Abstract Background Early heart failure with preserved ejection fraction (HFpEF) is characterised by exertional dyspnoea or intolerance. The non-specific nature of these symptoms and a lack of accurate diagnostic tools leave many undiagnosed and untreated. Whilst exercise right heart catheterisation is the recommended gold-standard, it is not widely available owing to technical challenges and its invasive nature. Exercise echocardiography offers a pragmatic compromise but its evidence-base in HFpEF diagnosis remains scarce, with significant variation in exercise protocols and assessment criteria. Purpose Using multimodality exercise imaging, the study aims to (1) correlate current recommended echocardiographic parameters at rest and exercise with functional capacity, symptom burden and adverse haemodynamic features (2) identify other echocardiographic parameters that interrogate mechanisms of exertional dyspnoea, thus improving early HFpEF diagnosis. Method Symptomatic patients with confirmed HFpEF or intermediate (INT) risk of HFpEF (as defined by the HFA-PEFF diagnostic algorithm) were prospectively enrolled alongside age-matched healthy control subjects. All participants underwent rest and 35W exercise echocardiography, exercise cardiac magnetic resonance imaging (e-CMR), 6-minute walk test (6MWT) and a Kansas City Cardiomyopathy Questionnaire (KCCQ-CSS). Results 46 HFpEF patients, 39 INT and 19 controls were recruited. The HFpEF and INT groups had similarly reduced functional capacity (6MWT HFpEF 363 vs. INT 384 vs. Control 492m) and worse patient-reported outcomes (KCCQ-CSS HFpEF 70 vs. INT 73 vs. Control 97) compared to age-matched controls. Despite more favourable serum NTproBNP, rest and stress E/e’ in the INT group, cardiac output augmentation during 35W exercise (ΔCI) on e-CMR was similarly blunted when compared to the HFpEF cohort (Table 1). Importantly, echocardiographic parameters in the current HFpEF diagnostic algorithm such as E/e’ and indexed left atrial volume (LAVI) do not correlate with 6MWT distance, KCCQ-CSS or ΔCI after adjusting for age, hypertension and body mass index (Figure A). Across this heterogeneous study cohort, rest and exercise LV septal S’ and RV S’ better correlated with 6MWT distance, KCCQ-CSS score and adverse haemodynamic features (ΔCI and right ventricular-pulmonary artery coupling) (Figures B-C). Conclusion Symptomatic patients at intermediate-risk of HFpEF share adverse haemodynamic features and functional impairment to those with diagnosed HFpEF. Using multimodality exercise imaging, we propose simple tissue doppler imaging parameters and assessment of cardiac reserve during exercise echocardiography better elicit mechanisms of exertional dyspnoea, beyond current recommendations. Further validation studies exploring these parameters are needed to advance the role of non-invasive imaging in early HFpEF diagnosis. Table 1 Figure 2
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