Exercise stress echocardiography for diagnosis of heart failure with preserved ejection fraction: a multicentre study

BACKGROUND AND AIMS: Exercise stress echocardiography is recommended as an alternative to invasive testing for diagnosing heart failure with preserved ejection fraction (HFpEF), but an evidence-based operational framework guiding its application is lacking. METHODS: Patients with chronic unexplained dyspnoea underwent invasive haemodynamic exercise testing with simultaneous echocardiography to test the hypotheses that (i) the current diagnostic algorithms (H2FPEF, HFA-PEFF, and HFpEF-ABA scores) could be enhanced when combined with exercise echocardiography; and (ii) incorporating resting left atrial (LA) compliance (LA reservoir strain divided by E/e') could further improve diagnostic triage, using separate cut points optimizing sensitivity and specificity. Findings were then validated in an international multicentre cohort. RESULTS: Of 482 patients, HFpEF was present in 386 and non-cardiac dyspnoea in 96. Sensitivity to detect HFpEF was only 55%-60% and accuracy 61%-67% using individual diagnostic scores with currently recommended exercise echocardiography. Addition of abnormal resting LA compliance to exercise echocardiography increased sensitivity to 84%-85% but increased the false-positive rate to 31%-43%. Applying separate cut points that optimize specificity and sensitivity (either exercise E/e' ≥ 13.8 or resting LA compliance ≤1.6% to rule-in HFpEF; both exercise E/e' < 7.2 and resting LA compliance >4.4% to rule-out HFpEF, remaining patients indeterminate who require invasive testing) improved sensitivity to 95%-99% among definitively classified patients and reduced the number of patients that require invasive exercise testing from ∼60% to ∼30%. Findings were replicated in a multicentre, international validation cohort of patients undergoing rest-exercise echocardiography and invasive exercise testing. CONCLUSIONS: Currently used non-invasive approaches to HFpEF diagnosis have inadequate sensitivity, indicating that exercise echocardiography cannot supplant invasive testing. Addition of LA strain imaging with optimized rule-in or rule-out values improves diagnostic triage by expanding non-invasive rule-in/rule-out classifications while identifying patients who still require invasive testing in the evaluation of HFpEF.