Sex Differences in the Effects of Perioperative Rehabilitation on Postoperative Pulmonary Complications After Cardiac Valve Surgery: A Prespecified Subgroup Analysis of the PORT Randomized Trial

Purpose: To evaluate whether biological sex modifies the association between perioperative rehabilitation and short-term postoperative pulmonary outcomes in patients undergoing cardiac valve surgery. Patients and Methods: This prespecified subgroup analysis was based on the PORT randomized controlled trial, a single-center prospective study including 818 adults undergoing elective valve surgery. Patients were randomized to usual care or additional perioperative rehabilitation. Usual care followed standard institutional protocols without structured therapist-led rehabilitation. The intervention group received a supervised program including patient education, inspiratory muscle training, active cycle of breathing techniques, and early mobilization from admission to discharge. The primary endpoint was a composite of in-hospital mortality, postoperative pulmonary complications (PPCs), and prolonged hospitalization (>7 days). Key secondary endpoints were radiologically confirmed pneumonia and pneumothorax within 7 days and before discharge. Sex-stratified multivariable Cox models were used to estimate adjusted hazard ratios (HRs), adjusting for age, body mass index, left ventricular ejection fraction category, Global Initiative for Chronic Obstructive Lung Disease category, hypertension, and smoking history. Results: Perioperative rehabilitation was not associated with a significant reduction in the primary composite outcome in either sex. Among female patients, it was associated with lower risks of PPCs (adjusted HR 0.55, 95% CI 0.36-0.83; P = 0.005) and pneumonia (adjusted HR 0.48, 95% CI 0.33-0.70; P < 0.001), with a lower risk of pneumothorax also observed (adjusted HR 0.40, 95% CI 0.17-0.99; P = 0.047). No significant associations were observed in male patients. A significant sex-by-treatment interaction was identified for pneumonia (P for interaction = 0.041). Conclusion: Perioperative rehabilitation was associated with improved short-term pulmonary outcomes in female patients, particularly for pneumonia, whereas no significant benefit was observed in males. These findings suggest a potential sex-specific response, which requires confirmation in future multicenter studies.