Table 2.

Key Questions and Gaps with Regard to the Understanding of HFpEF

Key Questions	Gaps in Evidence	Future Studies Needed
Phenotyping & Pathophysiology
Phenotyping HFpEF is promising to better individualize therapy, but it remains unclear how HFpEF phenotypes should be defined?	There can be several approaches to HFpEF classification, including pathophysiologic, clinical presentation, comorbidities, cardiac structure, and machine-learning. What are the roles of non-invasive imaging, biomarkers, or other approaches?	Further study is required to standardize the HFpEF phenotyping, identify discrete phenotypes that behave similarly and respond to treatment similarly, and identify the optimal roles of non-invasive imaging and biomarkers to categorize them.
Diagnosis
Currently, echocardiography is a central role for diagnosis of HFpEF. What are the roles of different modalities in the evaluation for HFpEF?	Other imaging modalities such as cardiac magnetic resonance, cardiac computed tomography, and positron emission tomography may be promising, but the data to support their usefulness require further investigation.	Future studies are needed to investigate the roles for difference modalities in the evaluation for HFpEF.
What are the expected roles of novel imaging techniques for HFpEF?	Recent studies have reported the possibility of machine learning-based echocardiographic analysis for diagnosis and phenotyping in HFpEF.	Future studies are needed to establish the roles of machine learning-based imaging in HFpEF, with appropriate standards against which the machine-learning approaches can be compared.
Because hemodynamics are often normal at rest in HFpEF, diastolic stress echocardiography may be useful to enhance diagnosis, but is this ready for standard practice?	Evidence to support its utility across multiple studies in HFpEF is not sufficient. E/e’ may not change with changes in filling pressure during exercise. How should we deal with E-A fusion during exercise? What is the optimal cutoff of E/e’ during exercise?	Further research is needed to validate the utility of exercise stress echocardiography, ideally in multicenter studies using simultaneous assessment using echocardiography and invasive hemodynamics, with blinded interpretation from disinterested observers.