Faculty Bibliography

BACKGROUND:Heart utilization from donation after circulatory death (DCD) donors remains highly variable across the United States, potentially resulting in missed transplantation opportunities. This study aimed to quantify the frequency of clinically viable, non-utilized DCD hearts and identify usage barriers. METHODS:We conducted a retrospective, national registry analysis of donors ≤55 years old who donated ≥1 organ, focusing primarily on DCDs. Donor characteristics, particularly age, warm ischemic time (WIT), and EF, as well as reasons for non-recovery and offer refusal, were analyzed. SRTR's heart yield model was employed to identify non-utilized DCD hearts clinically comparable to transplanted DCD hearts. RESULTS:In 2023, 613 DCD hearts were transplanted, accounting for 13.5% of all heart transplants. Only 15.5% of DCD hearts from donors ≤55 years old were utilized. Marked variation in risk-adjusted DCD heart yield was observed between states, OPOs, and Regions. Donors of transplanted DCD hearts had a median age of 32, WIT 24 minutes, and EF 63%. The yield model identified between 701-1,243 non-utilized DCD hearts with characteristics comparable to transplanted cases. Concerns about delayed progression to circulatory arrest after life support withdrawal was a key reason for non-utilization. CONCLUSIONS:Despite wider acceptance of DCD heart transplantation, an increasing proportion of DCD hearts remain unused despite favorable characteristics. Concerns related to delayed progression to circulatory arrest are a significant barrier to heart utilization. Addressing geographic variability and improving predictive models for donor viability could double DCD heart utilization and expand heart transplantation volume by approximately 700-1,200 (15-27%) annually.

BACKGROUND:As donation after circulatory determination of death (DCD) heart transplantation (HT) becomes more widely adopted, there is a need to establish the most clinically effective method of organ procurement. OBJECTIVE:This international, multicenter study compares outcomes of DCD-HT across Europe and the United States (US) between recipients whose donor hearts were retrieved using thoraco-abdominal normothermic regional perfusion (taNRP) to those whose hearts were recovered using direct procurement and perfusion (DPP). METHODS:This was a retrospective observational study across 20 heart transplant centers in Belgium, Spain, the United Kingdom (UK) and the US. This study included all patients undergoing DCD-HT at participating centers, from the start of each center's DCD program through 01/01/2023. DCD-HT with recovery using either taNRP or DPP were compared to one-another. Post-transplant outcomes included (i)survival at 1-year, (ii)incidence of severe primary graft dysfunction (PGD), (iii)episodes of treated, biopsy-proven acute-cellular rejection (ACR) in the first year following transplantation. RESULTS:504 DCD-HT took place in the study period. Survival at one year was similar for taNRP and DPP recipients (91% vs 88%, p=0.1). taNRP recipients had a lower rate of severe PGD (7.6% vs 19.2%, p<0.001) and fewer episodes of biopsy-proven, ACR requiring treatment in the first-year post-transplantation (13% vs 25%,p<0.001). CONCLUSION/CONCLUSIONS:In an international study of DCD-HT, recipients of hearts retrieved by taNRP technique had lower rates of severe PGD and fewer episodes of biopsy-proven ACR in the first year when compared with those retrieved utilizing DPP. These results should be further investigated with randomized control trials.

CLINICAL CONDITION/UNASSIGNED:The authors present the case of a young man who presented with cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation and microaxial flow pump complicated by acute spinal cord infarction (SCI) leading to bilateral lower extremity paraplegia. KEY QUESTIONS/UNASSIGNED:The key questions included the following: 1) What is the incidence and pathophysiology for SCI with mechanical circulatory support (MCS)?; 2) Which configurations of MCS carry a greater risk of SCI? How do we approach MCS escalation, recognizing that with each device we carry additive risk of complications?; 3) What data guide anticoagulation strategies for MCS?; and 4) What strategies can we implement to support patients who have suffered SCI from MCS? OUTCOME/RESULTS:Our patient was transitioned to a right ventricular assist device with Impella 5.5 as a bridge to therapy, and underwent cardiac transplantation 4 weeks after presentation with ongoing inpatient rehabilitation. TAKE-HOME MESSAGES/CONCLUSIONS:Contemporary MCS carries a small but significant risk of SCI which is often irreversible. More data are required to guide anticoagulation strategies for MCS and mitigate risk.

Heart transplantation remains a critical therapy for patients with end-stage heart failure, offering incremental survival and improved quality of life. One of the key components behind the success of heart transplantation is the condition and preservation of the donor heart. In this review, we provide a comprehensive overview of ischemic reperfusion injury, risk factors associated with primary graft dysfunction, current use of various preservation solutions for organ procurement and recent advancements in donor heart procurement technologies. This State-of-the-Art review will explore factors associated with bringing the "ideal" donor heart to the operating room in the contemporary era.

BACKGROUND:In the 2018 Organ Procurement and Transplantation Network donor heart allocation system, patients listed for re-transplantation due to cardiac allograft vasculopathy (CAV) are assigned to Status 4 unless hemodynamic criteria are met. We aim to examine waitlist outcomes of CAV patients among adult heart transplant candidates. METHODS:We examined waitlist mortality stratified by CAV and waitlist status among adult heart transplant candidates using Scientific Registry of Transplant Recipients data from 10/1/2018-11/1/2023. We analyzed waitlist mortality using Kaplan-Meier curves and doubly-robust Cox regressions adjusted for age, gender, sex, race, and dialysis. We compared CAV to non-CAV patients by initial waitlist status, first status of interest, and time-dependent status. RESULTS:Of 21,586 listed patients, 368 were listed for CAV. CAV patients were most often listed at Status 4 with lower proportions at Status 3/2/1 compared with non-CAV patients. Status 4 and Status 3 CAV candidates demonstrated higher than expected waitlist mortality compared to non-CAV counterparts (Status 4: HR 0.51, 95% CI 0.31-0.84; p < 0.01; Status 3: HR 0.61, 95% CI 0.23-1.64; p = 0.33) with similar mortality to non-CAV patients in Status 3 and 2, respectively (Status 4: HR 0.80, 95% CI 0.48-1.35; p = 0.4; Status 3: HR 1.07, 95% CI 0.40-2.86; p = 0.89). When stratifying by status tier, CAV waitlist patients ever listed at Status 4 and 3 had a higher probability of death compared to their non-CAV counterparts (Status 4: HR 1.99, 95% CI 1.20-3.31, p < 0.01; Status 3: HR 3.06, 95% CI 1.06-8.87, p = 0.04). CONCLUSIONS:After 2018, CAV patients had a higher risk of waitlist mortality at Status 4 and 3 compared to non-CAV patients. These results suggest that CAV patients are underprioritized in the current allocation system.

BACKGROUND/UNASSIGNED:Donation after circulatory death (DCD) with cardiopulmonary bypass for thoracoabdominal normothermic regional perfusion (TA-NRP) has led to increased use of donor hearts. Rejection rates and long-term survival outcomes are not known. METHODS/UNASSIGNED:A single-center retrospective cohort review of patients who underwent DCD heart transplantation from January 2020 to December 2023 was performed. Donor and recipient characteristics, operative characteristics, and posttransplantation outcomes were analyzed. Subgroup analysis comparing co-localized vs distant donors and recipients was performed. The primary end point was 1-year survival. Secondary end points included incidences of primary graft dysfunction (PGD), cardiac allograft vasculopathy (CAV), rejection rate, and overall mortality. Our TA-NRP protocol has remained the same, consisting of sternotomy, ligation of aortic arch vessels, establishment of cardiopulmonary bypass, reintubation, resuscitation of the heart, and cold static storage during transport. RESULTS/UNASSIGNED:< .005) ischemia times, without any other differences. CONCLUSIONS/UNASSIGNED:Outcomes after DCD heart transplantation using TA-NRP remain encouraging with acceptable rates of rejection, PGD, CAV, and survival at 1 year.

IMPORTANCE/UNASSIGNED:The advanced ambulatory heart failure (HF) population comprises patients who have progressed beyond the pillars of recommended stage C HF therapies but can still find meaningful life-years ahead. Although these patients are commonly encountered in practice, national databases selectively capture the small groups accepted for heart transplant listing or left ventricular assist devices. The epidemiology, trajectories, and therapies for other ambulatory patients with advanced HF are poorly understood. OBSERVATIONS/UNASSIGNED:In December 2022, the National Heart, Lung and Blood Institute convened a team of experts to identify knowledge gaps and research priorities for the ambulatory population with limiting daily symptoms and transition toward refractory end-stage D HF, designated as stage C2D. This article summarizes the findings from that 3-day workshop. Workshop participants surveyed the initial challenges and knowledge gaps for (1) recognition of ambulatory C2D HF, (2) estimation of the magnitude of the affected population and identifiable subpopulations, and (3) physiologic phenotypes, such as low cardiac output, right HF, cardiorenal syndromes, congestive hepatopathy and frailty, which offer distinct targets for existing and emerging therapies. Social drivers of HF and patient preferences for quality/length of survival were highlighted as essential modifiers for personalization of therapies. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Ten key points summarized workshop findings, with target cohorts for study proposed as a crucial next step. This workshop summary is intended as a call for action to address knowledge gaps and develop new strategies to improve outcomes in the large ambulatory population with C2D HF.

OBJECTIVE/UNASSIGNED:Anticoagulation monitoring in patients supported on extracorporeal membrane oxygenation is challenging given the risks of both bleeding and thrombotic complications. Based on our early clinical experience, we revised our heparin protocol by reducing our target anti-factor Xa assay from 0.3 to 0.7 U/mL to 0.15 to 0.5 U/mL, while instituting a partial thromboplastin time cutoff of 70 seconds. We evaluated the impact of this change on bleeding/thrombotic complications. METHODS/UNASSIGNED:A single-center retrospective study of adult patients on extracorporeal membrane oxygenation support was conducted from January 2015 to August 2022. Patients were stratified into groups based on protocol revision: Pre-Revision (2015-2018) or Post-Revision (2019-2022). Our primary end point was the incidence of bleeding/thrombotic complications. Time in therapeutic range was calculated to determine protocol adherence. Poisson regression was performed to correlate time in therapeutic range with the likelihood of complication. RESULTS/UNASSIGNED:008). CONCLUSIONS/UNASSIGNED:A modified heparin monitoring protocol defined by a lower therapeutic anti-factor Xa assay target and a set partial thromboplastin time cutoff correlated with decreases in bleeding/thrombotic complications in patients on extracorporeal membrane oxygenation.

BACKGROUND:Because of advances in medical treatment of heart failure, patients are living longer than in previous eras and may approach the need for advanced therapies, including heart transplantation, at older ages. This study assesses practices surrounding heart transplant in older adults (> 70 years) and examines short- and medium-term outcomes. METHODS AND RESULTS/RESULTS:This study is a retrospective analysis using the United Network for Organ Sharing (UNOS) database from 2010 to 2021. The absolute number of older adults being transplanted is increasing. Older adults were more likely to have had a prior malignancy or ischemic cardiomyopathy and less likely to be on extra-corporeal membrane oxygenation or have a high UNOS status prior to transplant. Mortality at 1-year was higher for older adults (27.8% vs. 23.4%), but at 5 years there was no significant difference (22.3% vs. 19.4%.). Older adults were more likely to die of malignancy or infection. Adults under 70 were more likely to die of cardiovascular causes or graft failure. There was less rejection in older adults. Mortality has not changed for older adults transplanted before versus after the 2018 UNOS allocation change. CONCLUSIONS:Carefully selected older adults may be considered for heart transplantation, given similar intermediate-term mortality.

The physiologic impact of pulsatile flow (PF) on end-organ perfusion during cardiopulmonary bypass (CPB) is controversial. Using an intra-aortic balloon pump (IABP) to maintain PF during CPB for patients undergoing heart transplantation (HT) may impact end-organ perfusion, with implications for postoperative outcomes. A single-center retrospective study of 76 patients bridged to HT with IABP was conducted between January 2018 and December 2022. Beginning in May 2022, patients received IABP-generated PF during CPB at an internal rate of 80 beats/minute. Fifty-eight patients underwent HT with the IABP turned off (IABP-Off), whereas 18 patients underwent HT with IABP-generated PF (IABP-On). The unmatched IABP-On group experienced shorter organ ischemia times (180 vs. 203 minutes, p = 0.015) and CPB times (104 vs. 116 minutes, p = 0.022). The cohort was propensity matched according to age, organ ischemia time, and CPB time. Elevations in postoperative lactates in the immediate (2.8 vs. 1.5, p = 0.062) and 24 hour (4.7 vs. 2.4, p = 0.084) postoperative periods trended toward significance in the matched IABP-Off group. There was no difference in postoperative vasoactive inotropic score (VIS), postoperative creatinine, or length of stay. This limited preliminary data suggest that maintaining counterpulsation to generate PF during CPB may improve end-organ perfusion in this patient population as suggested by lower postoperative lactate levels.