By Michael H. Crawford, MD
Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco
SYNOPSIS: A study of asymptomatic subjects without known cardiovascular disease undergoing treadmill exercise testing and followed for a mean of 20 years showed high-grade premature ventricular contractions during exercise recovery (but not during exercise) are predictive of subsequent cardiovascular mortality.
SOURCE: Refaat MM, Gharios C, Moorthy MV, et al. Exercise-induced ventricular ectopy and cardiovascular mortality in asymptomatic individuals. J Am Coll Cardiol 2021;78:2267-2277.
The predictive ability of high-grade premature ventricular contractions (PVCs) during treadmill exercise testing in asymptomatic individuals not suspected of having cardiovascular disease (CVD) is unclear, as is the importance of the timing of the PVCs during the testing period in such individuals. Refaat et al analyzed the Lipid Research Clinics Prevalence Study (LRCPS) database to clarify these issues.
The creators of the LRCPS recruited subjects from communities in North America from 1972 to 1976 to assess the relationship between lipid levels and outcomes. A randomized sample of 58% of the population that was asymptomatic was chosen to return for a second visit one year later. During this second visit, researchers collected comprehensive clinical information and conducted a treadmill exercise study using either the standard or modified Bruce protocol. From these 8,658 subjects, investigators excluded those with a history of or evidence for CVD, those with a systolic blood pressure < 90 mmHg or > 200 mmHg, diastolic blood pressure > 120 mmHg, R on T PVCs, ventricular tachycardia at rest, or unable to exercise on a treadmill.
The remaining 5,486 subjects were followed until death or the end of 1995. The mean age of the study population was 45 years. Forty-two percent were women, 95% were white, 43% were hypertensive, 50% had dyslipidemia, and 65% had smoked for some period or were current smokers. Over a mean 20-year follow-up, 15% died (37% of these were CV deaths). High-grade PVCs were present during exercise in 1.8%, during recovery in 2.4%, and both in 0.8%. Those with high-grade PVCs with exercise testing were older, more likely to be diabetic, be hypertensive, record ST depression during exercise, experience slower heart rate recovery, exercise for a shorter duration, and fail to hit 90% of maximum predicted heart rate. High-grade PVCs during exercise were associated with higher rates of CV mortality (20% vs. 5%; P < 0.001) and all-cause mortality (49% vs. 15%; P < 0.001). High-grade PVCs in recovery also were associated with a higher risk of CV mortality (27% vs. 5%; P < 0.001) and all-cause mortality (53% vs. 14%; P < 0.001).
After adjusting for clinical variables, high-grade PVCs during recovery were associated with a higher CV mortality risk (HR, 1.82; 95% CI, 1.19-2.79; P = 0.006). After correcting for exercise test variables, high-grade PVCs during recovery remained associated with CV mortality (HR, 1.68; 95% CI, 1.09-2.6; P = 0.02). These adjustments abrogated the association of high-grade PVCs during exercise with mortality. The results were not different in any subgroup defined by clinical variables. The authors concluded high-grade PVCs during recovery, but not during exercise, are associated with CV mortality.
COMMENTARY
The main strengths of this study were the fact it included many asymptomatic subjects of both sexes who were not suspected for CVD, and the mean follow-up was 20 years. Also, the analyses were adjusted for a comprehensive collection of clinical data. There were weaknesses, too. All the clinical data were collected only at baseline. Almost all the subjects were white, and the majority smoked tobacco. In addition, the study was enriched for subjects with dyslipidemia. Finally, there was no statin use at baseline, and there were no data on subsequent use once they were introduced to the market.
In clinical practice, most patients undergo exercise testing because of suspected or known CVD. Consequently, is this study of asymptomatic subjects of clinical value? Besides LRCPS, there are other potential applications of exercise testing in asymptomatic patients without known CVD. Examples include higher-risk individuals starting an exercise program, patients with long QT syndrome, patients prescribed class I antiarrhythmic agents, and subjects with reports of exercise-related ectopy from wearable devices. Also, I have observed that if individuals with exercise-induced ectopy need to be exercised again because there was a glitch in collecting imaging data, the ectopy is gone on the repeat study. Exercise-induced ectopy could be catecholamine-induced, but the rapid activation of the vagal nervous system in recovery quickly shuts down this type of physiologic ectopy. Repeating the exercise test can result in a less sympathetic response and could be useful for managing borderline cases in which some high-grade PVC activity spills into the early recovery phase.
A study of asymptomatic subjects without known cardiovascular disease undergoing treadmill exercise testing and followed for a mean of 20 years showed high-grade premature ventricular contractions during exercise recovery (but not during exercise) are predictive of subsequent cardiovascular mortality.
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