From bench to bedside: reversing established antibody responses and desensitization.

Purpose Of Review: Basic transplant immunology has primarily focused on the definition of mechanisms, but an often-stated aspirational goal is to translate basic mechanistic research into future therapy. Pretransplant donor-specific antibodies (DSA) mediate hyperacute as well as early antibody-mediated rejection (AMR), whereas DSA developing late posttransplantation may additionally mediate chronic rejection. Although contemporary immunosuppression effectively prevents early cellular rejection after transplant in nonsensitized patients, it is less effective at controlling preexisting HLA antibody responses or reversing DSA once established, thus underscoring a need for better therapies.

Current Desensitization Strategies in Heart Transplantation.

Heart transplant candidates sensitized to HLA antigens wait longer for transplant, are at increased risk of dying while waiting, and may not be listed at all. The increasing prevalence of HLA sensitization and limitations of current desensitization strategies underscore the urgent need for a more effective approach. In addition to pregnancy, prior transplant, and transfusions, patients with end-stage heart failure are burdened with unique factors placing them at risk for HLA sensitization.

How can we better inform our patients about post-heart transplantation survival? A conditional survival analysis.

Background: Conditional survival (CS) is a dynamic method of survival analysis that provides an estimate of how an individual's future survival probability changes based on time post-transplant, individual characteristics, and post-transplant events. This study sought to provide post-transplant CS probabilities for heart transplant recipients based on different prognostic variables and provide a discussion tool for the providers and the patients.

Methods: Adult heart transplant recipients from January 1, 2004, through October 18, 2018, were identified in the UNOS registry.

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.

De Novo Human Leukocyte Antigen Allosensitization in Heartmate 3 Versus Heartmate II Left Ventricular Assist Device Recipients.

Left ventricular assist devices (LVADs) are associated with the development of antihuman leukocyte antigen (HLA) antibodies, which can create a challenge for future transplantation in these patients. The differential effects of Heartmate 3 (HM3) versus Heartmate II (HMII) on de novo HLA allosensitization remain unknown. Patients who underwent HMII or HM3 implantation and had no prior HLA antibodies by solid-phase assay (Luminex) testing were included in this study.

T cell repertoire analysis suggests a prominent bystander response in human cardiac allograft vasculopathy.

T cells are implicated in the pathogenesis of cardiac allograft vasculopathy (CAV), yet their clonality, specificity, and function are incompletely defined. Here we used T cell receptor β chain (TCRB) sequencing to study the T cell repertoire in the coronary artery, endomyocardium, and peripheral blood at the time of retransplant in four cases of CAV and compared it to the immunoglobulin heavy chain variable region (IGHV) repertoire from the same samples. High-dimensional flow cytometry coupled with single-cell PCR was also used to define the T cell phenotype.

Desensitizing highly sensitized heart transplant candidates with the combination of belatacept and proteasome inhibition.

HLA antibodies pose a significant barrier to transplantation and current strategies to reduce allosensitization are limited. We hypothesized that augmenting proteasome inhibitor (PI) based desensitization with costimulation blockade (belatacept) to mitigate germinal center (GC) responses might increase efficacy and prevent rebound. Four highly sensitized (calculated panel reactive antibody [cPRA] class I and/or II >99%, complement-dependent cytotoxicity panel reactive antibody [CDC PRA+], C1q+) heart transplant candidates were treated with the combination of belatacept and PI therapy, which significantly reduced both class I and II HLA antibodies and increased the likelihood of identifying an acceptable donor.

Characteristics and Outcomes of Recipients of Heart Transplant With Coronavirus Disease 2019.

Importance: Recipients of heart transplant (HT) may be at increased risk of adverse outcomes attributable to infection with coronavirus disease 2019 (COVID-19) because of multiple comorbidities and clinically significant immunosuppression.

Objective: To describe the characteristics, treatment, and outcomes of recipients of HT with COVID-19.

Design, Setting, And Participants: This case series from a single large academic heart transplant program in New York, New York, incorporates data from between March 1, 2020, and April 24, 2020.

Desensitization in the Era of Precision Medicine: Moving From the Bench to Bedside.

Patients with antibodies to HLA wait longer for transplant and are at increased risk of adverse outcomes. For more than a decade, drug therapy approaches have been tested to modulate the immune system to prevent or reduce donor-specific antibody levels. Despite some studies reporting success in facilitating transplant, many patients do not respond or experience donor-specific antibody rebound, highlighting the diversity of the individual patient's immune response.

Advanced Therapies for Advanced Heart Failure in Women.

Women with advanced heart failure (HF) are underrepresented in trials of short-term and durable mechanical circulatory support although they derive similar benefit. In acute HF, intensive medical and interventional therapies are effective but underutilized. The smaller, newer generation, left ventricular assist devices (LVADs) have increased the feasibility of durable support in women.

VA-ECMO for cardiogenic shock in the contemporary era of heart transplantation: Which patients should be urgently transplanted?

With the impending United Network for Organ Sharing (UNOS) heart allocation policy giving VA-ECMO supported heart transplant (HT) candidates highest priority status (Tier 1), identifying patients in cardiogenic shock (CS) with severe and irreversible heart failure (HF) appropriate for urgent HT is critically important. In a center where wait times currently preclude this approach, we retrospectively reviewed 119 patients (ages 18-72) with CS from 1/2014 to 12/2016 who required VA-ECMO for >24 hours. Underlying aetiologies included postcardiotomy shock (45), acute coronary syndromes (33), and acute-on-chronic HF (16).

Heart rate in patients with reduced ejection fraction: relationship between single time point measurement and mean heart rate on prolonged implantable cardioverter defibrillator monitoring.

Background: Heart rate (HR) is a prognostic marker that is increasingly used as a therapeutic target in patients with cardiovascular disease. The association between resting and mean HR remains unclear. We therefore set out to determine the relationship between resting HR on the electrocardiogram (ECG) obtained at a single time point, and mean HR on implantable cardioverter defibrillator (ICD) interrogation amongst patients with a reduced left ventricular ejection fraction (LVEF).

Long-term management of end-stage heart failure.

End-stage heart failure manifests as severe and often relentless symptoms that define the clinical syndrome of heart failure, namely congestion and hypoperfusion. These patients suffer from dyspnea, fatigue, abdominal discomfort, and ultimately cardiac cachexia. Renal and hepatic dysfunction frequently further complicates the process.

Association of heart rate at hospital discharge with mortality and hospitalizations in patients with heart failure.

Background: Heart failure (HF) is associated with a high burden of morbidity and mortality. Hospital discharge is an opportunity for identification of modifiable prognostic factors in the transition to chronic HF.

Methods And Results: We examined the association of discharge heart rate with 30-day and 1-year mortality and hospitalization outcomes in a cohort of 9097 patients with HF discharged from hospital.

How aware of advanced care directives are heart failure patients, and are they using them?

Background: The increasing prevalence of heart failure and its unpredictable trajectory highlight the need for patients to make their end-of-life care wishes known using advanced care directives (ACDs). The paucity of literature addressing heart failure patients' decision-making processes and knowledge of ACDs underscores the need for investigation. The purposes of this study were to (1) determine patients' awareness, comprehension, and utilization of ACDs and (2) determine their knowledge of the process of cardiopulmonary resuscitation and their current resuscitation preference.