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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 role of cardiac natriuretic peptides in the management of patients with chronic heart failure (HF) remains uncertain. The purpose of this study was to evaluate whether natriuretic peptide-guided therapy, compared to clinically-guided therapy, improves mortality and hospitalization rate in patients with chronic HF. MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched for articles reporting natriuretic peptide-guided therapy in HF until August 2012. All randomized trials reporting clinical end-points (all-cause mortality and/or HF-related hospitalization and/or all-cause hospitalization) were included. Meta-analysis was performed to assess the influence of treatment on outcomes. Sensitivity analysis was performed to test the influence of potential effect modifiers and of each trial included in meta-analysis on results. Twelve trials enrolling 2,686 participants were included. Natriuretic peptide-guided therapy (either B-type natriuretic peptide [BNP]- or N-terminal pro-B-type natriuretic peptide [NT-proBNP]-guided therapy) significantly reduced all-cause mortality (Odds Ratio [OR]:0.738; 95% Confidence Interval [CI]:0.596 to 0.913; p = 0.005) and HF-related hospitalization (OR:0.554; CI:0.399 to 0.769; p = 0.000), but not all-cause hospitalization (OR:0.803; CI:0.629 to 1.024; p = 0.077). When separately assessed, NT-proBNP-guided therapy significantly reduced all-cause mortality (OR:0.717; CI:0.563 to 0.914; p = 0.007) and HF-related hospitalization (OR:0.531; CI:0.347 to 0.811; p = 0.003), but not all-cause hospitalization (OR:0.779; CI:0.414 to 1.465; p = 0.438), whereas BNP-guided therapy did not significantly reduce all-cause mortality (OR:0.814; CI:0.518 to 1.279; p = 0.371), HF-related hospitalization (OR:0.599; CI:0.303 to 1.187; p = 0.142) or all-cause hospitalization (OR:0.726; CI:0.509 to 1.035; p = 0.077). [corrected]. Use of cardiac peptides to guide pharmacologic therapy significantly reduces mortality and HF related hospitalization in patients with chronic HF. In particular, NT-proBNP-guided therapy reduced all-cause mortality and HF-related hospitalization but not all-cause hospitalization, whereas BNP-guided therapy did not significantly reduce both mortality and morbidity.

Aim The management of cardiogenic shock remains a clinical challenge even in well‐developed healthcare systems, best illustrated by its high mortality despite numerous innovative proposals for management. The aim of this study was to describe temporal trends in incidence, causes, use of mechanical circulatory support, and mortality in cardiogenic shock in Germany. Methods and results Data on all cardiogenic shock patients treated in German hospitals between 2005 and 2017 were obtained from the Federal Bureau of Statistics. The data set comprised 441 696 patients with cardiogenic shock, mean age 71 (±13.8) years, 171 383 (39%) female patients. Incidence rates increased from 33.1/100 000 population in 2005 (27 246 cases) to 51.7/100 000 population in 2017 (42 779 cases). Acute myocardial infarction was the most common cause of cardiogenic shock in 2005–07 (43 422 of 82 037 cases, 52.9%), but the proportion of cases caused by it decreased until 2014–17 (73 274 of 165 873 cases, 44.2%). Over time, intra‐aortic balloon pump (2005: 5104; 2017: 973 cases) was used less frequently, whereas use of extracorporeal‐membrane‐oxygenation (2007: 35; 2017: 2414 cases) and percutaneous left ventricular assist devices (2005: 27; 2017: 1323 cases) increased. Mortality remained high at around 60% without relevant temporal trends in patients without acute myocardial infarction and slightly decreased in patients with acute myocardial infarction. Conclusions In this large, nation‐wide study, annual incidence of cardiogenic shock was growing, its causes were changing, and mortality was high despite a shift towards use of novel mechanical circulatory support devices. This highlights the need to address the evidence gap in this field, in particular for cardiogenic shock caused by diseases other than acute myocardial infarction.

Heart failure (HF) represents a global pandemic. Although in HF with reduced ejection fraction (HFrEF) randomized controlled trials have provided effective treatments, prognosis still remains poor, with signals of undertreatment. HF with mid-range EF (HFmrEF) has no evidence-based therapy, and its characterization is ongoing. Trials in HF with preserved EF (HFpEF) have failed to provide any effective treatment, but there are several concerns about their design. Thus, current challenges in the HF field are: 1) optimizing the use of existing treatments in HFrEF; 2) developing and proving efficacy of new treatments, and of new use of existing treatments in HFpEF and HFmrEF. Here we describe how registry-based research can improve knowledge addressing the unmet needs in HF, and in particular we focus on the contribution of the Swedish Heart Failure Registry to this field.

Background Anemia is common in patients with heart failure (HF). Although iron testing is recommended, it is uncertain that solely emphasizing iron testing could result in lesser attention to other causes, like bleeding or cancer. This study aimed to evaluate the diagnostic work-up of incident anemia in patients with HF in routine care and associated health outcomes. Methods Observational study of 8932 non-anemic adults with HF in Stockholm, Sweden, was quantified for incidence of anemia, diagnostic work-up (recognition, laboratory/invasive testing) and treatment across severity of anemia and setting of care. Time-varying Cox regression explored associations between developing anemia and rate of major adverse cardiovascular events (MACE), HF hospitalization, cancer, and death. Results During median 2.7 years, 34% of patients developed incident anemia, and 13% developed severe anemia. Within 6 months from incident anemia, ferritin and transferrin saturation were tested in 44% overall and 65% of severe cases. Testing of liver enzymes, creatinine, and C-reactive protein was, however, done in > 90% of cases. Colonoscopy, esophagogastroduodenoscopy, urinalysis, and cystoscopy were performed in 2–10% of cases. Few patients were recognized with an ICD code diagnosis of anemia (16%). Treatments were infrequent: oral iron (10%), intravenous iron (16%), blood transfusions (6%), and erythropoietin-stimulating agents (< 1%). More anemia cases received treatment in cardiology care (43%) versus primary care (29%). New-onset anemia was associated with risk of MACE (adjusted HR 2.13, 95% CI 1.85–2.44), HF hospitalization (4.85, 4.30–5.48), cancer (3.41, 3.09–3.77), and death (2.04, 1.82–2.29). Conclusions One in three patients with HF experienced anemia, which was associated with adverse health outcomes. Testing for iron stores and invasive work-up was suboptimal. A large proportion of anemia events remained under-recognized and untreated, a pattern of care that warrants correction.

BackgroundLong-term outcome of contemporary myocardial perfusion scintigraphy (MPS) has not been assessed systematically.ObjectiveTo evaluate the association between results of MPS and long-term outcomes for patients with suspected coronary artery disease (CAD).MethodsElectronic databases were searched for Randomised controlled trials evaluating long-term outcome (≥12 months) of MPS in patients with suspected of CAD since year 2000. A meta-analysis adopting the random effects model was used to derive pooled estimates. The primary outcome was the composite of all-cause or cardiovascular mortality and non-fatal myocardial infarction as defined in individual trials, termed as major adverse cardiovascular event (MACE). Secondary outcome was all-cause or cardiovascular mortality. Positive MPS result was defined as reversible perfusion defect in any coronary artery territory.ResultsFour trials fulfilled the search criteria. A total of 1764 patient had MPS with a median follow-up of 35.7 months (range 17–57). The mean age was 59 years and 50% were male. Fifty-three per cent had hypertension, 43% had dyslipidaemia, 15% were current smokers and 61% had diabetes mellitus. The overall annual event rate was 1.42% for the composite MACE and 0.22% for all-cause or cardiovascular mortality. Compared with negative MPS results, positive MPS was associated with an increased risk of the composite MACE and all-cause or cardiovascular mortality with an annual event rate of 2.16% versus 0.66%, OR 2.71 (1.38, 5.32) and 0.34% versus 0.10%, OR 3.41 (1.44, 8.11), respectively.ConclusionIn this meta-analysis, reversible perfusion defect on MPS was associated with higher risk of composite MACE, and that of all-cause or cardiovascular mortality.

Heart failure (HF) is a long‐term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC‐HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs—in terms of quality of life—in European countries.

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). 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. 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.

Aims Factors influencing follow‐up referral decisions and their prognostic implications are poorly investigated in patients with heart failure (HF) with reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF) ejection fraction (EF). We assessed (i) the proportion of, (ii) independent predictors of, and (iii) outcomes associated with follow‐up in specialty vs. primary care across the EF spectrum. Methods and results We analysed 75 518 patients from the large and nationwide Swedish HF registry between 2000–2018. Multivariable logistic regression models were fitted to identify the independent predictors of planned follow‐up in specialty vs. primary care, and multivariable Cox models to assess the association between follow‐up type and outcomes. In this nationwide registry, 48 115 (64%) patients were planned for follow‐up in specialty and 27 403 (36%) in primary care. The median age was 76 [interquartile range (IQR) 67–83] years and 27 546 (36.5%) patients were female. Key independent predictors of planned follow‐up in specialty care included optimized HF care, that is follow‐up in a nurse‐led HF clinic [odds ratio (OR) 4.60, 95% confidence interval (95% CI) 4.41–4.79], use of HF devices (OR 3.99, 95% CI 3.62–4.40), beta‐blockers (OR 1.39, 95% CI 1.32–1.47), renin–angiotensin system/angiotensin‐receptor‐neprilysin inhibitors (OR 1.21, 95% CI 1.15–1.27), and mineralocorticoid receptor antagonists (OR 1.31, 95% CI 1.26–1.37); and more severe HF, that is higher NT‐proBNP (OR 1.13, 95% CI 1.06–1.20) and NYHA class (OR 1.13, 95% CI 1.08–1.19). Factors associated with lower likelihood of follow‐up in specialty care included older age (OR 0.29, 95% CI 0.28–0.30), female sex (OR 0.89, 95% CI 0.86–0.93), lower income (OR 0.79, 95% CI 0.76–0.82) and educational level (OR 0.77, 95% CI 0.73–0.81), higher EF [HFmrEF (OR 0.65, 95% CI 0.62–0.68) and HFpEF (OR 0.56, 95% CI 0.53–0.58) vs. HFrEF], and higher comorbidity burden, such as presence of kidney disease (OR 0.91, 95% CI 0.87–0.95), atrial fibrillation (OR 0.85, 95% CI 0.81–0.89), and diabetes mellitus (OR 0.92, 95% CI 0.88–0.96). A planned follow‐up in specialty care was independently associated with lower risk of all‐cause [hazard ratio (HR) 0.78, 95% CI 0.76–0.80] and cardiovascular death (HR 0.76, 95% CI 0.73–0.78) across the EF spectrum, but not of HF hospitalization (HR 1.06, 95% CI 1.03–1.10). Conclusions In a large nationwide HF population, referral to specialty care was linked with male sex, younger age, lower EF, lower comorbidity burden, better socioeconomic environment and optimized HF care, and associated with better survival across the EF spectrum. Our findings highlight the need for greater and more equal access to HF specialty care and improved quality of primary care.

Background Chronic kidney disease (CKD) is a risk factor for cardiovascular (CV) events in patients with heart failure (HF). It is unclear whether type 2 diabetes (T2D), closely intertwined with both HF and CKD, modifies the association between cardiovascular outcomes and CKD in HF patients, and whether this association differs according to ejection fraction (EF). Methods HF patients enrolled in the Swedish Heart Failure Registry from January 2017 to December 2021 were analyzed. Linkage with the National Diabetes Registry and other population registries provided extensive baseline information. Patients were stratified by T2D status and CKD stages, defined by estimated glomerular filtration rate (eGFR: <30, 30–44, 45–59, ≥ 60 ml/min/1.73 m 2 ). The primary outcome was the composite of time to first HF hospitalization (HHF) or CV death. Secondary outcomes were major adverse CV events (MACE, i.e. CV death, non-fatal myocardial infarction and stroke), CV death and all-cause death. Multivariable Cox regression models assessed the associations between eGFR and outcomes according to T2D, including interaction testing. A subgroup analysis was conducted by EF. Results Of 36,597 patients included, 8,053 (22%) had T2D, 23,562 (64.4%), 7122 (19.4%), 4477 (12.2%), 1436 (4.0%), were in the four eGFR categories (eGFR ≥ 60, 45–59, 30–44, and < 30 mL/min/1.73 m 2 , respectively), and 53%, 25%, 22% had HF with reduced, mildly-reduced, and preserved EF, respectively. Across eGFR, patients with vs. without T2D were younger, more often male, with higher CV comorbidity and more frequent use of cardio-renal drugs. Across EF categories, T2D patients had higher prevalence of CKD. Lower eGFR categories were progressively associated with higher risk of the primary outcome, independently of T2D. This was consistent across EF, except in HFpEF with eGFR < 30 ml/min/1.73 m 2 , where the magnitude of the association in T2D group was smaller than in non-T2D ( p -interaction < 0.01). Risks of MACE, CV death and all-cause mortality were higher for lower eGFR categories, with lower hazards in T2D group ( p -interaction < 0.01). Conclusions In a contemporary HF cohort, decreased kidney function was associated with a progressively higher risk of HHF/CV death, and T2D was not a risk modifier. Renal protection should therefore be implemented in HF regardless of T2D.