The clinical implications and future directions for the management of patients with heart failure with mid-range ejection fraction (HFmrEF) were summarized in a state-of-the-art review published October 11, in the journal JACC: Heart Failure.

Heart failure with borderline ejection fraction was first defined as the presence of HF symptoms and a left ventricular ejection fraction (LVEF) of 41% to 49% in the ACC/American Heart Association (AHA) 2013 guidelines. In 2016, the European Society of Cardiology defined HFmrEF as LVEF of 40% to 49%.

HFmrEF has not been as well studied as HF with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively) and little is known about effective therapies for this population of HF patients. Of the 6.5 million people in the U.S. with HF, 13% to 24% have HFmrEF. The clinical profile and prognosis for HFmrEF are similar with those in patients with HFpEF. The prevalence of coronary artery disease (CAD) in patients with HFmrEF is more similar with patients with HFrEF.

The underlying pathophysiology of HFmrEF is not clear, although it appears that it may be associated with both mild systolic and diastolic dysfunction. Mortality rates of patients with HFmrEF are closer to those with HFpEF, at about 3.0%, and lower than the 3.9% observed in patients with HFrEF. Similarly, readmission rates in HFmrEF fall between those seen in HFrEF and HFpEF.

Current guidelines emphasize management of comorbidities and risk factors for patients with HFmrEF, because no therapies have been conclusively shown to improve outcomes. However, the TOPCAT trial found that spironolactone reduced HF hospitalizations in patients with HF and LVEF >=45%, although there was no effect on the composite primary outcome. A stronger benefit was observed in patients with LVEF of 45% to 50%, prompting the addition of a guideline recommendation by the ACC/AHA for aldosterone antagonist treatment to decrease hospitalizations. In the CHARM-Preserved trial, the angiotensin receptor blocker (ARB) candesartan reduced the risk of HF hospitalization in patients with LVEF >40%.

Because uncontrolled hypertension is more often the precipitating factor for HF hospitalization in patients with HFmrEF than HFpEF or HFrEF, aldosterone antagonist or ARB therapy may be useful to manage hypertension and reduce the risk of LVEF decline in this population.

"Beyond close clinical monitoring and aggressive management of comorbidities, particularly CAD, there may be benefit to earlier initiation of neurohormonal blockade if otherwise indicated," wrote Jeffrey J. Hsu, MD, et al.