Briasoulis, Alexandros

Background Pulmonary hypertension (PH) and sensitization adversely affect heart transplant outcomes. Although left ventricular assist devices may reduce PH, they can increase sensitization. We examined the impact of sensitization on heart transplant outcomes in left ventricular assist device‐bridged patients and whether precapillary PH modifies this effect. Methods Adults bridged to heart transplant with an left ventricular assist device between 2005 and 2020 were identified from the United Network for Organ Sharing database. Patients with available panel‐reactive antibody (PRA) and hemodynamic data were included. Associations between PRA and survival and treated rejection were analyzed. Results Among 2469 patients, 1053 had precapillary PH (pulmonary vascular resistance [PVR] >2 Wood units [WU]) and 1416 had PVR ≤2 WU. Elevated PRA (>10%) occurred in 566 patients (24.8% with PVR >2 WU; 21.5% with PVR ≤2 WU). Overall, PRA >10% was associated with increased mortality (adjusted hazard ratio [aHR], 1.28 [95% CI, 1.04–1.58], P =0.022), driven by patients with PVR >2 WU (aHR, 1.82 [95% CI, 1.34–2.50], P <0.001), with no association in those with PVR ≤2 WU (aHR, 0.99 [95% CI, 0.47–1.32], P =0.92). PRA >10% was also associated with treated rejection overall (adjusted odds ratio [aOR], 1.41 [95% CI, 1.09–1.82], P =0.008), confined to the PVR >2 WU group (aOR, 1.87 [95% CI, 1.26–2.76], P =0.002) and absent in the PVR ≤2 WU group (aOR, 1.13 [95% CI, 0.80–1.59], P =0.49). Conclusions Elevated PRA predicts worse outcomes in LVAD‐bridged transplant recepients with precapillary PH, but not in those without precapillary PH.

ABSTRACT Background and Aim This study aimed to provide updated nationwide data on outcomes in heart transplantation for amyloid cardiomyopathy (ACM) compared with other cardiomyopathy etiologies. Methods United Network for Organ Sharing data for patients over 18 who underwent heart transplant for ACM, and other cardiomyopathies including DCM, ICM, RCM, and CHD were reviewed from 2001 through 2022. The data were analyzed with a propensity score‐matched analysis comparing ACM patients with transplant for the cardiomyopathies to measure primary outcomes, including 5‐year, 10‐year, and all‐cause mortality accounting for differences at baseline. Results Of 21 457 heart transplant recipients who met eligibility criteria, there was a 100% increase in the number of heart transplants for ACM from 2010 to 2020 ( p < 0.001). The unadjusted mortality did not differ significantly among ACM, DCM, ICM, RCM, and CHD groups, and 5‐year mortality was comparable between ACM and DCM patients. ACM patients had a significantly lower incidence of postoperative stroke ( p = 0.044), and risk factors for ACM transplant mortality were identified as mechanical ventilation at the time of transplant (HR: 3.8, p = 0.023) and older donor age (HR: 1.1, p = 0.015). Conclusions The number of heart transplants for ACM has increased in recent years, and overall outcomes in these ACM transplants have been similar compared to those for other cardiomyopathies. Despite historical concerns regarding poor prognosis and amyloid recurrence, carefully screened ACM patients can benefit from heart transplantation. Further research and optimization of ACM patient eligibility criteria alongside investigation of concurrent adjunctive therapies could optimize treatment of ACM with heart transplantation.

Background: Despite its use in patients awaiting heart transplant (HT), the impact of continuous inotropic support on short-term complications and long-term transplant outcomes remains unclear. This study evaluated inotrope use at the time of HT on perioperative complications and post-transplant survival, comparing outcomes at 30 days, 1 year, and 10 years with mechanical circulatory support (MCS) strategies including ECMO, IABP, and VADs. Methods: A retrospective analysis of the United Network for Organ sharing (UNOS) registry was performed, stratifying patients based on bridge strategy at the time of transplant: inotropes, ECMO, IABP, or VADs. Baseline characteristics, perioperative complications, and 30-day, 1-year, and 10-year post-transplant survival outcomes were analyzed across groups. Survival was assessed using Kaplan–Meier and Cox proportional hazards models. Results: Among the 11,801 heart transplant patients included, 9330 were on inotropes, 372 were on ECMO, 1072 received an IABP, and 1027 had VADs. Inotrope-bridged patients had significantly lower 30-day and 1-year mortality rates compared to the ECMO, IABP, and VAD groups. They also experienced reduced incidences of post-transplant dialysis and stroke. At 10 years, the inotrope group demonstrated superior long-term survival, with significantly lower mortality risk compared to ECMO (HR: 1.81; CI: 1.49–2.20, p < 0.001), IABP (HR: 1.19; CI: 1.06–1.32, p = 0.005), and VAD (HR: 1.18; CI: 1.10–1.27, p < 0.001). Conclusions: Continuous use of inotropes after waitlisting is associated with lower short, intermediate, and long-term mortality and does not lead to worse outcomes compared to ECMO, IABP, and VAD support. When mechanical support is not an option, inotropic therapy remains a viable and effective strategy.

(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.

Left ventricular assist devices (LVADs) have been increasingly used in patients with advanced heart failure, either as a destination therapy or as a bridge to heart transplant. Continuous flow (CF) LVADs have revolutionized advanced heart failure treatment. However, significant vascular pathology and complications have been linked to their use. While the newer CF-LVAD generations have led to a reduction in some vascular complications such as stroke, no major improvement was noticed in the rate of other vascular complications such as gastrointestinal bleeding. This review attempts to provide a comprehensive summary of the effects of CF-LVAD on vasculature, including pathophysiology, clinical implications, and future directions.

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.

AbstractBackgroundConcerns about the impact of the new donor heart allocation system on posttransplant outcomes have emerged after its implementation. We sought to evaluate the characteristics and outcomes of left ventricular assist device (LVAD) recipients transplanted before and after the implantation of the new policy on October 18, 2018.MethodsData on bridge to transplantation of adult patients with LVAD between January 2015 and October 2021, with durable LVAD as a (BTT), was queried from the United Network of Organ Sharing (UNOS) registry. The main outcomes were 30‐day all‐cause mortality, 30‐day fatal graft failure, 1‐year all‐cause mortality, treated acute rejection at 1 year and renal replacement therapy (RRT) for acute renal failure.ResultsIn our study, 7096 patients met the inclusion criteria including 2435 in the new allocation system. The transplanted patients in the new allocation system era had older donor age, longer ischemic time, and higher proportion of newer generation LVADs. Adjusted 30‐day all‐cause mortality was significantly lower for LVAD recipients in the new allocation system era (2.5% vs. 3.6%; sub‐hazard ratio [SHR] 0.36, 95% Confidence intervals [CI] 0.27–0.48, p < 0.001) without differences in the risk of fatal graft failure and 1‐year mortality (7.8% vs. 9.6%). Significantly lower adjusted 30‐day mortality with HVAD and HM3 devices than HM2 in the new allocation system era was found, without differences in 1‐year mortality. Acute allograft rejection requiring treatment was significantly lower (Odds Ratio 0.78, 95% CI 0.65–0.94, p = 0.01), whereas a trend toward higher risk of renal failure requiring RRT was identified.ConclusionsDespite changing donor characteristics and longer ischemic times, posttransplant outcomes in LVAD recipients have not worsened with the implementation of the new allocation system and this finding is related to the use of newer generation continuous flow LVADs.

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.

Contrast-induced nephropathy (CIN) is a type of acute kidney injury associated with intravascular administration of iodinated contrast, usually reversible. Contrast agents are an essential component of invasive and noninvasive coronary angiography. These agents have been modified over time to enhance patient safety and tolerability, but adverse reactions still occur. CIN has been variably defined, as a rise in serum creatinine of 0.5 mg/dl, or a 25% increase in serum creatinine above baseline within 24-72 hours after the procedure. The incidence of CIN varies based on the definition used and risk profile of the patients. CIN is rare among patients with normal renal function at baseline. In low-risk patients, CIN occurs in 1-5%, whereas in higher-risk populations, the incidence can be as high as 30%. CIN is also associated with a 5- to 20-fold increased risk of other early adverse events including in-hospital myocardial infarction, target vessel occlusion, and early mortality. The main prevention strategies are adequate intravenous hydration before, during and after the procedure as well as restriction of contrast load with maximum volume approximately no more than three times the serum creatinine clearance. Recent observational and small prospective randomized trials demonstrate the reduction of CIN incidence with HMG-CoA enzyme inhibitors. In this systematic review and meta-analysis we explore the effects of statin administration in prevention of CIN.

Background The presence of a durable left ventricular assist device ( LVAD ) is associated with increased risk of vasoplegia in the early postoperative period following heart transplantation ( HT ). However, preoperative predictors of vasoplegia and its impact on survival after HT are unknown. We sought to examine predictors and outcomes of patients who develop vasoplegia after HT following bridging therapy with an LVAD . Methods and Results We identified 94 patients who underwent HT after bridging with continuous‐flow LVAD from 2008 to 2018 at a single institution. Vasoplegia was defined as persistent low vascular resistance requiring ≥2 intravenous vasopressors within 48 hours after HT for >24 hours to maintain mean arterial pressure >70 mm Hg. Overall, 44 patients (46.8%) developed vasoplegia after HT . Patients with and without vasoplegia had similar preoperative LVAD , echocardiographic, and hemodynamic parameters. Patients with vasoplegia were significantly older; had longer LVAD support, higher preoperative creatinine, longer cardiopulmonary bypass time, and higher Charlson comorbidity index; and more often underwent combined organ transplantation. In a multivariate logistic regression model, older age (odds ratio: 1.08 per year; P =0.010), longer LVAD support (odds ratio: 1.06 per month; P =0.007), higher creatinine (odds ratio: 3.9 per 1 mg/dL; P =0.039), and longer cardiopulmonary bypass time (odds ratio: 1.83 per hour; P =0.044) were independent predictors of vasoplegia. After mean follow‐up of 4.0 years after HT , vasoplegia was associated with increased risk of all‐cause mortality (hazard ratio: 5.20; 95% CI, 1.71–19.28; P =0.003). Conclusions Older age, longer LVAD support, impaired renal function, and prolonged intraoperative CPB time are independent predictors of vasoplegia in patients undergoing HT after LVAD bridging. Vasoplegia is associated with worse prognosis; therefore, detailed assessment of these predictors can be clinically important.