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Aims: Patients hospitalized for acute heart failure (HF) could be enrolled in EMPULSE (NCT04157751) upon haemodynamic stabilization and between 24 h and 5 days after hospital admission. The timing of treatment initiation may influence the efficacy and safety of drugs such as empagliflozin. The aim of this study was to evaluate patient characteristics, clinical events, and treatment effects according to time from admission to randomization. Methods and results: The EMPULSE population was dichotomized by median time from hospital admission to randomization (1–2 days vs. 3–5 days). The primary outcome was a hierarchical composite endpoint of time to all‐cause death, number of HF events, time to first HF event, and a ≥5‐point difference in Kansas City Cardiomyopathy Questionnaire total symptom score change from baseline after 90 days, analysed using the win ratio (WR) method. Patients randomized later (3–5 days, average time 3.9 days; n = 312) had a higher risk of experiencing clinical events than patients randomized earlier (1–2 days, average time 1.7 days; n = 215). The treatment effect favoured empagliflozin versus placebo in patients randomized later (3–5 days: WR 1.69, 95% confidence interval [CI] 1.26–2.25) but was attenuated in patients randomized earlier (1–2 days: WR 1.04, 95% CI 0.74–1.44) (interaction p = 0.029). A similar pattern was observed for the composite of HF hospitalization or cardiovascular death and all‐cause hospitalizations (interaction p < 0.1 for both). The reduction of N‐terminal pro‐B‐type natriuretic peptide levels was more pronounced with empagliflozin among patients randomized later than in patients randomized earlier (interaction p = 0.004). Conclusions: Among patients hospitalized for acute HF enrolled in EMPULSE, those randomized later after hospital admission (3–5 days) experienced greater clinical benefit with empagliflozin than those randomized earlier (1–2 days). These findings should be confirmed in future studies before clinical application. [ABSTRACT FROM AUTHOR]

Aim: The EMPULSE (EMPagliflozin in patients hospitalised with acUte heart faiLure who have been StabilizEd) trial showed that, compared to placebo, the sodium–glucose cotransporter 2 inhibitor empagliflozin (10 mg/day) improved clinical outcomes of patients hospitalized for acute heart failure (HF). We investigated whether efficacy and safety of empagliflozin were consistent across the spectrum of left ventricular ejection fraction (LVEF). Methods and results: A total of 530 patients hospitalized for acute de novo or decompensated HF were included irrespective of LVEF. For the present analysis, patients were classified as HF with reduced (HFrEF, LVEF ≤40%), mildly reduced (HFmrEF, LVEF 41–49%) or preserved (HFpEF, LVEF ≥50%) ejection fraction at baseline. The primary endpoint was a hierarchical outcome of death, worsening HF events (HFE) and quality of life over 90 days, assessed by the win ratio. Secondary endpoints included individual components of the primary endpoint and safety. Out of 523 patients with baseline data, 354 (67.7%) had HFrEF, 54 (10.3%) had HFmrEF and 115 (22.0%) had HFpEF. The clinical benefit (hierarchical composite of all‐cause death, HFE and Kansas City Cardiomyopathy Questionnaire total symptom score) of empagliflozin at 90 days compared to placebo was consistent across LVEF categories (≤40%: win ratio 1.35 [95% confidence interval 1.04, 1.75]; 41–49%: win ratio 1.25 [0.66, 2.37)] and ≥50%: win ratio 1.40 [0.87, 2.23], pinteraction = 0.96) with a favourable safety profile. Results were consistent across individual components of the hierarchical primary endpoint. Conclusion: The clinical benefit of empagliflozin proved consistent across LVEF categories in the EMPULSE trial. These results support early in‐hospital initiation of empagliflozin regardless of LVEF. [ABSTRACT FROM AUTHOR]

Aim: Acute heart failure can be a life‐threatening medical condition. Delaying administration of intravenous furosemide (time‐to‐diuretics) has been postulated to increase mortality, but prior reports have been inconclusive. We aimed to evaluate the association between time‐to‐diuretics and mortality in the international REPORT‐HF registry. Methods and results: We assessed the association of time‐to‐diuretics within the first 24 h with in‐hospital and 30‐day post‐discharge mortality in 15 078 patients from seven world regions in the REPORT‐HF registry. We further tested for effect modification by baseline mortality risk (ADHERE risk score), left ventricular ejection fraction (LVEF) and region. The median time‐to‐diuretics was 67 (25th–75th percentiles 17–190) min. Women, patients with more signs and symptoms of heart failure, and patients from Eastern Europe or Southeast Asia had shorter time‐to‐diuretics. There was no significant association between time‐to‐diuretics and in‐hospital mortality (p > 0.1). The 30‐day mortality risk increased linearly with longer time‐to‐diuretics (administered between hospital arrival and 8 h post‐hospital arrival) (p = 0.016). This increase was more significant in patients with a higher ADHERE risk score (pinteraction = 0.008), and not modified by LVEF or geographic region (pinteraction > 0.1 for both). Conclusion: In REPORT‐HF, longer time‐to‐diuretics was not associated with higher in‐hospital mortality. However, we did found an association with increased 30‐day mortality, particularly in high‐risk patients, and irrespective of LVEF or geographic region. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT02595814. [ABSTRACT FROM AUTHOR]

Aim: The sodium–glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improved clinical outcomes in patients hospitalized for acute heart failure. In patients with chronic heart failure, SGLT2 inhibitors cause an early decline in estimated glomerular filtration rate (eGFR) followed by a slower eGFR decline over time than placebo. However, the effects of SGLT2 inhibitors on renal function during a hospital admission for acute heart failure remain largely unknown. Methods and results: Between 1 and 5 days after a hospitalization for acute heart failure, 530 patients with an eGFR >20 ml/min/1.73 m2 were randomized to 10 mg of empagliflozin or placebo and treated for 90 days. Renal function and electrolytes were measured at baseline, and after 15, 30 and 90 days. We evaluated the effect of empagliflozin on eGFR over time and the impact of baseline eGFR on the primary hierarchical outcome of death, worsening heart failure events and quality of life. Mean baseline eGFR was 52.4 ml/min/1.73 m2 in the empagliflozin group and 55.7 ml/min/1.73 m2 in the placebo group. Empagliflozin caused an initial decline in eGFR (−2 ml/min/1.73 m2 at day 15 compared to placebo). At day 90, eGFR was similar between empagliflozin and placebo. Investigator‐reported acute renal failure occurred in 7.7% of empagliflozin versus 12.1% of placebo patients. The overall clinical benefit (hierarchical composite of all‐cause death, heart failure events and quality of life) of empagliflozin was unaffected by baseline eGFR. Conclusion: In patients hospitalized for acute heart failure, empagliflozin caused an early modest decline in renal function which was no longer evident after 90 days. Acute renal events were similar in both groups. The clinical benefit of empagliflozin was consistent regardless of baseline renal function. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) leads to repeat hospitalisations and reduces the duration and quality of life. Pulmonary artery pressure (PAP)-guided HF management using the CardioMEMS™ HF system was shown to be safe and reduce HF hospitalisation (HFH) rates in New York Heart Association (NYHA) class III patients. However, these findings have not been replicated in health systems outside the United States. Therefore, the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) evaluated the safety, feasibility, and performance of this device in Germany, The Netherlands, and Ireland.Methods and Results: A total of 234 NYHA class III patients (68 ± 11 years, 22% female, ≥1 HFH in the preceding year) from 31 centres were implanted with a CardioMEMS sensor and underwent PAP-guided HF management. One-year rates of freedom from device- or system-related complications and from sensor failure (co-primary outcomes) were 98.3% [95% confidence interval (CI) 95.8-100.0] and 99.6% (95% CI 97.6-100.0), respectively. Survival rate was 86.2%. For the 12 months post- vs. pre-implant, HFHs decreased by 62% (0.60 vs. 1.55 events/patient-year; hazard ratio 0.38, 95% CI 0.31-0.48; P < 0.0001). After 12 months, mean PAP decreased by 5.1 ± 7.4 mmHg, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall/clinical summary scores increased from 47.0 ± 24.0/51.2 ± 24.8 to 60.5 ± 24.3/62.4 ± 24.1 (P < 0.0001), and the 9-item Patient Health Questionnaire sum score improved from 8.7 ± 5.9 to 6.3 ± 5.1 (P < 0.0001).Conclusion: Haemodynamic-guided HF management proved feasible and safe in the health systems of Germany, The Netherlands, and Ireland. Physician-directed treatment modifications based on remotely obtained PAP values were associated with fewer HFH, sustainable PAP decreases, marked KCCQ improvements, and remission of depressive symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Background: Depression and chronic heart failure (CHF) are common conditions, both of which are clinically and economically highly relevant. Major depression affects 20–40% of CHF patients and predicts adverse outcomes in terms of quality of life, morbidity and mortality as well as health care expenditure, independent of other factors of prognostic relevance. Aims: The purpose of the MOOD-HF trial is to clarify whether antidepressant pharmacotherapy improves outcome in CHF patients, and if so by which mechanism(s). Methods: MOOD-HF is a prospective, randomised, double-blind, placebo-controlled, 2-armed, parallel-group multicenter trial investigating the effects of the serotonin re-uptake inhibitor (SSRI) escitalopram on morbidity and mortality (primary endpoint), severity of depression, anxiety, cognitive function, quality of life and health care expenditure in 700 patients with symptomatic systolic CHF and major depression diagnosed by structured clinical interview. All patients will receive optimised pharmacotherapy for CHF. Duration of follow-up, including close safety monitoring, is 12–24 months from randomisation. Perspective: MOOD-HF is the first prospective randomised controlled trial to assess the effects of antidepressant pharmacotherapy on hard somatic endpoints, the mechanism(s) of action of SSRI treatment, as well as safety in New York Heart Association functional class II-IV CHF patients. The results are expected to promote the development of evidence-based recommendations for managing depression in the context of CHF. Trial registration: ISRCTN.org. Identifier: ISRCTN33128015 [Copyright &y& Elsevier]

Aims: Evidence for a pathophysiologic relevance of autoimmunity in human heart disease has substantially increased over the past years. Conformational autoantibodies stimulating the cardiac beta1-adrenoceptor (beta1-aabs) are considered of importance in heart failure development and clinical pilot studies have shown their prognostic significance in human 'idiopathic' cardiomyopathy., Methods: We recently developed a novel highly sensitive fluorescence-based functional assay to detect stimulating beta1-aabs. We will use this method to assess Etiology, Titre-Course, and effect on Survival (ETiCS) of beta1-aabs in a prospective multicentre study with serial follow-up of patients after a first acute myocarditis or myocardial infarction. Several European core laboratories will jointly study the hypothesis that both disorders may trigger autoimmune reactions leading to the generation of beta1-aabs and/or other heart-directed aabs. Further, sera from healthy controls and well-characterized patient cohorts with dilated, ischaemic, or hypertensive cardiomyopathy will be analysed retrospectively for beta1-aab prevalence, incidence, persistence, and/or clearance., Conclusion: ETiCS is so far the largest clinical diagnostic study projected to address cardiac autoimmunity. It attempts to unravel the pathophysiology of cardiac autoantibody formation and persistence/clearance. ETiCS will enhance current knowledge on autoimmunity in human heart disease and promote endeavours to develop novel therapies targeting cardiac aabs.