![]() ![]() A post-hoc analysis of treatment effect size across pre-specified LVEF subgroups showed that the beneficial effects of empagliflozin were limited to LVEF 40%, including recovered LVEF, is currently underway. This benefit was driven by a reduction in HF hospitalizations. In prespecified subgroup analysis, there was a suggestion of benefit in patients with LVEF 40%. Relative to valsartan, sacubitril-valsartan did not significantly reduce the composite endpoint of CV death and total hospitalizations for HF but did reduce HF hospitalizations. The angiotensin receptor neprilysin inhibitor (ARNi) sacubitril-valsartan was compared to valsartan in an RCT which included patients with HF and LVEF ≥45%. Spironolactone did, however, show an improvement in rates of HF hospitalizations. This was followed by an exploratory analysis of the trial, including only patients from the Americas, which did show a small benefit in the primary outcome. 1 The TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial of the mineralocorticoid receptor antagonist, spironolactone, in HFpEF failed to show an overall benefit in the primary composite outcome of all-cause mortality and HF hospitalizations. 1 Randomized controlled trials (RCTs) of beta blockers in HFpEF are a major unmet need.Īngiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), historically important in the management of HFrEF, have demonstrated a reduction in HF hospitalizations, but no reduction in all-cause or CV mortality in HFpEF. rate controlling only) may have differential effects in different HFpEF phenotypes. ![]() 5 To make matters more complicated, there is some evidence that the type of beta blocker (non-selective and vasodilating, such as nebivolol and carvedilol, vs. 4 However, recent research suggests that beta-blocker withdrawal is in fact associated with improved functional capacity of patients with HFpEF. 3 Observations from a large-scale registry suggested that in patients with HFpEF and a heart rate of ≥70 beats per minute, high dose beta blocker use was associated with lower all-cause mortality. Furthermore, the benefit of beta blockers in HF and atrial fibrillation across LVEF is equivocal. The pharmacologic interventions that have demonstrably reduced all-cause or cardiovascular (CV) mortality in HFrEF with LVEF 50%. 1 As LVEF increases in HF, non-cardiac comorbidities account for an increasing proportion of death and hospitalizations. Management of HFpEF ranges from lifestyle interventions, (diet, exercise training), management of modifiable risk factors and comorbidities (hypertension, coronary artery disease, atrial fibrillation, obesity, diabetes, cigarette smoking), to pharmacologic therapies, and health services. As our understanding of HFpEF continues to evolve, so does our approach to treatment. 2 The complex pathophysiology of HFpEF makes it a diagnostic and therapeutic challenge. 1 What was initially thought to result from LV diastolic dysfunction alone, is now increasingly being recognized as a multi-organ, systemic syndrome. Heart Failure with preserved ejection fraction (HFpEF) is currently defined as HF with left ventricular ejection fraction (LVEF) ≥50% and elevated LV filling pressures at rest or during exercise, diagnosed after careful exclusion of conditions that may mimic HFpEF. As LVEF increases, the proportional contribution of non-cardiac and non-HF events to death or hospitalization increases, highlighting the importance of managing comorbidities. ![]() Caloric restriction and exercise are under-recognized interventions in improving outcomes.To date, no medication classes have reduced cardiovascular or all-cause mortality in HFpEF.Renin-angiotensin aldosterone system inhibitors and sodium-glucose cotransport-2 inhibitors have emerged as promising drug therapies for reducing heart failure hospitalizations in HFpEF.The complex pathophysiology of heart failure with preserved ejection fraction (HFpEF) makes it a diagnostic and therapeutic challenge. ![]()
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