Frailty may modify the risk versus benefit of various therapeutic interventions in heart failure. In this study, the authors performed a post hoc analysis of the DAPA-HF trial to examine the effica... Visual Dapagliflozin and Frailty in HFrEF. Frailty may modify the risk versus benefit of various therapeutic interventions in heart failure. In this study, the authors performed a post hoc... Background: Frailty may modify the risk−benefit profile of certain treatments, and frail patients may have reduced tolerance to treatments. Objective: To investigate the efficacy of dapagliflozin a...

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

Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population. The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5–5.3, P = 0.018) for OSS and 2.8 (0.3–5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3–5.6, P = 0.028) for OSS and 2.9 (0.2–5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM. In iron-deficient patients with HF and left ventricular ejection fraction <50% who had stabilized after an episode of acute HF, treatment with IV FCM, compared with placebo, results in clinically meaningful beneficial effects on HRQoL as early as 4 weeks after treatment initiation, lasting up to Week 24.

With modern treatments for heart failure with reduced ejection fraction (EF), indicative of impaired cardiac systolic function, patients may exhibit an increase in EF. Limited data are available regarding the clinical management of this growing population, categorized as heart failure with improved EF (HFimpEF), which has a high event rate and has been excluded from virtually all prior heart failure outcomes trials. In a prespecified analysis of the DELIVER trial (NCT03619213), of a total of 6,263 participants with symptomatic heart failure and a left ventricular EF >40%, 1,151 (18%) had HFimpEF, defined as patients whose EF improved from ≤40% to >40%. Participants were randomized to 10 mg dapagliflozin or placebo daily and the primary outcome of the trial was a composite of cardiovascular death or worsening heart failure (heart failure hospitalization or an urgent heart failure visit). Participants with HFimpEF had similar event rates to those with an EF consistently >40%. In participants with HFimpEF, dapagliflozin reduced the primary composite outcome (hazard ratio (HR) = 0.74, 95% confidence interval (CI) = 0.56–0.97), first worsening heart failure events (HR = 0.84, 95% CI = 0.61–1.14), cardiovascular death (HR = 0.62, 95% CI = 0.41–0.96) and total worsening heart failure events (rate ratio = 0.68, 95% CI = 0.50–0.94) to a similar extent as for individuals with an EF consistently >40%. These data suggest that patients with HFimpEF who are symptomatic may benefit from the addition of a sodium/glucose cotransporter 2 inhibitor to previously instituted guideline-directed medical therapy to further reduce morbidity and mortality.

BACKGROUND: SGLT2 (sodium-glucose cotransporter-2) inhibitors reduce the risk of cardiovascular death or worsening heart failure (HF) in outpatients with HF. Data on initiation in patients hospitalized for HF are limited. METHODS: We conducted a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of in-hospital initiation of dapagliflozin (10 mg daily) in patients hospitalized for HF. The primary efficacy outcome was a composite of time to cardiovascular death or worsening HF through 2 months. Key safety outcomes included symptomatic hypotension and worsening kidney function. A prespecified meta-analysis of randomized trials evaluating initiation of SGLT2 inhibitors in patients hospitalized for HF was performed. RESULTS: Of 2401 patients (median age, 69 [Q1–Q3, 58–77] years, 815 [33.9%] women, 448 [18.7%] Black race, 1717 [71.5%] left ventricular ejection fraction ≤40%, 1074 [44.7%] newly diagnosed HF) randomized between September 2020 and March 2025, 1218 were assigned to dapagliflozin and 1183 to placebo. The primary outcome occurred in 133 patients (10.9%) in the dapagliflozin group and 150 (12.7%) in the placebo group (hazard ratio [HR], 0.86 [95% CI, 0.68–1.08]; P =0.20). A worsening HF event occurred in 115 (9.4%) and 122 (10.3%) patients in the dapagliflozin and placebo groups, respectively (HR, 0.91 [95% CI, 0.71–1.18]). Cardiovascular death occurred in 30 (2.5%) and 37 (3.1%) patients (HR, 0.78 [95% CI, 0.48–1.27]), and death from any cause occurred in 36 (3.0%) and 53 (4.5%) patients in the dapagliflozin and placebo groups, respectively (HR, 0.66 [95% CI, 0.43–1.00]). The rates of symptomatic hypotension were 3.6% and 2.2%, and the rates of worsening kidney function were 5.9% and 4.7% with dapagliflozin and placebo, respectively. In a meta-analysis of patients hospitalized for HF, SGLT2 inhibitors reduced the early risk of cardiovascular death or worsening HF (HR, 0.71 [95% CI, 0.54–0.93] P =0.012) and of all-cause death (HR, 0.57 [95% CI, 0.41–0.80]; P =0.001). CONCLUSIONS: In this trial, in-hospital initiation of dapagliflozin did not significantly reduce the risk of cardiovascular death or worsening HF through 2 months in hospitalized HF patients. However, the totality of randomized clinical trial data suggests that in-hospital initiation of SGLT2 inhibitors may reduce the early risk of cardiovascular death or worsening HF and of all-cause mortality. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04363697.

Aims The coronavirus disease-2019 (COVID-19) pandemic has changed the landscape of medical care delivery worldwide. We aimed to assess the influence of COVID-19 pandemic on hospital admissions and in-hospital mortality rate in patients with acute heart failure (AHF) in a retrospective, multicentre study. Methods and results From 1 January 2019 to 31 December 2020, a total of 101 433 patients were hospitalized in 24 Cardiology Departments in Poland. The number of patients admitted due to AHF decreased by 23.4% from 9853 in 2019 to 7546 in 2020 (P < 0.001). We noted a significant reduction of self-referrals in the times of COVID-19 pandemic accounting 27.8% (P < 0.001), with increased number of AHF patients brought by an ambulance by 15.9% (P < 0.001). The length of hospital stay was overall similar (7.7 ± 2.8 vs. 8.2 ± 3.7 days; P = not significant). The in-hospital all-cause mortality in AHF patients was 444 (5.2%) in 2019 vs. 406 (6.5%) in 2020 (P < 0.001). A total number of AHF patients with concomitant COVID-19 was 239 (3.2% of AHF patients hospitalized in 2020). The rate of in-hospital deaths in AHF patients with COVID-19 was extremely high accounting 31.4%, reaching up to 44.1% in the peak of the pandemic in November 2020. Conclusions Our study indicates that the COVID-19 pandemic led to (i) reduced hospital admissions for AHF; (ii) decreased number of self-referred AHF patients and increased number of AHF patients brought by an ambulance; and (iii) increased in-hospital mortality for AHF with very high mortality rate for concomitant AHF and COVID-19.