Reference Ranges and Physiologic Variations of Left E/e' Ratio in Healthy Adults: Clinical and Echocardiographic Correlates

Background: Transthoracic Doppler echocardiographic examination is commonly performed to define the diastolic ventricular function since it is widely available, noninvasive, and inexpensive with respect to other diagnostic imaging modalities. However, data regarding age- and gender-matched reference values are scanty and sometimes conflicting. This study aims to explore the physiologic variations of left ventricular (LV) E/e' ratio as assessed in a large cohort of healthy adults and to investigate clinical and echocardiographic correlates. Methods: From June 2007 to February 2014, 1168 healthy Caucasian adults (mean age 45.1 +/- 15.6 years) performed standard echocardiographic examination (transthoracic echocardiogram). Results: E/e' constantly increases across all the age classes (P < 0.0001, analyses of variance both for males and females) with a strong statistically significant linear positive correlation with age. Stepwise multiple linear regression analysis identified age (P < 0.0001), LV mass (P < 0.001), LV end-diastolic volume (P < 0.01), and left atrial volume (P < 0.001) as the only independent determinants of E/e' ratio (model R-2 = 0.54, P < 0.0001). Conclusions: In healthy subjects, transmitral E velocity to e' ratio changes in relation to the age: it increased with a statistically significant correlation in individuals older than 60 years. Hence, differences related to demographic and anthropometric measurements may potentially develop a misclassification of otherwise normal individuals when established on dichotomically suggested normal reference values. Our study can demonstrate that it is indispensable to apply specific cutoff related to the age and gender to properly assess LV diastolic function.