Shin, Doosup

Background: We sought to investigate temporal trends in patient characteristics, waitlist, and posttransplant outcomes after heart transplantation in the United States. Methods: Using data from the United Network of Organ Sharing, we identified adults listed for heart transplantation between 1991 and 2019. Patients were divided into 4 eras based on the 3 time points in which changes were made to the patient selection/allocation policy (Era 1=January 1991–January 1999; Era 2=January 1999–July 2006; Era 3=July 2006–October 2018; and Era 4=October 2018–March 2020), and patient characteristics, waitlist, and posttransplant outcomes were evaluated for each era. Results: Between 1991 and 2019, 95 179 patients were added to the heart transplantation waitlist. Compared with Era 1, patients listed in Era 4 were older (mean age: 50 versus 52 years) and with higher risk comorbidities (eg, 10% versus 28.8% diabetes, 23.3% versus 35.6% obese). Over the study period, 22 738 patients died or were permanently delisted for deterioration on the waitlist while 61 687 were transplanted. Compared with the preceding era, there was significant decrease in death or deterioration in the last 2 eras (sub-hazard ratio, 0.67 [95% CI, 0.65–0.70] for Era 3 versus Era 2 and sub-hazard ratio, 0.65 [95% CI, 0.58–0.73] for Era 4 versus 3). Across the years, 27.1% to 40.5% of those on the waitlist were transplanted. Among those transplanted, there was increase in the rates of in-hospital stroke (2.8% in Era 1 to 3.7% in Era 4), renal failure requiring dialysis (7.2%–17.1%), and length-of-stay (14–17days), P <0.001. However, this did not negatively impact short-term survival when compared with the preceding era (1-year graft survival from Era 1 to Era 4=84.1%, 86.4%, 90.4%, and 89.7%, respectively). Conclusions: There have been significant changes in the characteristics of patients listed for heart transplantation. Although transplant volume has increased, the wide supply-demand gap persisted. The last two changes in the allocation policy achieved their primary objective of reducing waitlist mortality.

Abstract Background The landscape of heart transplantation (HT) has changed significantly with respect to patient selection, surgical techniques, and patient outcomes. We sought to investigate temporal trends in patient characteristics, waitlist and post-transplant outcomes after HT in the U.S. Methods We queried the national database of the United Network of Organ Sharing (UNOS) to identify adults listed for HT in the U.S. between 1991 and 2019. Patients were divided into four eras based on the three time points in which changes were made to the patient selection/allocation policy (1999, 2006, and 2018), and patient characteristics as well as waitlist and post-transplant outcomes were evaluated for each era. Results Between 1991 and 2019, a total of 95,179 patients were added to the waitlist for HT in the U.S. Compared to era 1, patients listed in era 4 were older (mean age: 52.4 years), more female (27.6%) and ethnic minorities (40%), and with higher-risk comorbidities (28.8% diabetes, 35.6% obese). Over the study period, there were 22,070 waitlist deaths and 61,687 transplants. Compared to the preceding era, there was significant decrease in waitlist mortality in the last 2 eras (e.g., sub-hazard ratio for era 4 vs era 3 =0.37, 95% CI=0.32–0.44). For each year, only 27.1% to 40.5% of those on the waitlist were transplanted. Among those who were transplanted, there was increase in the rates of in-hospital stroke (2.8% in era 1 to 3.7% in era 4), renal failure requiring dialysis (7.2% to 17.1%), and hospital length of stay (14 to 17 days), p-values&lt;0.001 for all. However, this has not negatively impacted short-term survival when compared to the preceding era (1-year graft survival = 89.7% in era 4). Based on a projection model, we predict a 47% increase in living adult heart transplant recipients to to 44,366 in 2040. Conclusion There have been significant changes in the characteristics of patients listed for HT in the U.S., including an increasing proportion of high-risk co-morbidities. Although the transplant volume has increased, the wide supply-demand gap persisted. The last 2 changes in the allocation policy in 2006 and 2018 achieved their primary objective of reducing waitlist mortality. Funding Acknowledgement Type of funding sources: None.

Background: Acute cellular rejection is a major determinant of mortality and retransplantation after heart transplantation. We sought to evaluate the prognostic implications of coronary microcirculatory dysfunction assessed by index of microcirculatory resistance (IMR) for the risk of acute cellular rejection after heart transplantation. Methods: The present study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment 1 month after transplantation. IMR is microcirculatory resistance under maximal hyperemia. By measuring hyperemic mean transit time using 3 injections (4 mL each) of room-temperature saline under maximal hyperemia, IMR was calculated as hyperemic distal coronary pressure×hyperemic mean transit time. The primary end point was biopsy-proven acute cellular rejection of grade ≥2R during 2 years of follow-up after transplantation and was compared by using multivariable Cox proportional hazards regression according to IMR. The incremental prognostic value of IMR, in addition to the model with clinical factors, was evaluated by comparison of C-index, net reclassification index, and integrated discrimination index. Results: The mean age of recipients was 51.2±13.1 years (81.2% male), and the cumulative incidence of acute cellular rejection was 19.0% at 2 years. Patients with acute cellular rejection had significantly higher IMR values at 1 month than those without acute cellular rejection (23.1±8.6 versus 16.8±11.1, P =0.002). IMR was significantly associated with the risk of acute cellular rejection (per 5-U increase: adjusted hazard ratio, 1.18 [95% CI, 1.04–1.34], P =0.011) and the optimal cutoff value of IMR to predict acute cellular rejection was 15. Patients with IMR≥15 showed significantly higher risk of acute cellular rejection than those with IMR<15 (34.4% versus 3.8%; adjusted hazard ratio, 15.3 [95% CI 3.6–65.7], P <0.001). Addition of IMR to clinical variables showed significantly higher discriminant and reclassification ability for risk of acute cellular rejection (C-index 0.87 versus 0.74, P <0.001; net reclassification index 1.05, P <0.001; integrated discrimination index 0.20, P <0.001). Conclusions: Coronary microcirculatory dysfunction assessed by IMR measured early after heart transplantation showed significant association with the risk of acute cellular rejection. In addition to surveillance endomyocardial biopsy, early stratification using IMR could be a clinically useful tool to identify patients at higher risk of future acute cellular rejection after heart transplantation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02798731.