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Purpose Optimal size-matching metrics for prediction of outcomes after combined heart-kidney transplantation (HKT) are unknown. Methods Combined HKTs performed between January 2000 and April 2019 were analyzed using United Network of Organ Sharing registry. Size metrics (weight, height, body mass index (BMI) and predicted heart mass (PHM)) were divided into seven equally sized groups using donor-to-recipient ratio. Kaplan-Meier survival and Cox proportional hazard analyses were performed to assess composite risk of mortality or re-transplantation at 1-year. Results A total of 1,290 recipients were analyzed; 155 events occurred (n=153 deaths; n=4 re-transplants). Compared to a well-matched cohort, severe under-sizing by either PHM (0.56 to 0.85; hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.02-3.08, p=0.042) or weight (0.50 to 0.80; HR 2.00, 95% CI 1.14-3.52, p=0.015), but not BMI and height, was associated with an increased risk of events. Upon categorizing recipients into 4 groups based on presence or absence of severe under-sizing by either PHM or weight ratio, those whose donors were severely undersized for both were at significantly higher risk of poor outcomes (HR 2.74, 95% CI 1.78-4.19, p Conclusion Recipients of combined HKT whose donors were severely undersized based on both weight ratio and PHM had significantly worse outcomes compared to those whose donors were severely undersized by either parameter alone or not at all.

Purpose Circulating levels of b-type natriuretic peptide (BNP) are elevated following heart transplantation (HT), peak at 1-2 months post-HT, and decline over the course of several months but rarely return to normal. We sought to determine the time course of BNP level following combined heart-kidney transplantation (HKT) compared to HT alone. Methods Between July, 2014 and August, 2017, 11 patients underwent HKT; they were matched based on age, gender, race and body mass index (BMI) to 22 patients undergoing isolated HT. Baseline demographics, serial BNP levels, and estimated glomerular filtration rate (eGFR; ml/min/1.73 m 2 ) were monitored in patients at post-transplant days 30, 60, 90, 180 and 365. Wilcoxon rank-sum test was used to compared median BNP levels at different time points between the groups. Results Average age of HKT recipients was 54±18 years (82% females, 27% black Americans, BMI 25±5 kg/m2) and that of HT recipients was 55±14 years (82% females, 27% black Americans, BMI 26±3 kg/m2). As shown in the Figure, BNP values decreased significantly among HKT recipients by 90-days, and remained significantly lower at 1-year post-transplantation (p Conclusion Unlike HT alone, BNP levels were found to be near normal in the majority of HKT recipients within a much shorter period of time and remained low up to 1-year post-transplant. This finding can potentially be explained by improved renal function with kidney transplant ; although, the effect of KT on lusitropic properties of transplanted heart cannot be ruled out.

Purpose The shortage of suitable donors for heart transplantation (HT) contributes to wait-list mortality and increased reliance on mechanical circulatory support. Since the advent of direct-acting antivirals (DAA) for treatment of hepatitis C (HCV), utilization of hepatitis C-exposed donors is now a viable strategy to expand the donor pool and potentially reduce waitlist time. Methods Between September 2016 and October 2018, 58 patients underwent HT from HCV-exposed donors. All patients were treated with standard immunosuppression and, for those who developed HCV infection, with a course of DAA. Data collection and analysis were performed after obtaining informed patient consent and IRB approval. Results Baseline characteristics: Mean age of recipients at time of HT was 52 ± 13 years (72% male, 69% Caucasian, 41% on left ventricular assist device support). Mean age of donors was 30 ± 7 years. Among donors, results of HCV antibody (Ab) and nucleic acid testing (NAT) were: 47 Ab+/NAT+, 9 Ab+/NAT-, 2 Ab-/NAT+. Time to transplant: Among all patients, active waitlist time from time of consent to accept HCV-exposed donors was median 4 days (IQR 1, 17). Hepatitis C testing and treatment: No recipients of NAT- donor hearts developed HCV infection. Of the 49 patients who received NAT+ donor hearts, 46 (94%) developed HCV infection, including 27 patients who completed DAA therapy with cure demonstrated by absence of viremia at 12 weeks post-treatment (SVR12), 7 patients in whom treatment is ongoing or recently completed, and 7 patients who have yet to initiate treatment. By the time of ISHLT 2019, we expect to have SVR12 data for all infected patients who have completed treatment, 30 of whom will be at least one year post-HT. To date, there has been no suggestion of increased rates of rejection, graft dysfunction or vasculopathy among infected patients, nor has there been a suggestion of liver injury. Conclusion In the era of highly effective HCV pharmacotherapy, the use of HCV-exposed donors safely allows for expansion of the donor pool.

Purpose Donor-derived hepatitis C infection (dd-HCV) infection may increase risk of renal impairment (RI) among heart transplant (HT) recipients. Sofosbuvir, an integral component of anti-HCV direct-acting antivirals (DAAs), has also been linked to RI. To date, no prior study has examined the trends in renal function for HT recipients of dd-HCV infection, and assessed safety and efficacy of sofosbuvir-based DAAs. Methods Between September 2016 and June 2018, 46 HCV-naive patients and 1 with a history of treated-HCV pre-HT underwent HT from HCV-positive donors (follow-up through October 10th, 2018). Patients were treated with ledipasvir-sofosbuvir (genotype 1) or sofosbuvir-velpatasvir (genotype 3) for 12 or 24 weeks; no dose adjustments were made for renal function. Data on renal function were available for 23 patients who achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12; cohort A) and 18 patients who completed 1-year of follow-up (cohort B). Results Treatment of dd-HCV infection was initiated after a median of 6 weeks post-HT. In both cohorts, a non-significant change in median eGFR was noted (Cohort A: pre-transplant eGFR: 62 (IQR 51,84) to SVR12 eGFR: 49 ((IQR: 37, 82), p=0.43); Cohort B: pre-transplant eGFR: 65 (IQR: 54, 84) to 1-year post-HT eGFR: 56 ((IQR: 39, 75); p=0.29). Pre-treatment renal function or early initiation of DAAs post-transplant had no significant impact on changes in renal function during treatment. All patients tolerated DAAs well with 100% completion rate to the assigned therapy and duration, and 100% success at achieving SVR12. Conclusion In this first and largest reported case series to date of HT recipients with dd-HCV infection, we observed that neither the dd-HCV infection nor its treatment with Sofosbuvir-based DAAs increased the risk of RI. Sofosbuvir-based DAAs appear safe, tolerable and effective for HCV treatment even in presence of severe RI.

Purpose Prior to the advent of direct-acting antivirals (DAAs), donor-derived hepatitis C (dd-HCV) viremia predicted poor post-heart transplant (HT) outcomes, including a higher risk of coronary allograft vasculopathy (CAV) and death. Considering the success of DAAs to treat HCV and the shortage of organs for HT, we institutionalized a clinical protocol of using HCV+ donors. Using intracoronary ultrasound (ICUS) in patients acquiring post-HT HCV infection, we examined the risk of CAV in the current era. Methods Between September 1st 2016 and October 2nd 2018, 54 HCV-naive patients and 1 with a history of treated-HCV pre-transplant, underwent HT from HCV-positive donors (follow-up available through October 10th, 2018). Patients were treated with ledipasvir-sofosbuvir (genotype 1) or sofosbuvir-velpatasvir (genotype 3) for 12 or 24 weeks. ICUS of left anterior descending artery was performed at 6-months and 1-year post-HT for those developing donor-derived HCV (dd-HCV) infection using an automated, mechanical pullback at a rate of 1 mm/ second. Results The ICUS data were available for 20 patients at 6-months (cohort A) and 16 patients at 1-year (cohort B); 14 patients had serial data available at 6-months and 1-year (cohort C). Figures A and B show changes in maximum intima thickness (MIT) for the overall sample and cohort C. For cohort C, absolute change in MIT from 6-months to 1-year was +0.15 (median) (Inter-quartile range: -0.03, 0.42) and only one patient had an increase in MIT by >0.5mm. Two patients in cohort A (10%) and 4 patients in cohort B (25%) had angiographic CAV grade 1; one patient in each cohort had known coronary artery disease in the donor heart. None required percutaneous coronary intervention or re-transplant for CAV at 1-year. Conclusion Utilization of HCV-positive donors may represent a viable strategy to expand the donor pool in era of DAAs. Larger scale data on changes in MIT is required to appropriately assess the effect of dd-HCV infection on incident CAV.