potential subtypes. Machine learning modeling and interactome network detection techniques were used to explore the relationship between phenotype and genotype based on whole-exome sequencing data. Two subtypes were identified: subtype 2 characterized by stable course with asymmetric septal hypertrophy, and subtype 1 characterized by aggressive progression and left ventricular systolic dysfunction. Machine learning modeling based on personal whole-exome data accurately predicted subtype propensities using 46 genes with high mutation burden. Another cohort replicated the findings, showing increased left ventricular end-diastolic diameter and reduced ejection fraction in patients predicted as subtype 1. Echocardiography and genetic screening for the 46 genes can be used to classify HCM into two subtypes with distinct clinical outcomes.
FRONTIERS OF MEDICINE
(2023)
Article
Oncology
Veda N. Giri, Todd M. Morgan, David S. Morris, Jacob E. Berchuck, Colette Hyatt, Mary-Ellen Taplin
Summary: Inherited genetic mutations are closely associated with the risk of prostate cancer, and germline genetic testing plays an important role in determining treatment options and screening high-risk populations. Primary care is a critical field for clinicians to evaluate high-risk patients, individuals with prostate cancer, and survivors who may require germline genetic testing.
CA-A CANCER JOURNAL FOR CLINICIANS
(2022)
Article
Genetics & Heredity
Lola Cook, Jennifer Verbrugge, Tae-Hwi Schwantes-An, Jeanine Schulze, James C. Beck, Anna Naito, Anne Hall, Amanda K. Chan, Cynthia J. Casaceli, Karen Marder, Martha Nance, Michael A. Schwarzschild, Tanya Simuni, Anne-Marie Wills, Roy N. Alcalay
Summary: The purpose of this study was to assess the feasibility and impact of genetic testing and counseling for patients with Parkinson's disease (PD), with the potential to participate in gene-targeted clinical trials and improve clinical care. The results showed no significant differences in outcomes between local and remote sites, with both groups reporting high knowledge and satisfaction scores (>80%). It is urgent to increase access to PD genetic testing and counseling, which can inform future efforts to integrate them into clinical care for all PD patients.
GENETICS IN MEDICINE
(2023)
Review
Genetics & Heredity
Allison L. Cirino, Stephanie L. Harris, Andrea M. Murad, Brittany Hansen, Jennifer Malinowski, Jaime L. Natoli, Melissa A. Kelly, Susan Christian
Summary: This systematic review and meta-analysis examines the uptake and utility of genetic counseling and genetic testing for patients with hypertrophic cardiomyopathy (HCM) and their at-risk family members, as well as the impact on patient-reported outcomes (PROs). The findings suggest that approximately half to three-quarters of patients with HCM and their relatives undergo genetic testing or cascade screening. The results of PROs varied after genetic testing, but genetic counseling was associated with high satisfaction and improved PROs.
JOURNAL OF GENETIC COUNSELING
(2022)
Review
Cardiac & Cardiovascular Systems
Amy R. Kontorovich
Summary: Patients and families benefit from a multidisciplinary approach, including genetic counseling and genetic testing, to identify the genetic causes of cardiomyopathy. Genetic testing is most effective when performed on individuals with clear symptoms and targets specific genes associated with the specific form of cardiomyopathy. Variants of uncertain significance are common and should be interpreted with caution. Identifying impactful genetic variants can have important prognostic implications and aid in testing at-risk relatives. Personalized treatment approaches may be necessary based on specific genotypes and associated risk factors.
JACC-HEART FAILURE
(2023)
Review
Cardiac & Cardiovascular Systems
Tiago Rodrigues, Sofia Cavaco Raposo, Dulce Brito, Luis R. Lopes
Summary: This study systematically reviewed the role of exercise testing for prognostic stratification in hypertrophic cardiomyopathy patients. The main predictors of outcomes were abnormal heart rate recovery, abnormal blood pressure response, exercise-induced wall motion abnormalities, lower peak VO2, higher VE/VCO2, and pulmonary hypertension/exercise-induced pulmonary hypertension. Further investigation is needed to determine if exercise testing adds independent value to current risk stratification strategies.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2021)
Article
Health Care Sciences & Services
Kelly E. Ormond, Maia J. Borensztein, Miranda L. G. Hallquist, Adam H. Buchanan, William Andrew Faucett, Holly L. Peay, Maureen E. Smith, Eric P. Tricou, Wendy R. Uhlmann, Karen E. Wain, Curtis R. Coughlin
Summary: The research identified core concepts essential for informed consent for genetic testing through an expert consensus process, including the voluntary nature of testing, test recommendations and results, family impact, and potential risks.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Cardiac & Cardiovascular Systems
Iacopo Olivotto, James E. Udelson, Maurizio Pieroni, Claudio Rapezzi
Summary: Heart failure with preserved ejection fraction (HFpEF) is a major cause of cardiac morbidity and mortality, driven by aging populations and comorbidities. HFpEF is a complex condition involving cardiac remodeling, peripheral circulation, and various comorbidities. However, a subset of HFpEF is caused by specific genetic myocardial diseases, which can be targeted by innovative treatments. The prompt recognition of these genetic causes can significantly improve clinical practice and outcomes for HFpEF patients.
EUROPEAN HEART JOURNAL
(2023)
Editorial Material
Genetics & Heredity
Caroline F. Wright, David R. FitzPatrick, James S. Ware, Heidi L. Rehm, Helen V. Firth
GENETICS IN MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Edgar T. Hoorntje, Charlotte Burns, Luisa Marsili, Ben Corden, Victoria N. Parikh, Gerard J. te Meerman, Belinda Gray, Ahmet Adiyaman, Richard D. Bagnall, Daniela Q. C. M. Barge-Schaapveld, Maarten P. van den Berg, Marianne Bootsma, Laurens P. Bosman, Gemma Correnti, Johan Duflou, Ruben N. Eppinga, Diane Fatkin, Michael Fietz, Eric Haan, Jan D. H. Jongbloed, Arnaud D. Hauer, Lien Lam, Freyja H. M. van Lint, Amrit Lota, Carlo Marcelis, Hugh J. McCarthy, Anneke M. van Mil, Rogier A. Oldenburg, Nicholas Pachter, R. Nils Planken, Chloe Reuter, Christopher Semsarian, Jasper J. van der Smagt, Tina Thompson, Jitendra Vohra, Paul G. A. Volders, Jaap I. van Waning, Nicola Whiffin, Arthur van den Wijngaard, Ahmad S. Amin, Arthur A. M. Wilde, Gijs van Woerden, Laura Yeates, Dominica Zentner, Euan A. Ashley, Matthew T. Wheeler, James S. Ware, J. Peter van Tintelen, Jodie Ingles
Summary: This study investigated the clinical characteristics, genotype, and genetics of arrhythmogenic cardiomyopathy caused by truncating variants in the desmoplakin gene (DSPtv). The results showed that the location of DSPtv and individual disease status were independent risk factors for ventricular arrhythmia. Furthermore, the study found that disease-associated gene variants were more likely to occur in important regions of the DSP gene compared to the control group. This study highlights the importance of gene variants in arrhythmogenic cardiomyopathy and provides critical insights for clinical management.
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(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.
Article
Cardiac & Cardiovascular Systems
Domenico Filomena, Bert Vandenberk, Tom Dresselaers, Rik Willems, Johan Van Cleemput, Iacopo Olivotto, Tomas Robyns, Jan Bogaert
Summary: This study aimed to evaluate the presence and frequency of papillary muscle (PM) displacement in different phenotypes of hypertrophic cardiomyopathy (HCM). The study found that PM displacement was most common in the apical HCM group, followed by the mixed HCM and septal HCM groups. There appears to be a potential pathogenetic and mechanical link between apical PM displacement and apical HCM.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
(2023)
Article
Cardiac & Cardiovascular Systems
Giacomo Tini, Maddalena Graziosi, Beatrice Musumeci, Mattia Targetti, Domitilla Russo, Vanda Parisi, Alessia Argiro, Raffaello Ditaranto, Ornella Leone, Camillo Autore, Iacopo Olivotto, Elena Biagini
Summary: Diagnosis of arrhythmogenic cardiomyopathy (ACM) is often delayed, especially in cases involving left ventricular (LV) involvement, and this delay is associated with increased mortality at follow-up. The most common initial misdiagnoses are dilated cardiomyopathy, myocarditis, and idiopathic ventricular arrhythmia.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Rachel Lampert, Michael J. Ackerman, Bradley S. Marino, Matthew Burg, Barbara Ainsworth, Lisa Salberg, Maria Teresa Tome Esteban, Carolyn Y. Ho, Roselle Abraham, Seshadri Balaji, Cheryl Barth, Charles I. Berul, Martijn Bos, David Cannom, Lubna Choudhury, Maryann Concannon, Robert Cooper, Richard J. Czosek, Anne M. Dubin, James Dziura, Benjamin Eidem, Michael S. Emery, N. A. Mark Estes, Susan P. Etheridge, Jeffrey B. Geske, Belinda Gray, Kevin Hall, Kimberly G. Harmon, Cynthia A. James, Ashwin K. Lal, Ian H. Law, Fangyong Li, Mark S. Link, William J. McKenna, Silvana Molossi, Brian Olshansky, Steven R. Ommen, Elizabeth V. Saarel, Sara Saberi, Laura Simone, Gordon Tomaselli, James S. Ware, Douglas P. Zipes, Sharlene M. Day
Summary: This study aimed to determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with hypertrophic cardiomyopathy (HCM). The findings showed that individuals exercising vigorously did not have a higher rate of death or life-threatening arrhythmias compared to those exercising moderately or those who were sedentary. These results may provide useful information for discussions between patients and their doctors regarding exercise participation.
Article
Medicine, General & Internal
Niccolo Maurizi, Chiara Chiriatti, Carlo Fumagalli, Mattia Targetti, Silvia Passantino, Panagiotis Antiochos, Ioannis Skalidis, Chiara Chiti, Giulia Biagioni, Alessia Tomberli, Sara Giovani, Raffaele Coppini, Franco Cecchi, Iacopo Olivotto
Summary: Disopyramide has been found to be effective in reducing left ventricular outflow obstruction (LVOTO) and improving symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM). However, its real-world use and patient characteristics associated with a positive treatment response remain unclear. This study aimed to address these issues and found that disopyramide had a good treatment effect and a high level of safety in mildly symptomatic patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, General & Internal
Francesca Girolami, Alessia Gozzini, Eszter Dalma Palinkas, Adelaide Ballerini, Alessia Tomberli, Katia Baldini, Alberto Marchi, Mattia Zampieri, Silvia Passantino, Giulio Porcedda, Giovanni Battista Calabri, Elena Bennati, Gaia Spaziani, Lia Crotti, Franco Cecchi, Silvia Favilli, Iacopo Olivotto
Summary: Genetic counselling and testing are crucial in diagnosing and managing hypertrophic cardiomyopathy (HCM), enabling personalized treatment strategies and family cascade testing. The complexity of interpreting genetic data, especially with Next Generation Sequencing technologies, necessitates collaboration between cardiologists and geneticists to accurately evaluate the pathogenicity of identified genetic alterations. Effective communication between the team and families is essential for delivering the full potential of genetic testing in HCM patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, General & Internal
Gaia Spaziani, Francesca Bonanni, Francesca Girolami, Elena Bennati, Giovanni Battista Calabri, Chiara Di Filippo, Giulio Porcedda, Silvia Passantino, Stefano Nistri, Iacopo Olivotto, Silvia Favilli
Summary: This study compared the diagnostic performance of the newly introduced Q-score with the traditional Z-score in pediatric patients with bicuspid aortic valve (BAV). The results showed that ascending aorta dilation was more common in isolated BAV patients, but less common in BAV patients associated with aortic coarctation (CoA). Dilation was related to the presence and degree of aortic stenosis, but not to aortic regurgitation. The traditional nomograms may overestimate the prevalence of aortic dilation in children.
Article
Cardiac & Cardiovascular Systems
Valentina Quintero Santofimio, Adam Clement, Declan P. O'Regan, James S. Ware, Kathryn A. McGurk
Summary: Study finds that spinal curvature in patients with scoliosis affects cardiac function and increases the risk of cardiovascular events, such as heart failure and atrial fibrillation. These findings have important clinical implications for the management of scoliosis patients.
Article
Cardiac & Cardiovascular Systems
Matteo Beltrami, Elisa Fedele, Carlo Fumagalli, Francesco Mazzarotto, Francesca Girolami, Cecilia Ferrantini, Raffaele Coppini, Lorenzo Tofani, Bruno Bertaccini, Corrado Poggesi, Iacopo Olivotto
Summary: This study found that hypertrophic cardiomyopathy patients with MYBPC3 and MYH7 mutations showed differences in cardiac systolic function. MYBPC3 patients had a significant decline in systolic function during follow-up and a higher prevalence of severe systolic dysfunction. However, there were no significant differences between the two groups in other outcomes such as atrial fibrillation and heart failure.
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2023)
Article
Geriatrics & Gerontology
Carlo Fumagalli, Martina Smorti, Lucia Ponti, Francesca Pozza, Alessia Argiro, Giacomo Credi, Carlo Di Mario, Raffaele Marfella, Niccolo Marchionni, Iacopo Olivotto, Federico Perfetto, Andrea Ungar, Francesco Cappelli
Summary: The aim of this study was to investigate frailty and the quality of the caregiver relationship in older patients with transthyretin cardiac amyloidosis (ATTR-CA). The study found that 10% of patients were frail and 46% had depressive symptoms. Regression analyses showed that frailty and depression were associated with poorer perception of social support, and frailty and disease severity were associated with higher levels of conflict in the caregiver relationship. Overall, frailty was associated with worse perceived social support and caregiver relationship quality. Tertiary care heart failure clinics should actively support the patient-caregiver relationship to improve quality of life.
AGING CLINICAL AND EXPERIMENTAL RESEARCH
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Stephan A. C. Schoonvelde, Claudine W. B. Ruijmbeek, Judith M. A. Verhagen, Debby M. E. I. Hellebrekers, Marcel J. M. Kofflard, Michelle Michels, Alexander Hirsch
Summary: This case report presents three siblings with a pathogenic variant of the mitochondrially encoded tRNA isoleucine (MT-TI) gene, causing left ventricular hypertrophy (LVH). Cardiac MRI revealed a distinctive cardiac phenotype, including extensive LVH and decreased ejection fraction.
RADIOLOGY-CARDIOTHORACIC IMAGING
(2023)