Heart Failure Long-Term Registry Research Articles

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.

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]). 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. 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.

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.

To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes. Of 8,298 patients in the ESC-HF 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 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 HF hospitalization they were 1.38 (1.21-1.58), 1.17 (1.02-1.33), and 1.09 (0.93-1.27), respectively. Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced HF 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. This article is protected by copyright. All rights reserved.

Comprehensive characterization of non-cardiac comorbidities in acute heart failure: an analysis of ESC-HFA EURObservational Research Programme Heart Failure Long-Term Registry.

To evaluate the prevalence and associations of non-cardiac comorbidities (NCCs) with in-hospital and post-discharge outcomes in acute heart failure (AHF) across the ejection fraction (EF) spectrum. The 9326 AHF patients from European Society of Cardiology (ESC)-Heart Failure Association (HFA)-EURObservational Research Programme Heart Failure Long-Term Registry had complete information for the following 12 NCCs: anaemia, chronic obstructive pulmonary disease (COPD), diabetes, depression, hepatic dysfunction, renal dysfunction, malignancy, Parkinson's disease, peripheral vascular disease (PVD), rheumatoid arthritis, sleep apnoea, and stroke/transient ischaemic attack (TIA). Patients were classified by number of NCCs (0, 1, 2, 3, and ≥4). Of the AHF patients, 20.5% had no NCC, 28.5% had 1 NCC, 23.1% had 2 NCC, 15.4% had 3 NCC, and 12.5% had ≥4 NCC. In-hospital and post-discharge mortality increased with number of NCCs from 3.0% and 18.5% for 1 NCC to 12.5% and 36% for ≥4 NCCs.Anaemia, COPD, PVD, sleep apnoea, rheumatoid arthritis, stroke/TIA, Parkinson, and depression were more prevalent in HF with preserved EF (HFpEF). The hazard ratio (95% confidence interval) for post-discharge death for each NCC was for anaemia 1.6 (1.4-1.8), diabetes 1.2 (1.1-1.4), kidney dysfunction 1.7 (1.5-1.9), COPD 1.4 (1.2-1.5), PVD 1.2 (1.1-1.4), stroke/TIA 1.3 (1.1-1.5), depression 1.2 (1.0-1.5), hepatic dysfunction 2.1 (1.8-2.5), malignancy 1.5 (1.2-1.8), sleep apnoea 1.2 (0.9-1.7), rheumatoid arthritis 1.5 (1.1-2.1), and Parkinson 1.4 (0.9-2.1). Anaemia, kidney dysfunction, COPD, and diabetes were associated with post-discharge mortality in all EF categories, PVD, stroke/TIA, and depression only in HF with reduced EF, and sleep apnoea and malignancy only in HFpEF. Multiple NCCs conferred poor in-hospital and post-discharge outcomes. Ejection fraction categories had different prevalence and risk profile associated with individual NCCs.

The predictive value of precipitating factors on clinical outcomes in hospitalized patients with decompensated heart failure: insights from the Egyptian cohort in the European Society of Cardiology Heart Failure long-term registry

BackgroundKnowledge of the frequency of precipitating factors for acute heart failure (AHF) is important (either new-onset heart failure [NOHF] or worsening heart failure [WHF]), as this can guide strategies for prevention and treatment. Most data come only from Western Europe and North America; nevertheless, geographic differences do exist. We set out to study the prevalence of precipitating factors of AHF and their connection to patient characteristics and in-hospital and long-term mortality in patients from Egypt hospitalized for decompensated HF. Using the ESC-HF-LT Registry which is a prospective, multicenter, observational study of patients confessed to cardiology centers in the nations of Europe and the Mediterranean, patients presenting with AHF were recruited from 20 centers all over Egypt. Enrolling physicians were requested to report possible precipitants from among several predefined reasons.ResultsWe included 1515 patients (mean age 60 ± 12 years, 69% males). The mean LVEF was 38 ± 11%. Seventy-seven percent of the total population had HFrEF, 9.8% had HFmrEF, and 13.3% had HFpEF. The commonly reported precipitating factors for AHF hospitalization among study population were as follows (in decreasing order of frequency): infection in 30.3% of patients, acute coronary syndrome/myocardial ischemia (ACS/MI) in 26%, anemia in 24.3%, uncontrolled hypertension in 24.2%, atrial fibrillation (AF) in 18.3%, renal dysfunction in 14.6%, and non-compliance in 6.5% of patients. HFpEF patients had significantly higher rates of AF, uncontrolled hypertension, and anemia as precipitants for acute decompensation. ACS/MI were significantly more frequent in patients with HFmrEF. WHF patients had significantly higher rates of infection and non-compliance, whereas new-onset HF patients showed significantly higher rates of ACS/MI and uncontrolled hypertension. One-year follow-up revealed that patients with HFrEF had a significantly higher rate of mortality compared to patients with HFmrEF and HFpEF (28.3%, 19.5, and 19.4%, P = 0.004). Patients with WHF had a significantly higher rates of 1-year mortality when compared to those with NOHF (30.0% vs. 20.3%, P < 0.001). Renal dysfunction, anemia, and infection were independently connected to worse long-term survival.ConclusionsPrecipitating factors of AHF are frequent and substantially influence outcomes after hospitalization. They should be considered goals for avoiding AHF hospitalization and depicting those at highest risk for short-term mortality.

Participation in a clinical trial is associated with lower mortality but not lower risk of HF hospitalization in patients with heart failure: observations from the ESC EORP Heart Failure Long-Term Registry.

Abstract

Prevalence of obesity and its association with cardiometabolic risk factors, heart failure phenotype and mortality among patients hospitalized for heart failure in Egypt

BackgroundObesity is an established risk factor for cardiometabolic disease and heart failure (HF). Nevertheless, the relationship between obesity and HF mortality remains controversial.ResultsThe goal of this study was to describe the prevalence of obesity in patients hospitalized for HF in Egypt and investigate the relationship of obesity to cardiometabolic risk factors, HF phenotype and mortality. Between 2011 and 2014, 1661 patients hospitalized for HF across Egypt were enrolled as part of the European Society of Cardiology HF Long-term Registry. Obese patients, defined by a BMI ≥ 30 kg/m2, were compared to non-obese patients. Factors associated with mortality on univariate analysis were entered into a logistic regression model to identify whether obesity was an independent predictor of mortality during hospitalization and at one-year follow-up. The prevalence of obesity was 46.5% and was higher in females compared to males. Obese as compared to non-obese patients had a higher prevalence of diabetes mellitus (47.0% vs 40.2%, p = 0.031), hypertension (51.3% vs 33.0%, p < 0.001) and history of myocardial infarction (69.2% vs 62.8% p = 0.005). Obese patients as compared to non-obese patient were more likely to have acute coronary syndrome on admission (24.8% vs 14.2%, p < < 0.001). The dominant HF phenotype in obese and non-obese patients was HF with reduced ejection fraction (EF); however, obese patients as compared to non-obese patient had higher prevalence of HF with preserved EF (22.3% vs 12.4%, p < 0.001). Multivariable analysis demonstrated that obesity was associated with an independent survival benefit during hospitalization, (OR for mortality 0.52 [95% CI 0.29–0.92]). Every point increase in BMI was associated with an OR = 0.93 [95% CI 0.89–0.98] for mortality during hospitalization. The survival benefit was not maintained at one-year follow-up.ConclusionsObesity was highly prevalent among the study cohort and was associated with higher prevalence of cardiometabolic risk factors as compared to non-obese patients. Obesity was associated with an independent “protective effect” from in-hospital mortality but was not a predictor of mortality at 1-year follow-up.

Serum uric acid and outcomes in patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes: Analysis of the ESC-EORP Heart Failure Long-Term (HF LT) Registry

BackgroundRetrospective analyses of clinical trials indicate that elevated serum uric acid (sUA) predicts poor outcome in heart failure (HF). Uric acid can contribute to inflammation and microvascular dysfunction, which may differently affect different left ventricular ejection fraction (LVEF) phenotypes. However, role of sUA across LVEF phenotypes is unknown. ObjectivesWe investigated sUA association with outcome in a prospective cohort of HF patients stratified according to LVEF. MethodsThrough the Heart Failure Long-Term Registry of the European Society of Cardiology (ESC-EORP-HF-LT), 4,438 outpatients were identified and classified into: reduced (<40% HFrEF), mid-range (40–49% HFmrEF), and preserved (≥50% HFpEF) LVEF. Endpoints were the composite of cardiovascular death/HF hospitalization, and individual components. ResultsMedian sUA was 6.72 (IQ:5.48-8.20) mg/dl in HFrEF, 6.41 (5.02-7.77) in HFmrEF, and 6.30 (5.20-7.70) in HFpEF. At a median 372-day follow-up, the composite endpoint occurred in 648 (13.1%) patients, with 176 (3.6%) deaths and 538 (10.9%) HF hospitalizations. Compared with lowest sUA quartile (Q), Q-III and Q-IV were significantly associated with the composite endpoint (adjusted HR 1.68: 95% CI 1.11–2.54; 2.46: 95% CI 1.66–3.64, respectively). By univariable analyses, HFrEF and HFmrEF patients in Q-III and Q-IV, and HFpEF patients in Q-IV, showed increased risk for the composite endpoint (P<0.05 for all); after model-adjustment, significant association of sUA with outcome persisted among HFrEF in Q-IV, and HFpEF in Q-III-IV. ConclusionsIn a large, contemporary-treated cohort of HF outpatients, sUA is an independent prognosticator of adverse outcome, which can be appreciated in HErEF and HFpEF patients.

Abstract 12789: Clinical Factors Associated With Mortality Among Patients Hospitalized for Heart Failure in Egypt

Introduction: Heart failure (HF) is a growing public health burden in many low and middle-income countries (LMIC). However, most HF registries were conducted in high income countries, which often have different ethnic and cultural backgrounds from that of LMIC. Hypothesis: Independent clinical variables associated with mortality in patients hospitalized for HF in Egypt are different from those established in the United States (US). Methods: Between 2011 and 2014, 1,660 patients hospitalized for HF were enrolled from 20 centers across Egypt as part of the European Society of Cardiology HF long-term Registry. Deceased patients were compared to survivors, to identify demographic, clinical and biochemical variables associated with in-hospital and one-year mortality. Variables associated with mortality on univariate analysis, and independent variables identified in the Acute Decompensated Heart Failure National Registry (ADHERE) and in the Seattle Heart Failure Model, both based in the US, were entered into the multivariate logistic regression model. Results: In-hospital mortality was 5%. Only two independent clinical factors associated with in-hospital mortality were identified: elevated serum creatinine (sCr), OR=1.47 [95% CI: 1.23, 1.74] for every point increases above one mg/dl; and low admission systolic blood pressure (SBP), OR=1.54; [95% CI: 1.43, 1.65] for every 10 points decrease in SBP below 140 mmHg. At one-year follow up, mortality was 27%. Independent predictors of one-year mortality were: age, OR=1.47; [95% CI: 1.23,1.75] for every 10-year increase above 40; low discharge SBP, OR=1.30 [95% CI: 1.08, 1.52] for every 10 points decrease below 140 mmHg; low ejection fraction, OR=1.51 [95% CI: 0.59,0.73] for every 5 points decrease from 65%; chronic liver disease, OR=3.0 [95% CI: 1.51,5.88]; history of stroke, OR=3.2 [95% CI: 1.52,6.65]. These variables overlapped with those identified in US registries. Conclusions: Independent clinical variables associated with mortality after HF hospitalization in Egypt are similar to those reported in HF registries in the US.

Is heart failure misdiagnosed in hospitalized patients with preserved ejection fraction? From the European Society of Cardiology - Heart Failure Association EURObservational Research Programme Heart Failure Long-Term Registry.

AimsIn hospitalized patients with a clinical diagnosis of acute heart failure (HF) with preserved ejection fraction (HFpEF), the aims of this study were (i) to assess the proportion meeting the 2016 European Society of Cardiology (ESC) HFpEF criteria and (ii) to compare patients with restrictive/pseudonormal mitral inflow pattern (MIP) vs. patients with MIP other than restrictive/pseudonormal.Methods and resultsWe included hospitalized participants of the ESC‐Heart Failure Association (HFA) EURObservational Research Programme (EORP) HF Long‐Term Registry who had echocardiogram with ejection fraction (EF) ≥ 50% during index hospitalization. As no data on e', E/e' and left ventricular (LV) mass index were gathered in the registry, the 2016 ESC HFpEF definition was modified as follows: elevated B‐type natriuretic peptide (BNP) (≥100 pg/mL for acute HF) and/or N‐terminal pro‐BNP (≥300 pg/mL) and at least one of the echocardiographic criteria: (i) presence of LV hypertrophy (yes/no), (ii) left atrial volume index (LAVI) of >34 mL/m2), or (iii) restrictive/pseudonormal MIP. Next, all patients were divided into four groups: (i) patients with restrictive/pseudonormal MIP on echocardiography [i.e. with presumably elevated left atrial (LA) pressure], (ii) patients with MIP other than restrictive/pseudonormal (i.e. with presumably normal LA pressure), (iii) atrial fibrillation (AF) group, and (iv) ‘grey area’ (no consistent description of MIP despite no report of AF). Of 6365 hospitalized patients, 1848 (29%) had EF ≥ 50%. Natriuretic peptides were assessed in 28%, LV hypertrophy in 92%, LAVI in 13%, and MIP in 67%. The 2016 ESC HFpEF criteria could be assessed in 27% of the 1848 patients and, if assessed, were met in 52%. Of the 1848 patients, 19% had restrictive/pseudonormal MIP, 43% had MIP other than restrictive/pseudonormal, 18% had AF and 20% were grey area. There were no differences in long‐term all‐cause or cardiovascular mortality, or all‐cause hospitalizations or HF rehospitalizations between the four groups. Despite fewer non‐cardiac comorbidities reported at baseline, patients with MIP other than restrictive/pseudonormal (i.e. with presumably normal LA pressure) had more non‐cardiovascular (14.0 vs. 6.7 per 100 patient‐years, P < 0.001) and cardiovascular non‐HF (13.2 vs. 8.0 per 100 patient‐years, P = 0.016) hospitalizations in long‐term follow‐up than patients with restrictive/pseudonormal MIP.ConclusionsAcute HFpEF diagnosis could be assessed (based on the 2016 ESC criteria) in only a quarter of patients and confirmed in half of these. When assessed, only one in three patients had restrictive/pseudonormal MIP suggestive of elevated LA pressure. Patients with MIP other than restrictive/pseudonormal (suggestive of normal LA pressure) could have been misdiagnosed with acute HFpEF or had echocardiography performed after normalization of LA pressure. They were more often hospitalized for non‐HF reasons during follow‐up. Symptoms suggestive of acute HFpEF may in some patients represent non‐HF comorbidities.

Corrigendum to 'Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry' [Eur J Heart Fail 2020;22:92-102

Corrigendum to 'Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry' [Eur J Heart Fail 2020;22:92-102

Short-term treatments for acute cardiac care: inotropes and inodilators.

Acute heart failure (AHF) continues to be a substantial cause of illness and death, with in-hospital and 3-month mortality rates of 5% and 10%, respectively, and 6-month re-admission rates in excess of 50% in a range of clinical trials and registry studies; the European Society of Cardiology (ESC) Heart Failure Long-Term Registry recorded a 1-year death or rehospitalization rate of 36%. As regards the short-term treatment of AHF patients, evidence was collected in the ESC Heart Failure Long-Term Registry that intravenous (i.v.) treatments are administered heterogeneously in the critical phase, with limited reference to guideline recommendations. Moreover, recent decades have been characterized by a prolonged lack of successful innovation in this field, with a plethora of clinical trials generating neutral or inconclusive findings on long-term mortality effects from a multiplicity of short-term interventions in AHF. One of the few exceptions has been the calcium sensitizer and inodilator levosimendan, introduced 20 years ago for the treatment of acutely decompensated chronic heart failure. In the present review, we will focus on the utility of this agent in the wider context of i.v. inotropic and inodilating therapies for AHF and related pathologies.

Do chronic heart failure patients receive optimal decongestive interventions in a real‐life setting? Letter regarding the article ‘Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC‐EORP Heart Failure Long‐Term Registry’

We read with interest the recent investigation by Kapelios et al.1 concerning the analysis of the European Society of Cardiology Heart Failure Long-Term (ESC-HF-LT) registry. It underscores the widespread inertia in congestion management, as only 24% of patients underwent loop diuretic (LD) dose modification in ESC-HF-LT registry. Also, guideline-directed medication was better up-titrated in patients receiving LD dose adjustment, presuming that physician's discretion may be a stronger predictor of individualised therapy than patient's clinical status. The authors also found that successful decongestion is unlikely for patients with peripheral oedema.1 Still, peripheral oedema is not the best parameter to guide decongestion, given the high prevalence of causes other than chronic heart failure (CHF). In daily practice, clinical signs and symptoms remain the cornerstone of congestion assessment, but an extensive clinical investigation is crucial.2 Given the low rate of LD adjustments, it may be speculated that clinical assessment was not sufficiently extensive, at least in some patients.1 In contrast to down-titration, up-titration was related to worse outcome. The authors noted that extensive adjustment was done to prove the independence of up-titration as a risk factor. However, (de)congestion and CHF outcome interact by means of complex and incompletely investigated mechanisms, making full adjustment almost impossible. In addition, registries contain a limited number of variables, limiting the extent of adjustment. Theoretically, LD treatment can trigger various mechanisms of harm,3 but the adaptability of the human body is likely to counterbalance these effects,4 meaning that the effective impact of LD therapy remains unclear. Also, down-titration in patients with no clinical congestion might worsen the already existing haemodynamic congestion. The ESC-HF-LT registry revealed that de-escalation was unsuccessful in 52% of the cases although it only took place in 8.3% of all patients, questioning whether the right intervention was chosen for the right patient. Despite little support by the literature and effective down-titration in only roughly 4%, the Authors suggest to attempt LD de-escalation more often. We are convinced that the target should not be the reduction of LD dose per se but the achievement of euvolaemia with full decongestion. This is supported by the findings of the CHAMPION trial, where adjustment of therapy based on invasively measured filling pressures improved outcome. Importantly, LD therapy was the most common adjustment of therapy and, in the majority, it was LD up-titration.5 Therefore, comprehensive clinical assessment is crucial, which may include additional exams, such as cardiothoracic or long ultrasound to achieve euvolaemia. Unfortunately, clinical inertia is highly prevalent,1 resulting in suboptimal treatment.

Pronóstico al año en pacientes con insuficiencia cardiaca en España. Registro ESC-EORP-HFA Heart Failure Long-Term

Introduction and objectivesHeart failure (HF) is a growing health problem that constitutes an important burden to society. In spite of this, its importance is frequently underestimated, particularly regarding prognosis. This study estimates one-year prognosis among acute and chronic heart failure patients in Spain and the rest of Europe. Methods2829 HF patients (589 acute HF and 2240 chronic HF) treated by cardiologists were recruited in 27 Spanish hospitals that participate in the ESC-EORP-HFA Heart Failure Long-Term Registry (that includes a total of 12 440 patients from 211 hospitals) and followed-up for one year to monitor hospital admissions and death. ResultsAmong patients with acute HF, one-year mortality rate was 29.3% in Spain (95%CI, 25.6-33.2) and 27.7% in the rest of Europe (P=.4303). Among patients with chronic HF the corresponding figures were 6.4% (95%CI, 5.4-7.5) and 9.5% (P <.0001). One-year hospitalization cumulative incidence among acute HF patients was 46.2% (95%CI, 41.8-50.7) in Spain and 44.6% in Europe (P=.4977); 22.3% (95%CI, 20.6-24.1) and 30.0% respectively among chronic HF patients (P <.0001). ConclusionsThis study highlights the severity of HF, in particular when admission to hospitals is already needed, even in centers that adhere well to guidelines recommendations. Among patients admitted to hospital for HF, almost one third will die within a year of admission (including the 5.9% that die during the index admission) and almost half of them will either die or will need to be readmitted due to HF. The favorable comparison with Europe in chronic HF should be interpreted with caution due to limited control of potential confounders.

Unravelling the interplay between hyperkalaemia, renin-angiotensin-aldosterone inhibitor use and clinical outcomes. Data from 9222 chronic heart failure patients of the ESC-HFA-EORP Heart Failure Long-Term Registry.

We assessed the interplay between hyperkalaemia (HK) and renin-angiotensin-aldosterone system inhibitor (RAASi) use, dose and discontinuation, and their association with all-cause or cardiovascular death in patients with chronic heart failure (HF). We hypothesized that HK-associated increased death may be related to RAASi withdrawal. The ESC-HFA-EORP Heart Failure Long-Term Registry was used. Among 9222 outpatients (HF with reduced ejection fraction: 60.6%, HF with mid-range ejection fraction: 22.9%, HF with preserved ejection fraction: 16.5%) from 31 countries, 16.6% had HK (≥5.0 mmol/L) at baseline. Angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) was used in 88.3%, a mineralocorticoid receptor antagonist (MRA) in 58.7%, or a combination in 53.2%; of these, at ≥50% of target dose in ACEi: 61.8%; ARB: 64.7%; and MRA: 90.3%. At a median follow-up of 12.2 months, there were 789 deaths (8.6%). Both hypokalaemia and HK were independently associated with higher mortality, and ACEi/ARB prescription at baseline with lower mortality. MRA prescription was not retained in the model. In multivariable analyses, HK at baseline was independently associated with MRA non-prescription at baseline and subsequent discontinuation. When considering subsequent discontinuation of RAASi (instead of baseline use), HK was no longer found associated with all-cause deaths. Importantly, all RAASi (ACEi, ARB, or MRA) discontinuations were strongly associated with mortality. In HF, hyper- and hypokalaemia were associated with mortality. However, when adjusting for RAASi discontinuation, HK was no longer associated with mortality, suggesting that HK may be a risk marker for RAASi discontinuation rather than a risk factor for worse outcomes.

Correction to article by Crespo et al. “Hyperkalemia in heart failure patients in Spain and its impact on guidelines and recommendations: ESC-EORP-HFA Heart Failure Long-Term Registry”, Rev Esp Cardiol. 2020;73:313–323.

Correction to article by Crespo et al. “Hyperkalemia in heart failure patients in Spain and its impact on guidelines and recommendations: ESC-EORP-HFA Heart Failure Long-Term Registry”, Rev Esp Cardiol. 2020;73:313–323.

Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry.

Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66 ± 13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25-80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363-419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12-2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96-1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33-1.07; P = 0.083) and cardiovascular mortality (HR 0.62, 95% CI 0.38-1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01-1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09-0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29-0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37-0.87; P = 0.008) were independently associated with successful decrease. Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease.

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry.

This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P=0.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P<0.001) and there were no differences in causes of death. All-cause mortality and all-cause hospitalization increased with greater age in both sexes. Sex was not an independent predictor of 1-year all-cause mortality (restricted to patients with LVEF ≤45%). Mortality risk was significantly lower in patients of younger age, compared to patients aged >75 years. There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF ≤45%.

Hyperkalemia in heart failure patients in Spain and its impact on guidelines and recommendations: ESC-EORP-HFA Heart Failure Long-Term Registry.

Hyperkalemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction because it limits the use of effective drugs. We report estimates of the magnitude of this problem in routine clinical practice in Spain, as well as changes in potassium levels during follow-up and associated factors. This study included patients with acute (n=881) or chronic (n=3587) heart failure recruited in 28 Spanish hospitals of the European heart failure registry of the European Society of Cardiology and followed up for 1 year. Various outcomes were analyzed, including changes in serum potassium levels and their impact on treatment. Hyperkalemia (K+> 5.4 mEq/L) was identified in 4.3% (95%CI, 3.7%-5.0%) and 8.2% (6.5%-10.2%) of patients with chronic and acute heart failure, respectively, and was responsible for 28.9% of all cases of contraindication to mineralocorticoid receptor antagonist use and for 10.8% of all cases of failure to reach the target dose. Serum potassium levels were not recorded in 291 (10.8%) of the 2693 chronic heart failure patients with reduced ejection fraction. During follow-up, potassium levels increased in 179 of 1431 patients (12.5%, 95%CI, 10.8%-14.3%). This increase was directly related to age, diabetes, and history of stroke and was inversely related to history of hyperkalemia. This study highlights the magnitude of the problem of hyperkalemia in patients with heart failure in everyday clinical practice and the need to improve monitoring of this factor in these patients due to its interference with the possibility of receiving optimal treatment.

Should providers prescribe sacubitril/valsartan based on trial eligibility, approval indication, or guideline recommendations?

Should providers prescribe sacubitril/valsartan based on trial eligibility, approval indication, or guideline recommendations?

Sacubitril/valsartan eligibility and outcomes in the ESC-EORP-HFA Heart Failure Long-Term Registry: bridging between European Medicines Agency/Food and Drug Administration label, the PARADIGM-HF trial, ESC guidelines, and real world.

To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM-HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes. Outpatients with HFrEF in the ESC-EORP-HFA Long-Term Heart Failure (HF-LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM-HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM-HF and guideline criteria, respectively. Absent PARADIGM-HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub-optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub-optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB ≥ 10 mg enalapril (instead of ≥ 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM-HF and guidelines. One-year heart failure hospitalization was higher (12% and 17% vs. 12%) and all-cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM-HF. Among outpatients with HFrEF in the ESC-EORP-HFA HF-LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM-HF and guideline criteria for LCZ696 if requiring ≥ 20 mg and ≥ 10 mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM-HF enalapril group.