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A letter to the editor is presented in response to the article "Association of treatment with losartan vs candesartan and mortality among patients with heart failure" by Hviid A. and colleagues in the 2012 issue along with a reply from the authors to the same.

Abstract Background We studied the association between heart failure with reduced or preserved ejection fraction (EF) and the risk of acute kidney injury (AKI) in patients undergoing coronary artery bypass surgery (CABG). Methods We included all patients who underwent isolated CABG in Sweden 2003 to 2013. AKI was defined according to the Kidney Disease Improving Global Outcomes definition, as an increase in postoperative serum creatinine concentration by ≥26 μmol/L or ≥50%, compared to preoperative values. Adjusted odds ratios (OR) for AKI were calculated using logistic regression for patients with and without heart failure, and among patients with heart failure, by EF categories (<30% severely reduced; 30–40% moderately reduced; ≥50% preserved). Results Included were 36,403 patients of whom 3914 (11%) had heart failure. In patients with heart failure, 26% developed AKI compared with 14% in patients without heart failure. After adjustment for background characteristics, including preoperative kidney function and EF, the OR for AKI was 1.12 (95% CI 1.02–1.23) in patients with heart failure compared with no heart failure. Among patients with heart failure, the adjusted OR for AKI among patients with EF <30% vs. ≥50% was 1.32 (95% CI 1.06–1.65) and for 30–49% vs. ≥50% 1.06 (95% CI 0.87–1.28), respectively. Conclusion Patients with heart failure who underwent CABG had an increased risk for AKI postoperatively even after adjustment for comorbidity such as EF. Among patients with heart failure, having a severely reduced EF was associated with AKI compared to patents with preserved EF. Highlights • Patients with heart failure who underwent CABG had an increased risk for AKI. • Heart failure was associated with AKI even after adjustment for ejection fraction. • A severely reduced EF was associated with a higher risk of AKI among HF patients. [ABSTRACT FROM AUTHOR]

Abstract Aims To study prevalence and prognostic importance of diagnostic echocardiographic variables in patients with suspected heart failure with preserved ejection fraction (HFpEF) in the prospective KaRen register study. Methods and results KaRen patients were included following an acute HF-presentation, using Framingham criteria, B-type natriuretic peptide (BNP) >100 ng/L or N-terminal pro-BNP (NT-pro-BNP) >300 ng/L, and left ventricular (LV) ejection fraction ≥45%. Echocardiography was performed after 4–8 weeks and analyzed at a core laboratory. In this substudy HFpEF was diagnosed according to the ESC guidelines for heart failure 2016. A total of 539 patients were included with a follow-up after 4–8 weeks in 438 patients. Complete echocardiography and ECG were available in 356 patients. At least two abnormal echocardiographic criteria for HFpEF were found in 94% (n = 333). Echocardiographic signs of structural heart disease and diastolic dysfunction according to 4 criteria by ESC were found in 76% (n = 270). Diastolic dysfunction was graded as mild in 30% (n = 107), moderate in 27% (n = 97) or severe in 35% (n = 124). After multivariate analyses with adjustment for age, gender, EF and natriuretic peptides we found two independent predictors of worse prognosis: presence of moderate and severe diastolic dysfunction (HR 1.8, CI 1.2–2.7, p = 0.0037) and presence of a high number (≥4) of abnormal diastolic parameters (HR 2.0, CI 1.3–3.1, p = 0.0033). Conclusion The majority of KaRen patients with suspected HFpEF had diagnostic echocardiographic criteria for HFpEF according to ESC Guidelines. Our findings support using 2016 ESC HF guidelines for risk prediction in HFpEF. Highlights • A model for grading the diastolic dysfunction of the heart is proposed. • The ESC heart failure guidelines can be used for risk prediction in heart failure with preserved ejection fraction. [ABSTRACT FROM AUTHOR]

This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population. [ABSTRACT FROM AUTHOR]

A response by Lars H. Lund, Lina Benson and Maria-Eklind Cervenka to letters to the editor about their article "Association of candesartan vs losartan with all-cause mortality in patients with heart failure" that was published in volume 305, issue number 2 of the journal is presented.

The author reflects on the article "Adherence to the medical regime in patients with heart failure" by S. Muzzarelli presented in the journal. He discusses the aim of the study that was to assess the adherence to medical therapy in heart failure. He states that poor adherence limits the effectiveness of proven medical treatments.

The authors comment on the study "Sleep-Disordered Breathing in Heart Failure With Normal Left Ventricular Ejection Fraction," which appeared in the "European Journal of Heart Failure." A background of ethical standards adopted by most cardiovascular journals is presented. Some of the ethical issues raised by the study include the fact that the study was conducted without a priori approval by an Institutional Review Board (IRB) or ethics committee and it obtained left ventricular end-diastolic pressure by left and right heart catheterization.

Aims: In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex. Methods and results: Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all‐cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One‐year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT‐eligible, and RCT‐ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT‐eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62–0.83), while RCT males showed higher adjusted mortality rates compared to RCT‐eligible males (SMR 1.16; 95% CI 1.09–1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76–1.03 for females, SMR 1.43; 95% CI 1.33–1.53 for males). Conclusion: Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries. [ABSTRACT FROM AUTHOR]

Aims: To investigate the use of guideline‐directed medical therapies (GDMT) and associated outcomes in obese (body mass index ≥30 kg/m2) versus non‐obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods and results: Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non‐obese patients, use of treatments was 91% versus 86% for renin–angiotensin system inhibitors (RASi)/angiotensin receptor–neprilysin inhibitors (ARNi), 94% versus 91% for beta‐blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta‐blockers being independently associated with lower risk of all‐cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non‐obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non‐obese patients, whereas beta‐blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity. Conclusion: Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta‐blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non‐obese patients when considering competing risk. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to the article "What Do Good Doctors Try To Do," that was previously published in the 2003 issue of the journal "Archives of Internal Medicine."

Atrial fibrillation (AF) and heart failure with a preserved ejection fraction (HFpEF) are closely intertwined disorders that afflict millions of people, many of whom are obese or have diabetes mellitus or other proinflammatory conditions. These relationships may reflect the fact that patients with both AF and HFpEF have a more advanced stage of the underlying myopathy than patients with only AF or only HFpEF. [Extracted from the article]

Aims: Guidelines for the management of heart failure (HF) are evolving, and increasing emphasis is placed on patient‐centred care. As part of the REWOLUTION HF (REal WOrLd EdUcaTION in HF) programme, we conducted two international surveys aimed at assessing healthcare professionals' (HCPs) educational needs and patients' perspectives on the care of HF. Methods and results: Anonymous online questionnaires co‐developed by HF experts and patients assessed HCPs' educational needs (520 respondents, mostly cardiologists, in 67 countries) and patients' perceptions on HF impact and management (98 respondents in 18 countries). Among HCPs, 62.7% prioritized rapid initiation of all guideline‐mandated medications over up‐titration of some medications, and 87.7% always or frequently discussed treatment goals with patients. There was good agreement between HCPs and patients on key treatment goals, except for a greater emphasis on reducing hospitalizations among HCPs. The most frequently cited barriers to the provision of guideline‐recommended pharmacological therapy were treatment side effects/intolerance, complex treatment regimens, low blood pressure, cost/reimbursement issues, and low estimated glomerular filtration rate. Most patients (81.6%) reported no difficulties taking medications as prescribed, although 21.4% felt they were taking too many pills. Patients wanted more information about HF and its consequences, prognosis, and treatments (70.4%, 74.5% and 76.6%, respectively). Cardiologists were the preferred source of information about HF, followed by general practitioners and HF nurses. Conclusions: These surveys provide valuable insights into HCPs' needs about personalized care for patients with HF, as well as patients' perceptions, expectations and preferences. These findings will be helpful to develop patient‐centred, needs‐driven quality improvement programmes. [ABSTRACT FROM AUTHOR]

Aims: Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalizations and improved quality of life when used to treat ID at discharge in patients hospitalized for acute HF with left ventricular ejection fraction <50% in the AFFIRM‐AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden. Methods and results: The per country eligible population was calculated, aligning with the 2021 European Society of Cardiology (ESC) HF guidelines and the AFFIRM‐AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability‐adjusted life years (DALYs), hospitalization episodes and bed days, using AFFIRM‐AHF data. A Markov model was adapted to each country to estimate cost‐effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13 237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalizations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5215 in Sweden to 205 630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality‐adjusted life years), resulting in net savings to healthcare budgets within 1 year. Conclusions: This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realized through implementation of the ESC HF guideline recommendations regarding ID treatment. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a progressive disease characterized by variable durations of symptomatic stability often punctuated by episodes of worsening despite continued therapy. These periods of clinical worsening are increasingly recognized as a distinct phase in the history of HF, termed worsening HF (WHF). The definition of WHF continues to evolve from a historical focus solely on hospitalization to now include nonhospitalization events (eg, need for intravenous diuretic therapy in the emergency or outpatient setting). Most HF clinical trials to date have had HF hospitalization and death as primary endpoints, and only recently, some studies have included other WHF events regardless of location of care. This article reviews the evolution of the WHF definition, highlights the importance of considering the onset of WHF as an event that marks a new phase of HF, summarizes the latest clinical trials investigating novel therapies, and outlines unmet needs regarding identification and treatment of WHF. [Display omitted] • Management of patients with worsening heart failure is limited by the lack of a clear biological definition and specific guidelines. • It is important to recognize worsening heart failure as an indication that the disease has progressed to a new phase. • Additional research is needed to define criteria for assessment of worsening heart failure and guide management. [ABSTRACT FROM AUTHOR]

Aim: Epicardial adipose tissue (EAT) may play a role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). We investigated associations of EAT with proteomics, coronary flow reserve (CFR), cardiac structure and function, and quality of life (QoL) in the prospective multinational PROMIS‐HFpEF cohort. Methods and results: Epicardial adipose tissue was measured by echocardiography in 182 patients and defined as increased if ≥9 mm. Proteins were measured using high‐throughput proximity extension assays. Microvascular dysfunction was evaluated with Doppler‐based CFR, cardiac structural and functional indices with echocardiography and QoL by Kansas City Cardiomyopathy Questionnaire (KCCQ). Patients with increased EAT (n = 54; 30%) had higher body mass index (32 [28–40] vs. 27 [23–30] kg/m2; p < 0.001), lower N‐terminal pro‐B‐type natriuretic peptide (466 [193–1133] vs. 1120 [494–1990] pg/ml; p < 0.001), smaller indexed left ventricular (LV) end‐diastolic and left atrial (LA) volumes and tendency to lower KCCQ score. Non‐indexed LV/LA volumes did not differ between groups. When adjusted for body mass index, EAT remained associated with LV septal wall thickness (coefficient 1.02, 95% confidence interval [CI] 1.00–1.04; p = 0.018) and mitral E wave deceleration time (coefficient 1.03, 95% CI 1.01–1.05; p = 0.005). Increased EAT was associated with proteomic markers of adipose biology and inflammation, insulin resistance, endothelial dysfunction, and dyslipidaemia but not significantly with CFR. Conclusion: Increased EAT was associated with cardiac structural alterations and proteins expressing adiposity, inflammation, lower insulin sensitivity and endothelial dysfunction related to HFpEF pathology, probably driven by general obesity. Potential local mechanical or paracrine effects mediated by EAT remain to be elucidated. [ABSTRACT FROM AUTHOR]

Aims: Cardiac contractile dysfunction is prevalent in rheumatoid arthritis (RA), with an increased risk for heart failure. A hallmark of RA has increased levels of peptidyl arginine deaminases (PAD) that convert arginine to citrulline leading to ubiquitous citrullination, including in the heart. We aimed to investigate whether PAD‐dependent citrullination in the heart was linked to contractile function in a mouse model of RA during the acute inflammatory phase. Methods: We used hearts from the collagen‐induced arthritis (CIA) mice, with overt arthritis, and control mice to analyze cardiomyocyte Ca2+ handling and fractional shortening, the force‐Ca2+ relationship in isolated myofibrils, the levels of PAD, protein post‐translational modifications, and Ca2+ handling protein. Then, we used an in vitro model to investigate the role of TNF‐α in the PAD‐mediated citrullination of proteins in cardiomyocytes. Results: Cardiomyocytes from CIA mice displayed larger Ca2+ transients than controls, whereas cell shortening was similar in the two groups. Myofibrils from CIA hearts required higher [Ca2+] to reach 50% of maximum shortening, ie Ca2+ sensitivity was lower. This was associated with increased PAD2 expression and α‐actin citrullination. TNF‐α increased PAD‐mediated citrullination which was blocked by pre‐treatment with the PAD inhibitor 2‐chloroacetamide. Conclusion: Using a mouse RA model we found evidence of impaired cardiac contractile function linked to reduced Ca2+ sensitivity, increased expression of PAD2, and citrullination of α‐actin, which was triggered by TNF‐α. This provides molecular and physiological evidence for acquired cardiomyopathy and a potential mechanism for RA‐associated heart failure. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the quality of heart failure (HF) care using the European Society of Cardiology (ESC) quality indicators (QIs) for HF and to assess whether better quality of care is associated with improved outcomes. Methods and results: We performed a nationwide cohort study using the Swedish HF registry, consisting of patients with any type of HF at their first outpatient visit or hospitalization. Independent participant data for quality of HF care was evaluated against the ESC QIs for HF, and association with mortality estimated using multivariable Cox regression. In total, 43 704 patients from 80 hospitals across Sweden enrolled between 2013–2019 were included, with median follow‐up 23.6 months. Of the 16 QIs for HF, 13 could be measured and 5 were inversely associated with all‐cause mortality during follow‐up. Higher attainment (≥50% vs. <50% attainment) of the composite opportunity‐based score (combination of QIs into a single score) for patients with reduced ejection fraction was associated with lower all‐cause mortality (adjusted hazard ratio 0.81; 95% confidence interval 0.72–0.91). Attainment of the composite score was less in the outpatient than inpatient setting (adjusted odds ratio 0.85; 95% confidence interval 0.72–0.99). Quality of care varied across hospitals, with assessment of health‐related quality of life being the indicator with the widest variation in attainment (interquartile range 61.7%). Conclusion: Quality of HF care may be measured using the ESC HF QIs. In Sweden, attainment of HF care evaluated using the QIs demonstrated between and within hospital variation, and many QIs were inversely associated with mortality. [ABSTRACT FROM AUTHOR]

Aim: Half of heart failure (HF) patients have chronic kidney disease (CKD) complicating their pharmacological management. We evaluated physicians' and patients' patterns of use of evidence‐based medical therapies in HF across CKD stages. Methods and results: We studied HF patients with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction enrolled in the Swedish Heart Failure Registry in 2009–2018. We investigated the likelihood of physicians to prescribe guideline‐recommended therapies to patients with CKD, and of patients to fill the prescriptions within 90 days of incident HF (initiating therapy), to adhere (proportion of days covered ≥80%) and persist (continued use) on these treatments during the first year of therapy. We identified 31 668 patients with HFrEF (median age 74 years, 46% CKD). The proportions receiving a prescription for angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor–neprilysin inhibitors (ACEi/ARB/ARNi) were 96%, 92%, 86%, and 68%, for estimated glomerular filtration rate (eGFR) ≥60, 45–59, 30–44, and <30 ml/min/1.73 m2, respectively; for beta‐blockers 94%, 93%, 92%, and 92%, for mineralocorticoid receptor antagonists (MRAs) 45%, 44%, 37%, 24%; and for triple therapy (combination of ACEi/ARB/ARNi + beta‐blockers + MRA) 38%, 35%, 28%, and 15%. Patients with CKD were less likely to initiate these medications, and less likely to adhere to and persist on ACEi/ARB/ARNi, MRA, and triple therapy. Among stoppers, CKD patients were less likely to restart these medications. Results were consistent after multivariable adjustment and in patients with HFmrEF (n = 15 114). Conclusions: Patients with HF and CKD are less likely to be prescribed and to fill prescriptions for evidence‐based therapies, showing lower adherence and persistence, even at eGFR categories where these therapies are recommended and have shown efficacy in clinical trials. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "The prognostic significance of heart failure with preserved left ventricular ejection fraction: a literature-based meta-analysis," by J. B. Somaratne and colleagues published in the 2009 issue of the periodical is presented.

A reply by L.H. Lund, J.J. Williams, and P. Freda to a letter to the editor about their article "Ghrelin resistance ocurs in severe heart failure and resolves after heart transportation" is presented.

Aims: To investigate the association between catheter ablation for atrial fibrillation (AF) and mortality as well as hospitalization for heart failure (HF) in patients with HF across the ejection fraction (EF) spectrum.Methods and Results: Patients with first-time catheter ablation for AF (ablation group) compared to only medical treated AF patients (no ablation group) were identified from the Swedish Heart Failure Registry between 2005 and 2019. The primary outcome (all-cause mortality/first HF hospitalization) was assessed by Cox regression models in a 1:2 propensity score (PS) matched cohort and pre-specified EF subgroups (preserved EF [≥50%], mildly reduced EF [40-49%], reduced EF [<40%]) of this cohort. A total of 452 patients in the ablation group and 43 766 patients in the no ablation group were identified. After PS matching, 434 patients in the ablation group were compared to 868 patients in the no ablation group. Over a median follow-up of 2.6 years (0.0-14.1 years), catheter ablation was associated with a lower risk of the primary outcome (all-cause mortality/first HF hospitalization) (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.65-0.94). Results were consistent across all EF subgroups. In HF with preserved EF (HFpEF), catheter ablation was also associated with a lower risk of recurrent HF hospitalization (incidence rate ratio 0.17, 95% CI 0.07-0.42).Conclusion: In HF patients across the EF spectrum, catheter ablation for AF was associated with lower risk of the primary outcome (all-cause mortality/first HF hospitalization). This study supports catheter ablation as a treatment option for AF in HF patients, including those with HFpEF. [ABSTRACT FROM AUTHOR]

Knowledge on risk predictors of incident heart failure (HF) in patients with type 2 diabetes (T2D) is crucial given the frequent coexistence of the two conditions and the fact that T2D doubles the risk of incident HF. In addition, HF is increasingly being recognized as an important endpoint in trials in T2D. On the other hand, the diagnostic and prognostic performance of established cardiovascular biomarkers may be modified by the presence of T2D. The present position paper, derived by an expert panel workshop organized by the Heart Failure Association of the European Society of Cardiology, summarizes the current knowledge and gaps in evidence regarding the use of a series of different biomarkers, reflecting various pathogenic pathways, for the prediction of incident HF and cardiovascular events in patients with T2D and in those with established HF and T2D. [ABSTRACT FROM AUTHOR]

Aims: The recent definition of heart failure with improved ejection fraction outlined the importance of the longitudinal assessment of left ventricular ejection fraction (LVEF). However, long‐term progression and outcomes of this subgroup are poorly explored. We sought to assess the LVEF trajectories and their correlations with outcome in non‐ischaemic dilated cardiomyopathy (NICM) with improved ejection fraction (impEF). Methods and results: Consecutive NICM patients with baseline LVEF ≤40% enrolled in the Trieste Heart Muscle Disease Registry with ≥1 LVEF assessment after baseline were included. ImpEF was defined as a baseline LVEF ≤40%, and second evaluation showing both a ≥10% point increase from baseline LVEF and LVEF >40%. Transient impEF was defined by the documentation of recurrent LVEF ≤40% during follow‐up. The primary endpoint was a composite of all‐cause death, heart transplantation and left ventricular assist device (D/HT/LVAD). Among 800 patients, 460 (57%) had impEF (median time to improvement 13 months). Transient impEF was observed in 189 patients (41% of the overall impEF group) and was associated with higher risk of D/HT/LVAD compared with persistent impEF at multivariable analysis (hazard ratio 2.54; 95% confidence interval 1.60–4.04). The association of declining LVEF with the risk of D/HT/LVAD was non‐linear, with a steep increase up to 8% points reduction, then remaining stable. Conclusions: In NICM, a 57% rate of impEF was observed. However, recurrent decline in LVEF was observed in ≈40% of impEF patients and it was associated with an increased risk of D/HT/LVAD. [ABSTRACT FROM AUTHOR]

Aims: To assess the association between combination, dose and use of current guideline‐recommended target doses (TD) of renin–angiotensin system inhibitors (RASi), angiotensin receptor–neprilysin inhibitors (ARNi) and β‐blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure (HF) and reduced ejection fraction. Methods and results: Overall, 17 809 outpatients registered in the Swedish Heart Failure Registry (SwedeHF) from May 2000 to December 2018, with ejection fraction <40% and duration of HF ≥90 days were selected. Primary outcome was a composite of time to cardiovascular death and first HF hospitalization. Compared with no use of RASi or ARNi, the adjusted hazard ratio (HR) (95% confidence interval [CI]) was 0.83 (0.76–0.91) with <50% of TD, 0.78 (0.71–0.86) with 50%–99%, and 0.73 (0.67–0.80) with ≥100% of TD. Compared with no use of β‐blockers, the adjusted HR (95% CI) was 0.86 (0.76–0.91), 0.81 (0.74–0.89) and 0.74 (0.68–0.82) with <50%, 50%–99% and ≥100% of TD, respectively. Patients receiving both an angiotensin‐converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/ARNi and a β‐blocker at 50%–99% of TD had a lower adjusted risk of the primary outcome compared with patients only receiving one drug, i.e. ACEi/ARB/ARNi or β‐blocker, even if this was at ≥100% of TD. Conclusion: Heart failure with reduced ejection fraction patients using higher doses of RASi or ARNi and β‐blockers had lower risk of cardiovascular death or HF hospitalization. Use of two drug classes at 50%–99% of TD dose was associated with lower risk than one drug class at 100% of TD. [ABSTRACT FROM AUTHOR]

Aims: To perform a comprehensive characterization of acute heart failure (AHF) with preserved (HFpEF), versus mildly reduced (HFmrEF) versus reduced ejection fraction (HFrEF). Methods and results: Of 5951 participants in the ESC HF Long‐Term Registry hospitalized for AHF (acute coronary syndromes excluded), 29% had HFpEF, 18% HFmrEF, and 53% HFrEF. Hospitalization reasons were most commonly atrial fibrillation (more in HFmrEF and HFpEF), followed by ischaemia (HFmrEF), infection (HFmrEF and HFpEF), worsening renal function (HFrEF), and uncontrolled hypertension (HFmrEF and HFpEF). Hospitalization characteristics included lower blood pressure, more oedema and higher natriuretic peptides with lower ejection fraction, similar pulmonary congestion, more mitral regurgitation in HFrEF and HFmrEF and more tricuspid regurgitation in HFrEF. In‐hospital mortality was 3.4% in HFrEF, 2.1% in HFmrEF and 2.2% in HFpEF. Intravenous diuretic (∼80%) and nitrate (∼15%) use was similar but inotrope use greater in HFrEF (16%, vs. HFmrEF 7.4% vs. HFpEF 5.3%). Weight loss and estimated glomerular filtration rate improvement were greater in HFrEF, whereas reduction in natriuretic peptides was similar. Over 1 year post‐discharge, events per 100 patient‐years (95% confidence interval) in HFrEF versus HFmrEF versus HFpEF were: all‐cause death 22 (20–24) versus 17 (14–20) versus 17 (15–20); cardiovascular (CV) death 12 (10–13) versus 8.6 (6.6–11) versus 8.4 (6.9–10); non‐CV death 2.4 (1.8–3.1) versus 3.3 (2.1–4.8) versus 4.5 (3.5–5.9); all‐cause hospitalization 48 (45–51) versus 35 (31–40) versus 42 (39–46); HF hospitalization 29 (27–32) versus 19 (16–22) versus 17 (15–20); and non‐CV hospitalization 7.7 (6.6–8.9) versus 9.6 (7.5–12) versus 15 (13–17). Conclusion: In AHF, HFrEF is more severe and has greater in‐hospital mortality. Post‐discharge, HFrEF has greater CV risk, HFpEF greater non‐CV risk, and HFmrEF lower overall risk. [ABSTRACT FROM AUTHOR]

Aims: In patients with current or a history of hyperkalaemia, treatment with renin–angiotensin–aldosterone system inhibitors (RAASi) is often compromised. Patiromer, a novel potassium (K+) binder, may improve serum K+ levels and adherence to RAASi. Methods: The DIAMOND trial will enroll ∼820 patients with heart failure with reduced ejection fraction (HFrEF; ejection fraction ≤40%). Patients meeting the screening criteria will enter a single‐blinded run‐in phase where they will be started or continued on a mineralocorticoid receptor antagonist (MRA) titrated to 50 mg/day and other RAASi therapy to ≥50% target dose, and patiromer. Patiromer will be titrated up to a maximum three packs/day (8.4 g/pack) to achieve optimal doses of RAASi without hyperkalaemia. The run‐in phase will last up to 12 weeks, following which patients will undergo double‐blind randomization in a 1:1 ratio to receive either continued patiromer or placebo (patiromer withdrawal). The primary endpoint is the mean difference in serum K+ from randomization between patiromer and placebo arms. Secondary endpoints will include hyperkalaemia events with K+ value >5.5 mEq/L, durable enablement of MRA at target dose, investigator‐reported adverse events of hyperkalaemia, hyperkalaemia‐related clinical endpoints and an overall RAASi use score (using a 0–8‐point scale) comprising all‐cause death, occurrence of cardiovascular hospitalization or usage of comprehensive heart failure medication. Conclusion: The DIAMOND trial is designed to determine if patiromer can favourably impact K+ control in patients with HFrEF with hyperkalaemia or a history of hyperkalaemia leading to RAASi therapy compromise, and in turn improve RAASi use. [ABSTRACT FROM AUTHOR]

Aims: To develop a suite of quality indicators (QIs) for the evaluation of the quality of care for adults with heart failure (HF).Methods and Results: We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care for the management of HF by constructing a conceptual framework of HF care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. The Working Group comprised experts in HF management including Task Force members of the 2021 European Society of Cardiology (ESC) Clinical Practice Guidelines for HF, members of the Heart Failure Association (HFA), Quality Indicator Committee and a patient representative. In total, 12 main and 4 secondary QIs were selected across five domains of care for the management of HF: (1) structural framework, (2) patient assessment, (3) initial treatment, (4) therapy optimization, and (5) assessment of patient health-related quality of life.Conclusion: We present the ESC HFA QIs for HF, describe their development process and provide the scientific rationale for their selection. The indicators may be used to quantify and improve adherence to guideline-recommended clinical practice and thus improve patient outcomes. [ABSTRACT FROM AUTHOR]

Aims In patients with current or a history of hyperkalaemia, treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) is often compromised. Patiromer, a novel potassium (K+) binder, may improve serum K+ levels and adherence to RAASi. Methods The DIAMOND trial will enroll ~820 patients with heart failure with reduced ejection fraction (HFrEF; ejection fraction =40%). Patients meeting the screening criteria will enter a single-blinded run-in phase where they will be started or continued on a mineralocorticoid receptor antagonist (MRA) titrated to 50mg/day and other RAASi therapy to =50% target dose, and patiromer. Patiromer will be titrated up to a maximum three packs/day (8.4 g/pack) to achieve optimal doses of RAASi without hyperkalaemia. The run-in phase will last up to 12weeks, following which patients will undergo double-blind randomization in a 1:1 ratio to receive either continued patiromer or placebo (patiromer withdrawal). The primary endpoint is the mean difference in serum K+ from randomization between patiromer and placebo arms. Secondary endpoints will include hyperkalaemia events with K+ value >5.5 mEq/L, durable enablement of MRA at target dose, investigator-reported adverse events of hyperkalaemia, hyperkalaemia-related clinical endpoints and an overall RAASi use score (using a 0-8-point scale) comprising all-cause death, occurrence of cardiovascular hospitalization or usage of comprehensive heart failure medication. Conclusion The DIAMOND trial is designed to determine if patiromer can favourably impact K+ control in patients with HFrEF with hyperkalaemia or a history of hyperkalaemia leading to RAASi therapy compromise, and in turn improve RAASi use. [ABSTRACT FROM AUTHOR]

Aims To develop a suite of quality indicators (QIs) for the evaluation of the quality of care for adults with heart failure (HF). Methods and results We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care for the management of HF by constructing a conceptual framework of HF care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified Delphi method, and (iv) the evaluation of the feasibility of the developedQIs. TheWorking Group comprised experts in HF management including Task Force members of the 2021 European Society of Cardiology (ESC) Clinical Practice Guidelines for HF, members of the Heart Failure Association (HFA), Quality Indicator Committee and a patient representative. In total, 12 main and 4 secondary QIs were selected across five domains of care for the management of HF: (1) structural framework, (2) patient assessment, (3) initial treatment, (4) therapy optimization, and (5) assessment of patient health-related quality of life. Conclusion We present the ESC HFA QIs for HF, describe their development process and provide the scientific rationale for their selection. The indicators may be used to quantify and improve adherence to guideline-recommended clinical practice and thus improve patient outcomes. [ABSTRACT FROM AUTHOR]

Patients with heart failure (HF) are often cared for by non-cardiologists. The implications are unknown. In a nationwide HF cohort with reduced ejection fraction (HFrEF), we compared demographics, clinical characteristics, guideline-based therapy use and outcomes in non-cardiology vs. cardiology in-patient and out-patient care. Between 2000 and 2016, 36,076 patients with HFrEF were enrolled in the Swedish HF registry (19,337 [54%] in-patients overall), with 44% of in-patients and 45% of out-patients managed in non-cardiology settings. Predictors of treatment in non-cardiology were age > 75 years (adjusted odds ratio for non-cardiology 1.20; 95% confidence interval 1.14–1.27), lower education level (0.71; 0.66–0.76 for university vs. compulsory), valve disease (1.24; 1.18–1.31) and systolic blood pressure (SBP) >120 mmHg (1.05; 1.00–1.10). Non-cardiology care was significantly associated with lower use of beta-blockers (0.80; 0.74–0.86) and devices (intracardiac defibrillator [ICD] and/or cardiac resynchronization therapy [CRT]: 0.63; 0.56–0.71), and less frequent specialist follow-up (0.61; 0.57–0.65). Over 1-year follow-up the risk of all-cause mortality (adjusted hazard ratio 1.09; 1.03–1.15) was higher but the risk of first HF (re-) hospitalization was lower (0.93; 0.89–0.97) in non-cardiology vs. cardiology care. In HFrEF, non-cardiology care was independently associated with older ageand lower education. After covariate adjustment, non-cardiology care was associated with lower use of beta-blockers and devices, higher mortality, and lower risk of HF hospitalization. Access to cardiology care may not be equitable and this may have implications for use of guideline-based care and outcomes. • Approximately half of patients with HFrEF were treated in non-cardiology settings. • Non-cardiology care was associated with older age, lower education level, and lower use of beta-blockers and devices. • The risk of all-cause mortality was higher but the risk of first HF hospitalization lower in non-cardiology vs. cardiology care. [ABSTRACT FROM AUTHOR]

Aims: Iron deficiency (ID) is associated with poor prognosis regardless of anaemia. Intravenous iron improves quality of life and outcomes in patients with ID and heart failure (HF) with reduced ejection fraction (HFrEF). In the Swedish HF registry, we assessed (i) frequency and predictors of ID testing; (ii) prevalence and outcomes of ID with/without anaemia; (iii) use of ferric carboxymaltose (FCM) and its predictors in patients with ID. Methods and results: We used multivariable logistic regressions to assess patient characteristics independently associated with ID testing/FCM use, and Cox regressions to assess risk of outcomes associated with ID. Of 21 496 patients with HF and any ejection fraction enrolled in 2017–2018, ID testing was performed in 27%. Of these, 49% had ID and more specifically 36% had ID−/anaemia−, 15% ID−/anaemia+, 29% ID+/anaemia−, and 20% ID+/anaemia+ (48%, 39%, 13%, 30% and 18% in HFrEF, respectively). Risk of recurrent all‐cause hospitalizations was higher in patients with ID regardless of anaemia. Of 1959 patients with ID, 19% received FCM (24% in HFrEF). Important independent predictors of ID testing and FCM use were anaemia, higher New York Heart Association class, having HFrEF, and referral to HF specialty care. Conclusion: In this nationwide HF registry, ID testing occurred in only about a quarter of the patients. Among tested patients, ID was present in one half, but only one in five patients received FCM indicating low adherence to current guidelines on screening and treatment. [ABSTRACT FROM AUTHOR]

Aims: Whether to continue or stop mineralocorticoid receptor antagonists (MRA) after an episode of hyperkalaemia is a challenge in clinical practice. While stopping MRA may prevent recurrent hyperkalaemias, it deprives patients of their cardioprotection. We here assessed the association between stopping vs. continuing MRA therapy after hyperkalaemia and the subsequent risks of adverse health events. Methods and results: Observational study from the Stockholm CREAtinine Measurements (SCREAM) project 2006–2018. We identified patients initiating MRA and surviving a first‐detected episode of hyperkalaemia (plasma potassium >5.0 mmol/L). Using target trial emulation methods, we assessed the association between stopping vs. continuing MRA within 6 months after hyperkalaemia and subsequent outcomes. The primary outcome was the composite of hospital admission with heart failure, stroke, myocardial infarction, or death. The secondary outcome was occurrence of another hyperkalaemia event. Among 39 518 patients initiating MRA, we identified 7366 who developed hyperkalaemia. Median age was 76 years, 45% were women and 69% had a history of heart failure. Following hyperkalaemia, 2222 (30%) discontinued treatment. Compared with continuing MRA, stopping therapy was associated with a lower 2‐year risk of recurrent hyperkalaemia [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.72–0.79], but a higher risk of the primary outcome (HR 1.10, 95% CI 1.06–1.14). Similar results were observed in patients with heart failure, after censoring when treatment decision was changed, and across pre‐specified subgroups. Conclusions: Stopping MRA after an episode of hyperkalaemia was associated with reduced risk for recurrent hyperkalaemia, but higher risk of death or cardiovascular events. Recurrent hyperkalaemia was common in either strategy. [ABSTRACT FROM AUTHOR]

Objective. In patients with acute heart failure (HF) there is an inverse relation between blood pressure (BP) and mortality but the prognostic impact of the change in BP between admission and discharge is not known. The primary objective was to study the impact of the change in BP during a hospitalisation for acute HF on prognosis. Design. We studied 208 consecutive patients admitted with acute heart failure and discharged alive, age 77 ± 10 years, 49.5% women. Results. BP at admission was 145 ± 35/85 ± 9 mmHg compared to 132 ± 24/76 ±13 mmHg at discharge. The average number of BP lowering medications at admission and discharge was 2.1 ± 1.2 and 2.8 ± 1.0 respectively. The average number of BP lowering medications with dose increased at discharge compared to admission was 0.3 ± 0.5. Univariate predictors of all-cause mortality at 12 and/or 40 months were admission SBP and DBP, discharge DBP, decrease in SBP and DBP during hospitalisation, age, eGFR, number of added BP-lowering medications during the hospitalisation and left ventricular ejection fraction (LVEF). Multivariate predictors at 12 and/or 40 month were admission DBP, decrease in DBP, age, eGFR, LVEF and number of new BP-lowering medications added during the hospitalisation. Conclusions. A decrease in BP during hospitalisation for acute heart failure was a predictor of all cause mortality. A higher admission BP and the tolerability of added medications probably played a role, and our findings need confirmation in larger studies. [ABSTRACT FROM AUTHOR]

Background: In the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure) trial, sotagliflozin, a sodium-glucose cotransporter-1 and sodium-glucose cotransporter-2 inhibitor, reduced total occurrences of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure relative to placebo by 33%.Objective: To determine whether sotagliflozin increased the prespecified efficacy outcome of days alive and out of the hospital (DAOH) in the SOLOIST-WHF trial.Design: Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT03521934).Setting: 306 sites in 32 countries.Participants: 1222 patients with type 2 diabetes and reduced or preserved ejection fraction who were recently hospitalized for worsening heart failure.Intervention: 200 mg of sotagliflozin once daily (with a possible dose increase to 400 mg) or matching placebo.Measurements: The primary analysis included hospitalizations for any reason on the basis of investigator-reported incidence and duration of admissions after randomization. Days alive and out of the hospital and its converse (days dead and days in the hospital) were analyzed using prespecified Poisson regression models.Results: Although similar proportions of patients in the sotagliflozin and placebo groups were hospitalized at least once (38.5% vs. 41.4%), fewer patients in the sotagliflozin group were hospitalized more than once (16.3% vs. 22.1%). There were 64 and 76 deaths in the sotagliflozin and placebo groups, respectively. The DAOH rate in the sotagliflozin group was 3% higher than in the placebo group (rate ratio [RR], 1.03 [95% CI, 1.00 to 1.06]; P = 0.027). This difference was primarily driven by a reduction in the rate of days dead (RR, 0.71 [CI, 0.52 to 0.99]; P = 0.041) rather than by a reduction in the rate of days hospitalized for any cause. For every 100 days of follow-up, patients in the sotagliflozin group were alive and out of the hospital for 3% or 2.9 more days than those in the placebo group (91.8 vs. 88.9 days); this difference reflected a 2.6-day difference in days dead (6.3 vs. 8.9 days) and a 0.3-day difference in days in the hospital (1.9 vs. 2.2 days).Limitation: Other than heart failure, the primary reason for each hospitalization was unspecified.Conclusion: Sotagliflozin increased DAOH, a metric that may provide an additional patient-centered outcome to capture the totality of disease burden. Future studies are needed to quantify the consequences of increasing DAOH in terms of health economics and patient quality of life.Primary Funding Source: Sanofi at initiation and Lexicon Pharmaceuticals at completion. [ABSTRACT FROM AUTHOR]

In 2015, the first large‐scale placebo‐controlled trial designed to assess cardiovascular safety of glucose‐lowering with sodium–glucose co‐transporter 2 (SGLT2) inhibition in type 2 diabetes mellitus raised hypotheses that the class could favourably modify not only risk of atherosclerotic cardiovascular disease, but also hospitalization for heart failure, and the development or worsening of nephropathy. By the start of 2021, results from 10 large SGLT2 inhibitor placebo‐controlled clinical outcome trials randomizing ∼71 000 individuals have confirmed that SGLT2 inhibitors can provide clinical benefits for each of these types of outcome in a range of different populations. The cardiovascular and renal benefits of SGLT2 inhibitors appear to be larger than their comparatively modest effect on glycaemic control or glycosuria alone would predict, with three trials recently reporting that clinical benefits extend to individuals without diabetes mellitus who are at risk due to established heart failure, or albuminuric chronic kidney disease. This European Society of Cardiology position paper summarizes reported results from these 10 large clinical outcome trials considering separately each of the different types of cardiorenal benefit, summarizes key molecular and pathophysiological mechanisms, and provides a synopsis of metabolic effects and safety. We also describe ongoing placebo‐controlled trials among individuals with heart failure with preserved ejection fraction and among individuals with chronic kidney disease. [ABSTRACT FROM AUTHOR]

Patients admitted with worsening chronic HF ( I n i = 8316) had greater comorbidity burden and greater risk of all-cause death and HF readmission when compared to patients with new-onset HF ( I n i = 8860), with longer duration of HF being associated with greater risk. Acknowledging the complex puzzle that links heart failure hospitalizations to outcomes. Letter regarding the article 'Readmission and death in patients admitted with new-onset versus worsening of chronic heart failure: insights from a nationwide cohort'. [Extracted from the article]

Aims: We aimed to derive and validate clinically useful clusters of patients with heart failure with preserved ejection fraction (HFpEF; left ventricular ejection fraction ≥50%). Methods and results: We derived a cluster model from 6909 HFpEF patients from the Swedish Heart Failure Registry (SwedeHF) and externally validated this in 2153 patients from the Chronic Heart Failure ESC‐guideline based Cardiology practice Quality project (CHECK‐HF) registry. In SwedeHF, the median age was 80 [interquartile range 72–86] years, 52% of patients were female and most frequent comorbidities were hypertension (82%), atrial fibrillation (68%), and ischaemic heart disease (48%). Latent class analysis identified five distinct clusters: cluster 1 (10% of patients) were young patients with a low comorbidity burden and the highest proportion of implantable devices; cluster 2 (30%) patients had atrial fibrillation, hypertension without diabetes; cluster 3 (25%) patients were the oldest with many cardiovascular comorbidities and hypertension; cluster 4 (15%) patients had obesity, diabetes and hypertension; and cluster 5 (20%) patients were older with ischaemic heart disease, hypertension and renal failure and were most frequently prescribed diuretics. The clusters were reproduced in the CHECK‐HF cohort. Patients in cluster 1 had the best prognosis, while patients in clusters 3 and 5 had the worst age‐ and sex‐adjusted prognosis. Conclusions: Five distinct clusters of HFpEF patients were identified that differed in clinical characteristics, heart failure drug therapy and prognosis. These results confirm the heterogeneity of HFpEF and form a basis for tailoring trial design to individualized drug therapy in HFpEF patients. [ABSTRACT FROM AUTHOR]

Aims: The Heart Failure Association (HFA) of the European Society of Cardiology (ESC) developed the HFA Atlas to provide a contemporary description of heart failure (HF) epidemiology, resources, reimbursement of guideline-directed medical therapy (GDMT) and activities of the National Heart Failure Societies (NHFS) in ESC member countries.Methods and Results: The HFA Atlas survey was conducted in 2018-2019 in 42 ESC countries. The quality and completeness of source data varied across countries. The median incidence of HF was 3.20 [interquartile range (IQR) 2.66-4.17] cases per 1000 person-years, ranging from ≤2 in Italy and Denmark to >6 in Germany. The median HF prevalence was 17.20 (IQR 14.30-21) cases per 1000 people, ranging from ≤12 in Greece and Spain to >30 in Lithuania and Germany. The median number of HF hospitalizations was 2671 (IQR 1771-4317) per million people annually, ranging from <1000 in Latvia and North Macedonia to >6000 in Romania, Germany and Norway. The median length of hospital stay for an admission with HF was 8.50 (IQR 7.38-10) days. Diagnostic and management resources for HF varied, with high-income ESC member countries having substantially more resources compared with middle-income countries. The median number of hospitals with dedicated HF centres was 1.16 (IQR 0.51-2.97) per million people, ranging from <0.10 in Russian Federation and Ukraine to >7 in Norway and Italy. Nearly all countries reported full or partial reimbursement of standard GDMT, except ivabradine and sacubitril/valsartan. Almost all countries reported having NHFS or working groups and nearly half had HF patient organizations.Conclusions: The first report from the HFA Atlas has shown considerable heterogeneity in HF disease burden, the resources available for its management and data quality across ESC member countries. The findings emphasize the need for a systematic approach to the capture of HF statistics so that inequalities and improvements in care may be quantified and addressed. [ABSTRACT FROM AUTHOR]

Aims: Use of sodium–glucose co‐transporter 2 inhibitors (SGLT2i) in real‐world heart failure (HF) is poorly characterised. In contemporary patients with HF and type 2 diabetes mellitus (T2DM) we assessed over time SGLT2i use, clinical characteristics and outcomes associated with SGLT2i use. Methods and results: Type 2 diabetes patients enrolled in the Swedish HF Registry between 2016–2018 were considered. We performed multivariable logistic regression models to assess the independent predictors of SGLT2i use and Cox regression models in a 1:3 propensity score‐matched cohort and relevant subgroups to investigate the association between SGLT2i use and outcomes. Of 6805 eligible HF patients with T2DM, 376 (5.5%) received SGLT2i, whose use increased over time with 12% of patients on treatment at the end of 2018. Independent predictors of SGLT2i use were younger age, HF specialty care, ischaemic heart disease, preserved kidney function, and absence of anaemia. Over a median follow‐up of 256 days, SGLT2i use was associated with a 30% lower risk of cardiovascular (CV) death/first HF hospitalisation (hazard ratio 0.70, 95% confidence interval 0.52–0.95), which was consistent regardless of ejection fraction, background metformin treatment and kidney function. SGLT2i use was also associated with a lower risk of all‐cause and CV death, HF and CV hospitalisation, and CV death/myocardial infarction/stroke. Conclusion: In a contemporary HF cohort with T2DM, SGLT2i use increased over time, was more common with specialist care, younger age, ischaemic heart disease, and preserved renal function, and was associated with lower mortality and morbidity. [ABSTRACT FROM AUTHOR]

Background: Poor health-related quality of life (HRQL) is common in heart failure (HF), but there are few data on HRQL in HF and the association between HRQL and mortality outside Western countries.Methods: We used the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) to record HRQL in 23 291 patients with HF from 40 countries in 8 different world regions in the G-CHF study (Global Congestive Heart Failure). We compared standardized KCCQ-12 summary scores (adjusted for age, sex, and markers of HF severity) among regions (scores range from 0 to 100, with higher score indicating better HRQL). We used multivariable Cox regression with adjustment for 15 variables to assess the association between KCCQ-12 summary scores and the composite of all-cause death, HF hospitalization, and each component over a median follow-up of 1.6 years.Results: The mean age of participants was 65 years; 61% were men; 40% had New York Heart Association class III or IV symptoms; and 46% had left ventricular ejection fraction ≥40%. Average HRQL differed between regions (lowest in Africa [mean± SE, 39.5±0.3], highest in Western Europe [62.5±0.4]). There were 4460 (19%) deaths, 3885 (17%) HF hospitalizations, and 6949 (30%) instances of either event. Lower KCCQ-12 summary score was associated with higher risk of all outcomes; the adjusted hazard ratio (HR) for each 10-unit KCCQ-12 summary score decrement was 1.18 (95% CI, 1.17-1.20) for death. Although this association was observed in all regions, it was less marked in South Asia, South America, and Africa (weakest association in South Asia: HR, 1.08 [95% CI, 1.03-1.14]; strongest association in Eastern Europe: HR, 1.31 [95% CI, 1.21-1.42]; interaction P<0.0001). Lower HRQL predicted death in patients with New York Heart Association class I or II and III or IV symptoms (HR, 1.17 [95% CI, 1.14-1.19] and HR, 1.14 [95% CI, 1.12-1.17]; interaction P=0.13) and was a stronger predictor for the composite outcome in New York Heart Association class I or II versus class III or IV (HR 1.15 [95% CI, 1.13-1.17] versus 1.09 [95% CI, [1.07-1.11]; interaction P<0.0001). HR for death was greater in ejection fraction ≥40 versus <40% (HR, 1.23 [95% CI, 1.20-1.26] and HR, 1.15 [95% CI, 1.13-1.17]; interaction P<0.0001).Conclusion: HRQL is a strong and independent predictor of all-cause death and HF hospitalization across all geographic regions, in mildly and severe symptomatic HF, and among patients with preserved and reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078166. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated whether the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic was associated with changes in the pattern of acute cardiovascular admissions across European centers.Methods: We set-up a multicenter, multinational, pan-European observational registry in 15 centers from 12 countries. All consecutive acute admissions to emergency departments and cardiology departments throughout a 1-month period during the COVID-19 outbreak were compared with an equivalent 1-month period in 2019. The acute admissions to cardiology departments were classified into 5 major categories: acute coronary syndrome, acute heart failure, arrhythmia, pulmonary embolism, and other.Results: Data from 54,331 patients were collected and analyzed. Nine centers provided data on acute admissions to emergency departments comprising 50,384 patients: 20,226 in 2020 compared with 30,158 in 2019 (incidence rate ratio [IRR] with 95% confidence interval [95%CI]: 0.66 [0.58-0.76]). The risk of death at the emergency departments was higher in 2020 compared to 2019 (odds ratio [OR] with 95% CI: 4.1 [3.0-5.8], P < 0.0001). All 15 centers provided data on acute cardiology departments admissions: 3007 patients in 2020 and 4452 in 2019; IRR (95% CI): 0.68 (0.64-0.71). In 2020, there were fewer admissions with IRR (95% CI): acute coronary syndrome: 0.68 (0.63-0.73); acute heart failure: 0.65 (0.58-0.74); arrhythmia: 0.66 (0.60-0.72); and other: 0.68(0.62-0.76). We found a relatively higher percentage of pulmonary embolism admissions in 2020: odds ratio (95% CI): 1.5 (1.1-2.1), P = 0.02. Among patients with acute coronary syndrome, there were fewer admissions with unstable angina: 0.79 (0.66-0.94); non-ST segment elevation myocardial infarction: 0.56 (0.50-0.64); and ST-segment elevation myocardial infarction: 0.78 (0.68-0.89).Conclusion: In the European centers during the COVID-19 outbreak, there were fewer acute cardiovascular admissions. Also, fewer patients were admitted to the emergency departments with 4 times higher death risk at the emergency departments. [ABSTRACT FROM AUTHOR]

Aims: Renin–angiotensin–aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID‐19). We investigated the association between use of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID‐19 hospitalization/death in a large nationwide population. Methods and results: Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020. COVID‐19 cases were defined based on hospitalization/death for COVID‐19. Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID‐19 in the overall population, and of all‐cause mortality in COVID‐19 cases. We performed consistency analysis to quantify the impact of potential unmeasured confounding. Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID‐19. After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID‐19 (odds ratio 0.86, 95% confidence interval 0.81–0.91) in the overall population, and with reduced mortality in COVID‐19 cases (hazard ratio 0.89, 95% confidence interval 0.82–0.96). MRA use was not associated with risk of any outcome. Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use. Conclusions: In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID‐19. [ABSTRACT FROM AUTHOR]

Impaired left atrial (LA) function in heart failure with preserved ejection fraction (HFpEF) is associated with adverse outcomes. A subgroup of HFpEF may have LA myopathy out of proportion to left ventricular (LV) dysfunction; therefore, we sought to characterize HFpEF patients with disproportionate LA myopathy. In the prospective, multicenter, Prevalence of Microvascular Dysfunction in HFpEF study, we defined disproportionate LA myopathy based on degree of LA reservoir strain abnormality in relation to LV myopathy (LV global longitudinal strain [GLS]) by calculating the residuals from a linear regression of LA reservoir strain and LV GLS. We evaluated associations of disproportionate LA myopathy with hemodynamics and performed a plasma proteomic analysis to identify proteins associated with disproportionate LA myopathy; proteins were validated in an independent sample. Disproportionate LA myopathy correlated with better LV diastolic function but was associated with lower stroke volume reserve after passive leg raise independent of atrial fibrillation (AF). Additionally, disproportionate LA myopathy was associated with higher pulmonary artery systolic pressure, higher pulmonary vascular resistance, and lower coronary flow reserve. Of 248 proteins, we identified and validated 5 proteins (involved in cardiomyocyte stretch, extracellular matrix remodeling, and inflammation) that were associated with disproportionate LA myopathy independent of AF. In HFpEF, LA myopathy may exist out of proportion to LV myopathy. Disproportionate LA myopathy is a distinct HFpEF subtype associated with worse hemodynamics and a distinct proteomic signature, independent of AF. [ABSTRACT FROM AUTHOR]

Self‐care is essential in the long‐term management of chronic heart failure. Heart failure guidelines stress the importance of patient education on treatment adherence, lifestyle changes, symptom monitoring and adequate response to possible deterioration. Self‐care is related to medical and person‐centred outcomes in patients with heart failure such as better quality of life as well as lower mortality and readmission rates. Although guidelines give general direction for self‐care advice, health care professionals working with patients with heart failure need more specific recommendations. The aim of the management recommendations in this paper is to provide practical advice for health professionals delivering care to patients with heart failure. Recommendations for nutrition, physical activity, medication adherence, psychological status, sleep, leisure and travel, smoking, immunization and preventing infections, symptom monitoring, and symptom management are consistent with information from guidelines, expert consensus documents, recent evidence and expert opinion. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three European Society of Cardiology Associations, Heart Failure Association (HFA), European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI), focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains: (i) overcoming CRT under-utilization, (ii) better understanding of pre-implant characteristics, (iii) abandoning the term 'non-response' and replacing this by the concept of disease modification, and (iv) implementing a dedicated post-implant CRT care pathway. [ABSTRACT FROM AUTHOR]