Relevant Publications
Title: Gene Therapy in Cardiovascular Disease: Recent Advances and Future Directions in Science: A Science Advisory From the American Heart Association
Background/Objective: Cardiovascular disease remains the foremost cause of morbidity and mortality globally, affecting millions of individuals. Recent discoveries illuminate the substantial role of genetics in cardiovascular disease pathogenesis, encompassing both monogenic and polygenic mechanisms and identifying tangible targets for gene therapies.
Authors: Yuri Kim, Andrew P Landstrom, Svati H Shah, Joseph C Wu, Christine E Seidman, American Heart Association
Title: Interpreting Incidentally Identified Variants in Genes Associated With Heritable Cardiovascular Disease: A Scientific Statement From the American Heart Association
Background/Objective: Rapid advances in genetic technologies have led to expanding use of diagnostic, research, and direct-to-consumer exome and genome sequencing. Incidentally identified variants from this sequencing represent a significant and growing challenge to interpret and translate into clinical care and include variants in genes associated with heritable cardiovascular disease such as cardiac ion channelopathies, cardiomyopathies, thoracic aortic disease, dyslipidemias, and congenital/structural heart disease.
Authors: Andrew P. Landstrom, Anwar A. Chahal, Michael J. Ackerman, Sharon Cresci, Dianna M. Milewicz, Alanna A. Morris, Georgia Sarquella-Brugada, Christopher Semsarian, Svati H. Shah, Amy C. Sturm
Link: https://www.ahajournals.org/doi/10.1161/HCG.0000000000000092
Title: Genetic Testing for Heritable Cardiovascular Diseases in Pediatric Patients: A Scientific Statement From the American Heart Association
Background/Objective: Genetic diseases that affect the cardiovascular system are relatively common and include cardiac channelopathies, cardiomyopathies, aortopathies, hypercholesterolemias, and structural diseases of the heart and great vessels. The rapidly expanding availability of clinical genetic testing leverages decades of research into the genetic origins of these diseases, helping inform diagnosis, clinical management, and prognosis.
Authors: Andrew P Landstrom, Jeffrey J Kim, Bruce D Gelb, Benjamin M Helm, Prince J Kannankeril, Christopher Semsarian, Amy C Sturm, Martin Tristani-Firouzi, Stephanie M Ware; American Heart Association Council on Genomic and Precision Medicine; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Arteriosclerosis, Thrombosis and Vascular Biology; and Council on Lifestyle and Cardiometabolic Health
Title: Genes Associated With Hypertrophic Cardiomyopathy: A Reappraisal by the ClinGen Hereditary Cardiovascular Disease Gene Curation Expert Panel
Background/Objective: Hypertrophic cardiomyopathy (HCM) is an inherited cardiac condition affecting ∼1 in 500 and exhibits marked genetic heterogeneity. Previously published in 2019, 57 HCM-associated genes were curated providing the first systematic evaluation of gene-disease validity.
Authors: Sophie Hespe, Amber Waddell, Babken Asatryan, Emma Owens, Courtney Thaxton, Mhy-Lanie Adduru, Kailyn Anderson, Emily E Brown, Lily Hoffman-Andrews, Elizabeth Jordan, Katherine Josephs, Megan Mayers, Stacey Peters, Fergus Stafford, Richard D Bagnall, Lucas Bronicki, Bert Callewaert, C Anwar A Chahal, Cynthia A James, Olga Jarinova, Andrew P Landstrom, Elizabeth M McNally, Brittney Murray, Laura Muiño-Mosquera, Victoria Parikh, Chloe Reuter, Roddy Walsh, Bess Wayburn, James S Ware, Jodie Ingles
Title: Pathogenicity Assignment of Variants in Genes Associated With Cardiac Channelopathies Evolve Toward Diagnostic Uncertainty
Background/Objective: Accurately determining variant pathogenicity is critical in the diagnosis of cardiac channelopathies; however, it remains unknown how variant pathogenicity status changes over time. Our aim is to use a comprehensive analysis of ClinVar to understand the mutability of variant evaluation in channelopathy-associated genes to inform clinical decision-making around variant calling.
Authors: Michael B Rosamilia, Isa M Lu, Andrew P Landstrom
Title: Integrating clinical genetics in cardiology: Current practices and recommendations for education
Background/Objective: Recent advances in genetics can facilitate the identification of at-risk individuals and diagnosis of cardiovascular disorders. As a nascent field, more research is needed to optimize the clinical practice of cardiovascular genetics, including the assessment of educational needs to promote appropriate use of genetic testing.
Authors: Courtney L. Scherr, Kerstin Kalke, Sanjana Ramesh, Hoda Fakhari, Lisa M. Dellefave-Castillo, Maureen E. Smith, Callie Kalny, Elizabeth M. McNally, Laura J. Rasmussen-Torvik
Link: https://www.gimjournal.org/article/S1098-3600(22)00649-9/fulltext
Title: Addressing Cross-Specialty Clinical Genetics Education Needs
Background/Objective: Advances in genomics are transforming clinical practice, but there are too few genetics professionals to meet increasing demand. Moreover, many nongeneticist clinicians feel unprepared to incorporate genetics into practice. This study assessed clinicians’ unmet genomics educational needs at a single academic institution.
Authors: Karla J. Lindquist, Matthew J. Ryan, Maren T. Scheuner, Bani Tamraz, Elena Flowers, Julie Harris-Wai, Sawona Biswas, Katherine Hyland
Title: Implementation of genetic testing for heritable cardiac conditions: A scoping review
Background/Objective: Identify themes and knowledge gaps about the current state of cardiovascular genetic testing implementation from the nongenetics clinician’s perspective.
Authors: Ana Morales, Jessica Goehringer, Paige L. McDonald, Despina Sanoudou
Link: https://www.sciencedirect.com/science/article/pii/S2949774425014803?via%3Dihub
Title: Cardiomyopathy genetic testing: insights into demographics, counseling, and cascade screening
Background/Objective: Genetic testing (GT) is clinically indicated for patients with suspected inherited cardiomyopathy (CM) but is underutilized.
Authors: Quan M Bui, Elizabeth Silver, Alessia Argiro, Sarah Murray, Lauren Korty, Jorge Silva Enciso, Marcus A Urey, Neil C Chi, Kimberly N Hong, Eric D Adler
Title: Genetic Testing Practices and Pathological Assessments in Patients With End-stage Heart Failure Undergoing Heart Transplantation and Left Ventricular Assist Device Use
Background/Objective: Genetic cardiomyopathies (CMs) are increasingly recognized as causes of end-stage heart failure (ESHF). Identification of a genetic etiology in ESHF has important prognostic and family implications. However, genetic testing practices are understudied in patients with ESHF.
Authors: Elizabeth Silver, Alessia Argiro, Sarah S Murray, Lauren Korty, Grace Lin, Victor Pretorius, Marcus A Urey, Kimberly N Hong, Eric D Adler, Quan M Bui
Title: Direct-to-Consumer Genetic Testing for Cardiovascular Disease: A Scientific Statement From the American Heart Association
Background/Objective: Despite insufficient evidence to support direct-to-consumer genetic testing in routine clinical care, cardiovascular clinicians increasingly face questions about its utility and interpretation because individuals can purchase these tests directly from laboratories. A burgeoning marketplace offers an expanding array of testing options.
Authors: Leland E Hull, Aaron W Aday, Quan M Bui, Jasmine A Luzum, James M Muchira, Hannah Wand, C Anwar A Chahal, Mina K Chung, Anne E Kwitek, Silvana Molossi, Pradeep Natarajan; American Heart Association Data Science and Precision Medicine Committee of the Council on Genomic and Precision Medicine and Council of Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease
Title: Patient Perspectives on Genetic Testing in Transthyretin Amyloid Cardiomyopathy: Framing the Conversation to Improve Implementation
Background/Objective: Genetic testing is recommended in the evaluation of transthyretin amyloid cardiomyopathy (ATTR-CM) with the goal of improving diagnosis and facilitating cascade genetic testing of at-risk family members. This has become increasingly important with the availability of targeted therapeutics. However, utilization of genetic testing in ATTR-CM has been slow.
Authors: Quan M. Bui, Jocelyn S. Thompson, Taylor Berninger, Kimberly N. Hong, Cheryl Anderson, Larry A. Allen, Eric D. Adler, Marcus A. Urey, Cinnamon Bloss, Borsika A. Rabin
Link: https://www.onlinejcfi.org/article/S3050-6611(25)00003-6/fulltext
Title: The Genetic Evaluation of Dilated Cardiomyopathy
Background/Objective: Dilated cardiomyopathy (DCM) is a common cause of heart failure and is the primary indication for heart transplantation. A genetic etiology can be found in 20-35% of patients with DCM, especially in those with a family history of cardiomyopathy or sudden cardiac death at an early age.
Authors: Quan M Bui, Jeffrey Ding, Kimberly N Hong, Eric A Adler
Title: Integration of genetic testing into diagnostic pathways for cardiomyopathies: a clinical consensus statement by the ESC Council on Cardiovascular Genomics
Background/Objective: In the modern era, cardiologists managing patients and families with cardiomyopathies need to be familiar with every stage of the diagnostic pathway from clinical phenotyping to the prescription and interpretation of genetic tests. This clinical consensus statement from the ESC Council for Cardiovascular Genomics aims to promote the integration of genetic testing into routine cardiac care of patients with cardiomyopathies, as recommended in the 2023 ESC guidelines for cardiomyopathies.
Authors: Perry Elliott, Heribert Schunkert, Antoine Bondue, Elijah Behr, Lucie Carrier, Cornelia Van Duijn, Pablo García-Pavía, Pim van der Harst, Maryam Kavousi, Bart Loeys, Luis Rocha Lopes, Yigal Pinto, Alessandro Di Toro, Thomas Thum, Stefan Kääb, Mario Urtis, Eloisa Arbustini
Link: https://academic.oup.com/eurheartj/article/46/4/344/7915804#google_vignette
Title: European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases
Background/Objective: Addresses essential principles of genetic testing including modes of inheritance, different testing methodologies, and interpretation of variants. Additionally, the document presents the state of genetic testing for inherited arrhythmia syndromes, cardiomyopathies, sudden cardiac death (SCD), congenital heart disease(CHD), coronary artery disease, and heart failure.
Authors: Arthur A M Wilde, Christopher Semsarian, Manlio F Márquez, Alireza Sepehri Shamloo, Michael J Ackerman, Euan A Ashley, Eduardo Back Sternick, Héctor Barajas-Martinez, Elijah R Behr, Connie R Bezzina, Jeroen Breckpot, Philippe Charron, Priya Chockalingam, Lia Crotti, Michael H Gollob, Steven Lubitz, Naomasa Makita, Seiko Ohno, Martín Ortiz-Genga, Luciana Sacilotto, Eric Schulze-Bahr, Wataru Shimizu, Nona Sotoodehnia, Rafik Tadros, James S Ware, David S Winlaw, Elizabeth S Kaufman
Title: Is it time for a paradigm shift? Inclusion of APOE on genetic dyslipidemia panels
Background/Objective: APOE codes for apolipoprotein E (ApoE), which plays an important role in lipid and lipoprotein metabolism and homeostasis of tissue lipid content. Several variants in APOE have been associated with inherited dyslipidemias, and a subsequent increased risk of developing premature coronary artery disease (CAD).
Authors: Hannah E Ison, Mohammad Mowaswes, Ronen Durst, Thorsten Leucker, Joshua W Knowles, Emily E Brown
Title: Primary care providers’ perspectives on receiving opportunistic genomic results from a national study: The Million Veteran Program Return Of Actionable Results (MVP-ROAR) Study
Background/Objective: Patients are increasingly obtaining genetic health information and integrating it into their care with the help of their primary care provider (PCP). However, PCPs may not be adequately prepared to effectively utilize genetic results. Across the Veterans Health Administration health system, the Million Veteran Program Return Of Actionable Results-Familial Hypercholesterolemia (MVP-ROAR-FH) Study clinically confirms and returns genetic results associated with familial hypercholesterolemia (FH), identified in a national biobank program.
Authors: Anna L Johannsen, Morgan E Danowski, Kailyn E Sitter, Charlene L Preys, Haley L Gerety, Charles A Brunette, Kurt D Christensen, J Michael Gaziano, Joshua W Knowles, Sumitra Muralidhar, Amy C Sturm, Yan V Sun, Stacey B Whitbourne, Thomas Yi, VA Million Veteran Program, Jason L Vassy
Title: Development and utility of a clinical research informatics application for participant recruitment and workflow management for a return of results pilot trial in familial hypercholesterolemia in the Million Veteran Program
Background/Objective: The development of clinical research informatics tools and workflow processes associated with re-engaging biobank participants has become necessary as genomic repositories increasingly consider the return of actionable research results.
Authors: Charles A Brunette, Thomas Yi, Morgan E Danowski, Mark Cardellino, Alicia Harrison, Themistocles L Assimes, Joshua W Knowles, Kurt D Christensen, Amy C Sturm, Yan V Sun, Qin Hui, Saiju Pyarajan, Yunling Shi, Stacey B Whitbourne, J Michael Gaziano, Sumitra Muralidhar, Jason L Vassy
Title: Design and pilot results from the Million Veteran Program Return Of Actionable Results (MVP-ROAR) Study
Background/Objective: As a mega-biobank linked to a national healthcare system, the Million Veteran Program (MVP) can directly improve the health care of participants. To determine the feasibility and outcomes of returning medically actionable genetic results to MVP participants, the program launched the MVP Return of Actionable Results (MVP-ROAR) Study, with familial hypercholesterolemia (FH) as an exemplar actionable condition.
Authors: Jason L Vassy, Charles A Brunette, Thomas Yi, Alicia Harrison, Mark P Cardellino, Themistocles L Assimes, Kurt D Christensen, Poornima Devineni, J Michael Gaziano, Xin Gong, Qin Hui, Joshua W Knowles, Sumitra Muralidhar, Pradeep Natarajan, Saiju Pyarajan, Mary Gavin Sears, Yunling Shi, Amy C Sturm, Stacey B Whitbourne, Yan V Sun, Morgan E Danowski; Million Veteran Program