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

A diagnosis of heart failure (HF) represents a life-altering change for patients, with their quality of life and mortality compromised. Although its aetiology is rooted in various causes, the signs and symptoms of HF are invariably traced 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.

Defining HFpEF

1. LVEF measurement is not needed to diagnose HF, but LVEF metrics do improve HF management decisions. Measuring LVEF started as an arbitrary categorisation in clinical trials, with researchers eventually ascribing more practical importance to the distinction.
2. 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.

The authors wrote: 

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

3. 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.
4. Because outcomes from clinical trials involving HFpEF have been scant, experts recommend the inclusion of other biomarkers to establish more restrictive inclusion criteria in randomised trials such as increased natriuretic peptide cutoffs.
5. Higher thresholds, however, could possibly exclude participants with obesity or individuals who harbour lower levels of natriuretic peptides due to their genetics.
6. 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 the 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 manage hypertension, atrial fibrillation, coronary artery disease, and so forth.

1. For symptomatic patients, loop diuretics can be used first to improve symptoms and decrease the odds of hospitalisation. In patients with higher BNP, experts recommend sodium-glucose co-transporter 2 (SGLT2) inhibitors and a mineralocorticoid receptor antagonist (MRA) used together.
2. 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.
3. Devices such as shunts or remote pulmonary artery pressure monitors have also not proven to be effective.
4. In research published in Circulation, investigators found that the SGLT2 inhibitor empagliflozin decreased the risk of severe hospitalisation, which necessitated intensive care and the administration of inotropic and vasopressor drugs.
5. 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 hospitalisation in participants with HFpEF who took empagliflozin.
6. 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.
7. As for a possible mechanism explaining the benefits of empagliflozin in HFpEF, the authors floated the natriuretic effect—which is likely short-lived—but put more stock in improvements in inflammation and oxidative stress in the setting of HFpEF.

Disclaimer: This story is contributed by Naveed Saleh and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.