What is Heart Failure (HF) with mid-range ejection fraction (mrEF)?

From the Guidelines

Heart Failure (HF) with mid-range ejection fraction (mrEF) is a condition where the left ventricular ejection fraction (LVEF) is between 40-49%, representing a grey area between HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) 1.

Key Characteristics

• LVEF between 40-49% 1
• Primarily mild systolic dysfunction with features of diastolic dysfunction 1
• Dynamic trajectory, with patients potentially improving from HFrEF or deteriorating to HFrEF 1

Diagnosis

• Classic clinical signs and symptoms of HF, together with EF of 41% to 49% 1
• Elevated natriuretic peptide levels are supportive of the diagnosis, but normal levels do not exclude a diagnosis of HFmrEF 1
• Objective measures of cardiac dysfunction, such as increased LV filling pressures, are necessary to improve diagnostic specificity 1

Clinical Significance

• Differentiation of patients with HF based on LVEF is important due to different underlying aetiologies, demographics, co-morbidities, and response to therapies 1
• Therapies have been shown to reduce both morbidity and mortality in patients with HFrEF, but the optimal treatment for HFmrEF is unclear 1
• The European Society of Cardiology has developed a diagnostic algorithm to facilitate discrimination of HFpEF from noncardiac causes of dyspnea 1

From the Research

Definition of Heart Failure with Mid-Range Ejection Fraction (HFmrEF)

• HFmrEF is defined as the presence of typical symptoms of heart failure and a left ventricular ejection fraction (LVEF) of 40% to 49% 2, 3, 4, 5.
• This range of LVEF is less well studied compared with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) 2.

Clinical Characteristics and Prognosis

• Patients with HFmrEF have a clinical profile and prognosis that are closer to those of patients with HFpEF than those of HFrEF, with certain distinctions 2.
• HFmrEF is often associated with various cardiovascular and non-cardiovascular diseases, making its pathophysiological mechanisms complex and its clinical phenotypes diverse 3.
• Mortality rates among the HFmrEF population are significant, and are similar to those in patients with HFrEF and HFpEF 4.

Treatment and Management

• No randomized controlled trials exist in those with HFmrEF, though HFrEF and HFpEF studies that include overlap suggest some potential benefit of beta blockers, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors 4.
• Evidence from post hoc and subgroup analyses of randomized clinical trials and a trial of an SGLT1-SGLT2 inhibitor suggests that drugs that are effective in patients with HFrEF might also be effective in patients with HFmrEF 5.

Pathophysiology and Classification

• The pathophysiology of HFmrEF is complex and not fully understood, and its classification as a distinct entity or a transitional stage between HFrEF and HFpEF is controversial 3, 6.
• LVEF should be seen as simply one important element of a continuum throughout the heart failure syndrome, and not as a sole basis for classification 6.