Incremental prognostic and diagnostic value of exercise echocardiography in patients with indeterminate or abnormal diastolic function
Authors: Peteiro Vazquez J.C , Bouzas-Mosquera A , Martin-Alvarez E , Barbeito-Caamano C , Vazquez-Rodriguez J.M 
Published: October 2021

Abstract

Background
Exercise echocardiography (ExE) may assess LV systolic and diastolic function (DF). We aimed to assess the diagnostic and prognostic value of diastolic parameters at exercise (ratio of early LV inflow velocity to early tissue Doppler septal annulus velocity [E/e'] and systolic pulmonary artery pressure [sPAP]) in patients with indeterminate or abnormal resting DF referred for a clinically indicated ExE.

Methods
Data from 299 patients (72±9 years, 50% women) with LV-DF evaluated according to EACVI-Guidelines 2016, and LVEF ≥50 were extracted from our database. LV systolic and DF and mitral regurgitation (MR) were evaluated at rest. At peak exercise we assessed regional/global LV systolic function, MR, E/e', and sPAP. Abnormal ExE was defined as ischemia or fixed wall motion abnormalities, elevated E/e'values as &gt;15 at rest and at exercise. Considered events were overall mortality, myocardial infarction, admission for unstable angina or cardiac failure, revascularization, pulmonary thromboembolism, and stroke.

Results
Abnormal resting DF was present in 221 patients (29%), indeterminate in 78 (10%). Exercise E/e' &gt;15 was found in 37% of patients with abnormal DF, and in 21% with indeterminate DF; exercise E/e &gt;15 plus sPAP&gt;51 mmHg in 13% with abnormal DF, and in 9% with indeterminate DF. Based on exercise E/e' &gt;15 (n=16), change from altered relaxation to restrictive pattern with exercise (n=8), or maintenance of a restrictive pattern for &gt;65 years (n=4), indeterminate DF was reclassified to abnormal DF in 28/78 patients (36%). Among the other 50 patients with indeterminate DF and exercise E/e' ≤15, sPAP&gt;51 mmHg was found in 21, having these subjects altered relaxation at rest and at exercise (n=19) or atrial fibrillation (n=2). Abnormal ExE was seen in 18% of patients with indeterminate resting DF, in 30% with abnormal resting DF, and in 40% with raised exercise E/e'. During median follow-up of 1 year (25th-75th percentiles 0.4–1.7) there were 53 events including 12 deaths, 6 myocardial infarctions, and 18 cardiac failures. Independent predictors were history of coronary disease (HR=2.50, 95% CI=1.31–4.75, p=0.005), ACEI/ARAII (HR=0.43, 95% CI=0.23–0.81, p=0.008), positive clinical or exercise ECG testing (HR=2.42, 95% CI=1.33–4.40, p=0.004), peak LVEF (HR=0.94, 95% CI=0.92–0.96, p&lt;0.001), significant exercise MR (HR=3.96, 95% CI=1.58–9.97, p=0.004) and peak E/e'(HR= 1.06, 95% CI=1.02–1.10, p=0.004). Annualized event rates were 59% in patients with (+) ExE plus raised exercise E/e', 24% in those with (+) ExE and normal exercise E/e', 14% in (−) ExE and raised exercise E/e', and 5.4% with both variables normal (Figure).

Conclusions
ExE reclassified 21 to 36% of patients with indeterminate DF to abnormal DF, and was able to detect non-cardiac exercise-induced pulmonary hypertension. E/e'at postexercise further predicted outcome on top of ExE results in patients with indeterminate or abnormal resting DF.

Funding Acknowledgement
Type of funding sources: None.