Impact of neoadjuvant immunotherapy on postoperative cardiac adverse events in NSCLC: insights from a bidirectional cohort

BACKGROUND: The impact of neoadjuvant chemo-immunotherapy (nCIT) on perioperative cardiac safety in patients undergoing lung cancer resection remains unclear. This study aimed to evaluate the incidence and risk factors of postoperative cardiac adverse events (PCAEs) in patients receiving nCIT compared with neoadjuvant chemotherapy (nCT). METHODS: We conducted a bidirectional cohort study including 310 patients who received neoadjuvant therapy (nCT = 115; nCIT = 195), comprising both retrospective and prospective cases. Propensity score matching (PSM) at a 1:1 ratio was applied to balance baseline characteristics. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of PCAEs, including clinically important perioperative atrial fibrillation, myocardial injury after non-cardiac surgery, myocardial infarction, and heart failure. Variance inflation factors were calculated to assess multicollinearity, and model goodness-of-fit was evaluated. Subgroup and sensitivity analyses were conducted to examine the robustness of findings. RESULTS: Before PSM, the overall incidence of PCAEs was comparable between the nCT and nCIT groups [20.9% vs. 25.6%; odds ratio (OR) 1.307, 95% confidence interval (CI) 0.759-2.300; P = 0.342]. After PSM (n = 166), no significant difference in PCAEs was observed (19.3% vs. 18.1%; OR 0.924, 95% CI 0.423-2.017; P = 0.842). Multivariable analyses confirmed that nCIT was not independently associated with increased PCAEs before (Model 3 OR 1.137, 95% CI 0.573-2.299) or after PSM (Model 3 OR 1.462, 95% CI 0.510-4.387). Hypertension (OR 11.024, 95% CI 3.518-38.380; P < 0.001) and pericardial window creation (OR 8.310, 95% CI 2.186-34.139; P = 0.002) were identified as strong independent predictors of PCAEs. Subgroup and sensitivity analyses consistently showed no elevated cardiac risk associated with nCIT across sex, hypertension status, surgical approach, ACEI/ARB use, CCB use, or treatment era. CONCLUSIONS: In this bidirectional cohort study, nCIT did not increase the risk of postoperative cardiac adverse events compared with nCT. Hypertension and pericardial window creation were significant independent risk factors for PCAEs. These findings support the perioperative cardiac safety of nCIT in lung cancer surgery.