Vigorous Exercise in Patients With Congenital Long QT Syndrome: Results of the Prospective, Observational, Multinational LIVE-LQTS Study
Authors: Lampert Rachel , Day Sharlene , Ainsworth Barbara , Burg Matthew , Marino Bradley S. , Salberg Lisa , Tome Esteban Maria Teresa , Abrams Dominic J. , Aziz Peter F. , Barth Cheryl , Behr Elijah R. , Bell Cheyanne , Berul Charles I. , Bos Johan M. , Bradley David , Cannom David S. , Cannon Bryan C. , Concannon Maryann Anandi , Cerrone Marina , Czosek Richard J. , Dubin Anne M. , Dziura James , Erickson Christopher C. , Estes N.A. Mark , Etheridge Susan P. , Goldenberg Ilan , Gray Belinda , Haglund-Turnquist Carla , Harmon Kimberly , James Cynthia A. , Johnsrude Christopher , Kannankeril Prince , Lara Alice , Law Ian H. , Li Fangyong , Link Mark S. , Molossi Silvana M. , Olshansky Brian , Noseworthy Peter A. , Saarel Elizabeth V. , Sanatani Shubhayan , Shah Maully , Simone Laura , Skinner Jonathan , Tomaselli Gordon F. , Ware James Simon , Webster Gregory , Zareba Wojciech , Zipes Douglas P. , Ackerman Michael J. 
Published: July 2024

BACKGROUND:
Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long QT syndrome (LQTS) remains unknown.

METHODS:
The National Institutes of Health–funded LIVE-LQTS study (Lifestyle and Exercise in the Long QT Syndrome) prospectively enrolled individuals 8 to 60 years of age with phenotypic and/or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as ≥6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis.

RESULTS:
Among the 1413 participants (13% <18 years of age, 35% 18–25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, 49% with LQT1, 91% were treated with beta-blockers, left cardiac sympathetic denervation, and/or implantable cardioverter defibrillator), 52% participated in vigorous exercise (55% of these competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57–1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67–2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup.

CONCLUSIONS:
Among individuals diagnosed with phenotypic and/or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. These data further inform shared decision-making discussions between patient and physician about exercise and competitive sports participation.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02549664.