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.

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.

The Hemodynamic Effects of Aortic Regurgitation in Patients Supported by a HeartMate 3 Left Ventricular Assist Device.

BACKGROUND: Aortic regurgitation (AR) is a common complication following left ventricular assist device (LVAD) implantation. We evaluated the hemodynamic implications of AR in patients with HeartMate 3 (HM3) LVAD at baseline and in response to speed changes. METHODS AND RESULTS: Clinically stable outpatients supported by HM3 who underwent a routine hemodynamic ramp test were retrospectively enrolled in this analysis. Patients were stratified based on the presence of at least mild AR at baseline speed. Hemodynamic and echocardiographic parameters were compared between the AR and non-AR groups. Sixty-two patients were identified. At the baseline LVAD speed, 29 patients (47%) had AR, while 33 patients (53%) did not. Patients with AR were older and supported on HM3 for a longer duration. At baseline speed, all hemodynamic parameters were similar between the groups including central venous pressure, pulmonary capillary wedge pressure, pulmonary arterial pressures, cardiac output and index, and pulmonary artery pulsatility index (p > 0.05 for all). During the subacute assessment, AR worsened in some, but not all, patients, with increases in LVAD speed. There were no significant differences in 1-year mortality or hospitalization rates between the groups, however, at 1-year, ≥ moderate AR and right ventricular failure (RVF) were detected in higher rates among the AR group compared to the non-AR group (45% vs. 0%; p < 0.01, and 75% vs. 36.8%; p = 0.02, respectively). CONCLUSIONS: In a cohort of stable outpatients supported with HM3 who underwent a routine hemodynamic ramp test, the presence of mild or greater AR did not impact the ability of HM3 LVADs to effectively unload the left ventricle during early subacute assessment. Although the presence of AR did not affect mortality and hospitalization rates, it resulted in higher rates of late hemodynamic-related events in the form of progressive AR and RVF.

Pumping for Two: Pregnancy in Patients Supported With a Left Ventricular Assist Device.

This review discusses the challenges and outcomes associated with pregnancy during left ventricular assist device (LVAD) support. Women account for a third of the heart failure population in the United States. Left ventricular assist devices have emerged as a safe and effective treatment option for patients with advanced heart failure. Pregnancy during LVAD support can occur, and it presents significant risks to both mother and fetus, including hemodynamic stress, thrombotic events, medication-associated teratogenicity, and uterine impingement. This literature review identified 10 cases of confirmed pregnancy during LVAD support, of which eight resulted in successful births. Maternal and fetal mortality occurred in one case, and there was a spontaneous abortion in one case. The review highlights the importance of a multidisciplinary approach, promotion of shared decision-making, thoughtful anticoagulation, adjustment of LVAD speed, and medication optimization to maintain hemodynamic support during pregnancy. Hemodynamic changes during pregnancy include increased cardiac output, heart rate, and plasma volume, as well as decreased systemic vascular resistance, which can impact LVAD support. Despite reduced pulsatility in LVAD-supported patients, ovulation and reproductive capacity might be preserved, and viable pregnancies may be achieved with appropriate management. The review provides insights into the risks and considerations for a viable pregnancy during LVAD support, including the need for ongoing research to inform joined decision-making.

The utilization of molecular microscope in management of heart transplant recipients in the era of noninvasive monitoring.

INTRODUCTION: Monitoring for graft rejection is a fundamental tenet of post-transplant follow-up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor-derived cell-free DNA (dd-cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB. METHODS: This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection. CONCLUSIONS: We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies.

Aortic Root Thrombosis in patients with HeartMate 3 left ventricular assist device support.

BACKGROUND: Aortic root thrombosis(ART) is a complication of continuous-flow left ventricular assist device therapy. However, the incidence and related complications of ART in HeartMate 3 (HM3) patients remain unknown. METHODS: Patients who underwent HM3 implantation from November 2014 to August 2020 at a quaternary academic medical center were included. Demographics and outcomes were abstracted from the medical record. Echocardiograms and contrast-enhanced computed tomography studies were reviewed to identify patients who developed ART and/or moderate or greater aortic insufficiency (AI) on HM3 support. RESULTS: The study cohort included 197 HM3 patients with a median postimplant follow-up of 17.5 months. Nineteen patients (9.6%) developed ART during HM3 support, and 15 patients (7.6%) developed moderate or greater AI. Baseline age, gender, race, implantation strategy, and INTERMACS classification were similar between the ART and no-ART groups. ART was associated with an increased risk of death, stroke, or aortic valve (AV) intervention (subhazard ratio [SHR] 3.60 [95% confidence interval (CI) 1.71-7.56]; p = 0.001) and moderate or greater AI (SHR 11.1 [CI 3.60-34.1]; p < 0.001) but was not associated with a statistically significantly increased risk of death or stroke on HM3 support (2.12 [0.86-5.22]; p = 0.10). Of the 19 patients with ART, 6 (31.6%) developed moderate or greater AI, necessitating more frequent AV interventions (ART: 5 AV interventions [3 surgical repairs, 1 surgical replacement, 1 transcatheter replacement; 26.3%]; no-ART: 0). CONCLUSIONS: Nearly 10% of HM3 patients developed ART during device support. ART was associated with increased risk of a composite end-point of death, stroke, or AV intervention as well as moderate or greater AI.

Extracorporeal photopheresis and its role in heart transplant rejection: prophylaxis and treatment.

Heart transplantation is the gold standard therapeutic option for select patients with end-stage heart failure. Unfortunately, successful long-term outcomes of heart transplantation can be hindered by immune-mediated rejection of the cardiac allograft, specifically acute cellular rejection, antibody-mediated rejection, and cardiac allograft vasculopathy. Extracorporeal photopheresis is a cellular immunotherapy that involves the collection and treatment of white blood cells contained in the buffy coat with a photoactive psoralen compound, 8-methoxy psoralen, and subsequent irradiation with ultraviolet A light. This process is thought to cause DNA and RNA crosslinking, ultimately leading to cell destruction. The true mechanism of therapeutic action remains unknown. In the last three decades, extracorporeal photopheresis has shown promising results and is indicated for a variety of conditions. The American Society for Apheresis currently recommends the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma, scleroderma, psoriasis, pemphigus vulgaris, atopic dermatitis, graft-versus-host disease, Crohn's disease, nephrogenic systemic fibrosis, and solid organ rejection in heart, lung, and liver transplantation. In this review, we aim to explore the proposed effects of extracorporeal photopheresis and to summarize published data on its use as a prophylactic and therapy in heart transplant rejection.

The impact of telemedicine in cardiac critical care.

Telemedicine was recognized in the 1970s as a legitimate entity for applying the use of modern information and communications technologies to the delivery of health services. Telecardiology is one of the fastest growing fields in telemedicine. The advancement of technologies and Web-based applications has allowed better transmission of health care delivery. This article discusses current advancements, the scope of telemedicine in cardiology, and its application to the critically ill. The impact of telecardiology consultation continues to evolve and includes many promising applications with potential positive implications for admission rates, morbidity, and mortality.