Impact of heart failure on the clinical profile and outcomes in patients with atrial fibrillation treated with rivaroxaban. Data from the EMIR study

Background: The aim of this study was to analyze the impact of the presence of heart failure (HF) on the clinical profile and outcomes in patients with atrial fibrillation (AF) anticoagulated with rivaroxaban. Methods: Observational and non-interventional study that included AF adults recruited from 79 Spanish centers, anticoagulated with rivaroxaban ≥ 6 months before inclusion. Data were analyzed according to baseline HF status. Results: Out of 1,433 patients, 326 (22.7%) had HF at baseline. Compared to patients without HF, HF patients were older (75.3 ± 9.9 vs. 73.8 ± 9.6 years; p = 0.01), had more diabetes (36.5% vs. 24.3%; p < 0.01), coronary artery disease (28.2% vs. 12.9%; p < 0.01), renal insufficiency (31.7% vs. 22.6%; p = 0.01), higher CHA2DS2-VASc (4.5 ± 1.6 vs. 3.2 ± 1.4; p < 0.01) and HAS-BLED (1.8 ± 1.1 vs. 1.5 ± 1.0; p < 0.01). After a median follow-up of 2.5 years, among HF patients, annual rates of stroke/systemic embolism/transient ischemic attack, MACE-non-fatal myocardial infarction, revascularization and cardiovascular death-, cardiovascular death, and major bleeding were 1.2%, 3.0%, 2.0%, and 1.4%, respectively. Compared to those patients without HF, HF patients had greater annual rates of MACE (3.0% vs. 0.5%; p < 0.01) and cardiovascular death (2.0% vs. 0.2%; p < 0.01), without significant differences regarding other outcomes, including thromboembolic or bleeding events. Previous HF was an independent predictor of MACE (odds ratio 3.4; 95% confidence interval 1.6-7.3; p = 0.002) but not for thromboembolic events or major bleeding. Conclusions: Among AF patients anticoagulated with rivaroxaban, HF patients had a worse clinical profile and a higher MACE risk and cardiovascular mortality. HF was independently associated with the development of MACE, but not with thromboembolic events or major bleeding

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO2 study

The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study included 29 patients (32.2% of the total), with 14 assigned to the placebo group and 15 to the dapagliflozin, as part of the double-blind, randomized clinical trial [DAPA-VO2 (NCT04197635)]. Blood samples were collected at baseline and after 30 days, and Klotho and FGF-23 levels were measured using ELISA Kits. Between-treatment changes (raw data) were analyzed by using the Mann-Whitney test and expressed as median (p25%–p75%). Linear regression models were utilized to analyze changes in the logarithm (log) of klotho and FGF-23. The median age was 68.3 years (60.8–72.1), with 79.3% male and 81.5% classified as NYHA II. The baseline medians of left ventricular ejection fraction, glomerular filtration rate, NT-proBNP, klotho, and FGF-23 were 35.8% (30.5–37.8), 67.4 ml/min/1.73 m2 (50.7–82.8), 1,285 pg/ml (898–2,305), 623.4 pg/ml (533.5–736.6), and 72.6 RU/ml (62.6–96.1), respectively. The baseline mean peak oxygen uptake was 13.1 ± 4.0 ml/kg/min. Compared to placebo, patients on dapagliflozin showed a significant median increase of klotho [Δ+29.5, (12.9–37.2); p = 0.009] and a non-significant decrease of FGF-23 [Δ−4.6, (−1.7 to −5.4); p = 0.051]. A significant increase in log-klotho (p = 0.011) and a decrease in log-FGF-23 (p = 0.040) were found in the inferential analysis. In conclusion, in patients with stable HFrEF, dapagliflozin led to a short-term increase in klotho and a decrease in FGF-23

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Outcomes and predictive value of the 2MACE score in patients with atrial fibrillation treated with rivaroxaban in a prospective, multicenter observational study: The EMIR study.

The aim of the study was to evaluate the performance of the 2MACE in patients with atrial fibrillation (AF) treated with rivaroxaban and to improve the accuracy of 2MACE. This was a post-authorization and observational study of AF adults treated with rivaroxaban for ≥ 6 months. The primary endpoint was any of the major adverse cardiac events (MACE), namely, cardiovascular death, non-fatal myocardial infarction, and myocardial revascularization. The area under the curve (AUC) was calculated to evaluate the performance of 2MACE, and a new score, 2MACER to predict MACE. A total of 1433 patients were included (74.2 ± 9.7 years, CHA₂DS₂-VASc 3.5 ± 1.5, 26.9% 2MACE ≥ 3). The annual event rates (follow-up 2.5 years) were 1.07% for MACE, 0.66% for thromboembolic events and 1.04% for major bleeding. Patients with 2MACE ≥ 3 (vs. In clinical practice, AF patients anticoagulated with rivaroxaban exhibit a low risk of events. 2MACE score acts as a modest predictor of a higher risk of adverse outcomes in this population. 2MACER did not significantly increase the ability of 2MACE to predict MACE

Outcomes and predictive value of the 2MACE score in patients with atrial fibrillation treated with rivaroxaban in a prospective, multicenter observational study: The EMIR study

Background: The aim of the study was to evaluate the performance of the 2MACE in patients with atrial fibrillation (AF) treated with rivaroxaban and to improve the accuracy of 2MACE. Methods: This was a post-authorization and observational study of AF adults treated with rivaroxaban for ≥ 6 months. The primary endpoint was any of the major adverse cardiac events (MACE), namely, cardiovascular death, non-fatal myocardial infarction, and myocardial revascularization. The area under the curve (AUC) was calculated to evaluate the performance of 2MACE, and a new score, 2MACER to predict MACE. Results: A total of 1433 patients were included (74.2 ± 9.7 years, CHA2DS2-VASc 3.5 ± 1.5, 26.9% 2MACE ≥ 3). The annual event rates (follow-up 2.5 years) were 1.07% for MACE, 0.66% for thromboembolic events and 1.04% for major bleeding. Patients with 2MACE ≥ 3 (vs. &lt; 3) had higher risk of stroke/systemic embolism/transient ischemic attack (odds ratio [OR] 5.270; 95% CI 2.216–12.532), major bleeding (OR 4.624; 95% CI 2.163–9.882), MACE (OR 3.202; 95% CI 1.548–6.626) and cardiovascular death (OR 3.395; 95% CI 1.396–8.259). 2MACE was recalculated giving 1 more point to patients with baseline a glomerular filtration rate &lt; 50 mL/min/1.73 m2 (2MACER); 2MACER vs. 2MACE: IDI 0.1%, p = 0.126; NRI 23.9%, p = 0.125; AUC: 0.651 (95% CI 0.547–0.755) vs. 0.638 (95% CI 0.534–0.742), respectively; p = 0.361. Conclusions: In clinical practice, AF patients anticoagulated with rivaroxaban exhibit a low risk of events. 2MACE score acts as a modest predictor of a higher risk of adverse outcomes in this population. 2MACER did not significantly increase the ability of 2MACE to predict MACE