Impact of preexisting heart disease on survival and postoperative outcomes in pancreatic cancer: A TriNetX analysis

Background: Cardiovascular comorbidity is common among patients with pancreatic ductal adenocarcinoma (PDAC) and may influence both long-term survival and perioperative risk, yet its impact in contemporary practice is not well defined. We performed a retrospective database study using TriNetx, a multinational deidentified dataset, to identify patients with PDAC and to examine associations between heart disease, survival, and complications of pancreaticoduodenectomy (PD). Methods: Using the TriNetx database, we identified patients with PDAC and stratified the cohort by presence or absence of heart disease (ischemic, structural, heart failure). Subgroup analysis was performed of patients who underwent PD. The primary outcome is overall survival, and secondary outcome is rate of post-PD complications. Propensity score matching was performed for age, sex, stage, and comorbidities. Kaplan-Meier curves and log-rank testing were used to determine survival between the groups and multivariable logistic regression was used to evaluate associations between heart disease and postoperative complications. Among patients undergoing PD, secondary outcomes include postoperative pancreatic leak, myocardial infarction (MI), acute kidney injury (AKI), surgical site infection (SSI), and venous thromboembolism (VTE), rates were evaluated using multivariable logistic regression. Results: We identified 226,966 patients with PDAC, of whom 45,936 (20%) had preexisting heart disease and 181,030 (80%) did not; 12,840 underwent PD. Propensity matched median overall 5-year survival was 703 days for patients without heart disease versus 611 days for those without (HR = 0.90, p < 0.0001). In the matched surgical cohort, preexisting heart disease was associated with increased risk of post-operative myocardial infarction (RR = 3.34, p < 0.0001) and acute kidney injury (RR = 1.34, p < 0.0001) but not associated with post-operative pancreatic leak (RR = 1.11, p = 0.18), abscess (RR = 1.15, p = 0.16), or surgical site infection (RR = 1.13, p = 0.16). Among propensity matched cohorts of patients with PDAC and heart disease who did and did not undergo PD, those who underwent PD had significant improvement in 1-year overall survival (82% vs 63%, p < 0.0001). Conclusions: In this large, real-world cohort of patients with PDAC, preexisting heart disease was an important determinant of overall survival and perioperative morbidity, with clinically meaningful differences in median survival and postoperative complication profiles. The benefit of PD does not seem to be lost to patients with cardiac risk factors, with significant improvement in overall survival seen in the group who underwent PD. These findings may inform risk stratification, treatment selection, and perioperative optimization strategies for this high-risk population.