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:Despite the goal of the 2018 revision to the heart allocation policy to reduce reliance on exception requests through improved granularity in status criteria, there has been a dramatic rise in exception requests. OBJECTIVES/OBJECTIVE:This study evaluated trends in exception use over the first 6 years of the updated policy, assessing associated clinical factors, temporal changes, and impact on waitlist outcomes. METHODS:This retrospective transplant registry analysis included all adult isolated heart transplant candidates from October 18, 2018, to September 30, 2024. Candidates were stratified by exception use, listing era, and region. Exception use was compared using Wilcoxon rank-sum and chi-squared tests, with multilevel logistic regression assessing independent associations. Trends over time and across UNOS (United Network for Organ Sharing) regions were evaluated, and a competing risks framework examined time to transplant and waitlist mortality. RESULTS:Among 26,330 candidates, 38.6% used exception requests, with a statistically significant increase over time, particularly in higher priority statuses. Exception use was more common among Black, non-Hispanic candidates, and candidates with blood type O, and less likely for patients with blood type A (P < 0.001). Additionally, pretransplant isolated durable left ventricular assist devices were less common in candidates who requested exceptions (19.0% vs 31.6%; P < 0.001). Overall, 39.9% of exception candidates were listed at status 1 or 2 compared to 29% of nonexception candidates, and 69.2% of exception candidates were removed from the waitlist at status 1 or 2 compared with 37% of nonexception candidates. CONCLUSIONS:The rising use of exceptions underscores ongoing limitations in allocation criteria, and disparities suggesting inequities in access to higher listing status. Policy refinements are needed to ensure a balance between medical urgency and equitable allocation.

BACKGROUND:Donor-derived cell-free DNA (dd-cfDNA) has emerged as a biomarker for antibody-mediated rejection (AMR), but its performance characteristics have not been evaluated in a large contemporary heart transplant population. OBJECTIVES/OBJECTIVE:The study aimed to characterize the incidence and timing of biopsy-proven AMR and evaluate the performance characteristics of dd-cfDNA for AMR. METHODS:The authors included 2,240 subjects from the SHORE (Surveillance HeartCare Outcomes Registry) registry transplanted between 2017 and 2022 with verified biopsy, dd-cfDNA, echocardiographic, and donor-specific antibody (DSA) data. They evaluated the performance characteristics of dd-cfDNA for AMR and the incidence of AMR in different clinical contexts. RESULTS:AMR was present in 2.6% of biopsies with significant variability depending on the clinical context: AMR occurred in 1.1% of biopsies with normal graft function and no DSAs vs 20.4% of biopsies with known DSA and graft dysfunction. In patients with neither DSA nor graft dysfunction, the incidence of AMR was 0.7% for dd-cfDNA levels <0.20%, 1.2% for levels between 0.20% and 0.49%, and 6.7% for dd-cfDNA levels ≥0.50%. In patients with known DSA but no graft dysfunction, the incidence of AMR was 1.4% for dd-cfDNA levels <0.20%, 4.8% for levels between 0.20% and 0.49%, and 15.5% for dd-cfDNA levels ≥0.50%. CONCLUSIONS:The authors document significant context dependent variability of AMR incidence and the utility of dd-cfDNA in predicting biopsy yield. These data complement prior studies on the interpretation of peripheral gene expression profiling and dd-cfDNA for rejection monitoring and should further obviate the need for surveillance biopsies. (Surveillance HeartCare Outcomes Registry [SHORE]; NCT03695601).

Guideline-directed medical therapy is the backbone of heart failure treatment. However, patients continue to experience heart failure symptoms, impaired quality of life, and reduced functional status despite guideline-directed medical and device treatment. There is a void in treatment alternatives between guideline-directed therapy and the advanced heart failure surgical options of heart transplant (HT) and left ventricular assist device (LVAD). Cardiac contractility modulation and baroreceptor activation therapies are shown to improve heart failure symptoms, quality of life, and exertional capacity in select patients and complement our current treatment paradigm. The purpose of this paper is to review these novel Food and Drug Administration (FDA)-approved heart failure therapies and facilitate the identification of appropriate candidates.

PURPOSE OF REVIEW/OBJECTIVE:Hypertension is one of the most common comorbidities affecting patients after solid organ transplantation. Here we review the mechanisms leading to hypertension, along with common practices in terms of medical management. Glucagon-like peptide-1 receptor (GLP-1R) agonists, baroreflex therapy, and renal denervation are common interventions utilized prior to heart transplant. Special considerations for their management throughout the perioperative and postoperative period are covered here. RECENT FINDINGS/RESULTS:Most common medical management includes utilization of calcium channel blockers, followed by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. GLP-1R agonists have shown significant benefit in recent cardiovascular outcome trials. Preoperative management centers around risks associated with slowed gastric emptying, while reinitiation after heart transplant must take into consideration initiation and tolerance of immunosuppressive therapies. Baroreflex activation therapy has been approved for therapy of heart failure, with many patients proceeding to heart transplant. The device is frequently deactivated after transplantation, with little published experience regarding reinitiation of therapy after heart transplant. There is renewed interest in renal denervation as a treatment for refractory hypertension. The incidence of hypertension after heart transplant in those patients that have undergone previous renal denervation remains unknown, however there is limited experience with its use after renal transplant. SUMMARY/CONCLUSIONS:Further studies are required to elucidate optimal medical management of hypertension following heart transplantation. GLP-1R agonists, baroreflex activation therapy, and renal denervation are emerging therapies prior to transplant that require further investigation.

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.