Evaluation of age at symptom onset, proband status, and sex as predictors of disease severity in pediatric catecholaminergic polymorphic ventricular tachycardia
Por:
Kallas D, Roston TM, Franciosi S, Brett L, Lieve KVV, Kwok SY, Kannankeril PJ, Krahn AD, LaPage MJ, Etheridge S, Hill A, Johnsrude C, Perry J, Knight L, Fischbach P, Balaji S, Tisma-Dupanovic S, Law I, Atallah J, Backhoff D, Kamp A, Kubus P, Kean A, Aziz PF, Kovach J, Lau Y, Kron J, Clur SA, Sarquella-Brugada G, Wilde AAM and Sanatani S
Publicada:
1 nov 2021
Ahead of Print:
1 oct 2021
Categoría:
Cardiology and cardiovascular medicine
Resumen:
BACKGROUND Children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for sudden death, and a risk stratification tool does not exist.
OBJECTIVE The purpose of this study was to determine whether proband status, age at symptom onset, and/or sex are independent predictors of cardiac events.
METHODS A multicenter, ambispective, cohort of pediatric CPVT patients was categorized by sex, proband status, and age at symptom onset (D1: first decade of life [symptom onset <10 years] or D2: second decade of life [symptom onset 10-18 years, inclusive]). Demographics, therapy, genetics, and outcomes were compared between groups.
RESULTS A total of 133 patients were included and stratified into 58 D1 and 75 D2 patients (68 female and 65 male; 106 probands and 27 relatives). Localization of RYR2 variants to hotspots differed based on proband status and age at symptom onset. The cardiac event rate was 33% (n = 44/133), inclusive of a 3% (n = 4/133) mortality rate, over a median of 6 years (interquartile range 3-11) after time of symptom onset. Proband status, rather than age at of symptom onset or sex, was an independent predictor of time to first cardiac event (P = .008; hazard ratio = 4.4). The 5-, 10and 15-year event-free survival rates for probands were 77%, 56%, and 46%, respectively, and for relatives were 96%, 91%, and 86%, respectively. Event risk after diagnosis was 48% (32/67) in patients on beta-blocker or flecainide alone vs 10% (5/48) in patients on beta-blocker plus flecainide and/or left cardiac sympathetic denervation (P <.001).
CONCLUSION Proband status, but not age at symptom onset or male sex, independently predicted an earlier onset of cardiac events. A larger sample size would enable a comprehensive investigation of other risk factors.
Filiaciones:
Kallas D:
BC Children's Hospital, Vancouver-Canada
Roston TM:
BC Children's Hospital, Vancouver-Canada
Franciosi S:
BC Children's Hospital, Vancouver-Canada
Brett L:
BC Children's Hospital, Vancouver-Canada
Lieve KVV:
Amsterdam University Medical Center, Amsterdam-Netherlands
European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart
Kwok SY:
Hong Kong Children's Hospital, Hong Kong-SAR China
Kannankeril PJ:
Vanderbilt University Medical Center, Nashville-USA
Krahn AD:
Division of Cardiology, University of British Columbia, Vancouver-Canada
LaPage MJ:
University of Michigan, Ann Arbor-USA
Etheridge S:
University of Utah, Salt Lake City-USA
Hill A:
Children's Hospital Los Angeles, Los Angeles-USA
Johnsrude C:
University of Louisville, Louisville-USA
Perry J:
Rady Children's Hospital, San Diego-USA
Knight L:
Sibley Heart Center, Children's Healthcare of Atlanta, Atlanta-USA
Fischbach P:
Sibley Heart Center, Children's Healthcare of Atlanta, Atlanta-USA
Balaji S:
Oregon Health Science University, Portland-USA
Tisma-Dupanovic S:
Nemours Children's Clinic, Orlando-USA
Law I:
University of Iowa Stead Family Children's Hospital, Iowa City-USA
Atallah J:
University of Alberta, Edmonton-Canada
Backhoff D:
University of Gottingen, Gottingen-Germany
Kamp A:
Nationwide Children's Hospital, Columbus-USA
Kubus P:
Motol University Hospital, Prague-Czech Republic
Kean A:
Indiana University School of Medicine, Indianapolis-USA
Aziz PF:
Cleveland Clinic, Cleveland-USA
Kovach J:
Children's Hospital of Wisconsin, Milwaukee-USA
Lau Y:
University Alabama Birmingham, Birmingham-USA
Kron J:
Virginia Commonwealth University, Richmond-USA
Clur SA:
Amsterdam University Medical Center, Amsterdam-Netherlands
European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart
Sarquella-Brugada G:
Hospital Sant Joan de Déu, Barcelona-Spain
European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart
Wilde AAM:
Amsterdam University Medical Center, Amsterdam-Netherlands
European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart
Sanatani S:
BC Children's Hospital, Vancouver-Canada
Green Submitted
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