Risk of Sudden Death in Patients With RASopathy Hypertrophic Cardiomyopathy.

Autor:	Lynch A; Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto Ontario, Canada., Tatangelo M; Ted Rogers Computational Program, Ted Rogers Centre for Heart Research, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada., Ahuja S; Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada., Steve Fan CP; Ted Rogers Computational Program, Ted Rogers Centre for Heart Research, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada., Min S; Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada., Lafreniere-Roula M; Applied Health Research Centre, St Michael's Hospital of Unity Health Toronto, Toronto, Ontario, Canada., Papaz T; Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada; Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada., Zhou V; Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada., Armstrong K; Department of Pediatrics, BC Children's Hospital, Vancouver, British Columbia, Canada., Aziz PF; Department of Pediatrics, Cleveland Clinic Children's Hospital, Cleveland, Ohio, USA., Benson LN; Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto Ontario, Canada., Butts R; Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas, USA., Dragulescu A; Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto Ontario, Canada., Gardin L; Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada., Godown J; Department of Pediatrics, Monroe Carrell Jr Children's Hospital at Vanderbilt University, Nashville, Tennessee, USA., Jeewa A; Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto Ontario, Canada., Kantor PF; Department of Pediatrics, Children's Hospital of Los Angeles, Los Angeles, California, USA., Kaufman BD; Department of Pediatrics, Lucile Packard Children's Hospital, Stanford University, Palo Alto, California, USA., Lal AK; Department of Pediatrics, Primary Children's Hospital, University of Utah, Salt Lake City, Utah, USA., Parent JJ; Department of Pediatrics, Riley Children's Hospital, Indianapolis, Indiana, USA., Richmond M; Department of Pediatrics, Morgan Stanley Children's Hospital, Columbia University Medical Center, New York, New York, USA., Russell MW; Department of Pediatrics, University of Michigan Health System, Ann Arbor, Michigan, USA., Balaji S; Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA., Stephenson EA; Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto Ontario, Canada., Villa C; Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, Ohio, USA., Jefferies JL; Department of Pediatrics, University of Tennessee Health Sciences Centre, Memphis, Tennessee, USA., Whitehill R; Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, Georgia, USA., Conway J; Department of Pediatrics, Stollery Children's Hospital, Edmonton, Alberta, Canada., Howard TS; Department of Pediatrics, Texas Children's Hospital, Houston, Texas, USA., Nakano SJ; Department of Pediatrics, Children's Hospital Colorado, Aurora, Colorado, USA., Rossano J; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA., Weintraub RG; Department of Cardiology, The Royal Children's Hospital of Melbourne, Melbourne, Victoria, Australia., Mital S; Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto Ontario, Canada; Ted Rogers Computational Program, Ted Rogers Centre for Heart Research, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada. Electronic address: seema.mital@sickkids.ca.
Jazyk:	angličtina
Zdroj:	Journal of the American College of Cardiology [J Am Coll Cardiol] 2023 Mar 21; Vol. 81 (11), pp. 1035-1045.
DOI:	10.1016/j.jacc.2023.01.012
Abstrakt:	Background: Genetic defects in the RAS/mitogen-activated protein kinase pathway are an important cause of hypertrophic cardiomyopathy (RAS-HCM). Unlike primary HCM (P-HCM), the risk of sudden cardiac death (SCD) and long-term survival in RAS-HCM are poorly understood. Objectives: The study's objective was to compare transplant-free survival, incidence of SCD, and implantable cardioverter-defibrillator (ICD) use between RAS-HCM and P-HCM patients. Methods: In an international, 21-center cohort study, we analyzed phenotype-positive pediatric RAS-HCM (n = 188) and P-HCM (n = 567) patients. The between-group differences in cumulative incidence of all outcomes from first evaluation were compared using Gray's tests, and age-related hazard of all-cause mortality was determined. Results: RAS-HCM patients had a lower median age at diagnosis compared to P-HCM (0.9 years [IQR: 0.2-5.0 years] vs 9.8 years [IQR: 2.0-13.9 years], respectively) (P < 0.001). The 10-year cumulative incidence of SCD from first evaluation was not different between RAS-HCM and P-HCM (4.7% vs 4.2%, respectively; P = 0.59). The 10-year cumulative incidence of nonarrhythmic deaths or transplant was higher in RAS-HCM compared with P-HCM (11.0% vs 5.4%, respectively; P = 0.011). The 10-year cumulative incidence of ICD insertions, however, was 5-fold lower in RAS-HCM compared with P-HCM (6.9% vs 36.6%; P < 0.001). Nonarrhythmic deaths occurred primarily in infancy and SCD primarily in adolescence. Conclusions: RAS-HCM was associated with a higher incidence of nonarrhythmic death or transplant but similar incidence of SCD as P-HCM. However, ICDs were used less frequently in RAS-HCM compared to P-HCM. In addition to monitoring for heart failure and timely consideration of advanced heart failure therapies, better risk stratification is needed to guide ICD practices in RAS-HCM. Competing Interests: Funding Support and Author Disclosures The project was supported through funding from the Ted Rogers Centre for Heart Research, the Heart and Stroke Foundation/Robert M Freedom Chair, and the Canadian Institutes of Health Research to Dr Mital. Dr Lynch is supported by a Heart Failure Research Fellowship from Bristol Myers Squibb, Mitacs, and Myant. Dr Mital has served as a consultant for Bristol Myers Squibb and Tenaya Therapeutics; and has received unrestricted education funding from Bristol Myers Squibb. Dr Conway has served as a medical monitor for the PumpKIN trial; and has received unrestricted education funding from Abbott. Dr Rossano has served as a consultant for Merck, Bayer, Myokardia, and Cytokinetics. Dr Kantor has served as a consultant for Novartis and AstraZeneca. Dr Balaji has served as a consultant for Milestone Pharmaceuticals and Janssen Pharmaceuticals; and has received a research support grant from the Medtronic External Research Program. Dr Godown has served as a consultant for Daiichi-Sankyo. Dr Aziz has served on the Medical Advisory Board for Medtronic. Dr Jeewa has served as a medical monitor for the PumpKIN trial; and has served as a consultant for Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu