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.

"Durable left ventricular assist devices as a bridge to transplantation in The Old and The New World".

Heart transplantation remains the gold standard treatment for end-stage heart failure patients without contraindications. However, limited donor availability and long wait times have created a need for left ventricular assist devices (LVAD) to be used as a bridge to transplantation in appropriately selected patients. Improvements in LVAD technology have resulted in improved short- and long-term outcomes, further supporting the use of these devices for a bridge-to-transplant (BTT) indication. LVAD utilization as BTT exhibits notable disparities worldwide, mainly due to variations in organ availability, allocation policies, and financial constraints. Although Europe has experienced a consistent increase in the use of LVAD for this purpose, the United Network for Organ Sharing 2018 policy amendment resulted in a significant reduction in the number of LVADs used for BTT in the US. To overcome this issue, modifications in the US allocation policy to consider factors such as days on device support, age, and type of complications may be necessary to potentially increase implantation rates.The authors provide an overview comparing the current state of heart transplantation in the US and Europe, with a particular focus on how distinct allocation policies and organ availability impact medical practices. Additionally, the review will examine critical aspects ranging from patient selection and pre-implantation optimization to post-transplant outcomes.

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.

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.

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.

Sex differences in patients undergoing heart transplantation and LVAD therapy.

INTRODUCTION: Left ventricular assist device (LVAD) and heart transplantation (HT) are the two life-sustaining therapies that have revolutionized the management of end-stage heart failure (HF). Yet, significant sex differences exist with respect to their use and effects. AREAS COVERED: This review summarizes sex differences in the utilization, outcomes, and complications of LVAD and HT. Particular emphasis is placed on leading clinical trials in the field, historical and recent large registries-based analyses, as well as contemporary technological and policy changes affecting these differences. EXPERT OPINION: Women with advanced HF remain under-treated with guideline-directed medical therapy and are less likely to be referred for consideration for LVAD and HT. This remains true despite newer LVAD technology and the new heart transplant allocation system. Community outreach, education, as well as increased representation of women in clinical research may reduce inequities.