Heart Failure With Preserved Ejection Fraction Management: 5 Things to Know

Daniel N. Silverman, MD; Sheldon E. Litwin, MD; Ryan J. Tedford, MD, FACC


October 07, 2020

Editorial Collaboration

Medscape &

Patients with heart failure with preserved ejection fraction (HFpEF) represent approximately 50% of all HF cases. Whereas several proven medical therapies are available for HF with reduced ejection fraction (HFrEF), there is a paucity of evidence-based treatments for HFpEF. Nonetheless, a stepwise set of management practices can be followed to optimize the care of patients with this challenging syndrome.

Here are five things to know about HFpEF.

1. Diagnostic challenges abound when it comes to HFpEF.

Diagnosing HFpEF can present quite a challenge to physicians. Not only is there no single diagnostic test or biomarker specific for HFpEF, but patients with HFpEF may have several comorbidities (eg, obesity, pulmonary disease, diabetes) that can mimic symptoms of HF, such as dyspnea on exertion or fatigue. Although transthoracic echocardiography is a critical component to assess and establish preserved left ventricular [LV] systolic function, the presence or absence of any of the following may be insufficient to rule in or out the diagnosis of HFpEF:

  • Diastolic dysfunction;

  • Signs of elevated filling pressures; or

  • Elevated right ventricular (RV) systolic pressures.

To further confound the diagnosis, it is also not uncommon for patients with HFpEF to have normal B-type natriuretic peptide (BNP) levels. This is particularly the case in patients with obesity, who often have significantly lower BNP levels than their nonobese counterparts.

In the patient with dyspnea who has an LV ejection fraction (LVEF) ≥ 50%, the gold standard for diagnosing HFpEF remains invasive hemodynamic assessment with right heart catheterization. Elevated LV filling pressures (generally a pulmonary artery wedge pressure > 15 mm Hg) have been the traditional hemodynamic threshold for diagnosing HFpEF. Right heart catheterization also provides the opportunity to determine the presence and severity of concomitant pulmonary hypertension due to left heart disease, as well as rule out pulmonary arterial hypertension.

Normal left-sided filling pressures at rest, however, do not exclude a diagnosis of HFpEF. Provocative maneuvers, such as exercise or fluid bolus, during right heart catheterization may reveal abnormal elevation of filling pressures suggestive of left heart disease. For this reason, it is critical to "stress the system" in cases wherein HF is suspected but results of the resting assessment are unclear.

Although invasive hemodynamics can help clarify the diagnosis, right heart catheterization may not be practical, feasible, or even necessary, depending on the pretest probability of HFpEF. As such, the European Society of Cardiology (ESC) recently developed the following four-step HFA-PEFF diagnostic algorithm:

Step 1: Pretest assessment

Step 2: Diagnostic workup

Step 3: Advanced workup

Step 4: Etiologic/final workup

The pretest assessment, which conforms to the initial diagnostic workup recommendations in the 2016 ESC HF guidelines, incorporates the clinical history, signs and symptoms, basic cardiac testing, and laboratory studies. The diagnostic workup includes comprehensive echocardiography and, if not previously assessed, natriuretic peptides; points are assigned on the basis of major (2 points) or minor (1 point) findings. Patients with a score ≥ 5 are considered to have HFpEF. Advanced workup (diastolic stress testing, invasive hemodynamic stress testing) is recommended for those whose score is 2-4 points. In the final workup, patients may undergo additional advanced testing (eg, cardiac biopsy, CT, genetic testing) to determine a specific known cause of HFpEF.

The H2FPEF score is a tool used to predict the likelihood of HFpEF in patients with dyspnea. This scoring system, which was derived from a retrospective analysis of both patients with HFpEF and control patients who underwent invasive hemodynamic exercise testing, can also be utilized to predict whether a patient's dyspnea is due to HFpEF or a noncardiac condition.

After making the diagnosis of HFpEF, physicians then need to determine the underlying cause when possible (eg, infiltrative, pericardial, genetic, or hypertrophic cardiomyopathy) because this may have specific therapeutic implications. Recent studies looking at autopsy samples and endomyocardial biopsies suggest that cardiac amyloid is prevalent in patients with HFpEF. Because noninvasive diagnostic testing and targeted therapy are now widely available, amyloid should always be considered in the differential diagnosis.


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