Major Adverse Cardiovascular Events after liver transplantation: A call for a shared definition

Cardiovascular complications are a leading cause of morbidity and mortality after liver transplantation. Major Adverse Cardiovascular Events (MACE) are increasingly used as composite endpoints in both clinical trials and observational studies; however, definitions are highly variable, limiting comparability. Liver transplant recipients present unique pathophysiological features and perioperative risks that are not adequately captured by standard cardiovascular frameworks. We conducted a systematic review of 49 studies reporting MACE after liver transplantation, including randomized trials, prospective and retrospective cohort studies, and registry-based analyses. Data on study design, follow-up, MACE definitions, and the components included in composite endpoints were extracted and analyzed descriptively. None of the studies applied the classical three-point MACE definition (non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death). Components included in composite endpoints varied widely: myocardial infarction and heart failure were reported in 78% of studies, stroke in 69%, arrhythmias in 47%, and cardiac death in 35%. Pulmonary embolism was inconsistently included. Heart failure and arrhythmias accounted for a substantial proportion of events, whereas ischemic events represented a minority. Based on event frequency, pathophysiology, and prognostic relevance, we propose that post-transplant MACE include coronary artery disease (defined as myocardial infarction, unstable angina requiring hospitalization, or coronary revascularization, including elective procedures), stroke, heart failure requiring hospitalization, clinically significant arrhythmias (including perioperative events within 30 days of transplantation), cardiac arrest, and cardiovascular death. All non-fatal components should require cardiovascular hospitalization. Pulmonary embolism should be excluded. This definition represents the authors' proposal and requires further consensus and formal validation. A structured international process, ideally using Delphi methodology and a position paper endorsed by transplant societies, could provide a reference framework for future studies, improving comparability, risk stratification, and clinical management of liver transplant recipients.