Comparative Analysis of Ischemia-Reperfusion Injury in Heart Transplantation: A Single-Center Study Evaluating Conventional Ice-Cold Storage versus the Paragonix SherpaPak Cardiac Transport System.

BACKGROUND: Since the 2018 allocation system change in heart transplantation (HT), ischemic times have increased, which may be associated with peri-operative and post-operative complications. This study aimed to compare ischemia reperfusion injury (IRI) in hearts preserved using ice-cold storage (ICS) and the Paragonix SherpaPak TM Cardiac Transport System (CTS). METHODS: From January 2021 to June 2022, consecutive endomyocardial biopsies from 90 HT recipients were analyzed by a cardiac pathologist in a single-blinded manner: 33 ICS and 57 CTS. Endomyocardial biopsies were performed at three-time intervals post-HT, and the severity of IRI manifesting histologically as coagulative myocyte necrosis (CMN) was evaluated, along with graft rejection and graft function. RESULTS: The incidence of IRI at weeks 1, 4, and 8 post-HT were similar between the ICS and CTS groups. There was a 59.3% statistically significant reduction in CMN from week 1 to 4 with CTS, but not with ICS. By week 8, there were significant reductions in CMN in both groups. Only 1 out of 33 (3%) patients in the ICS group had an ischemic time >240 mins, compared to 10 out of 52 (19%) patients in the CTS group. During the follow-up period of 8 weeks to 12 months, there were no significant differences in rejection rates, formation of de novo donor-specific antibodies and overall survival between the groups. CONCLUSION: The CTS preservation system had similar rates of IRI and clinical outcomes compared to ICS despite longer overall ischemic times. There is significantly more recovery of IRI in the early post operative period with CTS. This study supports CTS as a viable option for preservation from remote locations, expanding the donor pool.

Utility of a fusion protein T-cell co-stimulation blocker Belatacept in heart transplant recipients: Real world experience from a high volume center.

BACKGROUND: Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. METHODS: A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023. RESULTS: Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (± 12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p = .054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p = .24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%). CONCLUSION: In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.

Evolution of Mechanical Circulatory Support for advanced heart failure.

This comprehensive review highlights the significant advancements in Left Ventricular Assist Device (LVAD) therapy, emphasizing its evolution from the early pulsatile flow systems to the cutting-edge continuous-flow devices, particularly the HeartMate 3 (HM3) LVAD. These advancements have notably improved survival rates, reduced complications, and enhanced the quality of life (QoL) for patients with advanced heart failure. The dual role of LVADs, as a bridge-to-transplantation and destination therapy is discussed, highlighting the changing trends and policies in their application. The marked reduction in hemocompatibility-related adverse events (HRAE) with the HM3 LVAD, compared to previous models signifies ongoing progress in the field. Challenges such as managing major infections are discussed, including innovative solutions like energy transfer systems aimed at eliminating external drivelines. It explores various LVAD-associated complications, including HRAE, infections, hemodynamic-related adverse events, and cardiac arrhythmias, and underscores emerging strategies for predicting post-implantation outcomes, fostering a more individualized patient care approach. Tools such as the HM3 risk score are introduced for predicting survival based on pre-implant factors, along with advanced imaging techniques for improved complication prediction. Additionally, the review highlights potential new technologies and therapies in LVAD management, such as hemodynamic ramp tests for optimal speed adjustment and advanced remote monitoring systems. The goal is to automate LVAD speed adjustments based on real-time hemodynamic measurements, indicating a shift towards more effective, patient-centered therapy. The review concludes optimistically that ongoing research and potential future innovations hold the promise of revolutionizing heart failure management, paving the way for more effective and personalized treatment modalities.

Validation of the HeartMate 3 survival risk score in a large left ventricular assist device center.

OBJECTIVE: The HeartMate 3 survival risk score was recently validated in the Multicenter study Of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 to predict patient-specific survival in HeartMate 3 left ventricular assist device candidates. The HeartMate 3 survival risk score stratifies individuals into tertiles according to survival probability. METHODS: We performed a single-center retrospective review of all HeartMate 3 left ventricular assist device recipients between September 2017 and August 2022. Baseline characteristics were collected from the electronic medical records. HeartMate 3 survival risk scores were calculated for all eligible patients. One- and 2-year Kaplan-Meier survival analyses were conducted. A univariate and multivariable Cox regression model was used to identify predictors. RESULTS: A total of 181 patients were included in this final analysis. The median age was 62 years, 83% were male, and 26% were Interagency Registry for Mechanically Assisted Circulatory Support Profile 1. The mean HeartMate 3 survival risk score for the entire cohort was 2.66 ± 0.66. Two-year survivals in the high, average, and low survival groups were 93.5% ± 3.2%, 81.6% ± 7.4%, and 82.0% ± 6.6%, respectively. As a continuous variable, the unadjusted HeartMate 3 survival risk score was a significant predictor of mortality (hazard ratio, 2.20; 95% CI, 1.08-4.45; P = .029). The areas under the curve were 0.70 and 0.66 at 1 and 2 years, respectively. We were unable to demonstrate the discriminatory ability of the HeartMate 3 survival risk score using the original stratification, but we found significantly increased survival in the high survival group using a binary cutoff (hazard ratio, 4.8; 95% CI, 1.01-20.9; P = .038). CONCLUSIONS: The unadjusted HeartMate 3 survival risk score was associated with postimplant survival in patients outside of the Multicenter study Of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 but did not remain an independent predictor after adjusting for ischemic etiology and severe diabetes. The HeartMate 3 survival risk score was able to identify patients at high survival using a binary cutoff, but we were unable to demonstrate its discriminatory ability among the previously published risk tertiles.