From the Guidelines
An ejection fraction (EF) of 45% indicates heart failure with mildly reduced ejection fraction (HFmrEF). This classification is based on the most recent guidelines from the American College of Cardiology/American Heart Association, which define HFmrEF as a left ventricular ejection fraction (LVEF) of 41%-49% 1. According to these guidelines, patients with HFmrEF have structural heart abnormalities but may have minimal or no symptoms yet.
Key Considerations
- The classification of HFmrEF is crucial for guiding treatment and management decisions.
- Treatment for HFmrEF typically includes medications such as ACE inhibitors or ARBs, beta-blockers, and SGLT2 inhibitors, as well as lifestyle modifications like sodium restriction, regular physical activity, and smoking cessation.
- Regular monitoring of symptoms, blood pressure, and kidney function is essential to prevent progression to symptomatic heart failure.
Management and Treatment
- Medications: ACE inhibitors like lisinopril (10-40 mg daily) or ARBs such as losartan (50-100 mg daily), beta-blockers like metoprolol succinate (25-200 mg daily), and SGLT2 inhibitors like empagliflozin (10 mg daily) may be prescribed.
- Lifestyle modifications: sodium restriction (<2g daily), regular physical activity, smoking cessation, and limiting alcohol intake.
- Monitoring: regular assessment of symptoms, blood pressure, and kidney function to prevent further cardiac remodeling and deterioration of heart function.
Clinical Implications
- The goal of treatment is to prevent further cardiac remodeling and deterioration of heart function.
- HFmrEF can progress to symptomatic heart failure if not properly managed, highlighting the importance of regular monitoring and adherence to treatment plans.
- The classification and treatment of HFmrEF are supported by recent guidelines and studies, including the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1 and the standardized definitions for evaluation of heart failure therapies 2.
From the FDA Drug Label
PARAGON-HF, was a multicenter, randomized, double-blind trial comparing sacubitril and valsartan and valsartan in 4,796 adult patients with symptomatic heart failure with left ventricular ejection fraction greater than or equal to 45%, and structural heart disease [either left atrial enlargement (LAE) or left ventricular hypertrophy (LVH)] The median left ventricular ejection fraction was 57%. In an analysis of the relationship between LVEF and outcome in PARADIGM-HF and PARAGON-HF, patients with LVEF below normal treated with sacubitril and valsartan experienced greater risk reduction (Figure 7) The efficacy of sacubitril and valsartan was evaluated in a multinational, randomized, double-blind trial PANORAMA-HF comparing sacubitril and valsartan (n = 187) and enalapril (n = 188) in pediatric patients aged 1 month to less than 18 years old due to systemic left ventricular systolic dysfunction (LVEF ≤ 45% or fractional shortening ≤ 22.
The stage of heart failure with an Ejection Fraction (EF) of 45% is Heart Failure with Mildly Reduced Ejection Fraction (HFrEF) or Heart Failure with Preserved Ejection Fraction (HFpEF) cannot be determined with the information provided, as the terms HFrEF and HFpEF are not explicitly mentioned in the label. However, based on the information that patients with LVEF ≤ 45% were included in the PANORAMA-HF trial, it can be inferred that an EF of 45% is considered below normal. 3
From the Research
Heart Failure Classification
- Heart failure can be classified into two main categories: Heart Failure with Reduced Ejection Fraction (HFrEF) and Heart Failure with Preserved Ejection Fraction (HFpEF).
- HFrEF is defined as the presence of typical symptoms of heart failure and a left ventricular ejection fraction ≤ 40% 4.
- HFpEF is defined as a left ventricular ejection fraction ≥ 50% 5.
Ejection Fraction of 45%
- An ejection fraction of 45% falls between the definitions of HFrEF and HFpEF.
- According to the definition of HFrEF, an ejection fraction of 45% is above the threshold of ≤ 40% 4.
- According to the definition of HFpEF, an ejection fraction of 45% is below the threshold of ≥ 50% 5.
- There is no specific classification for an ejection fraction of 45% in the provided studies.
Management of Heart Failure
- The management of heart failure depends on the classification of heart failure, either HFrEF or HFpEF.
- For HFrEF, there are effective guideline-directed medical therapies available 4.
- For HFpEF, the treatment is largely focused on management of symptoms and comorbidities, and there are no approved treatments specifically indicated for HFpEF 6.