Vigorous exercise not linked to risk for death, arrhythmias in long QT syndrome
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Key takeaways:
- In people with long QT syndrome, vigorous exercise did not raise risk for death or arrhythmias vs. nonvigorous exercise.
- The findings were similar in those who played competitive sports and those who did not.
PHILADELPHIA — In people with congenital long QT syndrome, vigorous exercise did not raise risk for death or ventricular arrhythmias compared with nonvigorous exercise, according to the results of the LIVE-LQTS study.
However, noninferiority could not be declared because the confidence intervals were wide.
In addition, researchers reported at the American Heart Association Scientific Sessions, the results were the same regardless of whether people played competitive sports.
Prospective data
“The benefits of exercise, physical and psychological, are well described,” Rachel Lampert, MD, FACC, Robert W. Berliner Professor of Medicine (Cardiology) at Yale School of Medicine, said during a presentation. “However, concern for the risk of arrhythmia and sudden death has led to restrictions on vigorous exercise for individuals with long QT syndrome, as well as other cardiovascular diseases. Prospective data are lacking, however, on the actual risk of vigorous exercise for individuals with long QT syndrome. The objective of this study was to determine whether engagement in vigorous exercise, including competitive sports, is associated with an increased risk for life-threatening ventricular arrhythmia and/or mortality in individuals with long QT syndrome followed prospectively over 3 years.”
Lampert and colleagues enrolled 1,413 people (mean age, 28 years; 67% women; 94% white) from 42 sites in five countries with a diagnosis of manifest or concealed long QT syndrome (LQTS) who were able to complete a questionnaire and did not have any conditions precluding exercise.
All participants were classified into three exercise categories: vigorous, moderate or sedentary, and the moderate and sedentary groups were combined into one nonvigorous category for the statistical analysis. Vigorous exercise was defined as at least one activity with metabolic equivalents of task (METs) of 6 or more for at least 60 hours per year; moderate exercise was defined as all activities with METs of 4 to less than 6 for at least 60 hours per year; and sedentary was defined as not meeting the vigorous or moderate criteria. Within the vigorous group, participants were classified as competitive or noncompetitive physical activity.
The primary endpoint was survival free from the composite outcome of death, resuscitated cardiac arrest, arrhythmic syncope and appropriate shock from an implantable cardioverter defibrillator at 3 years.
Among the cohort, 54.9% had no prior syncope, cardiac arrest, ventricular tachycardia or ventricular fibrillation and 25.5% had an ICD, according to the researchers. The vigorous group was younger, more likely to be male, less likely to have an ICD, less likely to have prior symptoms and numerically more likely to have a prolonged QT compared with the nonvigorous group.
The rate of the primary endpoint was low — 2.6% overall, 2.7% in the nonvigorous group and 2.6% in the vigorous group — Lampert said, noting that the rates translated to 8.6 events per 1,000 patient-years in the nonvigorous group (95% CI, 5.4-13.6) and 8.3 events per 1,000 patient-years in the vigorous group (95% CI, 5.2-13.1).
In the nonvigorous group, there was one sudden death and one resuscitated cardiac arrest, and in the vigorous group, there was one resuscitated cardiac arrest, Lampert said, noting none of those incidents occurred during exercise.
The HRs for the primary endpoint were 0.97 in the unadjusted model (95% CI, 0.57-1.67; P = .93) and 1.17 in the model adjusted for prespecified covariates (95% CI, 0.67-2.04; P = .64), she said.
In the model adjusted for prespecified covariates, the 95% CI upper bound of 2.04 was above the threshold of 1.5 to declare noninferiority, Lampert said.
The results did not vary by LQT1 vs. LQT2 phenotype, symptomatic status or status of resting QTc, she said, noting that when the analysis was restricted to individuals aged 14 to 22 years, there remained no differences between the groups in the primary outcome.
In addition, Lampert said, compared with all other participants, those in the competitive subgroup of the vigorous group did not have elevated risk for the primary outcome (HR = 0.74; 95% CI, 0.19-2.96; P = .72).
Material for shared decision-making
“While the very low event rate led to the study being underpowered to detect small differences, as indicated by the wide confidence intervals in both directions, this low event rate in both groups should inform discussions between patients and physicians regarding vigorous exercise participation in the context of expert management and assessment of long QT syndrome using an individualized shared decision-making framework,” Lampert said.
In a discussant presentation, Aarti S. Dalal, DO, associate director of pediatric electrophysiology and assistant professor of pediatrics (cardiology) at Vanderbilt University Medical Center, said current management of this population “is based on data from over 2 decades ago, when we first began to understand what were the specific cardiac triggers of the different genotypes in patients with long QT syndrome.”
She noted that a 2013 Heart Rhythm Society guideline called the issue “still a matter of debate” and recommended that low-risk patients be allowed to participate in competitive sports “in special cases,” but did not recommend participation for higher-risk patients. A 2015 American College of Cardiology/American Heart Association guideline recommended looser restrictions, but only slightly, and in 2020, a European Society of Cardiology guideline recommended not allowing phenotype-positive patients with LQTS to participate in competitive sports, she said.
“That is not necessarily what our patients want to do,” she said. “We have guidelines and recommendations telling us we should not be letting our patients participate in these activities, but then we have single-center retrospective reviews suggesting that maybe the risk is not as high as we think it is. ... Here we have a prospective international study [including] high-risk patients. When you look at the breakdown of the data, it truly demonstrated that there was no significant difference in the cardiac event rate between these two groups. ... The takeaway here is, yes, neither group was demonstrated as superior ... but what we do learn is that the rate of cardiac events is low.”
A major factor is that the patients in LIVE-LQTS were appropriately treated at LQTS specialty clinics, Dalal said, noting that 80% were on beta-blockers and one-quarter had ICDs. “When you then allow those patients to exercise, the risk of cardiac events is actually low. ... In shared decision-making, we know the risk isn’t zero, but it isn’t necessarily higher if we do allow them to participate in exercise.”
Perspective
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Meagan M. Wasfy, MD, MPH, FACC
Using a similar design as the recently published LIVE-HCM study, which focused on patients with hypertrophic cardiomyopathy, this study evaluated the relationship between self-reported physical activity and clinical events in participants with congenital LQTS.
Participants came from 42 sites in five countries and additionally could self-enroll, and were followed for 3 years for clinical events. Events included the relevant ones for this diagnosis, specifically sudden death, sudden cardiac arrest, ICD therapies and syncope that was suspicious for arrhythmia. Given the background concern that athletes with LQTS might be at higher risk continuing vs. discontinuing sport, the primary analysis was designed to address whether events in those participating in larger amounts of exercise, equivalent to slow jogging or more vigorous activity for 60 hours or greater per year, was noninferior to lower physical activity levels.
In this large and well-treated cohort of participants with LQTS, more than half were considered vigorous exercisers and around one-quarter participated in competitive sports. Event rates were low and similar in the two groups. Event rates were lower than anticipated, resulting in large confidence intervals on the HRs comparing vigorous to nonvigorous exercisers that crossed the noninferiority margin (1.5). Therefore, noninferiority of vigorous vs. nonvigorous exercise was not demonstrated.
The investigators are to be commended for the successful completion of this study, which builds upon prior single-center work and represents the largest cohort of LQTS patients in which the relationship of physical activity and event risk has been studied to date. The most important message we can take from this study is that the rate of clinically meaningful events in these well-treated patients with LQTS is very low, lower than even the investigators had anticipated in the study design, which gives us reassurance in such individuals, regardless of whether they exercise a little or a lot.
Counseling of athletes with CV conditions often relies heavily on a process of shared decision-making, in which physicians and patients discuss and contextualize the risks of sport continuation vs. discontinuation. While the study didn’t meet its prespecified goal to identify if vigorous exercise was similar, ie, noninferior, to lower levels of exercise, this study gives us concrete numbers regarding risk in well-treated patients with LQTS that are still really helpful to use in these shared decision-making discussions.
While we often are making decisions regarding sport for bins of time similar to the follow-up in this study — for example, the duration of high school or college — it would be great to have longer-term follow-up of this cohort, including updated assessments of activity levels over time and how these relate to events.
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Lampert R, et al. FS.06. Exercise is life (and death) - Approaches in athletes, arrhythmias and heart failure. Presented at: American Heart Association Scientific Sessions; Nov. 11-13, 2023; Philadelphia.
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