Primary graft dysfunction (PGD) remains the leading cause of early morbidity and mortality after heart transplantation. Despite consensus definitions, clinicians still rely on subjective, indirect assessments of graft performance to determine when to initiate ECMO after transplant concludes risking delayed support initiation. No real-time, physiology-based marker currently guides early PGD recognition or standardizes ECMO decision-making across centers.

To evaluate the utility of the cardiac power output index adjusted for vasoactive support (CPOI-VIS) as an early, dynamic, and clinically actionable physiologic marker of PGD, capable of predicting imminent ECMO requirement and short-term outcomes after heart transplantation.

All adult heart transplant recipients at a single center (January 2020 to June 2025 [n = 547]) were retrospectively analyzed. Multiorgan recipients, congenital heart disease, and patients leaving the operating room on ECMO were excluded. CPOI-VIS was calculated hourly for the first 72 postoperative hours and censored at ECMO initiation. Dynamic 6-hour risk modeling, rolling ROC analyses, and unsupervised functional trajectory phenotyping was used to characterize CPOI-VIS behavior and its association with ECMO within 72 hours. The primary endpoint was ECMO initiation; secondary endpoints included 90-day mortality, renal replacement therapy, and ICU length of stay.

Sixteen patients (2.9%) required ECMO within 72 hours. CPOI-VIS values diverged immediately between ECMO and non-ECMO groups (p < 0.001). For every 1-unit decrease in CPOI-VIS, the associated hazard of ECMO in the next 6 hours more than doubled (HR 2.23; 95% CI 1.66-2.99; C-index 0.96). Across 0 to 72 hours, discrimination remained consistently high (median AUC 0.98; IQR 0.96-0.99) with a stable predictive threshold (median 4.8; IQR 3.9-5.7). Among those crossing CPOI-VIS < 4.8W/m², early ECMO (<24 hours) was associated with markedly lower 90-day mortality compared with later initiation (0% vs 40%), with a >93% posterior probability of benefit. A “low CPOI-VIS” trajectory was strongly associated with ECMO, renal failure, prolonged ICU stay, and increased 90-day mortality.

CPOI-VIS is a robust, physiology-based, real-time marker of early graft dysfunction after heart transplantation that reliably identifies patients at high risk for imminent hemodynamic collapse and may guide earlier ECMO initiation.