Patients with chronic heart failure (CHF) have metabolic abnormalities, leading to a catabolic syndrome, with progressive loss of skeletal muscle in advanced stages of the disease. Leptin, the product of an obesity gene, has been associated with energy expenditure and weight regulation. The aim of this study was to assess serum levels of leptin and its soluble receptor in relation to exercise intolerance and neurohumoral activation in patients with CHF. We investigated 53 patients with CHF left ventricular ejection fraction (LVEF) 25"1%, age 56.6"1.3 years, Maximal oxygen uptake (VO max) 16.3"0.6 mlyminØkg) sub-classified 2 according to peak oxygen consumption of ) or (14 mlyminØkg and 11 age-matched controls (LVEF 70"1, age 60.5"4.0 years, (VO max) 26.9"1.6 mlyminØkg). Body mass index-adjusted serum levels of leptin and soluble leptin receptor were 2 increased in patients with CHF compared to the controls (0.28"0.03 vs. 0.22"0.04 ngØm ymlØkg and 32.6"1.9 ngyml vs. correlated with an increased serum concentration of TNFa (rs0.749, P-0.01) in this subgroup of patients with CHF. We conclude that patients with advanced CHF show elevated serum levels of leptin and its soluble receptor. This finding indicates that leptin may participate in the catabolic state leading to the development of cardiac cachexia in the course of CHF.

BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Background: Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear. Methods: In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Results: Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L [95% CI, 8.4 to 3.6]; P =0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6–27.7]; P =0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51±19 versus 54±17 mL/min per 1.73 m²; P =0.599) or injury (total urinary protein, 492±845 versus 503±847 mg/g creatinine; P =0.975; and urinary α1-microglobulin, 55.4±38.6 versus 31.3±33.6 mg/g creatinine; P =0.066) with more pronounced decrease in NT-proBNP in the empagliflozin group compared with placebo (−1861 versus −727.2 pg/mL after 5 days; quotient in slope, 0.89 [95% CI, 0.83–0.95]; P <0.001). There were no differences in the incidence of safety events between groups. Conclusions: Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04049045.

New cerebral embolic events occur after transcatheter closure of the left atrial appendage. However, most of the lesions demonstrate no gliotic transformation at follow-up. In all patients, the cerebral lesions were clinically unapparent.

Background: Patients at high-bleeding risk (HBR) undergoing percutaneous coronary intervention represent a challenging patient population. The use of drug-coated balloon (DCB) allows shorter duration of dual antiplatelet therapy compared with drug-eluting stents (DES) and reduces thrombotic risk due to the absence of a permanent implant. The present analysis aimed to investigate if the effect of DCB versus DES differed between patients with and without HBR treated with percutaneous coronary intervention in small coronary arteries. Methods: This prespecified subgroup analysis of a multicenter, randomized, noninferiority trial included 758 patients with de novo lesions in coronary vessels <3 mm and an indication for percutaneous coronary intervention, randomized to DCB (n=382) or second-generation DES (n=376). Patients were followed over 3 years for major adverse cardiac events. Results: Of the 758 patients randomized, 155 (20%) had HBR; these patients had higher mortality at 3 years (hazard ratio [95% CI], 3.09 [1.78–5.36]; P <0.001). Rates of major bleeding events were overall low but tended to be lower after DCB versus DES (1.6% versus 3.7%; P =0.064), were similar in patients with HBR (4.5% versus 3.4%) but less frequent in DCB-versus DES-treated patients without HBR (0.9% versus 3.8%). There was no difference in major adverse cardiac events between DCB and DES regardless of bleeding risk (HBR, hazard ratio: 1.16 [0.51–2.62]; P =0.719 versus non-HBR, 0.96 [0.62–1.49]; P =0.863). Conclusions: DCBs were similarly safe and effective as current-generation DES in the treatment of coronary arteries <3 mm, regardless of bleeding risk. In patients treated with DCB, there was a trend towards a reduction of severe bleeding events at 3 years. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01574534.