Focus on HFpEF and potential therapies

By Naveed Saleh, MD, MS | Medically reviewed by James Beckerman, MD, FACC
Published May 11, 2022

Key Takeaways

  • Nearly half of all heart-failure cases are categorized as having preserved ejection fraction. Heart failure with preserved ejection fraction (HFpEF) is difficult to treat, and a focus of modern cardiology.

  • Patients with HFpEF need to have their comorbid medical conditions closely monitored and managed. They also need to engage in lifestyle changes such as improved diet, exercise, and weight loss.

  • SGLT2 inhibitors have recently been shown to improve outcomes in those with HFpEF.

A diagnosis of heart failure (HF) represents a life-altering change for patients, with their quality of life and mortality compromised. Although its etiology is rooted in various causes, the signs and symptoms of HF invariably trace back to the ventricle operating at a higher filling pressure.

Manifestation of congestion presents across the gamut of left ventricular ejection fraction (LVEF), and is nondiscriminatory based on this measure.

Nearly half of all people with HF exhibit a near normal—or preserved—LVEF.

Treatment of patients with heart failure with preserved ejection fraction (HFpEF) is therefore considered a major focus in cardiology, and relevant to physicians from various fields who care for cardiac patients in differing capacities.

Defining HFpEF

LVEF measurement is not needed to diagnose HF, but LVEF metrics do improve HF management decisions. Measuring LVEF started as an arbitrary categorization in clinical trials, with researchers eventually ascribing more practical importance to the distinction.

Looking back, researchers were initially more concerned about treating HF with reduced LVEF, and evidence-based data from clinical trials on HFpEF was limited, according to the authors of a study published in Circulation Research.[] Eventually, it became evident that HFpEF required its own therapies and devices.

“Patients with HFpEF are currently considered the larger unmet need in cardiology,” the authors wrote. “In addition, the appropriateness of testing new therapies against placebo in this population, rather than on top of known multiple proven agents and devices, has enhanced the appeal to conduct major randomized clinical trials in these patients, and many are currently underway.”

In addition to high left ventricular filling pressures and normal or near-normal LVEF (≥ 50%), patients with HFpEF demonstrate normal LV volumes and diastolic dysfunction. If a patient has no HF signs or symptoms but exhibits diastolic dysfunction on echo, they’re not diagnosed with HFpEF.[]

Because outcomes from clinical trials involving HFpEF have been scant, experts recommend the inclusion of other biomarkers to establish more restrictive inclusion criteria in randomized trials such as increased natriuretic peptide cutoffs.

Higher thresholds, however, could possibly exclude participants with obesity or individuals who harbor lower levels of natriuretic peptide due to their genetics.

While fine-tuning biomarkers for inclusion in HFpEF trials, researchers are also considering cardiac structural criteria. Better identification of those at risk for HFpEF, however, doesn’t necessarily mean that the underlying mechanisms of disease will be better targeted.

Patient management

The goals of treatment in patients with HFpEF are to attenuate symptoms of HF, increase functional status, and decrease hospital readmissions, as well as to manage hypertension, atrial fibrillation, coronary artery disease, and so forth.

For symptomatic patients, loop diuretics can be used first to improve symptoms and decrease odds of hospitalization. In patients with higher BNP, experts recommend sodium-glucose co-transporter 2 (SGLT2) inhibitors and a mineralocorticoid receptor antagonist (MRA) used together.

Clinical trials evaluating other agents such as ARBs, ACE inhibitors, calcium-channel blockers, and sacubitril-valsartan haven’t indicated efficacy in more general patient populations.

Devices such as shunts or remote pulmonary artery pressure monitors have also not proven to be effective.

In research published in Circulation, investigators found that the SGLT2 inhibitor empagliflozin decreased the risk of severe hospitalization, which necessitated intensive care and the administration of inotropic and vasopressor drugs.[]

The investigators also found that this agent lowered the risk of outpatient decompensation of heart-failure events such as urgent care visits, diuretic intensification, and drops in functional class. Results from the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction) demonstrated there was a 29% decreased risk of hospitalization in participants with HFpEF who took empagliflozin.

The authors stressed that therapeutic alternatives for those with HFpEF are limited, and the clinical benefits of empagliflozin in individuals with HPpEF are comparable with patients who have HF with reduced ejection fraction.

As for a possible mechanism explaining the benefits of empagliflozin in HFpEF, the authors floated natriuretic effect—which is likely short-lived—but put more stock in improvements in inflammation and oxidative stress in the setting of HFpEF.

What does this mean for you?

Having a patient with HFpEF is challenging, and death rates are higher than in the general population. Although newer treatments such as SGLT2 inhibitors are available, treatment options remain limited. Keep in mind that it’s important to manage comorbid conditions to decrease health risk. Also, promote lifestyle interventions such as proper diet, exercise, weight loss, and cardiac rehabilitation.

Related: Environmental factors that contribute to higher heart disease rates
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