Orthostatic stress echocardiography as a useful test to measure variability of transvalvular pressure gradients in aortic stenosis

Recently several studies have reported the importance of upright posture during exercise in the detection of provocable (latent) or labile left ventricular outflow tract gradients (LVOTG) in hypertrophic cardiomyopathy or other obstructing conditions[1‐9]. Importantly, dynamic and also passive orthostatic tests are helpful in other diseases predisposing to LVOTG[5, 10]. In hypertrophic cardiomyopathy, verification of LVOTG in the upright position prior to exercise is essential. In some studies, rapid increase of LVOTG was reported only after passive orthostatic stress tests[5, 7]; and in such circumstances, exercise provocation is not necessary or even contraindicated due to risk of syncope.

As far as we are aware, the orthostatic response of valvular gradients in aortic stenosis (AS) has not been performed yet. However, low-exercise (i.e. low-stress test) was proposed apart from aggressive dobutamine stimulation[11]. This examination was performed in the supine position[11]. According to the experts, exercise testing should be considered only in patients with severe AS with equivocal or no symptoms and who are eligible for aortic valve replacement[12].

The different anatomical conditions, such as flexible (muscular) subvalvular obstruction versus stiffness (atherosclerotic) valvular stenosis may induce different hemodynamic response to preload reduction in the upright position. The aim of this study was to assess the influence of the orthostatic stress test on changes in aortic pressure gradients in AS patients.

We performed a full, standard echocardiography in the supine position. We obtained the M-mode and two-dimensional echocardiograms for each patient which was followed by a pulsed and continuous-wave Doppler ultrasound. We used conventional techniques to measure the echocardiographic parameters. The stress role in the orthostatic test was assessed in a total of 56 AS patients who did not demonstrate other serious valvular diseases. Patients were required prospectively during period of one year. We have included all AS patients without exclusion criteria as follows. 21 patients were excluded from the study for three reasons: 1) atrial fibrillation (significant beat-to-beat variability of measured gradients, 2) suboptimal Doppler signal during orthostatic test, and 3) aortic gradient significantly higher in suprasternal or right parasternal windows than in the apical window (different direction of stenosed blood jets) in the supine position. The last limitation (#3) is methodologically important because during the orthostatic examination only the transapical measurement was used. The modifying role of atrial fibrillation in AS has been recently described[13]. Ultimately, we analyzed 35 AS patients (20 males, 15 females, mean age 74.8 ± 9.2 years).

The study has been accepted by local Ethic Committee of Collegium Medicum Jagiellonian University (KBET/130/B/2011).

All patients were symptomatic. The wide range of severity of AS was examined (maximum aortic gradient in the supine position from 30 to 146 mmHg). Data of individual patients were presented in Figure 1. Example of gradient measurement were displayed in Figure 2 (supine) and Figure 3 (upright) – common response with gradient decrease about 15%. The remaining echocardiographic parameters were summarized in Table 1. With regards to the statistical trends, the maximum aortic gradient significantly decreased after orthostatic stress (87.5 ± 28.6 to 75.8 ± 23.7 mmHg p > 0.01). In 7 patients (increasing responders) the peak aortic gradient slightly increased during the stress test (5 experienced only a few percent increase and in 2 by nearly 10%). These 2 patients made up our minigroup who showed positive response, in contrast to the remaining 28 AS patients whose gradient decreased up to 40% (decreasing responders).

With an increasing prevalence of patients with valvular heart disease, a dedicated management approach is needed[14]. The evaluation of valve defect only under resting conditions might underestimate the full impact of the lesion and its clinical effects[15]. Orthostatic-induced alterations in Doppler echocardiographic measures of ventricular function have not been well-defined and in very recent study[16] echocardiographic changes from the supine to the sitting position were measured in a small group. However, the sitting position causes less hemodynamic stress (but is more comfortable) than the standing position. Standing is a fundamental activity of daily life[1] and may induce a fall in cardiac patients predisposed to syncope due to (sub) valvular obstruction. The Orthostatic test is a provocative maneuver that is definitely physiologically based and most relevant to conditions under which patients predisposed to (pre)syncope incur symptoms. In HCM patients standing is recommended as a physiologic provocative maneuver[6‐8] and in some patients standing may guide therapy. Measuring subvalvular gradients by echocardiography in the supine position, as is routine practice for assessing patients, does not reflect the pathophysiology of this pathology during daily activities, which trigger the symptoms that patients report to their cardiologists.

In the current study among AS patients, the mean value of maximum aortic gradient significantly decreases after orthostatic stress. In minority patients peak aortic gradient slightly increases during the stress test (mainly by a few percent) in contrast there is a decrease in the majority of AS patients (sometimes more than one-third). All patients were symptomatic. In previous studies with different patients i.e. asymptomatic[12, 17] exercise as stress was preferred and the provocation of the gradient was measured in the (semi) supine position. This methodology facilitates the measurement of the gradient. Additionally in the supine position, the left ventricular preload is greater than in the upright position. From a methodological point of view, the standing position is more natural and reflects a more physiological condition during everyday activity than the supine position[6]. In every-day life, AS patients have experienced syncope mostly in the upright position. Using the orthostatic test, we tried to reproduce the physiological conditions occurring during daily life.

We postulate that future Guidelines of Scientific Societies should recommend the orthostatic stress test (isolated or combined with exercise) to be employed in groups of patients with predisposition/presence of subvalvular or valvular gradients.

We did not calculate LV diastolic and systolic volumes in the standing position. In the standing position, we concentrated on the gradient measurements from the apical window. However, we did not perform short and long parasternal axis imaging. Additionally, we cannot simultaneously measure both gradient and LV dimensions, and we chose to focus on gradient recording as the main aim of this study. The measurement of LV dimensions in the standing position is difficult to obtain, and the alternative stress test, i.e. lower body negative pressure (LBNP), may provide an opportunity to measure LV unloading in the supine position (the most suitable for echocardiography). However LBNP is not a natural stress test in contrast to the natural standing position which is common everyday activity. The orthostatic stress test has additional advantages. It is fast, simple, without any cost and any devices.

In a majority of AS patients the transvalvular gradient decreased after standing. Generally, the easy, fast and costless orthostatic stress test may be helpful in the assessment of AS patients especially those predisposed to syncope due to hemodynamic disturbances.

Written informed consent was obtained from the patients for publication of this report and any accompanying images.