Heart Preservation Research Articles

Recipient Outcomes With Extended Criteria Donors Using Advanced Heart Preservation: An Analysis of the GUARDIAN-Heart Registry

PurposeThe prevalence of end stage heart failure and patients that could benefit from heart transplantation requires an expansion of the donor pool, relying on the transplant community to continually re-evaluate and expand the use of extended criteria donor organs. Introduction of new technologies such as the Paragonix SherpaPak Cardiac Transport System aids in this shift. We seek to analyze the impact of the SherpaPak system on recipient outcomes who receive extended criteria organs in the GUARDIAN Heart Registry. MethodsBetween October 2015-December 2022, 1,113 adults from 15 US centers receiving donor hearts utilizing either SherpaPak (N=560) or conventional ice storage (Ice, N=453) were analyzed from the GUARDIAN-Heart registry using summary statistics. A previously published set of criteria was used to identify extended criteria donors, which included 193 SherpaPak and 137 ice. ResultsThere were a few baseline differences among recipients in the 2 cohorts, most notably IMPACT Scores, distance traveled and total ischemic time were significantly greater in SherpaPak, and significantly more donor hearts in the SherpaPak cohort had >4 hours total ischemia time. Post-transplant MCS utilization (SherpaPak 22.3% vs. ice 35.0%, p=0.012) and new ECMO/VAD (SherpaPak 7.8% vs. ice 15.3%, p=0.033) was significantly reduced, and the rate of severe PGD (SherpaPak 6.2% vs. ice 13.9%, p=0.022) was significantly reduced by over 50% in hearts preserved using SherpaPak. One-year survival between cohorts was similar (SherpaPak 92.9% vs. ice 89.6%, p=0.27). ConclusionThis subgroup analysis demonstrates that SherpaPak can be safely used to utilize extended criteria donors, with low severe PGD rates.

Non-ischaemic preservation of the donor heart in heart transplantation: protocol design and rationale for a randomised, controlled, multicentre clinical trial across eight European countries

IntroductionIschaemic cold static storage (ICSS) is the gold standard in donor heart preservation. This ischaemic time frame renders a time constraint and risk for primary graft dysfunction. Cold oxygenated heart...

Donor Heart Preservation: Current Knowledge and the New Era of Machine Perfusion

Heart transplantation remains the conventional treatment in end-stage heart failure, with static cold storage (SCS) being the standard technique used for donor preservation. Nevertheless, prolonged cold ischemic storage is associated with the increased risk of early graft dysfunction attributed to residual ischemia, reperfusion, and rewarming damage. In addition, the demand for the use of marginal grafts requires the development of new methods for organ preservation and repair. In this review, we focus on current knowledge and novel methods of donor preservation in heart transplantation. Hypothermic or normothermic machine perfusion may be a promising novel method of donor preservation based on the administration of cardioprotective agents. Machine perfusion seems to be comparable to cold cardioplegia regarding donor preservation and allows potential repair treatments to be employed and the assessment of graft function before implantation. It is also a promising platform for using marginal organs and increasing donor pool. New pharmacological cardiac repair treatments, as well as cardioprotective interventions have emerged and could allow for the optimization of this modality, making it more practical and cost-effective for the real world of transplantation. Recently, the use of triiodothyronine during normothermic perfusion has shown a favorable profile on cardiac function and microvascular dysfunction, likely by suppressing pro-apoptotic signaling and increasing the expression of cardioprotective molecules.

Hypothermic oxygenated perfusion (HOPE) safely and effectively extends acceptable donor heart preservation times: Results of the Australian and New Zealand trial

BackgroundCold static storage (CSS) preservation of donor hearts for periods longer than 4 hours increases the risk of primary graft dysfunction (PGD). The aim of the study was to determine if hypothermic oxygenated perfusion (HOPE) could safely prolong the preservation time of donor hearts. MethodsWe conducted a non-randomised, single arm, multi-center investigation of the effect of HOPE using the XVIVO Heart Preservation System on donor hearts with a projected preservation time of 6-8 hours on 30-day recipient survival and allograft function post-transplant. Each center completed 1 or 2 short preservation time followed by long preservation time cases. PGD was classified as occurring in the first 24 hours after transplantation or secondary (SGD) occurring at any time with a clearly defined cause. Trial survival was compared with a comparator group based on data from the International Society of Heart and Lung Transplantation Registry. ResultsWe performed heart transplants using 7 short and 29 long preservation time donor hearts placed on the HOPE system. The mean preservation time for the long preservation time cases was 414 minutes, the longest being 8 hours and 47 minutes. There was 100% survival at 30 days. One long preservation time recipient developed PGD, and 1 developed SGD. One short preservation time patient developed SGD. 30-day survival was superior to the ISHLT comparator group despite substantially longer preservation times in the trial patients. ConclusionsHOPE provides effective preservation out to preservation times of nearly 9 hours allowing retrieval from remote geographic locations.

Better then ice! Utilization of Paragonix SherpaPak for human donor heart preservation – our experience

Better then ice! Utilization of Paragonix SherpaPak for human donor heart preservation – our experience

Utilization of Paragonix Sherpapak Cardiac Transport System for the Preservation of Donor Hearts After Circulatory Death

Donation after circulatory death (DCD) heart transplantation is being increasingly adopted by transplant centers. The optimal method of DCD heart preservation during transport after in situ thoracoabdominal normothermic regional perfusion (TA-NRP) is not known. We evaluated our experience with the Paragonix SherpaPak Cardiac Transport System (SCTS) for the transport of DCD cardiac allografts after TA-NRP recovery between January 2021 and December 2022. We collected and evaluated donor characteristics, allograft ischemic intervals, and recipient baseline demographic and clinical variables, and short-term outcomes. Twelve recipients received DCD grafts recovered with TA-NRP and transported in SCTS during the study period. The median age of 10 male and 2 female donors was 32 years (min 15, max 38). The median duration of functional warm ischemia was 12 minutes (min 8, max 22). Hearts were preserved in SCTS for a median of 158 minutes (min 37, max 224). Median recipient age was 61 years (min 28, max 70). Ten recipients (83%) survived to hospital discharge, with one death attributable to graft dysfunction (8%). The median vasoactive-inotropic (VIS) score at 72 hours post-transplantation of the entire cohort was 6 (min 0, max 15). The median length of intensive care unit stay in hospital survivors was 5 days (min 3, max 17) days and hospital stay 17 days (min 9, max 37). The Paragonix SCTS provides efficacious preservation of DCD grafts for ≥3.5 hours. Organs transported with this device showed satisfactory post-transplantation function.

A Paradigm Shift in Heart Preservation: Improved Post-transplant Outcomes in Recipients of Donor Hearts Preserved with the SherpaPak System.

Traditional ice storage has been the historic standard for preserving donor's hearts. However, this approach provides variability in cooling, increasing risks of freezing injury. To date, no preservation technology has been reported to improve survival after transplantation. The Paragonix SherpaPak Cardiac Transport System (SCTS) is a controlled hypothermic technology clinically used since 2018. Real-world evidence on clinical benefits of SCTS compared to conventional ice cold storage (ICS) was evaluated. Between October 2015 and January 2022, 569 US adults receiving donor hearts preserved and transported either in SCTS (n = 255) or ICS (n = 314) were analyzed from the Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN-Heart) registry. Propensity matching and a subgroup analysis of >240 minutes ischemic time were performed to evaluate comparative outcomes. Overall, the SCTS cohort had significantly lower rates of severe primary graft dysfunction (PGD) (p = 0.03). When propensity matched, SCTS had improving 1-year survival (p = 0.10), significantly lower rates of severe PGD (p = 0.011), and lower overall post-transplant MCS utilization (p = 0.098). For patients with ischemic times >4 hours, the SCTS cohort had reduced post-transplant MCS utilization (p = 0.01), reduced incidence of severe PGD (p = 0.005), and improved 30-day survival (p = 0.02). A multivariate analysis of independent risk factors revealed that compared to SCTS, use of ice results in a 3.4-fold greater chance of severe PGD (p = 0.014). Utilization of SCTS is associated with a trend toward increased post-transplant survival and significantly lower severe PGD and MCS utilization. These findings fundamentally challenge the decades-long status quo of transporting donor hearts using ice.

Combined triiodothyronine and preconditioning improves cardiac diastolic dysfunction in ex vivo rat hearts subjected to normothermic perfusion: a new method for donor heart preservation

Combined triiodothyronine and preconditioning improves cardiac diastolic dysfunction in ex vivo rat hearts subjected to normothermic perfusion: a new method for donor heart preservation

Graft preservation in heart transplantation: current approaches.

Heart transplantation (HTx) represents the current best surgical treatment for patients affected by end-stage heart failure. However, with the improvement of medical and interventional therapies, the population of HTx candidates is increasingly old and at high-risk for mortality and complications. Moreover, the use of "extended donor criteria" to deal with the shortage of donors could increase the risk of worse outcomes after HTx. In this setting, the strategy of donor organ preservation could significantly affect HTx results. The most widely used technique for donor organ preservation is static cold storage in ice. New techniques that are clinically being used for donor heart preservation include static controlled hypothermia and machine perfusion (MP) systems. Controlled hypothermia allows for a monitored cold storage between 4°C and 8°C. This simple technique seems to better preserve the donor heart when compared to ice, probably avoiding tissue injury due to sub-zero °C temperatures. MP platforms are divided in normothermic and hypothermic, and continuously perfuse the donor heart, reducing ischemic time, a well-known independent risk factor for mortality after HTx. Also, normothermic MP permits to evaluate marginal donor grafts, and could represent a safe and effective technique to expand the available donor pool. However, despite the increasing number of donor hearts preserved with these new approaches, whether these techniques could be considered superior to traditional CS still represents a matter of debate. The aim of this review is to summarize and critically assess the available clinical data on donor heart preservation strategies employed for HTx.

CARD27: Morphologic and functional assessment of beating heart in normothermic ex-situ preservation

Background: Heart transplantation remains the treatment of choice for patients experiencing end-stage heart failure. The emergence of cardiac ex situ machine perfusion not only facilitates the use of donor heart through the avoidance of potentially damaging ischemia during graft storage, it also opens new horizons for more sensitive monitoring of graft quality in the transplant field, and morphologic-functional assessment. Methods: Twenty-five domestic adult pigs, weighing 93.1±13.1kg were selected for this study. Until cardiectomy, all pigs received Principles of Laboratory Animal Care. The pig heart were cannulated, and then connected to the Portable System for Normothermic Ex-Situ HeartPreservation (our made). In the Heart Preservation System (HPS), oxygenated blood is perfused by a centrifugal pump into the aorta, perfusing the coronary arteries. After the end of experiment, (6-14 hour) pig heart was arrested with normothermic blood cardioplegia and disconnected. The pig isolated heart was conditioned with Levosimendan while in the system and hemofiltration was applied in the HPS in order to protect and improve donor heart function. Ex-Situ Heart Perfusion process was accompanied with morphologic-functional assessment such as echocardiography, contrast-enhanced magnetic resonance, thermodilution technique and biochemistry. Results: Mean (SD) ischemic time was 19.2 (±3.3) min. Mean ex vivo perfusion time was 560 (±143) min. Time of sinus rhythm restoration was 2.3 (5.7) min. All isolated hearts had stable perfusion, biochemical, as well as myocardial functional parameters measured by echocardiography and thermodilution technique, and histological characteristics in the perfusion system. MRI structural images showed no infiltrates alterations in myocardium. Mean venous lactate trend are with normal levels at the end of perfusion 1.6 (±0.6). Conclusion: Normothermic Ex-Situ Heart Perfusion provides near to physiologic, reproducible approach to sustain the isolated heart for long period of time. Multiparametric assessment of organ morphology and function is feasible in Ex-Situ Heart Perfusion, and may improve organ assessment, leading to a better selection for transplant.Figure 1. Simplified schema of the experimental design and protocol.

CARC17: Outcomes in Heart Transplant Recipients with Sex Mismatched Organs: A Subgroup Analysis of the GUARDIAN-Heart Registry

Background: Donor and recipient sex mismatch in heart transplantation is considered a risk factor for poor outcomes. The mechanisms for this are poorly understood. We sought to assess whether a male to female or female to male donor mismatch influences outcomes following transplants using donor hearts preserved with the SherpaPak Cardiac Transport System (CTS). The CTS provides controlled hypothermic heart preservation during transportation which may abate cold injury to the donor heart. Methods: The GUARDIAN-Heart registry is an international, multicenter registry assessing outcomes following heart transplantation using donor organs preserved with CTS compared to standard ice transportation (ICE). A subgroup analysis of sex-mismatched donors and recipients resulted in cohorts of 121 ICE transplants compared to 141 CTS transplants. Summary statistics were used for comparing the groups. Further analysis with ongoing enrollment will be available for presentation. Results: The baselines of the two groups were similar, including the proportion of female to male mismatches (57% (ICE) vs 56%, (CTS), p = 0.87) and the percent undersized by >15% (17.4% (ICE) vs 22.5% (CTS), p = 0.33), except there was significantly longer total ischemic time in transplants using CTS by 26 minutes (195.2 vs 221.2 minutes, p = 0.004) and distance traveled to procure the organs was 44% farther (251.6 vs 445.7 miles, p < 0.001, ICE vs CTS, respectively). Post-transplant, the incidence of severe PGD was similar (11.7% vs 7.8%, p = 0.29, ICE vs CTS, respectively), as was the total length of ICU and hospital stay. The CTS cohort demonstrated a significant improvement in both 30 day (95% vs 100%, p = 0.01) and in-hospital survival (92.6% vs 99.3%, p = 0.005, ICE vs CTS, respectively). Conclusions: Despite significantly longer ischemic times, use of the SherpaPak CTS resulted in improved early survival when compared to heart transplants using standard ice transport.

Initial Australian Experience With the XVIVO Non-Ischaemic Hypothermic Perfusion Device for Heart Preservation

Due to the current demand for donor hearts, the limits of acceptable organs are increasingly being pushed. Previous literature has shown that prolonged ischaemic time in transport remains a key limitation, with excess morbidity such as early primary graft dysfunction requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) (rates of up to 30% have been reported). This study highlighted outcomes from the first 10 patients who received a donor heart retrieved on the XVIVO hypothermic perfusion organ care device at St Vincent’s Hospital, Sydney.

CARD16: Prolonged Normothermic Ex Vivo Heart Perfusion with Hemofiltration in Resting and Intermittent Working-heart Models

Introduction: Cold static storage (5C) or normothermic (37C) ex vivo heart perfusion (NEVHP) in the beating but resting mode (Langendorff) successfully preserves hearts for transplantation for up to 6 hours. Previous attempts to prolong the preservation period increases morbidity and mortality following transplantation. In addition, the 6-hour limit imposes geographic restrictions for recipients, prevents optimal organ assessment, and reduces the number of hearts available for transplantation. We have successfully maintained 10 consecutive pediatric hearts (60±8.8 g) for 24 hours using NEVHP with hemofiltration in the beating, resting-heart mode. Although this prolonged NEVHP model was successful, cardiac function could not be comprehensively assessed in the beating, resting-heart mode. We sought to expand our prolonged NEVHP model to include intermittent left atrial (LA) perfusion that would allow cardiac assessment in the working-heart mode. Methods: We performed 24-hour NEVHP on 5 consecutive hearts (276 ±22.6 g). Following anesthetic induction, sternotomy, cardioplegia administration, explantation, and back-table instrumentation, NEVHP was initiated in beating, resting mode. After 1 hour the circuit was transitioned to LA perfusion working-heart mode for 30 minutes, baseline working-heart parameters were documented (Figure 1) and perfusion was returned to beating, resting-heart mode. Intermittent LA perfusion with working-heart assessment was performed every 4-6 hours. Final working-heart measurements were obtained at 24 hours. Results: All hearts survived 24 hours and all maintained working-heart parameters statistically identical to baseline. Mean LA pressure was 8.2±7.5 mmHg, peak left ventricle (LV) pressure was 33.9±8.7 mmHg, mean LV pressure was 12.0±13.7 mmHg, peak aortic pressure was 35.6±7.8 mmHg, mean aortic pressure was 22.8±7.7 mmHg, coronary resistance 0.15±0.05 mmHg/L/min, and lactate levels were 2.7±0.6 mmol/L. Conclusions: We have successfully developed and validated a porcine NEVHP model for assessment of cardiac function in the working-heart mode using intermittent LA perfusion. While intermittent LA perfusion is an important step toward comprehensive ex vivo assessment of donor heart function, proof of cardiac preservation following prolonged NEVHP still requires successful transplantation and complete assessment in the recipient. We plan to perform this as our next step toward prolonged ex vivo heart preservation. Techniques and cannula for intermittent LA perfusion in the pediatric model will also be developed.

Organ Preservation in the 2020s: XVIVO Heart Box (Part 2)

The XVIVO Heart Box (XHB) is an emerging technology in cardiac transplantation that protects the donor heart via non-ischaemic heart preservation (NIHP). A first-in-human trial utilising XHB demonstrated its safe use in human cardiac transplantation [ [1] Nilsson J, Jernryd V, Qin G, Paskevicius A, Metzsch C, Sjöberg T, et al. A nonrandomized open-label phase 2 trial of nonischemic heart preservation for human heart transplantation. Nat Commun. 2020;11:2976. Google Scholar ]. In response, an Australian and New Zealand multicentre trial of extended (6–8 hours) NIHP of donor hearts for transplantation utilising XHB is underway. The current study is an open-labelled, single-arm, multicentre clinical trial. It aims to investigate the effect of NIHP on donor hearts with extended ischaemic time (6–8 hours) with respect to immediate and long-term post-transplant heart allograft function.

Research Highlights.

Research Highlights.

Rat Model of Normothermic Ex-Situ Perfused Heterotopic Heart Transplantation.

Heart transplantation is the most effective therapy for end-stage heart failure. Despite the improvements in therapeutic approaches and interventions, the number of heart failure patients waiting for transplantation is still increasing. The normothermic ex situ preservation technique has been established as a comparable method to the conventional static cold storage technique. The main advantage of this technique is that donor hearts can be preserved for up to 12 h in a physiologic condition. Moreover, this technique allows resuscitation of the donor hearts after circulatory death and applies required pharmacologic interventions to improve donor function after implantation. Numerous animal models have been established to improve normothermic ex situ preservation techniques and eliminate preservation-related complications. Although large animal models are easy to handle compared to small animal models, it is costly and challenging. We present a rat model of normothermic ex situ donor heart preservation followed by heterotopic abdominal transplantation. This model is relatively cheap and can be accomplished by a single experimenter.

Donor heart ischemic time can be extended beyond 9 hours using hypothermic machine perfusion in sheep

The global shortage of donor hearts available for transplantation is a major problem for the treatment of end-stage heart failure. The ischemic time for donor hearts using traditional preservation by standard static cold storage (SCS) is limited to approximately 4 hours, beyond which the risk for primary graft dysfunction (PGD) significantly increases. Hypothermic machine perfusion (HMP) of donor hearts has been proposed to safely extend ischemic time without increasing the risk of PGD. Using our sheep model of 24 hours brain death (BD) followed by orthotopic heart transplantation (HTx), we examined post-transplant outcomes in recipients following donor heart preservation by HMP for 8 hours, compared to donor heart preservation for 2 hours by either SCS or HMP. Following HTx, all HMP recipients (both 2 hours and 8 hours groups) survived to the end of the study (6 hours after transplantation and successful weaning from cardiopulmonary bypass), required less vasoactive support for hemodynamic stability, and exhibited superior metabolic, fluid status and inflammatory profiles compared to SCS recipients. Contractile function and cardiac damage (troponin I release and histological assessment) was comparable between groups. Overall, compared to current clinical SCS, recipient outcomes following transplantation are not adversely impacted by extending HMP to 8 hours. These results have important implications for clinical transplantation where longer ischemic times may be required (e.g., complex surgical cases, transport across long distances). Additionally, HMP may allow safe preservation of "marginal" donor hearts that are more susceptible to myocardial injury and facilitate increased utilization of these hearts for transplantation.

(120) Heart Preservation with the Organ Care System in Extended Criteria Donor Hearts: A Single Center Experience

(120) Heart Preservation with the Organ Care System in Extended Criteria Donor Hearts: A Single Center Experience

(621) How Long Can We Go? Redefining the Upper Limit of Ischemic Times for Hypothermic Donor Heart Preservation

(621) How Long Can We Go? Redefining the Upper Limit of Ischemic Times for Hypothermic Donor Heart Preservation

(1084) Successful Heart Transplantation Using a Portable Normothermic Ex-Vivo Donor Heart Preservation System for Extended Criteria Donor after Circulatory Death: A Case Series with Extended Perfusion Times

(1084) Successful Heart Transplantation Using a Portable Normothermic Ex-Vivo Donor Heart Preservation System for Extended Criteria Donor after Circulatory Death: A Case Series with Extended Perfusion Times