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

Prevalence, characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced, mildly reduced, and preserved ejection fraction: An analysis of the ESC Heart Failure Long-Term Registry

AIMS To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]). METHODS AND RESULTS Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23-1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07-1.74) but not AR (adjusted HR 1.13, 95% CI 0.96-1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category. CONCLUSIONS In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category

Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin

Introduction and objectivesMitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies.MethodsProtein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA.ResultsSignificant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group.ConclusionDecreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features

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

Hyponatraemia and changes in natraemia during hospitalization for acute heart failure and associations with in-hospital and long-term outcomes - from the ESC-HFA EORP Heart Failure Long-Term Registry

AIMS: To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes. METHODS AND RESULTS: Of 8298 patients in the European Society of Cardiology Heart Failure Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35-1.89), Yes/No 1.35 (1.14-1.59), and No/Yes 1.18 (0.96-1.45). For death or heart failure hospitalization they were 1.38 (1.21-1.58), 1.17 (1.02-1.33), and 1.09 (0.93-1.27), respectively. CONCLUSION: Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk

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)