Diastolic stress echocardiography in patients with normal resting diastolic function: prognostic utility in presence and absence of myocardial ischemia
Authors: Alam L , Omar A M , Konje S , Gandhi K , Moras E , Meister D , Pena M , Perez Lizardo C , Mancero B , Zipf E , Kim G H , Elias J , Argulian E 
Published: October 2022

Abstract

Background
Abnormal diastolic response to exercise is reportedly associated with worse cardiovascular events. However, this has not been well studied in patients with normal diastolic function at rest.

Purpose
We sought to study diastolic response to exercise in patients referred for exercise stress echocardiography (ExE) and to explore its association with adverse outcomes in the presence and absence of exercise-induced myocardial ischemia.

Methods
In a retrospective study, patients referred for ExE to assess myocardial ischemia between April 2017 and December 2018 were enrolled. Patients were included if they had guideline-defined normal diastolic function at rest and availability of a full set of post exercise diastolic variables (post exercise tissue Doppler derived septal mitral annular early diastolic velocity (e'), ratio of pulsed Doppler derived mitral forward flow early diastolic velocity (E) over e' (E/e') and continuous wave Doppler derived maximum tricuspid regurgitation velocity (TRV)). The patients were followed for a median of 3.4 years for the occurrence of composite death, acute coronary syndrome, cardiac hospitalization, and need of follow-up ischemia testing. Abnormal exercise diastolic variables were defined as e' &lt;7 cm/s, E/e' &gt;15, and TRV &gt;2.8 m/s.

Results
We studied 492 patients [age: 55.7±12.9 year, 268 (54%) women, EF: 61±5.8%]. Mean achieved metabolic equivalents of tasks (METs) was 9.7±3.1, and a total of 49 (10%) patients had evidence of exercise-induced ischemia. At rest, mean left atrial volume index was 25.4±12 ml, e' was 8±2 cm/s, E/e' was 9.5±2.4, and TRV was 2.1±0.44 m/s. Post exercise e' was 10±3 cm/s [&lt;7cm/s in 63 (13%)], E/e' was 11.1±3.9 [&gt;15 in 95 (19%)], and TRV was 2.37±0.68 m/s [&gt;2.8 m/s in 152 (31%)]. Ischemic ExE was found to be strongly associated with the outcome (HR: 4.46, 95% CI: 2.8 to 7.1, p&lt;0.001). In addition, all diastolic variables predicted the outcome in isolation if they were abnormal (e': 2.28, 95% CI: 1.4 to 3.7, p=0.001, E/e': 1.81; 95% CI: 1.15 to 2.84, p=0.01; TRV: 1.58, 95% CI: 1.17 to 2.13, p=0.003). When combined, however, association with the outcome was seen only when 2 or 3 of these variables were abnormal simultaneously (Figure 1A). When patients were stratified by ischemia and abnormal diastolic variables (figure 1B), patients with 2 or 3 abnormal variables were more likely to experience the outcome compared to patients with 0 or 1 abnormal variables in both absence of ischemia (p&lt;0.001) and presence of ischemia (p=0.016). The stratified groups were different in their clinical and exercise profiles, with worse profiles in patients with both ischemia and 2 or 3 abnormal variables, and best profiles in patients with no ischemia and 0 or 1 abnormal variables.

Conclusions
In patients referred for ExE to assess ischemia with normal baseline diastolic function, exercise can unmask abnormal diastolic properties and stratify patients' risk regardless of the overt myocardial ischemia.

Funding Acknowledgement
Type of funding sources: None.