Adult Orthotopic Heart Transplantation Recipients Research Articles

Conversion between sirolimus and everolimus in heart transplant recipients.

Sirolimus and everolimus are mechanistic target of rapamycin inhibitors (mTORi) that may be included in immunosuppression regimens for orthotopic heart transplant (OHT) recipients. mTORi play a role in slowing progression of cardiac allograft vasculopathy; however, they have poor tolerability, sometimes necessitating a change between agents or therapies. The literature surrounding a conversion between mTORi are incongruent, thus this study was designed to assess the concentration/dose ratio for each medication around the time of conversion to provide guidance for a conversion strategy between mTORi. We conducted a retrospective study of adult OHT recipients who were maintained on both sirolimus- and everolimus-based immunosuppression regimens. The primary outcome was the concentration/dose (C/d) ratio of sirolimus to everolimus. Secondary outcomes included changes in hematologic and lipid labs and patient-reported intolerances. The C/d ratio of sirolimus was 4.42, whereas the everolimus ratio was 2.23, resulting in a sirolimus: everolimus ratio of 1.98. Secondarily, after converting between mTORi, 93% of patients who reported intolerance(s) to one agent had a resolution of that intolerance. In our patient population, everolimus appeared better tolerated than sirolimus, with significantly more patients having no reported intolerances and significantly fewer patients experiencing edema. Other lab values were similar between patients receiving sirolimus and everolimus, except for an increased hemoglobin level in those receiving everolimus. The conversion ratio of 1:2 observed in our population suggests OHT recipients may require an increased dose of EVL compared with SRL to maintain the same goal trough levels. A conversion between mTORi appeared to improve tolerability and did not lead to clinically significant worsening of any measured lab value.

Outcomes of heart transplant recipients bridged with percutaneous versus durable left ventricular assist devices.

The new United Network for Organ Sharing (UNOS) heart allocation policy prioritizes temporary percutaneous over durable left ventricular assist devices (LVAD) as bridge to transplant. We sought to examine 1-year outcomes of heart transplant recipients bridged with Impella versus durable LVADs. All primary adult orthotopic heart transplant recipients registered in UNOS between January 2016 and June 2021 were analyzed. Recipients were identified as being bridged with isolated durable or percutaneous LVAD at the time of transplant. Baseline characteristics were compared and 1-year survival was examined using the Kaplan Meier method and multivariable Cox proportional hazards regression. During our study period, heart transplant recipients bridged with LVADs were divided between 5422(94%) durable and 324(6%) percutaneous options. Impella-bridged recipients were more likely to be status 1A under the old allocation system (98% vs. 70%, p<.01) and status 2 or higher under the new allocation system (99% vs. 24%, p<.01). Impella-bridged recipients were less likely to be obese (27% vs. 42%, p<.01), have ischemic cardiomyopathy (27% vs. 34%, p<.01), and were more likely to be on inotropic agents at the time of transplant (68% vs. 6%, p<.01). One-year post-transplant survival was not significantly different between the two groups on univariable (HR .87, 95% CI .56-1.37) or multivariable analysis (aHR .63, 95% CI .37-1.07). Following the UNOS allocation policy change, Impella utilization has increased with no significant difference in 1-year survival compared to bridge with durable LVADs. Impella may be a reasonable alternative to durable LVADs in select patients.

Clinical trends, risk factors, and temporal effects of post-transplant dialysis on outcomes following orthotopic heart transplantation in the 2018 United States heart allocation system

This study evaluated the current clinical trends, risk factors, and temporal effects of post-transplant dialysis on outcomes following orthotopic heart transplantation after the 2018 United States adult heart allocation policy change. The United Network for Organ Sharing (UNOS) registry was queried to analyze adult orthotopic heart transplant recipients after the October 18, 2018 heart allocation policy change. The cohort was stratified according to the need for post-transplant de novo dialysis. The primary outcome was survival. Propensity score-matching was performed to compare the outcomes between 2 similar cohorts with and without post-transplant de novo dialysis. The impact of post-transplant dialysis chronicity was evaluated. Multivariable logistic regression was performed to identify risk factors for post-transplant dialysis. A total of 7,223 patients were included in this study. Out of these, 968 patients (13.4%) developed post-transplant renal failure requiring de novo dialysis. Both 1-year (73.2% vs 94.8%) and 2-year (66.3% vs 90.6%) survival rates were lower in the dialysis cohort (p < 0.001), and the lower survival rates persisted in a propensity-matched comparison. Recipients requiring only temporary post-transplant dialysis had significantly improved 1-year (92.5% vs 71.6%) and 2-year (86.6 % vs 52.2%) survival rates compared to the chronic post-transplant dialysis group (p < 0.001). Multivariable analysis demonstrated low pretransplant estimated glomerular filtration (eGFR) and bridge with extracorporeal membrane oxygenation (ECMO) were strong predictors of post-transplant dialysis. This study demonstratesthat post-transplant dialysis is associated with significantly increased morbidity and mortality in the new allocation system. Post-transplant survival is affected by the chronicity of post-transplant dialysis. Low pretransplant eGFR and ECMO are strong risk factors for post-transplant dialysis.

Left ventricular assist device bridging to heart transplantation: Comparison of temporary versus durable support.

Since the revision of the United States heart allocation system, increasing use of mechanical circulatory support has been observed as a means to support acutely ill patients. We sought to compare outcomes between patients bridged to orthotopic heart transplantation (OHT) with either temporary (t-LVAD) or durable left ventricular assist devises (d-LVAD) under the revised system. The United States Organ Network database was queried to identify all adult OHT recipients who were bridged to transplant with either an isolated t-LVAD or d-LVAD from 10/18/2018 to 9/30/2020. The primary outcome was 1-year post-transplant survival. Predictors of mortality were also modeled, and national trends of LVAD bridging were examined across the study period. About 1,734 OHT recipients were analyzed, 1,580 (91.1%) bridged with d-LVAD and 154 (8.9%) bridged with t-LVAD. At transplant, the t-LVAD cohort had higher total bilirubin levels and greater prevalence of pre-transplant intravenous inotrope usage and mechanical ventilation. Median waitlist time was also shorter for t-LVAD. At 1 year, there was a non-significant trend of increased survival in the t-LVAD cohort (94.8% vs 90.1%; p=0.06). After risk adjustment, d-LVAD was associated with a 4-fold hazards for 1-year mortality (hazard ratio 3.96, 95% confidence interval 1.42-11.03; p=0.009). From 2018 to 2021, t-LVAD bridging increased, though d-LVAD remained a more common bridging strategy. Since the 2018 allocation change, there has been a steady increase in t-LVAD usage as a bridge to OHT. Overall, patients bridged with these devices appear to have least equivalent 1-year survival compared to those bridged with d-LVAD.

Diltiazem as a cyclosporine A-sparing agent in heart transplantation: Benefits beyond dose reduction.

Diltiazem (DZ) is widely prescribed in transplant recipients because of its drug-drug interactions with calcineurin inhibitors (CNI). However, these interactions have been primarily investigated in renal transplantation, and data regarding the long-term efficacy and safety of DZ in orthotopic heart transplantation (OHT) are still sparse.Our study aimed to elucidate the extent to which the co-prescription of DZ reduces the dose required to maintain adequate blood levels of cyclosporine A (CsA) and the resulting effect on morbidity and mortality in OHT recipients.We performed a retrospective single-center analysis of OHT recipients on a long-term immunosuppressive regimen based on CsA and mycophenolate mofetil (MMF).The study population consisted of 95 adult OHT recipients with a mean follow-up of 15.8 ± 6.7 years. DZ was co-prescribed in 39 subjects (41.1%) and was associated with a 28.6% reduction of the mean CsA daily dose (P < .001). Patients on DZ had less frequent rejection episodes (P = .002), better renal function (P = .009) and a lower rate of end-stage renal disease (P = .008). Additionally, they developed later cardiac allograft vasculopathy (CAV). We observed no prognostic relevance of DZ co-prescription in univariate and multivariate Cox-regression analyses.In addition to reducing the CsA dose required to maintain adequate blood through levels, DZ may have nephroprotective properties in OHT. The co-administration of DZ may decelerate the development of CAV and reduce the frequency of the rejection episodes. However, the beneficial influence on morbidity has no impact on mortality.

Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation.

Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR- and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR- or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. HREC/13/SVH/66 and HREC/17/SVH/80. ACTRN12618000672257.

The Utility of Concomitant ECMO and IABP as a Bridge to Heart Transplant

<h3>Purpose</h3> Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to bridge patients to orthotopic heart transplantation (OHT). However, there is scarce data on concomitant venting using intra-aortic balloon pumps (IABP). We sought to compare OHT-recipients bridged with VA-ECMO-alone versus VA-ECMO+IABP. <h3>Methods</h3> The UNOS database was used to analyze adult OHT recipients bridged with VA-ECMO between 1/1/2011 and 11/30/2020. Patients were grouped as being supported by VA-ECMO or by VA-ECMO+IABP at the time of transplant. <h3>Results</h3> In total, 316 patients were included, of whom 250 (79%) were supported by ECMO and 66 (21%) by ECMO+IABP. Recipient age, gender, ethnicity, BMI, smoking history, primary diagnosis, creatinine, and ECMO duration did not vary between cohorts. At the time of listing, ECMO+IABP patients were more likely to be ventilated (40 [16%] vs 20 [30.3%], p=0.008), dependent on IABP (32 [12.8%] vs 39 [59.1%], p <0.001), and require inotropy (118 [47.2%] vs 39 [59.1%], p=0.086) than patients on ECMO alone to achieve similar hemodynamics. At time of transplant, ECMO+IABP achieved similar hemodynamics as ECMO alone, as measured by cardiac output (3.7 [2.8-5.1] vs 3.9 [2.9-5.0] L/min), PA systolic pressure (38 [31-48] vs 40 [34-52.5] mmHg), PA mean pressure (27 [20.5-34.5] vs 30 [23-38] mmHg), and PCWP (21 [14-27] vs 23 [16-28] mmHg) (all p=ns). There was no difference in post-transplant incidence of dialysis (58 [23.2%] vs 16 [24.2%], p=0.865) and stroke (23 [9.2%] vs 6 [9.1%], p=0.669), or length of stay (21.5 [15-35] vs 22 [13-34] days, p=0.430). Post-transplant survival was similar between groups (Figure 1, p=0.783). <h3>Conclusion</h3> While a greater array of life-support interventions was required at listing by the ECMO+IABP group than the ECMO-alone group, both had similar hemodynamic profiles at time of transplant. With no difference in post transplant survival, these findings suggest that combination ECMO+IABP support can take more critically ill patients to transplant and achieve comparable outcomes.

Post-Transplant Extracorporeal Membrane Oxygenation for Severe Primary Graft Dysfunction to Support the Use of Marginal Donor Hearts.

Severe primary graft dysfunction (PGD) is the leading cause of early postoperative mortality following orthotopic heart transplantation (OHT). Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used as salvage therapy. This study aimed to evaluate the outcomes in adult OHT recipients who underwent VA-ECMO for severe PGD. We retrospectively reviewed 899 adult (≥18 years) patients who underwent primary OHT at our institution between 1997 and 2017. Recipients treated with VA-ECMO (19, 2.1%) exhibited a higher incidence of previous cardiac surgery (p = .0220), chronic obstructive pulmonary disease (p = .0352), and treatment with a calcium channel blocker (p = .0018) and amiodarone (p = .0148). Cardiopulmonary bypass (p = .0410) and aortic cross-clamp times (p = .0477) were longer in the VA-ECMO cohort and they were more likely to have received postoperative transfusion (p = .0013); intra-aortic balloon pump (IABP, p < .0001), and reoperation for bleeding or tamponade (p < .0001). The 30-day, 1-year, and overall survival after transplantation of non-ECMO patients were 95.9, 88.8, and 67.4%, respectively, compared to 73.7, 57.9, and 47.4%, respectively in the ECMO cohort. Fourteen (73.7%) of the ECMO patients were weaned after a median of 7 days following OHT (range: 1–12 days). Following OHT, VA-ECMO may be a useful salvage therapy for severe PGD and can potentially support the usage of marginal donor hearts.

Redo orthotopic heart transplantation in the current era

ObjectiveThis study aims to investigate the trends, outcomes, and risk factors for mortality after redo orthotopic heart transplantation. MethodsThe United Network for Organ Sharing registry was used to identify adult orthotopic heart transplantation recipients from 2000 to 2020 and stratify into primary and redo cohorts. Five-year post-transplant survival was compared between 2 propensity-matched cohorts. Multivariable modeling was performed to identify risk-adjusted predictors of redo post-transplant mortality, both conditional and nonconditional on shorter-term survival. ResultsA total of 40,711 recipients were analyzed, 39,657 (97.4%) primary and 1054 (2.6%) redo. Redo recipients had a lower median age and were more frequently bridged with intravenous inotropes, intra-aortic balloon pump, or extracorporeal membrane oxygenation (all P < .05). One- and 5-year survivals were lower after redo orthotopic heart transplantation (90.0% vs 83.4% and 77.6% vs 68.6%, respectively) and remained lower after comparing 2 propensity-matched cohorts. Multivariable modeling found factors such as increasing donor age and graft ischemic times, along with pretransplant mechanical ventilation and blood transfusion, to negatively affect 90-day survival. Contingent on 1-year survival, donor factors such as hypertension (hazard ratio, 1.51; 95% confidence interval, 1.15-2.00, P = .004) and left ventricular ejection fraction less than 50% (hazard ratio, 2.22, 95% confidence interval, 1.16-4.24, P = .016) negatively affected survival at 5 years. ConclusionsAlthough infrequently performed, redo orthotopic heart transplantation remains associated with worse post-transplant outcomes compared with primary orthotopic heart transplantation. Although several high-risk features were identified to affect post-retransplant outcomes in the acute perioperative period, donor characteristics such as hypertension and decreased ejection fraction continue to have lasting negative impacts in the longer term.

De novo tacrolimus extended-release tablets (LCPT) versus twice-daily tacrolimus in adult heart transplantation: Results of a single-center non-inferiority matched control trial.

Extended‐release tacrolimus for prophylaxis of allograft rejection in orthotopic heart transplant (OHT) recipients is currently not FDA‐approved. One such extended‐release formulation of tacrolimus known as LCPT allows once‐daily dosing and improves bioavailability compared to immediate‐release tacrolimus (IR‐tacrolimus). We compared the efficacy and safety of LCPT to IR‐tacrolimus applied de novo in adult OHT recipients. Twenty‐five prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR‐tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 1 year was compared using non‐inferiority analysis. LCPT demonstrated non‐inferiority to IR‐tacrolimus, with a primary outcome risk reduction of 20% (90% CI: ‐40%, ‐.5%; non‐inferiority P = .001). Tacrolimus trough levels peaked at 2–3 months and were higher in LCPT (median 14.5 vs. 12.7 ng/ml; P = .03) with similar dose levels (LCPT vs. IR‐tacrolimus: .08 vs. .09 mg/kg/day; P = .33). Cardiovascular‐related readmissions were reduced by 62% (P = .046) in LCPT patients. The complication rate per transplant admission and all‐cause readmission rate did not differ significantly. These results suggest that LCPT is non‐inferior in efficacy to IR‐tacrolimus with a similar safety profile and improved bioavailability in OHT.

Outcomes of Heart Transplant Recipients Bridged with Percutaneous versus Durable LVADs

<h3>Purpose</h3> The new UNOS heart allocation policy prioritizes patients with percutaneous ventricular support devices over durable LVADs. We examined one-year survival of heart transplant recipients successfully bridged with Impella versus durable LVADs in the most recent era. <h3>Methods</h3> We retrospectively reviewed all primary adult orthotopic heart transplant recipients in the UNOS registry between Jan 1, 2016 to June 12, 2020. Recipients were identified as having an isolated durable LVAD or Impella device at the time of transplant. Those bridged with ECMO, RVAD, BIVAD, or TAH were excluded. One-year survival was examined with the Kaplan Meier method and multivariable Cox proportional hazards regression. <h3>Results</h3> Of 10,492 heart transplant recipients in the study period, 4610(44%) were bridged with a durable LVAD and 158(2%) with Impella. Impella use increased following the UNOS allocation policy change (3% vs 1% of transplants, p<0.01) and a higher proportion were status 1 or 2 compared to those bridged with durable LVADs (96% vs 26%, p<0.01). Median days between listing and transplant were 40, 218, and 13 days for no MCS, durable LVAD, and Impella, respectively (p<0.01). Impella-bridged recipients were less likely to be obese (26% vs 41%, p<0.01), have diabetes (24% vs 31%, p<0.01), ischemic cardiomyopathy (28% vs 35%, p<0.01), prior cardiac surgery (27% vs 73%, p<0.01), and were more likely to be on inotropes at the time of transplant (65% vs 6%, p<0.01). On multivariate analysis, neither bridge with durable LVAD (aHR 1.25, 95% CI 0.97-1.62, p = 0.08) nor Impella (aHR 1.07, 95% CI 0.55-2.08, p=0.84) was associated with a difference in one-year survival following heart transplantation. <h3>Conclusion</h3> Impella utilization as bridge to transplant has tripled in the current era of heart transplantation with no significant difference in one-year survival compared to those bridged with durable LVADs. Percutaneous LVAD platforms can be cautiously considered in the sickest patients requiring LVAD bridge to transplantation.

Comparison of Outcomes in Heart Transplant Recipients Receiving CMV Prophylaxis with CMV IVIG with Valganciclovir versus Valganciclovir Alone

<h3>Purpose</h3> Cytomegalovirus (CMV) remains one of the most common opportunistic infections affecting orthotopic heart transplant (OHT) patients, with seronegative (R-) recipients receiving transplants from seropositive donors (D+) being at the highest risk. CMV intravenous immune globulin (CMV IVIG) use for prophylaxis has been limited since the release of valganciclovir (VGC) due to efficacy, infusion-related toxicities, and cost. The ISHLT guidelines for the care of heart transplant recipients state there may be a role for CMV IVIG in high risk (D+/R-) OHT in combination with VGC, but it is not clearly defined. The goal of this study is to evaluate if adding CMV IVIG to VGC impacts the rates of CMV infection. <h3>Methods</h3> This is a retrospective, pre-post study of CMV high risk adult OHT recipients transplanted between 1/1/2015-12/31/2018 (n=51). In 9/2017, the institutional protocol for prophylaxis of high risk CMV OHT recipients changed. Previously, high risk patients were given CMV IVIG for 3 months in addition to VGC 900 mg daily for 6 months (or renal dose equivalent). After the protocol change, patients received VGC alone for 6 months. CMV infection was defined as evidence of CMV replication regardless of symptoms. CMV disease was defined as evidence of CMV infection with attributable symptoms. <h3>Results</h3> Of the CMV high risk OHT recipients, 29 received CMV IVIG+VGC and 22 received VGC alone. There were no differences in baseline characteristics, immunosuppressive regimens, renal function, or VGC dosing between cohorts (Table 1). There was no difference in the rates of CMV infection at 1 year between cohorts (34.5% vs. 18.2%; p=0.225). Furthermore, there was no difference in rates of CMV pneumonia (6.9% vs 0%, p=0.499) or CMV colitis (0% vs 4.5%, p=0.431) between cohorts. Overall, only one patient had breakthrough CMV and that patient was on VGC therapy alone. <h3>Conclusion</h3> CMV IVIG appears to have no added benefit in preventing CMV infections in the era of VGC therapy.

Cardiac transplantation outcomes in patients with amyloid cardiomyopathy

Amyloid cardiomyopathy (ACM) is a progressive and life-threatening disease caused by abnormal protein deposits within cardiac tissue. The most common forms of ACM are caused by immunoglobulin derived light chains (AL) and transthyretin (TTR). Orthotopic heart transplantation (OHT) remains the definitive treatment for patients with end stage heart failure. In this study, we perform a contemporary multicenter analysis evaluating post OHT survival in patients with ACM. We conducted a multicenter analysis of 40,044 adult OHT recipients captured in the United Network for Organ Sharing (UNOS) registry from 1987-2018. Patients were characterized as ACM or non-ACM. Baseline characteristics were obtained, and summary characteristics were calculated. Outcomes of interest included post-transplant survival, infection, treated rejection, and the ability to return to work. Racial differences in OHT survival were also analyzed. Unadjusted associations between ACM and non-ACM survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models. Three hundred ninety-eight patients with a diagnosis of ACM were identified of which 313 underwent heart only OHT. ACM patients were older (61 vs 53; P < .0001) and had a higher proportion of African Americans (30.7% vs 17.6%; P < .0001). Median survival for ACM was 10.2 years vs 12.5 years in non-ACM (P = .01). After adjusting for confounding, ACM patients had a higher likelihood of death post-OHT (HR 1.39 CI: 1.14, 1.70; P = .001). African American ACM patients had a higher likelihood of survival compared to White ACM patients (HR 0.51 CI 0.31-0.85; P = .01). No difference was observed in episodes of treated rejection (OR 0.63 CI 0.23, 1.78; P = .39), hospitalizations for infections (OR 1.24 CI: 0.85, 1.81; P = .26), or likelihood of returning to work for income (OR 1.23 CI: 0.84, 1.80; P = .30). In this analysis of OHT in ACM, ACM was associated with a higher likelihood of post-OHT mortality. Racial differences in post-OHT were observed with African American patients with ACM having higher likelihood of survival compared to White patients with ACM. No differences were observed in episodes of treated rejection, hospitalization for infection, or likelihood to return to work for income.

Twenty-year survival following orthotopic heart transplantation in the United States.

This study evaluated 20-year survival after adult orthotopic heart transplantation (OHT). The United Network of Organ Sharing Registry database was queried to study adult OHT recipients between 1987 and 1998 with over 20-year posttransplant follow-up. The primary and secondary outcomes were 20-year survival and cause of death after OHT, respectively. Multivariable logistic regression was used to identify significant independent predictors of long-term survival, and long-term survival was compared among cohorts stratified by number of predictors using Kaplan Meier survival analysis. 20,658 patients undergoing OHT were included, with a median follow-up of 9.0 (IQR, 3.2-15.4) years. Kaplan-Meier estimates of 10-, 15-, and 20-year survival were 50.2%, 30.1%, and 17.2%, respectively. Median survival was 10.1 (IQR, 3.9-16.9) years. Increasing recipient age (>65 years), increasing donor age (>40 years), increasing recipient body mass index (>30), black race, ischemic cardiomyopathy, and longer cold ischemic time (>4 h) were adversely associated with a 20-year survival. Of these 6 negative predictors, presence of 0 risk factors had the greatest 10-year (59.7%) and 20-year survival (26.2%), with decreasing survival with additional negative predictors. The most common cause of death in 20-year survivors was renal, liver, and/or multisystem organ failure whereas graft failure more greatly impacted earlier mortality. This study identifies six negative preoperative predictors of 20-year survival with 20-year survival rates exceeding 25% in the absence of these factors. These data highlight the potential for very long-term survival after OHT in patients with end-stage heart failure and may be useful for patient selection and prognostication.

Effect of Blood Product Transfusion on Perioperative Outcomes After Heart Transplantation

The objective of this study was to identify transfusion-related in-hospital outcomes in orthotopic heart transplantation (OHT) recipients. Retrospective chart review. Tertiary care hospital. Adult OHT recipients undergoing transplantation between January 2010 and December 2016. None. The primary composite outcome was occurrence of any of the following events during admission for OHT: (1) graft dysfunction requiring mechanical circulatory support (MCS); (2) respiratory failure requiring tracheostomy; (3) renal failure requiring hemodialysis; (4) 30-day mortality; (5) complication requiring readmission to intensive care unit; (6) sepsis; and (7) stroke. The authors evaluated these outcomes in relation to all blood component transfusions received intraoperatively and in the first 24 hours postoperatively. The study included 197 patients and the primary composite outcome was present in 72 (36.6%). After adjusting for propensity score, red blood cell (RBC) transfusion was associated with composite outcomes (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.05-1.31, p = 0.004), postoperative MCS use (OR 1.36, 95% CI 1.18-1.58, p < 0.001), acute renal failure requiring hemodialysis (OR 1.21, 5% CI 1.06-1.38, p = 0.004), and 30-day mortality (OR 1.29, 95% CI 1.05-1.59, p = 0.02). Fresh frozen plasma was associated with composite outcome (OR 1.07, 95% CI [1.003-1.15], p = 0.042) and renal failure (OR 1.08, 95% CI 1.08 [1.002-1.17], p = 0.04). Intra- and postoperative transfusions (first 24 hours) of RBC and FFP were associated with adverse postoperative composite outcomes in patients undergoing OHT.

Comparison of Outcomes in Heart Transplant Recipients Receiving CMV Prophylaxis with CMV IVIG with Valganciclovir versus Valganciclovir Alone

Cytomegalovirus (CMV) remains one of the most common opportunistic infections affecting orthotopic heart transplant (OHT) patients, with seronegative (R-) recipients receiving transplants from seropositive donors (D+) being at the highest risk. CMV intravenous immune globulin (CMV IVIG) use for prophylaxis has been limited since the release of valganciclovir (VGC) due to efficacy, infusion-related toxicities, and cost. The ISHLT guidelines for the care of heart transplant recipients state there may be a role for CMV IVIG in high risk (D+/R-) OHT in combination with VCG, but it is not clearly defined. The goal of this study is to evaluate if adding CMV IVIG to VGC impacts the rates of CMV infection. This is a retrospective, pre-post study of CMV high risk adult OHT recipients transplanted between 1/1/2015-12/31/2018 (n=51). In 9/2017, the institutional protocol for prophylaxis of high risk CMV OHT recipients changed. Previously, high risk patients were given CMV IVIG for 3 months in addition to VGC 900 mg daily for 6 months (or renal dose equivalent). After the protocol change, patients received VGC alone for 6 months. CMV infection was defined as evidence of CMV replication regardless of symptoms. CMV disease was defined as evidence of CMV infection with attributable symptoms. Of the CMV high risk OHT recipients, 29 received CMV IVIG+VGC and 22 received VGC alone. There were no differences in baseline characteristics, immunosuppressive regimens, renal function, or VGC dosing between cohorts (Table 1). There was no difference in the rates of CMV infection at 1 year between cohorts (34.5% vs. 18.2%; p=0.225). Furthermore, there was no difference in rates of CMV pneumonia (6.9% vs 0%, p=0.499) or CMV colitis (0% vs 4.5%, p=0.431) between cohorts. Overall, only one patient had breakthrough CMV and that patient was on VGC therapy alone. CMV IVIG appears to have no added benefit in preventing CMV infections in the era of VGC therapy.

Discontinuing amiodarone treatment prior to heart transplantation lowers incidence of severe primary graft dysfunction.

Recent studies have shown an increased incidence of primary graft dysfunction (PGD) in patients treated with amiodarone prior to orthotopic heart transplant (OHT). We hypothesized that discontinuation of amiodarone before OHT may lower the incidence of severe PGD. This was a single-center retrospective study of 381 adult OHT recipients between January 2010 and June 2017. Within 6months prior to OHT, 197 did not receive amiodarone (Group 1), 142 continued amiodarone to OHT (Group 2), and 42 had amiodarone treatment discontinued before OHT (Group 3). 53 (13.9%) participants developed severe PGD, 13 (6.6%) of which were in Group 1, 36 (25.4%) were in Group 2, and 4 (9.5%) were in Group 3 (P<.001). Multivariable analysis revealed continued amiodarone treatment to OHT (Group 2; OR, 3.70; 95% CI, 1.26-10.88; P=.018) to be an independent risk factor for the development of severe PGD when Group 1 served as the reference group. Moreover, patients in Group 3 had no difference in the risk of severe PGD (OR=0.416, 95% CI=0.08-2.15; P=.296). We found that discontinuing amiodarone treatment prior to OHT resulted a lower incidence of severe PGD.

The role of estrogen, immune function and aging in heart transplant outcomes

BackgroundAging and loss of estrogen suppress immune function, potentially improving survival after orthotopic heart transplant (OHT). The effect of female aging on OHT outcomes is unknown. MethodsBetween 1995 and 2015, 41,299 adult OHT recipients (24.3% women) were studied using a retrospective multi-institutional cohort. Patients were stratified by age and gender into premenopausal (18–39 years), perimenopausal (40–49 years), and postmenopausal (≥50 years) groups. Kaplan-Meier survival analyses and risk-adjusted models examined gender differences across groups at one, five, and ten years. ResultsKaplan-Meier survival was equivalent for postmenopausal women and men, and lower for premenopausal women than men at all time points (p ≤ 0.05). Postmenopausal women had higher risk-adjusted five-year survival than premenopausal women (AOR 1.61, 95% CI 1.15–2.25, p = 0.006). ConclusionsPremenopausal women have lower unadjusted survival than men after OHT. Post-menopausal women have significantly better five-year survival than pre-menopausal women. Menopause may contribute to improved survival after OHT.

Impact of Donor Obesity on Outcomes After Orthotopic Heart Transplantation.

BackgroundThe impact of donor obesity on the outcome of orthotopic heart transplantation has not been studied. The aim of this study was to investigate the impact of donor obesity on the outcomes of adult orthotopic heart transplantation recipients.Methods and ResultsData were obtained from the United Network for Organ Sharing database. All adult (age ≥18 years) patients undergoing orthotopic heart transplantation from 2000 through 2016 were included (n=31 920). We stratified the cohort by donor body mass index (BMI); 13 015 patients (40.8%) received a heart from a normal‐weight donor (BMI 18.5–24.9), 11 271 patients (35.3%) received a heart from an overweight donor (BMI 25.0–29.9), 4910 patients (15.4%) received a heart from an obese donor (BMI 30.0–34.9), and 2724 patients (8.5%) received a heart from an extremely obese donor (BMI ≥35). The cohort of obese donors was older, included a higher incidence of diabetes mellitus, and had a higher creatinine. Our data also showed that the recipients of obese donor grafts were older, had a higher BMI, creatinine, percentage of diabetes mellitus, and longer total waiting period. There was no significant difference detected in the survival likelihood (P=0.08) of patients based on a donor's BMI‐based categorized cohort. There were no significant differences found in the overall survival probability among 4 groups in the adjusted survival analyses (P=0.25).ConclusionsThis study demonstrated that patients receiving higher BMI donor hearts might not be subjected to an increased risk of death, at least during the short term after transplant, compared with those using the normal‐weight donors.

Amiodarone use in patients listed for heart transplant is associated with increased 1-year post-transplant mortality

Pre-transplant amiodarone use has been postulated as a risk factor for morbidity and mortality after orthotopic heart transplantation (OHT). We assessed pre-OHT amiodarone use and tested the hypothesis that it is associated with impaired post-OHT outcomes. We performed a retrospective cohort analysis of adult OHT recipients from the registry of the International Society for Heart and Lung Transplantation (ISHLT). All patients had been transplanted between 2005 and 2013 and were stratified by pre-OHT amiodarone use. We derived propensity scores using logistic regression with amiodarone use as the dependent variable, and assessed the associations between amiodarone use and outcomes with Kaplan-Meier analysis after matching patients 1:1 based on propensity score, and with Cox regression with adjustment for propensity score. Of the 14,944 OHT patients in the study cohort, 32% (N = 4,752) received pre-OHT amiodarone. Amiodarone use was higher in recent years (29% in 2005 to 2007, 32% in 2008 to 2010, 35% in 2011 to 2013). Amiodarone-treated patients were older and more frequently had a history of sudden cardiac death (27% vs 13%) and pre-OHT mechanical circulatory support. Key donor characteristics and allograft ischemia times were similar between groups. In propensity-matched analyses, amiodarone-treated patients had higher rates of cardiac reoperation (15% vs 13%) and permanent pacemaker (5% vs 3%) after OHT and before discharge. Amiodarone-treated patients also had higher 1-year mortality (hazard ratio 1.15, 95% confidence interval 1.02 to 1.30), but the risks of early graft failure, retransplantation and rehospitalization were similar between groups. Amiodarone use before OHT was independently associated with increased 1-year mortality. The need for amiodarone therapy should be carefully and continuously assessed in patients awaiting OHT.