Cardiac Graft Assessment in the Era of Machine Perfusion: Current and Future Biomarkers

Bona, M C; Wyss, Rahel K.; Arnold, Marlène; Méndez-Carmona, Natalia; Sanz, María-Nieves; Guensch, Dominik P.; Barile, Lucio; Carrel, Thierry; Longnus, Sarah L.

doi:10.1161/jaha.120.018966

Cited by 16 publications

(6 citation statements)

References 96 publications

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“…The role of serial lactate measurement in biochemically assessing organ viability is controversial, with some suggesting it is an inconsistent and insensitive marker of early graft function. 24,25 Within our more contemporary group 2, we attempted to better understand the relationship between donor heart viability and lactate trends during NMP. We performed histopathological analysis of the 2 donor hearts declined based on lactate profiles, as can be noted in the results and in Figure 6, both AHs demonstrated an underlying cardiomyopathy.…”

Section: Lactate Profilesmentioning

confidence: 99%

Heart Transplantation From DCD Donors in Australia: Lessons Learned From the First 74 Cases

et al. 2022

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Heart transplantation from donation after circulatory death (DCD) donors has the potential to substantially increase overall heart transplant activity. The aim of this report is to review the first 8 y of our clinical heart transplant program at St Vincent’s Hospital Sydney, to describe how our program has evolved and to report the impact that changes to our retrieval protocols have had on posttransplant outcomes. Since 2014, we have performed 74 DCD heart transplants from DCD donors utilizing a direct procurement protocol followed by normothermic machine perfusion. Changes to our retrieval protocol have resulted in a higher retrieval rate from DCD donors and fewer rejections of DCD hearts during normothermic machine perfusion. Compared with our previously reported early experience in the first 23 transplants, we have observed a significant reduction in the incidence of severe primary graft dysfunction from 35% (8/23) to 8% (4/51) in the subsequent 51 transplant recipients (P < 0.01). The only withdrawal time interval significantly associated with severe primary graft dysfunction was the asystolic warm ischemic time: 15 (12–17) versus 13 (11–14) min (P < 0.05). One- and 5-y survival of DCD heart transplant recipients was 94% and 88%, comparable to that of a contemporary cohort of donation after brain death recipients: 87 and 81% (P-value was not significant). In conclusion, heart transplantation from DCD donors has become a major contributor to our overall transplant activity accounting for almost 30% of all transplants performed by our program in the last 2 y, with similar DCD and donation after brain death outcomes.

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Section: Lactate Profilesmentioning

confidence: 99%

Heart Transplantation From DCD Donors in Australia: Lessons Learned From the First 74 Cases

et al. 2022

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“…Study results revealed that hypothermic machine perfusion (HMP) between 4 and 10°C contributes to the reduction of the active metabolic state in cardiac grafts, as measured by low lactate and other myocardial markers expression, thereby minimizing the risk of the accumulation of toxic metabolites while maintaining cardiac viability ( 26 ). Examination of various metabolic markers, including oxygen consumption and lactate levels, demonstrated notable correlations with myocardial function during machine perfusion ( 4 ). The Arrhenius equation can be used to estimate the organ's oxygen demand during cardiac preservation.…”

Section: Discussionmentioning

confidence: 99%

“…In the United States alone, about 20% of patients on the heart transplant waiting list die or become too sick to remain good transplant candidates ( 3 ). Approaches to decrease organ shortage include the use of extended-criteria donors (ECDs) or donation after circulatory death (DCD) as well as the emergence of ex-situ machine perfusion (MP) systems as an alternative to the standard of care, the static cold storage ( 4 ). It has been estimated that DCD heart transplantation can increase the heart donor pool by about 30% ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Novel portable hypothermic machine perfusion preservation device enhances cardiac viability of donated human hearts

Andrijauskaite,

Veraza,

Lopez

et al. 2024

Front. Cardiovasc. Med.

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IntroductionHeart transplant remains the gold standard treatment for patients with advanced heart failure. However, the list of patients waiting for a heart transplant continues to increase. We have developed a portable hypothermic oxygenated machine perfusion device, the VP.S ENCORE®, to extend the allowable preservation time. The purpose of this study was to test the efficacy of the VP.S. ENCORE® using deceased donors derived hearts.MethodsHearts from brain-dead donors not utilized for transplant (n = 11) were offered for research from the Texas Organ Sharing Alliance (TOSA), South and Central Texas' Organ Procurement Organization (OPO) and were preserved in the VP.S ENCORE® for 4 (n = 2), 6 (n = 3), and 8 (n = 3) hours or were kept in static cold storage (SCS) (n = 3). After preservation, the hearts were placed in an isolated heart Langendorff model for reperfusion and evaluated for cardiac function.ResultsThe mean donor age was 37.82 ± 12.67 with the youngest donor being 19 and the oldest donor being 58 years old. SCS hearts mean weight gain (%) was −1.4 ± 2.77, while perfused at 4 h was 5.6 ± 6.04, perfused at 6 h 2.1 ± 6.04, and 8 h was 7.2 ± 10.76. Venous and arterial lactate concentrations were less than 2.0 mmol/L across all perfused hearts. Left ventricular contractility (+dPdT, mmHg/s) for 4 h (1,214 ± 1,064), 6 (1,565 ± 141.3), and 8 h (1,331 ± 403.6) were within the range of healthy human heart function. Thus, not significant as compared to the SCS group (1,597 ± 342.2). However, the left ventricular relaxation (mmHg/s) was significant in 6-hour perfused heart (p < 0.05) as compared to SCS. Gene expression analysis of inflammation markers (IL-6, IL-1β) showed no significant differences between SCS and perfused hearts, but a 6-hour perfusion led to a downregulated expression of these markers.DiscussionThe results demonstrate that the VP.S ENCORE® device enhances cardiac viability and exhibits comparable cardiac function to a healthy heart. The implications of these findings suggest that the VP.S ENCORE® could introduce a new paradigm in the field of organ preservation, especially for marginal hearts.

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“…Ex situ machine perfusion (MP) is an exciting frontier in donor assessment. Although not currently part of our program's algorithm, we acknowledge the tremendous potential of these devices to facilitate the use of extended criteria donors and promote organ recovery through therapeutic drug and nutrient delivery [58]. Normothermic machine perfusion permits visual inspection of contractile function and coronary blood flow under conditions that mimic human physiology, a capacity with potentially high importance considering evaluations of left ventricular contractility using machine perfusion are strongly correlated with posttransplant cardiac function [59].…”

Section: Machine Perfusion Assessmentmentioning

confidence: 99%

Evaluation of donor heart for transplantation

et al. 2022

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Cardiac transplantation is considered the gold-standard treatment option for patients suffering from end-stage heart failure refractory to maximum medical therapy. A major determinant of graft function and recipient survival is a comprehensive evaluation of the donor allograft. Challenges arise when designing and implementing an evidence-based donor evaluation protocol due to the number of influential donor-specific characteristics and the complex interactions that occur between them. Here, we present our systematic approach to donor evaluation by examining the impact that relevant donor variables have on graft function and recipient outcomes.

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Cardiac Graft Assessment in the Era of Machine Perfusion: Current and Future Biomarkers

Cited by 16 publications

References 96 publications

Heart Transplantation From DCD Donors in Australia: Lessons Learned From the First 74 Cases

Heart Transplantation From DCD Donors in Australia: Lessons Learned From the First 74 Cases

Novel portable hypothermic machine perfusion preservation device enhances cardiac viability of donated human hearts

Evaluation of donor heart for transplantation

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