Cardio-Renal-Metabolic Outcomes Associated With the Use of GLP-1 Receptor Agonists After Heart Transplantation.

BACKGROUND: The use of glucagon-like-peptide 1 receptor agonists (GLP1-RA) has dramatically increased over the past 5 years for diabetes mellitus type 2 (T2DM) and obesity. These comorbidities are prevalent in adult heart transplant (HT) recipients. However, there are limited data evaluating the efficacy of this drug class in this population. The aim of the current study was to describe cardiometabolic changes in HT recipients prescribed GLP1-RA at a large-volume transplant center. METHODS: We retrospectively reviewed all adult HT recipients who received GLP1-RA after HT for a minimum of 1-month. Cardiometabolic parameters including body mass index (BMI), lipid panel, hemoglobin A1C, estimated glomerular filtration rate (eGFR), and NT-proBNP were compared prior to initiation of the drug and at most recent follow-up. We also evaluated for significant dose adjustments to immunosuppression after drug initiation and adverse effects leading to drug discontinuation. RESULTS: Seventy-four patients were included (28% female, 53% White, 20% Hispanic) and followed for a median of 383 days [IQR 209, 613] on a GLP1-RA. The majority of patients (n = 56, 76%) were prescribed semaglutide. The most common indication for prescription was T2DM alone (n = 33, 45%), followed by combined T2DM and obesity (n = 26, 35%). At most recent follow-up, mean BMI decreased from 33.3 to 31.5 kg/m2 (p < 0.0001), HbA1C from 7.3% to 6.7% (p = 0.005), LDL from 78.6 to 70.3 mg/dL (p = 0.018) and basal insulin daily dose from 32.6 to 24.8 units (p = 0.0002). CONCLUSION: HT recipients prescribed GLP1-RA therapy showed improved glycemic control, weight loss, and cholesterol levels during the study follow-up period. GLP1-RA were well tolerated and were rarely associated with changes in immunosuppression dosing.

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.

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.

Hemodynamic Optimization by Invasive Ramp Test in Patients Supported With HeartMate 3 Left Ventricular Assist Device.

In patients supported by the HeartMate 3 left ventricular assist device (HM3 LVAD), pump speed adjustments may improve hemodynamics. We investigated the hemodynamic implications of speed adjustments in HM3 recipients undergoing hemodynamic ramp tests. Clinically stable HM3 recipients who underwent routine invasive hemodynamic ramp tests between 2015 and 2022 at our center were included. Filling pressure optimization, defined as central venous pressure (CVP) <12 mm Hg and pulmonary capillary wedge pressure (PCWP) <18 mm Hg, was assessed at baseline and final pump speeds. Patients with optimized pressures were compared to nonoptimized patients. Overall 60 HM3 recipients with a median age of 62 years (56, 71) and time from LVAD implantation of 187 days (124, 476) were included. Optimized filling pressures were found in 35 patients (58%) at baseline speed. Speed was adjusted in 84% of the nonoptimized patients. Consequently, 39 patients (65%) had optimized pressures at final speed. There were no significant differences in hemodynamic findings between baseline and final speeds ( p > 0.05 for all). Six and 12 month readmission-free rates were higher in optimized compared with nonoptimized patients ( p = 0.03 for both), predominantly due to lower cardiac readmission-free rates ( p = 0.052). In stable outpatients supported with HM3 who underwent routine ramp tests, optimized hemodynamics were achieved in only 2 of 3 of the patients. Patients with optimized pressures had lower all-cause readmission rates, primarily driven by fewer cardiac-related hospitalizations.