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Background: National data demonstrate that increasing opportunities exist for organ donation among hepatitis C virus (HCV)-infected individuals., Methods: We developed a clinical practice protocol for the acceptance of HCV+ organs for HCV- patients who underwent heart transplantation (HT) and retrospectively reviewed the outcomes at our institution. Inclusion criteria were as follows: all adult patients listed for HT. Exclusion criteria were as follows: pre-existing HIV or active hepatitis B viremia in the recipient/donor., Results: We transplanted 21 patients from HCV+ donors. Nineteen were viremic donors, and 2 were non-viremic donors. The recipients included 18 patients who underwent HT alone, and 3 patients who underwent combined heart-kidney transplants. There was no HCV transmission from the non-viremic donors (n = 2). All 19 recipients of the viremic donors developed HCV infection (100% transmission). The median age of the viremic donors was 34 years (interquartile range 30-46), and 84.2% were considered US Public Health Service-increased risk. Induction immunosuppression consisted of anti-thymocyte globulin (7/21), basiliximab (7/21), or none (8/21). Maintenance immunosuppression comprised tacrolimus, mycophenolate mofetil, and prednisone. Post-operative Week 2 HCV viral load was not related to induction. Direct anti-viral agent (DAA) therapy for a 12-week course consisted of glecaprevir/pibrentasvir (14/19, 74%), sofosbuvir/velpatasvir (2/19, 11%), elbasvir/grazoprevir (2/19, 11%), and ledipasvir/sofosbuvir (1/19, 5%). All the patients on DAA therapy cleared viremia. The sustained virological response rate at 12 weeks in 18 evaluable patients was 100%., Conclusions: We report successful single-center experience using HCV+ organs for HT into HCV- recipients. We believe that there is utility in using such organs to expand the current donor pool. Further long-term follow-up is needed., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The optimal immunosuppressive therapy (IST) for patients with AL amyloid undergoing orthotopic heart transplantation (OHT) is not well defined. Our study aims to present the IST and outcomes after OHT in patients with cardiac amyloidosis at a large quaternary university hospital. In a retrospective chart review, we performed a case series of all patients with AL amyloid who underwent OHT from Jan 2017 to Oct 2020. We assessed their IST and outcomes of survival, infection and rejection. We identified 7 patients with AL amyloidosis who underwent OHT. Three patients (43%) had Mayo Stage 3, and 4 (57%) patients had stage 4. Autologous stem cell transplant (ASCT) was performed in 4 patients with a median time from OHT to ASCT of 429 days. In patients who had bone marrow biopsy, amyloid was present in 21% and the mean plasma cells visualized by immunohistochemistry was 4.41%. IST after OHT consisted of a calcineurin inhibitor, antimetabolite and steroids initially. Some required treatment with bortezomib/daratumumab for sub-optimal duration or hematologic response to AL amyloid therapies prior to OHT at which time antimetabolite was stopped. Median time to antimetabolite withdrawal was 317 days. Median times to introduction of daratumumab and bortezomib after OHT were 283 and 388 days, respectively. Figure 1 displays the time series of IST. Renal involvement was the more prevalent extracardiac organ (57%), followed by gastrointestinal (43%), carpal tunnel (29%), and peripheral neuropathy (29%). We did not observe any mortality, graft failure, episodes of acute cellular or antibody-mediated rejection. One patient had clostridium difficile infection who was admitted for monitoring. In those that require ongoing AL amyloid therapies following OHT, it may be safe to discontinue antimetabolite in efforts to minimize complications from over-immunosupression without compromising risk of rejection. Personalized IST in this traditionally high-risk population should be considered. [ABSTRACT FROM AUTHOR]

Purpose Ongoing opioid epidemic has led to an increase in hepatitis C virus (HCV)+ organs. Given excellent cure rates with direct acting antivirals (DAAs), there is interest in using such organs for transplant. Methods We implemented a protocol to transplant HCV+ organs into HCV-recipients. This included patient/ provider education, 2-stage informed consent process, detailed donor/ recipient testing, and DAA therapy in the recipient. Inclusion criteria: All adult patients listed for heart transplant (HT). Exclusion criteria: Pre-existing human immunodeficiency virus or active hepatitis B viremia in the recipient/ donor. Results We transplanted 20 patients from HCV+ donors; 18 were viremic donors and 2 were non-viremic. Recipients included 17 HT alone and 3 combined heart-kidney transplants. There was no HCV transmission from non-viremic donors; all 18 recipients of viremic donors developed acute HCV infection. Among viremic donors, median age was 33.5 years, 89% were male, and 83% were PHS increased risk. Following HCV genotypes were noted: 1a (n=9), 1b (n=2), 2/2b (n=3), 3 (n=4) and 4 (n=1, concomitant 2b). Antiviral resistance testing was negative/indeterminate in all cases. Viremia was detected at day 3 in 69% (cut off >15 copies/ml) and week 1 in 87%. No recipient developed acute liver failure. Induction immunosuppression used: none (7/18, 39%), thymoglobulin (6/18, 33%), basiliximab (4/18, 22%), or both (1/18, 6%). Maintenance immunosuppression consisted of steroids, tacrolimus and mycophenolate mofetil as per center protocol. DAAs for 12-week course (one patient awaiting treatment): glecaprevir/pibrentasvir (13/17, 76%), sofosbuvir/velpatasvir (2/17, 12%), and elbasvir/grazoprevir (2/17, 12%). All patients on DAAs cleared viremia, sustained virological response rate at 12 weeks (SVR12) was 90% based on 10 evaluable patients (others need further follow-up; one died of un-related causes before SVR12 could be assessed). One patient developed cardiac allograft vasculopathy (from a non-viremic donor; none from viremic donors). Conclusion We report successful single-center experience utilizing HCV+ organs for heart/ heart-kidney transplantation into HCV-negative recipients. There is utility in using such organs in order to expand the current donor pool. Further long-term follow-up is needed. [ABSTRACT FROM AUTHOR]

Patients diagnosed with Heparin-Induced Thrombocytopenia (HIT) present a unique challenge when requiring Cardiopulmonary Bypass (CPB). The use of bivalirudin during CPB in patients with renal disease is not an ideal option due to increased risk of bleeding. This is due to prolonged half-life and lack of a reversal agent. Cangrelor, a P2Y12 receptor antagonist which inhibits platelet activation and aggregation, may prevent the thrombosis cascade associated with HIT. A 53 year old male presented with ST elevation myocardial infarction and cardiogenic shock requiring inotropes and vasopressors as well as mechanical support with Impella CP®. He had a prolonged hospital course, complicated by HIT, type II. He was placed on bivalirudin and his platelet count improved. In the setting of ongoing cardiogenic shock and renal failure, he was listed for heart and kidney transplant. His platelet count was 202k on the day of heart transplant. Intraoperatively, he received a loading dose of cangrelor, 30 mcg/kg, followed by an infusion of 4 mcg/kg/min. VerifyNow P2Y12 reaction unit (PRU) assay was used, and PRU was maintained at <180. A standard heparin bolus was given 15 minutes after the cangrelor bolus. Once ACT was >450 seconds, CPB was instituted. Cangrelor infusion was discontinued 5 minutes prior to heparin reversal with protamine. The patient was successfully weaned from CPB. Due to anticipated coagulopathy, the chest was packed and left open. The following day, the chest was closed, and he received a kidney transplant without complications. He was discharged on post operative day number 28. This is the first report of a dual organ transplant (heart and kidney) with acute HIT in whom a combination of cangrelor with heparin was used as an alternative intraoperative anticoagulation strategy. Previous reports of cardiac surgery in HIT using antiplatelet therapy in combination with heparin were limited by hypotension (prostacyclines) and bleeding (glycoprotein IIb-IIIa antagonists). Cangrelor has a short half-life of 3-6 minutes, potentially reducing bleeding complications. Further research and efficacy of long term outcomes with the use of cangrelor and heparin for CBP in patients with HIT is warranted. [ABSTRACT FROM AUTHOR]

Immunosuppression induction is commonly utilized in heart transplant (HT) to prevent acute rejection and/or delay calcineurin inhibitor (CNI) initiation. However, guidance on whether to use induction and preferred agent(s) are not well defined. This is reflected by high practice variability across centers. According to ISHLT registry data, 54% of adult HT cases utilized induction, 31% with an IL-2R antagonist and 23% with a T-cell depleting agent. Our center has primarily utilized 3 strategies based on rejection risk and need to delay CNI: IL-2R antagonist (basiliximab), T-cell depleting (anti-thymocyte globulin, rabbit (rATG)), or no induction. Our study's objective was to compare these strategies' safety and effectiveness. A retrospective chart review was conducted at a large academic medical center, including HT cases performed between January 2015 and April 2019. Patients were stratified by induction strategy used at the time of transplant. The primary outcomes were rate of biopsy-proven acute cellular rejection (ACR) grade 2R or higher, treated antibody mediated rejection (AMR), and any infection within one year of transplantation. From January 2015 to April 2019, 145 total HTs were included in our study (123 heart, 20 heart-kidney, and 2 heart-liver). rATG was the most common induction strategy used (36%), followed by no induction (35%), and basiliximab (26%). Four patients (3%) received 1 dose of basiliximab but were switched to rATG. ACR rates were not statistically different among induction groups: 22% with no induction, 11% with basiliximab, 17% with rATG, and 0% with combination (p = 0.51). AMR rates were also not statistically different: 6% with no induction, 5% with basiliximab, 4% with rATG, and 0% with combination (p = 0.93). There was no difference detected in donor-specific antibody (DSA) formation at 1 year (p = 0.81). The percentages of patients with any infection were: 53% with no induction, 55% with basiliximab, 62% with rATG, and 75% with combination (p = 0.90). Incidences of ACR, AMR, DSA formation, and infection were not statistically different among induction strategies at one year post-transplant. It may be beneficial to individualize induction strategies based on recipient factors at the time of transplantation. Long term outcomes in this patient cohort are yet to be determined. [ABSTRACT FROM AUTHOR]