Prediction model for leaflet thrombosis in patients undergoing transcatheter aortic valve implantation: the EFFORT study.

BACKGROUND: Leaflet thrombosis (LT) is a multifaceted and underexplored condition that can manifest following transcatheter aortic valve implantation (TAVI). The objective of this study was to formulate a prediction model based on laboratory assessments and clinical parameters, providing additional guidance and insight into this relatively unexplored aspect of post-TAVI complications. METHODS: The present study was an observational prospective hypothesis-generating study, including 101 patients who underwent TAVI and a screening for LT (the primary endpoint) by multidetector computed tomography (MDCT). All images were acquired on a third-generation dual-source CT system. Levels of von Willebrand factor (vWF) activity, hemoglobin (Hb), and lactate dehydrogenase (LDH) were measured among other parameters. A predictive score utilizing binary logistic regression, Kaplan-Meier time-to-event analysis, and receiver operating characteristics (ROC) analysis was established. RESULTS: LT (11 subclinical and 2 clinical) was detected in 13 of 101 patients (13%) after a median time to screening by MDCT of 105 days (IQR, 98-129 days). Elevated levels of vWF activity (> 188%) pre-TAVI, decreased Hb values (< 11.9 g/dL), as well as increased levels of LDH (> 312 U/L) post-TAVI and absence of oral anticoagulation (OAC) were found in patients with subsequent LT formation as compared to patients without LT. The established EFFORT score ranged from - 1 to 3 points, with an increased probability for LT development in patients with ≥ 2 points (85.7% of LT cases) vs < 2 points (14.3% of LT cases; p < 0.001). Achieving an EFFORT score of ≥ 2 points was found to be significantly associated with a 10.8 times higher likelihood of developing an LT (p = 0.001). The EFFORT score has an excellent c-statistic (area under the curve (AUC) = 0.89; 95% CI 0.74-1.00; p = 0.001) and a high negative predictive value (98%). CONCLUSION: An EFFORT score might be a helpful tool to predict LT development and could be used in risk assessment, if validated in confirmatory studies. Therefore, the score has the potential to guide the stratification of individuals for the planning of subsequent MDCT screenings.

High concentration of symmetric dimethylarginine is associated with low platelet reactivity and increased bleeding risk in patients with acute coronary syndrome.

BACKGROUND: Dual antiplatelet therapy (DAPT) prevents ischemic events in patients with acute coronary syndrome (ACS), but is associated with increased risk of bleeding events. Symmetric dimethylarginine (SDMA) is one of nitric oxide (NO)-related pathway metabolites and stands as a promising biomarker of early chronic kidney disease (CKD) and cardiovascular diseases (CVDs). OBJECTIVES: Our study evaluated the role of SDMA in predicting bleeding events in patients after ACS treated with DAPT. METHODS: We compared plasma concentrations of NO-related pathway metabolites in patients with ACS (n = 291) and investigated the prognostic value of SDMA as a bleeding predictor during 1-year follow-up. We measured the metabolites concentration using ultra performance liquid chromatography. Platelet reactivity was determined using impedance aggregometry. RESULTS: Patients with the highest quartile (4th) of SDMA concentration had significantly lower platelet aggregation compared to those in the 1st-3rd quartiles of SDMA, based on ADP + PGE1-, AA-, and ADP-induced platelet reactivity tests (p = 0.0004, p = 0.002, p = 0.014, respectively). Patients with major or minor bleeding events had significantly higher concentrations of SDMA as compared to those without bleeding events or to those with minimal bleeding events (p = 0.019, p = 0.019, respectively). CONCLUSION: Higher SDMA concentration is associated with lower platelet reactivity and is associated with major and minor bleeding events in patients with ACS on DAPT. Therefore, SDMA stands as a potential biomarker for individualization of duration and potency of antiplatelet therapies in the ACS population at high risk of bleeding complications.

Subclinical Leaflet Thrombosis After Transcatheter Aortic Valve Replacement: A Meta-Analysis.

This meta-analysis and systematic review was performed to evaluate the clinical relevance of subclinical leaflet thrombosis (SLT) following transcatheter aortic valve replacement. PubMed, Web of Science, and CENTRAL were searched for eligible randomized and nonrandomized studies until November 2020. Risk ratios (RRs) or odds ratios and 95% CIs were calculated, using a random-effects model. Overall, 25 studies were eligible for the analysis and comprised a total of 11,098 patients. The median incidence of SLT was 6% at a median follow-up of 30 days. Use of intra-annular valves was associated with 2-fold greater risk for the development of SLT compared with use of supra-annular valves. There was no difference in the risk for SLT (RR: 0.97; 95% CI: 0.72-1.29; P = 0.83) between single-antiplatelet therapy (SAPT) and dual-antiplatelet therapy (DAPT), whereas oral anticoagulation (OAC) was associated with a 58% relative risk reduction for SLT (RR: 0.42; 95% CI: 0.29-0.61; P < 0.00001) compared with SAPT and DAPT. In patients with diagnosed leaflet thrombosis at follow-up, the risk for stroke or transient ischemic attack was increased by 2.6-fold (RR: 2.56; 95% CI: 1.60-4.09; P < 0.00001) compared with patients without leaflet thrombosis. In patients diagnosed with SLT, the odds of SLT resolution increased by 99% after switch from antiplatelet agents to OAC (odds ratio: 0.01; 95% CI: 0.00-0.06; P < 0.00001). To summarize, indication-based use of OAC after transcatheter aortic valve replacement is associated with a lower risk for SLT compared with SAPT and DAPT. Switching to OAC seems to be effective for SLT resolution. As SLT increased the odds of stroke or transient ischemic attack in the included population, further studies are needed to investigate whether screening tests for SLT and appropriate antithrombotic therapy improve long-term valve functionality and clinical prognosis.

Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis.

Dual antiplatelet therapy (DAPT) and subsequent P2Y12 inhibitor monotherapy, particularly ticagrelor, is an emerging treatment strategy in patients undergoing percutaneous coronary intervention (PCI). This meta-analysis was designed to investigate whether short-term DAPT followed by ticagrelor monotherapy is associated with a favorable outcome as compared with standard DAPT (1-3 months of DAPT was termed "short-term" DAPT, 6-12 months DAPT was termed "standard" DAPT). The primary outcome was the composite of major adverse cardiovascular events (MACE) comprising myocardial infarction, stroke, and cardiovascular death. Secondary outcomes included all-cause mortality and net adverse clinical events (NACE; myocardial infarction, stroke, all-cause death, stent thrombosis, and major bleeding). The primary safety outcome was major bleeding. Three studies comprising 26,143 patients were included. The risk of MACE was similar between the two treatment groups (risk ratio (RR) 0.86, 95% confidence interval (CI), 0.72-1.02, P = 0.08, I2  = 22%). Short-term DAPT followed by ticagrelor monotherapy resulted in a 20% relative risk reduction of all-cause mortality (RR 0.80, 95% CI, 0.65-0.98, P = 0.03, I2  = 0%) and an 18% relative risk reduction of NACE (RR 0.82, 95% CI, 0.71-0.94, P = 0.005, I2  = 33%) as compared with standard DAPT. Short-term DAPT followed by ticagrelor monotherapy significantly decreased the risk of major bleeding (RR 0.67, 95% CI, 0.49-0.92, P = 0.01, I2  = 65%). In patients with acute coronary syndrome, short-term DAPT followed by ticagrelor monotherapy resulted in an unchanged ischemic risk but a significantly lower bleeding risk compared with standard DAPT. Short-term DAPT followed by ticagrelor monotherapy compared with standard DAPT resulted in a favorable safety and efficacy profile. Direct comparisons of aspirin vs. ticagrelor monotherapy following PCI are needed.