We appreciate the caution by Hammoudi et al. regarding routine clinical application of E/e’ as a noninvasive measure of LV filling pressure in subjects with normal ejection fraction. It is true that several studies have shown that correlation between PCWP and E/e’ in healthy individuals at rest and with exercise is poor. The lack of correlation is due to the fact that e’ increases with higher preload and also with exercise in normal subjects so that E/e’ remains normal as shown by Ha et al. and Bruengger et al. with exercise as well as at rest. The elevation of filling pressure with fluid infusion in normal subjects is transient since augmented relaxation would normalize filling pressure relatively quickly with no clinical consequence. However, in patients with reduced myocardial relaxation, E/e’ has been shown to track left atrial or pulmonary capillary wedge pressure well, including a good correlation between the simultaneous intra-left atrial pressure and E/e’.

We have to admit that there are several technical challenges and clinical conditions which may make the interpretation of E/e’ difficult as a non-invasive measure of left ventricular filling pressure, but in most cases we should be able to assess whether a patient has increased filling pressure with exercise. E/e’ measurement has been part of our stress echocardiography protocol since 2008 and this practice has helped our evaluation of patients with exertional dyspnea, which is the most common referral reason for an exercise echocardiography. As mentioned in our editorial, the diagnostic yield from exercise echocardiography for patients with dyspnea has doubled after diastolic evaluation was added routinely to our exercise echocardiography protocol at Mayo Clinic. E/e’ was also found to correlate well with exercise capacity, and when added to clinical substrates for developing heart failure, half of the subjects were reclassified to stage B heart failure from stage A. One of the most powerful features of echocardiography is to be able to assess intracardiac hemodynamics noninvasively, and E/e’ is a simple hemodynamic measure that can help many of our patients whose exertional dyspnea needs a comprehensive diagnostic evaluation. If E/e’ is not diagnostic or difficult to be interpreted, unexplained exertional dyspnea requires cardiac catheterization to measure intracardiac hemodynamics at rest and with exercise.