Donor Hearts Research Articles

(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

(568) Impact of Dcd Donor Hearts on Transplant Outcomes: A Propensity-Matched Analysis

(568) Impact of Dcd Donor Hearts on Transplant Outcomes: A Propensity-Matched Analysis

(189) Non-Ischaemic Heart Preservation to Improve Donor Heart Quality

(189) Non-Ischaemic Heart Preservation to Improve Donor Heart Quality

(397) Use of the SherpaPak Cardiac Transport System for Infant and Pediatric Donor Hearts: An Initial Experience

(397) Use of the SherpaPak Cardiac Transport System for Infant and Pediatric Donor Hearts: An Initial Experience

(744) Comparison of Heart Transplantation Outcomes in Recipients of Insulin-Dependent Diabetic Donor Hearts Based Upon Duration of Insulin Use

(744) Comparison of Heart Transplantation Outcomes in Recipients of Insulin-Dependent Diabetic Donor Hearts Based Upon Duration of Insulin Use

(988) Coincidence of Early Graft Rejection and Replication of Human Herpesvirus 6 in the Donor Heart Associated with a CD38+ Lineage of Negative T Cells

(988) Coincidence of Early Graft Rejection and Replication of Human Herpesvirus 6 in the Donor Heart Associated with a CD38+ Lineage of Negative T Cells

(70) Normothermic Regional Perfusion in Donation after Circulatory Death Heart Donors May Not Have a Detrimental Effect on Lung Transplant Outcomes

(70) Normothermic Regional Perfusion in Donation after Circulatory Death Heart Donors May Not Have a Detrimental Effect on Lung Transplant Outcomes

Research Highlights.

Research Highlights.

Better Than Ice: Advancing the Technology of Donor Heart Storage With the Paragonix SherpaPak.

Better Than Ice: Advancing the Technology of Donor Heart Storage With the Paragonix SherpaPak.

Electron Transport Chain Inhibition to Decrease Injury in Transplanted Donation After Circulatory Death Rat Hearts.

Donation after circulatory death (DCD) donor hearts sustain ischemic damage and are not routinely used for heart transplantation. DCD heart injury, particularly reperfusion injury, is primarily mediated by releasing reactive oxygen species from the damaged mitochondria (complex I of the electron transport chain). Amobarbital (AMO) is a transient inhibitor of complex I and is known to reduce releasing reactive oxygen species generation. We studied the beneficial effects of AMO in transplanted DCD hearts. Sprague-Dawley rats were assigned to 4 groups-DCD or DCD + AMO donors and control beating-heart donors (CBD) or CBD + AMO donors (n = 6-8 each). Anesthetized rats were connected to a ventilator. The right carotid artery was cannulated, heparin and vecuronium were administered. The DCD process started by disconnecting the ventilator. DCD hearts were procured after 25 minutes of in-vivo ischemia, whereas CBD hearts were procured without ischemia. At procurement, all donor hearts received 10 mL of University of Wisconsin cardioplegia solution. The CBD + AMO and DCD + AMO groups received AMO (2 mM) dissolved in cardioplegia. Heterotopic heart transplantation was performed by anastomosing the donor aorta and pulmonary artery to the recipient's abdominal aorta and inferior vena cava. After 14 days, transplanted heart function was measured with a balloon tip catheter placed in the left ventricle. Compared with CBD hearts, DCD hearts had significantly lower developed pressure. AMO treatment significantly improved cardiac function in DCD hearts. Treatment of DCD hearts at the time of reperfusion with AMO resulted in an improvement of transplanted heart function that was comparable with the CBD hearts.

Normothermic ex vivo heart perfusion with NLRP3 inflammasome inhibitor Mcc950 treatment improves cardiac function of circulatory death hearts after transplantation.

The utilization of donation after circulatory death (DCD) hearts can enlarge the donor pool. However, DCD hearts suffer from serious ischemia/reperfusion injury (IRI). Recent studies found that the activation of NLRP3 inflammasome could play a significant role in organ IRI. Mcc950, which is a novel inhibitor of the NLRP3 inflammasome, can be applied to treat various kinds of cardiovascular diseases. Therefore, we hypothesized that the treatment of mcc950 could protect DCD hearts preserved with normothermic ex vivo heart perfusion (EVHP) against myocardial IRI via inhibiting NLRP3 inflammasome in a rat heart transplantation model of DCD. Donor-heart rats were randomly divided into four groups: Control group; Vehicle group; MP-mcc950 group; and MP + PO-mcc950 group. Mcc950 was added into the perfusate of normothermic EVHP in the MP-mcc950 and MP + PO-mcc950 groups, and was injected into the left external jugular vein after heart transplantation in the MP + PO-mcc950 group. Cardiac functional assessment was performed. The level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-associated protein of donor hearts were evaluated. The treatment with mcc950 significantly increased the developed pressure (DP), dP/dtmax, and dP/dtmin of the left ventricular of DCD hearts at 90 min after heart transplantation in both MP-mcc950 and MP + PO-mcc950 groups. Furthermore, mcc950 added into perfusate and injected after transplantation in both MP-mcc950 and MP + PO-mcc950 groups significantly attenuated the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome compared with the vehicle group. Normothermic EVHP combined with mcc950 treatment can be a promising and novel DCD heart preservation strategy, which can alleviate myocardial IRI via inhibiting NLRP3 inflammasome.

Performance of an Irrigated Bipolar Radiofrequency Ablation Clamp on Explanted Human Hearts

BackgroundBipolar radiofrequency (RF) clamps are commonly used during surgical ablation for atrial fibrillation (AF). This study examined the efficacy of an irrigated bipolar RF clamp to create transmural lesions in an ex vivo human heart model. MethodsTen donor hearts, turned down for transplantation, were explanted and arrested with cold cardioplegia. The ablations of the Cox Maze IV procedure were performed using the Cardioblate LP (Medtronic, Inc) irrigated bipolar RF clamp. In the first 5 hearts, each lesion was created with a single application of RF, whereas in the remaining 5 hearts, each lesion was created with a double application of RF without unclamping. Each lesion was cross-sectioned and stained with 2,3,5-triphenyl-tetrazolium chloride to assess ablation depth and transmurality. ResultsA total of 100 lesions were analyzed. In the single-ablation group, 222 of 260 sections (85%) and 37 of 50 lesions (74%) were transmural. The efficacy improved significantly in the double-ablation group, in which 348 of 359 sections (97%, P < .001) and 46 of 50 lesions (92%, P = .017) were transmural. Overall, in nontransmural lesions, the epicardial fat thickness was significantly greater (1.69 ± 0.70 mm vs 0.45 ±0.10 mm, P < .001) than the transmural lesions. ConclusionsA single ablation on human atrial tissue with an irrigated bipolar RF clamp was insufficient to reliably create transmural lesions, but a double ablation significantly increased the lesion and section transmurality. Nontransmural lesions were associated with significantly thicker layers of epicardial fat, which likely decreased tissue energy delivery due to the higher resistance of fat to current flow.

Ex Vivo Gene Delivery to Porcine Cardiac Allografts Using a Myocardial-Enhanced Adeno-Associated Viral Vector.

Transplantation, the gold standard intervention for organ failure, is a clinical field that is ripe for applications of gene therapy. One of the major challenges in applying gene therapy to this field is the need for a method that achieves consistent and robust gene delivery to allografts. Normothermic ex vivo perfusion is a growing organ preservation method and a device for cardiac preservation was recently approved by the Food and Drug Administration (FDA) (Organ Care System, OCS™; TransMedics, Inc., Andover, MA); this device maintains donor hearts in a near physiologic state while they are transported from the donor to the recipient. This study describes the administration of recombinant adeno-associated viral vectors (rAAVs) during ex vivo normothermic perfusion for the delivery of transgenes to porcine cardiac allografts. We utilized a myocardial-enhanced AAV3b variant, SASTG, assessing its transduction efficiency in the OCS perfusate relative to other AAV serotypes. We describe the use of normothermic ex vivo perfusion to deliver SASTG carrying the Firefly Luciferase transgene to porcine donor hearts in four heterotopic transplant procedures. Durable and dose-dependent transgene expression was achieved in the allografts in 30 days, with no evidence of off-target transgene expression. This study demonstrates the feasibility and efficiency of delivering genes to a large animal allograft utilizing AAV vectors during ex vivo perfusion. These findings support the idea of gene therapy interventions to enhance transplantation outcomes.

Heart Transplant Using a Donor Heart With Only a Persistent Left Superior Vena Cava: A Case Report

A persistent left superior vena cava (PLSVC) is a congenital anomaly wherein the left superior cardinal vein fails to regress. We describe the case of a successful orthotopic heart transplant using a donor heart with a PLSVC and congenital absence of a right superior vena cava (SVC) in a recipient with normal anatomy. After donor cardiectomy, the donor organ's PLSVC was ligated near the insertion site into the coronary sinus. The recipient underwent cardiectomy such that the native SVC was left with a long right atrial cuff. A modified bicaval technique was used to anastomose the recipient's right atrial cuff directly to the donor's right atrial appendage. This technique restored the recipient's normal anatomy, and we demonstrated that donor hearts with a PLSVC and absent right SVC might be used for transplant. Without other disqualifying abnormalities, surgeons should consider accepting these organs for life-saving transplant operations.

Assessment of the Desire and Readiness of Taif Residents for Heart Donation After Death.

Background/aim Heart transplantation is often the only preferable treatment for end-stage heart failure (HF); however, there are insufficient organ donors in Saudi Arabia. In this study, we aimed to understand the desire and readiness of Taif populations for heart donation after death. Methods We carried out a descriptive cross-sectional study among Taif residents in November 2022. A questionnaire designed from a previous survey was distributed among the participants. The questionnaire included sociodemographic data and questions assessing their desire for heart donation. Results The study included 405 subjects who have accepted to participate in the study. About half of the participants were aged 18 to 32 years (43.5%), most were females, were non-employed, and had a university degree. Of them, 86.2% accepted the concept of organ transplantation, 81% accepted the concept of heart transplantation, and one-third of the participants desired to donate their hearts. The participants with a university degree reported significantly less acceptance of the concept of heart transplantation (p-value=0.026), and those employed showed a significantly stronger desire for organ donation to a relative after death (p-value=0.049). In addition, younger participants showed a significantly higher willingness for organ donation to a relative or non-relative after death (p-value=0.017 and 0.009, respectively). Employed participants were significantly more willing to undergo heart transplantation surgery if needed (p-value=0.044). Conclusion Awareness campaigns could be established in the community and popularized during contact with the health system to build trust in the organ donation system, stress the importance of heart donation in saving the lives of more patients, and reduce the shortage of organ transplantation.

A national pilot of donation after circulatory death (DCD) heart transplantation within the United Kingdom

The United Kingdom (UK) was one of the first countries to pioneer heart transplantation from donation after circulatory death (DCD) donors. To facilitate equity of access to DCD hearts by all UK heart transplant centers and expand the retrieval zone nationwide, a Joint Innovation Fund (JIF) pilot was provided by NHS Blood and Transplant (NHSBT) and NHS England (NHSE). The activity and outcomes of this national DCD heart pilot program are reported. This is a national multi-center, retrospective cohort study examining early outcomes of DCD heart transplants performed across 7 heart transplant centers, adult and pediatric, throughout the UK. Hearts were retrieved using the direct procurement and perfusion (DPP) technique by 3 specialist retrieval teams trained in ex-situ normothermic machine perfusion. Outcomes were compared against DCD heart transplants before the national pilot era and against contemporaneous donation after brain death (DBD) heart transplants, and analyzed using Kaplan-Meier analysis, chi-square test, and Wilcoxon's rank-sum. From September 7, 2020 to February 28, 2022, 215 potential DCD hearts were offered of which 98 (46%) were accepted and attended. There were 77 potential donors (36%) which proceeded to death within 2 hours, with 57 (27%) donor hearts successfully retrieved and perfused ex situ and 50 (23%) DCD hearts going on to be transplanted. During this same period, 179 DBD hearts were transplanted. Overall, there was no difference in the 30-day survival rate between DCD and DBD (94% vs 93%) or 90 day survival (90% vs 90%) respectively. There was a higher rate of ECMO use post-DCD heart transplants compared to DBD (40% vs 16%, p=0.0006), and DCD hearts in the pre pilot era, (17%, p=0.002). There was no difference in length of ICU stay (9 DCD vs 8 days DBD, p=0.13) nor hospital stay (28 DCD vs 27 DBD days, p=0.46). During this pilot study, 3 specialist retrieval teams were able to retrieve DCD hearts nationally for all 7 UK heart transplant centers. DCD donors increased overall heart transplantation in the UK by 28% with equivalent early posttransplant survival compared with DBD donors.

Long-distance donor heart procurement using an innovative cold static storage system.

The global lack of donor shortage poses a major limitation for heart transplantation. New concepts with expanded donor inclusion criteria comprise extended transport distances and prolonged ischemic times with the aim of reaching a larger number of potential donors. Recent developments in cold storage solutions may allow more donor hearts with prolonged ischemic times to be use for transplantation in the future. We present our experience during a long-distance donor heart procurement with the longest reported transport distance and transport time in the current literature. This was made possible through the use of SherpaPak™, an innovative cold storage system which allows for controlled temperatures during transportation.

Do vasoactive medications impact donor hearts clinical outcomes in pediatric heart transplantation?

There is limited data examining donor vasopressor and/or inotrope medications (vasoactives) on pediatric orthotopic heart transplant (OHT) outcomes. We aim to evaluate the effects of vasoactives on pediatric OHT outcomes. The United Network for Organ Sharing database was retrospectively reviewed from January 2000 to March 2018 for donor hearts. Exclusion criteria included multiorgan transplants and recipient age >18. Donors receiving vasoactives at the time of procurement were compared to donors not on vasoactives, including the number of vasoactives and the type. End-points of interest were survival at 30 days and 1year as well as post-transplant rejection at 1year. Logistic and Cox models were used to quantify survival end-points. Of 6462 donors, 3187 (49.3%) were receiving at least one vasoactive. Comparing any vasoactive medication versus none, there was no difference in 30-day survival (p= .27), 1 year survival (p= .89), overall survival (p= .68), or post-transplant rejection (p= .98). There was no difference in 30-day survival for donors receiving 2 or more vasoactive infusions (p= .89), 1 year survival (p= .53), overall survival (p= .75), or post-transplant rejection at 1year (p= .87). Vasopressin was associated with decreased 30-day mortality (OR=0.22; p= .028), dobutamine with decreased 1-year mortality (OR=0.37; p= .036), overall survival (HR=0.51; p= .003), and decreased post-transplant rejection (HR=0.63; p= .012). There is no difference in pediatric OHT outcomes when the cardiac donor is treated with vasoactive infusions at procurement. Vasopressin and dobutamine were associated with improved outcomes. This information can be used to guide medical management and donor selection.

Utility of Recipient Cardiothoracic Ratio in Predicting Delayed Chest Closure after Heart Transplantation.

Predicted cardiac mass (PCM) has been well validated for size matching donor hearts to heart transplantation recipients. We hypothesized that cardiothoracic ratio (CTR) could be reflective of recipient-specific limits of oversizing, and sought to determine the utility of donor to recipient PCM ratio (PCMR) and CTR in predicting delayed chest closure after heart transplantation. A retrospective review of prospectively collected data on 38 consecutive heart transplantations performed at our institution from 2017 to 2020 was performed. Donor and recipient PCM were estimated using Multi-Ethnic Study of Atherosclerosis predictive models. Receiver operating characteristic analysis was performed to determine the discriminatory power of the ratio of PCMR to CTR in predicting delayed sternal closure. Of the 38 patients, 71.1% (27/38) were male and the median age at transplantation was 58 (interquartile range [IQR]: 47-62) years. Ischemic cardiomyopathy was present in 31.6% of recipients (12/38). Median recipient CTR was 0.63 [IQR: 0.59-0.66]. Median donor to recipient PCMR was 1.07 [IQR: 0.96-1.19], which indicated 7% oversizing. Thirteen out of 38 (34.2%) underwent delayed sternal closure. Primary graft dysfunction occurred in 15.8% (6/38). PCMR/CTR showed good discriminatory power in predicting delayed sternal closure [area under the curve: 80.4% (65.3-95.6%)]. PCMR/CTR cut-off of 1.7 offered the best trade-off between the sensitivity (69.6%) and specificity (91.7%). CTR could be helpful in guiding the recipient-specific extent of oversizing donor hearts. Maintaining the ratio of PCMR to CTR below 1.7 could avoid excessive oversizing of the donor heart.