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This article discusses the use of calcium channel blockers (CCBs) in the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF). The article highlights that while certain therapies have been approved for heart failure with reduced ejection fraction (HFrEF) and have shown benefits for HFmrEF and HFpEF, the evidence base for beta-blockade in HFpEF is poor. The article presents a study that analyzes the association of CCBs on outcomes in patients with HFmrEF and HFpEF, finding that CCB use was associated with no difference in cardiovascular death or heart failure hospitalization. However, CCB use was associated with a lower risk of death due to pump failure and a higher risk of non-fatal stroke. The article suggests that dihydropyridine CCBs could be considered for managing comorbidities in patients with HFmrEF and HFpEF without increasing the risk of heart failure-related outcomes. The study has limitations, and further research is needed to fully understand the effects of CCBs in these patient populations. Overall, the article provides valuable insights into the use of medications in heart failure treatment and calls for a reconsideration of traditional concepts regarding indicated and contraindicated therapies. [Extracted from the article]

Aims: To compare the cost‐effectiveness of immediate and 12‐month delayed initiation of dapagliflozin treatment in patients with a history of hospitalization for heart failure (HHF) from the UK, Canadian, German, and Spanish healthcare perspectives. Methods and results: A cost‐utility analysis was conducted using a decision‐analytic Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire scores, type 2 diabetes mellitus status and incidence of heart failure (HF) events. Patient‐level data for patients with prior HHF from the Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial were used to inform the model inputs on clinical events and utility values. Healthcare costs were sourced from the relevant national reference databases and the published literature. Compared to standard therapy, immediate initiation of dapagliflozin decreased HHF (187 events), urgent HF visits (32 events) and cardiovascular mortality (18 events). Standard therapy was associated with lifetime costs of £13 224 and 4.02 quality‐adjusted life years (QALYs). Twelve‐month delayed initiation of dapagliflozin was associated with total discounted lifetime costs and QALYs of £16 660 and 4.61, respectively, compared to £16 912 and 4.66, respectively, for immediate initiation. Compared to standard therapy, immediate and 12‐month delayed initiation of dapagliflozin yielded an incremental cost‐effectiveness ratio (ICER) of £5779 and £5821, respectively. Compared to 12‐month delayed initiation, immediate initiation of dapagliflozin had an ICER of £5263. Results were similar from the Canadian, German, and Spanish healthcare perspectives. Conclusion: Both immediate and 12‐month delayed initiation of dapagliflozin are cost‐effective. However, immediate initiation provides greater clinical benefits, with almost 10% additional QALYs gain, compared to 12‐month delayed initiation of dapagliflozin and should be considered standard of care. [ABSTRACT FROM AUTHOR]

Aims Heart failure with mildly reduced ejection fraction (HFmrEF) is associated with a favourable prognosis compared with heart failure (HF) with reduced ejection fraction (EF). We assessed whether left ventricular ejection fraction (LVEF) trajectory can be used to identify groups of patients with HFmrEF who have different clinical outcomes in a large retrospective study of patients with serial imaging. Methods and results Patients with HF and ≥2 echocardiograms performed ≥6 months apart were included if the LVEF measured 40–49% on the second study. Patients were classified as HFmrEF-Increasing if LVEF had increased ≥10% (n = 450), HFmrEF-Decreasing if LVEF had decreased ≥10% (n = 512), or HFmrEF-Stable if they did not meet other criteria (n = 389). The primary outcome was all-cause mortality or cardiovascular hospitalization after the second echocardiogram. Associations with time to first event were assessed with multivariable Cox analyses adjusted for age, co-morbidities, and medications. In total, 1351 patients with HFmrEF (median age 74, 64.2% male) were included with 28.8% exhibiting stable LVEF. During median follow-up of 15.3 months, the composite outcome occurred in 811 patients. During follow-up, patients with HFmrEF-Increasing were less likely to experience the primary outcome [adjusted hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.60–0.88, P < 0.001] compared with HFmrEF-Stable. Patients with HFmrEF-Decreasing were more likely to experience the composite outcome in unadjusted analyses (unadjusted HR 1.19, 95% CI 1.01–1.40, P = 0.040) but not adjusted analyses (adjusted HR 1.16, 95% CI 0.98–1.37, P = 0.092). Associations with death or HF hospitalizations were similar (HFmrEF-Increasing: adjusted HR 0.72, 95% CI 0.59–0.88, P = 0.005; HFmrEF-Decreasing: adjusted HR 1.20, 95% CI 1.01–1.44, P = 0.044). Patients with HFmrEF-Decreasing had a similar risk of the composite outcome as patients with HF with reduced EF (adjusted HR 1.03, 95% CI 0.89–1.20, P = 0.670). Patients with HFmrEF-Increasing were less likely to experience the composite outcome compared with patients with HF with preserved EF (adjusted HR 0.73, 95% CI 0.62–0.87, P < 0.001). Conclusions Amongst patients with HFmrEF, those exhibiting positive LVEF trajectory were less likely to experience adverse outcomes after correcting for important confounders including medical therapy. Categorizing HFmrEF patients based on LVEF trajectory provides meaningful clinical information and may assist clinicians with management decisions. [ABSTRACT FROM AUTHOR]

Aims Among patients with heart failure (HF) and reduced ejection fraction (HFrEF), those with atrial fibrillation (AF) may respond differently to certain treatments than patients without AF. We investigated the efficacy and safety of dapagliflozin in patients with HFrEF with and without AF in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on new-onset AF. Methods and results The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized, 1910 (40.3%) had 'any AF' (history of AF or AF on enrolment electrocardiogram). Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in patients with and without any AF [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.62-0.92 and 0.74, 95% CI 0.62-0.88, respectively; p for interaction = 0.88]. Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and improvement of Kansas City Cardiomyopathy Questionnaire total symptom score. Among patients without AF at baseline, dapagliflozin did not significantly reduce the risk of new-onset AF compared with placebo (HR 0.86, 95% CI 0.60-1.22). However, patients with new-onset AF had a 5 to 6-fold higher risk of adverse outcomes when compared to those without incident AF. Conclusions Dapagliflozin, compared with placebo, reduced the risk of worsening HF events, cardiovascular death, and all-cause death, and improved symptoms, in patients with and without AF. Dapagliflozin did not reduce the risk of new-onset AF. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to determine factors associated with long‐term recovery of left ventricular ejection fraction (LVEF) in patients with heart failure with reduced EF (HFrEF) and if further recovery also occurs in this group. Methods and results: Among 621 participants enrolled in the Alberta Heart Failure Etiology and Analysis Team (HEART) Study, 316 with Stage C HF underwent comprehensive imaging and biomarker testing at enrolment and at 1‐year follow up. Using pre‐enrolment data, HF with recovered EF (HFrecEF) was defined as an absolute improvement ≥5% in LVEF from the prior lowest LVEF value, with a final LVEF value > 35% at or prior to study baseline. Participants with all LVEF > 40% were included for comparison. Hospitalization‐free survival to 5 years was performed. The median cohort age was 66 years, and time from diagnosis was 4 years; 82% were male patients. Of the 316 patients, 95 (30%) patients had HFrecEF and 56 (18%) patients pHFrEF. On multivariate analysis, only shorter duration of HF was predictive of HFrecEF status. Over 1 year, LVEF increased in the HFrecEF group 4.0% (0.15–7.90, P = 0.042) as compared with persistent HFrEF, who in turn demonstrated higher baseline serum high sensitivity Troponin‐T with further increase at follow up 0.55(0.33–0.86, P = 0.011). No change in any parameter in the HFpEF/HFmrEF group at follow up was observed. Conclusions: Patients with HFrecEF demonstrate evidence of additional late improvement in LVEF and unchanged troponin levels, in contrast to those with persistent HFrEF, where LVEF does not improve and serum troponin rises over time. These data help to inform mechanisms relating to late LV remodelling. [ABSTRACT FROM AUTHOR]

B This article refers to 'Dosing of losartan in men versus women with heart failure with reduced ejection fraction: the HEAAL trial' by J.P. Ferreira I et al i ., published in this issue on pages 1477-1484. b It is well known that women have been under-represented in early clinical trials of heart failure (HF). The authors noted that clinical factors associated with female sex may have suggested more frail patients, who were possibly less able to tolerate high-dose medical therapy - a plausible underlying reason for the difference in dose-response relationship. [Extracted from the article]

Aims: Ivabradine is a selective sinus node inhibitor indicated in patients with symptomatic chronic heart failure on stable guideline‐recommended heart failure therapy including appropriate doses of beta‐blockers. The use in cardiogenic shock remains off label and has been considered a contraindication due to the theoretical risk of attenuating compensatory tachycardia. Tachycardia, especially in the context of inotropic therapy, may be deleterious, resulting in increased myocardial oxygen consumption and reduction in diastolic filling. As ivabradine does not have negative inotropic action, it may present a potential means to manage tachycardia in cardiogenic shock. We present a case series of four patients with cardiogenic shock started on ivabradine who were unable to tolerate beta‐blockers. Methods and results: Five patients identified with cardiogenic shock defined as a severe reduction in cardiac index (<2.0 L/min/m2) and elevated filling pressures on inotropic therapy were started on ivabradine in patients with sinus tachycardia [heart rate (HR) >100] who were intolerant to beta‐blockers. Each patient had a cardiac magnetic resonance imaging, echocardiogram, and coronary angiogram for determination of aetiology. Invasive haemodynamics via pulmonary artery catheterization were measured during initiation and titration of ivabradine (baseline, 6, 12, 24, and 48 h after ivabradine administration) with continuous telemetry monitoring for any dysrhythmia or bradyarrhythmias. All patients tolerated ivabradine initiation, and at 24 h, an observed decrease in HR (106 ± 6.8 vs. 91.6 ± 6.4 b.p.m., P = 0.04), pulmonary arterial occlusion pressure (30.4 ± 4.8 vs. 24 ± 5.1 mmHg, P = 0.04), and right atrial pressure (16.8 ± 6.2 vs. 9 ± 4.3 mmHg, P = 0.0002). An improvement was observed in mixed venous oxygen saturation (SvO2) (51 ± 8.8 vs. 64.8 ± 5.3%, P < 0.04), stroke volume (37.2 ± 7.6 vs. 49.2 ± 12.9 mL, P < 0.04), and right and left ventricular stroke work index (Table 1). No significant changes were observed with mean arterial pressure (73.4 ± 7.5 vs. 75.8 ± 5.0 mmHg, P = 0.81) and thermodilution‐derived cardiac index (1.7 ± 0.2 vs. 2.5 ± 0.7 L/min/m2, P = 0.58). Inotropic support was weaned successfully in three of five patients (88 ± 30 h) with subsequent titration of beta‐blocker therapy. Two patients improved clinically but ultimately required left ventricular assist device implantation. All patients were discharged alive from hospital at 17 ± 7.9 days following ivabradine initiation. Conclusions: In our small non‐randomized series of patients in cardiogenic shock, ivabradine was safely used to reduce HR in patients previously intolerant of beta‐blockade. There are limited data surrounding the use of ivabradine in cardiogenic shock, and future studies should be undertaken to determine the optimal HR in humans with cardiogenic shock and whether systematic limitation of peak HR may improve outcomes. [ABSTRACT FROM AUTHOR]

B This article refers to 'A machine learning risk score predicts mortality across the spectrum of left ventricular ejection fraction' by B. Greenberg I et al i ., published in this issue on pages 995-999. b The desire to predict future events has been a basic human quality. It is therefore not surprising that numerous attempts to estimate mortality from heart failure (HF) have been made.1,2 In most cases, a predictive model is constructed by performing one or more regression techniques upon a clinical dataset and validated in a different dataset. In this context, risk prediction for HF outcomes would seem a particularly good fit for ML applications. [Extracted from the article]