Dose-Response Effect of Physical Prehabilitation on Major Cardiac and Cerebrovascular Events and Disability Levels After Cardiac Surgery in Frail PatientsTake-Home Points

Background: Prehabilitation enhances patients’ resilience to surgical stress and may improve postoperative outcomes. However, the dose response of prehabilitation on outcomes remains unknown. Research Question: Does a twice-weekly supervised outpatient exercise program before elective cardiac surgery in patients with frailty have dose-response effects on 90-day postoperative major cardiac and cerebrovascular events (MACCEs) and disability levels? Study Design and Methods: This was a post hoc analysis of the PREhabilitation for improving QUality of recovery after ELective cardiac surgery (PREQUEL) trial that compared physical prehabilitation (up to 19 sessions over 10 weeks) with usual care in participants with very mild to moderate frailty. Primary outcomes included the 90-day risk of MACCEs and changes in disability levels measured by the World Health Organization Disability Assessment Schedule 2.0 score. Secondary outcomes were preoperative changes in the 6-minute walk test distance, submaximal metabolic equivalents of tasks, and frailty measures. We used a generalized estimating equation model to examine the association between the dose of prehabilitation and the risk of MACCEs. Causal inference was assessed by dose-response function models while allowing nonlinearity. Results: Of the 143 participants, 135 underwent cardiac surgery. No exercise-induced adverse events occurred in 64 participants during 551 sessions. The dose of prehabilitation was not associated with the risk of MACCEs (16 participants with 24 episodes; adjusted OR/session, 0.98; 95% CI, 0.88-1.09). However, improvements in disability levels, 6-minute walk test distance, and metabolic equivalents of tasks were directly related to the number of consecutive doses of prehabilitation before surgery. Improvements in clinical frailty after exercise training were observed in a few patients after 7 weeks of training. Interpretation: In cardiac patients with frailty, a greater number of consecutive doses of physical prehabilitation had favorable effects on improving preoperative exercise capacity and lowering disability levels at 90 days after surgery. Clinical Trial Registration: Chinese Clinical Trials Registry; No.: ChiCTR1800016098; URL: https://www.chictr.org.cn/indexEN.html