High-grade premature ventricular contractions (PVCs) during recovery from – but not during – exercise testing predict long-term cardiovascular (CV) mortality, a new retrospective analysis reports.

The study, published online Monday and in the Dec. 7 issue of the Journal of the American College of Cardiology, investigated whether high-grade PVCs during stress testing predict mortality in asymptomatic individuals – finding that only PVCs occurring during recovery were associated with long-term risk of CV mortality.

Led by Marwan M. Refaat, MD, from the American University of Beirut Medical Center, the authors noted that exercise test parameters, such as exercise duration or ST segment changes, can be predictive of CV risk and mortality independently of other clinical risk factors, in both symptomatic and asymptomatic patients.

However, whether the presence of PVCs during exercise treadmill testing has prognostic implications remains controversial, especially in asymptomatic individuals, they noted.

“In the current study, we show that high-grade PVCs during recovery from stress testing and not during the exercise period were associated with long-term CV mortality in asymptomatic individuals, independent of clinical and exercise test variables,” said Refaat and colleagues.

“To our knowledge, this is the first study to assess the prognostic implications of PVC timing in asymptomatic patients not suspected of having heart disease.”

The relevance of PVC timing?

The authors noted that exercise-induced PVCs have been associated with an increase in CV risk in patients with suspected or known coronary heart disease, “especially if they were high grade and occurred during recovery from stress testing.”

One suggested mechanism is that PVCs occurring during recovery are caused by insufficient vagal reactivation following exercise, “which, in itself, is associated with an increase in mortality,” noted Refaat and colleagues.

They noted that previous studies have associated high-grade exercise-induced PVCs with mortality in asymptomatic individuals not suspected of having heart disease.

“However, whether differential PVC timing (ie, during exercise or recovery) carries differential prognostic value has not been shown in asymptomatic individuals to date,” they noted.

“If recovery PVCs carry worse prognosis than exercise PVCs, this would provide additional evidence in support of the hypothesis that PVC timing is an important predictor of CV risk tied to the degree of vagal activity and independent of coronary heart disease.”

Study details

To investigate the impact of PVC timing and its potential association with CV and all-cause mortality in asymptomatic individuals, Refaat and colleagues performed a retrospective analysis of 5,486 people with 20-year follow-up data taking part in the Lipid Research Clinics Program.

They reported that high-grade exercise-induced PVCs were seen in 101 (1.8%) participants during exercise, 133 (2.4%) during recovery, and in 42 (0.8%) both during exercise and recovery.

Individuals with high-grade PVCs were found to be significantly older and had higher prevalence of hypertension, diabetes mellitus and high-density lipoprotein (HDL) <40 mg/dL.

Over an average follow-up period of 20.2 years, those with high-grade PVCs during both exercise and recovery had significantly higher rates of all-cause mortality and CV mortality.

Using a step-wise Cox proportional hazards model, the authors then adjusted the results for age, gender, clinical risk factors, and indicators of exercise performance. In these fully adjusted models, high-grade PVCs during recovery remained significantly associated with higher risk of CV mortality (hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.09-2.60; P= 0.02), but there was no significant association between PVCs with all-cause mortality.

PVCs occurring during the exercise phase were not associated with increased risk, they said.

Clinical implication

Refaat and colleagues also revealed that while PVCs occurring during recovery were associated with long-term risk of CV mortality in asymptomatic individuals, the addition of PVCs during recovery to a model that included traditional clinical risk factors for CV disease did not improve its ability to further discriminate or reclassify the 20-year risk of CV mortality for persons in this cohort.

“This shows that in asymptomatic individuals, and to date, the evidence in favor of the routine incorporation of exercise-induced PVC data into exercise tolerance test results seems limited,” said the authors.

Writing in an accompanying editorial, Sandeep Saha, MD, MS, from the Oregon Heart Center, Salem, noted that although exercise stress testing is “widely used” for diagnosis and risk stratification of symptomatic patients with suspected or known coronary artery disease (CAD), “its clinical utility in asymptomatic individuals remains uncertain.”

“The current study shows for the first time that high-grade exercise-induced PVCs during recovery—but not during exercise—is associated with a higher risk of CV death in asymptomatic adults without previous CV disease, even after adjustment for demographic and clinical variables and non-ischemic parameters of exercise performance,” he said.

However, the editorialist noted that despite the identification of a significant association between recovery PVCs and CV mortality, the study shows no prognostic value, as it was not able to demonstrate the utility of using PVCs during recovery in reclassification of long-term CV mortality risk in this population.

“Therefore, these findings support the current guidelines that do not recommend exercise stress testing as a screening test in patients at low risk for CAD,” he said.

However, Refaat and colleagues also noted that the findings may have important clinical implications at the individual patient level: “For instance, during review of exercise stress tests for asymptomatic patients, health care providers could identify individuals at increased risk of CV mortality after noting high-grade PVCs during the recovery phase of exercise tests.”

“This could prompt the clinician to schedule more frequent follow-up and to intensify efforts to reduce this risk,” they noted.

Sources:

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.

Saha SA. Premature Ventricular Complexes During Exercise in Asymptomatic Adults: Do They Deserve a Closer Look? J Am Coll Cardiol 2021;78:2278-2280.

Image Credit: Photographee.eu – stock.adobe.com