Faculty Bibliography

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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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.

BACKGROUND:The use of direct acting antivirals (DAA) has expanded transplantation from hepatitis C viremic donors (HCV-VIR). Our team has conducted an open-label, prospective trial to assess outcomes transplanting HCV-viremic hearts. Glecaprevir/Pibrentasvir (GLE/PIB) was our sole DAA. METHODS:Serial quantitative hepatitis C virus (HCV) RNA PCR was obtained to assess HCV viral titers. Between January 2018 to June 2019, a total of 50 recipients were transplanted. Of these, 22/50 (44%) were from HCV-VIR, the remaining 28 from non-viremic (HCV NON-VIR) donors. An 8 week course of GLE/PIB was initiated at 1 week post-transplant. RESULTS:There was no difference in demographic or clinical parameters between groups. All 22 recipients of HCV-VIR transplants became viremic. GLE/PIB was effective in decreasing viremia to undetectable levels by 6 weeks post-transplant in all patients. The median time to first undetectable HCV quantitative PCR was (4.3 weeks, IQR: 4-5.7 weeks). All patients demonstrated sustained undetectable viral load through 1 year follow up. There was no difference in survival at one year between HCV NON-VIR 28/28: (100%) vs. HCV-VIR 21/22 (95%) recipients. CONCLUSIONS:Our center reports excellent outcomes in transplanting utilizing hearts from HCV-VIR donors. No effect on survival or co-morbidity was found. An 8 week GLE/PIB course was safe and effective when initiated approximately 1 week post-transplant.

PURPOSE: Heart transplantation from Hepatitis C (HCV) viremic donors is becoming increasingly used due to advent of direct acting antiviral drugs with almost 100% cure. There are limited data about its impact on cardiac allograft vasculopathy (CAV). We report the incidence of CAV in heart transplant recipients from HCV viremic donors (nucleic amplification test positive; NAT+) compared to non-HCV infected donors (NAT-).
METHOD(S): We retrospectively reviewed coronary angiograms with intravascular ultrasound (IVUS) of heart transplant recipients at our institution from January 5, 2018 to September 17, 2019. The presence of CAV was graded according to ISHLT guidelines. IVUS was performed as per our lab protocol on the left main and left anterior descending arteries. Maximal intimal thickness (MIT) was measured with advanced quantification software as per protocol. MIT >= 5mm was considered significant for future adverse outcomes.
RESULT(S): LHC and IVUS was performed on 24 heart transplant recipients (mean age 56; 70% male) at 1- year post transplant. Eleven of these patients were transplanted from NAT+ donors. Thirteen patients received a NAT- donor heart. Two recipients (18.7%) of NAT+ donors had CAV grade >= 1 compared to 2 (16.7%) from NAT- donors (p=1). MIT >= 5mm was seen in 88.9% of NAT+ vs 50% of NAT- recipients (p=0.14) (Figure). The mean MIT was 76mm and 65mm for NAT+ and NAT- group, respectively. Both NAT+ and NAT- donor recipients exhibit mostly eccentric (84.2%) and few (15.7%) demonstrated concentric plaques. There was no heterogeneity in the data after adjusting for risk factors for CAD and donor LHC.
CONCLUSION(S): Our data show no difference in the presence of (CAV >= grade 1) or subclinical atherosclerosis at 1 year among NAT+ donor recipients. HCV viremia is a known risk factor for accelerated atherosclerosis and the consequence of prolonged donor viremia on the recipient is not known. A larger cohort and further longitudinal follow-up is needed to assess the validity of this trend and its prognostic implications.
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PURPOSE: Passive transmission of hepatitis C (HCV) viremia from actively infected donors to uninfected recipients at the time of heart transplantation may modulate response to alloantigens and risk of allograft rejection. We evaluated the one-year incidence of acute cellular rejection (ACR) in patients transplanted from nucleic amplification testing positive (NAT+) HCV donors compared to those from NAT negative (NAT-) donors.
METHOD(S): Since January 2018, 25 patients completed one-year follow-up. All recipients underwent right ventricular endomyocardial biopsy (EMB) per our institution protocol. ACR was graded according to both the 1990 and the revised 2004 International Society for Heart and Lung Transplantation (ISHLT) criteria. All NAT+ donor recipients developed viremia detected by RT-PCR. Mixed models were used to assess the association between donor HCV NAT status, recipient viremia, tacrolimus levels and ACR in the first year post-transplant.
RESULT(S): Twelve NAT+ recipients (mean age 60, 67% male) and 13 NAT- recipients (mean age 54, 77% male) completed one-year follow-up; 182 and 191 EMB were performed, respectively. NAT+ recipients were associated with higher grade rejection compared with NAT- recipients (p=0.041). At least one episode of high grade rejection (2R/3A) occurred in 4 NAT+ recipients (33%) compared with 2 NAT- recipients (15%). At least one episode of low grade rejection (1R/1B or 1R/2) occurred in 11 NAT+ recipients (92%) compared with 7 NAT- recipients (54%). These findings were independent of the presence and magnitude of viremia and tacrolimus levels. No episodes of ACR 3R or antibody mediated rejection were detected during one-year follow-up in either group. There was no allograft dysfunction or mortality related to ACR in either group.
CONCLUSION(S): One year data from our institution demonstrate increased ACR in heart transplant recipients from NAT+ donors. Most of the rejection episodes in the NAT+ group were low grade and did not translate into any adverse outcomes through one-year follow-up.
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Purpose: In October 2018, a new US adult heart allocation scheme was enacted in which the etiology of cardiomyopathy can play a significant role in the prioritization of patients listed for transplantation. Given this, we embarked on a review of the diagnoses of patients who underwent therapy for advanced heart failure at our center.
Method(s): We retrospectively reviewed the etiology of cardiomyopathy of patients receiving either durable ventricular assist device (VAD) or orthotopic heart transplantation (OHT) at NYU Langone Medical Center in New York, NY between January 2011 and October 2018. We evaluated for discrepancies between the primary HF diagnosis at time of operation with the ultimate diagnosis, combining both clinical follow-up data and cardiac pathology.
Result(s): During the study period, a total of 110 patients were treated with advanced therapies, of which the majority (74.5%) were male. 40.9% were African American, 35.4% Caucasian, 4.5% Asian, and 23.6% Hispanic. 86.3% underwent VAD and 22.0% underwent OHT. The average age of those undergoing OHT and VAD were 58 and 61 respectively. The most common reported etiology of HF was dilated cardiomyopathy (57.3%), followed by ischemic (36.3%), familial DCM (1.8%), amyloidosis (1.8%), restrictive cardiomyopathy (1.8%), and sarcoidosis (0.9%). On final review of the diagnoses in these patients, 14 (12.7%) had a final diagnosis that was inconsistent with the prior reported one. 5 were clerical errors, but 9 were significant deviations from the prior diagnosis. The most common diagnoses that were misidentified prior to VAD or OHT were cardiac sarcoidosis (2), cardiac amyloidosis (2), and hypertrophic cardiomyopathy (2). Among those 9 patients, 7 patients received VAD with 5 eventually requiring OHT (median days to OHT = 248); 2 patients directly received OHT. All of those are alive except one patient who was lost to follow-up (transferred care to another center). Patients in whom the diagnosis was misidentified prior to VAD or OHT had smaller LV dimensions on transthoracic echocardiography on average than other LVAD or OHT patients with non-ischemic cardiomyopathy.
Conclusion(s): In this single-center review, we found that the majority of HF patients undergoing VAD and OHT had a correct diagnosis for their heart failure prior to treatment, although notably 8.1% had a missed diagnosis at time of intervention (VAD or OHT). Appropriately identifying the subtype of cardiomyopathy remains challenging especially in advanced HF patients but can significantly impact waiting list time in the current organ allocation scheme. A normal or minimally increased LV dimension on echocardiogram in a patient with advanced non-ischemic cardiomyopathy may warrant further workup for another diagnosis.
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