Heart failure with mildly reduced ejection fraction (HFmrEF): where are we now?

Area of Science:

• Cardiology
• Heart Failure Research

Background:

• Heart failure with mildly reduced ejection fraction (HFmrEF), or mid-range EF, encompasses patients with left ventricular ejection fraction (LVEF) of 40-49%.
• HFmrEF bridges the gap between HFrEF (EF < 40%) and HFpEF (EF ≥ 50%), exhibiting intermediate etiologies, risk factors, and comorbidities.
• LVEF in the HFmrEF range can fluctuate, leading to transitions between HF classifications and complicating its distinct phenotype.

Purpose of the Study:

• To synthesize current evidence on HFmrEF, emphasizing its spectrum nature rather than a discrete phenotype.
• To highlight the management implications and biological overlap of HFmrEF with other heart failure classifications.
• To guide future research directions for HFmrEF.

Main Methods:

• Review of current evidence and clinical trial data related to HFmrEF.
• Analysis of subgroup data from trials investigating HF therapies.
• Synthesis of guideline recommendations and emerging treatment approaches for HFmrEF.

Main Results:

• HFmrEF patients share risk factors with HFrEF but have comorbidity profiles and prognoses closer to HFpEF.
• Mortality and quality-of-life metrics for HFmrEF generally fall between HFrEF and HFpEF.
• Standard neurohormonal therapies (beta-blockers, RAS inhibitors, ARNIs, MRAs) and SGLT2 inhibitors demonstrate benefits in HFmrEF, reducing hospitalizations and/or mortality.
• Finerenone has shown improved outcomes in HFmrEF, and guidelines recommend SGLT2 inhibitors (Class I).

Conclusions:

• HFmrEF should be viewed as a clinical spectrum with significant overlap in pathophysiology with HFrEF and HFpEF.
• Management of HFmrEF largely mirrors that of HFrEF, with established therapies proving effective.
• Emerging therapies like SGLT2 inhibitors and finerenone offer significant benefits, solidifying treatment approaches for HFmrEF.