Medical Technology

Post-Exercise PVCs Tied to Higher CV Mortality Risk

People who experience high-grade premature ventricular contractions (PVCs) during the recovery period following exercise may be a higher risk for later cardiovascular mortality, a new study suggests.

For two decades, investigators followed close to 5500 asymptomatic adults who underwent a baseline exercise treadmill test and found that those with high-grade PVCs that occurred during the recovery phase had an approximately 70% to 80% higher risk of future cardiovascular death, independent of standard cardiovascular risk factors and other exercise-related measures.

Conversely, high-grade PVCs occurring only during exercise were not associated with increased risk, after adjusting for clinical/exercise factors.

Adding high-grade exercise-induced PVCs during recovery to a risk prediction model for long-term cardiovascular mortality did not improve risk discrimination. 

“Don’t overlook those high-grade PVCs that occur in recovery, in particular if they are frequent, multifocal, 2 or more in a row, or R-on-T, as they identify higher risk individuals who may benefit from intensification of preventative efforts,” senior author Samia Mora, MD, MHS, associate professor, Harvard Medical School, Boston, Massachusetts, and a cardiologist at Brigham and Women’s Hospital, told | Medscape Cardiology.

The study was published online November 29 in the Journal of the American College of Cardiology.

“Uncertain” Clinical Significance

Certain parameters on exercise stress testing, such as exercise duration or ST-segment changes, have been shown to predict cardiovascular mortality and risk, independent of clinical risk factors, in asymptomatic as well as symptomatic patients. However, whether the presence of PVCs during an exercise treadmill test has any important prognostic implications “remains controversial,” especially in asymptomatic patients, the researchers write.

PVCs have been associated with increased cardiovascular risk in patients with suspected or known coronary heart disease, especially high-grade PVCs (defined as frequent, multifocal, or repetitive, including ventricular tachycardia and R-on-T-type), but it’s not known whether the timing of these PVCs, that is, during exercise or recovery, holds clinical prognostic relevance in asymptomatic individuals, they add.

“There is a lot of risk information — beyond ST changes or exercise capacity — from exercise testing that is often overlooked,” Mora observed. “PVCs often occur during the exercise or recovery phases of stress testing, yet the clinical significance of these complexes is uncertain.”

She and her colleagues “wanted to find out if the timing of occurrence of the high-grade PVCs carried prognostic information in a population that was asymptomatic at baseline.”

To investigate the question, the researchers looked at asymptomatic participants in the Lipid Research Clinics Prevalence Study (n = 5486, mean baseline age 45.4 years, 42% female).

Participants comprised three broad populations: occupational groups, household or residential groups, and parents of schoolchildren, and were drawn from 10 primary care centers in North America.

After the first screening visit, a sample including all participants with elevated lipid levels and an additional random sample of 15% (58% of the total study participants) were invited back for visit 2.

During visit 2, they underwent a medical interview, physical examination, an array of fasting blood studies, and treadmill exercise testing using the Bruce protocol. Participants were then followed for a mean of 20.2 years.

ECGs were recorded at rest; at the end of each stage of exercise; immediately after exercise; and then at 2, 4, and 6 minutes after exercise.

High-grade PVCs were defined as frequent (>10 per minute), multifocal, ≥ 2 PVCs in a row (including ventricular tachycardia), or R-on-T type PVCs.

Insufficient Vagal Reactivation?

During the follow-up period, there were 840 (15.3%) deaths due to any cause, of which 37% were cardiovascular in nature.

Participants who experienced high-grade PVCs during exercise or recovery tended to be older, compared with those without high-grade PVCs, and were also more likely to have diabetes and hypertension. Additionally, their exercise stress test showed greater likelihood of ischemia. They had significantly lower duration of exercise and heart rate recovery and were less likely to achieve their predefined target heart rate.

Women were more likely to experience PVCs during recovery than men.

Of the participants, 1.8% experienced high-grade PVCs during exercise, 2.4% during recovery, and 0.8% during both.

After adjusting for demographic and clinical factors (age, sex, diabetes, hypertension, lipids, smoking, body mass index, and family history of premature coronary disease), high-grade PVCs during recovery were significantly associated with cardiovascular mortality (HR, 1.82; 95% CI, 1.19 – 2.79; P = .006).

The finding remained significant, even after the researchers further adjusted for exercise duration, exercise duration, heart rate recovery, achieving target heart rate, and ST-segment depression (HR, 1.68; 1.09 – 2.60; P = .020).

By contrast, high-grade PVCs that occurred during the exercise phase were not associated with increased risk.

When the researchers analyzed specific clinical subgroups categorized by sex, diabetes, hypertension, and hyperlipidemia, they obtained similar findings.

However, when they added high-grade PVCs during recovery to a model that also included clinical variables, they found it did not significantly improve mortality risk discrimination (based on 3 indices: Harrell’s C-index, the integrated discrimination improvement index, and the category-free net reclassification index).

“The mechanism for the association of high-grade PVCs during recovery but not during exercise with cardiovascular mortality remains to be determined,” Mora commented.

“One strong possibility could relate to insufficient vagal reactivation post-exercise, as it is known that the parasympathetic system kicks in right after stopping exercise in order to counteract the sympathetic system of the autonomic nervous system.”

She said that future research “should investigate other mechanisms underlying post-exertional ventricular ectopy.”

“Not An Innocuous Finding”

Commenting on the study for | Medscape Cardiology, Sandeep Saha, MD, a cardiac electrophysiologist at Oregon Heart Center, and consulting cardiac electrophysiologist with Salem Health Hospitals and Clinics in Salem, Oregon, noted that improved healthcare literacy and the wider availability of wearable cardiac rhythm monitors “have led to more self-referrals from asymptomatic individuals who may detect exercise-induced PVCs on their devices, which, in turn, may lead to more referrals for exercise stress testing or referrals to cardiologists for evaluation of the same.”

Saha, who authored an accompanying editorial, said the findings help cardiologists “to potentially identify patients at higher risk of CV events by looking for exercise-induced PVCs during recovery, and then advising the referring providers to perform a more detailed CV risk assessment in these individuals, looking for previously undiagnosed CV risk factors…and structural heart disease.”

Exercise-induced PVCs “are not an innocuous finding on an exercise stress test; and, based on frequency and timing of these PVCs with relation to the exercise, should alert the clinician to pursue further risk assessment for undiagnosed conditions that may portend a higher cardiovascular risk even in asymptomatic individuals,” said Saha.

Mora was supported by NHLBI. Co-author Charbel Gharios, MD, was supported by the Fogarty International Center and Office of Dietary Supplements of the National Institutes of Health via the Scholars in Health Research Program (SHARP) at the American University of Beirut. Mora has served as a consultant to Pfizer and Quest Diagnostics for work unrelated to the current study. The other authors and Saha have disclosed no relevant financial relationships.

J Am Coll Cardiol. Published online November 29, 2021. Abstract, Editorial

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