Roig Raimon Casamitjana, Li Selena S, Asheghan Mostafa, Olverson George, Vincent Doug, Bolger-Chen Maya, Ajenu Emmanuella, Higuita Manuela Lopera, Tessier Shannon N, Osho Asishana, D'Alessandro David A, Rabi S Alireza, Nezami Farhad R
Division of Cardiac Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Comput Biol Med. 2025 May;189:109922. doi: 10.1016/j.compbiomed.2025.109922. Epub 2025 Mar 3.
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.
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.
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.
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.
心脏移植的结果和存活率取决于植入功能良好器官的能力,但在植入前仍缺乏可靠、客观的心脏功能测量方法。缺乏标准化方案和先进技术导致评估不一致且主观,增加了术后移植物功能障碍的风险,这是移植后短期发病和死亡的主要原因。体外心脏灌注(EVHP)提供了一个在植入前评估供体心脏的平台,利用机器灌注使心脏恢复到跳动的生理状态。美国食品药品监督管理局(FDA)批准的器官护理系统(OCS)被广泛用于心脏的评估和体外保存,特别是来自循环死亡供体(DCD)的心脏。然而,它不允许对心脏功能进行生理评估,因为虽然心脏继续跳动,但其腔室仍无灌注液,因此无法进行任何功能性工作。
在本研究中,我们开发并验证了一个集总参数数学模型,以在体外灌注期间评估供体心脏,使用定制的、内部的EVHP装置,该装置允许左心室负荷。
我们证明了我们的数学模型能够准确预测血流动力学参数,从而能够在EVHP期间对心脏进行性能分析。我们的模型生成压力-容积环,允许计算射血分数,并通过超声心动图进行的实验测量进行了验证。
这个有前景的工具展示了利用数学建模评估供体心脏的独特机会,简化了它们的性能评估。最终,对EVHP上的供体心脏进行更准确的评估可能会改善我们对可用供体心脏的利用,解决持续限制移植能力的供体器官短缺问题。