Impact of carfilzomib-based desensitization on heart transplantation of sensitized candidates.

Background: Allosensitization in heart transplant candidates is associated with longer transplant wait times and post-transplant complications. We summarize our experience with desensitization using carfilzomib, an irreversible proteasome inhibitor that causes plasma cell apoptosis.

Methods: One cycle of desensitization consisted of plasmapheresis and carfilzomib 20 mg/m on days 1, 2, 8, 9, 15, and 16 with intravenous immune globulin 2 g/kg after carfilzomib on day 16.

Report from the 2018 consensus conference on immunomodulating agents in thoracic transplantation: Access, formulations, generics, therapeutic drug monitoring, and special populations.

In 2009, the International Society for Heart and Lung Transplantation recognized the importance and challenges surrounding generic drug immunosuppression. As experience with generics has expanded and comfort has increased, substantial issues have arisen since that time with other aspects of immunomodulation that have not been addressed, such as access to medicines, alternative immunosuppression formulations, additional generics, implications on therapeutic drug monitoring, and implications for special populations such as pediatrics and older adults. The aim of this consensus document is to address critically each of these concerns, expand on the challenges and barriers, and provide therapeutic considerations for practitioners who manage patients who need to undergo or have undergone cardiothoracic transplantation.

Ethical considerations regarding heart and lung transplantation and mechanical circulatory support during the COVID-19 pandemic: an ISHLT COVID-19 Task Force statement.

To understand the challenges for thoracic transplantation and mechanical circulatory support during the current coronavirus disease 2019 pandemic, we propose separating the effects of the pandemic into 5 distinct stages from a healthcare system perspective. We discuss how the classical ethical principles of utility, justice, and efficiency may need to be adapted, and we give specific recommendations for thoracic transplantation and mechanical circulatory support centers to balance their clinical decisions and strategies for advanced heart and lung disease during the current pandemic.

Gene expression profiling and racial disparities in outcomes after heart transplantation.

Background: African Americans (AAs) have lower survival rates after heart transplantation (HTx) than Caucasians. The aim of this analysis was to evaluate racial differences in gene expression and their associations with survival and the composite outcome of death, retransplant, rejection with hemodynamic compromise, and graft dysfunction in the Outcomes AlloMap Registry.

Methods: Registry participants included low-risk Caucasian and AA heart transplant recipients with a baseline and at least 1 follow-up gene expression test (AlloMap(C)) within the first year after HTx.

Infectious complications after heart transplantation in patients screened with gene expression profiling.

Background: The risk of infection after heart transplantation is highest within the first year and represents the leading cause of early mortality. In this cohort of patients enrolled in the Outcomes AlloMap Registry (OAR), we sought to describe infection episodes (IEp) resulting in hospitalization, in the early (<1 year) and late (≥1 year) post-transplant period and determine the impact of immunosuppression on incidence of infection.

Methods: The primary aim was to assess the incidence and nature of IEp.

Thrombotic events with proliferation signal inhibitor‒based immunosuppression in cardiac transplantation.

Background: Some literature exists potentially linking proliferation signal inhibitors (PSIs) to venous thromboembolism (VTE). We sought to determine the impact of PSIs on development of VTE in heart transplant (HT) patients while controlling for other risk factors.

Methods: The incidence and predisposing factors of VTE were analyzed in this retrospective review of patients >18 years who underwent HT January 2000 to October 2016.

Risk evaluation using gene expression screening to monitor for acute cellular rejection in heart transplant recipients.

Background: Gene expression profiling (GEP) was developed for non-invasive surveillance of acute cellular rejection. Despite its widespread use, there has been a paucity in outcome data for patients managed with GEP outside of clinical trials.

Methods: The Outcomes AlloMap Registry (OAR) is an observational, prospective, multicenter study including patients aged ≥ 15 years and ≥ 55 days post-cardiac transplant.

Substantial Reduction in Driveline Infection Rates With the Modification of Driveline Dressing Protocol.

Background: Driveline infection (DLI) is a cause of morbidity and mortality in patients with continuous-flow left ventricular assist devices (CF-LVADs). We hypothesized that an alternate dressing protocol would decrease the rate of DLIs.

Methods And Results: A retrospective review of CF-LVAD implants at a single institution from January 2010 to October 2015 was conducted.

Outcomes associated with mammalian target of rapamycin (mTOR) inhibitors in heart transplant recipients: A meta-analysis.

Background: Data evaluating mTOR inhibitor use heart transplant (HT) patients comes from relatively small studies and controversy exists regarding their specific role. We performed a meta-analysis of randomized trials to evaluate the efficacy and safety of mTOR inhibitors in HT patients.

Methods: We performed a systematic literature search of Medline and Embase through July 2017 identifying studies evaluating mTOR inhibitors in HT patients reporting effects on coronary allograft vasculopathy (CAV), renal function, acute cellular rejection (ACR), cytomegalovirus (CMV) infection, and discontinuation due to adverse drug events (ADE).

Optimal low-density lipoprotein concentration for cardiac allograft vasculopathy prevention.

Cardiac allograft vasculopathy (CAV) is a major risk factor influencing graft loss and patient survival following orthotopic heart transplant. Allograft vasculopathy is a multifactorial process, which includes both immunologic and non-immunologic mechanisms. Given the non-immunological risk factors for vasculopathy, particularly hyperlipidemia, it is intuitive that reducing a patient's LDL would help attenuate the disease process.

Effects of Isavuconazole on the Plasma Concentrations of Tacrolimus among Solid-Organ Transplant Patients.

We evaluated the interaction between isavuconazole and tacrolimus among 55 organ transplant recipients. After isavuconazole discontinuation, the tacrolimus concentration/dose ratio normalized by weight (C/D) was reduced by 16%. Liver transplant recipients experienced the largest C/D reduction.

Low vitamin D exposure is associated with higher risk of infection in renal transplant recipients.

Background: Vitamin D is a steroid hormone with multiple vital roles within the immune system. Various studies evaluated the influence of vitamin D on infections postrenal transplantation and found contrasting results. This study aimed to assess the relationship between vitamin D status and the incidence of infection in renal transplant recipients.

Evaluation of Direct Oral Anticoagulation Therapy in Heart and Lung Transplant Recipients.

Context: Anticoagulation therapy is common in thoracic transplant recipients. Direct oral anticoagulants (DOACs) are alternatives to warfarin therapy, but characterization of their use in solid organ transplant is absent.

Objective: The primary objective of this study was to describe a thoracic transplant patient population initiated on DOAC therapy.

Assessing Anticoagulation Practice Patterns in Patients on Durable Mechanical Circulatory Support Devices: An International Survey.

Anticoagulation in mechanical circulatory support (MCS) patients dictated by local practice, and therefore uniform standards for management are lacking. To characterize the worldwide variance in anticoagulation and antiplatelet therapy in patients with MCS devices, a 42 item survey was created and distributed electronically in August 2014. The survey assessed the center-perceived thromboembolic risk (minimal, low, moderate, or high) and characterized the antiplatelet and anticoagulant strategies for the Thoratec HeartMate II (HMII) and HeartWare HVAD (HVAD).

Cost-effectiveness of routine surveillance endomyocardial biopsy after 12 months post-heart transplantation.

Background: Despite low risk of late rejection after heart transplant (HT), surveillance endomyocardial biopsies (EMBs) are often continued for years. We assessed the cost-effectiveness of routine EMB after 12 months post-HT.

Methods And Results: Markov model compared the following surveillance EMB strategies to baseline strategy of stopping EMB 12 months post-HT: (1) every 4 months during year 2 post-HT, (2) every 6 months during year 2, (3) every 4 months for years 2 to 3, and (4) every 6 months for years 2 to 3.

Blood pressure control in continuous flow left ventricular assist devices: efficacy and impact on adverse events.

Background: Continuous flow (CF) left ventricular assist devices (LVAD) are afterload sensitive and therefore pump performance is affected by hypertension. In addition, poorly controlled hypertension may increase the risk of aortic insufficiency (AI) and stroke. Blood pressure regimens after CF LVAD have not been studied and their impact on rates of AI and stroke are unknown.

Optical coherence tomography for characterization of cardiac allograft vasculopathy after heart transplantation (OCTCAV study).

Background: Optical coherence tomography (OCT) is a novel intravascular imaging modality with excellent spatial resolution. This study explored the utility of OCT in cardiac transplantation for the detection and characterization of early changes associated with coronary allograft vasculopathy (CAV).

Methods: Fifteen consecutive patients, 1 to 4 years after transplant with no angiographic evidence of CAV, underwent successful OCT imaging using the Fourier-domain OCT system (C7-XR, St.

Heart transplantation for adults with congenital heart disease: results in the modern era.

Background: Heart transplantation in adults with congenital heart disease (CHD) has historically been associated with sub-optimal survival compared with other indications for transplantation. The purpose of this study was to evaluate survival outcomes after heart transplantation in a contemporary cohort of adults with CHD and to identify risk factors for mortality that may help guide recipient and donor selection.

Methods: We performed a retrospective analysis of our adult heart transplant database, from January 2001 to February 2011, identifying 19 patients who underwent transplantation for CHD.

Alemtuzumab for cytolytic induction of immunosuppression in heart transplant recipients.

Objective: To review available evidence about the safety and efficacy of alemtuzumab for induction of immunosuppression in heart transplant recipients.

Data Sources: Searches of MEDLINE, EMBASE, and Cochrane databases were conducted. Key search terms included alemtuzumab, Campath-1H, CD52, lymphocyte, cytolytic, induction, immunosuppression, rejection, and cardiac transplantation.

Persistent strong anti-HLA antibody at high titer is complement binding and associated with increased risk of antibody-mediated rejection in heart transplant recipients.

Background: Sensitized heart transplant candidates are evaluated for donor-specific anti-HLA IgG antibody (DSA) by Luminex single-antigen bead (SAB) testing (SAB-IgG) to determine donor suitability and help predict a positive complement-dependent cytotoxicity crossmatch (CDC-XM) by virtual crossmatching (VXM). However, SAB testing used for VXM does not correlate perfectly with CDC-XM results and individual transplant programs have center-specific permissible thresholds to predict crossmatch positivity. A novel Luminex SAB-based assay detecting C1q-binding HLA antibodies (SAB-C1q) contributes functional information to SAB testing, but the relationship between SAB strength and complement-binding ability is unclear.

Invasive aspergillosis among heart transplant recipients is rare but causes rapid death due to septic shock and multiple organ dysfunction syndrome.

Between 2000 and 2011, proven or probable invasive aspergillosis (IA) was diagnosed in 1.7% (8/455) of heart transplant (HTx) recipients at our center, in the absence of antifungal prophylaxis. All patients had invasive pulmonary infections and 75% (6/8) were diagnosed during 2 separate 3-month periods.