Cardiac Comorbidity Burden and Post-Liver Transplant Outcomes: A Propensity-Matched Multicenter Analysis

Background/Objectives: Cardiac comorbidities are increasingly common among liver transplant candidates, particularly those with metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis. Although the Liver Transplant Comorbidity Index identifies coronary artery disease (CAD) as a predictor of post-transplant mortality, the impact of overall cardiac comorbidity burden on early outcomes after liver transplantation remains unclear. We evaluated the association between pre-transplant cardiac comorbidities and early post-transplant outcomes, with emphasis on MASH-related cirrhosis. Methods: We performed a retrospective cohort study using the TriNetX US Collaborative Research Network. Adults undergoing first-time isolated liver transplantation through May 2026 were included. Pre-transplant CAD, heart failure (HF), and atrial fibrillation (AF) documented within 12 months before transplantation were identified using ICD-10-CM codes. Patients were categorized by cardiac comorbidity burden (0–3 conditions). Recipients with any cardiac comorbidity underwent 1:1 propensity score matching to those without cardiac disease using 16 baseline demographic, clinical, and laboratory variables, including MELD-Na. The estimand was the average treatment effect in the treated patients. Primary outcomes comprised 30- and 90-day all-cause mortality. Secondary outcomes included a prespecified restricted major adverse cardiac event (MACE) composite, limited to hard endpoints (death, myocardial infarction, cardiac arrest, ischemic stroke), and a broader composite, i.e., acute kidney injury, prolonged mechanical ventilation, vasopressor requirement, renal replacement therapy, ICU and hospital length of stay, and 90-day readmission. Results: Among 5124 recipients, 986 (19.2%) exhibited at least one cardiac comorbidity. After matching, 974 patients remained in each group. Pre-transplant cardiac comorbidity was associated with higher 30- and 90-day mortality and increased risks of all secondary outcomes. The association with MACE persisted but was attenuated when restricted to hard endpoints (90-day RR 1.55; 95% CI 1.19–2.03) when compared with the broad composite (RR 1.75; 95% CI 1.40–2.18). MASH recipients with cardiac comorbidities experienced numerically higher event rates than did non-MASH recipients, but interaction estimates were imprecise and non-significant. In separate matched analyses, AF was most strongly associated with MACE, whereas CAD showed the strongest association with mortality. Conclusions: Pre-transplant cardiac comorbidity burden is associated with worse early post-transplant outcomes. Although MASH-cirrhosis recipients experienced numerically higher event rates, exploratory subgroup analyses did not demonstrate statistically significant differences from the non-MASH recipients. These findings may help refine cardiac risk prediction and perioperative planning, but they do not establish that intensified cardiac risk stratification or perioperative optimization improve outcomes. Prospective studies incorporating detailed cardiac, donor, operative, frailty, and medication data are needed to validate these associations and determine whether targeted risk-stratification and perioperative strategies can improve post-transplant outcomes.