Implementing Precision Medicine for Dilated Cardiomyopathy: Insights from The DCM Consortium DOI Creative Commons
Elizabeth Jordan, Hanyu Ni, P. Parker

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

ABSTRACT Background Clinical genetic evaluation of dilated cardiomyopathy (DCM) is implemented variably or not at all. Identifying needs and barriers to evaluations will enable strategies enhance precision medicine care. Methods An online survey was conducted in June 2024 among cardiologist investigators the DCM Consortium from US advanced heart failure/transplant (HF/TX) programs collect demographics, training, program characteristics, practices for DCM, implementation needs. in-person discussion followed. Results Twenty-five cardiologists (28% female, 12% Hispanic, 68% White) participated 15 discussion; genetics training backgrounds varied greatly. testing by all with annual uptake ranging 5%-70% (median 25%). Thirteen respondents (52%) did use selection criteria whereas others selected patients based on specific clinical family history data. Eight (32%) ordered themselves, remainder had managed mostly a counselor expertise (16/17; 94%). Six themes were distilled open-ended responses regarding thoughts future included access services, navigating uncertainty, knowledge needs, cost concerns, family-based care barriers, institutional infrastructure limitations. Following an discussion, four areas identified focused effort: improved reimbursement integration HF/TX teams, provider education resources, more research find missing heritability resolve uncertain results. Conclusions have challenges provision evaluations; targeted plans facilitate are needed.

Language: Английский

Prioritizing the primary prevention of heart failure: Measuring, modifying and monitoring risk DOI Creative Commons

Ruchi Patel,

Tejasvi Peesay, Vaishnavi Krishnan

et al.

Progress in Cardiovascular Diseases, Journal Year: 2024, Volume and Issue: 82, P. 2 - 14

Published: Jan. 1, 2024

Language: Английский

Citations

9
Genomics of pediatric cardiomyopathy DOI Creative Commons
Teresa M. Lee, Stephanie M. Ware, Alicia M. Kamsheh

et al.

Pediatric Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Abstract Cardiomyopathy in children is a leading cause of heart failure and cardiac transplantation. Disease-associated genetic variants play significant role the development different subtypes disease. Genetic testing increasingly being recognized as standard care for diagnosing this heterogeneous group disorders, guiding management, providing prognostic information, facilitating family-based risk stratification. The increase clinical research within field has led to new insights into disorders. Mutations genes encoding sarcomere, cytoskeletal, Z-disk, sarcolemma proteins appear major causing overlapping phenotypes called cardioskeletal myopathies through “final common pathway” links. For myocarditis, high frequency infectious exposures wide spectrum presentation suggest that factors mediate course disease, including alleles, an association with cardiomyopathy, undiagnosed arrhythmogenic cardiomyopathy. Finally, while we have made strides elucidating architecture pediatric understanding implications uncertain significance remains issue. need continued innovation great, particularly basis drive forward targeted precision medicine gene therapy efforts. Impact skeletal myopathy can occur same patient secondary mutations encode sarcomeric or cytoskeletal proteins, which are expressed both muscle groups, highlighting there final pathways myocarditis likely complex interaction multiple environmental factors, suggesting utility patients those higher groups. Given prevalence testing, better bioinformatic tools pipelines needed resolve their meaning.

Language: Английский

Citations

1
Heart failure with improved ejection fraction: Beyond diagnosis to trajectory analysis DOI
Anthony V. Pensa, Sadiya S. Khan, Ravi V. Shah

et al.

Progress in Cardiovascular Diseases, Journal Year: 2024, Volume and Issue: 82, P. 102 - 112

Published: Jan. 1, 2024

Language: Английский

Citations

8
Pathophysiology of dilated cardiomyopathy: from mechanisms to precision medicine DOI
Marta Gigli, Davide Stolfo,

Marco Merlo

et al.

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 11, 2024

Language: Английский

Citations

5
Whole genome sequencing in early onset advanced heart failure DOI Creative Commons
Erik Linnér, Tomasz Czuba, Olof Gidlöf

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 5, 2025

Language: Английский

Citations

0
Early Phenotype Identification DOI
Karolina M. Zaręba, Ray E. Hershberger

JACC. Cardiovascular imaging, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
Leveraging Transcriptional Readouts as a Platform for Drug Repurposing in Cardiomyopathy DOI
Ahmed I. Mahmoud, Hesham A. Sadek

Circulation, Journal Year: 2025, Volume and Issue: 151(20), P. 1449 - 1450

Published: May 19, 2025

Language: Английский

Citations

0
TTN novel splice variant in familial dilated cardiomyopathy and splice variants review: a case report DOI Creative Commons

P. Ponce León,

Paula Franco,

Nicole Hinojosa

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: June 13, 2024

This case report details the identification of a novel likely pathogenic splicing variant in TTN gene, associated with dilated cardiomyopathy (DCM), 42-year-old male patient presenting early-onset heart failure and reduced ejection fraction. DCM is nonischemic condition characterized by left biventricular dilation systolic dysfunction, approximately one-third cases being familial often linked to genetic mutations. The encoding largest human protein essential for muscle contraction sarcomere structure, implicated about 25% through mutations, especially truncating variants. Our investigation revealed previously unreported G > C mutation at splice acceptor site intron 356 TTN, confirmed Sanger sequencing not found population databases, suggesting contribution understanding etiology. emphasizes critical role gene cardiac function complexity underlying DCM. A comprehensive literature review highlighted prevalence significance variants particularly those affecting titin A-band, which known its stability. variant's underscores importance screening patients DCM, offering insights into disease's transmission potential therapeutic targets. findings contribute expanding knowledge factors demonstrating necessity integrating diagnostics cardiovascular medicine. supports growing evidence linking mutations specific regions development counseling testing managing disease.

Language: Английский

Citations

2
Implementing a New Algorithm for Reinterpretation of Ambiguous Variants in Genetic Dilated Cardiomyopathy DOI Open Access
Alexandra Pérez-Serra, Rocío Toro, Estefanía Martinez-Barrios

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3807 - 3807

Published: March 29, 2024

Dilated cardiomyopathy is a heterogeneous entity that leads to heart failure and malignant arrhythmias. Nearly 50% of cases are inherited; therefore, genetic analysis crucial unravel the cause for early identification carriers at risk. A large number variants remain classified as ambiguous, impeding an actionable clinical translation. Our goal was perform comprehensive update previously with ambiguous role, applying new algorithm already available tools. In cohort 65 diagnosed dilated cardiomyopathy, total 125 were ambiguous. reanalysis resulted in reclassification 12% from unknown likely benign or pathogenic due improved population frequencies. For all remaining variants, we used our algorithm; 60.9% showed potential but not confirmed deleterious 24.5% role. Periodically updating frequencies cheap fast action, making it possible clarify role variants. Here, help most specific algorithms facilitate interpretation cardiomyopathy.

Language: Английский

Citations

1
The Role of Ventricular Assist Devices in Patients With Heart Failure Due to Dilated Cardiomyopathy: A Systematic Review DOI Open Access
Billy McBenedict, Wilhelmina N Hauwanga,

Emmanuel S Amadi

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 6, 2024

Dilated cardiomyopathy (DCM) is a prevalent heart muscle disease characterized by ventricular dilation and systolic dysfunction, leading to severe failure (HF) often requiring transplantation (HTx). This systematic review aimed synthesize information regarding the role of assist devices (VADs) in managing HF patients due DCM. A comprehensive search was conducted across PubMed, Embase, Scopus, Web Science, Cochrane databases for studies published between 2014 2024. Inclusion criteria were involving adult with DCM treated VADs. Exclusion included non-human studies, pediatric populations, non-peer-reviewed articles. Thirty-one met inclusion criteria. The demonstrated that use VADs resulted significant improvements left ejection fraction (LVEF), myocardial fibrosis reduction, reverse remodeling. Studies reported enhanced survival rates, reduced symptoms, better quality life. served as critical bridge HTx and, some cases, long-term destination therapy. However, complications such thrombus formation, anemia, kidney noted, emphasizing need vigilant monitoring management. Continuous advancements VAD technology patient management protocols found be essential optimizing outcomes. We conclude play crucial advanced providing mechanical circulatory support, improving cardiac function, enhancing Despite associated complications, are invaluable HF, offering both immediate therapeutic benefits. Future research should focus on minimizing further enhance

Language: Английский

Citations

1