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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).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.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).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.

Purpose ImmuKnow, an immune cell function assay that quantifies overall immune system activity can assist in post-transplant immunosuppression adjustment. The utility of pretransplant ImmuKnow results representing a patient's baseline immune system activity is unknown. We sought to assess if pretransplant ImmuKnow results are predictive of rejection at the time of first biopsy in a cardiac transplant population.. Methods 81 cardiac transplant patients with pre-transplant ImmuKnow results (out of 110 total transplant patients) were identified. ImmuKnow results were analyzed according to the clinical interpretation ranges (low, medium, high activity). Pre-transplant clinical characteristics, induction immunosuppression use, early postoperative tacrolimus levels (Day 7 post transplant), and first endomyocardial biopsy results were collected for all patients. Logistic regression was used to estimate the association of the pre-transplant ImmunKnow group with clinically significant early rejection (≥ 1R/2), and to determine if the association was modified by the use of induction therapy and early tacrolimus levels. Results Significant early rejection was found in 15 patients (18.5%). Early rejection occurred in 0/15 patients with low pretransplant ImmuKnow levels vs. 15/64 patients with moderate or high pre-transplant ImmunoKnow levels (p=0.04). Induction immunosuppression was used for 26 patients (32.1%). The most common reason for induction was dual organ transplantation. Of the 55 patients without induction immunosuppression, 13 had rejection (23.6%). The mean ImmuKnow level in the non-rejection group was 391 ng/ml of ATP compared to 516 ng/ml of ATP for those with rejection (p=0.06). Lower pretransplant ImmuKnow levels among non-rejection patients was not diminished when controlling for tacrolimus level. Conclusion Patients with low pre-transplant ImmunoKnow levels had a lower risk of early rejection when compared with patients with medium or high levels. After adjusting for tacrolimus level, this relationship was maintained. Our study suggests a possible utility in performing pretransplant ImmunoKnow to identify patients at-risk for early rejection who may benefit from intensified upfront immunosuppression.

Purpose The Lavare Cycle (LC) is a pre-programmed speed modulation algorithm in the HVAD device designed to automatically increase both ventricular and pump washing. The ReVOLVE trial suggested a reduction in adverse outcomes including stroke. We assessed the effect LC ON compared to LC OFF on HVAD implants. Methods We conducted a retrospective, single center study from 4/2017 to 6/2020 including all 46 patients who received a HVAD implant. The LC became available to our center on 06/2018. For the majority of patients LC was turned on at the time of implant admission. The primary endpoints were cerebrovascular events (CVE) by INTERMACS definition and survival between LC ON versus LC OFF. Secondary endpoints were GI bleeding and pump thrombosis rates. Results Fourty six patients (median age 57 years, 78% male, 58% non-ischemic cardiomyopathy) were implanted with HVAD device from 4/2017 to 6/2020. The median duration of HVAD support was 648 (245-902) days. The LC was activated in 33/46 patients. Median time to cycle activation in the LC ON group from implantation was, median (IQR): 4 (1-36) days. The LC ON group experienced less incidence of CVEs, with 6/33 (18%) in the ON vs. OFF 6/13 (46%), p=0.04 (Fig 1A). The median time of CVE from implant was for LC ON and OFF 223 and 104 days, respectively. Survival was significantly improved in the LC ON 31/33 (94%) vs OFF 7/13 (54%), p=0.003 (Fig 1B). There were however 7/33 GI bleeding events in the ON group while zero events in the OFF, p=0.08. Pump thrombosis events were equal rate in the ON 3/33 (9%) vs OFF 1/13 (8%), p=0.43. Conclusion LC ON was associated with a significant lower number of CVE (p =0.04) and better survival (p=0.003). The important impact of speed modulation on reducing neurologic events should be confirmed in a larger HVAD patient population.

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-). Methods 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. Results 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 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.

Purpose Despite improvements in selection and management of patients on extra-corporeal membrane oxygenation (ECMO) the overall outcomes of patients in cardiogenic shock (CS) supported with veno-arterial (VA) ECMO can be improved. In particular, a significant percentage of patients who survive ECMO do not survive to hospital discharge. We reviewed our ECMO outcomes with a specific focus on reducing the inter-stage mortality for patients with cardiogenic shock supported with VA-ECMO. Methods We conducted a retrospective, single center study from 11/2016 to 10/2020, reviewing all adult VA-ECMO cases. Patients who were offered VA-ECMO support as part of a bridge to lung transplant or intra-operative support for lung transplant and eCPR (n=30) were excluded. Based on one specific inter-stage mortality we adjusted our strategy and divided our patients on ERA1 (11/2016-11/2018) and ERA2 (11/2018 -10/2020). This leaves ERA1 (n= 38) and ERA2 (n= 36) patients. Patient demographics, baseline characteristics and clinical outcomes were compared. Results There was no difference in demographics between groups: median age or gender between the ERA 1 versus ERA 2 (p= 0.42 and p = 0.17, respectively). The groups were the same in terms of indication for ECMO (STEMI/ADHF/PCCS) and cannulation strategies were similar (peripheral and central). Although there was a trend toward lower inter-stage mortality (39% vs 21%, p = 0.07), this did not reach statistical significance. Survival to discharge was 60% and 79% (p=0.07) in ERA 1 and ERA 2, respectively. For the cohort of patients who were bridged with inter-stage VV-ECMO in ERA2, the survival to discharge rate was 7/9 (78%) The conversion strategy resulted in a longer ECMO period of 8±1 versus 5±1 days, (p Conclusion Reducing inter-stage mortality for patients with cardiogenic shock supported by VA-ECMO remains an area for improvement. Selecting patients with evidence of recovery of ventricular function but need for a period of support for gas exchange (VV ECMO) may be helpful in reducing mortality in these patients.

Purpose Currently, there are patients who meet criteria for lung transplant who are denied listing because of underlying heart disease. Likewise, there are patients who meet criteria for heart transplant but are denied listing because of lung disease. In addition, end-stage pulmonary hypertension has become more commonly treated with bilateral lung transplantation. From 2006 to 2018, no adult heart-lung transplantation (HLT) was performed in New York State. Given this unmet need our center has renewed interest in HLT. Methods All patients who underwent HLT from 06/2019 to 09/2020 were reviewed. Patients were listed per standard UNOS guidelines. The primary outcome was hospital and 1year survival. Results 10 patients (50% male; mean age 54±8 years) underwent HLT during this period. All patients had been deemed not appropriate candidates for isolated heart or lung transplant at more than one transplant center. The indication for HLT was interstitial lung disease (ILD) with ischemic cardiomyopathy (n=4), nonischemic cardiomyopathy with PAH (n=2), PAH with RV failure (n=2), and ILD with RV failure (n=2). Median lung allocation score and heart waitlist status were 71 (IQR: 41-85) and 2 (IQR: 1-3) respectively. Three patients had re-operative sternotomies. Two patients bridged to transplant with VA-ECMO, two with VV-ECMO and three patients required IABP. One patient received a DCD donor heart-lung block utilizing normothermic regional perfusion, and two patients received Hep C+ donor organs. One patient was left on central VA-ECMO postoperatively for early lung PGD. No lung PGD grade 3 at 72 hours or significant heart PGD at any time point were observed. At a median follow up of 287 (IQR: 108-401 days), all patients are alive at home. Conclusion Our initial center experience demonstrates that appropriately selected patients with end stage heart and lung disease who would otherwise die without transplantation can be offered HLT with excellent short-term outcomes.

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. Methods 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. Results 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 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.

Purpose Aortic valve opening in patients with continuous flow LVADs is felt to be important to prevent root stasis and minimize complications. Optimal characterization of the aortic valve opening has not been delineated. We described Aortic Valve Opening Time (AVOT), a novel quantitative measure of aortic valve opening in patients with continuous flow LVADs. Methods From April 2017 to August 2018, sequential patients implanted with HVAD had serial echocardiograms. Aortic valve opening status and AVOT were analyzed longitudinally at 3 month intervals. AVOT was measured using M-mode echocardiography, quantified as the time interval between initial aortic leaflet opening to leaflet closure. The longest AVOT of each echocardiogram was used. Results Over a period of 17 months, 24 patients were studied. Mean age was 52 ± 3 years, and 75% were male. The mean speed was 2627 ± 26 rpm. During longitudinal follow up post implant, the aortic valve always opened in 10 (42%), intermittently opened in 4 (16%) and remained closed in 10 patients (42%). For patients in whom the aortic valve persistently or intermittently opened, the mean AVOT was 110 ± 22 msec. Patients with AVOT longer than 150 msec had less aortic and mitral regurgitation compared to those with AVOT less than 150 msec, irrespective of frequency of aortic valve opening or device speed. Conclusion Aortic valve opening time is a novel characterization of the aortic valve in patients with continuous flow devices, independent of frequency of aortic valve opening. The relationship between the AVOT and outcomes needs to be defined.

Purpose Due to advances in curative therapy for Hepatitis C infection, hearts from hepatitis C viremic (HCV) donors were successfully transplanted in selected patients. We assessed the relationship between the magnitude of recipient and time to HCV viremia clearance after transplantation. Methods From January until October 2018, 12 patients received heart transplantation from donors with active HCV viremia. All recipients developed viremia within one week and were treated with glecaprevir/pibrentasvir (Mavyret) for a duration of 8 weeks. HCV viral load was monitored weekly by real-time PCR . Results The mean age was 60 ± 8years, 33% were females, and 9 patients had non-ischemic cardiomyopathy (75%). All recipients (100%) had detectable HCV viremia at 1-week post heart transplant ; the lowest detectable viral load was 1. 36 log IU/ml and the highest was 7.06 log IU/ml, with a mean of 4.47 ± 2.13 log IU/ml (ref range 1.18 - 8 log IU/mL). Complete clearance of HCV viremia varied from 1 to 6 weeks with a mean of 2.8 ± 2.1 weeks. There was an association between the level of initial viremia and time to viral load clearance (Fig). At an average of 147 ± 88 days follow up, HCV viral load was undetectable in all patients. Forty percent of patients developed hepatitis C antibodies . There was no correlation between the level of initial viremia, duration of viremia clearance, genotype status and antibody response . Conclusion Heart transplantation from donors with active hepatitis C is safe with rapid clearance of viremia in all exposed patients. Time to viral clearance is related to initial viremic load. A sustained antibody response did not develop in all patients. This may be related to immunosuppression or relatively low level and duration of viremia.

Iron deficiency is common in heart failure (HF) patients, and is associated with increased risk of adverse clinical outcomes. Clinical trials of intravenous iron supplementation in iron-deficient HF patients have demonstrated short-term improvement in functional capacity and quality of life. In some trials, the benefits of iron supplementation were independent of the hemoglobin levels. Additional investigations of iron supplementation are needed to characterize the mechanisms contributing to clinical benefit and long-term safety in HF.

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. Methods 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. Results 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. Conclusions 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.

Purpose Transmission of HCV infection can induce an inflammatory response, but its impact on accentuating the immune response on the allograft is unknown. Methods From January to October 2018, 25 hepatitis C seronegative patients were transplanted with 12 patients from HCV viremic donors (NAT+). Incidence of acute cellular and humoral rejection were compared between the 2 groups. All patients received standard triple immunotherapy and those who developed HCV were treated with glecaprevir/pibrentasvir (Mavyret) for 8 weeks. Results For all patients, the retrospective flow cytometry crossmatch was negative for both T and B cells and no DSA were detected. Hep C viremia developed at 1-week post-transplant in all recipients of HCV donors. At a mean follow up of 147 ± 88 days in the HCV group: there were 4 grade 2R/ 3A rejection (33%) and 7 grade 1R/2 (58%). In the nonviremic group: there were 2 patients who had grade 2R/3A (20%) and 4 had grade 1R/2 (30%). No grade 3R or humoral rejection was identified in either group. Only grade 1R/2 rejection was statistically significant between the 2 groups. There was no difference in the type of inflammatory cells in the endomyocardial biopsy between the two groups. Conclusion Early biopsy of heart transplantation from donors with active hepatitis C is not associated with high grade cellular or any humoral rejection. The 1R/2A rejections seems to be more frequent in the HCV group and did not correlate with the level of viremia. Longer follow up and the impact on chronic allograft vasculopathy would need to be assessed in the future.

Purpose Advances in cure for active hepatitis C (HCV) have prompted consideration of HCV positive donors to address the continued shortage of organs. We have offered the option to accept HCV + donors, without any donor restrictions, to all patients on the waiting list. Methods From January to October 2018, 25 patients were transplanted, 12 patients from HCV viremic donors (NAT+). All recipients were seronegative at the time of transplantation. All patients were consented to receive an HCV donor as part of an IRB study. Survival and natural history of viral transmission and treatment were evaluated. Results 25 patients were transplanted with a mean age of 57 ± 12years, 28% females and 11 were blood type O (44%). All the recipients from HCV NAT + donors developed hep C viremia at 1-week postransplant. Therapy with glecaprevir/pibrentasvir (Mavyret) was initiated once seroconversion was established for duration of 8 weeks. All patients received standard triple immunotherapy. The HCV viremia cleared at a mean of 2.8 ± 2.1 weeks after initiation of therapy with a sustained viremic response at last follow up. There were no differences in early rejection rate or grade between patients receiving hearts from viremic versus non viremic donors. There were no significant abnormalities of liver function tests in patients with viremia. The shortest time on the waiting list was 3 days and the longest time was 197 days with a mean of 62 days. Eight recipients (32%) waited less than one month. At a mean follow up of 147 ± 88 days there was 100% graft and patient survival in both groups with no PGD. Conclusion While experience continues to grow, heart transplantation from donors with active hepatitis C is safe with excellent short term survival and rapid clearance of viremia. All patients develop viremia and respond to current antiviral therapy. These hearts represent an important potential resource from an underutilized donor pool and should be considered for transplantation. Long-term follow up is necessary.