TY - JOUR
T1 - Risk of Sudden Death in Patients With RASopathy Hypertrophic Cardiomyopathy
AU - Lynch, Aine
AU - Tatangelo, Mark
AU - Ahuja, Sachin
AU - Steve Fan, Chun Po
AU - Min, Sandar
AU - Lafreniere-Roula, Myriam
AU - Papaz, Tanya
AU - Zhou, Vivian
AU - Armstrong, Kathryn
AU - Aziz, Peter F.
AU - Benson, Lee N.
AU - Butts, Ryan
AU - Dragulescu, Andreea
AU - Gardin, Letizia
AU - Godown, Justin
AU - Jeewa, Aamir
AU - Kantor, Paul F.
AU - Kaufman, Beth D.
AU - Lal, Ashwin K.
AU - Parent, John J.
AU - Richmond, Marc
AU - Russell, Mark W.
AU - Balaji, Seshadri
AU - Stephenson, Elizabeth A.
AU - Villa, Chet
AU - Jefferies, John L.
AU - Whitehill, Robert
AU - Conway, Jennifer
AU - Howard, Taylor S.
AU - Nakano, Stephanie J.
AU - Rossano, Joseph
AU - Weintraub, Robert G.
AU - Mital, Seema
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/3/21
Y1 - 2023/3/21
N2 - 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.
AB - 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.
KW - Noonan syndrome
KW - RASopathy
KW - hypertrophic cardiomyopathy
KW - implantable cardioverter-defibrillator
KW - pediatric
KW - sudden cardiac death
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UR - http://www.scopus.com/inward/citedby.url?scp=85149708328&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2023.01.012
DO - 10.1016/j.jacc.2023.01.012
M3 - Article
C2 - 36922089
AN - SCOPUS:85149708328
SN - 0735-1097
VL - 81
SP - 1035
EP - 1045
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 11
ER -