Aims: A significant number of patients with non-valvular atrial fibrillation (NVAF) are ineligible for nonvitamin K oral anticoagulants (NOACs) due to previous major bleeding or because they are at high bleeding risk (HBR). In this setting the indication for percutaneous left atrial appendage closure (LAAO) is a valuable alternative. We aimed to evaluate the efficacy and safety of NOACs versus LAAO indication in NVAF patients at HBR (HAS-BLED ≥3).Methods and results: All consecutive patients who underwent successful LAAO (n=193) and those treated with NOACs (n=189) (dabigatran, apixaban or rivaroxaban) were included. A 1:1 propensity score matching (PSM) was used to match LAAO and NOACs patients. At baseline, patients in the LAAO group had higher HAS-BLED (4.2% vs 3.3%, p<0.001) and lower CHADS-VASc (4.3% vs 4.7%, p=0.005) scores. After 1:1 PSM, 192 patients were enrolled in the final analysis (LAAO n=96; NOACs n=96). At two-year follow-up, no significant differences in thromboembolic (7.3% vs 6.3%, p=0.966) and ISTH major bleeding event rates (6.7% vs 4.8% p=0.503) were found between the two unmatched groups. All-cause death was significantly higher in the LAAO group (18.7% vs 10.6%; p=0.049). After PSM, all-cause death, thromboembolic and ISTH major bleeding event rates were similar between the groups. Significant independent predictors of all-cause death were dialysis (HR 5.65, p<0.001) and age (HR 1.08, 95% CI: 1.05-1.13, p<0.001). Conclusions:In NVAF patients at HBR, LAAO and NOACs performed similarly in terms of thromboembolic and major bleeding events up to two-year follow-up. Our findings warrant further investigation in randomised trials and therefore can be considered as hypothesis-generating.

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Background Limited real-world data are available regarding the outcome of patients treated with inappropriate dose of nonvitamin-K antagonist oral anticoagulants (NOACs). Objective To assess the prevalence and factors associated with inappropriate dose prescription of NOACs and to evaluate adverse events that come from this inappropriate prescription. Methods Single-center multidisciplinary registry including nonvalvular atrial fibrillation patients treated with NOACs. Based on guidelines criteria for dose reduction, two subcohorts were defined as treated with appropriate or inappropriate NOACs dose. Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox–Mantel test. Results A total of 760 nonvalvular atrial fibrillation patients were included; 32% patients were treated with dabigatran, 34% with apixaban, 24% with rivaroxaban and 10% with edoxaban. An inappropriate dose was prescribed in 96 patients (12.6%), and in most cases (68%) it was too low. Rivaroxaban (15%) and apixaban (18.5%) were the most frequently prescribed with an inappropriate dose. Patients treated with an inappropriate dose were elderly people, with low-creatinine clearance value, who had experienced previous bleeding and with a high CHADS2 VASc score. In 2 years, a trend for higher numbers of thromboembolic events (5.2 vs. 3.3%, P = 0.348) and less major bleeding (2.1 vs. 4.2%, P = 0.316) has been observed in patients with inappropriate NOACs prescriptions. Conclusion Nearly 13% of patients were treated with an inappropriate dose of NOACs, in this single-center study. A trend for higher numbers of thromboembolic events was observed in these patients. The results should be considered as hypothesis generating.

Substance use disorders (SUDs) are characterized by a recurrent and maladaptive use of drugs and/or alcohol. Cognitive behavioral therapies (CBTs) comprise different types of interventions: traditional CBT and the more recent "third wave" behavior therapies, such as acceptance and commitment therapy (ACT), dialectical behavior therapy (DBT), mindfulness-based cognitive therapy (MBCT), and schema therapy (ST). We searched English-language articles published between 2014 and present. This review includes randomized controlled trials (RCTs), quasi-RCTs, pilot studies, and reviews of CBTs for SUDs available on PubMed. Results seem to indicate that CBT and MBCT are effective interventions for SUDs; however, the studies showed a high degree of heterogeneity, so no exhaustive conclusions could be outlined at this time. ACT and DBT in SUD management are limited to few studies and results are therefore inconclusive.

Background Right ventricular (RV) function demonstrated a strong impact on survival of patients with advanced heart failure with reduced ejection fraction (HFrEF). In particular, increased RV pulsatile afterload (RVPA) was associated with poor prognosis. Several right heart catheterization-derived parameters have been proposed to characterize RVPA, including pulmonary artery compliance (PAC), elastance (PAE) and pulsatile index (PAPi). However, among these indices, the best prognostic indicator is undetermined. Purpose To assess the prognostic relevance of RVPA parameters in patients with advanced HFrEF evaluated for heart transplantation. Methods 149 patients with end-stage HFrEF underwent right heart catheterization during the evaluation for heart transplantation. All patients were clinically followed up until death or any censoring events including heart transplantation, left ventricular assist device (LVAD) and hospitalization for acute heart failure. Cox regression and ROC-curve analysis were used to test the prognostic value of RVPA determinants. Multivariate regression models with C-statistics were used to test the independent predictive value of RVPA indices. Results The mean age of the study population was 56.6±10.1 years and 85.2% were male. The most frequent aetiology of HFrEF was ischemic cardiomyopathy (52.3%). Mean LV ejection fraction was 25.7±10.2%. During a mean follow up time of 17±15 months, 29 (19.5%) patients met the primary endpoint: 9 (6%) patients died, 4 (2.68%) patients underwent an urgent heart transplantation, 11 (7.3%) patients underwent urgent LVAD implantation (as bridge to transplantation therapy) and 5 (3.3%) were hospitalized for HF. Patients who met the primary endpoint were significantly older patients (61.2±7.8 vs 55.4±10.2, p=0.006) and with worse hemodynamic profile than event-free survivors (PAC [1.8±0.8 vs. 2.7±2.0, p=0.01], mPAP [33.5±11.3 vs. 29.3±11.0, p=0.05], PVR [3.0±1.6 vs. 2.6±2.0, p=0.09] and PAE [1.12±0.5 vs. 0.98±0.6, p=0.04]). Among the RVPA parameters PAC&lt;1.9 mL/mmHg (HR 4.0, CI 1.3–6.0, p=0.007) and PAE&gt;0.9 mmHg/mL (HR 2.5, 95% CI 1.1–5.2, p=0.02) were associated with the primary endpoint. On the contrary, PAPi was not significantly associated with the outcome. PAC demonstrated a superior predictive value for the composite adverse outcome compared with pulmonary vascular resistances (PVR) (AUC comparison p=0.019) and PAPi (p=0.03) but similar compared with PAE (p=0.19) and mPAP (p=0.51). In multivariable regression models, PAC, but not PAE showed incremental prognostic value compared with cardiac index (p=0.02). Conclusions Hemodynamic indices of RVPA are associated with worse survival in patients with end-stage heart failure. In particular, PAC and PAE demonstrated superior prognostic value compared with PAPi and steady-state PVR. Moreover, PAC showed incremental prognostic value compared with cardiac index in patients awaiting heart transplantation. Funding Acknowledgement Type of funding sources: None.