In-hospital heart rate reduction and its relation to outcomes of heart failure patients with sinus rhythm: Results from the Polish part of the European Society of Cardiology Heart Failure Pilot and Long-Term Registries

Background: Currently, there is no information on whether in-hospital heart rate (HR) reduction has an influence on risk of death or rehospitalization. The study evaluates the relation between inhospital HR reduction in heart failure (HF) patients on mortality and rehospitalization within 1-year observation. Methods: The analysis included patients hospitalized in Poland with sinus rhythm from the European Society of Cardiology Heart Failure Pilot (ESC-HF-Pilot) and ESC Heart Failure Long-Term Registries (ESC-HF-LT), who were divided into two groups: reduced HR and not-reduced HR. HR reduction was defined as a reduced value of HR at discharge compared to admission HR. The primary endpoint was 1-year all-cause death, the secondary endpoint was 1-year all-cause death or rehospitalization for worsening HF. Results: The final analysis included 747 patients; 491 reduced HR (65.7%) and 256 not-reduced HR (34.3%). The primary endpoint occurred in 58/476 (12.2%) from reduced HR group and in 26/246 (10.5%) from not-reduced HR group (p = 0.54). In the reduced HR group, independent predictors of primary endpoint were age, New York Heart Association class at admission, serum sodium level at admission and systolic blood pressure at discharge. In the not-reduced HR group the independent predictor of primary endpoint was diastolic blood pressure at discharge. The secondary endpoint was observed in 180 patients, 124/398 (31.2%) from reduced HR and 56/207 (27.1%) from the not-reduced HR group (p = 0.30). In the not-reduced HR group only angiotensin converting-enzyme inhibitor usage at discharge was independently associated with lower risk of the secondary endpoint. Conclusions: In-hospital HR reduction did not influence on the outcomes of HF patients in sinus rhythm

Efficacy and safety of intermittent intravenous outpatient administration of levosimendan in patients with advanced heart failure: the LION-HEART multicentre randomised trial

Aims. The LION‐HEART study was a multicentre, double‐blind, randomised, parallel‐group, placebo‐controlled trial evaluating the efficacy and safety of intravenous administration of intermittent doses of levosimendan in outpatients with advanced chronic heart failure. Methods and results. Sixty‐nine patients from 12 centres were randomly assigned at a 2:1 ratio to levosimendan or placebo groups, receiving treatment by a 6‐hour intravenous infusion (0.2 μg/kg/min without bolus) every 2 weeks for 12 weeks. The primary endpoint was the effect on serum concentrations of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) throughout the treatment period in comparison with placebo. Secondary endpoints included evaluation of safety, clinical events and health‐related quality of life (HRQoL). The area under the curve (AUC, pg.day/mL) of the levels of NT‐proBNP over time for patients who received levosimendan was significantly lower than for the placebo group (344 × 103 [95% Confidence Interval (CI) 283 × 103−404 × 103] vs. 535 × 103 [443 × 103−626 × 103], p = 0.003). In comparison with the placebo group, the patients on levosimendan experienced a reduction in the rate of heart failure hospitalisation (hazard ratio 0.25; 95% CI 0.11-0.56; P = 0.001). Patients on levosimendan were less likely to experience a clinically significant decline in HRQoL over time (P = 0.022). Adverse event rates were similar in the two treatment groups. Conclusions. In this small pilot study, intermittent administration of levosimendan to ambulatory patients with advanced systolic heart failure reduced plasma concentrations of NT‐proBNP, worsening of HRQoL and hospitalisation for heart failure. The efficacy and safety of this intervention should be confirmed in larger trials

Prognostic value of discharge heart rate in acute heart failure patients: More relevant in atrial fibrillation?

Aims: The prognostic impact of heart rate (HR) in acute heart failure (AHF) patients is not well known especially in atrial fibrillation (AF) patients. The aim of the study was to evaluate the impact of admission HR, discharge HR, HR difference (admission-discharge) in AHF patients with sinus rhythm (SR) or AF on long- term outcomes. Methods: We included 1398 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentre, prospective registry. Logistic regression models were used to estimate the association between admission HR, discharge HR and HR difference and one- year all-cause mortality and HF readmission. Results: The mean age of the study population was 72+/-12years. Of these, 594 (42.4%) were female, 655 (77.8%) were hypertensive and 655 (46.8%) had diabetes. Among all included patients, 745 (53.2%) had sinus rhythm and 653 (46.7%) had atrial fibrillation. Only discharge HR was associated with one year all-cause mortality (Relative risk (RR)=1.182, confidence interval (CI) 95% 1.024-1.366, p=0.022) in SR. In AF patients discharge HR was associated with one year all cause mortality (RR=1.276, CI 95% 1.115-1.459, p</=0.001). We did not observe a prognostic effect of admission HR or HRD on long-term outcomes in both groups. This relationship is not dependent on left ventricular ejection fraction. Conclusions: In AHF patients lower discharge HR, neither the admission nor the difference, is associated with better long-term outcomes especially in AF patients

Heart rate control and its predictors in patients with heart failure and sinus rhythm. Data from the European Society of Cardiology Long-Term Registry

Background: Higher resting heart rate (HR) in patients with heart failure (HF) and sinus rhythm (SR) is associated with increased mortality. In patients hospitalized for HF, the aim herein, was to assess the use and dosage of guideline-recommended HR lowering medications, HR control at discharge and predictors of HR control. Methods: In the present study, were Polish participants of the European Society of Cardiology HF Long-Term (ESC-HF-LT) Registry. Those selected were hospitalized for HF,  with reduced ejection fraction (HFrEF) and SR at discharge (n = 236). The patients were divided in two groups ( &lt; 70 and ≥ 70 bpm). Logistic regression was used to identify the predictors of HR ≥ 70 bpm. Results: Of patients with HFrEF and SR, 59% had HR ≥ 70 bpm at hospital discharge. At discharge, 96% and only 0.5% of the patients with HFrEF and SR received beta-blocker and ivabradine, respectively. In the HF groups &lt; 70 and ≥ 70 bpm, only 11% and 4% of patients received beta-blocker target doses, respectively. There was no difference in the use of other guideline-recommended medications. Age, New York Heart Association class, HR on admission and lack of HR lowering medications were predictors of discharge HR ≥ 70 bpm. Conclusions: Heart rate control after hospitalization for HFrEF is unsatisfactory, which may be attributed to suboptimal doses of beta-blockers, and negligence in use other HR lowering drugs (including ivabradine)

Heart failure patients with a previous coronary revascularisation: results from the ESC-HF registry

Background: Coronary revascularization is common in heart failure (HF). Aims: Clinical characteristic and assessment of in-hospital and long-term outcomes in patients hospitalized for HF with or without a previous percutaneous coronary intervention (PCI) or a coronary artery bypass grafting (CABG). Methods: The primary endpoint (PE) (all-cause death) and the secondary endpoint (SE) (all-cause death or hospitalization for HF-worsening) were assessed at one-year in 649 inpatients of the ESC-HF Pilot Survey. Additionally, occurrence of death during index hospitalization was evaluated. Results: PCI/CABG-patients (32.7%) were more frequently male, smokers, had myocardial infarction, hypertension (HT), peripheral artery disease and diabetes. The non-PCI/CABG-patients more often had a cardiogenic shock and died in-hospital. The PE occurred in 33 of the 212 PCI/CABG-patients (15.6%) and in 56 of the 437 non-PCI/CABG-patients (12.8%; P=0.3). The SE occurred in 82 of the 170 PCI/CABG-patients (48.2%) and in 122 of the 346 non-PCI/CABG-patients (35.3%; P=0.01). Independent predictors of the PE in the PCI/CABG-patients were: lower left ventricular ejection fraction, use of antiplatelets; in the non-PCI/CABG-patients were: age, ACS at admission. Independent predictors of the SE in the PCI/CABG-patients were: diabetes, NYHA (New York Heart Association) class at admission, HT; in the non-PCI/CABG-patients were: NYHA class, haemoglobin at admission. Serum sodium concentration at admission was a predictor of the PE and the SE in both groups. Heart rate at discharge was a predictor of the PE and the SE in the non-PCI/CABG patients. Conclusions: The revascularized HF patients had a similar mortality and higher risk of death or hospitalizations at 12 months compared with the non-PCI/CABG-patients. The revascularized patients had more comorbidities, while the non-PCI/CABG-patients had a higher incidence of cardiogenic shock and in-hospital mortality.Background: Coronary revascularisation is common in heart failure (HF). Aim: Clinical characteristic and assessment of in-hospital and long-term outcomes in patients hospitalised for HF with or without a previous percutaneous coronary intervention (PCI) or a coronary artery bypass grafting (CABG). Methods: The primary endpoint (PE) (all-cause death) and the secondary endpoint (SE) (all-cause death or hospitalisation for HF-worsening) were assessed at one year in 649 inpatients of the ESC-HF Pilot Survey. Additionally, occurrence of death during index hospitalisation was evaluated. Results: PCI/CABG-patients (32.7%) were more frequently male, smokers, and had myocardial infarction, hypertension, pe¬ripheral artery disease, and diabetes. The non-PCI/CABG-patients more often had cardiogenic shock and died in-hospital. The PE occurred in 33 of the 212 PCI/CABG-patients (15.6%) and in 56 of the 437 non-PCI/CABG-patients (12.8%; p = 0.3). The SE occurred in 82 of the 170 PCI/CABG-patients (48.2%) and in 122 of the 346 non-PCI/CABG-patients (35.3%; p = 0.01). Independent predictors of the PE in the PCI/CABG-patients were: lower left ventricular ejection fraction and use of anti¬platelets; in the non-PCI/CABG-patients were: age and acute coronary syndrome at admission. Independent predictors of SE in the PCI/CABG-patients were: diabetes, New York Heart Association (NYHA) class at admission, and hypertension; in the non-PCI/CABG-patients they were: NYHA class and haemoglobin at admission. Serum sodium concentration at admission was a predictor of PE and SE in both groups. Heart rate at discharge was a predictor of PE and SE in the non-PCI/CABG patients. Conclusions: The revascularised HF patients had a similar mortality and higher risk of death or hospitalisation at 12 months compared with the non-PCI/CABG-patients. The revascularised patients had more comorbidities, while the non-PCI/CABG-patients had a higher incidence of cardiogenic shock and in-hospital mortality

Specialized proresolving mediators protect against experimental autoimmune myocarditis by modulating Ca2+ handling and NRF2 activation

Specialized proresolving mediators and, in particular, 5(S), (6)R, 7-trihydroxyheptanoic acid methyl ester (BML-111) emerge as new therapeutic tools to prevent cardiac dysfunction and deleterious cardiac damage associated with myocarditis progression. The cardioprotective role of BML-111 is mainly caused by the prevention of increased oxidative stress and nuclear factor erythroid-derived 2-like 2 (NRF2) down-regulation induced by myocarditis. At the molecular level, BML-111 activates NRF2 signaling, which prevents sarcoplasmic reticulum–adenosine triphosphatase 2A down-regulation and Ca2+ mishandling, and attenuates the cardiac dysfunction and tissue damage induced by myocarditis.This work was supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (SAF-2017-84777R), Instituto de Salud Carlos III (ISCIII) (PI17/01093, PI17/01344, and PI20/01482), Sociedad Española de Cardiología, Proyecto Traslacional 2019 and Asociación del Ritmo Cardiaco (SEC, España), Proyecto Asociación Insuficiencia Cardiaca (Trasplante Cardiaco) 2020, Fondo Europeo de Desarrollo Regional, Fondo Social Europeo, and CIBERCV, a network funded by ISCIII, Spanish Ministry of Science, Innovation and Universities (PGC2018-097019-B-I00), Ministerio de Economía, Industria y Competitividad/Agencia Estatal de Investigación 10.13039/501100011033 PID2020-113238RB-I00, PID2019-105600RB-I00, the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria grant PRB3 [PT17/0019/0003-ISCIII-SGEFI/ERDF, ProteoRed]), and “la Caixa” Foundation (project code HR17-00247). The Centro Nacional de Investigaciones Cardiovasculares is supported by the ISCIII, the Ministerio de Ciencia, Innovación y Universidades. Dr Ruiz-Hurtado is Miguel Servet I researcher of ISCIII (CP15/00129 Carlos III Health Institute). Dr Tamayo and R.I. Jaén, and M. Gil-Fernández were or currently are PhD students funded by the Formación de Profesorado Universitario program of the Spanish Ministry of Science, Innovation and Universities (FPU17/06135; FPU16/00827, FPU1901973)

Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants

BACKGROUND: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. METHODS: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. RESULTS: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P&lt;0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF &gt;35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P&lt;0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. CONCLUSIONS: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.</p

Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants

BACKGROUND: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. METHODS: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and males and females compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. RESULTS: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 male; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between males and females (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 males and 3 females; log-rank P35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P<0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. CONCLUSIONS: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF

A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure. (C) 2019 The Authors. Published by Elsevier B.V.Peer reviewe

Effects of serelaxin in patients with acute heart failure

Background: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. Methods: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. Results: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. Conclusions: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778. opens in new tab.