The following are summary points to remember from this review about features of heart failure with mid-range ejection fraction (HFmrEF) and how they compare with the more well-studied HF groups:

1. The percentage of the HF population that falls into the HFmrEF category is between 13% and 24%, suggesting that approximately 1.6 million individuals in the United States have HFmrEF.
2. Patients with HFmrEF have clinical characteristics that are more similar to those of the HF with preserved EF (HFpEF) cohort than HF with reserved EF (HFrEF).
3. Clinical characteristics of patients with HFmrEF include older age, female gender, comorbidities (hypertension, chronic obstructive pulmonary disease [COPD], and diabetes mellitus), laboratory values (creatinine, B-type natriuretic peptide [BNP], and troponin), and medication use (beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers).
4. The HFmrEF population is more similar to the HFrEF population regarding the comorbidity of coronary artery disease (CAD).
5. In patients with HFmrEF, uncontrolled hypertension is more often the precipitating factor for HF hospitalization compared with the other HF groups.
6. The European Society of Cardiology (ESC) guidelines suggest that patients with HFmrEF likely have mild systolic dysfunction as well as diastolic dysfunction. The authors of this review question whether HFmrEF is in itself a distinct clinical syndrome or whether patients with HFmrEF are “in transition” between HFrEF and HFpEF.
7. Mortality rates are modestly higher among patients with HFrEF, but similar between those with HFmrEF and HFpEF. In the OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) trial, the mortality rates were 3.9% for patients with HFrEF, 3.0% for HFmrEF, and 2.9% for HFpEF. A study of the Swedish Heart Failure registry reported that chronic kidney disease was more strongly predictive of mortality in patients with HFmrEF and HFrEF than in patients with HFpEF, whereas a separate study reported that COPD and age ≥85 years were associated with a higher risk of mortality within 1 year after hospital discharge in the HFmrEF group compared with the other two groups.
8. No therapies have conclusively been shown to improve outcomes in patients with HFmrEF. Therefore, the American Heart Association/American College of Cardiology and the ESC guidelines for the HFmrEF population currently focus on management of risk factors and comorbidities. Diuretic therapy is recommended to help alleviate symptoms in those who exhibit signs of congestion.
9. In the TIME-CHF (Trial of Intensified Versus Standard Medical Therapy in Elderly Patients With Congestive Heart Failure) study, N-terminal proBNP–guided management was found to improve HF hospitalization-free survival in patients with HFmrEF and HFrEF, but not in patients with HFpEF. The role of biomarkers in the management of HFmrEF, however, remains to be determined.
10. Screening for and management of CAD is an acceptable approach that may help prevent further progression of left ventricular systolic dysfunction in patients with HFmrEF, as they have been shown to have a higher rate of transitioning to HFrEF compared with patients with HFpEF. Also, management of hypertension is a reasonable approach.

Keywords: Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Antagonists, Biomarkers, Comorbidity, Coronary Artery Disease, Creatinine, Diabetes Mellitus, Diuretics, Geriatrics, Heart Failure, Hypertension, Natriuretic Peptide, Brain, Peptide Fragments, Pulmonary Disease, Chronic Obstructive, Renal Insufficiency, Chronic, Risk Factors, Secondary Prevention, Stroke Volume, Troponin, Ventricular Dysfunction, Left

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