Evaluating cardiac function in ex vivo heart perfusion using lumped parameter models

Abstract

Background

Heart transplant outcomes and survival depend on the ability to implant well-functioning organs, but there remain no reliable, objective measures of cardiac function prior to implantation. The lack of standardized protocols and advanced technologies results in inconsistencies and subjective assessments, increasing the risk for postoperative graft dysfunction, the leading cause of short-term morbidity and mortality after transplant. Ex-vivo heart perfusion (EVHP) provides a platform to evaluate donor hearts prior to implantation, using machine perfusion to reanimate the heart to a beating, physiologic state. The FDA-approved Organ Care System (OCS) is widely utilized for the evaluation and ex vivo preservation of hearts, particularly from donors after circulatory death (DCD). However, it does not permit a physiological assessment of heart function because, while the heart continues to beat, its chambers remain devoid of perfusate and thus are unable to perform any functional work.

Method

In this study, we developed and validated a lumped parameter mathematical model to assess donor hearts during ex-vivo perfusion, using a customized, in-house EVHP setup that allows left ventricular loading.

Results

We demonstrate the ability of our mathematical model to accurately predict hemodynamic parameters, enabling performance analysis of hearts during EVHP. Our model generates pressure-volume loops, allowing for the computation of ejection fraction, and was verified with experimental measurements taken via echocardiography.

Conclusion

This promising tool demonstrates the unique opportunity to utilize mathematical modeling in the assessment of donor hearts, streamlining their performance evaluation. Ultimately, a more accurate assessment of donor hearts on EVHP may improve our utilization of available donor hearts, addressing the donor organ shortage that continues to limit transplant capabilities.