Poster T20 - Dynamic Heart Performance Assessment: Mathematical Models for Tackling Heart Transplantation Challenges in Real Time

Introduction: Cardiac transplantation, often considered the ultimate treatment for end-stage heart failure, encounters a significant obstacle in the form of organ availability mismatched with the high demand from recipients. Normothermic ex-vivo heart perfusion (EVHP) platforms have emerged as a promising solution to expand the heart transplantation pool by enhancing the functionality of discarded hearts. However, there exists a pressing need for standardized assessment of the efficacy of this approach. To address this gap, we propose leveraging well-established mathematical modeling techniques to facilitate such assessment. Our approach involves applying mathematical modeling to an ex vivo experiment comparing a set of Swine hearts at two different cold storage times, thereby demonstrating the practical application of this methodology in evaluating the effectiveness of EVHP.

Materials and

Methods: In collaboration with our clinical partners, we successfully restored the function of swine hearts following different cold storage times, as determined by their cold ischemia time (CIT). Our team developed an in-house ex-vivo heart perfusion system capable of assessing heart function in both Langendorff and loaded models. Various signals, including left ventricle pressure, aortic tube pressure, and flow rates, were measured during the heart runs and utilized to optimize our computational model (Fig.1). Leveraging MATLAB Simulink, we constructed a lumped parameter model (LPM) of the cardiovascular system, incorporating passive electrical elements and active voltage/current sources. Model parameters were fine-tuned to match experimental and clinical recordings, minimizing error using the sum squared error (SSE) cost function.

Results, Conclusions, and Discussions: We have developed a comprehensive model that captures the dynamic behavior of the left heart, including the corresponding pressure and flow dynamics at various positions within the vascular tree. This robust model offers diverse waveforms representing functional variables across different pathological conditions in relevant anatomical segments. Through rigorous validation against experimental data and existing models, our approach demonstrates real-time computational efficiency using ordinary differential equations. Importantly, our model enables non-invasive extraction of functional information from multiple locations, eliminating the need for invasive measurements in clinical settings. Intriguingly, our findings challenge the conventional belief that longer CIT pose a greater risk to heart function upon reperfusion. Our ex-vivo reperfusion experiments revealed comparable heart function in hearts subjected to longer CIT durations compared to those with shorter or no CIT. The swine heart subject to a 0hr CIT showed an estimated ejection fraction of 32% whereas the 5hr CIT one showed an ejection fraction of 34% (Fig.2). This observation carries significant implications, potentially expanding the pool of viable donor hearts by allowing procurement from more distant sites.
Our model accurately replicates the hemodynamic waveforms observed in the ex vivo experimental setup. Utilizing these outputs in conjunction with echocardiography measurements conducted during the experiments, we are able to successfully extract key metrics of heart function. Performance analysis, including the computation of pressure-volume loops from which stroke volume and ejection fraction are derived, indicates comparable function between the two experimental conditions with different CIT. The developed physiological lumped-parameter model (LPM) serves as a comprehensive tool that advances our understanding of cardiovascular function. This innovative approach has the potential to revolutionize transplantation research by streamlining the prompt evaluation of heart function and contractility, while also reducing the costs associated with ex vivo and in vivo experimentation in normothermic ex vivo heart perfusion (EVHP).

Acknowledgements (Optional): The authors acknowledge the assistance provided by George Olverson and Doug Vincent in conducting the experiments.