Faculty Bibliography

Thoracic organs from Hepatitis C virus (HCV) positive donors are not commonly used for transplantation. The development of direct-acting antivirals (DAA) for HCV treatment has led to renewed interest in using HCV-positive organs. We evaluated HCV transmission rates, viremia clearance, and short-term outcomes in HCV-negative patients who received HCV-positive thoracic organs at our institution. From January 1, 2018 to May 31, 2019, 38 patients underwent HCV-positive thoracic organ transplantation (16 lungs and 22 hearts). Heart recipients were started on glecaprevir/pibrentasvir, a pangenotypic DAA, when they developed HCV viremia. Lung recipients were empirically started on glecaprevir/pibrentasvir within the first three post-transplant days. The primary outcome was cure of HCV defined as sustained virologic response at 12 weeks (SVR12). All heart recipients developed HCV viremia with median initial viral load of 64,565 IU/mL (interquartile range: 1660 to 473,151). The median time from DAA initiation to viremia clearance was 19 days (confidence interval: 15-27 days). 11 out of 16 (68.8%) lung recipients developed HCV viremia with median initial viral load of 26 IU/mL (interquartile range: 15 to 143). The median time from DAA initiation to viremia clearance was 10 days (confidence interval: 6-17 days). 5 out of 16 (31.3%) lung recipients never became viremic. All patients demonstrated SVR12. Thoracic organ transplantation from HCV viremic donors is safe with excellent short-term survival. Early initiation of HCV treatment results in rapid viremia clearance and SVR12. Long-term outcomes and optimal timing of DAA initiation remains to be determined.

Purpose: As an early epicenter in the coronavirus pandemic, our center modified induction immunosuppression strategies for transplantation. We sought to determine if changes in induction immunosuppression secondary to the COVID-19 pandemic impacted the incidence of acute rejection.
Method(s): Adult kidney transplant recipients at NYU Langone Health between 09/2019 and 08/2020 were retrospectively identified. Patients who received a multiorgan transplant or whose induction regimen was changed due to clinical course were excluded. Patients transplanted before and after 3/17/2020 were grouped as pre-pandemic (PRE) and post-pandemic (POST), respectively, based on temporary interruption of transplantation. Induction immunosuppression discordance was identified by blind adjudication from a standard protocol. Reduced induction agent use (basiliximab given when pre-pandemic protocol indicated rabbit anti-thymocyte globulin (rATG)) was compared between groups using a Chi-square test. Biopsyproven acute rejection (BPAR) and the incidence of rejection was compared using a Poisson regression model.
Result(s): 203 kidney transplant recipients were retrospectively identified. 38 patients were excluded, leaving 165 patients for analysis. Median patient age was 57 years, 67% were male, and diabetes mellitus (35%) was the most common cause of renal disease. Discordance from protocol induction agent was 16% in the PRE group and 28% in the POST group (p=0.06). More patients received reduced induction with basiliximab in lieu of rATG in the POST group than the PRE group (26% vs. 7%, p=0.001). BPAR occurred in 5 PRE (5%) and 6 POST (11%) patients (p=0.19). The incidence of rejection was 0.13 and 0.75 rejection episodes/1,000-patient days for the PRE and POST groups, respectively; this was significantly different between the 2 time periods (unadjusted IRR 5.69, 95% CI 1.74-18.6, p=0.004).
Conclusion(s): More patients received reduced induction immunosuppression driven by the COVID-19 pandemic concerns. These COVID-related changes in immunosuppression may have contributed to a trend in increased acute rejection in a preliminary analysis

BACKGROUND/UNASSIGNED:There is a lack of robust data evaluating outcomes of enoxaparin "bridge" therapy in left ventricular assist device (LVAD) patients. METHODS/UNASSIGNED:We performed a retrospective study of HeartMate II (HM II) and HeartWare HVAD recipients that received therapeutic enoxaparin as "bridge" therapy to describe bleeding and thrombotic events and compare outcomes between devices. The primary endpoint was the incidence of bleeding within 30 days of "bridge" episode. Major bleeding was defined by INTERMACS criteria. RESULTS/UNASSIGNED:= .02). We observed 3 (1%) thromboembolic events in 2 (4%) patients with an HVAD device. On multivariate analysis, the presence of a HM II device was associated with a 4-fold increased risk of bleeding. CONCLUSION/UNASSIGNED:We found the use of enoxaparin "bridge" therapy to be associated with a higher incidence of bleeding in patients with a HM II device compared with an HVAD device. Assessment of device- and patient-specific factors should be evaluated to minimize bleeding events.

Purpose: During the COVID 19- pandemic, there is no consensus on management strategies for treating infected heart transplant patients. The outcomes of these patients vary by institution. We report our center experience and management strategies to date.
Method(s): All patients who received heart transplantation, from January 4th 2018 to September 25th 2020 and were diagnosed with SARS-CoV-2 were included and full chart review was performed.
Result(s): There were 113 heart transplants at our institution by September 2020. A total of 13 (12%) patients were infected with SARS-CoV-2: 9 (69%) isolated heart, 3 heart -kidney (23%) and 1 heat- lung (8%). The median (IQR) time from transplant to diagnosis was 10 (5-16) months. The mean age was 57 years and 50% were male; 50% were of Hispanic ethnicity. The main presenting symptoms were fever (43%), cough (86%) and SOB (43%). Chest x-ray was abnormal in all patients. We evaluated all patients and 79% were hospitalized and 21% were closely monitored as outpatients. None of our patients were hospitalized at outside institutions. Two (14%) required intubation and none required V-V ECMO support. The immunotherapy was modified in all patients: MMF and prednisone were discontinued, tacrolimus dose was reduced. COVID19 treatment was: 71% received hydroxychloroquine, 50% azithromycin, 15% remdesevir, 7% convalescent plasma. All hospitalized patients received anticoagulation. One patient had 2R/3A rejection within 30 days prior to diagnosis. Graft function was maintained in all patients with median LVEF% 65 (59-65%) except one patient who had received thymoglobulin 2 weeks prior to COVID 19 infection (LVEF 30%). The patient had a prolonged intubation but ultimately recovered and was discharged from the hospital. The one death (7.1%) was a heart - kidney recipient who concomitantly presented with pseudomonas sepsis and severe neutropenia. The remaining patients have all been discharged home.
Conclusion(s): We present our single center experience in managing COVID 19 infected heart transplant patients. We implemented uniform management strategies by incorporating aggressive reduction of immunosuppression, frequent scheduled contacts with infected outpatients and making sure all infected patients requiring hospitalization were treated at a transplant center.
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Pump thrombosis remains a feared complication for patients implanted with durable left ventricular assist devices. Optimal treatment is unknown, but consists of either pharmacologic fibrinolysis or surgical pump exchange. Fibrinolysis is less invasive, but carries a significant risk of intracerebral hemorrhage. We present four cases of LVAD pump thrombosis successfully treated with a novel protocol that consists of low-dose four-factor prothrombin complex concentrate to reverse baseline INR elevation prior to alteplase administration to minimize the risk for intracerebral hemorrhage.

BACKGROUND/UNASSIGNED:Patients with cardiogenic shock after percutaneous coronary intervention (PCI) may require mechanical circulatory support (MCS). The combination of dual antiplatelet therapy with cangrelor and continuous anticoagulation required for MCS may increase the risk of bleeding. OBJECTIVE/UNASSIGNED:The objective of the study is to describe the complications and outcomes of patients who received cangrelor during MCS following PCI. METHODS/UNASSIGNED:This is a single-center, retrospective, observational case series of 17 patients who received cangrelor while on MCS from June 2017 to September 2019. RESULTS/UNASSIGNED:In a case series of 17 patients, 8 patients (47%) were supported with an Impella device and 4 patients (24%) with venoarterial (VA) extracorporeal membrane oxygenation (ECMO); 5 required (29%) concomitant VA ECMO and Impella support in the setting of cardiogenic shock. All patients received triple antithrombotic therapy with aspirin, heparin, and cangrelor. Cangrelor was commonly initiated at a median dose of 0.75 (range 0.5-4) µg/kg/min. Cangrelor dose adjustments included changes in increments up to 0.25 µg/kg/min with review of P2Y12 levels. A total of 10 patients (59%) experienced a bleeding event, most commonly located at the peripheral cannulation site (40%) and in the gastrointestinal tract (30%). Seven (70%) and 3 (30%) of the bleeding complications were classified as major and minor, respectively. No patient developed in-stent thrombosis during the hospitalization; 14 (82%) patients survived their MCS course. CONCLUSION AND RELEVANCE/UNASSIGNED:This case series suggests that cangrelor doses less than 0.75 µg/kg/min may be beneficial. Larger studies should evaluate alternative dosing regimens.

Bleeding following cardiac surgery that warrants transfusion of blood products is associated with significant complications, including increased mortality at 1 year following surgery. Factor concentrates, such as prothrombin complex concentrate (PCC), or recombinant activated factor VII (rFVIIa) have been used off-label for bleeding in cardiac surgery that is refractory to conventional therapy. The objective of this retrospective study is to assess the hemostatic effectiveness of 4-factor PCC or rFVIIa for bleeding after a broad range of cardiac surgeries. Patients were included if they were at least 18 years of age and had undergone cardiac surgery with bleeding requiring intervention with 4-factor PCC or rFVIIa. There were no differences observed in the number of packed red blood cells (4-factor PCC: 2 units vs. rFVIIa: 2 units), fresh frozen plasma (0 units vs. 1 unit) or platelet (2 units vs. 2 units) transfusions following the administration of 4-factor PCC or rFVIIa. The patients in the rFVIIa group, required more cryoprecipitate than those in the 4-factor PCC group (4-factor PCC: 2 units (range 0-6) vs. rFVIIa: 2 units (range 0-8), p = 0.03). There were no differences in secondary outcomes of chest tube output at 2, 6, 12 and 24 hours, nor was there a difference in reexploration rates or the median length of stay in the intensive care unit. Thromboembolic complications at 30 days were similar between the two groups (4-factor PCC: 13% vs. rFVIIa 26%, p = 0.08). The total median dose requirement for 4-factor PCC was 1000 units (15 units/kg) and 2 mg (20 mcg/kg) for rFVIIa. The results demonstrate feasibility of utilizing the minimum amount of drug in order to achieve a desired effect. Both 4-factor PCC and rFVIIa appear to be safe and effective options for the management of bleeding associated with cardiac surgery.

BACKGROUND:Increased utilization of hepatitis C virus (HCV)-positive donors has increased transplantation rates. However, high levels of viremia have been documented in recipients of viremic donors. There is a knowledge gap in how transient viremia may impact acute cellular rejections (ACRs). METHODS:In this study, 50 subjects received hearts from either viremic or non-viremic donors. The recipients of viremic donors were classified as nucleic acid amplification testing (NAT)+ group, and the remaining were classified as NAT-. All patients were monitored for viremia levels. Endomyocardial biopsies were performed through 180 days, evaluating the incidence of ACRs. RESULTS:A total of 50 HCV-naive recipients received hearts between 2018 and 2019. A total of 22 patients (44%) who received transplants from viremic donors developed viremia at a mean period of 7.2 ± 0.2 days. At that time, glecaprevir/pibrentasvir was initiated. In the viremia period (<56 days), 14 of 22 NAT+ recipients (64%) had ACR vs 5 of 28 NAT- group (18%) (p = 0.001). Through 180 days, 17 of 22 NAT+ recipients (77%) had a repeat rejection biopsy vs 12 of 28 NAT- recipients (43%) (p = 0.02). NAT+ biopsies demonstrated disparity of ACR distribution: negative, low-grade, and high-grade ACR in 84%, 12%, and 4%, respectively, vs 96%, 3%, and 1%, respectively, in the NAT- group (p = 0.03). The median time to first event was 26 (interquartile range [IQR]: 8-45) in the NAT+ group vs 65 (IQR: 44-84) days in the NAT-. Time to first event risk model revealed that NAT+ recipients had a significantly higher rate of ACR occurrences, adjusting for demographics (p = 0.004). CONCLUSIONS:Transient levels of viremia contributed to higher rates and severity of ACRs. Further investigation into the mechanisms of early immune activation in NAT+ recipients is required.

To determine the impact of tocilizumab, a monoclonal antibody against the interleukin 6 receptor, on survival in patients with coronavirus disease 2019.