Search

Aims: Heart failure outcomes remain poor despite advances in therapy. The European Society of Cardiology Heart Failure III Registry (ESC HF III Registry) aims to characterize HF clinical features and outcomes and to assess implementation of guideline‐recommended therapy in Europe and other ESC affiliated countries. Methods: Between 1 November 2018 and 31 December 2020, 10 162 patients with chronic or acute/worsening HF with reduced, mildly reduced, or preserved ejection fraction were enrolled from 220 centres in 41 European or ESC affiliated countries. The ESC HF III Registry collected data on baseline characteristics (hospital or clinic presentation), hospital course, diagnostic and therapeutic decisions in hospital and at the clinic visit; and on outcomes at 12‐month follow‐up. These data include demographics, medical history, physical examination, biomarkers and imaging, quality of life, treatments, and interventions – including drug doses and reasons for non‐use, and cause‐specific outcomes. Conclusion: The ESC HF III Registry will provide comprehensive and unique insight into contemporary HF characteristics, treatment implementation, and outcomes, and may impact implementation strategies, clinical discovery, trial design, and public policy. [ABSTRACT FROM AUTHOR]

Aims: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real‐world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD. Methods and results: We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30–44, 45–59 or ≥60 ml/min/1.73 m2, respectively. An eGFR ≥60 ml/min/1.73 m2 and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98–1.10), all‐cause death (HR 1.02, 95% CI 0.97–1.08) as well as of all‐cause hospitalization (HR 0.99, 95% CI 0.95–1.02) across the eGFR spectrum including also severe CKD. Conclusions: The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum. [ABSTRACT FROM AUTHOR]

Aims: Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity‐induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b–3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF. Methods: In phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6‐min walk distance (6MWD) of 30–400 m with a <50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ‐TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ‐TSS. The sample size provides 85% power to detect placebo‐adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ‐TSS at overall two‐sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo. Conclusion: ENDEAVOR is the first phase 2b–3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF. [ABSTRACT FROM AUTHOR]

Aims: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality/morbidity in heart failure (HF). We explored the implementation of SGLT2i over time, and patient characteristics associated with their use, in a large, nationwide population with HF with reduced ejection fraction (HFrEF). Methods and results: Patients with HFrEF (ejection fraction <40%), no type 1 diabetes, estimated glomerular filtration rate (eGFR) <20 ml/min/1.73 m2 and/or on dialysis, registered in the Swedish HF Registry between 1 November 2020 and 5 August 2022 were included. Independent predictors of use were investigated by multivariable logistic regressions. Of 8192 patients, 37% received SGLT2i. Use increased overall from 20.5% to 59.0% over time, from 46.2% and 12.5% to 69.8% and 55.4% in patients with and without type 2 diabetes, from 14.7% and 22.3% to 58.0% and 59.8% in eGFR <60 versus ≥60 ml/min/1.73 m2, from 21.0% and 18.9% to 61.6% and 52.0% in males versus females, from 24.2% and 18.0% to 60.8% and 57.7% in patients with versus without recent HF hospitalization, from 26.1% and 19.8% to 54.7% and 59.6% in inpatients versus outpatients, and from 20.2% and 21.2% to 59.2% and 58.7% in those with HF duration <6 versus ≥6 months, respectively. Important characteristics associated with SGLT2i use were male sex, recent HF hospitalization, specialized HF follow‐up, lower ejection fraction, type 2 diabetes, higher education level, use of other HF/cardiovascular interventions. Older age, higher blood pressure, atrial fibrillation and anaemia were associated with less use. Discontinuation rate at 6 and 12 months was 13.1% and 20.0%, respectively. Conclusions: Use of SGLT2i increased three‐fold over 2 years. Although this indicates a more rapid translation of trial results and guidelines into clinical practice compared to previous HF drugs, further efforts are advocated to complete the implementation process while avoiding inequities across different patient subgroups and discontinuations. [ABSTRACT FROM AUTHOR]

Aims: Iron deficiency (ID) is common in heart failure (HF) and linked with poor prognosis regardless of anaemia. We assessed temporal trends in ID testing, ID prevalence, ID incidence, iron need, and outcomes associated with ID in HF across the ejection fraction (EF) spectrum. Methods and results: From the Swedish HF registry, we enrolled 15 197 patients from Region Stockholm with available EF and collected laboratory tests from routine practice. Iron screening improved since 2016 but remained <25% as of 2018. In 1486 patients with iron biomarkers at baseline, the prevalence of ID was 55% (HF with reduced EF 54%; mildly reduced EF 51%; preserved EF 61%). Iron need was ≥1500 mg in 72% of patients. ID was independently associated with higher risk for HF rehospitalizations (incidence rate ratio [IRR] 1.62, 95% confidence interval [CI] 1.13–2.31) and with cardiovascular (CV) death or repeated HF hospitalizations (IRR 1.63, 95% CI 1.15–2.30) regardless of EF (p‐interaction 0.21 and 0.26, respectively), but not with all‐cause death, CV death, or first HF hospitalization. Among 96 patients without ID at baseline and with follow‐up iron biomarkers, 21% developed ID within 6 months. Conclusions: Iron deficiency screening improved over time but is still limitedly implemented, despite being highly prevalent and incident, and independently associated with CV death or HF rehospitalizations regardless of EF. Most patients with ID had an iron need necessitating either repeated administrations of intravenous iron or a preparation permitting >1000 mg doses. These data highlight the need for improved screening for ID in HF. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that initiation versus non-initiation of sacubitril/valsartan is associated with a more favorable subsequent change in left ventricular ejection fraction (LVEF) in a real-world setting. A prospective, non-randomized, double-arm, open-label, cohort study had been conducted across 687 centers in 17 European countries enrolling HFrEF patients aged ≥18 years with symptoms of HF (New York Heart Association [NYHA] II–IV) and "reduced LVEF". For the current analysis, 2602 patients with LVEF measured at baseline and follow-up were chosen, of which 860 (33%, mean age 67 years, 26% women) were started on sacubitril/valsartan at baseline and 1742 (67%, 68 years, 23% women) were not. Patients started on sacubitril/valsartan had higher NYHA class and lower LVEF. LVEF increased from mean 32.7% to 38.1% in the sacubitril/valsartan group versus from 35.9% to 38.7% in the non-sacubitril/valsartan group (mean difference in increase 2.6%, p < 0.001). LVEF increased from baseline in 64% versus 53% of patients and increased by ≥5% (absolute %) in 50% versus 35% of patients in the sacubitril/valsartan versus non-sacubitril/valsartan groups, respectively. In the overall cohort, initiation of sacubitril/valsartan was independently associated with any increase in LVEF (adjusted odds ratio [OR] 1.49 [1.26–1.75]) and with increase by ≥5% (OR 1.65 [1.39–1.95]). Initiating versus not initiating sacubitril/valsartan was independently associated with a greater subsequent increase in LVEF in this real-world setting. Reverse cardiac remodeling may be one mechanism of benefit of sacubitril/valsartan. • In this European prospective observational analysis of 2602 patients with HFrEF, there was a greater mean increase in LVEF in patients initiated on sacubitril/valsartan as compared to usual care over 12 months follow-up • The association between initiation of sacubitril/valsartan and subsequent increase in LVEF was independent of baseline variables and other therapy • The findings from this analysis indicate that initiation of sacubitril/valsartan may lead to favorable LV remodeling, and this may be one reason sacubitril/valsartan improves outcomes [ABSTRACT FROM AUTHOR]

Aims: To investigate incidence, predictors and prognostic implications of longitudinal New York Heart Association (NYHA) class changes (i.e. improving or worsening vs. stable NYHA class) in heart failure (HF) across the ejection fraction (EF) spectrum. Methods and results: From the Swedish HF Registry, 13 535 patients with EF and ≥2 NYHA class assessments were considered. Multivariable multinomial regressions were fitted to identify the independent predictors of NYHA change. Over a 1‐year follow‐up, 69% of patients had stable, 17% improved, and 14% worsened NYHA class. Follow‐up in specialty care predicted improving NYHA class, whereas an in‐hospital patient registration, lower EF, renal disease, lower mean arterial pressure, older age, and longer HF duration predicted worsening. The association between NYHA change and subsequent outcomes was assessed with multivariable Cox models. When adjusting for the NYHA class at baseline, improving NYHA class was independently associated with lower while worsening with higher risk of all‐cause and cardiovascular mortality, and first HF hospitalization. After adjustment for the NYHA class at follow‐up, NYHA class change did not predict morbidity/mortality. NYHA class assessment at baseline and follow‐up predicted morbidity/mortality on top of the changes. Results were consistent across the EF spectrum. Conclusion: In a large real‐world HF population, NYHA class trajectories predicted morbidity/mortality after extensive adjustments. However, the prognostic role was entirely explained by the resulting NYHA class, i.e. the follow‐up value. Our results highlight that considering one‐time NYHA class assessment, rather than trajectories, might be the preferable approach in clinical practice and for clinical trial design. [ABSTRACT FROM AUTHOR]

This article discusses a study that analyzed the safety and efficacy of the drug dapagliflozin in patients with heart failure (HF) and preserved or mildly reduced ejection fraction (HFpEF or HFmrEF) and chronic obstructive pulmonary disease (COPD). The study found that patients with COPD had a higher risk of cardiovascular death or worsening HF compared to those without COPD. However, dapagliflozin was equally effective in reducing this risk in both groups. The article suggests that COPD and HFpEF may share underlying pathophysiological mechanisms and that dapagliflozin may have potential benefits in treating COPD. [Extracted from the article]

In particular, wild-type (wt) ATTR amyloidosis is increasingly recognized as a common cause of HFpEF.[2] Diagnosing HFpEF in cardiac amyloidosis or diagnosing cardiac amyloidosis in HFpEF? B This article refers to 'Value of the HFA-PEFF and H SB 2 sb FPEF scores in patients with heart failure and preserved ejection fraction caused by cardiac amyloidosis' by D. Tomasoni I et al i ., published in this issue on pages 2374-2386. b Heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly common and projected to be the dominant form of HF in the future.[1] Cardiac amyloidosis (CA), caused by immunoglobulin light-chain (AL) amyloidosis or transthyretin (ATTR) amyloidosis are under-recognized causes of cardiomyopathy and HF. [Extracted from the article]

[Display omitted] [ABSTRACT FROM AUTHOR]

Background: Heart transplantation (HTx) and implantable left ventricular assist systems (LVAS) improve outcomes in advanced heart failure but may be underutilized. We hypothesized that screening can identify appropriate candidates.Methods and Results: The ScrEEning for advanced Heart Failure treatment (SEE-HF) study was a multicentre prospective study screening patients with existing cardiac resynchronization therapy (CRT) and/or implantable cardioverter-defibrillator (ICD) for ejection fraction ≤40% and New York Heart Association (NYHA) class III-IV, and subsequently for guideline-based HTx and LVAS indication. Of 1722 (mean age 64 ± 14 years, 26% women) patients screened at eight centres in seven European countries, 121 (7.0%) were eligible and 99 (5.7%; mean age 61 ± 10 years, 19% women) patients were enrolled for detailed assessment. Twenty-six of the 99 enrolled patients (26%) were eligible for either HTx or LVAD (18 eligible for HTx; 7 eligible for LVAD; and 1 eligible for both). Eleven patients were listed for HTx and three received an LVAS. Eligible patients were 61 ± 8 years and 19% women, whereas those actually receiving intervention were 56 ± 8 years and 8% women.Conclusions: Among patients with CRT and/or ICD, a minority have NYHA class III-IV heart failure and ejection fraction ≤40%. Among these, however, more than one-quarter have an unrecognized need for HTx or LVAS. When patients are offered intervention based on screening, many decline. Discrepancies exist between clinical and patient equipoise. Clinical Trial Registration ClinicalTrials.gov Unique Identifier: NCT00894387. [ABSTRACT FROM AUTHOR]

Aims Cardiac resynchronization therapy (CRT) improves outcomes in heart failure (HF) but may be underutilized. The reasons are unknown. Methods and results We linked the Swedish Heart Failure Registry to national registries with ICD-10 (International Classification of Diseases-10th Revision) co-morbidity diagnoses and demographic and socio-economic data. In patients with EF ≤39% and NYHA II-IV, we assessed prevalence of CRT indication and CRT use. In those with CRT indication, we assessed the association between 37 potential baseline covariates and CRT non-use using multivariable generalized estimating equation (GEE) models. Of 12 807 patients (mean age 71±12 years, 28% female), 841 (7%) had CRT, 3094 (24%) had an indication for but non-use of CRT, and 8872 (69%) had no indication. Important variables independently associated with CRT non-use were: HF duration <6months [risk ratio (RR) 1.21, 95% confidence interval (CI) 1.17-1.24]; non-cardiology planned follow-up (RR 1.14, 95% CI 1.09-1.18); age >75 years (RR 1.13, 95% CI 1.09-1.18); non-cardiology care at baseline (RR 1.10, 95% CI 1.07-1.14); small-town non-university centre (RR 1.08, 95% CI 1.05-1.12); female sex (RR 1.07 95% CI 1.03-1.10) (all P < 0.05); as was absence of AF, living alone; psychiatric diagnosis; smoking; and non-use of HF drugs. Education, income, cancer, or HF characteristics were not independently associated with CRT non-use. Conclusion In this population-wide HF registry, CRT was underutilized. Non-use was associated mostly with demographic and organizational, but not clinical or socio-economic factors. This calls for programmes to raise awareness of CRT indications and improve access and referrals to cardiology specialists. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a heterogeneous syndrome, and the specific sub-category HF with mildly reduced ejection fraction (EF) range (HFmrEF; 41–49% EF) is only recently recognised as a distinct entity. Cluster analysis can characterise heterogeneous patient populations and could serve as a stratification tool in clinical trials and for prognostication. The aim of this study was to identify clusters in HFmrEF and compare cluster prognosis. Latent class analysis to cluster HFmrEF patients based on their characteristics was performed in the Swedish HF registry (n = 7316). Identified clusters were validated in a Dutch cross-sectional HF registry-based dataset CHECK-HF (n = 1536). In Sweden, mortality and hospitalisation across the clusters were compared using a Cox proportional hazard model, with a Fine-Gray sub-distribution for competing risks and adjustment for age and sex. Six clusters were discovered with the following prevalence and hazard ratio with 95% confidence intervals (HR [95%CI]) vs. cluster 1: 1) low-comorbidity (17%, reference), 2) ischaemic-male (13%, HR 0.9 [95% CI 0.7–1.1]), 3) atrial fibrillation (20%, HR 1.5 [95% CI 1.2–1.9]), 4) device/wide QRS (9%, HR 2.7 [95% CI 2.2–3.4]), 5) metabolic (19%, HR 3.1 [95% CI 2.5–3.7]) and 6) cardio-renal phenotype (22%, HR 2.8 [95% CI 2.2–3.6]). The cluster model was robust between both datasets. We found robust clusters with potential clinical meaning and differences in mortality and hospitalisation. Our clustering model could be valuable as a clinical differentiation support and prognostic tool in clinical trial design. [Display omitted] • Six distinct clusters: young-low comorbidity burden, ischaemic-male, atrial fibrillation, wide-QRS, metabolic, cardio-renal. • The cluster model was robust, clusters could be replicated in an external validation cohort of 1536 Dutch HFmrEF patients. • A pragmatic approach was used in defining the cluster model with 10 variables, we found overlap with other cluster studies. [ABSTRACT FROM AUTHOR]

The historical classification of heart failure (HF) has considered two distinct subgroups, HF with reduced ejection fraction (HFrEF), generally classified as EF below 40%, and HF with preserved ejection fraction (HFpEF) variably classified as EF above 40%, 45% or 50%. One of the principal reasons behind this distinction was related to presence of effective therapy in HFrEF, but not in HFpEF. Recently the expanding knowledge in the specific subgroup of patient with a LVEF between 41% and 49% and the potential benefit of new therapies and of those used in patients with LVEF below 40%, has led to rename this group as HF with mildly reduced EF (HFmrEF). In this review we discuss the reasons behind this modification, we summarize the main characteristics of HFmrEF the similarities and differences with the two other EF categories, and finally we provide a comprehensive overview of the current available evidence supporting the treatment of patients with HFmrEF. [Display omitted] Summary Figure. Summary of pro and cons for treatment of heart failure with mildly reduced ejection fraction. [ABSTRACT FROM AUTHOR]

Aims: We assessed eligibility for omecamtiv mecarbil (OM) in a real-world cohort with heart failure with reduced ejection fraction (HFrEF) according to the selection criteria of the GALACTIC-HF trial (trial scenario) and selected trial´s criteria more likely to impact real-world use (pragmatic scenario). Methods and results: We included 31,015 patients with HFrEF lasting ≥3 months and registered in the Swedish HF registry between 2000–2021. Trial eligibility was calculated by applying all the GALACTIC-HF selection criteria. The pragmatic scenario considered only the New York Heart Association class, history of worsening HF, N-terminal pro-B-type natriuretic peptides (NT-proBNP), blood pressure and renal failure criteria defined as in the trial. Eligibility for OM in chronic HFrEF was 21% and 36% in the trial and pragmatic scenarios, respectively. Eligibility was higher in those with EF<30% (trial: 27%, pragmatic: 44%), in-patients (trial:30%, pragmatic:57%), severe HF (trial: 35%, pragmatic: 60%), NYHA class III-IV (trial: 26%, pragmatic: 45%), and NT-proBNP≥5,000pg/mL (trial: 30%, pragmatic: 51%). The criteria that most limited eligibility were history of a recent worsening HF event (60% eligible in chronic HFrEF), elevated NT-proBNP (82% eligible), and deviating blood pressure (82% eligible). Overall, eligible patients were characterized by more severe HF and higher CV event-rates in both scenarios, and higher comorbidity burden in the pragmatic scenario. Conclusion: Approximately 21% of real-world chronic HFrEF patients would be eligible for OM according to the GALACTIC-HF selection criteria, and 36% according to the criteria more likely to affect OM use in clinical practice. Criteria in both scenarios identified a patient-group with severe HF and high CV event-rates. [ABSTRACT FROM AUTHOR]

Aims: The aim of this analysis was to provide data on the overall comorbidity burden, both cardiovascular (CV) and non‐CV, in a large real‐world heart failure (HF) population across the ejection fraction (EF). Methods and results: Patients with HF from the Swedish HF Registry between 2000 and 2021 were included. Of 91 463 patients (median age 76 years [interquartile range 67–82]), 98% had at least one among the 17 explored comorbidities (94% at least one CV and 85% at least one non‐CV comorbidity). All comorbidities, except for coronary artery disease (CAD), were more frequent in HF with preserved EF (HFpEF). Patients with multiple comorbidities were older, more likely female, inpatients, with HFpEF, worse New York Heart Association class and higher N‐terminal pro‐B‐type natriuretic peptide levels. In a multivariable Cox model, 12 comorbidities were independently associated with a higher risk of death from any cause. The highest risk was associated with dementia (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.45–1.65), chronic kidney disease (HR 1.37, 95% CI 1.34–1.41), chronic obstructive pulmonary disease (HR 1.32, 95% CI 1.28–1.35). Obesity was associated with a lower risk of all‐cause death (HR 0.81, 95% CI 0.79–0.84). CAD and valvular heart disease were associated with a higher risk of all‐cause and CV mortality, but not non‐CV mortality, whereas cancer and musculo‐skeletal disease increased the risk of non‐CV mortality. A significant interaction with EF was observed for several comorbidities. Occurrence of CV and non‐CV outcomes was related to the number of CV and non‐CV comorbidities, respectively. Conclusion: The burden of both CV and non‐CV comorbidities was high in HF regardless of EF, but overall higher in HFpEF. Multimorbidity was associated with a high risk of death with a different burden on CV or non‐CV outcomes. [ABSTRACT FROM AUTHOR]

Despite worsening heart failure (HF) being extremely common, expensive, and associated with substantial risk of death, there remain no dedicated clinical practice guidelines for the specific management of these patients. The lack of a management guideline is despite a rapidly evolving evidence-base, as a number of recent clinical trials have demonstrated multiple therapies to be safe and efficacious in this high-risk population. Herein, we propose a framework for treating worsening HF with reduced ejection fraction with the sense of urgency it deserves. This includes treating congestion; managing precipitants; and establishing a foundation of rapid-sequence, simultaneous, and/or in-hospital initiation of quadruple medical therapy for HF with reduced ejection fraction, with the top priority being at least low doses of all 4 medications. Moreover, to maximally reduce residual clinical risk, we further propose consideration of upfront simultaneous use of vericiguat (ie, quintuple medical therapy) and administration of intravenous iron for those who are iron deficient. [Display omitted] • Clinical practice guidelines do not specifically address management of patients with worsening HFrEF. • Management of patients with worsening HFrEF should include simultaneous or rapid sequence initiation of the 4 classes of medications that form the cornerstones of therapy. • To reduce residual risk, simultaneous use of vericiguat and intravenous iron should be considered. [ABSTRACT FROM AUTHOR]

Aims: The Heart Failure Association of the European Society of Cardiology has recently proposed to optimize guideline‐directed medical treatments according to patient's profiles. The aim of this analysis was to investigate prevalence/characteristics/treatments/outcomes for individual profiles. Methods and results: Patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Swedish Heart Failure Registry (SwedeHF) between 2013 and 2021 were considered. Among 108 profiles generated by combining different strata of renal function (by estimated glomerular filtration rate [eGFR]), systolic blood pressure (sBP), heart rate, atrial fibrillation (AF) status and presence of hyperkalaemia, 93 were identified in our cohort. Event rates for a composite of cardiovascular (CV) mortality or first HF hospitalization were calculated for each profile. The nine most frequent profiles accounting for 70.5% of the population had eGFR 30–60 or ≥60 ml/min/1.73 m2, sBP 90–140 mmHg and no hyperkalaemia. Heart rate and AF were evenly distributed. The highest risk of CV mortality/first HF hospitalization was observed in those with concomitant eGFR 30–60 ml/min/1.73 m2 and AF. We also identified nine profiles with the highest event rates, representing only 5% of the study population, characterized by no hyperkalaemia, even distribution among the sBP strata, predominance of eGFR <30 ml/min/1.73 m2 and AF. The three profiles with eGFR 30–60 ml/min/1.73 m2 also showed sBP <90 mmHg. Conclusions: In a real‐world cohort, most patients fit in a few easily identifiable profiles; the nine profiles at highest risk of mortality/morbidity accounted for only 5% of the population. Our data might contribute to identifying profile‐tailored approaches to guide drug implementation and follow‐up. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium–glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype‐based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence‐based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy. [ABSTRACT FROM AUTHOR]

A recent study published in the European Journal of Heart Failure investigated the effects of acyl ghrelin infusion on growth hormone (GH) release in patients with heart failure and reduced ejection fraction (HFrEF). The study found that acyl ghrelin significantly increased circulating GH levels in these patients. The researchers also observed a correlation between acyl ghrelin and GH concentrations. These findings suggest that treatment with acyl ghrelin may lead to an appropriate rapid GH response and increased cardiac output in patients with HFrEF. However, the study had a modest sample size, and further research is needed to confirm these results. [Extracted from the article]

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]

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]

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: 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]

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 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]

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]

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]

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]

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]

Aims: 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.Methods and Results: 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.Conclusions: 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%. [ABSTRACT FROM AUTHOR]

Aim: The prognostic value of natriuretic peptides in the management of heart failure (HF) patients with ejection fraction (EF) <40% is well established, but is less known for those with EF ≥40% managed in primary care (PC). Therefore, the aim of this study is to describe the prognostic significance of plasma NT-proBNP in such patients managed in PC. Subjects: We included 924 HF patients (48% women) with EF ≥40% and NT-proBNP registered in the Swedish Heart Failure Registry. Follow-up was 1100 ± 687 days. Results: One-, three- and five-year mortality rates were 8.1%, 23.9% and 44.7% in patients with EF 40–50% (HFmrEF) and 7.3%, 23.6% and 37.2% in patients with EF ≥50% (HFpEF) (p = 0.26). Patients with the highest mean values of NT-proBNP had the highest all-cause mortality but wide standard deviations (SDs). In univariate regression analysis, there was an association only between NT-proBNP quartiles and all-cause mortality. In HFmrEF patients, hazard ratio (HR) was 1.96 (95% CI 1.60–2.39) p < 0.0001) and in HFpEF patients, HR was 1.72 (95% CI 1.49–1.98) p < 0.0001). In a multivariate Cox proportional hazard regression analysis, adjusted for age, NYHA class, atrial fibrillation and GFR class, this association remained regarding NT-proBNP quartiles [HR 1.83 (95% CI 1.38–2.44), p < 0.0001] and [HR 1.48 (95% CI 1.16–1.90), p = 0.0001], HFmrEF and HFpEF, respectively. Conclusion: NT-proBNP has a prognostic value in patients with HF and EF ≥40% managed in PC. However, its clinical utility is limited due to high SDs and the fact that it is not independent in this population which is characterized by high age and much comorbidity. It is uncertain whether NT-proBNP predicts risk in heart failure with preserved ejection fraction (EF > 40%, HFpEF) managed in primary care. We show that high NT-proBNP predicts increased all-cause mortality in HFpEF-patients managed in primary care. The clinical use is however limited due to large standard deviations, many co-morbidities and high age. Many of these co-morbidities contribute to all-cause mortality and management of these patients should also focus on these co-morbidities. [ABSTRACT FROM AUTHOR]

There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed. [ABSTRACT FROM AUTHOR]

Traditionally, the main indication for cardiopulmonary exercise testing (CPET) in heart failure (HF) was for the selection of candidates to heart transplantation: CPET was mainly performed in middle-aged male patients with HF and reduced left ventricular ejection fraction. Today, CPET is used in broader patients' populations, including women, elderly, patients with co-morbidities, those with preserved ejection fraction, or left ventricular assistance device recipients, i.e. individuals with different responses to incremental exercise and markedly different prognosis. Moreover, the diagnostic and prognostic utility of symptom-limited CPET parameters derived from submaximal tests is more and more considered, since many patients are unable to achieve maximal aerobic power. Repeated tests are also being used for risk stratification and evaluation of intervention, so that these data are now available. Finally, patients, physicians and healthcare decision makers are increasingly considering how treatments might impact morbidity and quality of life rather than focusing more exclusively on hard endpoints (such as mortality) as was often the case in the past. Innovative prognostic flowcharts, with CPET at their core, that help optimize risk stratification and the selection of management options in HF patients, have been developed. [ABSTRACT FROM AUTHOR]

There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed. [ABSTRACT FROM AUTHOR]

Traditionally, the main indication for cardiopulmonary exercise testing (CPET) in heart failure (HF) was for the selection of candidates to heart transplantation: CPET was mainly performed in middle-aged male patients with HF and reduced left ventricular ejection fraction. Today, CPET is used in broader patients' populations, including women, elderly, patients with co-morbidities, those with preserved ejection fraction, or left ventricular assistance device recipients, i.e. individuals with different responses to incremental exercise and markedly different prognosis. Moreover, the diagnostic and prognostic utility of symptom-limited CPET parameters derived from submaximal tests is more and more considered, since many patients are unable to achieve maximal aerobic power. Repeated tests are also being used for risk stratification and evaluation of intervention, so that these data are now available. Finally, patients, physicians and healthcare decision makers are increasingly considering how treatments might impact morbidity and quality of life rather than focusing more exclusively on hard endpoints (such as mortality) as was often the case in the past. Innovative prognostic flowcharts, with CPET at their core, that help optimize risk stratification and the selection of management options in HF patients, have been developed. [ABSTRACT FROM AUTHOR]

Aims: Clinical features and outcomes in the novel phenotype heart failure with mid-range ejection fraction [HFmrEF, ejection fraction (EF) 40-49%] were compared with heart failure with reduced EF (HFrEF, EF <40%) and preserved EF (HFpEF, EF ≥50%).Methods and Results: In the Swedish Heart Failure Registry, we assessed the association between baseline characteristics and EF group using multivariable logistic regressions, and the association between EF group and all-cause mortality using multivariable Cox regressions. Of 42 061 patients, 56% had HFrEF, 21% had HFmrEF, and 23% had HFpEF. Characteristics were continuous for age (72 ± 12 vs. 74 ± 12 vs. 77 ± 11 years), proportion of women (29% vs. 39% vs. 55%), and 13 other characteristics. Coronary artery disease (CAD) was distinctly more common in HFrEF (54%) and HFmrEF (53%) vs. HFpEF (42%); adjusted odds ratio for CAD in HFmrEF vs. HFpEF was 1.52 [95% confidence interval (CI) 1.41-1.63]. For six additional characteristics HFmrEF resembled HFrEF, for seven characteristics HFmrEF resembled HFpEF, and for 10 characteristics there was no pattern. The adjusted hazard ratio (HR) for mortality in HFrEF vs. HFpEF was 1.35 (95% CI 1.14-1.60) at 30 days, 1.26 (95% CI 1.17-1.35) at 1 year, and 1.20 (95% CI 1.14-1.26) at 3 years. In contrast, HFmrEF and HFpEF had a similar prognosis (HR 1.06, 95% CI 0.86-1.30 at 30 days; HR 1.08, 95% CI 1.00-1.18 at 1 year; and HR 1.06, 95% CI 1.00-1.12 at 3 years). Three-year mortality was higher in HFmrEF than in HFpEF in the presence of CAD (HR 1.11, 95% CI 1.02-1.21), but not in the absence of CAD (HR 1.02, 95% CI 0.94-1.12; P for interaction <0.001).Conclusions: HFmrEF was an intermediate phenotype, except that CAD was more common in HFmrEF and HFrEF vs. HFpEF, crude all-cause mortality was lower in HFmrEF and HFrEF, adjusted all-cause mortality was lower in HFmrEF and HFpEF, and CAD portended a higher adjusted risk of death in HFmrEF and HFrEF. [ABSTRACT FROM AUTHOR]

Aims: As the role of chronic kidney disease (CKD) in different types of heart failure (HF) is poorly understood, our aim was to compare CKD in HF with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF) with regard to prevalence, associations and prognostic role.Methods and Results: Patients in the Swedish Heart Failure Registry were divided into three groups based on EF (≥50%, 40-49% and <40%). CKD was defined as an estimated glomerular filtration rate ≤60 mL/min.1.73 m2 . Associations between covariates and CKD and between CKD and mortality were assessed with multivariable regressions. Of 40 230 patients, 8875 (22%) had HFpEF, 8374 (21%) had HFmrEF, and 22 981 (57%) had HFrEF, with a CKD prevalence of 56%, 48%, and 45%, respectively. Associations between covariates and CKD were similar in all EF groups. One-year mortality with vs. without CKD was 23% vs. 13% in HFpEF, 22% vs. 8% in HFmrEF, and 23% vs. 8% in HFrEF (P < 0.001 for all). After adjustment, CKD was more strongly associated with death in HFrEF and HFmrEF than in HFpEF [hazard ratio (HR) and 95% confidence interval (CI); 1.49 (1.42-1.56) and 1.51 (1.40-1.63) vs. 1.32 (1.24-1.42); P for interaction <0.001]. In receiver operating characteristic (ROC) analyses, CKD was also a stronger predictor of death in HFrEF and HFmrEF than in HFpEF [area under the curve (AUC) 0.699 (0.689-0.709) and 0.700 (0.683-0.716) vs. 0.629 (0.613-0.645)].Conclusion: CKD was associated with similar covariates regardless of EF. Although CKD was more common in HFpEF than in HFmrEF and HFrEF, it may have more of a 'bystander' role in HFpEF, being less associated with mortality and with lower prognostic discrimination. [ABSTRACT FROM AUTHOR]

Aims As the role of chronic kidney disease (CKD) in different types of heart failure (HF) is poorly understood, our aim was to compare CKD in HF with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF) with regard to prevalence, associations and prognostic role. Methods and results Patients in the Swedish Heart Failure Registry were divided into three groups based on EF (≥50%, 40–49% and <40%). CKD was defined as an estimated glomerular filtration rate ≤60 mL/min.1.73 m2. Associations between covariates and CKD and between CKD and mortality were assessed with multivariable regressions. Of 40 230 patients, 8875 (22%) had HFpEF, 8374 (21%) had HFmrEF, and 22 981 (57%) had HFrEF, with a CKD prevalence of 56%, 48%, and 45%, respectively. Associations between covariates and CKD were similar in all EF groups. One-year mortality with vs. without CKD was 23% vs. 13% in HFpEF, 22% vs. 8% in HFmrEF, and 23% vs. 8% in HFrEF (P < 0.001 for all). After adjustment, CKD was more strongly associated with death in HFrEF and HFmrEF than in HFpEF [hazard ratio (HR) and 95% confidence interval (CI); 1.49 (1.42–1.56) and 1.51 (1.40–1.63) vs. 1.32 (1.24–1.42); P for interaction <0.001]. In receiver operating characteristic (ROC) analyses, CKD was also a stronger predictor of death in HFrEF and HFmrEF than in HFpEF [area under the curve (AUC) 0.699 (0.689–0.709) and 0.700 (0.683–0.716) vs. 0.629 (0.613–0.645)]. Conclusion CKD was associated with similar covariates regardless of EF. Although CKD was more common in HFpEF than in HFmrEF and HFrEF, it may have more of a ‘bystander’ role in HFpEF, being less associated with mortality and with lower prognostic discrimination. [ABSTRACT FROM AUTHOR]

Aims Clinical features and outcomes in the novel phenotype heart failure with mid-range ejection fraction [HFmrEF, ejection fraction (EF) 40–49%] were compared with heart failure with reduced EF (HFrEF, EF <40%) and preserved EF (HFpEF, EF ≥50%). Methods and results In the Swedish Heart Failure Registry, we assessed the association between baseline characteristics and EF group using multivariable logistic regressions, and the association between EF group and all-cause mortality using multivariable Cox regressions. Of 42 061 patients, 56% had HFrEF, 21% had HFmrEF, and 23% had HFpEF. Characteristics were continuous for age (72 ± 12 vs. 74 ± 12 vs. 77 ± 11 years), proportion of women (29% vs. 39% vs. 55%), and 13 other characteristics. Coronary artery disease (CAD) was distinctly more common in HFrEF (54%) and HFmrEF (53%) vs. HFpEF (42%); adjusted odds ratio for CAD in HFmrEF vs. HFpEF was 1.52 [95% confidence interval (CI) 1.41–1.63]. For six additional characteristics HFmrEF resembled HFrEF, for seven characteristics HFmrEF resembled HFpEF, and for 10 characteristics there was no pattern. The adjusted hazard ratio (HR) for mortality in HFrEF vs. HFpEF was 1.35 (95% CI 1.14–1.60) at 30 days, 1.26 (95% CI 1.17–1.35) at 1 year, and 1.20 (95% CI 1.14–1.26) at 3 years. In contrast, HFmrEF and HFpEF had a similar prognosis (HR 1.06, 95% CI 0.86–1.30 at 30 days; HR 1.08, 95% CI 1.00–1.18 at 1 year; and HR 1.06, 95% CI 1.00–1.12 at 3 years). Three-year mortality was higher in HFmrEF than in HFpEF in the presence of CAD (HR 1.11, 95% CI 1.02–1.21), but not in the absence of CAD (HR 1.02, 95% CI 0.94–1.12; P for interaction <0.001). Conclusions HFmrEF was an intermediate phenotype, except that CAD was more common in HFmrEF and HFrEF vs. HFpEF, crude all-cause mortality was lower in HFmrEF and HFrEF, adjusted all-cause mortality was lower in HFmrEF and HFpEF, and CAD portended a higher adjusted risk of death in HFmrEF and HFrEF. [ABSTRACT FROM AUTHOR]

Aims Symptom severity assessed by NYHA functional class and QRS duration are essential criteria for selection of heart failure (HF) patients for CRT. This study assessed the relationship between NYHA class, QRS duration, and survival in a nationwide HF registry. Methods and results We studied 13 423 patients with HF in NYHA class II-IV and LVEF <40% in the Swedish Heart Failure Registry. Survival was followed via the Swedish Population Registry. Of 12 534 patients without CRT (age 71±12 years, 29% women), 51% and 49% were in NYHA class II and III-IV, respectively. Patients in NYHA class II compared with class III-IV were younger (69 vs. 73 years), and had a better systolic function (49% vs. 58% with LVEF <30%), P <0.001 for all, and a favourable co-morbidity profile. QRS duration was 116±29 ms in NYHA class II and 119±29 ms in NYHA class III-IV with QRS ≥120 ms found in 37% vs. 44%, and an LBBB in 23% vs. 28% (P < 0.001 for all). Upon multivariable Cox regression adjusting for 40 clinically relevant variables, mortality risk was higher in NYHA class III-IV vs. class II, with a hazard ratio (HR) of 1.31, 95% confidence interval (CI) 1.23-1.40. Mortality was also higher with QRS prolongation ≥120 ms vs. narrow QRS. The HR in NYHA class II patients with non-LBBB was 1.19 (95% CI 1.05-1.36) and in those with LBBB it was 1.16 (95% CI 1.03-1.41). The corresponding HRs in NYHA class III-IV were 1.33 (95% CI 1.21-1.47) and 1.12 (95% CI 1.02-1.22). There was no significant interaction between the effects of NYHA class and QRS duration or morphology on mortality. Applying different scenarios to estimate guideline adherence, fewer patients with NYHA class II (range 14.4-42.6%) compared with NYHA class III-IV (18.0-45.4%) had received a CRT device when indicated. Conclusions In HF with reduced LVEF, QRS prolongation is common and independently linked to worse survival. The increase in mortality risk associated with QRS prolongation of both LBBB and non-LBBB morphology is similar in NYHA class II and III-IV. [ABSTRACT FROM AUTHOR]

Background Heart failure with reduced ejection fraction (HFrEF) exhibits a “reverse metabolic profile”. Whether this profile exists in HF with preserved ejection fraction (HFpEF) is unknown. We tested the hypothesis that HFpEF and HFrEF are similar regarding concentrations of and prognostic impact of leptin and adiponectin. Methods In patients with HFpEF( n = 79), HFrEF( n = 84), and controls( n = 71), we analyzed serum leptin and adiponectin concentrations, their correlations, and associations with outcome. Results Leptin levels in HFpEF and HFrEF were increased ( p < 0.05) compared to controls; with the highest levels in HFpEF, median (IQR), 23.1 (10.2–51.0), vs. HFrEF 15.0 (6.2–33.2), and vs. controls 10.8 (5.4–18.9) ng/mL.There was no difference between HFpEF and HFrEF p = 0.125 (adjusted for gender, BMI and age). Leptin was inversely associated with NT-proBNP ( r = − 0.364 p = 0.001) and associated with better outcome in HFrEF (HR per ln increase of leptin 0.76, 95% CI 0.58–0.99, p = 0.044) but not in HFpEF. Crude levels of adiponectin were similar in HFpEF: 11.8 (7.9–20.1), HFrEF: 13.7 (7.0–21.1), and controls: 10.5 (7.4–15.1) μg/L. In men, adjusted similarly as leptin, there was no difference between HFpEF and HFrEF, p = 0.310 but, compared to controls, higher levels in HFpEF ( p = 0.044) and HFrEF ( p = 0.001). Adiponectin correlated positively with NT-proBNP; r = 0.396 p < 0.001 and higher levels were associated with adverse outcome only in HFrEF (HR per ln increase 2.88 (95% CI 1.02–8.14, p = 0.045). Conclusion HFpEF and HFrEF share elevated levels of leptin and adiponectin. However, the concept of reverse metabolic profile could not be confirmed in HFpEF, suggesting that HFpEF might have a conventional metabolic profile, rather than a distinct HF syndrome. [ABSTRACT FROM AUTHOR]

Background In acute decompensated heart failure (ADHF) with preserved ejection fraction (HFpEF) there are no surrogate endpoints for early phase trials. The aim of the current study was to evaluate whether a reduction in natriuretic peptides (NP) between acute hospital presentation to stable follow-up is associated with improved mortality and morbidity. Methods Patients presenting acutely to the hospital for ADHF with HFpEF enrolled in the Karolinska Rennes (KaRen) study and reporting N-terminal pro-B-type NP or B-type NP assessment at baseline hospital presentation and at 4–8 weeks follow-up were prospectively studied. Logistic regression analyses were performed to detect the predictors of baseline and changes in NPs. Cox regression models were performed to assess the impact of NP reductions on mortality and the composite of mortality and HF hospitalization. Results Of 361 patients (median follow-up 585 days), 267 (74%) reported an improvement in NPs, while 94 (26%) reported worsening. At baseline, the independent predictors of lower NPs were higher glomerular filtration rate (Odds Ratio [OR] per unit: 1.013; 95% Confidence Interval [CI]: 1.005–1.021) and younger age (OR per year: 0.972; CI: 0.947–0.998). Improvement in NPs at follow-up was predicted by higher heart rate at baseline (OR per bpm: 1.014; CI: 1.003–1.025). After adjustments, the hazard ratio for all-cause death was 0.730 (CI: 0.456–1.169) and for the composite outcome 0.814 (CI: 0.582–1.139) for patients who improved vs. worsened in NP levels. Conclusions In patients presenting acutely to the hospital with HFPEF, an improvement in NP levels did not independently and significantly predict improved mortality and/or morbidity. NPs as surrogate endpoints in acute HFpEF require further study. [ABSTRACT FROM AUTHOR]

Aims: In heart failure with reduced ejection fraction, drug and device therapy improve survival. We studied contemporary trends in utilization of evidence-based therapy and associated survival.Methods and Results: We studied 5908 patients with NYHA class II-IV heart failure, EF <30%, and duration of heart failure ≥6 months registered in the Swedish Heart Failure Registry between 2003 and 2012. Regression using generalized estimation equations was used to examine temporal trends in crude and risk-adjusted rates of utilization of evidence-based heart failure therapy and 30-day, 1-year, and 3-year survival. In 2003 vs. 2012, the risk-adjusted use of therapy and P-values for trends were as follows: renin-angiotensin system antagonists, 88% vs. 86% (P = 0.091); beta-blockers, 85% vs. 93% (P = 0.008); mineralocorticoid receptor antagonists, 53% vs. 42% (P < 0.001); CRT, 2.4% vs. 8.2% (P = 0.074); and implantable cardioverter-defibrillators, 4.0% vs. 10.7% (P = 0.004). During the same period, the risk-adjusted 30-day, 1-year, and 3-year survival was 92% vs. 94% (P = 0.532), 81% vs. 77% (P = 0.260), and 58% vs. 54% (P = 0.425), respectively.Conclusions: In this large nationwide registry, over the last decade the use of evidence-based drug therapy was high and remained stable over time, but, despite an increased use of device therapy, the absolute use was poor. This was associated with an absence of improvement in survival. The improvements in therapy and prognosis over the last generation may be levelling off, and efforts should be directed at improving implementation of evidence-based therapy. [ABSTRACT FROM AUTHOR]