Propensity score-based analysis of long-term follow-up in patients supported with durable centrifugal left ventricular assist devices:the EUROMACS analysis

OBJECTIVES: The HeartWare HVAD (HW) and the HeartMate3 (HM3) are presently the most commonly used continuous-flow left ventricular assist devices worldwide. We compared the outcomes of patients supported with either of these 2 devices based on data from the EUROMACS (European Registry for Patients with Mechanical Circulatory Support). METHODS: A retrospective analysis of the survival and complications profile in propensity score-matched adult patients enrolled in the EUROMACS between 01 January 2016 and 01 September 2020 and supported with either an HW or HM3. Matching included demographic parameters, severity of cardiogenic shock and risk-modifying end-organ parameters that impact long-term survival. Survival on device and major postoperative adverse events were analysed. RESULTS: Following 1:1 propensity score matching, each group consisted of 361 patients. Patients were well balanced (<0.1 standardized mean difference). The median follow-up was similar in both groups [396 (interquartile range (IQR) 112-771) days for HW and 376 (IQR 100-816) days for HM3]. The 2-year survival was similar in both groups [HW: 61% 95% confidence interval (CI) (56-67%) vs HM3: 68% 95% CI (63-73%) (stratified hazard ratio for mortality: 1.13 95% CI (0.83-1.54), P = 0.435].The cumulative incidence for combined major adverse events and unexpected readmissions was similar in both groups [subdistribution hazard ratio (SHR) 1.0 (0.84-1.21), P = 0.96]. Patients in the HW group demonstrated a higher risk of device malfunction [SHR 2.44 (1.45-3.71), P < 0.001], neurological dysfunction [SHR 1.29 (1.02-1.61), P = 0.032] and intracranial bleeding [SHR 1.76 (1.13-2.70), P = 0.012]. CONCLUSIONS: Mid-term survival in both groups was similar in a propensity-matched analysis. The risk of device malfunction, neurological dysfunction and intracranial bleeding was significantly higher in HW patients

R-848 triggers the expression of TLR7/8 and suppresses HIV replication in monocytes

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication.</p> <p>Methods</p> <p>Eighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848.</p> <p>Results</p> <p>We found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes.</p> <p>Conclusions</p> <p>Our study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.</p

The Impact of Beta Blockers on Survival in Heart Transplant Recipients: Insights from the Zabrze HTx Registry

Introduction. The data assessing the impact of beta blocker (BB) medication on survival in patients after heart transplantation (HTx) are scarce and unequivocal; therefore, we investigated this population. Methods. We retrospectively analyzed the HTx Zabrze Registry of 380 consecutive patients who survived the 30-day postoperative period. Results. The percentage of patients from the entire cohort taking BBs was as follows: atenolol 24 (17%), bisoprolol 67 (49%), carvedilol 11 (8%), metoprolol 28 (20%), and nebivolol 8 (6%). The patients receiving BBs were older (56.94 ± 14.68 years vs. 52.70 ± 15.35 years, p=0.008) and experienced an onset of HTx earlier in years (11.65 ± 7.04 vs. 7.24 ± 5.78 p≤0.001). They also had higher hematocrit (0.40 ± 0.05 vs. 0.39 ± 0.05, p=0.022) and red blood cells (4.63 (106/μl) ± 0.71 vs. 4.45 (106/μl) ± 0.68, p=0.015). Survival according to BB medication did not differ among the groups (p=0.655) (log-rank test). Univariate Cox proportional hazard regression analysis revealed that the following parameters were associated with unfavorable diagnosis: serum concentration of albumin (g/l) HR: 0.87, 95% CI (0.81–0.94), p=0.0004; fibrinogen (mg/dl) HR: 1.006, 95% CI (1.002–1.008), p=0.0017; and C-reactive protein (mg/l) HR: 1.014, 95% CI (1.004–1.023), p=0.0044. Conclusions. The use of BBs in our cohort of patients after HTx was not associated with survival benefits

Development and Validation of a Practical Model to Identify Patients at Risk of Bleeding After TAVR

Objectives: No standardized algorithm exists to identify patients at risk of bleeding after transcatheter aortic valve replacement (TAVR). The aim of this study was to generate and validate a useful predictive model. Background: Bleeding events after TAVR influence prognosis and quality of life and may be preventable. Methods: Using machine learning and multivariate regression, more than 100 clinical variables from 5,185 consecutive patients undergoing TAVR in the prospective multicenter RISPEVA (Registro Italiano GISE sull'Impianto di Valvola Aortica Percutanea; NCT02713932) registry were analyzed in relation to Valve Academic Research Consortium-2 bleeding episodes at 1 month. The model's performance was externally validated in 5,043 TAVR patients from the prospective multicenter POL-TAVI (Polish Registry of Transcatheter Aortic Valve Implantation) database. Results: Derivation analyses generated a 6-item score (PREDICT-TAVR) comprising blood hemoglobin and serum iron concentrations, oral anticoagulation and dual antiplatelet therapy, common femoral artery diameter, and creatinine clearance. The 30-day area under the receiver-operating characteristic curve (AUC) was 0.80 (95% confidence interval [CI]: 0.75–0.83). Internal validation by optimism bootstrap-corrected AUC was 0.79 (95% CI: 0.75–0.83). Score quartiles were in graded relation to 30-day events (0.8%, 1.1%, 2.5%, and 8.5%; overall p <0.001). External validation produced a 30-day AUC of 0.78 (95% CI: 0.72–0.82). A simple nomogram and a web-based calculator were developed to predict individual patient probabilities. Landmark cumulative event analysis showed greatest bleeding risk differences for top versus lower score quartiles in the first 30 days, when most events occurred. Predictivity was maintained when omitting serum iron values. Conclusions: PREDICT-TAVR is a practical, validated, 6-item tool to identify patients at risk of bleeding post-TAVR that can assist in decision making and event prevention