Additive prognostic value of exercise echocardiography in symptomatic patients with normal or abnormal left ventricular diastolic function
Authors: Peteiro Vazquez J.C , Bouzas-Mosquera A , Martin-Alvarez E , Barbeito-Caamano C , Vazquez-Rodriguez J 
Published: October 2021

Abstract

Background
Exercise echocardiography (ExE) may assess left ventricular (LV) systolic and diastolic function. We aimed to assess the value of diastolic parameters at exercise (early LV inflow velocity to early tissue Doppler annulus velocity [E/e']) in patients with normal or abnormal resting diastolic function (DF) referred for a clinically indicated ExE.

Methods
LV systolic and DF according to EACVI Guidelines-2016, and mitral regurgitation (MR) were evaluated at rest in 773 patients (age 67±12 years) with preserved LVEF (≥50). At peak exercise we assessed regional/global LV systolic function, MR and E/e'. Abnormal ExE was defined as ischemia or fixed wall motion abnormalities and raised E/e'values as &gt;15 at rest and at exercise (e' at the septal level). Patients were grouped as complaining or not of dyspnea. Events were overall mortality, myocardial infarction, admission for unstable angina or cardiac failure, coronary revascularization, pulmonary thromboembolism, and stroke.

Results
Abnormal resting DF was present in 221 patients (29%), indeterminate in 78 (10%). Percentages were similar among the 431 patients with dyspnea (27%/11%) and the 342 without (31%/ 9%), as they were E/e values &gt;15 at rest and at exercise (16% and 18% with dyspnea; 16% and 21% without). Exercise E/e' &gt;15 was found in 37% of patients with abnormal DF, 21% with undeterminate DF, and 6% with normal DF (p&lt;0.001). Patients with abnormal resting DF had more frequently abnormal ExE (30%) in comparison with indeterminate (18%) or normal DF (17%, p&lt;0.001). Patients with abnormal ExE had more frequently abnormal resting DF than patients with normal ExE (42% vs 25%, p&lt;0.001) and similar indeterminate DF (9% vs 10%). Also, they had raised E/e' values at rest in 29% and at exercise in 25%, in comparison with normal ExE (16% at rest, 13% at exercise, both p&lt;0.001). During median follow-up of 0.9 years (25–75th percentiles 0.4–1.7) there were 109 events. Independent predictors were age (HR=1.03, 95% CI=1.01–1.06, p=0.001), male gender (HR=2.00, 95% CI=1.31–3.07, p=0.001), history of coronary disease (HR=1.63; 95% CI=1.05–2.51, p=0.03), positive clinical or exercise ECG testing (HR=1.92, 95% CI=1.31–2.81, p=0.001), peak exercise LVEF (HR=0.93, 95% CI=0.91–0.94, p&lt;0.001), and exercise E/e'(HR= 1.05, 95% CI=1.01–1.08, p=0.009). Neither resting E/e' values nor resting abnormal DF by EACVI Guidelines-2016 were independent predictors. Annualized event-rates were 38% in patients with (+) ExE plus (+) exercise E/e', 21% in those with (+) ExE and (−) exercise E/e', 11.5% in (−) ExE and (+) exercise E/e', and 3.7% with both variables normal (Figure).

Conclusions
Diastolic dysfunction results at rest and at exercise were similar between patients with or without dyspnea referred for ExE, but they were associated to abnormal ExE. Exercise E/e' reclassified 21% of patients with indeterminate DF and further predicted outcome on top of ExE results.

Funding Acknowledgement
Type of funding sources: None.