Sherif F: E/e’ Ratio: An Index of LV Filling Pressures Revisited.

There is a clinical need for the assessment of cardiac function in patients who present with symptoms and signs of pulmonary and systemic congestion. Echocardiography has been utilized over the years to answer this question. It is possible to study left ventricular (LV) systolic and diastolic function as well as pulmonary artery pressures and right ventricular function using this technique. With respect to LV diastolic function, an ideal assessment includes evaluation of LV relaxation and LV filling pressures. There are several parameters that when properly acquired and analyzed can predict the 2 fundamental aspects noted above of LV diastolic function. The mitral annulus early diastolic recoil velocity (e’) recorded by tissue Doppler imaging (TDI) was introduced as an index of LV relaxation. Further, e’ velocity is combined with mitral peak velocity E to predict LV filling pressures1. I will discuss the supporting literature for the last statement and point to the limitations in its application.

There are a number of animal2, 3 and human4–6 studies that have shown a significant relation between e’ velocity and LV relaxation as assessed invasively by the time constant of LV relaxation (tau). Importantly, there are other variables that determine e’ velocity which include LV preload and elastic recoil2, 3. The effect of preload depends on the presence or absence of abnormal LV relaxation such that in normal hearts there is a significant positive relation between LV filling pressures and mitral e’ velocity. On the other, this effect is much less in the presence of impaired LV relaxation2. Likewise, there are human studies showing that e’ velocity is affected by factors that affect function at the cellular level as beta-adrenergic receptors7, tumor necrosis factor-alpha and inducible nitric oxide synthase8.

Given the predominant effect of LV relaxation on e’ velocity in the Presence of cardiac disease, we reasoned that it can be used to correct for the effects of LV relaxation on mitral E velocity and thus E/e’ ratio can be used as an index of LV filling pressures1. E/e’ ratio was evaluated in several cardiac diseases including heart failure (patients with reduced EF and those with normal EF), cardiomyopathy and atrial fibrillation1, 6, 9–11. In addition to diagnostic applications, there are many studies that have reported on its ability to predict clinical events including single center and epidemiologic studies (see reference 12 for a summary of these studies). Furthermore, E/e’ ratio has been acquired by CMR and validated against echocardiography and cardiac catheterization13.

Notwithstanding the established utility of this index, there are a number of limitations to its use. These include the presence of mitral valve disease, moderate to severe mitral annular calcification, left bundle branch block, pacemaker rhythm, constrictive pericarditis12, 14 and the ratio cannot be applied in normal hearts as e’ is heavily dependent on LV filling pressures in this setting15. Overall and specifically in these conditions it is important to use a comprehensive approach12 and other novel indices of LV diastolic function as time delay between mitral E and annular e’, LV and left atrial diastolic strain rates, and LV untwisting rate14, 16–17 can be considered.

References

1. 

Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA Quiñones Ma: Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997; 30: 1527–1533

2. 

Nagueh SF, Sun H, Kopelen HA, Khoury DS Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler. J Am Coll Cardiol. 2001; 37: 278–285

3. 

Opdahl A, Remme EW, Helle-Valle T, Lyseggen E, Vartdal T, Pettersen E, Edvardsen T, Smiseth OA Determinants of left ventricular early- diastolic lengthening velocity: independent contributions from left ventricular relaxation, restoring forces, and lengthening load. Circulation. 2009; 119: 2578–86

4. 

Oki T, Tabata T, Yamada H, Wakatsuki T, Shinohara H, Nishikado A et al Clinical application of pulsed tissue Doppler imaging for assessing abnormal left ventricular relaxation. AM J Cardiol. 1997; 79: 921–8

5. 

Sohn D, Chai I, Lee D, Kim HC, Kim HS, Oh BH et al Assessment of mitral annulus velocity by Doppler tissue imaging in evaluation of left ventricular diastolic function. J Am Coll Cardiol. 1997; 30: 474–80

6. 

Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM et al Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study. Circulation 2000; 102: 1788–94

7. 

Shan K, Bick RJ, Poindexter BJ, Shimoni S, Letsou GV, Reardon MJ, Howell JF, Zoghbi WA, Nagueh SF Relation of tissue Doppler derived myocardial velocities to myocardial structure and beta-adrenergic receptor density in humans. J Am Coll Cardiol. 2000; 36: 891–896

8. 

Kalra DK, Ramchandani M, Zhu X, Lawrie G, Reardon MJ, Mann DL, Zoghbi WA, Nagueh SF Relation of tissue Doppler-derived myocardial velocities to serum levels and myocardial gene expression of tumor necrosis factor-alpha and inducible nitric oxide synthase in patients with ischemic cardiomyopathy having coronary artery bypass grafting. AM J Cardiol. 2002; 90: 708–712

9. 

Nagueh SF, Bhatt R, Vivo RP, Krim SR, Sarvari SI, Russell K, Edvardsen T, Smiseth OA, Estep JD Echocardiographic evaluation of hemodynamics in patients with decompensated systolic heart failure. Circ Cardiovasc Imaging. 2011; 4: 220–227

10. 

Kasner M, Westermann D, Steendijk P, Gaub R, Wilkenshoff U, Weitmann K et al Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study Circulation. 2007; 11: 637–47

11-. 

Sohn DW, Song JM, Zo JH, Chai IH, Kim HS, Chun HG et al Mitral annulus velocity in the evaluation of left ventricular diastolic function in atrial fibrillation. J Am soc Echocardiogr. 1999; 12: 927–31

12. 

Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA Evangelista a. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am soc Echocardiogr. 2009; 22: 107–133

13. 

Paelinck BP, de Roos A, Bax JJ et al Feasibility of tissue magnetic resonance imaging: a pilot study in comparison with tissue Doppler imaging and invasive measurement. J Am Coll Cardiol. 2005; 45: 1109–16

14. 

Diwan A, McCulloch M, Lawrie G, Reardon MJ, Nagueh SF Doppler estimation of left ventricular filling pressures in patients with mitral valve disease. Circulation. 2005; 111: 3281–3289

15. 

Firstenberg MS, Levine BD, Garcia MJ, Greenberg NL, Cardon L, Morehead AJ et al Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers. J Am Coll Cardiol. 2000; 36: 1664–9

16. 

Min PK, Ha JW, Jung JH, Choi EY, Choi D, Rim SJ et al Incremental value of measuring the time difference between onset of mitral inflow and onset of early diastolic mitral annulus velocity for the evaluation of left ventricular diastolic pressures in patients with normal systolic function and an indeterminate E/E’. AM J Cardiol. 2007; 100: 326–30

17. 

Mor-Avi V, Lang RM, Badano LP, Belohlavek M, Cardim NM, Derumeaux G, Galderisi M, Marwick T, Nagueh SF, Sengupta PP, Sicari R, Smiseth OA, Smulevitz B, Takeuchi M, Thomas JD, Vannan M, Voigt JU, Zamorano JL ular filling pressures:Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr. 2011; 24: 277–313



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