Deliberating the Diagnostic Dilemma of Heart Failure With Preserved Ejection Fraction

Abstract

There is a lack of consensus on how we define heart failure with preserved ejection fraction (HFpEF), with wide variation in diagnostic criteria across society guidelines. This lack of uniformity in disease definition stems in part from an incomplete understanding of disease pathobiology, phenotypic heterogeneity, and natural history. We review current knowledge gaps and existing diagnostic tools and algorithms. We present a simple approach to implement these tools within the constraints of the current knowledge base, addressing separately (1) hospitalized individuals with rest congestion, where diagnosis is more straightforward; and (2) individuals with exercise intolerance, where diagnosis is more complex. Here, a potential role for advanced or provocative testing, including evaluation of hemodynamic responses to exercise is considered. More importantly, we propose focus areas for future studies to develop accurate and feasible diagnostic tools for HFpEF, including animal models that recapitulate human HFpEF, and human studies that both address a fundamental understanding of HFpEF pathobiology, and new diagnostic approaches and tools, as well. In sum, there is an urgent need to more accurately define the syndrome of HFpEF to inform diagnosis, patient selection for clinical trials, and, ultimately, future therapeutic approaches.

Keywords: diagnosis; exercise test; heart failure.

Figure 1.. Contributors to diagnostic dilemma of HFpEF and summary of diagnostic tools.

We place HFpEF diagnosis within the context of the natural history of the disease (panel A). We recognize limited understanding with respect to factors driving progression of cardiac remodeling and extracardiac involvement (panels B and C). Broadly, we propose to categorize individuals with HFpEF into non-hospitalized individuals with exercise intolerance vs hospitalized individuals with rest congestion in order to examine relevant diagnostic tools and approaches (panel D and E). Central to this conceptual framework is the recognition of major current knowledge gaps (right-hand side of figure).

Figure 2.. Practical approach to diagnostic tools.

In individuals suspected to have HFpEF, first steps include evaluating for rest congestion and consideration of potential secondary causes. If no diagnosis has been made, first-line diagnostic tools include echocardiography, natriuretic peptide levels, and objective assessment of functional capacity. Algorithms including HFA-PEFF and H₂FPEF may be helpful in estimating probability of HFpEF. In individuals where diagnosis remains unclear, advanced testing can be considered including rest and exercise invasive hemodynamic measures, and diastolic stress testing in experienced centers.