Assessing the Risk of Heart Failure With Preserved Ejection Fraction in Individuals With Exertional Dyspnea

How can patients with exertional dyspnea who are at risk of heart failure with preserved ejection fraction (HFpEF) be identified?

In the United States, heart failure affects 27 per 1,000 Medicare beneficiaries and was associated with more than 300,000 deaths in 2014 and 1.2 million hospitalizations in 2017.¹ The American Heart Association (AHA), American College of Cardiology (ACC), and the Heart Failure Society of America (HFSA) define heart failure as a clinical syndrome caused by structural or functional challenges in the way blood fills or is ejected from the ventricles. HFpEF describes heart failure with a left ventricular ejection fraction of 50% or greater.¹

Recent advances have led to effective treatments for HFpEF. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been shown to reduce the composite of cardiovascular mortality and hospitalization for heart failure in those with HFpEF.² Other studies have shown that glucagon-like peptide-1 receptor agonists may help decrease heart failure exacerbations and improve quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire.³ AHA/ACC/HFSA guidelines recommend blood pressure and atrial fibrillation control and use of SGLT-2 inhibitors for individuals with HFpEF. They also recommend that mineralocorticoid receptor antagonists, angiotensin receptor blockers, and angiotensin receptor blocker–neprilysin inhibitors should be considered in patients with HFpEF.¹

With availability of effective treatments, a tool that helps identify patients with exertional dyspnea who have HFpEF would be useful for guiding evaluation and management. An early clinical prediction rule, the H₂FPEF score, was developed from a cohort of 414 patients, 267 of whom had HFpEF, determined by elevated pulmonary capillary wedge pressures at rest or during exercise in the setting of an ejection fraction of 50% or greater. The factors used in the H₂FPEF score include body mass index, use of antihypertensive medication, atrial fibrillation, pulmonary hypertension, age, and filling pressures shown on echocardiography. The score was validated with a cohort of 100 additional patients and had an area under the curve (AUC) of 0.886 (values of more than 0.8 are generally considered good).⁴

The European Society of Cardiology released an alternative diagnostic pathway for HFpEF called the Heart Failure Association-Pretest assessment, Echocardiography and natriuretic peptide, Functional testing, Final aetiology (HFA-PEFF) score, which assigns points for different functional and structural findings on echocardiography and varying levels of elevated brain natriuretic peptide (BNP; different cutoffs for BNP are used based on whether a patient is in sinus rhythm or atrial fibrillation).⁵ This score was validated in two cohorts of 270 and 459 patients, with an AUC of 0.90.⁶

The H₂FPEF and HFA-PEFF scores may require more information than is available during an ambulatory encounter for exertional dyspnea in a setting without immediate access to echocardiography or BNP testing. To address the need for a screening tool based on readily available information that can guide the decision for further testing, the HFpEF-ABA tool was developed.⁷ The derivation cohort included 414 patients, and the validation cohort included 736 patients. Elevated pulmonary capillary wedge pressures at rest or during exercise were used as the reference standard for HFpEF in both cohorts. Patients with reduced ejection fraction were excluded. The tool was additionally validated in a cohort of 456 patients who required hospitalization for decongestion of HFpEF and a cohort of 3,076 patients with HFpEF in the Veterans Administration health system.⁷