Center Volume Predicts Improved Early Outcomes in Multiorgan Heart Transplantation.

PURPOSE: Center volume is associated with improved survival after isolated heart transplant, but its impact on multiorgan heart transplant (MHT) outcomes is unknown. This study examines the impact of institutional MHT volume on MHT outcomes. METHODS: Adult patients undergoing first time MHT from 2011 to 2021 were identified in the United Network for Organ Sharing database. Transplant centers were annually classified as low-, medium-, or high-volume if they performed <3, 3 to 5, or ≥6 MHTs that year, respectively. Graft failure was defined as death, failure, or re-transplantation of any allograft. RESULTS: A total of 1860 MHTs were performed at 104 centers, including 482 (26%) at low-, 601 (32%) at medium-, and 777 (42%) at high-MHT volume centers. Noncardiac allografts included kidney (83%), liver (16%), and lung (2%). The proportion of MHTs performed at high-volume centers increased from 10% in 2011 to 62% in 2021. Recipient age, race, and body mass index did not vary by center volume (all P > .05). Patients at high-volume centers were more likely to be in the intensive care unit pre-transplant (58% vs 44%, P < .001) and have shorter waitlist times (47 vs 92 days, P < .001) than those at low-volume centers. 30-day graft survival was higher in combined medium- and high-volume compared with low-volume centers (95% vs 92%, P = .004). Increasing center MHT volume was protective against 30-day graft failure (adjusted hazard ratio 0.93 [0.88-0.98]) on multivariate Cox regression. CONCLUSIONS: Higher MHT volume is associated with improved early graft survival after MHT, which may justify centralizing the performance of MHTs to high-volume centers.

Emerging Racial Differences in Heart Transplant Waitlist Outcomes for Patients on Temporary Mechanical Circulatory Support.

Temporary mechanical circulatory support (tMCS) is increasingly used for patients awaiting heart transplantation. Although examples of systemic inequity in cardiac care have been described, biases in tMCS use are not well characterized. This study explores the racial disparities in tMCS use and waitlist outcomes. The United Network for Organ Sharing database was used to identify adults listed for first-time heart transplantation from 2015 to 2021. White and non-White patients on extracorporeal membrane oxygenation, intra-aortic balloon pump, or temporary left ventricular assist device were identified. Waitlist outcomes of mortality, transplantation, and delisting were analyzed by race using competing risks regression. The effect of the new heart allocation system was also assessed. A total of 16,811 patients were included in this study, with 10,377 self-identifying as White and 6,434 as non-White. White patients were more often male, privately ensured, and had less co-morbidities (p <0.05). tMCS use was found to be significantly higher in non-White patients (p <0.001). Among those on tMCS, non-White patients were more likely to be delisted because of illness (subhazard ratio 1.34 [1.09 to 1.63]) and less likely to die while on the waitlist (subhazard ratio 0.76 [0.61 to 0.93]). This disparity was not present before the implementation of the new heart allocation system. tMCS use was proportional to the risk factors identified in the non-White cohort. After the implementation of the new heart allocation system, White patients were more likely to die, whereas non-White patients were more likely to be delisted. Further work is needed to determine the causes of and potential solutions for disparities in the waitlist outcomes.

Extended criteria donor organ use for heart-lung transplantation in the modern era.

BACKGROUND: Demand for donor hearts and lungs exceeds their supply. Extended Criteria Donor (ECD) organs are used to help meet this demand, but their impact on heart-lung transplantation outcomes is poorly characterized. METHODS AND RESULTS: The United Network for Organ Sharing was queried for data on adult heart-lung transplantation recipients (n = 447) from 2005‒2021. Recipients were stratified based on whether they received ECD hearts and/or lungs. Morbidity was analyzed using Kruskal-Wallis, chi-square, and Fisher's exact tests. Mortality was analyzed using Kaplan-Meier estimation, log-rank tests and Cox regression. Sixty-five (14.5%) patients received two ECD organs, 134 (30.0%) received only an ECD lung, and 65 (14.5%) only an ECD heart. Recipients of two ECD organs were older, more likely to have diabetes, and more likely transplanted from 2015‒2021 (p < 0.05). Groups did not differ by pre-transplant diagnosis, intensive care unit disposition, life support use, or hemodynamics. Group five-year survival rates ranged from 54.5% to 63.2% (p = 0.428). Groups did not differ by 30-day mortality, strokes, graft rejection, or hospital length of stay. CONCLUSIONS: Using ECD hearts and/or lungs for heart-lung transplantation is not associated with increased mortality and is a safe strategy for increasing donor organ supply in this complex patient population.

Extended criteria donor organ use for heart-lung transplantation in the modern era

Abstract Background: Demand for donor hearts and lungs exceeds their supply. Extended Criteria Donor (ECD) organs are used to help meet this demand, but their impact on heart-lung transplantation outcomes is poorly characterized. Methods and results: The United Network for Organ Sharing was queried for data on adult heart-lung transplantation recipients (n = 447) from 2005‒2021. Recipients were stratified based on whether they received ECD hearts and/or lungs. Morbidity was analyzed using Kruskal-Wallis, chi-square, and Fisher's exact tests. Mortality was analyzed using Kaplan-Meier estimation, log-rank tests and Cox regression. Sixty-five (14.5%) patients received two ECD organs, 134 (30.0%) received only an ECD lung, and 65 (14.5%) only an ECD heart. Recipients of two ECD organs were older, more likely to have diabetes, and more likely transplanted from 2015‒2021 (p < 0.05). Groups did not differ by pre-transplant diagnosis, intensive care unit disposition, life support use, or hemodynam-ics. Group five-year survival rates ranged from 54.5% to 63.2% (p = 0.428). Groups did not differ by 30-day mortality, strokes, graft rejection, or hospital length of stay. Conclusions: Using ECD hearts and/or lungs for heart-lung transplantation is not associated with increased mortality and is a safe strategy for increasing donor organ supply in this complex patient population.

Tricuspid surgery at time of mitral surgery improves survival free from severe tricuspid regurgitation but not quality of life.

Objective: The choice to operate on moderate tricuspid regurgitation (TR) during mitral surgery is challenging owing to limited mid-term data. We assess whether concomitant tricuspid operations improve mid-term quality of life, morbidity, or mortality. Methods: An institutional database identified mitral surgery recipients with moderate TR at the time of surgery from 2010 to 2019. Patients were stratified by the presence of a concomitant tricuspid operation. Quality of life at the last follow-up was assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Morbidity was compared using the χ2 test, Mann-Whitney U test, and Student t test. Survival was analyzed with Kaplan-Meier estimation. Results: Of 210 mitral surgery recipients, 67 (31.9%) underwent concomitant tricuspid surgery. The concomitant tricuspid surgery cohort had greater preoperative dialysis use (10.5% vs 3.5%; P = .043) but similar age, New York Heart Association class, and cardiac surgery history relative to the nonconcomitant cohort (P > .05 for all). The concomitant tricuspid surgery cohort had a longer cardiopulmonary bypass time (144 minutes vs 122 minutes; P = .005) but a similar rate of mitral repair (P = .220). Postoperative KCCQ-12 scores reflected high quality of life in both cohorts (95.1 vs 89.1; P = .167). The concomitant tricuspid surgery cohort trended toward a higher perioperative pacemaker placement rate (22.8% vs 12.7%; P = .088) but were less likely to develop severe TR (0.0% vs 13.0%; P = .004). Overall survival was comparable between the 2 cohorts at 1 year (84.9% vs 81.6%; P = .628) and 5 years (73.5% vs 57.9%; P = .078). Five-year survival free from severe TR was higher in the concomitant cohort (73.5% vs 54.3%; P = .032). Conclusions: Concomitant tricuspid surgery for moderate TR is associated with increased 5-year survival free from severe TR but not with increased quality of life.

Heart-kidney transplant versus heart transplant in the obese: a propensity-matched analysis.

OBJECTIVES: The decision to perform simultaneous heart-kidney transplant (HKT) rather than isolated heart transplant (IHT) for patients with advanced kidney disease is challenging. Limited data exist to guide this decision in obese patients. We sought to compare mortality after HKT and IHT in obese patients with non-dialysis-dependent kidney disease. METHODS: The United Network for Organ Sharing was queried for data on adult heart transplant recipients from 2000 to 2022. Inclusion criteria were obesity, estimated glomerular filtration rate <45 ml/min/1.73 m2 and no pretransplant dialysis. HKT and IHT recipients were propensity matched. Morbidity was compared using chi-squared, Fisher's exact and McNemar's tests. Survival was assessed with Kaplan-Meier estimation. Risk factors for mortality were examined with Cox regression. RESULTS: A total of 289 HKT and 1920 IHT recipients met inclusion criteria. Heart-kidney recipients had higher baseline creatinine and rates of intensive care unit disposition than IHT recipients (both standardized mean differences >0.10). Propensity matching resulted in 239 pairs of HKT and IHT recipients with minimal differences in baseline characteristics. Heart-kidney recipients had higher 5- and 10-year survival than IHT recipients on unmatched (77% vs 69%, P = 0.011 and 58% vs 48%, P = 0.008) and propensity matched analyses (77% vs 68%, P = 0.026 and 57% vs 39%, P = 0.007). Heart-kidney transplantation was protective against 10-year mortality on multivariable regression (hazard ratio 0.585, P = 0.002). CONCLUSIONS: In obese patients with non-dialysis-dependent kidney disease, HKT may decrease long-term mortality relative to IHT and should be strongly considered as a preferred treatment.

Antithrombotic therapy for durable left ventricular assist devices - current strategies and future directions.

Left ventricular assist devices (LVADs) improve survival and quality of life for patients with advanced heart failure but are associated with high rates of thromboembolic and hemorrhagic complications. Antithrombotic therapy is required following LVAD implantation, though practices vary. Identifying a therapeutic strategy that minimizes the risks of thromboembolic and hemorrhagic complications is critical to optimizing patient outcomes and is an area of active investigation. This paper reviews strategies for initiating and maintaining antithrombotic therapy in durable LVAD recipients, focusing on those with centrifugal-flow devices.

Failure to rescue: obesity increases the risk of mortality following early graft failure in heart transplantation in UNOS database patients.

OBJECTIVES: Early graft failure (EGF) is a devastating postoperative complication following heart transplant. Institutional studies have modelled donor and recipient risk factors predictive of graft failure. To date, no studies have assessed specific recipient profiles associated with mortality after recipients suffer from EGF. The objective of this study was to identify this recipient profile. METHODS: We performed a retrospective review of patients in the United Network for Organ Sharing database undergoing heart transplant from August 2000 to September 2019. EGF was defined as graft dysfunction at 24 hours post-heart transplant. The primary outcome was 90-day mortality. To isolate recipient characteristics associated with mortality, we performed the univariate analysis on 24 recipient characteristics adjusted for high-risk donor characteristics (ischaemic time, donor age, race mismatch, BUN/creatinine ratio) predictive of 1-year mortality (P < 0.2). We then performed backward stepwise multivariable regression adjusted for identified donor characteristics to determine recipient characteristics associated with mortality after EGF (P < 0.05). RESULTS: We identified 302 patients diagnosed with post-transplant EGF. Among these patients, mortality was 82% within 90 days of transplantation. Adjusted univariate analysis identified 7 factors associated with mortality. Adjusted backward stepwise multivariable regression identified BMI > 30 as predictive of mortality at 90 days after EGF. CONCLUSIONS: Patients who develop EGF after heart transplant are at high risk for mortality. Careful discussion regarding transplant candidacy and risk is warranted in obese patients. In addition, minimizing donor factors associated with graft dysfunction is critical during preoperative planning in these recipients.

Sofosbuvir, a nucleotide polymerase inhibitor, for the treatment of chronic hepatitis C virus infection.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection is ubiquitous, affecting approximately 180 million individuals worldwide and around 3.2 million in the United States. While peginterferon and ribavirin alone continue to be used, the treatment landscape for patients with genotype 1 has recently changed to include one of two protease inhibitors: boceprevir and telaprevir. Despite this, effective therapies for chronic HCV for all genotypes represent a largely unmet need. AREAS COVERED: Sofosbuvir , formally labeled GS-7977, is an HCV NS5B nucleotide polymerase inhibitor that has entered multiple Phase III trials. Phase II trials demonstrated that treatments including sofosbuvir have higher sustained virologic response rates for genotypes 1, 2, 3, 4 and 6 in comparison with treatments that include only peginterferon and ribavirin. In addition, the side-effect profile of sofosbuvir and ribavirin dual treatment has an improved tolerability in comparison with treatment regimes that include interferon-based options. EXPERT OPINION: The hope and expectation is that interferon is eliminated from the armamentarium of HCV therapy and that all-oral therapies prove effective although interferon in combination with multiple drugs may still be required to treat select patients. In addition, there is a need to develop effective therapies for all HCV genotypes with simple and well-tolerated regimes.