(1) Background: Heart failure is an extremely impactful health issue from both a social and quality-of-life point of view and the rate of patients with this condition is destined to rise in the next few years. Transplantation remains the mainstay of treatment for end-stage heart failure, but a shortage of organs represents a significant problem that prolongs time spent on the waiting list. In view of this, the selection of donor and recipient must be extremely meticulous, considering all factors that could predispose to organ failure. One of the main considerations regarding heart transplants is the risk of graft rejection and the need for immunosuppression therapy to mitigate that risk. In this study, we aimed to assess the characteristics of patients who need immunosuppression treatment for rejection within one year of heart transplantation and its impact on mid-term and long-term mortality. (2) Methods: The United Network for Organ Sharing (UNOS) Registry was queried to identify patients who solely underwent a heart transplant in the US between 2000 and 2021. Patients were divided into two groups according to the need for anti-rejection treatment within one year of heart transplantation. Patients’ characteristics in the two groups were assessed, and 1 year and 10 year mortality rates were compared. (3) Results: A total of 43,763 patients underwent isolated heart transplantation in the study period, and 9946 (22.7%) needed anti-rejection treatment in the first year. Patients who required treatment for rejection within one year after transplant were more frequently younger (49 ± 14 vs. 52 ± 14 years, p < 0.001), women (31% vs. 23%, p < 0.001), and had a higher CPRA value (14 ± 26 vs. 11 ± 23, p < 0.001). Also, the rate of prior cardiac surgery was more than double in this group (27% vs. 12%, p < 0.001), while prior LVAD (12% vs. 11%, p < 0.001) and IABP (10% vs. 9%, p < 0.01) were more frequent in patients who did not receive anti-rejection treatment in the first year. Finally, pre-transplantation creatinine was significantly higher in patients who did not need treatment for rejection in the first year (1.4 vs. 1.3, p < 0.01). Most patients who did not require anti-rejection treatment underwent heart transplantation during the new allocation era, while less than half of the patients who required treatment underwent transplantation after the new allocation policy implementation (65% vs. 49%, p < 0.001). Patients who needed rejection treatment in the first year had a higher risk of unadjusted 1 year (HR: 2.25; 95% CI: 1.88–2.70; p < 0.001), 5 year (HR: 1.69; 95% CI: 1.60–1.79; p < 0.001), and 10 year (HR: 1.47; 95% CI: 1.41–1.54, p < 0.001) mortality, and this was confirmed at the adjusted analysis at all three time-points. (4) Conclusions: Medical treatment of acute rejection was associated with significantly increased 1 year mortality compared to patients who did not require anti-rejection therapy. The higher risk of mortality was confirmed at a 10 year follow-up. Further studies and newer follow-up data are required to investigate the role of anti-rejection therapy in the heart transplant population.

Background: The clinical characteristics of mTOR (mammalian target of rapamycin) inhibitors use in heart transplant recipients and their outcomes have not been well described. Methods and Results: We compared patients who received mTOR inhibitors within the first 2 years after heart transplantation to patients who did not by inquiring the United Network for Organ Sharing (UNOS) database between 2010 and 2018. The primary end point was all‐cause mortality with retransplantation as a competing event. Rejection, malignancy, hospitalization for infection, and renal transplantation were secondary end points. There were 1619 (9%) and 15 686 (81%) mTOR inhibitors+ and mTOR inhibitors− patients, respectively. Body mass index, induction, cardiac allograft vasculopathy, calculated panel reactive antibody, and fewer days in 1A status were independently associated with mTOR inhibitors+ status. Over a follow‐up of 10.4 years, there was no difference in all‐cause mortality after adjusting for donor and recipient characteristics (adjusted subdistribution hazard ratio, 1.03 [0.90–1.19]; P =0.66). mTOR inhibitors+ were independently associated with increased risk for rejection (odds ratio [OR], 1.43 [1.11–1.83]; P =0.005) and basal skin cancer (OR, 1.35 [1.19–1.51]; P =0.012) but not for infection or renal transplantation. Conclusions: mTOR inhibitors are used in <10% patients in the first 2 years after heart transplantation and are noninferior to contemporary immunosuppression regimens in terms of all‐cause mortality, infection, malignancy, or renal transplantation. They are associated with risk for rejection.

Aims: Pulmonary artery pressure (PAP)-guided therapy in patients with heart failure (HF) using the CardioMEMS (CMM) device, an implantable PAP sensor, has been shown to reduce HF hospitalizations in previous studies. We sought to evaluate the clinical benefit of the CMM device in regard to 30, 90, and 180 day readmission rates in real-world usage. Methods and results: We queried the Nationwide Readmissions Database (NRD) to identify patients who underwent CMM implantation (International Classification of Diseases 9 and 10 codes) between the years 2014 and 2019 and studied their HF readmissions. Moreover, we compared CMM patients and their readmissions with a matched cohort of patients with HF but without CMM. Multivariable Cox regression analysis was performed to adjust for other predictors of readmissions. Prior to matching, we identified 5 326 530 weighted HF patients without CMM and 1842 patients with CMM. After propensity score matching for several patients and hospital-related characteristics, the cohort consisted of 1839 patients with CMM and 1924 with HF without CMM. Before matching, CMM patients were younger (67.0 ± 13.5 years vs. 72.3 ± 14.1 years, P < 0.001), more frequently male (62.7% vs. 51.5%, P < 0.001), with higher rates of prior percutaneous coronary intervention (16.9% vs. 13.2%, P = 0.002), peripheral vascular disease (29.6% vs. 17.8%, P < 0.001), pulmonary circulatory disorder (38.7% vs. 23.2%, P < 0.001), atrial fibrillation (51.2% vs. 45.3%, P = 0.002), prior left ventricular assist device (1.8% vs. 0.2%, P < 0.001), high income (32.2% vs. 16.4%, P < 0.001), and acute kidney disease (43.8% vs. 29.9%, P < 0.001). Readmission rates at 30 days were 17.3% vs. 20.9% for patients with vs. without CMM, respectively, and remained statistically significant after matching (17.3% vs. 21.5%, P = 0.002). The rates of 90 day (29.6% vs. 36.5%, P = 0.002) and 180 day (39.6% vs. 46.6%, P = 0.009) readmissions were lower in the CMM group. In a multivariable regression model, CMM was associated with lower risk of readmissions (hazard ratio 0.75, 95% confidence interval 0.63–0.89, P = 0.001). Conclusions: The CMM device was associated with reduced HF rehospitalization rates in a nationally representative cohort of HF patients, validating the clinical trial that led to the approval of this device and its utilization in the treatment of HF.

Background: Sotatercept, a first-in-class activin-signaling inhibitor, demonstrated efficacy in pulmonary arterial hypertension (PAH) in the pivotal PULSAR and STELLAR trials. However, whether these benefits and the drug’s distinct safety profile translate to routine clinical practice in the treatment of idiopathic PAH remains unclear. Methods: We conducted a retrospective study using the TriNetX global health research network. Adult patients with idiopathic PAH treated with standard-of-care (SoC) background therapies were identified. Those receiving add-on sotatercept were matched 1:1 with patients on background therapy alone using propensity score matching. Results: A total of 1378 matched patients (689 per arm) were included. The median follow-up was 13.8 months for the SoC group and 10.3 months for the sotatercept group; therefore, the analysis was limited to up to 12 months. Sotatercept was associated with a 49% reduction in the risk of all-cause mortality (HR = 0.51, p = 0.002). A significant reduction was observed in all-cause hospitalizations for the sotatercept arm (HR = 0.44; 12-month rate 6.3% vs. 11.5%, p = 0.010). Safety analysis revealed 2.5-fold increased odds of epistaxis (OR = 2.68, p < 0.001) and 4-fold increased odds of erythrocytosis (OR = 4.26, p < 0.001) with sotatercept, while thrombocytopenia rates were similar (OR = 0.98, p = 0.946). Sotatercept seems to be associated with a higher risk of hypertension compared to background therapy alone (OR = 1.85, p = 0.155). Conclusions: In this large real-world cohort, the addition of sotatercept to SoC background therapy significantly improved survival in idiopathic PAH. While bleeding events, erythrocytosis and elevated blood pressure seemed to be more frequent with sotatercept, the overall safety profile was acceptable, suggesting that the substantial survival and hospitalization benefits outweigh these risks in routine clinical practice.

Data regarding the role of N-terminal Pro-B-type natriuretic peptide (NT-pro BNP) in patients with a continuous-flow left ventricular assist device (CFLVAD) is scarce. To evaluate the prognostic implications of measuring both absolute values and changes in NT-pro BNP concentrations in ambulatory patients with a CFLVAD, we performed a retrospective study of 168 consecutive patients who had an LVAD implantation at our institution and survived beyond their index hospitalization. Of these, 127 patients (56.2 ± 12.5 years, 21.2% female) had NT-pro BNP measured at 1 and 3 months postdischarge in ambulatory settings. Compared to the NT-pro BNP concentration at 1 month, 94 patients (74%) had a decline, and 33 patients (26%) had an increase in concentrations, from their 1 month baseline. After a median follow-up of 17 months, a total of 53 (41.7%) adverse events occurred. Of these, 37 (69.8%) were heart failure (HF) hospitalizations, and 16 (30.2%) were deaths. For each 1,000 unit increase in NT-pro BNP concentration at 3 months, there was a 17% increase in the risk of HF hospitalization or death (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.04–1.32, p = 0.007). Conversely, each 1000 unit decline during the same time, was associated with an 11% decrease in the risk of HF hospitalization or death (HR = 0.89, 95% CI = 0.77–0.98, p = 0.04). In conclusion, in patients with a CFLAD, an increase in NT-pro BNP concentration from 1 to 3 months is associated with an increased risk of HF hospitalization and death. In contrast, a decline is associated with a reduction in the risk of HF hospitalization and death.