2024 update in heart failure.

In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium-glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called 'high-intensity care' strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and the 6 min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article.

The management of heart failure in Sweden-the physician's perspective: a survey.

Aims: To assess the barriers to guideline-directed medical therapy (GDMT) use in heart failure (HF), diagnostic workup and general knowledge about HF among physicians in Sweden. Methods: A survey about the management of HF was sent to 828 Swedish physicians including general practitioners (GPs) and specialists during 2021-2022. Answers were reported as percentages and comparisons were made by specialty (GPs vs. specialists). Results: One hundred sixty-eight physicians participated in the survey (40% females, median age 43 years; 41% GPs and 59% specialists). Electrocardiography and New York Heart Association class evaluations are mostly performed once a year by GPs (46%) and at every outpatient visit by specialists (40%). Echocardiography is mostly requested if there is clinical deterioration (60%). One-third of participants screen for iron deficiency only if there is anemia. Major obstacles to implementation of different drug classes in HF with reduced ejection fraction are related to side effects, with no significant differences between specialties. Device implantation is deemed appropriate regardless of aetiology (69%) and patient age (86%). Specialists answered correctly to knowledge questions more often than GPs. Eighty-six percent of participants think that GDMT should be implemented as much as possible. Most participants (57%) believe that regular patient assessment in nurse-led HF clinics improve adherence to GDMT. Conclusion: Obstacles to GDMT implementation according to physicians in Sweden mainly relate to potential side effects, lack of specialist knowledge and organizational aspects. Further efforts should be placed in educational activities and structuring of nurse-led clinics.

Differences in presentation, diagnosis and management of heart failure in women. A scientific statement of the Heart Failure Association of the ESC.

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.

Cardiovascular magnetic resonance parametric techniques to characterize myocardial effects of anthracycline therapy in adults with normal left ventricular ejection fraction: a systematic review and meta-analysis.

BACKGROUND: The cardiotoxic effects of anthracyclines therapy are well recognized, both in the short and long term. Echocardiography allows monitoring of cancer patients treated with this class of drugs by serial assessment of left ventricle ejection fraction (LVEF) as a surrogate of systolic function. However, changes in myocardial function may occur late in the process when cardiac damage is already established. Novel cardiac magnetic resonance (CMR) parametric techniques, like native T1 mapping and extra-cellular volume (ECV), may detect subclinical myocardial damage in these patients, recognizing early signs of cardiotoxicity before development of overt cancer therapy-related cardiac dysfunction (CTRCD) and prompting tailored therapeutic and follow-up strategies to improve outcome. METHODS AND RESULTS: We conducted a systematic review and a meta-analysis to investigate the difference in CMR derived native T1 relaxation time and ECV values, respectively, in anthracyclines-treated cancer patients with preserved EF versus healthy controls. PubMed, Embase, Web of Science and Cochrane Central were searched for relevant studies. A total of 6 studies were retrieved from 1057 publications, of which, four studies with 547 patients were included in the systematic review on T1 mapping and five studies with 481 patients were included in the meta-analysis on ECV. Three out of the four included studies in the systematic review showed higher T1 mapping values in anthracyclines treated patients compared to healthy controls. The meta-analysis demonstrated no statistically significant difference in ECV values between the two groups in the main analysis (Hedges´s g =3.20, 95% CI -0.72-7.12, p =0.11, I2 =99%), while ECV was significantly higher in the anthracyclines-treated group when sensitivity analysis was performed. CONCLUSIONS: Higher T1 mapping and ECV values in patients exposed to anthracyclines could represent early biomarkers of CTRCD, able to detect subclinical myocardial changes present before the development of overt myocardial dysfunction. Our results highlight the need for further studies to investigate the correlation between anthracyclines-based chemotherapy and changes in CMR mapping parameters that may guide future tailored follow-up strategies in this group of patients.

Eligibility for omecamtiv mecarbil in a real-world heart failure population: Data from the Swedish Heart Failure Registry.

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.

Effect of SGLT2-Inhibitors on Polygraphic Parameters in Elderly Patients Affected by Heart Failure, Type 2 Diabetes Mellitus, and Sleep Apnea.

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 SpO2 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.

Sex differences in the prognostic role of achieving target doses of heart failure medications: Data from the Swedish Heart Failure Registry.

AIMS: Guidelines recommend target doses (TD) of heart failure (HF) with reduced ejection fraction (HFrEF) medications regardless of sex. Differences in pharmacokinetics and pharmacodynamics may explain heterogeneity in treatment response, adverse reactions, and tolerability issues across sexes. The aim of this study was to explore sex-based differences in the association between TD achievement and mortality/morbidity in HFrEF. METHODS AND RESULTS: Patients with HFrEF and HF duration ≥6 months registered in the Swedish HF Registry between May 2000 and December 2020 (follow-up until December 2021) were analysed. Treatments of interest were renin-angiotensin system inhibitors (RASI) or angiotensin receptor-neprilysin inhibitors (ARNI), and beta-blockers. Multivariable Cox regression models were performed to explore the risk of cardiovascular mortality or hospitalization for HF across dose categories in females versus males. A total of 17 912 patients were analysed (median age 77.0 years, interquartile range [IQR] 70.0-83.0), 29% were female. Over a median follow-up of 1.33 years (IQR 0.29-3.22), for RASI/ARNI there was no significant difference in outcome for females achieving 50-99% versus 100% of TD (hazard ratio 0.92, 95% confidence interval 0.83-1.03), whereas males showed a gradual lowering in risk together with the achievement of higher % of TD (p-interaction = 0.030). For beta-blockers the achievement of TD was associated with the lowest risk of outcome regardless of sex. CONCLUSIONS: Our findings suggest that females and males might differently benefit from the same dose of RASI/ARNI, and do represent a general call for randomized controlled trials to consider sex-specific up-titration schemes when testing HFrEF treatments in need of up-titration.

How to tackle therapeutic inertia in heart failure with reduced ejection fraction. A scientific statement of the Heart Failure Association of the ESC.

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.

Multidisciplinary care of peripartum heart failure: A scientific statement of the Heart Failure Association of the ESC.

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.

Cause-specific death in heart failure across the ejection fraction spectrum: A comprehensive assessment of over 100 000 patients in the Swedish Heart Failure Registry.

AIM: To assess cause-specific death in patients with heart failure with preserved, mildly reduced, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF). METHODS AND RESULTS: Data were analysed from the Swedish Heart Failure Registry (SwedeHF) and the National Patient Register of patients enrolled in SwedeHF 2000-2021. Cox proportional hazards regression models were performed and adjusted for age, sex and time period. Among 100 584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (interquartile range) was 75 (66-82) and 36% were female. Of those who died within 5 years, most deaths were ascribed to cardiovascular (CV) causes across all ejection fraction (EF) categories. Within 5 years, HFpEF had higher adjusted risk of non-CV death (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.28-1.38, p < 0.001) and lower adjusted risk of CV death (HR 0.85, 95% CI 0.82-0.88, p < 0.001) compared to HFrEF. Ischaemic heart disease (IHD) and cancer were the most common causes of CV and non-CV death regardless of EF category. The incidence rate of CV death due to IHD was highest in HFrEF while incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation increased with increasing EF. The incidence rates of non-CV deaths due to cancer, respiratory disease, and infections increased with increasing EF. CONCLUSION: Cardiovascular death was more common than non-CV death across all EF categories although the risk of non-CV death within 5 years was higher with increasing EF. IHD and cancer were the most common causes of CV and non-CV deaths, respectively, regardless of EF category.

Glucagon-like peptide-1 receptor agonists use and associations with outcomes in heart failure and type 2 diabetes. Data from the Swedish Heart Failure and Swedish National Diabetes Registries.

AIMS: To assess 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 (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 by Cox regressions in a 1:1 propensity score-matched cohort. Of 8188 patients enrolled in 2017-2021, 9% received a GLP-1 RA. Independent predictors of GLP-1 RA use were age<75, 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 lower risk of major adverse CV events (CV death, non-fatal stroke/transient ischemic attack or myocardial infarction), CV and all-cause death. In patients with body mass index≥30 kg/m2, GLP-1 RA use was also associated with 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.

Impact of coronary microvascular dysfunction in heart failure with preserved ejection fraction: a meta-analysis.

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.

Physician perceptions, attitudes, and strategies towards implementing guideline-directed medical therapy in heart failure with reduced ejection fraction. A survey of the Heart Failure Association of the ESC and the ESC Council for Cardiology Practice.

27 March 2024: This article published in Early View in error. The article is under embargo and will republish after 11th May 2024.

Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.

Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.

Previous heart failure hospitalization, spironolactone, and outcomes in heart failure with preserved ejection fraction - a secondary analysis of TOPCAT.

BACKGROUND: Hospitalization for heart failure (HHF) is associated with poor postdischarge outcomes but the role of time since most recent HHF and potential treatment interactions are unknown. We aimed to assess history of and time since previous HHF, associations with composite of cardiovascular (CV) death and total HHF, first HHF and interactions with randomization to spironolactone, in heart failure with preserved ejection fraction. METHODS AND RESULTS: We assessed these objectives using uni- and multivariable regressions and spline analyses in TOPCAT-Americas. Among 1,765 patients, 66% had a previous HHF. Over a median of 2.9 years, 1,064 composite events of CV death or total HHFs occurred. Previous HHF was associated with more severe HF, and was independently associated with the composite outcome (HR 1.26, 95%CI 1.05-1.52, P = .014), and all secondary outcomes. A shorter time since most recent HHF appeared to be associated with subsequent first HHF, but not the composite of CV death or total HHF. Spironolactone had a significant interaction with previous HHF (interaction-P .046). Patients without a previous HHF had a larger effect of spironolactone on the composite outcome (HR 0.63, 95%CI 0.46-0.87, P = .005) than patients with a previous HHF (HR 0.91, 95%CI 0.78-1.06, P = .224). CONCLUSION: In TOPCAT-Americas, previous HHF was associated with CV death and first and total HHF. Duration since most recent HHF seemed to be associated with time to first HHF only. Spironolactone was associated with better outcomes in patients without a previous HHF. This interaction is hypothesis-generating and requires validation in future trials.

Implications of Atrial Fibrillation for Guideline-Directed Therapy in Patients With Heart Failure: JACC State-of-the-Art Review.

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.

Implantable cardioverter defibrillator and cardiac resynchronization treatment in people with type 2 diabetes: a comparison with age- and sex matched controls from the general population.

BACKGROUND: Increased risk of severe tachyarrhythmias is reported in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to explore if treatment with cardiac implantable electronic device (CIED) such as implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy- pacemaker and -defibrillator (CRT-P/CRT-D) differed in patients with vs. without T2DM. A secondary aim was to identify patient characteristics indicating an increased CIED treatment. METHOD: 416 162 adult patients with T2DM from the Swedish National Diabetes Registry and 2 081 087 controls from the Swedish population, matched for age, sex and living area, were included between 1/1/1998 and 31/12/2012 and followed until 31/12/2013. They were compared regarding prevalence of ventricular tachycardia (VT) at baseline and the risk of receiving a CIED during follow-up. Multivariable Cox regression analysis was performed to estimate the risk of CIED-treatment and factors identifying patients with such risk. RESULTS: Ventricular fibrillation (VF) (0.1% vs 0.0004%) and (VT) (0.2% vs. 0.1%) were more frequent among patients with T2DM compared to controls. CIED-treatment was significantly increased in patients with T2DM both in unadjusted and adjusted analyses. HR and 95% CI, after adjustment for sex, age, marital status, income, education, country of birth, coronary artery disease and congestive heart failure, were 1.32 [1.21-1.45] for ICD, 1.74 [1.55-1.95] for CRT-P and 1.69 [1.43-1.99] for CRT-D. Blood-pressure and lipid lowering therapies were independent risk factors associated to receiving CIED, while female sex was protective. CONCLUSIONS: Although the proportion of VT/VF was low, patients with T2DM had a higher prevalence of these conditions and increased risk for treatment with CIED compared to controls. This underlines the importance of recognizing that T2DM patients have an increased need of CIED.

GLP-1-ra and heart failure-related outcomes in patients with and without history of heart failure: an updated systematic review and meta-analysis.

AIMS: Glucagon-like peptide-1 receptor agonists (GLP1-ra) have shown to reduce cardiovascular (CV) events in patients with diabetes, including heart failure (HF) hospitalizations. However, whether such benefit consistently occurs in patients with history of HF remains uncertain. We performed a systematic review and meta-analysis to assess the impact of GLP1-ra on CV outcomes in patients with and without HF history. METHODS AND RESULTS: All randomized, placebo-controlled trials evaluating GLP1-ra and reporting CV outcomes stratified by HF history were searched in Pubmed from inception to November 12th, 2023. The primary outcome was HF hospitalizations. Secondary outcomes included CV death, the composite of CV death and hospitalizations for HF, and major adverse cardiovascular events (MACE). Hazard ratio (HR) and 95% confidence interval (CIs) were used as effect estimates and calculated with a random-effects model. 68,653 patients (GLP1-ra = 34,301, placebo = 34,352) from 10 trials were included. GLP1-ra reduced HF hospitalization (no HF: HR = 0.79, 95% CI 0.63-0.98; HF: HR = 1.00, 95% CI 0.82-1.24, pinteraction = 0.12), CV death (no HF: HR = 0.81, 95% CI 0.71-0.92; HF: HR = 0.97, 95% CI 0.81-1.15, pinteraction = 0.11), and the composite of HF hospitalizations and CV death (no HF: HR = 0.80, 95% CI 0.72-0.89; HF: HR = 1.00 95% CI 0.88-1.15, pinteraction = 0.010) only in patients without history of HF, despite a significant interaction between HF history and treatment effect was detected only for the latter. MACE were reduced in both subgroups without significant interaction between HF history and treatment effect (no HF: HR = 0.86, 95% CI 0.78-0.96; HF: HR = 0.83, 95% CI 0.72-0.95, pinteraction = 0.69). CONCLUSION: GLP1-ra do not decrease HF-hospitalization risk, despite a potential benefit in patients without history of HF, but are effective in reducing ischemic events irrespective of the presence of HF. PROSPERO-registered (CRD42022371264).

Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

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.