2022 Top Story in Cardiology: Heart Failure With Preserved Systolic Function

The prevalence of heart failure (HF) with preserved systolic function (HFpEF) has been increasing in the past 10 years, comprising almost 50% of the decompensated HF admissions.¹ Failure of a clear definition from professional societies, the syndrome had been defined as an ejection fraction (EF) >40%, primarily based on registries and not necessarily by physiologic definitions. Clinical trials have instead guided the care of HFpEF, with disappointing results.^2-4 It became clear in registries that the group of patients with decompensated HF and high EFs were more likely to be older women with less ischemic disease and multiple comorbidities, such as diabetes, hypertension, and obesity among others.¹ Although trials such as I-PRESERVE,² CHARM-Preserved,⁴ and even TOPCAT³ were disappointing and on marginal findings sometimes tempered by geography, mineralocorticoid antagonists (spironolactone) earned a place in the update of the 2013 guidelines, published in 2017 as a 2b recommendation.⁵ Other recommendations included logical and basic items such as controlling blood pressure pressure and investigating the presence of ischemia and arrhythmias; no recommendation, however, was definitive. Enter the SGLT2 inhibitors, which, amazingly, in patients with or without diabetes and/or the presence of HF, clearly reduced HF hospitalizations in those with lower EFs, although the exact mechanism of such a benefit was and is still not clear.⁶ As the field learned from the PARAGON trial of sacubitril/valsartan, EF was important in that, as it rose, the effect of the drug was diminished or even reversed; thus, the definition of HFpEF changed to EF >50%. It was logical and parallel to PARAGON that the successful SGLT2 inhibitors in HF with a reduced EF would be tested in the HFpEF environment. The EMPEROR-Preserved trial was the first one reported and published with markedly positive findings in patients defined by HFpEF or EF >40% where the data had been less clear.⁷ Empagliflozin reduced the combined endpoint of cardiovascular death or HF hospitalization in patients with EF >40% regardless of the presence of diabetes by 21%, with a significant hazard ratio of 0.87.

This study led to the ACC/AHA 2022 guidelines categorizing the use of SGLT2 inhibitors in patients with HFpEF and EF >40% as a 2a recommendation, while keeping spironolactone as a 2b and adding sacubitril/valsartan also as a 2b recommendation.⁸ For the first time, a drug has received a higher recommendation for HFpEF, giving clinicians a guide to therapy.

In summary, in HFpEF, where trials had failed to identify the “ideal” drug, for the first time the field has been given a non-debatable HFpEF trial providing guidance to clinicians in this very difficult-to treat yet growing syndrome.