Thymoglobulin induction in heart transplantation: patient selection and implications for maintenance immunosuppression.

Clinical data relating to rabbit antithymocyte globulin (rATG) induction in heart transplantation are far less extensive than for other immunosuppressants, or indeed for rATG in other indications. This was highlighted by the low grade of evidence and the lack of detailed recommendations for prescribing rATG in the International Society for Heart and Lung Transplantation (ISHLT) guidelines. The heart transplant population includes an increasing frequency of patients on mechanical circulatory support (MCS), often with ongoing infection and/or presensitization, who are at high immunological risk but also vulnerable to infectious complications. The number of patients with renal impairment is also growing due to lengthening waiting times, intensifying the need for strategies that minimize calcineurin inhibitor (CNI) toxicity. Additionally, the importance of donor-specific antibodies (DSA) in predicting graft failure is influencing immunosuppressive regimens. In light of these developments, and in view of the lack of evidence-based prescribing criteria, experts from Germany, Austria, and Switzerland convened to identify indications for rATG induction in heart transplantation and to develop an algorithm for its use based on patient characteristics.

Comparison of feasibility and results of frailty assessment methods prior to left ventricular assist device implantation.

AIMS: Assessing frailty and sarcopenia is considered a valuable cornerstone of perioperative risk stratification in advanced heart failure patients. The lack of an international consensus on a diagnostic standard impedes its implementation in the clinical routine. This study aimed to compare the feasibility and prognostic impact of different assessment tools in patients undergoing continuous-flow left ventricular assist device (cf-LVAD) implantation. METHODS AND RESULTS: We prospectively compared feasibility and prognostic values of six frailty/sarcopenia assessment methods in 94 patients prior to cf-LVAD implantation: bioelectrical impedance analysis (BIA), computed tomography (CT)-based measurement of two muscle areas/body surface area [erector spinae muscle (TMESA/BSA) and iliopsoas muscle (TPA/BSA)], physical performance tests [grip strength, 6 min walk test (6MWT)] and Rockwood Clinical Frailty Scale (RCFS). Six-month mortality and/or prolonged ventilation time >95 h was defined as the primary endpoint. BIA and CT showed full feasibility (100%); physical performance and RCFS was limited due to patients' clinical status (feasibility: 87% grip strength, 62% 6MWT, 88% RCFS). Phase angle derived by BIA showed the best results regarding the prognostic value for 6 month mortality and/or prolonged ventilation time >95 h (odds ratio (OR) 0.66 [95% confidence interval (CI): 0.46-0.92], P = 0.019; area under the curve (AUC) 0.65). It provided incremental value to the clinical risk assessment of EuroSCORE II: C-index of the combined model was 0.75 [95% CI; 0.651-0.848] compared with C-index of EuroSCORE II alone, which was 0.73 (95% CI: 0.633-0.835). Six-month survival was decreased in patients with reduced body cell mass derived by BIA or reduced muscle area in the CT scan compared with patients with normal values: body cell mass 65% (95% CI: 51.8-81.6%) vs. 83% (95% CI: 74.0-93.9%); P = 0.03, TMESA/BSA 65% (95% CI: 51.2-82.2%) vs. 82% (95% CI: 73.2-93.0%); P = 0.032 and TPA/BSA 66% (95% CI: 53.7-81.0%) vs. 85% (95% CI: 75.0-95.8%); P = 0.035. CONCLUSIONS: Bioelectrical impedance analysis parameters and CT measurements were shown to be suitable to predict 6-month mortality and/or prolonged ventilation time >95 h in patients with advanced heart failure prior to cf-LVAD implantation. Phase angle had the best predictive capacity and sarcopenia diagnosed by reduced body cell mass in BIA or muscle area in CT was associated with a decreased 6 month survival.

Impact of Muscle Mass as a Prognostic Factor for Failed Waiting Time Prior to Heart Transplantation.

Objectives: Clinical deterioration during the waiting time impairs the prognosis of patients listed for heart transplantation. Reduced muscle mass increases the risk for mortality after cardiac surgery, but its impact on resilience against deterioration during the waiting time remains unclear. Methods: We retrospectively analyzed data from 93 patients without a VAD who were listed in Eurotransplant status "high urgent (HU)" for heart transplantation between January 2015 and October 2020. The axial muscle area of the erector spinae muscles at the level of thoracic vertebra 12 indexed to body surface area (TMESA/BSA) measured in the preoperative thoracic computed tomography scan was used to measure muscle mass. Results: Forty patients (43%) underwent emergency VAD implantation during the waiting time and four patients (4%) died during the waiting time. The risk of emergency VAD implantation/death during the waiting time decreased by 10% for every cm2/m2 increase in muscle area [OR 0.901 (95% CI: 0.808-0.996); p = 0.049]. After adjusting for gender [OR 0.318 (95% CI: 0.087-1.073); p = 0.072], mean pulmonary artery pressure [OR 1.061 (95% CI: 0.999-1.131); p = 0.060], C-reactive protein [OR 1.352 (95% CI: 0.986-2.027); p = 0.096], and hemoglobin [OR 0.862 (95% CI: 0.618-1.177); p = 0.360], TMESA/BSA [OR 0.815 (95% CI: 0.698-0.936); p = 0.006] remained an independent risk factor for emergency VAD implantation/death during the HU waiting time. Conclusion: Muscle area of the erector spinae muscle appears to be a potential, easily identifiable risk factor for emergency VAD implantation or death in patients on the HU waiting list for heart transplantation. Identifying patients at risk could help optimize the outcome and the timing of VAD support.

Diagnostic and Prognostic Value of a TDI-Derived Systolic Wall Motion Analysis as a Screening Modality for Allograft Rejection after Heart Transplantation.

BACKGROUND: Despite the risk for complications, allograft surveillance after orthotopic heart transplantation (OHT) is performed by cardiac catheterization and biopsies. We investigated the diagnostic and prognostic value of a TDI-derived systolic wall motion analysis of the posterobasal wall of the left ventricle (Sm) as a screening modality in OHT aftercare. METHODS: We examined data of 210 eligible patients who underwent OHT between 2010 and 2020. Forty-four patients who had died within the initial hospital stay were excluded. For 166 patients, baseline and follow-up data were analyzed. The mean age at OHT was 46.2 (±11.4) years; 76.5% were male. RESULTS: Within the observational period, 22 (13.3%) patients died. In total, 170 episodes of acute cellular or humoral rejections occurred (84 ISHLT1R; 13 ISHLT2R; 8 ISHLT3R; 65 AMR), and 29 catheterizations revealed cardiac allograft vasculopathy (5 CAV1; 4 CAV2; 20 CAV3). Individual Sm radial/longitudinal remained stable within the follow-up period (11.5 ± 2.2 cm/s; 10.9 ± 2.1 cm/s). Patients with acute rejections and CAV3 showed significant Sm radial/longitudinal reductions (AMR1: 1.6 ± 1.9 cm/s, confidence interval (CI) 0.77-0.243, p < 0.001; 1.8 ± 2.0 cm/s, CI 0.92-0.267, p < 0.001. ISHLT1R: 1.7 ± 1.8 cm/s, CI 1.32-2.08, p < 0.001; 2.0 ± 1.6 cm/s, CI 1.66-2.34, p < 0.001. CAV3: 1.3 ± 2.5 cm/s, CI 0.23-2.43, p < 0.017; 1.4 ± 2.8 cm/s, CI 0.21-2.66, p < 0.021). Lower Sm was associated with a threefold increase in all-cause mortality (hazard ratio (HR) 3.24, CI 1.2-8.76, p = 0.020; HR 2.92, CI 1.19-7.18, p = 0.019). Overall, Sm-triggered surveillance led to 0.75 invasive diagnostics per patient post-OHT year. CONCLUSIONS: Sm remained stable in the post-OHT course. Reductions indicated ISHLT1R, AMR1 and CAV3 and were associated with higher all-cause mortality. Sm-triggered surveillance may be referred to as a safe, high-yield screening modality in OHT aftercare.