No abstract

Background ST ‐segment–elevation myocardial infarction is associated with an intense acute inflammatory response and risk of heart failure. We tested whether interleukin‐1 blockade with anakinra significantly reduced the area under the curve for hsCRP (high sensitivity C‐reactive protein) levels during the first 14 days in patients with ST ‐segment–elevation myocardial infarction (VCUART3 [Virginia Commonwealth University Anakinra Remodeling Trial 3]). Methods and Results We conducted a randomized, placebo‐controlled, double‐blind, clinical trial in 99 patients with ST ‐segment–elevation myocardial infarction in which patients were assigned to 2 weeks treatment with anakinra once daily (N=33), anakinra twice daily (N=31), or placebo (N=35). hsCRP area under the curve was significantly lower in patients receiving anakinra versus placebo (median, 67 [interquartile range, 39–120] versus 214 [interquartile range, 131–394] mg·day/L; P <0.001), without significant differences between the anakinra arms. No significant differences were found between anakinra and placebo groups in the interval changes in left ventricular end‐systolic volume (median, 1.4 [interquartile range, −9.8 to 9.8] versus −3.9 [interquartile range, −15.4 to 1.4] mL; P =0.21) or left ventricular ejection fraction (median, 3.9% [interquartile range, −1.6% to 10.2%] versus 2.7% [interquartile range, −1.8% to 9.3%]; P =0.61) at 12 months. The incidence of death or new‐onset heart failure or of death and hospitalization for heart failure was significantly lower with anakinra versus placebo (9.4% versus 25.7% [ P =0.046] and 0% versus 11.4% [ P =0.011], respectively), without difference between the anakinra arms. The incidence of serious infection was not different between anakinra and placebo groups (14% versus 14%; P =0.98). Injection site reactions occurred more frequently in patients receiving anakinra (22%) versus placebo (3%; P =0.016). Conclusions In patients presenting with ST ‐segment–elevation myocardial infarction, interleukin‐1 blockade with anakinra significantly reduces the systemic inflammatory response compared with placebo. Clinical Trial Registration URL : https://www.clinicaltrials.gov/ . Unique identifier: NCT 01950299.

No abstract

Background Canagliflozin reduces hospitalizations for heart failure (HF) in type 2 diabetes mellitus (T2DM). Its effect on cardiorespiratory fitness and cardiac function in patients with established HF with reduced ejection fraction (HFrEF) is unknown. Methods We conducted a double‐blind randomized controlled trial of canagliflozin 100 mg or sitagliptin 100 mg daily for 12 weeks in 88 patients, and measured peak oxygen consumption (VO2) and minute ventilation/carbon dioxide production (VE/VCO2) slope (co‐primary endpoints for repeated measure ANOVA time_x_group interaction), lean peak VO2, ventilatory anaerobic threshold (VAT), cardiac function and quality of life (ie, Minnesota Living with Heart Failure Questionnaire [MLHFQ]), at baseline and 12‐week follow‐up. Results The study was terminated early due to the new guidelines recommending canagliflozin over sitagliptin in HF: 17 patients were assigned to canagliflozin and 19 to sitagliptin, total of 36 patients. There were no significant changes in peak VO2 and VE/VCO2 slope between the two groups (P = .083 and P = .98, respectively). Canagliflozin improved lean peak VO2 (+2.4 mL kgLM−1 min−1, P = .036), VAT (+1.5 mL kg−1 min−1, P = .012) and VO2 matched for respiratory exchange ratio (+2.4 mL Kg−1 min−1, P = .002) compared to sitagliptin. Canagliflozin also reduced MLHFQ score (−12.1, P = .018). Conclusions In this small and short‐term study of patients with T2DM and HFrEF, interrupted early after only 36 patients, canagliflozin did not improve the primary endpoints of peak VO2 or VE/VCO2 slope compared to sitagliptin, while showing favourable trends observed on several additional surrogate endpoints such as lean peak VO2, VAT and quality of life.

The effects of empagliflozin on cardiorespiratory fitness in patients with type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) are unknown. In this pilot study we determined the effects of empagliflozin 10 mg/d for 4 weeks on peak oxygen consumption (VO ) in 15 patients with T2DM and HFrEF. As an exploratory analysis, we assessed whether there was an interaction of the effects of empagliflozin on peak VO of loop diuretics. Empagliflozin reduced body weight (-1.7 kg; P = .031), but did not change peak VO (from 14.5 mL kg min [12.6-17.8] to 15.8 [12.5-17.4] mL kg min ; P = .95). However, patients using loop diuretics (N = 9) demonstrated an improvement, whereas those without loop diuretics (N = 6) experienced a decrease in peak VO (+0.9 [0.1-1.4] vs -0.9 [-2.1 to -0.3] mL kg min ; P = .001), and peak VO changes correlated with the baseline daily dose of diuretics (R = +0.83; P < .001). Empagliflozin did not improve peak VO in patients with T2DM and HFrEF. However, as a result of exploratory analysis, patients concomitantly treated with loop diuretics experienced a significant improvement in peak VO .

No abstract

Background: Sarcopenia is a prevalent condition in elderly patients and has been associated with adverse outcomes following transcatheter aortic valve replacement (TAVR). The present study aimed to determine the predictive value of serum creatinine-cystatin C ratio, that is, "Sarcopenia Index" (SI) as a surrogate marker of sarcopenia, and investigate its association with clinical outcomes after TAVR. Methods:We conducted a retrospective observational study of patients undergoing TAVR between January, 2016 and December, 2018 at Hospital Italiano de Buenos Aires, Argentina. Patients were excluded if <65-years old, presented previous surgical aortic valve replacement, severe chronic kidney disease, or hemodialysis requirement.The SI was obtained at baseline before TAVR. All-cause mortality and/or readmissions for congestive heart failure (CHF) were defined as the primary endpoint.Results: In total 100 patients met inclusion criteria for the purpose of the study. Sarcopenia Index was significantly correlated with Timed Up and Go (r = À0.272, p = .010) and Gait Speed (r = À0.278, p = .005). During follow-up, 5/100 patients died within 30 days and a total of 10/100 patients died at 1-year follow-up. Moreover, survival curves were significantly worse (Log-rank test = p = .02) and CHF readmissions were more prevalent in the lowest SI tertile (Log-rank test = p = .01).In multivariate Cox regression analysis, we identified low SI (cutoff ≤66) as an independent predictor of long-term adverse outcomes (HR = 4.01, 95% CI = 1.31-12.27, p = .015) at 1-year follow-up.Conclusion: Sarcopenia Index, surrogate for the degree of skeletal muscle mass (SMM), could be used as a predictor of adverse outcomes in patients undergoing TAVR.

Interleukin-1 (IL-1) receptor antagonist (anakinra) has been shown to be effective in steroid-dependent recurrent pericarditis resistant to nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine. We sought to evaluate the acute efficacy of anakinra given early in patients with acute pericarditis. We enrolled patients within 24 hours of presentation of a first or recurrent episode of acute pericarditis who were experiencing severe pain (≥6 in 11-point Likert scale), despite treatment with at least one dose of NSAIDs and of colchicine. The primary outcome was pain relief at 24 hours. Subcutaneous anakinra 100 mg was administered in all patients, whereas NSAIDs and colchicine were suspended for 24 hours. Serum levels of interleukin-6 (IL-6) were measured at baseline and 24 hours. Data are reported as median (interquartile range). We treated 5 patients (4 male and 1 female; 38 [31–54] years old). Anakinra significantly reduced pain from 6.0 (6.0–7.5) to 4.0 (2.5–4.0) at 6 hours (P = 0.012 vs. baseline) and to 2.0 (1.5–2.5) at 24 hours (P = 0.0025 vs. baseline). No patients required rescue pain medication. IL-6 levels were also significantly reduced from 95.3 (24.2–155.1) to 23.9 (4.5–71.9) pg/mL at 24 hours (P = 0.037). The reduction in pain intensity paralleled the reduction in IL-6 serum levels (R = +0.966, P = 0.007). No adverse events related to treatment occurred. The administration of anakinra given early in acute pericarditis treatment course rapidly and significantly improved chest pain from acute pericarditis. The improvement is correlated with a reduction in IL-6 levels.