We would like to thank Dr Tozzi for his thoughtful letter regarding our report titled “Elevated Left Ventricular Outflow Tract Velocities on Exercise Stress Echocardiography May Be a Normal Physiologic Response in Healthy Youth.” Stress echocardiography (SE) was initially developed in 1979 and has seen substantial success in the evaluation of patients with known or suspected coronary artery disease, with proven applicability to clinical questions of diagnosis, prognosis, and follow-up and similar degrees of accuracy as competing technologies such as radionuclide perfusion imaging. The use of SE has expanded to the evaluation of patients with hypertrophic cardiomyopathy (HCM) largely as a means of inducing latent left ventricular outflow tract (LVOT) obstruction in symptomatic patients with no resting obstruction, a technique supported by both the American College of Cardiology and the American Heart Association in recent guidelines. As mentioned in Dr Tozzi’s letter, there are now multiple studies showing that acquiring exercise data in the upright position generates higher LVOT velocities than acquiring the data in the supine position in both healthy subjects and those with HCM. Because upright positioning is more physiologic, and techniques exist with which accurate SE data can be obtained in this position, it seems logical that this would be the standard approach for this type of testing. Interestingly, even as increasingly more studies are published evaluating the LVOT using exercise SE, standardization of this measurement and specific guidelines on SE for this indication are lacking and seem warranted.

We agree that environmental influences such as eating or drinking before exercise and overall hydration status may have an impact on exercise hemodynamics, perhaps explaining increased velocities across the LVOT demonstrated in this and other studies, although this topic requires further study in larger cohorts of healthy subjects. Furthermore, the importance of a complete resting evaluation to delineate specific cardiac anatomy that may be predictive of pathologic obstruction, such as abnormalities of the mitral valve, cannot be overemphasized. Abnormalities of the mitral valve or aortic valve or narrowing of the LVOT in general may be suggestive of pathology, and therefore the detection of LVOT obstruction during exercise in this setting would be concerning and needs to be considered in combination with the remainder of the patient’s medical and family history. Our study demonstrated the presence of increased flow velocities across the LVOT immediately after exercise, more often in the setting of dynamic intracavitary narrowing. We did not appreciate flow acceleration due to mitral-septal contact in the presence of systolic anterior motion of the mitral valve. Although there are studies documenting labile subaortic obstruction during exercise in adults, at times due to systolic anterior motion, this is not something we were able to reproduce in our study, and therefore, detection of systolic anterior motion with exercise would raise our concern for pathology such as HCM.

If a child with a structurally normal heart and a benign family history is found to have flow acceleration across the LVOT with exercise due to dynamic intracavitary narrowing, although the etiology could be multifactorial, the utility of a comprehensive evaluation and treatment, as suggested by Dr Tozzi, is unclear. Indeed, as he mentions, the interpretation of stress test results must be patient specific and take into account the reason for exercise testing as well as the physiologic state of the patient at the time of testing. Most important, our data suggest that the measurement of exercise-induced LVOT velocities alone may not help distinguish a child with HCM from a child without this disease.

Dr Tozzi’s insight into other variables that may be important in the evaluation of patients suspected of having HCM are important, namely, the status of the right ventricle. Patients who have HCM with right ventricular involvement but no LVOT obstruction at rest may be at risk when intravascularly volume depleted at peak exercise. Differences in ventricular filling in normal patients compared with patients with HCM during head-up tilt-table testing have previously been demonstrated. As Dr Tozzi alludes to, reduced preload in the setting of a noncompliant right ventricle could potentially reduce cardiac output to a critical level and result in reduced systemic output and reduced coronary perfusion. Published data demonstrate that the presence of restrictive right ventricular physiology has significant predictive value, irrespective of other detrimental risk factors. Our work has found that increased LVOT velocities can develop in pediatric patients who have no ostensible evidence of HCM, and volume depletion may be important.

Finally, the interpretation of physiologic data from SE in a child remains limited by a lack of normative data for comparison. Additionally, standardized protocols are needed for pediatric SE to address important issues such as the most appropriate timing of data acquisition (during or immediately after exercise), the most appropriate position for data acquisition (upright or supine), and the most appropriate method for Doppler interrogation of the LVOT (pulsed-wave or continuous-wave Doppler). Once defined, these protocols could be used to expand our understanding of the mechanism with which increased LVOT velocities occur.