Donation After Brain Death Hearts Research Articles

Increasing Utilization of Extended Criteria Donor Hearts for Transplantation: The OCS Heart EXPAND Trial

BackgroundExtended criteria donor (ECD) hearts available with donation after brain death (DBD) are underutilized for transplantation due to limitations of cold storage. ObjectivesThis study evaluated use of an extracorporeal perfusion system on donor heart utilization and post-transplant outcomes in ECD DBD hearts. MethodsIn this prospective, single-arm, multicenter study, adult heart transplant recipients received ECD hearts using an extracorporeal perfusion system if hearts met study criteria. The primary outcome was a composite of 30-day survival and absence of severe primary graft dysfunction (PGD). Secondary outcomes were donor heart utilization rate, 30-day survival, and incidence of severe PGD. The safety outcome was the mean number of heart graft–related serious adverse events within 30 days. Additional outcomes included survival through 2 years benchmarked to concurrent nonrandomized control subjects. ResultsA total of 173 ECD DBD hearts were perfused; 150 (87%) were successfully transplanted; 23 (13%) did not meet study transplantation criteria. At 30 days, 92% of patients had survived and had no severe PGD. The 30-day survival was 97%, and the incidence of severe PGD was 6.7%. The mean number of heart graft–related serious adverse events within 30 days was 0.17 (95% CI: 0.11-0.23). Patient survival was 93%, 89%, and 86% at 6, 12, and 24 months, respectively, and was comparable with concurrent nonrandomized control subjects. ConclusionsUse of an extracorporeal perfusion system resulted in successfully transplanting 87% of donor hearts with excellent patient survival to 2 years post-transplant and low rates of severe PGD. The ability to safely use ECD DBD hearts could substantially increase the number of heart transplants and expand access to patients in need. (International EXPAND Heart Pivotal Trial [EXPANDHeart]; NCT02323321; Heart EXPAND Continued Access Protocol; NCT03835754)

Outcomes of Heart Transplant Donation After Circulatory Death

BackgroundHeart transplantation using donation after circulatory death (DCD) allografts is increasingly common, expanding the donor pool and reducing transplant wait times. However, data remain limited on clinical outcomes. ObjectivesWe sought to compare 6-month and 1-year clinical outcomes between recipients of DCD hearts, most of them recovered with the use of normothermic regional perfusion (NRP), and recipients of donation after brain death (DBD) hearts. MethodsWe conducted a single-center retrospective observational study of all adult heart-only transplants from January 2020 to January 2023. Recipient and donor data were abstracted from medical records and the United Network for Organ Sharing registry, respectively. Survival analysis and Cox regression were used to compare the groups. ResultsDuring the study period, 385 adults (median age 57.4 years [IQR: 48.0-63.7 years]) underwent heart-only transplantation, including 122 (32%) from DCD donors, 83% of which were recovered with the use of NRP. DCD donors were younger and had fewer comorbidities than DBD donors. DCD recipients were less often hospitalized before transplantation and less likely to require pretransplantation temporary mechanical circulatory support compared with DBD recipients. There were no significant differences between groups in 1-year survival, incidence of severe primary graft dysfunction, treated rejection during the first year, or likelihood of cardiac allograft vasculopathy at 1 year after transplantation. ConclusionsIn the largest single-center comparison of DCD and DBD heart transplantations to date, outcomes among DCD recipients are noninferior to those of DBD recipients. This study adds to the published data supporting DCD donors as a safe means to expand the heart donor pool.

Myocardial edema, inflammation, and injury in human heart donated after circulatory death are sensitive to warm ischemia and subsequent cold storage

BackgroundSingle-dose del Nido solution was recently used in human donation after circulatory death (DCD) heart procurement. We compared the effect of del Nido cardioplegia on myocardial edema, inflammatory response, and injury in human DCD hearts and human donation after brain death (DBD) hearts with different warm ischemic times (WIT) and subsequent cold saline storage times (CST). MethodsA total of 24 human hearts, including 6 in the DBD group and 18 in the DCD group—were procured for the research study. The DCD group was divided into 3 subgroups based on WIT: 20, 40, and ≥60 minutes. All hearts received 1 L of del Nido cardioplegia before being placed in cold saline for 6 hours. Left ventricular biopsies were performed at 0, 2, 4, and 6 hours. Temporal changes in myocardial edema, inflammatory cytokines (TNF-α, IL-6, and IL-1β), and histopathology injury scores were compared between the DBD and DCD groups. ResultsDCD hearts showed more profound changes in myocardial edema, inflammation, and injury than DBD hearts at baseline and subsequent CST. The DCD heart with WIT of 20 and 40 minutes with CST of 4 and 2 hours, respectively, appeared to have limited myocardial edema, inflammation, and injury. DCD hearts with WIT ≥60 minutes showed severe myocardial edema, inflammation, and injury at baseline and subsequent CST. ConclusionsSingle-dose cold del Nido cardioplegia and subsequent cold normal saline storage can preserve both DCD and DBD hearts. DCD hearts have been shown to be able to tolerate a WIT of 20 minutes and subsequent CST of 4 hours without experiencing significant myocardial edema, inflammation, and injury.

Donation after circulatory death improves probability of heart transplantation in waitlisted candidates and results in post-transplant outcomes similar to those achieved with brain-dead donors

ObjectiveTo quantitate the impact of heart donation after circulatory death (DCD) donor utilization on both waitlist and post-transplant outcomes in the United States. MethodsThe United Network for Organ Sharing database was queried to identify all adult waitlisted and transplanted candidates between October 18, 2018, and December 31, 2022. Waitlisted candidates were stratified according to whether they had been approved for donation after brain death (DBD) offers only or also approved for DCD offers. The cumulative incidence of transplantation was compared between the 2 cohorts. In a post-transplant analysis, 1-year post-transplant survival was compared between unmatched and propensity-score-matched cohorts of DBD and DCD recipients. ResultsA total of 14,803 candidates were waitlisted, including 12,287 approved for DBD donors only and 2516 approved for DCD donors. Overall, DCD approval was associated with an increased sub-hazard ratio (HR) for transplantation and a lower sub-HR for delisting owing to death/deterioration after risk adjustment. In a subgroup analysis, candidates with blood type B and status 4 designation received the greatest benefit from DCD approval. A total of 12,238 recipients underwent transplantation, 11,636 with DBD hearts and 602 with DCD hearts. Median waitlist times were significantly shorter for status 3 and status 4 recipients receiving DCD hearts. One-year post-transplant survival was comparable between unmatched and propensity score–matched cohorts of DBD and DCD recipients. ConclusionsThe use of DCD hearts confers a higher probability of transplantation and a lower incidence of death/deterioration while on the waitlist, particularly among certain subpopulations such as status 4 candidates. Importantly, the use of DCD donors results in similar post-transplant survival as DBD donors.

CARC18: Donor Heart Refusal Following Circulatory Death: An Analysis Of UNOS Refusal Codes

Purpose: Due to the severe shortage of donor hearts, many patients with end-stage cardiac disease die before receiving potentially lifesaving transplantation. In the past, heart donation was restricted to donation after brain death (DBD). Utilizing hearts following controlled donation after circulatory determined death (DCD) is a promising development that could significantly increase the number of hearts available for transplantation. Recent studies demonstrate that survival following transplantation of controlled DCD hearts achieves results similar to transplantation using DBD hearts. Currently, the majority of DCD hearts are discarded because most do not meet the strict criteria required for controlled DCD. Of those that meet controlled DCD criteria, the majority are still refused by the recipient institutions. We sought to explore this discrepancy and characterize the reasons that institutions refuse hearts that appear to meet controlled DCD criteria. Methods: All United Network for Organ Sharing (UNOS) refusal codes used for both DCD and DBD donors in the United States for the years 2021 and 2022 were compiled and analyzed. Rates of donor heart refusal were compared using a Z-test. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to characterize the basis for DCD heart refusal. Results: During the study period 83.3% (2,578/3,094) of potential DCD hearts were declined for transplantation, while 35.5% (3,770/10,610) of potential DBD hearts were declined (p<0.01). Specifically, in 2022 refusal code data demonstrated that DCD hearts were more likely to be declined due to prolonged warm ischemic time than DBD hearts (OR 2.781; 95% CI, 4.253-1.818; p<0.01) and more likely to be declined due to organ preservation concerns (OR 1.612; 95% CI, 2.044-1.272; p<0.01). The most frequently used refusal code for DCD hearts was neurological function. In 2022, 29% (24,989/86,196) of all DCD refusals were attributed to neurological function, presumably because retained neurological function prolonged the period of warm ischemia. Conclusion: The high DCD refusal rates do not appear to align with previous publications showing that results following transplantation of controlled DCD hearts are similar to DBD. Further analysis of transplant recipient team criteria that result in DCD heart refusal should be considered. Understanding and addressing the specific reasons for refusal may substantially increase the number of donor hearts available for transplantation.

Gaseous Persufflation to Preserve DCD Hearts: An Ovine Model

Donation after circulatory death (DCD) heart transplantation has become a clinical tool in the last 5 years. Outcomes are favourable in comparison with DBD (donation after brain death) organs. However, DCD transplantation remains a niche method employed in a few select centres due to the complexity of the procurement and storage techniques necessitated by the high metabolic demands of the heart. Gaseous persufflation, first described by Magnus in 1902, may be a simpler, cheaper, and more efficacious way of storing DCD or DBD hearts compared with current clinical techniques. While a small amount of work has been published on gas persufflation of hearts, a robust and replicable model describing procurement, persufflation, and reanimation that allows administration of reperfusion injury modulators, akin to a clinical scenario, is yet to be described.

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.

Comparing Cardiac Mechanics and Myocardial Fibrosis in DBD and DCD Heart Transplant Recipients

BackgroundHeart transplantation (HTx) after donation after circulatory death (DCD) is an expanding practice but is associated with increased warm ischemic time. The impact of DCD HTx on cardiac mechanics and myocardial fibrosis has not been reported. We aimed to compare cardiac mechanics and myocardial fibrosis using cardiovascular magnetic resonance (CMR) imaging in donation after brain death (DBD) and DCD HTx recipients and healthy controls. Methods and ResultsConsecutive HTx recipients between March 2015 and March 2021 who underwent routine surveillance CMR imaging were included. Cardiac mechanics were assessed using CMR feature tracking to compute global longitudinal strain, global circumferential strain, and right ventricular free-wall longitudinal myocardial strain. Fibrosis was assessed using late gadolinium enhancement imaging and estimation of extracellular volume. There were 82 (DBD n = 42, DCD n = 40) HTx recipients (aged 53 years, interquartile range 41–59 years, 24% female) who underwent CMR imaging at median of 9 months (interquartile range 6–14 months) after transplantation. HTx recipients had increased extracellular volume (29.7 ± 3.6%) compared with normal ranges (25.9%, interquartile range 25.4–26.5). Myocardial strain was impaired after transplantation compared with controls (global longitudinal strain –12.6 ± 3.1% vs –17.2 ± 1.8%, P < .0001; global circumferential strain –16.9 ± 3.1% vs –19.2 ± 2.0%, P = .002; right ventricular free-wall longitudinal strain –15.7 ± 4.5% vs –21.6 ± 4.7%, P < .0001). There were no differences in fibrosis burden (extracellular volume 30.6 ± 4.4% vs 29.2 ± 3.2%; P = .39) or cardiac mechanics (global longitudinal strain –13.1 ± 3.0% vs –12.1 ± 3.1%, P = .14; global circumferential strain –17.3 ± 2.9% vs –16.6 ± 3.1%, P = .27; right ventricular free-wall longitudinal strain –15.9 ± 4.9% vs –15.5 ± 4.1%, P = .71) between DCD and DBD HTx. ConclusionsHTx recipients have impaired cardiac mechanics compared with controls, with increased myocardial fibrosis. There were no differences in early CMR imaging characteristics between DBD and DCD heart transplants, providing further evidence that DCD and DBD HTx outcomes are comparable.

Abstract 11945: Improved Outcomes in Severe Primary Graft Dysfunction Following Heart Transplantation With Donation After Circulatory Death Compared to Donation After Brain Death

Introduction: Primary graft dysfunction (PGD), the leading cause of early mortality after heart transplant, is more common following heart donation after circulatory death (DCD) than following donation after brain death (DBD). We conducted a single-center, retrospective cohort study to compare the incidence, severity, and outcomes of patients experiencing PGD after DCD compared to DBD heart transplant. Methods: We reviewed the medical records of all adult heart transplant recipients at our institution between March 2016 and December 2021. Patients undergoing multi-organ transplant were excluded. PGD was diagnosed within 24 hours after transplant according to modified ISHLT criteria and was classified by severity and ventricles involved. Results: A total of 459 qualifying patients underwent heart transplant during the study period, of whom 65 (14%) were DCD recipients and 394 (86%) were DBD recipients. The incidence of PGD in DCD and DBD recipients was 34% and 23%, respectively (p = 0.070). DCD recipients were more likely to experience severe, biventricular PGD than DBD recipients (19% vs. 7.3%, p = 0.004). Among patients with severe PGD, DCD recipients experienced shorter duration of mechanical circulatory support (ECMO, VAD, or balloon pump; mean 6.0 ± 2.5 vs. 12.1 ± 11.3 days, p = 0.039; Figure), shorter post-transplant hospital length of stay (32.4 ± 41.1 vs. 61.9 ± 47.7 days, p = 0.004), and a trend toward improved 60-day survival (100% vs. 80%, p = 0.170) and one-year survival (92% [95% CI: 76%-100%] vs. 69% [53%-84%]). Conclusions: DCD heart transplant recipients were more likely to experience severe, biventricular PGD than DBD recipients. Despite this, short- and medium-term outcomes among patients with severe PGD were improved in DCD compared to DBD recipients. These data suggest different mechanisms of graft dysfunction and recovery following DCD compared to DBD and support the expansion of the heart donor pool with DCD in most potential recipients.

Improved Outcomes in Severe Primary Graft Dysfunction After Heart Transplantation Following Donation After Circulatory Death Compared With Donation After Brain Death

Primary graft dysfunction (PGD), the leading cause of early mortality after heart transplantation, is more common following donation after circulatory death (DCD) than donation after brain death (DBD). We conducted a single-center, retrospective cohort study to compare the incidence, severity and outcomes of patients experiencing PGD after DCD compared to DBD heart transplantation. Medical records were reviewed for all adult heart transplant recipients at our institution between March 2016 and December 2021. PGD was diagnosed within 24 hours after transplant according to modified International Society for Heart and Lung Transplant criteria. A total of 459 patients underwent isolated heart transplantation during the study period, 65 (14%) following DCD and 394 (86%) following DBD. The incidence of moderate or severe PGD in DCD and DBD recipients was 34% and 23%, respectively (P = 0.070). DCD recipients were more likely to experience severe biventricular PGD than DBD recipients (19% vs 7.4%; P = 0.004). Among patients with severe PGD, DCD recipients experienced shorter median (Q1, Q3) duration of post-transplant mechanical circulatory support (6 [4, 7] vs 9 [5, 14] days; P = 0.039), shorter median post-transplant hospital length of stay (17 [15, 29] vs 52 [26, 83] days; P = 0.004), and similar 60-day survival rates (100% [95% CI: 76.8%-100%] vs 80.0% [63.1%-91.6%]; P = 0.17) and overall survival (log-rank; P = 0.078) compared with DBD recipients. DCD heart transplant recipients were more likely to experience severe, biventricular PGD than DBD recipients. Despite this, DCD recipients with severe PGD spent fewer days on mechanical circulatory support and in the hospital than similar DBD patients. These findings suggest that patterns of graft dysfunction and recovery may differ between donor types, and they support the expansion of the heart-donor pool with DCD.

Organ Care System Heart Perfusion Registry (OHP Registry) - Overview of a National Data Repository of Ex-Vivo Perfusion in DBD and DCD Heart Transplantation

<h3>Purpose</h3> Organ Care System (OCS, Transmedics Inc) is the first clinically available system for ex-vivo normothermic heart perfusion. OHP Registry is a prospective real-world registry of Donation after Brain Death (DBD) or Donation after Circulatory Death (DCD) heart transplantation in hearts perfused and assessed on OCS Heart. OHP Registry will collect OCS ex-vivo perfusion & assessment parameters and post-transplant short & long-term clinical outcomes of heart transplant recipients in the U.S. <h3>Methods</h3> All adult heart transplant recipients of DBD or DCD heart allografts perfused and assessed on OCS Heart technology will be included, along with data on hearts perfused and assessed on OCS Heart but not transplanted. OCS Heart perfusion and assessment parameters will be prospectively collected. All recipients will be followed up to 5 years post-transplant. Patient and graft survival will be compared to a UNOS/SRTR cohort of heart transplant recipients of cold stored donor hearts transplanted at the same OHP Registry centers over the same period of time. <h3>Results</h3> Endpoints: Patient and graft survival at 1, 2, 3, 4, 5 years post-transplantation. Incidence of moderate or severe heart primary graft dysfunction (left or right ventricle) defined according to ISHLT 2014 consensus definitions. OCS Heart utilization rate defined as the number of hearts transplanted by OCS perfusion and assessment, divided by the total number of hearts perfused and assessed on the OCS Heart System. <h3>Conclusion</h3> We anticipate analyses of OHP Registry will provide important data that will inform clinical care. We plan to present regular updates at future ISHLT Annual Meetings.

Donation after Circulatory Death Heart Transplantation - The First 5 Years a Successful Leap in Activity

<h3>Purpose</h3> Donation after circulatory death (DCD) heart transplantation was reinstated in response to the critical shortage of donor hearts from donation after brain death (DBD). Promising early results prompted centres in Europe, Australia and United States to adopt this practice. A clinical DCD heart transplant programme was initiated at our centre in March 2015. We aim to review our experience to date. <h3>Methods</h3> The study included recipients of DCD heart transplant from 1^st of March 2015 to 31^st October 2020. Comparison was made with the concurrent group of DBD heart recipients from our centre who were matched on donor and recipient characteristics. DCD hearts were retrieved by one of the three methods practised at our institution: 1. Thoraco-abdominal normothermic regional perfusion followed by <i>ex-situ</i> machine perfusion (TANRP-MP), 2. TANRP followed by cold storage (TANRP-CS) or 3. Direct procurement and perfusion (DPP) utilising <i>ex-situ</i> machine perfusion. All DBD hearts were preserved by cold storage. The 2 primary outcome measures were survival and primary graft dysfunction requiring temporary mechanical circulatory support (MCS). <h3>Results</h3> 85 DCD heart transplants were performed over the studied period. 62 hearts were retrieved by DPP, 20 by TANRP-MP and 3 by TANRP-CS. 30-day patient survival was comparable between groups (p=0.76), with 95% for DCD and 94% for DBD. 90% of DCD patients survived to 1 year vs 91% of their DBD matches. 5-year survival was 87% in the DCD and 83% in the DBDs. 33% of DCD patients required MCS post-transplant vs 24% of DBD patients (p=0.24). Support with V-A ECMO was necessary for 11 DCD and 5 DBD recipients (p=0.21). Early cardiac function appeared better in the DCD group (CI 2.3 vs 1.9, p=0.08). Secondary outcome measures were similar between the groups, table 1. <h3>Conclusion</h3> DCD heart transplantation appears to be equivalent to traditional DBD transplantation. 5-year outcomes of our 85-patient cohort including acute rejection rates support this conclusion.

Donation after circulatory death hearts recipients compared to donation after brain death heart recipients have comparable systolic left ventricular function and better myocardial strain at 1 year

Abstract Purpose Cardiac transplantation from donation after circulatory death (DCD) has been implemented at our hospital since February 2015. Despite encouraging results some concerns may be raised about the impact of the warm ischemia and reperfusion injury on the myocardium status at longer follow-up. Therefore, we aimed to analyse systolic performance of the left ventricle at 1 year follow in DCD and donation after brain death (DBD) cardiac recipients, as assessed by echocardiography with myocardial deformation imaging. Methods We identified 46 consecutive DCD cardiac recipients who were transplanted from February 2015 to August 2018 and we matched them with 46 DBD cardiac recipients. Six and 7 patients from DCD and DBD group, respectively, died in the first-year post transplant. In the remaining patients we have compared the classical echocardiographic measurements as well as global longitudinal strain (GLS) and global circumferential strain (GCS) at 1-year follow-up. Results DCD and DBD patients did not present with differences in terms of classical echocardiographic parameters of left ventricular (LV) structure and systolic function at one-year follow-up. LVEDV was similar in DCD and DBD patients (101±24 vs. 95±32 ml, p=0.4 respectively), as well as LVESV (42±13 vs. 42±16 ml, p=0.9, respectively), LV ejection fraction (58±6 vs. 56±8%, p=0.22) and LV mass (156±39 vs. 163±38 gr, p=0.2, respectively). In contrast, myocardial deformation parameters, such as GLS and GCS, were better in DCD than in DBD (16.1 vs. −14.5%, p&amp;lt;0.01; and −25.2 vs. 22.3%, p&amp;lt;0.05, respectively). The diastolic LV function parameters were similar in DCD and DBD group, as evidenced by E wave velocity, A wave velocity and deceleration time of mitral inflow, however E over E prime was lower in DCD than in DBD recipients (7.7±8.7, p&amp;lt;0.05). Fractional area change of the right ventricle was higher in DCD in comparison with DBD (46±7 vs. 40±7%, p&amp;lt;0.01) while right atrial volume index was lower in DCD than in DBD (25±8 vs. 29±9 ml/m2, p&amp;lt;0.01). Other parameters of RV function (systolic excursion of the tricuspid annulus, TAPSE) were similar in both groups. Conclusion DCD and DBD heart recipients present with similar systolic LV function at 1-year follow, as assessed by classical echocardiographic parameters. DCD cardiac recipients have better myocardial deformation parameters as assessed by the speckle tracking, better systolic right ventricular function and lower filling pressures of the left ventricle. Funding Acknowledgement Type of funding source: None

A 5-year single-center early experience of heart transplantation from donation after circulatory-determined death donors

In an effort to address the increasing demand for heart transplantation within the United Kingdom (UK), we established a clinical program of heart transplantation from donation after circulatory-determined death (DCD) donors in 2015. After 5 years, we report the clinical early outcomes and impact of the program. This is a single-center, retrospective, matched, observational cohort study comparing outcomes of hearts transplanted from DCD donors from March 1, 2015 to February 29, 2020 with those from matched donation after brain death (DBD) donors at Royal Papworth Hospital (RPH) (Cambridge, UK). DCD hearts were either retrieved using thoracoabdominal normothermic regional perfusion or the direct procurement and perfusion technique. All DBD hearts were procured using standard cold static storage. The primary outcomes were recipient 30-day and 1-year survival. During the 5-year study, DCD heart donation increased overall heart transplant activity by 48% (79 for DCD and 164 for DBD). There was no difference in survival at 30days (97% for DCD vs 99% for DBD, p = 1.00) or 1 year (91% for DCD vs 89% for DBD, p = 0.72). There was no difference in the length of stay in the intensive care unit (7 for DCD vs 6 for DBD days, p = 0.24) or in the hospital (24 for DCD vs 25 for DBD days, p = 0.84). DCD heart donation increased overall heart transplant activity at RPH by 48%, with no difference in 30-day or 1-year survival in comparison with conventional DBD heart transplantations. DCD heart donation is set to make a dramatic difference in the number of patients who can benefit from heart transplantation.

DCD donations and outcomes of heart transplantation: the Australian experience.

There is increasing clinical utilization of hearts from the donation after circulatory death (DCD) pathway with the aim of expanding the donor pool and mitigating the ever-present discrepancy between the inadequate availability of good quality donor hearts and the rising number of patients with end-stage heart failure. This article reviews the rationale, practice, logistical factors, and 5-year experience of DCD heart transplantation at St Vincent's Hospital, Sydney. Between July 2014 and July 2019, 69 DCD donor retrievals were undertaken resulting in 49 hearts being instrumented on an ex situ normothermic cardiac perfusion device. Seventeen (35%) of these hearts were declined and the remaining 32 (65%) were used for orthotopic DCD heart transplantation. At 5years of follow-up, the 1-, 3-, and 5-year survival was 96%, 94%, and 94% for DCD hearts compared with 89%, 83%, and 82% respectively for donation after brain death (DBD) hearts (n.s). The immediate post-implant requirement for temporary extra-corporeal membrane oxygenation (ECMO) support for delayed graft function was 31% with no difference in rejection rates when compared with the contemporaneous cohort of patients transplanted with standard criteria DBD hearts. DCD heart transplantation has become routine and incorporated into standard clinical practice by a handful of pioneering clinical transplant centres. The Australian experience demonstrates that excellent medium-term outcomes are achievable from the use of DCD hearts. These outcomes are consistent across the other centres and consequently favour a more rapid and wider uptake of heart transplantation using DCD donor hearts, which would otherwise be discarded.

The Commonalities and Differences in Mitochondrial Dysfunction Between ex vivo and in vivo Myocardial Global Ischemia Rat Heart Models: Implications for Donation After Circulatory Death Research.

Heart transplantation is the ultimate treatment option for patients with advanced heart failure. Since hearts from donation after brain death (DBD) donors are limited, donation after circulatory death (DCD) donor hearts could be another source for heart transplantation. DCD process involves ischemia-reperfusion (IR) injury. Mitochondrial dysfunction contributes to IR and is well established in the ex vivo (buffer perfused) ischemia animal model. However, DCD hearts undergo in vivo ischemia with a variable “ischemic period.” In addition, the DCD hearts are exposed to an intense catecholamine surge that is not seen with ex vivo perfused hearts. Thus, the severity of mitochondrial damage in in vivo ischemia hearts could differ from the ex vivo ischemia hearts even following the same period of ischemia. The aim of our current study is to identify the mitochondrial dysfunction in DCD hearts and propose strategies to protect mitochondria. Adult Sprague Dawley rat hearts underwent in vivo or ex vivo ischemia for 25 min. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated from hearts following ischemia. We found that both ex vivo and in vivo ischemia led to decreased oxidative phosphorylation in SSM and IFM compared to time control or DBD hearts. The proportion of damage to SSM and IFM, including proton leak through the inner membrane, was higher with ex vivo ischemia compare to in vivo ischemia. Time control hearts showed a decrease in SSM and IFM function compared to DBD hearts. The calcium retention capacity (CRC) was also decreased in SSM and IFM with ex vivo and in vivo ischemia, indicating that ischemic damage to mitochondria sensitizes mitochondrial permeability transition pores (MPTP). Our study found differential mitochondrial damage between the in vivo ischemia and the ex vivo ischemia setup. Therefore, consideration should be given to the mode of ischemia while evaluating and testing myocardial protective interventions targeting mitochondria to reduce IR injury in hearts.

Donor heart and lung procurement: A consensus statement

Heart and lung procurements are multiphased processes often accompanied by an array of complex logistics. Approaches to donor evaluation and management, organ procurement, and organ preservation vary among individual procurement teams. Because early graft failure remains a major cause of mortality in contemporary thoracic organ transplant recipients, we sought to establish some standardization in the procurement process. This paper, in this vein, represents an international consensus statement on donor heart and lung procurement and is designed to serve as a guide for physicians, surgeons, and other providers who manage donors to best optimize the clinical status for the procurement of both heart and lungs for transplantation. Donation after brain death (DBD) and donation after circulatory determination death (referred to as donation after circulatory death [DCD] for the remainder of the paper) for both heart and lung transplantation will be discussed in this paper. Although the data available on DCD heart donation are limited, information regarding the surgical technique for procurement is included within this consensus statement. Furthermore, this paper will focus on adult DBD and DCD heart and lung procurement. Currently, no certification, which is either recognized and/or endorsed by the transplant community at large, exists for the training of a cardiothoracic procurement surgeon. Nevertheless, establishing a training curriculum and credentialing requirements are beyond the scope of this paper.

Heart transplantation from donation after circulatory death donors: Present and future.

The first successful human heart transplantation was reported on 3 December 1967, by Christiaan Barnard in South Africa. Since then this life-saving procedure has been performed in over 120 000 patients. A limitation to the performance of this procedure is the availability of donor hearts with as many as 20% of patients dying before a donor's heart is available for transplant. Today, hearts for transplantation are procured from individuals experiencing donation after brain death (DBD). Interestingly, this, however,was not always the case as the first heart transplants occurred after circulatory death. Revisiting the availability of hearts for transplant from those experiencingdonation after circulatory death (DCD) could further expand the number of hearts suitable for transplantation. There are several considerations pertinent to transplanting hearts from those undergoing circulatory death. In this review, we summarize the main distinctions between DBD and DCD heart donation and discuss the research relevant to increasing the number of hearts available for transplantation by including individual's hearts that experience circulatory death.

First to 50: Early Outcomes Following Heart Transplantation at Royal Papworth Hospital from Donation after Circulatory Determined Death (DCD) Donors

Purpose The demand for heart transplantation has increased by 162% in the United Kingdom over the last decade. In an attempt to address both wait list mortality and prolonged waiting times, a programme of DCD heart transplantation was implemented at Royal Papworth Hospital in March 2015. We report the early outcomes of the first 50 DCD heart transplants and compare them to a matched cohort of donation after brain death (DBD) heart transplants. Methods DCD hearts were retrieved either by; Normothermic Regional Perfusion followed by ex-situ heart perfusion (NRP-ESHP), NRP followed by cold storage (NRP-CS) or Direct Procurement and Perfusion using ESHP alone (DPP-ESHP). During NRP, perfusion was restored to the arrested heart within the donor with the exclusion of the cerebral circulation whilst DPP hearts were removed directly. A retrospective cohort of DBD heart transplants, matched for donor and recipient characteristics was used as a comparison group. All DBD hearts were transported using static cold storage. Outcome measures for this study included 30 day survival as well post transplant inotrope dependence, mechanical support, initial cardiac performance, ventilator duration, intensive care duration and length of hospital stay. Results From 1st March 1 2015 to 10th October 50 DCD heart transplants were performed at our institute. Sixteen DCD hearts were transplanted following (NRP-ESHP), 32 hearts following (DPP-ESHP) and 2 hearts following (NRP-CS). The 30-day survival post transplant was 100% in both DCD and DBD groups. All other outcome variables were comparable between groups with the exception of Dopamine reliance post transplant, table 1. Values are median (IQR) or n (%) Conclusion After 50 DCD heart transplants, the results continue to show that DCD heart transplantation can be performed safely with comparable early outcomes to those achieved with DBD heart transplantation.

Outcome after heart transplantation from donation after circulatory-determined death donors

The requirement for heart transplantation is increasing, vastly outgrowing the supply of hearts available from donation after brain death (DBD) donors. Transplanting hearts after donation after circulatory-determined death (DCD) may be a viable additive alternative to DBD donors. This study compared outcomes from the largest single-center experience of DCD heart transplantation against matched DBD heart transplants. DCD hearts were retrieved using normothermic regional perfusion (NRP) or direct procurement and perfusion (DPP). During NRP, perfusion was restored to the arrested heart within the donor with the exclusion of the cerebral circulation, whereas DPP hearts were removed directly. All hearts were maintained on machine perfusion during transportation. A retrospective cohort of DBD heart transplants, matched for donor and recipient characteristics, was used as a comparison group. The primary outcome measure of this study (set by the United Kingdom regulatory body) was 90-day survival. There were 28 DCD heart transplants performed during the 25-month study period. Survival at 90 days was not significantly different between DCD and matched DBD transplant recipients (DCD, 92%; DBD, 96%; p = 1.0). Hospital length of stay, treated rejection episodes, allograft function, and 1-year survival (DCD, 86%; DBD, 88%; p = 0.98) were comparable between groups. The method of retrieval (NRP or DPP) was not associated with a difference in outcome. These results suggest that heart transplantation from DCD heart donation provides comparable short-term outcomes to traditional DBD heart transplants and can serve to increase heart transplant activity in well-selected patients.