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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., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose of Review: Measurement of heart rate (HR) and rhythm is used to identify patients at increased risk of disease progression, guide selection of treatments and gauge response to therapy., Recent Findings: Lowering HR with a pure HR lowering agent (ivabradine) in heart failure with reduced ejection fraction (HFrEF) and sinus rate more than 70 beats/min despite beta blockade has been shown to improve outcomes. Additionally, coadministration of ivabradine and beta blockade may enhance symptoms and HR control. In the case of patients with heart failure and preserved ejection fraction (HFpEF), or with paced rhythm, optimal HR control is not known. Also, in atrial fibrillation the relationship between HR and outcomes is not clear and minimal evidence for HR reduction to less than 100 beats/min exists. Reasons for this disconnect between atrial fibrillation and sinus rhythm are not known., Summary: HR continues to be a critical vital sign in assessment and forms the basis for a treatment target in patients with HFrEF at rates more than 70 beats/min. The target for HR patients with HFpEF and those who are paced continuously or in atrial fibrillation is less clear and at present is recommended to be in the 60-100 beats/min range at rest. Further study is needed to refine treatment strategies in these latter patients.