This editorial refers to ‘Ratio of transmitral early filling velocity to early diastolic strain rate predicts long-term risk of cardiovascular morbidity and mortality in the general population’, by M.C.H. Lassen et al., doi:10.1093/eurheartj/ehy164. The search for non-invasive indexes of left ventricular (LV) filling pressures has, for many years, been a hot topic in echocardiographic research. During the last few decades, several echocardiographic indexes have been introduced combining the ratio of E (transmitral early diastolic flow velocity) to e’ [early diastolic mitral annulus velocity by pulsed wave tissue Doppler imaging (TDI)]1 or, more recently, to e’SR [peak early diastolic LV longitudinal strain rate by speckle tracking echocardiography (STE)].2 These indexes were associated with pulmonary capillary wedge pressure (PCWP) and were introduced as non-invasive markers of LV end-diastolic pressure (LVEDP). The ratio E/e’ has been extensively studied and has been established as both a simplified marker of elevated filling pressures and a prognostic marker in cardiovascular subgroups, as well as in the general population.3–5 Even if a mechanistic rationale for this association has been introduced,1 the correlations that have been reported have been quite modest and with quite a large amount of scatter, especially in patients without LV systolic dysfunction.6 This indicates that factors other than those incorporated in the index E/e’ may be of importance, as demonstrated in the recommended algorithm from the European Association of Cardiovascular Imaging and the American Society of Echocardiography (Figure 1). Figure 1 View largeDownload slide A modified algorithm for the estimation of left ventricular filling pressures in patients with depressed LVEF and patients with myocardial disease and normal LVEF. Modified from the 2016 European Association of Cardiovascular Imaging and the American Society of Echocardiography recommendations for the evaluation of left ventricular diastolic function by echocardiography.5 (modified with permission from reference 5). LA, left atrium; LAP, left atrial pressure; TR, tricuspid regurgitation. Figure 1 View largeDownload slide A modified algorithm for the estimation of left ventricular filling pressures in patients with depressed LVEF and patients with myocardial disease and normal LVEF. Modified from the 2016 European Association of Cardiovascular Imaging and the American Society of Echocardiography recommendations for the evaluation of left ventricular diastolic function by echocardiography.5 (modified with permission from reference 5). LA, left atrium; LAP, left atrial pressure; TR, tricuspid regurgitation. The ratio E/e’SR has also been introduced as a promising marker of filling pressures.2 However, the closest correlation to PCWP was observed when using peak strain rate (SR) during isovolumic relaxation (IVR), and only a modest correlation to PCWP when using peak e’SR during early filling,2 which is the parameter most frequently used in clinical studies.7 e’ by pulsed wave TDI have inborn methodological limitations affecting the ratio E/e’, such as angle dependency, as well as the fact that measurements are being sampled from only one or two locations in the LV base, usually in a four-chamber view. One of the strengths of pulsed wave TDI for assessing e’ is the relative independency of top quality images, and e’ may therefore be used in a wide spectrum of patients. This is in contrast to STE-derived measures, like e’SR, being more dependent on good image quality, which again might limit the clinical utility in patients with insufficient image quality. The angle independency achieved by using STE and the incorporation of the diastolic longitudinal deformation rate of the entire LV wall are possible benefits of using E/e’SR rather than E/e’ for assessing LV filling pressures. As a large LV may have greater velocities, the normalization to LV length, as included in the SR approach, may be of importance. In clinical practice, some LV segments are often excluded in the calculation of e’SR due to suboptimal image quality. Whether this exclusion may reduce the accuracy of e’SR and E/e’SR is unknown, but it might potentially affect the results. Even if using e’SR rather than e’ may potentially reduce the scatter and improve the correlations when comparing the index to LVEDP or PCWP, E/e’SR is still an imperfect marker of LV filling pressure. Early diastolic LV deformation is, in general, governed by active LV relaxation, restoring forces as well as early diastolic LV load.8,9 Moreover, diastolic function is an interplay between three-dimensional LV deformation, atrial function, and pulmonary vein flow. Therefore, reducing the assessment of LV diastolic function to an approach only including transmitral flow velocity and longitudinal diastolic myocardial velocity or strain rate will always be a simplification. Transmitral early diastolic flow velocity reflects the blood velocity through an echocardiographic sample area, which is fixed with respect to the thoracic wall. As the mitral annulus moves towards the atrium during early diastole, the LV engulfs a certain volume of blood that shifts compartment from the left atrium (LA) to LV with only limited flow velocity. Thus, E primarily reflects the rapid movement of blood travelling through the echocardiographic sample volume, whereas the volume of blood being engulfed by the LV base is reflected by the LV long axis measures. Therefore, an alternative mechanical understanding of the ratios E/e’ and E/e’SR is that they reflect the relationship between the early diastolic pressure-driven fraction of LV filling and the mitral annular displacement-driven filling fraction of the LV. As early diastolic deformation rates and velocities decrease with reduced LV diastolic function and increasing filling pressures, the magnitude of both indexes will increase with relatively small changes in E. In this issue of the European HeartJournal, Lassen et al. describe the prognostic properties of E/e’SR in the general population, and compare it to established echocardiographic measures as well as clinical prognostic markers.10 In a population without known cardiovascular disease with a follow-up of 11 years, E/e’SR provided independent and incremental prognostic information when compared to E/e’, where e’ was assessed by color TDI, and remained a strong independent predictor of myocardial infarction, heart failure admission, or cardiovascular death after adjusting for demographical, clinical, and echocardiographic measures. Interestingly, E/e’SR carried better information of prognosis in participants with preserved systolic function [global longitudinal strain (GLS) above 18%], as opposed to those with reduced systolic function. However, in the calculation of e’, they used color TDI rather than the widely evaluated pulsed wave TDI. One should be aware that a parameter achieved from a two-dimensional-based echocardiographic method like STE and color TDI, will be less accurate in terms of the highest amplitude regarding e’SR. This fact did not preclude the results from Lassen et al., but should obviously be taken into account before guiding patients about their prognosis. As E/e’ has been shown to carry less prognostic information in patients with preserved left ventricular ejection fraction (LVEF), the current study is promising by virtue of its exploration of prognostic information gained by using E/e’SR. Until the variation between different STE software has been overcome, one should be careful using E/e’SR in the prognostic evaluation of patients. E/e’ has been confirmed in numerous studies to be associated with filling pressures in various clinical conditions, as well as being an important prognostic marker of CV disease.3–5 E/e’SR showed promising prognostic properties for CV disease in the study by Lassen et al. Importantly, future studies are needed to determine the usefulness of this echocardiographic index in the clinical and prognostic evaluation of patients. Even if the mechanistic understanding of E/e’SR is not complete, the prognostic information, especially in individuals without LV systolic dysfunction, is promising. GLS has repeatedly shown superior predictive power in patients with suspicion of LV dysfunction11,12 after acute coronary syndromes13,14 and in patients with heart failure stage B.15 The predictive power and clinical use of both systolic and diastolic parameters and ratios should therefore be further explored in future prospective multicenter trials, including E/e’SR, E/e’, and GLS. 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For permissions, please email: email@example.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)
European Heart Journal – Oxford University Press
Published: May 15, 2018
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