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The 2018 OPTN heart allocation policy was modified with a stated goal of improving access to individuals with the greatest medical need through improved stratification of risk. Criteria were created to identify patients with the highest risk (Status 1 and 2) to facilitate timely transplantation. This study sought to evaluate changes in wait times for the highest priority patients since implementation of the 2018 policy. All adult single-organ transplant recipients were identified in the UNOS registry from 10/18/18 through 7/8/22. Patients were identified from the date they were upgraded to Status 1 or 2 and separated to 4 periods: 10/2018-9/2019, 9/2019-8/2020, 8/2020-7/2021, & 7/2021-6/2022. Outcomes were compared by blood type and UNOS region. 897 patients were upgraded to Status 1 (n=197, 194, 231, & 290 in each period) and there was no clinically meaningful change in median waitlist time during the study period (4 days (IQR 2-7), 4 days (IQR 2-9), 4 days (IQR 2-7), 5 days (IQR 2-9)). There was also no difference by blood type or listing region (Figures 1A & B). 4,523 patients were upgraded to Status 2 (n=861, 1,076, 1,242, & 1,344 in each period), and the median waitlist time incrementally increased during each period: 7 days (IQR 4-13) to 8 (IQR 4-17) to 9 (IQR 5-20) to 12 (IQR 6-25), p<0.0001. Wait time was consistently longest for Blood Type O and shortest for Type AB & Type A (Figure 1C). Regional variations in wait time continue, however wait time increased in every region over time (Figure 1D). After adjusting for age, gender, race, cPRA>50%, UNOS region, recipient BMI, and blood type, time period continued to be significantly associated with longer wait time for Status 2 (p<0.0001). Status 1 wait time has been consistent since implementation of the 2018 heart allocation policy change. However, Status 2 wait time continues to increase with variation by region and blood type, limiting the ability to improve transplant access to individuals with the greatest medical need. [ABSTRACT FROM AUTHOR]

Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). CAV results in impaired blood flow in the epicardial coronaries and microvasculature. Reduction in myocardial blood flow reserve (MBFR) by cardiac PET has been associated with adverse post-HT events. This study sought to investigate the prognostic implication of isolated microvascular CAV. Consecutive adult HT recipients who underwent cardiac N13 ammonia PET for assessment of CAV from 2016-2019 were included. Primary outcome was death or retransplant. Patients were classified into 2 groups according to MBFR >2 or ≤2. Microvascular CAV was defined as an MBFR≤2 without epicardial CAV on PET (SDS<2) or angiography (ISHLT CAV 0). Mixed CAV had both ischemia on PET (SDS≥2) or angiography (ISHLT CAV 1+) and MBFR≤2. 465 patients were included, with median age of 61 years, median time from transplant of 7.8 years, and 26.2% were women. 139 (29.9 %) patients had MBFR≤2, which was associated with a 3-fold increased risk of death/retransplant (HR 3.0, 95% CI 2.0-4.4, p<0.0001). Patients with reduced MBFR were further divided into microvascular (n=114) and mixed CAV (n=25). Mixed CAV was associated with 3.7 times the risk of death/retransplant (95% CI 2.1-6.6, p<0.0001). Microvascular CAV (PET or angiography definition) more than doubled the risk of death/retransplant (HR 2.1, 95% CI 1.4-3.2, p<0.0001; HR 2.1, 95% CI 1.3-3.2, p=0.001, Figure 1A & B). In a multivariable model with significant univariate predictors including sex, time post-HT, PSI use, statin use, ISHLT CAV 2 or 3, DM, GFR<60, prior ACR, prior AMR, and DSA, Microvascular CAV (HR 1.8, 95% CI 1.2-2.7, p=0.006) remained independently associated with an increased risk of death/retransplant. Isolated Microvascular CAV is a harbinger of death/retransplant. This highlights the clinical utility of measuring MBFR to help risk stratify patients following HT. [ABSTRACT FROM AUTHOR]

Adult congenital heart disease (ACHD) patients have the potential for increased sensitization and complications deriving from repeated interventions. Donor-derived cell-free-DNA (dd-cfDNA) test is a non-invasive method for surveillance of allograft injury. We sought to characterize dd-cfDNA in ACHD recipients and its impact on post-heart transplant (HT) outcomes. We performed a retrospective analysis of patients who underwent HT in our institution between January 2005 and January 2021, and who had at least one dd-cfDNA result. Multiorgan recipients were excluded. Patients with a history of ACHD were compared to adult HT recipients with no history of ACHD (control group). Dd-cfDNA was considered positive if >0.12%. Samples reported as <0.12% were analyzed as 0.11%. A total of 418 patients were identified; 23 ACHD patients and 395 control patients were included. ACHD patients were younger (38 years vs. 56 years, p <0.001) and the majority (73%) were male. The median dd-cfDNA did not differ between the groups (p=0.49). Endomyocardial biopsy proven allograft rejection, graft dysfunction, formation of donor specific antibody, and cardiac allograft vasculopathy did not differ between the groups during the follow-up period (2100 days in the ACHD group vs 1430 days in the control group, p=0.09). In this retrospective single center study, HT recipients with a history of ACHD did not demonstrate significantly elevated dd-cfDNA levels as compared to control. ACHD patients similarly did not have a higher incidence of endomyocardial biopsy proven allograft rejection or graft dysfunction. [ABSTRACT FROM AUTHOR]

Improvements in cancer therapies have led to a growing population of cancer survivors (CS) who are recipients of heart transplantation (HT). CS have been shown to have long-term alterations in immune function from prior cancer treatments leading to challenges in management of immunosuppression. Post-HT donor-derived cell-free-DNA (dd-cfDNA) testing is a noninvasive method used to detect allograft rejection. We sought to evaluate the effect of pre-HT malignancy on dd-cfDNA and post-HT outcomes. All consecutive patients who underwent HT at our institution between 1990 to 2022 with at least one dd-cfDNA result were included in the analysis. Dd-cfDNA results in the CS group were compared to patients free from malignancy (FFM). Dd-cfDNA was considered positive if >0.12%. For the purpose of this analysis, samples reported as <0.12% were analyzed as 0.11%. A total of 588 patients were identified. There were 47 (8%) patients in the CS group and 541 (92%) patients in the FFM group. CS were older at the time of transplant (60 vs 54 years, p = 0.03) with a median time from active malignancy to HT of 8 [3.5, 16.5] years. Leukemia/lymphoma was the most common cancer type (27.7%) followed by breast, prostate, and gastrointestinal (13% each). In the CS group, 38.3% of the dd-cfdNA samples were positive compared to 29.4% in the FFM group (p=0.004). The prevalence of donor-specific antibodies (DSA) was similar in the CS and FFM groups, 23.7% and 23.4%, respectively (p=0.86). There was no difference in biopsy-proven cellular and antibody-mediated rejection or graft failure during the follow-up period (1450 and 1830 days in CS vs. FFM groups, respectively; p=0.62). In our cohort, the CS group had higher rates of positive donor-derived cell-free-DNA results compared to patients without preexisting malignancy. Future studies are needed to assess the immunosuppression protocols of both groups and assess if this can be the cause of the differences we found. [ABSTRACT FROM AUTHOR]

Scholars warn that partisan divisions in the mass public threaten the health of American democracy. We conducted a megastudy ( n = 32,059 participants) testing 25 treatments designed by academics and practitioners to reduce Americans' partisan animosity and antidemocratic attitudes. We find that many treatments reduced partisan animosity, most strongly by highlighting relatable sympathetic individuals with different political beliefs or by emphasizing common identities shared by rival partisans. We also identify several treatments that reduced support for undemocratic practices-most strongly by correcting misperceptions of rival partisans' views or highlighting the threat of democratic collapse-which shows that antidemocratic attitudes are not intractable. Taken together, the study's findings identify promising general strategies for reducing partisan division and improving democratic attitudes, shedding theoretical light on challenges facing American democracy.

Background: Cardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial coronary arteries and the microvasculature. A leading cause of post-transplant mortality, CAV affects 50% of heart transplant recipients within 10 years of heart transplant., Objectives: This analysis examined the outcomes of heart transplant recipients with reduced myocardial blood flow reserve (MBFR) and microvascular CAV detected by 13 N-ammonia positron emission tomography (PET) myocardial perfusion imaging., Methods: A total of 181 heart transplant recipients who underwent PET to assess for CAV were included with a median follow-up of 4.7 years. Patients were classified into 2 groups according to the total MBFR: >2.0 and ≤2.0. Microvascular CAV was defined as no epicardial CAV detected by PET and/or coronary angiography, but with an MBFR ≤2.0 by PET., Results: In total, 71 (39%) patients had an MBFR ≤2.0. Patients with an MBFR ≤2.0 experienced an increased risk for all outcomes: 7-fold increase in death or retransplantation (HR: 7.05; 95% CI: 3.2-15.6; P < 0.0001), 12-fold increase in cardiovascular death (HR: 12.0; 95% CI: 2.64-54.12; P = 0.001), and 10-fold increase in cardiovascular hospitalization (HR: 10.1; 95% CI: 3.43-29.9; P < 0.0001). The 5-year mean survival was 302 days less than those with an MBFR >2.0 (95% CI: 260.2-345.4 days; P < 0.0001). Microvascular CAV (adjusted HR: 3.86; 95% CI: 1.58-9.40; P = 0.003) was independently associated with an increased risk of death or retransplantation., Conclusions: Abnormal myocardial blood flow reserve, even in the absence of epicardial CAV, identifies patients at a high risk of death or retransplantation. Measures of myocardial blood flow provide prognostic information in addition to traditional CAV assessment., Competing Interests: Funding Support and Author Disclosures Dr Clerkin has been supported by National Institutes of Health K23 HL148528. Dr Topkara has been supported by National Institutes of Health K08 HL146964. Dr Colombo has received consulting fees from Abbott. Dr Einstein has received speaker fees from Ionetix; has received consulting fees from W. L. Gore and Associates; and his institution has grants/grants pending from Canon Medical Systems, GE Healthcare, Roche Medical Systems, and W. L. Gore and Associates. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The association between socioeconomic status (SES), sex, race / ethnicity and outcomes during hospitalization for heart failure (HF) has not previously been investigated., Methods and Results: We analyzed HF hospitalizations in the United States National Inpatient Sample between 2015 and 2017. Using a hierarchical, multivariable Poisson regression model to adjust for hospital- and patient-level factors, we assessed the association between SES, sex, and race / ethnicity and all-cause in-hospital mortality. We estimated the direct costs (USD) across SES groups. Among 4,287,478 HF hospitalizations, 40.8% were in high SES, 48.7% in female, and 70.0% in White patients. Relative to these comparators, low SES (homelessness or lowest quartile of median neighborhood income) (relative risk [RR] 1.02, 95% confidence interval [CI] 1.00-1.05) and male sex (RR 1.09, 95% CI 1.07-1.11) were associated with increased risk, whereas Black (RR 0.79, 95% CI 0.76-0.81) and Hispanic (RR 0.90, 95% CI 0.86-0.93) race / ethnicity were associated with a decreased risk of in-hospital mortality (5.1% of all hospitalizations). There were significant interactions between race / ethnicity and both, SES (P < .01) and sex (P = .04), such that racial/ethnic differences in outcome were more pronounced in low SES groups and in male patients. The median direct cost of admission was lower in low vs high SES groups ($9324.60 vs $10,940.40), female vs male patients ($9866.60 vs $10,217.10), and Black vs White patients ($9077.20 vs $10,019.80). The median costs increased with SES in all demographic groups primarily related to greater procedural utilization., Conclusions: SES, sex, and race / ethnicity were independently associated with in-hospital mortality during HF hospitalization, highlighting possible care disparities. Racial/ethnic differences in outcome were more pronounced in low SES groups and in male patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Yarkoni's argument risks skepticism about the very possibility of social science: If social phenomena are too causally complex, normal scientific methods could not possibly untangle them. We argue that the problem of causal complexity is best approached at the level of scientific communities and institutions, not the modeling practices of individual scientists.