Heart Failure With Preserved Ejection Fraction (HFpEF)

Heart failure is a clinical syndrome resulting from complex pathophysiological processes that impair ventricular structure or function. These impairments prohibit the ventricle from either filling with or ejecting blood. The signs and symptoms of heart failure, particularly dyspnea, fatigue, and congestion, are demonstrative of the most current definition of heart failure—"an inability of the heart to pump blood to the body commensurate with its needs, or to so do only at the cost of increased filling pressures."

Heart failure is a significant public health issue; the incidence and prevalence of heart failure are increasing in the United States and across the globe. Additionally, heart failure is the end stage of many disease processes, and the risk of developing heart failure increases with increasing age. Heart failure is frequently a progressive disease process, and progression is associated with decreased survival, regardless of underlying etiology. To underline these risks and the progression of disease, the American College of Cardiology and American Heart Association (ACC/AHA) have described and defined the following stages of heart failure:

1. Stage A: At Risk for Heart Failure - patients at risk for heart failure without symptoms, structural heart disease, or cardiac biomarkers of (ventricular) stretch or injury. Therapeutic interventions at this stage aim to modify underlying risk factors for the development of heart failure.

2. Stage B: Pre-Heart Failure - patients with evidence of increased filling pressures by invasive or noninvasive methods or patients with risk factors and increased biomarkers of stretch or cardiac injury that are not explained by other disease processes. Therapeutic interventions at this stage aim to treat risk and structural heart disease to prevent heart failure.

3. Stage C: Symptomatic Heart Failure - patients with structural heart disease with current or previous symptoms of heart failure. Therapeutic interventions at this stage aim to reduce symptoms, morbidity, and mortality.

4. Stage D: Advanced Heart Failure - patients with marked symptoms of heart failure that interfere with daily life and with recurrent hospitalizations despite attempts to optimize guideline-directed medical therapy. Therapeutic interventions at this stage aim to reduce symptoms, morbidity, and mortality.

Separate from the ACC/AHA Stage of Heart Failure is the New York Heart Association (NYHA) Classification of Heart Failure. This classification is a subjective assessment by a clinician to characterize the functional capacity and symptoms of patients with ACC/AHA stage C or D heart failure. The NYHA Classification is an independent predictor of mortality and is employed clinically to determine the suitability of therapeutic interventions for patients with stage C or D heart failure. The 4 NYHA heart failure classes are as follows:

1. Class I: asymptomatic

2. Class II: symptomatic with moderate activity

3. Class III: symptomatic with mild activity

4. Class IV: symptomatic at rest.

Heart failure is further classified by left ventricular ejection fraction (LVEF). The prognosis and response to treatment of patients with heart failure differs significantly when patients are stratified based on LVEF. In 2022, the ACC, AHA, and Heart Failure Society of America (HFSA) released guidelines for the management of heart failure that incorporate the following classification of heart failure by LVEF:

1. Heart Failure with Reduced Ejection Fraction (HFrEF): patients with an LVEF ≤40%

2. Heart Failure with Improved Ejection Fraction (HFimpEF): patients with a previous LVEF ≤40% and a subsequent measurement of LVEF >40%

3. Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF): patients with an LVEF 41% to 49% with evidence of spontaneous or provokable increased left ventricular filling pressures (LVFPs), characterized by elevated natriuretic peptides or hemodynamic measurements. HFmrEF is sometimes referred to as heart failure with midrange ejection fraction in the literature.

4. Heart Failure with Preserved Ejection Fraction (HFpEF): patients with an LVEF ≥50% with evidence of spontaneous or provokable increased left ventricular filling pressures (LVFPs), characterized by elevated natriuretic peptides or hemodynamic measurements.

The diagnosis of HFpEF can be challenging, particularly in patients with overt signs or symptoms of congestion. However, approximately 50% of patients with heart failure are classified as HFpEF; not all patients with HFpEF will progress to HFrEF. HFpEF is a heterogeneous clinical syndrome with many phenotypes, and the underlying pathophysiological processes of HFpEF differ from those of HFrEF. While all patients with heart failure have ventricular diastolic dysfunction, diastolic dysfunction is considered part of the normal again process and is not synonymous with HFpEF.

Patients with HFpEF have increased rates of morbidity and mortality compared to patients without heart failure. However, therapeutic interventions are available to reduce symptoms, improve functional status and quality of life, and reduce hospital admission rates. Clinical understanding of HFpEF continues to evolve, and clinical trials to improve outcomes for patients with HFpEF are ongoing.