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Despite major advancements in heart failure (HF) management and guideline recommendations over the past two decades, real-world evidence highlights suboptimal implementation of guideline-directed medical therapy (GDMT) for HF with reduced ejection fraction (HFrEF). Low blood pressure (BP) is common in HFrEF patients and represents a major perceived barrier to implementing life-saving treatments in clinical practice, as physicians are often concerned about symptomatic hypotension and its consequences. Although low BP can be seen in those hospitalized with signs of shock, the most common scenario involves non-severe, asymptomatic hypotension in patients receiving foundational therapy for HFrEF, where premature down-titration or discontinuation of GDMT should be avoided. This clinical consensus statement provides a comprehensive overview of low BP in HFrEF, including its definition, risk factors, and effects of HF therapies on BP. We propose management pathways to optimize HFrEF treatment in the context of low BP, ultimately aiming to improve patient outcomes., (© 2025 European Society of Cardiology.)

Aims: To describe the baseline characteristics of the participants in the VICTOR (Vericiguat Global Study in Patients with Chronic Heart Failure; NCT05093933) trial and compare them to recent trials in patients with heart failure and reduced ejection fraction (HFrEF)., Methods and Results: Baseline characteristics were evaluated in 6105 patients randomized to vericiguat or placebo. The mean age of the participants was 67 ± 11 years, 23.6% were women, 64.4% were White, and 10.7% were self-identified Black. Overall, 29.1% of participants were enrolled in Latin and South America, 27.8% and 18.5% in Eastern and Western Europe, 14.0% in Asia-Pacific and 10.6% in North America. The mean left ventricular ejection fraction was 30 ± 7% and 79% had New York Heart Association class II symptoms. Mean estimated glomerular filtration rate was 70.9 ± 24.0 ml/min/1.73 m 2 . Median N-terminal pro-B-type natriuretic peptide level was 1476 (970-2495) pg/ml and 47.5% of participants had no prior hospitalization for heart failure. Baseline therapy included 94.4% beta-blockers, 94.3% renin-angiotensin system modulation (including 56.0% on an angiotensin receptor-neprilysin inhibitor), 77.7% mineralocorticoid receptor antagonists, 59.1% sodium-glucose cotransporter 2 inhibitors, and 32.9% implantable cardioverter-defibrillators. Overall characteristics were relatively similar to other recent HFrEF trials but the VICTOR trial enrolled a higher proportion of participants receiving contemporary drug and device therapy., Conclusion: The VICTOR trial enrolled the most optimally treated population in a phase III heart failure trial. These features will facilitate assessment of the benefit of vericiguat and elucidate the outcomes of patients on up-to-date medical therapy., (© 2025 Merck Sharp & Dohme LLC. Bayer AG and The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background and Aims: Ambulatory patients presenting with signs or symptoms of heart failure (HF) should undergo natriuretic peptide testing. Rates of death, HF hospitalization, and healthcare costs were examined in patients thus identified with suspected de novo HF., Methods: This population-based study (REVOLUTION HF) encompassing two large healthcare regions in Sweden examined patients who presented to outpatient care for the first time between 1 January 2015 and 31 December 2020, who had a recorded sign (peripheral oedema) or symptom (dyspnoea) of HF, and whose N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured >300 ng/L within ±30 days of that sign or symptom. Characteristics, outcomes, healthcare patterns, and healthcare costs for these patients were followed for 1 year. Comparisons were made with matched controls without history of HF, its signs, its symptoms, or elevated NT-proBNP., Results: Overall, 5942 patients (median age 78.7 years; 54% women) presented with suspected de novo HF. Within 1 year, 29% had received a HF diagnosis. Patients with suspected de novo HF had higher rates of all-cause death (11.7 vs. 6.5 events/100 person-years) and HF hospitalizations (12.5 vs. 2.2 events/100 person-years) than matched controls (n = 2048), with the highest event rates in the weeks after presentation. Rates were higher with higher NT-proBNP levels. Although some patients already used HF guideline-directed medical therapies for other indications, initiation of new medications was variable. Healthcare costs were higher in patients with suspected de novo HF than in matched controls, driven mostly by HF and chronic kidney disease., Conclusions: Patients with suspected HF and elevated NT-proBNP had high mortality and morbidity in the weeks after presentation, and accrued substantial healthcare costs, highlighting an urgent need for prompt identification, evaluation, and treatment of HF., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The Heart Failure Frailty Score (HFFS) is a novel, multidimensional tool to assess frailty in patients with heart failure (HF). It has been developed to overcome limitations of existing frailty assessment tools while being practical for clinical use. The HFFS reflects the concept of frailty as a multidimensional, dynamic and potentially reversible state, which increases vulnerability to stressors and risk of poor outcomes in patients with HF., Methods and Results: The HFFS was developed through a Delphi consensus process involving 54 international experts. This approach involved iterative rounds of questionnaires and interviews, where a panel of experts provided their opinions on specific questions prepared by the Steering Committee. The experts were invited to vote and share their views anonymously, using a 5-point Likert scale over iterative rounds. An 80% threshold was set for agreement or disagreement for each statement. Twenty-two variables from four domains (clinical, functional, psycho-cognitive and social) have been selected for inclusion in the HFFS after the third round of the Delphi process. A shorter version (S-HFFS), including 10 variables, has also been developed for daily clinical use., Conclusions: The HFFS is a new multidimensional tool for the identification of frailty in patients with HF. It should also enables healthcare providers to identify potential 'red flags' for frailty in order to develop personalized care plans. The next step will be to validate the new score in patients with HF., (© 2025 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, the soluble guanylate cyclase stimulator vericiguat reduced the risk of hospitalization for heart failure (HHF) or cardiovascular death in patients with heart failure (HF) and reduced ejection fraction (HFrEF) with recent worsening HF. The effect of vericiguat in patients with HFrEF without recent worsening HF remains unknown. The VICTOR (Vericiguat Global Study in Participants with Chronic Heart Failure) trial was designed to assess the efficacy and safety of vericiguat in patients with ejection fraction ≤40% without recent worsening HF on a background of current foundational HFrEF therapy., Methods: The primary endpoint for VICTOR is time to first event for the composite of HHF or cardiovascular death. The trial will also assess the effect of vericiguat on time to cardiovascular death, time to HHF, total HHF, and all-cause death. As an event-driven trial, at least 1080 primary events are expected, but follow-up will continue until the targeted number of at least 590 cardiovascular deaths has been reached. Approximately 6000 participants will be randomized to vericiguat or placebo., Conclusion: VICTOR is the first large event-driven HFrEF trial performed in the contemporary era of quadruple foundational guideline-directed medical therapy, in a compensated ambulatory HF population. VICTOR will add important information to the evidence of the effects of vericiguat across the spectrum of patients with HFrEF., (© 2024 Bayer AG, Merck Sharp & Dohme LLC and The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Left ventricular hypertrophy (LVH) has been associated with an increased risk of cardiovascular (CV) disease and linked to increased morbidity and mortality. In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), hypertension is common, and patients with these co-morbidities additionally have a high prevalence of LVH. This analysis of the prespecified pooled FIDELITY analysis comprising the randomized, double-blind, placebo-controlled, multicentre FIDELIO-DKD and FIGARO-DKD phase III studies aimed to explore the CV and kidney effects of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in patients with CKD and T2D stratified by a diagnosis of LVH at baseline., Methods and Results: A diagnosis of LVH in the FIDELITY patient population was determined at baseline using investigator-reported electrocardiogram (ECG) findings. The two efficacy outcomes, assessed by baseline LVH, were the composite CV outcome of time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure (HHF), and a composite kidney outcome of time to onset of kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) ≥57% from baseline over ≥4 weeks, or kidney-related death. Safety outcomes by baseline LVH were reported as treatment-emergent adverse events. At baseline out of 13 026 patients in FIDELITY, 96.5% had hypertension and 9.6% had investigator-reported LVH. The relative risk reduction for the composite CV and kidney outcomes with finerenone versus placebo was lower in the LVH subgroup; however, the treatment effect of finerenone was not modified by baseline LVH for either outcome (P interaction  = 0.1075 for composite CV outcome and P interaction  = 0.1782 for composite kidney outcome). Analysis of the composite CV outcome components showed a greater reduction in the risk of HHF versus placebo for patients with baseline LVH compared with those without (P interaction  = 0.0024). Overall safety events were comparable between the LVH subgroups and treatment arms. Treatment-emergent hyperkalaemia was observed more frequently with finerenone versus placebo, but discontinuation rates were low in both treatment arms and between LVH subgroups., Conclusions: In conclusion, the overall CV and kidney benefits of finerenone versus placebo were not modified by the presence of LVH at baseline, with overall safety findings being similar between LVH subgroups. A greater benefit was observed for HHF in patients with versus without LVH, suggesting that LVH may be a predictor of the treatment effect of finerenone on HHF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Gene therapy has recently become a reality in the treatment of cardiovascular diseases. Strategies to modulate gene expression using antisense oligonucleotides or small interfering RNA are proving to be safe and effective in the clinic. Adeno-associated viral vector-based gene delivery and CRISPR-Cas9-based genome editing have emerged as efficient strategies for gene delivery and repair in humans. Overall, gene therapy holds the promise not only of expanding current treatment options, but also of intervening in previously untackled causal disease mechanisms with little side effects. This scientific statement provides a comprehensive overview of the various modalities of gene therapy used to treat heart failure and some of its risk factors, and their application in the clinical setting. It discusses specifically the possibilities of gene therapy for hereditary heart diseases and (non)-genetic heart failure. Furthermore, it addresses safety and clinical trial design issues and challenges for future regulatory strategies., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Physicians' adherence to guideline-recommended heart failure (HF) treatment remains suboptimal, especially regarding the target doses. In particular, there is evidence that non-cardiologists are less compliant with HF guideline recommendations. This is likely to have a detrimental impact on patients' survival, readmissions and quality of life. Thus, the present document aims to address the reasons underlying low implementation and under-dosing of guideline-directed medical therapy in HF and to update a guidance for the initiation and rapid titration of HF drugs. In particular, aim of this document is to provide practical indications for drug implementation, to be applied not only by cardiologists but also by GPs and internal medicine doctors., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Atrial fibrillation (AF) remains the most common cardiac arrhythmia worldwide and is associated with significant morbidity and mortality. The European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) have recently released the 2024 guidelines for the management of AF. This review highlights 10 novel aspects of the ESC/EACTS 2024 Guidelines. The AF-CARE framework is introduced, a structural approach that aims to improve patient care and outcomes, comprising of four pillars: [C] Comorbidity and risk factor management, [A] Avoid stroke and thromboembolism, [R] Reduce symptoms by rate and rhythm control, and [E] Evaluation and dynamic reassessment. Additionally, graphical patient pathways are provided to enhance clinical application. A significant shift is the new emphasis on comorbidity and risk factor control to reduce AF recurrence and progression. Individualized assessment of risk is suggested to guide the initiation of oral anticoagulation to prevent thromboembolism. New guidance is provided for anticoagulation in patients with trigger-induced and device-detected sub-clinical AF, ischaemic stroke despite anticoagulation, and the indications for percutaneous/surgical left atrial appendage exclusion. AF ablation is a first-line rhythm control option for suitable patients with paroxysmal AF, and in specific patients, rhythm control can improve prognosis. The AF duration threshold for early cardioversion was reduced from 48 to 24 h, and a wait-and-see approach for spontaneous conversion is advised to promote patient safety. Lastly, strong emphasis is given to optimize the implementation of AF guidelines in daily practice using a patient-centred, multidisciplinary and shared-care approach, with the simultaneous launch of a patient version of the guideline., Competing Interests: Conflict of interest: All authors and collaborators have participated in the 2024 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guideline on Atrial Fibrillation Task force and have submitted declarations of interest which are reported in a supplementary document to the guidelines., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: There is a gap in knowledge about implementing diagnostic tools and therapy for heart failure with preserved ejection fraction (HFpEF) in clinical practice. This survey aimed to assess real-world practice in HFpEF diagnosis and treatment in the international medical community., Methods: An independent academic web-based 29-question survey was designed by a group of heart failure specialists and posted by email and through scientific societies and social networks to a broad community of physicians worldwide., Results: 1.460 physicians from 95 countries answered the survey, with a mean age of 42.2±10.4 years, 39.4 % females, and 85.1 % were cardiologists. The left ventricular ejection fraction cut-off value selected for HFpEF diagnosis was 50 % for 89 % of participants. The scores for the probability of diagnosis of HFpEF were used only by 47.2 %, and H2FPEF was the most used score (31 %). Natriuretic peptides were used by 87.4 % of participants for the diagnostic workup, while the diastolic stress test was only used by 26.2 %. 54.4 % of participants chose SGLT2 inhibitors as their first drug treatment, followed by diuretics (18.6 %) and ACE inhibitors (8.4 %)., Conclusions: In an international academic survey on HFpEF management, the criteria for screening and diagnosis of HFpEF patients remain aligned with classic international guidelines with a low use of diagnostic scores. SGLT2i is the leading therapeutic drug class used for this heterogeneous patient population. These results raise the need to improve education and awareness on diagnosing and managing HFpEF patients., Competing Interests: Declaration of competing interest CS has received honoraria as speaker for Speaker for Novartis, Servier, Merck, Sanofi Pfizer, Astrazeneca, Boehringer Ingelheim, Novo Nordisk, Ely Lilly and as advisor for Bayer, Merck and Novo Nordisk, CF has received travel fees from Pfizer, NM has received consulting fees from Bayer and Amgen and as speaker for Astrazeneca, Novartis and Boehringer Ingelheim, support for attending meetings from Astrazeneca and Novartis, FR has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, were made directly to the University of Zurich). The Department of Cardiology (University Hospital of Zurich/University of Zurich) reports research-, educational- and/or travel grants from Abbott, Abiomed, Alnylam,Amarin, Amgen, Astra Zeneca, At the Limits Ltd., Bayer, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, CM Microport, Concept Medical, CTI, Daiichi Sankyo, Edwards Lifesciences, FomF GmbH, Hamilton Health Sciences, IHF, Innosuisse, IumiraDX, Kantar, LabPoint, MedAlliance, Medcon International, Medical Education Global Solutions, Medtronic, MicroPort, Monocle, Novartis, Novo Nordisk, OM Pharma, Pfizer, Quintiles Switzerland Sarl, RecorMedical, Roche Diagnostics, Roche Pharma, Sahajanand IN, Sanofi, Sarstedt AG, Servier, Terumo Deutschland, Trama Solutions, V- Wave, Vifor, ZOLL. These grants do not impact on Prof. Ruschitzka`s personal remuneration. IJI received support for travel to meetings from Novartis. DM received payment as a speaker for Novartis, Pfizer, Astra Zeneca and support for attending meetings from Pfizer, Astrazeneca and abbot. GR reports grants and personal fees from Astra Zeneca, personal fees and other from Boheringer Ingelheim, other from Bayer, personal fees from Anlylam, other from Medtronic, grants from Servier, grants and non-financial support from Menarini, personal fees from Viatris, grants from Vifor Pharma, outside the submitted work. GGR reports personal fees from Pfizer, personal fees from CSL Vifor, personal fees from Astra Zeneca, personal fees from PTC therapeutics, personal fees from Bristol MS, personal fees from Boehringer Ingelheim, personal fees from Servier, outside the submitted work; GE reports personal fees from NOVO NORDISK, during the conduct of the study; IM reports grants from Boehringer Ingelheim, during the conduct of the study, SZ Served on advisory boards for, or speaker engagements with Abbott, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Medtronic, Merck, Novartis, Novo-Nordisk, Pfizer and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Boehringer Ingelheim, Merck, Novartis, Pfizer, Salubris Bio and Served on advisory boards for, or speaker engagements with Abbott, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Medtronic, Merck, Novartis, Novo-Nordisk, Pfizer and Vifor Pharma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: We analysed baseline characteristics and guideline-directed medical therapy (GDMT) use and decisions in the European Society of Cardiology (ESC) Heart Failure (HF) III Registry., Methods and Results: Between 1 November 2018 and 31 December 2020, 10 162 patients with acute HF (AHF, 39%, age 70 [62-79], 36% women) or outpatient visit for HF (61%, age 66 [58-75], 33% women), with HF with reduced (HFrEF, 57%), mildly reduced (HFmrEF, 17%) or preserved (HFpEF, 26%) ejection fraction were enrolled from 220 centres in 41 European or ESC-affiliated countries. With AHF, 97% were hospitalized, 2.2% received intravenous treatment in the emergency department, and 0.9% received intravenous treatment in an outpatient clinic. AHF was seen by most by a general cardiologist (51%) and outpatient HF most by a HF specialist (48%). A majority had been hospitalized for HF before, but 26% of AHF and 6.1% of outpatient HF had de novo HF. Baseline use, initiation and discontinuation of GDMT varied according to AHF versus outpatient HF, de novo versus pre-existing HF, and by ejection fraction. After the AHF event or outpatient HF visit, use of any renin-angiotensin system inhibitor, angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist and loop diuretics was 89%, 29%, 92%, 78%, and 85% in HFrEF; 89%, 9.7%, 90%, 64%, and 81% in HFmrEF; and 77%, 3.1%, 80%, 48%, and 80% in HFpEF., Conclusion: Use and initiation of GDMT was high in cardiology centres in Europe, compared to previous reports from cohorts and registries including more primary care and general medicine and regions more local or outside of Europe and ESC-affiliated countries., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are prevalent comorbidities associated with significant morbidity/mortality. We assessed prevalence of, patient profiles and outcomes associated with COPD across the ejection fraction (EF) spectrum., Methods: HF patients enrolled in the Swedish HF registry between 2005 and 2021 were considered. Multivariable logistic regression models were fitted to assess patient characteristics independently associated with COPD and Cox regression models for investigating the associations between COPD and outcomes, that is, morbidity/mortality., Results: Among 97 904 HF patients, COPD prevalence was 13%, highest in HF with preserved EF [HFpEF: 16%, HF with mildly reduced EF (HFmrEF): 12%, HF with reduced EF (HFrEF): 11%]. Key patient characteristics independently associated with a diagnosis of COPD included higher EF, female sex, smoking, obstructive sleep disorder, peripheral artery disease, a lower educational level, more severe HF, more likely mineralocorticoid receptor antagonist and diuretic use but less likely use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin-receptor-neprilysin inhibitors (not in HFrEF), beta-blockers, HF device therapies, and follow-up in HF nurse-led clinics. COPD was independently associated with a 15% higher risk of cardiovascular (CV) death/HF hospitalization [hazard ratio: 1.15 (95% confidence interval: 1.11-1.18)], CV death, non-CV death, all-cause death and HF hospitalizations, regardless of EF., Conclusions: COPD was present in every eight patient with HF, and more common with preserved EF. Patients with COPD had more severe HF, heavier comorbidity burden and worse morbidity/mortality regardless of EF. Our results call for improved diagnostic and management strategies in patients with HF and COPD., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Real-world data show that guidelines are insufficiently implemented, and particularly guideline-directed medical therapies (GDMT) are underused in patients with heart failure and reduced ejection fraction (HFrEF) in clinical practice. The Council for Cardiology Practice and the Heart Failure Association of the European Society of Cardiology (ESC) developed a survey aiming to (i) evaluate the perspectives of the cardiology community on the 2021 ESC heart failure (HF) guidelines, (ii) pinpoint disparities in disease management, and (iii) propose strategies to enhance adherence to HF guidelines., Methods and Results: A 22-question survey regarding the diagnosis and treatment of HFrEF was delivered between March and June 2022. Of 457 physicians, 54% were general cardiologists, 19.4% were HF specialists, 18.9% other cardiac specialists, and 7.7% non-cardiac specialists. For diagnosis, 52.1% employed echocardiography and natriuretic peptides (NPs), 33.2% primarily used echocardiography, and 14.7% predominantly relied on NPs. The first drug class initiated in HFrEF was angiotensin-converting enzyme inhibitors/angiotensin receptor-neprilysin inhibitor (ACEi/ARNi) (91.2%), beta-blockers (BB) (73.8%), mineralocorticoid receptor antagonists (MRAs) (53.4%), and sodium-glucose cotransporter 2 (SGLT2) inhibitors (48.1%). The combination ACEi/ARNi + MRA+ BB was preferred by 39.3% of physicians, ACEi/ARNi + SGLT2 inhibitors + BB by 33.3%, and ACEi/ARNi + BB by 22.2%. The time required to initiate and optimize GDMT was estimated to be <1 month by 8.3%, 1-3 months by 52%, 3-6 months by 31.8%, and >6 months by 7.9%. Compared to general cardiologists, HF specialists/academic cardiologists reported lower estimated time-to-initiation, and more commonly preferred a parallel initiation of GDMT rather than a sequential approach., Conclusion: Participants generally followed diagnostic and treatment guidelines, but variations in HFrEF management across care settings or HF specialties were noted. The survey may raise awareness and promote standardized HF care., (© 2024 European Society of Cardiology.)

Patients with heart failure (HF), particularly those with impaired renal function receiving renin-angiotensin-aldosterone system inhibitors (RAASis), are at risk of hyperkalaemia; when hyperkalaemia is severe, this can have serious clinical consequences. The incidence, prevalence, and risk factors for hyperkalaemia reported in randomized trials of RAASis may not reflect clinical practice due to exclusion of patients with elevated serum potassium (sK + ) or severe renal impairment: information on patients managed in routine clinical care is important to understanding the actual burden of hyperkalaemia. This paper reviews the available clinical epidemiology data on hyperkalaemia in HF and considers areas requiring further research. Observational studies published since 2017 that focused on hyperkalaemia, included patients with HF, and had ≥1000 participants were considered. Hyperkalaemia occurrence in HF varied widely from 7% to 39% depending on the setting, HF severity, follow-up length, and concomitant medications. Rates were lowest in patients with newly diagnosed HF and highest in patients with greater disease severity; comorbidities, such as chronic kidney disease and diabetes, and RAASi use, reflected commonly identified risk factors for hyperkalaemia in patients with HF. Hyperkalaemia was most often mild; however, from the limited data available, persistence of mild hyperkalaemia was associated with an increased risk of mortality and major adverse cardiovascular events. There were also limited data available on the progression of hyperkalaemia. Recurrence was common, occurring in one-quarter to two-fifths of hyperkalaemia cases. Despite HF guidelines recommending close monitoring of sK + , 55-93% of patients did not receive appropriate testing before or after initiation of RAASi or in follow-up to moderate/severe hyperkalaemia detection. Many of the observational studies were retrospective and from a single country. There is a need for international, prospective, longitudinal, observational studies, such as the CARE-HK in HF study (NCT04864795), to understand hyperkalaemia's prevalence, incidence, and severity; to identify and characterize cases that persist, progress, and recur; to highlight the importance of sK + monitoring when using RAASi; and to assess the impact of newer HF therapies and potassium binders in clinical practice. Data from both clinical trials and observational studies with adjustments for confounding variables will be needed to assess the contribution of hyperkalaemia to clinical outcomes., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Several mechanisms have been identified in the aetiopathogenesis of heart failure with preserved ejection fraction (HFpEF). Among these, coronary microvascular dysfunction (CMD) may play a key pathophysiological role. We performed a systematic review and meta-analysis to investigate the prevalence, echocardiographic correlates, and prognostic implications of CMD in patients with HFpEF., Methods and Results: A systematic search for articles up to 1 May 2023 was performed. The primary aim was to assess the prevalence of CMD. Secondary aims were to compare key echocardiographic parameters (E/e' ratio, left atrial volume index [LAVi], and left ventricular mass index [LVMi]), clinical outcomes [death and hospitalization for heart failure (HF)], and prevalence of atrial fibrillation (AF) between patients with and without CMD. Meta-regressions according to baseline patient characteristics and study features were performed to explore potential heterogeneity sources. We identified 14 observational studies, enrolling 1138 patients with HFpEF. The overall prevalence of CMD was 58%. Compared with patients without CMD, patients with HFpEF and CMD had larger LAVi [mean difference (MD) 3.85 confidence interval (CI) 1.19-6.5, P < 0.01)], higher E/e' ratio (MD 2.76 CI 1.54-3.97; P < 0.01), higher prevalence of AF (odds ratio 1.61 CI 1.04-2.48, P = 0.03) and higher risk of death or hospitalization for HF [hazard ratio 3.19, CI 1.04-9.57, P = 0.04]., Conclusions: CMD is present in little more than half of the patients with HFpEF and is associated with echocardiographic evidence of more severe diastolic dysfunction and a higher prevalence of AF, doubling the risk of death or HF hospitalization., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Despite the progress in the care of individuals with heart failure (HF), important sex disparities in knowledge and management remain, covering all the aspects of the syndrome, from aetiology and pathophysiology to treatment. Important distinctions in phenotypic presentation are widely known, but the mechanisms behind these differences are only partially defined. The impact of sex-specific conditions in the predisposition to HF has gained progressive interest in the HF community. Under-recruitment of women in large randomized clinical trials has continued in the more recent studies despite epidemiological data no longer reporting any substantial difference in the lifetime risk and prognosis between sexes. Target dose of medications and criteria for device eligibility are derived from studies with a large predominance of men, whereas specific information in women is lacking. The present scientific statement encompasses the whole scenario of available evidence on sex-disparities in HF and aims to define the most challenging and urgent residual gaps in the evidence for the scientific and clinical HF communities., (© 2024 European Society of Cardiology.)

Heart failure (HF) is a syndrome characterized by signs and symptoms resulting from structural or functional cardiac abnormalities, confirmed by elevated natriuretic peptides or evidence of congestion. HF patients are classified according to left ventricular ejection fraction (LVEF). Worsening HF (WHF) is associated with increased short- and long-term mortality, re-hospitalization, and healthcare costs. The standard treatment of HF includes angiotensin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, mineralocorticoid-receptor antagonists, beta-blockers, and sodium-glucose-co-transporter 2 inhibitors. To manage systolic HF by reducing mortality and hospitalizations in patients experiencing WHF, treatment with vericiguat, a direct stimulator of soluble guanylate cyclase (sGC), is indicated. This drug acts by stimulating sGC enzymes, part of the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway, regulating the cardiovascular system by catalyzing cGMP synthesis in response to NO. cGMP acts as a second messenger, triggering various cellular effects. Deficiencies in cGMP production, often due to low NO availability, are implicated in cardiovascular diseases. Vericiguat stimulates sGC directly, bypassing the need for a functional NO-sGC-cGMP axis, thus preventing myocardial and vascular dysfunction associated with decreased sGC activity in heart failure. Approved by the FDA in 2021, vericiguat administration should be considered, in addition to the four pillars of reduced EF (HFrEF) therapy, in symptomatic patients with LVEF < 45% following a worsening event. Cardiac rehabilitation represents an ideal setting where there is more time to implement therapy with vericiguat and incorporate a greater number of medications for the management of these patients. This review covers vericiguat's metabolism, molecular mechanisms, and drug-drug interactions.

Aims: To assess the use and associations with outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in a real-world population with heart failure (HF) and type 2 diabetes mellitus (T2DM)., Methods and Results: The Swedish HF Registry was linked with the National Diabetes Registry and other national registries. Independent predictors of GLP-1 RA use were assessed by multivariable logistic regressions and associations with outcomes were assessed by Cox regressions in a 1:1 propensity score-matched cohort. Of 8188 patients enrolled in 2017-21, 9% received a GLP-1 RA. Independent predictors of GLP-1 RA use were age <75 years, worse glycaemic control, impaired renal function, obesity, and reduced ejection fraction (EF). GLP-1 RA use was not significantly associated with a composite of HF hospitalization (HHF) or cardiovascular (CV) death regardless of EF, but was associated with a lower risk of major adverse CV events (CV death, non-fatal stroke/transient ischaemic attack, or myocardial infarction), and CV and all-cause death. In patients with body mass index ≥30 kg/m2, GLP-1 RA use was also associated with a lower risk of HHF/CV death and HHF alone., Conclusions: In patients with HF and T2DM, GLP-1 RA use was independently associated with more severe T2DM, reduced EF, and obesity and was not associated with a higher risk of HHF/CV death but with longer survival and less major CV adverse events. An association with lower HHF/CV death and HHF was observed in obese patients. Our findings provide new insights into GLP-1 RA use and its safety in HF and T2DM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Frailty is highly prevalent in patients with heart failure (HF), but a concordant definition of this condition is lacking. The Heart Failure Association of the European Society of Cardiology (HFA-ESC) proposed in 2019 a new multi-domain definition of frailty, but it has never been validated., Methods and Results: Patients from the HELP-HF registry were stratified according to the number of HFA-ESC frailty domains fulfilled and to the cumulative deficits frailty index (FI) quintiles. Prevalence of frailty and of each domain was reported, as well as the rate of the composite of all-cause death and HF hospitalization, its single components, and cardiovascular death in each group and quintile. Among 854 included patients, 37 (4.3%), 206 (24.1%), 365 (42.8%), 217 (25.4%), and 29 (3.4%) patients fulfilled zero, one, two, three, or four domains, respectively, while 179 patients had a FI < 0.21 and were considered not frail. The 1-year risk of adverse events increased proportionally to the number of domains fulfilled (for each criterion increase, all-cause death or HF hospitalization: hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.27-1.62; all-cause death: HR 1.72, 95% CI 1.46-2.02, HF hospitalizations: subHR 1.21, 95% CI 1.04-1.31; cardiovascular death: HR 1.77, 95% CI 1.45-2.15). Consistent results were found stratifying the cohort for FI quintiles. The FI as a continuous variable demonstrated higher discriminative ability than the number of domains fulfilled (area under the curve = 0.68 vs. 0.64, p = 0.004)., Conclusion: Frailty in patients at risk for advanced HF, assessed via a multi-domain approach and the FI, is highly prevalent and identifies those at increased risk of adverse events. The FI was found to be slightly more effective in identifying patients at increased risk of mortality., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF) reduces morbidity and mortality, but its implementation is often poor in daily clinical practice. Barriers to implementation include clinical and organizational factors that might contribute to clinical inertia, i.e. avoidance/delay of recommended treatment initiation/optimization. The spectrum of strategies that might be applied to foster GDMT implementation is wide, and involves the organizational set-up of heart failure care pathways, tailored drug initiation/optimization strategies increasing the chance of successful implementation, digital tools/telehealth interventions, educational activities and strategies targeting patient/physician awareness, and use of quality registries. This scientific statement by the Heart Failure Association of the ESC provides an overview of the current state of GDMT implementation in HFrEF, clinical and organizational barriers to implementation, and aims at suggesting a comprehensive framework on how to overcome clinical inertia and ultimately improve implementation of GDMT in HFrEF based on up-to-date evidence., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Recent guidelines recommend four core drug classes (renin-angiotensin system inhibitor/angiotensin receptor-neprilysin inhibitor [RASi/ARNi], beta-blocker, mineralocorticoid receptor antagonist [MRA], and sodium-glucose cotransporter 2 inhibitor [SGLT2i]) for the pharmacological management of heart failure (HF) with reduced ejection fraction (HFrEF). We assessed physicians' perceived (i) comfort with implementing the recent HFrEF guideline recommendations; (ii) status of guideline-directed medical therapy (GDMT) implementation; (iii) use of different GDMT sequencing strategies; and (iv) barriers and strategies for achieving implementation., Methods and Results: A 26-question survey was disseminated via bulletin, e-mail and social channels directed to physicians with an interest in HF. Of 432 respondents representing 91 countries, 36% were female, 52% were aged <50 years, and 90% mainly practiced in cardiology (30% HF). Overall comfort with implementing quadruple therapy was high (87%). Only 12% estimated that >90% of patients with HFrEF without contraindications received quadruple therapy. The time required to initiate quadruple therapy was estimated at 1-2 weeks by 34% of respondents, 1 month by 36%, 3 months by 24%, and ≥6 months by 6%. The average respondent favoured traditional drug sequencing strategies (RASi/ARNi with/followed by beta-blocker, and then MRA with/followed by SGLT2i) over simultaneous initiation or SGLT2i-first sequences. The most frequently perceived clinical barriers to implementation were hypotension (70%), creatinine increase (47%), hyperkalaemia (45%) and patient adherence (42%)., Conclusions: Although comfort with implementing all four core drug classes in patients with HFrEF was high among physicians, a majority estimated implementation of GDMT in HFrEF to be low. We identified several important perceived clinical and non-clinical barriers that can be targeted to improve implementation., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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., Competing Interests: FL has no conflicts of interest to declare. NØ has no conflicts of interest to declare. MM reports grants and other from Amgen, Abbott Vascular, Edwards Therapeutics, Servier, WindTree Therapeutics, Actelion, Livanova, Vifor Pharma. GR reports no conflicts of interest. UD reports research grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Vifor, Boston Scientific, Roche Diagnostics and honoraria/consultancies from Amgen, Pfizer and AstraZeneca all outside the present manuscript. PM has no conflicts of interest to declare. CH none related to the present work; unrelated to the present work: consulting fees from Novartis, Roche Diagnostics, and AnaCardio; speaker fees from Novartis and Merck Sharp & Dohme. LHL none related to the present work; unrelated to the present work: grants, consulting, honoraria: Abbot, Alleviant, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Edwards, FineHeart, MedScape/WebMD, Merck/MSD, Novartis, Novo Nordisk, OrionPharma, Pharmacosmos, Radcliffe Cardiology, Roche, Sanofi, Servier, Translational Medicines Academy, Vifor; Stock ownership: AnaCardio. GS received financial support from Cytokinetics for performing this investigator-initiated study. GS reports grants and personal fees from Vifor, personal fees and grants from Boehringer Ingelheim, grants and personal fees from AstraZeneca, personal fees from Roche, grants and personal fees from Servier, grants and personal fees from Novartis, grants and personal fees from Cytokinetics, personal fees from Medtronic, grants from Boston Scientific, grants and personal fees from Pharmacosmos, grants from Merck, grants from Bayer, personal fees from INTAS, personal fees from Abbott, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials, (Copyright: © 2024 Lindberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: Existing data on the association between blood pressure levels and adverse cardiovascular outcomes in patients with heart failure (HF) are inconsistent. The optimal blood pressure targets for patients with HF remain uncertain. This study sought to assess the associations between blood pressure (systolic [SBP] and diastolic blood pressure [DBP]) levels and adverse cardiovascular disease (CVD) outcomes in patients with HF., Methods and Results: A systematic review and meta-analysis were conducted using MEDLINE, Embase, the Cochrane Library, and Web of Science databases up to 5 May 2023. The outcomes of interest included adverse cardiovascular events and all-cause mortality. Pooled relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Forty-three unique observational cohort studies, comprising 120 643 participants with HF, were included. The pooled RRs (95% CIs) for SBP thresholds of ≥140 mmHg versus <140 mmHg were 0.92 (0.83-1.01) for all-cause mortality, 0.83 (0.67-1.04) for CVD death, and 0.98 (0.80-1.21) for HF hospitalization. The pooled RR (95% CI) for SBP thresholds of ≥160 mmHg versus <160 mmHg and all-cause mortality was 0.67 (0.62-0.74). SBP levels below <130, <120, and <110 mmHg were each associated with an increased risk of various cardiovascular endpoints and all-cause mortality. The pooled RR (95% CI) for DBP thresholds of ≥80 mmHg versus <80 mmHg and all-cause mortality was 0.86 (0.67-1.10). A 10 mmHg increase in SBP or DBP was associated with a reduction in all-cause mortality and other cardiovascular endpoints., Conclusions: The findings suggest that lower and normal baseline SBP levels (<130, <120, and <110 mmHg) may be associated with future risk of worse outcomes in patients with HF. Optimal baseline blood pressure levels for these patients may lie within the range of ≥140 mmHg for SBP. In the absence of observational studies with repeated blood pressure measurements or definitive trials evaluating optimal blood pressure targets, individualized blood pressure targets based on patients' unique circumstances are warranted in HF management., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Obstructive sleep apneas (OSAs) and central sleep apneas (CSAs) are the most common comorbidities in Heart Failure (HF) that are strongly associated with all-cause mortality. Several therapeutic approaches have been used to treat CSA and OSA, but none have been shown to significantly improve HF prognosis. Our study evaluated the effects of a 3-months treatment with sodium-glucose cotransporter type 2 inhibitor (SGLT2i) on polygraphic parameters in patients with sleep apnea (SA) and HF, across the spectrum of ejection fraction, not treated with continuous positive air pressure (CPAP). A group of 514 consecutive elderly outpatients with HF, type 2 diabetes mellitus (T2DM) and SA, eligible for treatment with SGLT2i, were included in the investigation before starting any CPAP therapy. The two groups were compared with the t -test and Mann-Whitney test for unpaired data when appropriate. Then, a simple logistic regression model was built using 50% reduction in AHI as the dependent variable and other variables as covariates. A multivariate stepwise logistic regression model was constructed using the variables that linked with the dependent variable to calculate the odds ratio (OR) for the independent predictors associated with the reduction of 50% in AHI. The treated group experienced significant improvements in polygraphic parameters between baseline values and follow-up with reduction in AHI (28.4 ± 12.9 e/h vs. 15.2 ± 6.5 e/h; p < 0.0001), ODI (15.4 ± 3.3 e/h vs. 11.1 ± 2.6 e/h; p < 0.0001), and TC90 (14.1 ± 4.2% vs. 8.2 ± 2.0%; p < 0.0001), while mean SpO 2 improved (91. 3 ± 2.3 vs. 93.8 ± 2.5); p < 0.0001. These benefits were not seen in the untreated population. The use of SGLT2i in patients suffering from HF and mixed-type SA not on CPAP therapy significantly contributes to improving polygraphic parameters.

Frailty is highly prevalent among patients with heart failure (HF) and independently predicts adverse outcomes. However, optimal frailty definitions, assessments, and management in HF remain unclear. Frailty is common in HF, affecting up to 80% of patients depending on population characteristics. Even pre-frailty doubles mortality risk versus robust patients. Frailty worsens HF prognosis through systemic inflammation, neurohormonal changes, sarcopenia, and micronutrient deficiency. Simple screening tools like gait speed and grip strength predict outcomes but lack HF-specificity. Comprehensive geriatric assessment is ideal but not always feasible. Exercise, nutrition, poly-pharmacy management, and multidisciplinary care models can help stablize frailty components and improve patient-centred outcomes. Frailty frequently coexists with and exacerbates HF. Routine frailty screening should guide supportive interventions to optimize physical, cognitive, and psychosocial health. Further research on HF-specific frailty assessment tools and interventions is warranted to reduce this dual burden., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2024. Korean Society of Heart Failure.)

Cardio-oncology is a rapidly growing field of cardiovascular (CV) medicine that has resulted from the continuously increasing clinical demand for specialized CV evaluation, prevention and management of patients suffering or surviving from malignant diseases. Dealing with CV disease in patients with cancer requires special knowledge beyond that included in the general core curriculum for cardiology. Therefore, the European Society of Cardiology (ESC) has developed a special core curriculum for cardio-oncology, a consensus document that defines the level of experience and knowledge required for cardiologists in this particular field. It is structured into 8 chapters, including (i) principles of cancer biology and therapy; (ii) forms and definitions of cancer therapy-related cardiovascular toxicity (CTR-CVT); (iii) risk stratification, prevention and monitoring protocols for CTR-CVT; (iv) diagnosis and management of CV disease in patients with cancer; (v) long-term survivorship programmes and cardio-oncology rehabilitation; (vi) multidisciplinary team management of special populations; (vii) organization of cardio-oncology services; (viii) research in cardio-oncology. The core curriculum aims at promoting standardization and harmonization of training and evaluation in cardio-oncology, while it further provides the ground for an ESC certification programme designed to recognize the competencies of certified specialists., (© 2023 European Society of Cardiology.)

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., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Sodium and fluid restriction has traditionally been advocated in patients with heart failure (HF) due to their sodium and water avid state. However, most evidence regarding the altered sodium handling, fluid homeostasis and congestion-related signs and symptoms in patients with HF originates from untreated patient cohorts and physiological investigations. Recent data challenge the beneficial role of dietary sodium and fluid restriction in HF. Consequently, the European Society of Cardiology HF guidelines have gradually downgraded these recommendations over time, now advising for the limitation of salt intake to no more than 5 g/day in patients with HF, while contemplating fluid restriction of 1.5-2 L/day only in selected patients. Therefore, the objective of this clinical consensus statement is to provide advice on fluid and sodium intake in patients with acute and chronic HF, based on contemporary evidence and expert opinion., (© 2024 European Society of Cardiology.)

Heart failure is the most common cardiovascular complication during pregnancy and the postpartum period. It is associated with increased risk of maternal morbidity and mortality as well as potentially life-threatening foetal pathology. Management of heart failure in pregnancy requires expert knowledge of cardiovascular disease as well as obstetrics which underscores the importance of multidisciplinary cardio-obstetrics teams in order to optimize diagnosis, treatment and outcome. This includes counselling of women at risk before and during the course of pregnancy in order to strengthen the relationship between medical specialists and patients, as well as to allow patient-centred delivery of care and improve quality of life., (© 2024 European Society of Cardiology.)

Heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) represent over half of heart failure cases but lack proven effective therapies beyond sodium-glucose cotransporter 2 inhibitor and diuretics. HFmrEF and HFpEF are heterogeneous conditions requiring precision phenotyping to enable tailored therapies. This review covers concepts on precision medicine approaches for HFmrEF and HFpEF. Areas discussed include HFmrEF mechanisms, anti-inflammatory and antifibrotic treatments for obesity-related HFpEF, If inhibition for HFpEF with atrial fibrillation, and mineralocorticoid receptor antagonism for chronic kidney disease-HFpEF. Incorporating precision phenotyping and matched interventions in HFmrEF and HFpEF trials will further advance therapy compared to blanket approaches., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (© 2024. Korean Society of Heart Failure.)

Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular conditions that frequently coexist. Among patients with HF, more than one-half also have AF. Both are associated with significant morbidity and mortality. Moreover, the prevalence of each is increasing globally, and this trend is expected to continue owing to an aging population and increased life expectancy. Diagnosis of AF in a patient with HF is associated with greater symptom burden, more frequent hospitalizations, and a worse prognosis. Guideline-directed medical therapy (GDMT) for HF can affect the incidence of AF. Once present, AF can influence the efficacy of some components of GDMT for HF. In this review, we discuss the effect of GDMT for HF across the spectrum of ejection fraction on prevention of AF as well as the benefit of GDMT in patients with vs without AF., Competing Interests: Funding Support and Author Disclosures Dr O’Meara is supported by the Montreal Heart Institute’s Carolyn & Richard J. Renaud Chair for Research in Heart Failure, with fees paid through her institution for this chair, for a Canadian Heart Function Alliance (CHFA) Team Grant, funded by the CIHR (steering committee member), and for involvement in the following trials as a steering committee member for DAPA-ACT and GARDEN-HF (TIMI group and AstraZeneca), for HEART-FID (steering committee member, American Regent), CARDINAL-HF (steering committee member, Cardurion), and HERMES (national lead investigator, Novo Nordisk); and has received consulting or speaker fees from AstraZeneca, Boehringer Ingelheim, Bayer, and Novartis. Dr Savarese has received grants and personal fees from Vifor, AstraZeneca, Pharmacosmos, and Novartis; has received grants from Boehringer Ingelheim, Boston Scientific, Merck, and Bayer; has received personal fees from Servier, Cytokinetics, Medtronic, Edwards Lifesciences, Teva, and Abbott; and receives funding through the EU Horizon Programme and the Swedish Heart and Lung Foundation. Dr Vardeny has received research support (paid to institution) from the National Institutes of Health, the Food and Drug Administration, AstraZeneca, Bayer, and Cardurion; and has received personal consulting fees from Cardior and Cytokinetics. Dr Allen has received grant funding from the Patient-Centered Outcomes Research Institute and the National Institutes of Health; and has received consulting fees from ACI Clinical, Boston Scientific, Cytokinetics, Novartis, and Quidel. Dr Gottlieb has received consulting fees from Cytokinetics. Dr Zainab serves on the Heart Failure Publication Committee of Cytokinetics. Dr Morris has received consulting fees or honoraria from Abbott, Acorai, BI Lilly, Cytokinetics, Edwards, Ionis, Merck, Novo Nordisk, and Regeneron. Dr Desai works under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures used for public reporting and pay for performance programs; and has received research grants and consulting for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, SCPharmaceuticals, and Vifor. Dr Teerlink has received consulting fees from Cytokinetics. Dr Saldarriaga-Giraldo has served as a speaker for AstraZeneca, Novartis, Servier, Abbott, Medtronic, Pfizer, Roche, Sanofi, Boehringer Ingelheim, Elly Lilly, Bayer, and Merck; has served as a principal investigator for Amgen, Novartis, Merck, and Bayer; and has served as an advisor for Medtronic, Novartis, Bayer, AstraZeneca, Boehringer Ingelheim, Servier, and Novo Nordisk. Dr Lindenfeld has received grant funding from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and AstraZeneca; and has received consulting fees from Abbott, Alleviant, AstraZeneca, Axon, Bayer, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards Lifesciences, Merck, Medtronic, VWave, and Vascular Dynamics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care., (© 2024 European Society of Cardiology.)

Document Reviewers: Rudolf A. de Boer (CPG Review Co-ordinator) (Netherlands), P. Christian Schulze (CPG Review Co-ordinator) (Germany), Elena Arbelo (Spain), Jozef Bartunek (Belgium), Johann Bauersachs (Germany), Michael A. Borger (Germany), Sergio Buccheri (Sweden), Elisabetta Cerbai (Italy), Erwan Donal (France), Frank Edelmann (Germany), Gloria Färber (Germany), Bettina Heidecker (Germany), Borja Ibanez (Spain), Stefan James (Sweden), Lars Køber (Denmark), Konstantinos C. Koskinas (Switzerland), Josep Masip (Spain), John William McEvoy (Ireland), Robert Mentz (United States of America), Borislava Mihaylova (United Kingdom), Jacob Eifer Møller (Denmark), Wilfried Mullens (Belgium), Lis Neubeck (United Kingdom), Jens Cosedis Nielsen (Denmark), Agnes A. Pasquet (Belgium), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Bianca Rocca (Italy), Xavier Rossello (Spain), Leyla Elif Sade (United States of America/Türkiye), Hannah Schaubroeck (Belgium), Elena Tessitore (Switzerland), Mariya Tokmakova (Bulgaria), Peter van der Meer (Netherlands), Isabelle C. Van Gelder (Netherlands), Mattias Van Heetvelde (Belgium), Christiaan Vrints (Belgium), Matthias Wilhelm (Switzerland), Adam Witkowski (Poland), and Katja Zeppenfeld (Netherlands) All experts involved in the development of this Focused Update have submitted declarations of interest. These have been compiled in a report and simultaneously published in a supplementary document to the Focused Update. The report is also available on the ESC website www.escardio.org/guidelines See the European Heart Journal online for supplementary documents that include evidence tables., (© 2024 European Society of Cardiology.)

Right-sided heart failure and tricuspid regurgitation are common and strongly associated with poor quality of life and an increased risk of heart failure hospitalizations and death. While medical therapy for right-sided heart failure is limited, treatment options for tricuspid regurgitation include surgery and, based on recent developments, several transcatheter interventions. However, the patients who might benefit from tricuspid valve interventions are yet unknown, as is the ideal time for these treatments given the paucity of clinical evidence. In this context, it is crucial to elucidate aetiology and pathophysiological mechanisms leading to right-sided heart failure and tricuspid regurgitation in order to recognize when tricuspid regurgitation is a mere bystander and when it can cause or contribute to heart failure progression. Notably, early identification of right heart failure and tricuspid regurgitation may be crucial and optimal management requires knowledge about the different mechanisms and causes, clinical course and presentation, as well as possible treatment options. The aim of this clinical consensus statement is to summarize current knowledge about epidemiology, pathophysiology and treatment of tricuspid regurgitation in right-sided heart failure providing practical suggestions for patient identification and management., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Aims were to evaluate (1) reclassification of patients from heart failure with mildly reduced (HFmrEF) to reduced (HFrEF) ejection fraction when an EF = 40% was considered as HFrEF, (2) role of EF digit bias, ie, EF reporting favouring 5% increments; (3) outcomes in relation to missing and biased EF reports, in a large multinational HF registry., Methods and Results: Of 25,154 patients in the European Society of Cardiology (ESC) HF Long-Term registry, 17% had missing EF and of those with available EF, 24% had HFpEF (EF≥50%), 21% HFmrEF (40%-49%) and 55% HFrEF (<40%) according to the 2016 ESC guidelines´ classification. EF was "exactly" 40% in 7%, leading to reclassifying 34% of the HFmrEF population defined as EF = 40% to 49% to HFrEF when applying the 2021 ESC Guidelines classification (14% had HFmrEF as EF = 41% to 49% and 62% had HFrEF as EF≤40%). EF was reported as a value ending with 0 or 5 in ∼37% of the population. Such potential digit bias was associated with more missing values for other characteristics and higher risk of all-cause death and HF hospitalization. Patients with missing EF had higher risk of all-cause and CV mortality, and HF hospitalization compared to those with recorded EF., Conclusions: Many patients had reported EF = 40%. This led to substantial reclassification of EF from old HFmrEF (40%-49%) to new HFrEF (≤40%). There was considerable digit bias in EF reporting and missing EF reporting, which appeared to occur not at random and may reflect less rigorous overall care and worse outcomes., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Imaging plays an integral role in all aspects of managing heart disease and cardiac imaging is a core competency of cardiologists. The adequate delivery of cardiac imaging services requires expertise in both imaging methodology-with specific adaptations to imaging of the heart-as well as intricate knowledge of heart disease. The European Society of Cardiology (ESC) and the European Association of Cardiovascular Imaging have developed and implemented a successful education and certification programme for all cardiac imaging modalities. This programme equips cardiologists to provide high quality competency-based cardiac imaging services ensuring they are adequately trained and competent in the entire process of cardiac imaging, from the clinical indication via selecting the best imaging test to answer the clinical question, to image acquisition, analysis, interpretation, storage, repository, and results dissemination. This statement emphasizes the need for competency-based cardiac imaging delivery which is key to optimal, effective and efficient, patient care., (This article has been co-published with permission in the European Heart Journal, European Heart Journal – Cardiovascular Imaging, and European Heart Journal – Imaging Methods and Practice. © 2023 the European Society of Cardiology The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.)

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 m 2 , respectively. An eGFR ≥60 ml/min/1.73 m 2 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., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Heart failure is a chronic progressive condition, with considerable burden on patients' quality of life and economic burden for the healthcare systems. Before the approval of empagliflozin, there were no proven effective treatments for patients with heart failure with left ventricular ejection fraction (HF LVEF) > 40%. The aim of this study was to evaluate the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone for patients with HF LVEF > 40%, from the perspective of the healthcare systems of the United Kingdom (UK), Spain, and France, and to quantify the healthcare costs for these patients., Methods and Results: A lifetime Markov cohort state-transition model was developed based on discrete health states defined by Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score quartiles to track disease severity. Model inputs relied primarily on the EMPEROR-Preserved trial data or obtained from published literature or country-specific databases, as well as local guidelines for the requirements for the conduct of the economic evaluation of healthcare technologies. The total lifetime cost of receiving SoC per patient was £10 092, €15 765, and €14 958 in the UK, Spain, and France, respectively, which increased by £1407, €1148, and €1485, respectively, with the addition of empagliflozin to the SoC. Empagliflozin + SoC was associated with significantly reduced number of hospitalization for HF or cardiovascular death compared with SoC alone, which was a key driver offsetting its drug acquisition costs. The incremental cost-effectiveness ratio per quality-adjusted life year (QALY) gained was consistently favourable at £14 851, €11 706, and €15 447 in the UK, Spain, and France, respectively. Scenario analysis using the New York Heart Association functional class showed similar results. Probabilistic sensitivity analyses showed more than 50% probability for cost-effectiveness for a willingness-to-pay (WTP) threshold of £/€20 000/QALY for the three countries., Conclusions: Empagliflozin was found to be the first targeted treatment option that is clinically effective and cost-effective for patients with HF LVEF > 40%. Prescribing empagliflozin with SoC to patients with HF LVEF > 40% is expected to improve clinical outcomes and patients' quality of life and substantially below accepted WTP threshold for the healthcare systems in the UK, Spain, and France., (© 2023 Boehringer Ingelheim. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Early start and patient profile-oriented heart failure (HF) management has been recommended. In this post hoc analysis from the SHIFT trial, we analysed the treatment effects of ivabradine in HF patients with systolic blood pressure (SBP) < 110 mmHg, resting heart rate (RHR) ≥ 75 b.p.m., left ventricular ejection fraction (LVEF) ≤ 25%, New York Heart Association (NYHA) Class III/IV, and their combination., Methods and Results: The SHIFT trial enrolled 6505 patients (LVEF ≤ 35% and RHR ≥ 70 b.p.m.), randomized to ivabradine or placebo on the background of guideline-defined standard care. Compared with placebo, ivabradine was associated with a similar relative risk reduction of the primary endpoint (cardiovascular death or HF hospitalization) in patients with SBP < 110 and ≥110 mmHg [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.74-1.08 vs. HR 0.80, 95% CI 0.72-0.89, P interaction = 0.34], LVEF ≤ 25% and >25% (HR 0.85, 95% CI 0.72-1.01 vs. HR 0.80, 95% CI 0.71-0.90, P interaction = 0.53), and NYHA III-IV and II (HR 0.83, 95% CI 0.74-0.94 vs. HR 0.81, 95% CI 0.69-0.94, P interaction = 0.79). The effect was more pronounced in patients with RHR ≥ 75 compared with <75 (HR 0.76, 95% CI 0.68-0.85 vs. HR 0.97, 95% CI 0.81-0.1.16, P interaction = 0.02). When combining these profiling parameters, treatment with ivabradine was also associated with risk reductions comparable with patients with low-risk profiles for the primary endpoint (relative risk reduction 29%), cardiovascular death (11%), HF death (49%), and HF hospitalization (38%; all P values for interaction: 0.40). No safety concerns were observed between study groups., Conclusions: Our analysis shows that RHR reduction with ivabradine is effective and improves clinical outcomes in HF patients across various risk indicators such as low SBP, high RHR, low LVEF, and high NYHA class to a similar extent and without safety concern., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Current European heart failure (HF) guidelines suggest the use of risk score: among them, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score has demonstrated to be one of the most accurate. However, the risk scores are still poorly implemented in clinical practice, also due to the lack of strong evidence regarding their external validation in different populations. Thus, the current study was designed as an external validation test of the MECKI score in an international multicentre setting., Methods and Results: The study cohort consisted of patients diagnosed with HF with reduced ejection fraction (HFrEF) across international centres (not Italian), retrospectively recruited. Collected data included demographics, HF aetiology, laboratory testing, electrocardiogram (ECG), echocardiographic findings, and cardiopulmonary exercise testing (CPET) results as described in the original MECKI score publication. A total of 1042 patients across 8 international centres (7 European and 1 Asian) were included and followed up from 1998 till 2019. Patients were divided according to the calculated MECKI scores into three subgroups: (i) MECKI score <10%, (ii) 10-20%, and (iii) ≥ 20%. Survival analysis comparison among the three MECKI score subgroups showed a worse prognosis in patients with higher MECKI score value: median event-free survival times were 4396 days for MECKI score <10%, 3457 days for 10-20%, and 1022 days for ≥20% (P < 0.0001). Receiver operating characteristic (ROC) curves and area under the ROC curves (AUC) were like those reported in the original internal validation studies., Conclusion: In patients diagnosed with HFrEF, the power of the MECKI score was confirmed in terms of prognosis and risk stratification, supporting its implementation as advised by the HF guidelines., Competing Interests: Conflict of interest: None related to the present manuscript. Giuseppe Rosano received support from Menarini, Servier, Boheringer Ingelheim, and AstraZeneca and is President of the Heart Failure Association., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)