Exercise test protocol

Supine exercise is technically less demanding but also less physiological than upright exercise. It should be underscored that orthostatic exercise reflects physical exercise during everyday activity and reduces the preload more than supine exercise.

Recently, Lafitte et al. [4] clearly documented that the 2^nd approach could not be considered to be a pure evaluation of exercise dynamics and also postulated that 3^rd option is not adequate because dramatic pre-load variations were observed a few seconds after the end of exercise. They [4] further stressed that, when the subject was upright at the termination of exercise, there was a large decrease in venous blood return to the heart, yielding a decreased left ventricular volume, a decreased wall stress, a continued sympathetic drive, and a hyperkinetic state like that observed during dobutamine-induced stress.

In the two most recent publications, Wittlieb-Weber et al. [5, 6] stated that, since upright positioning was more physiologic, it seems logical that this would be the standard approach for LVOTG assessment. According to these authors, since increasingly more studies had been, and would be, published in evaluating the LVOTG by exercise stress echocardiography, standardization of this measurement and specific guidelines on stress echocardiography for this indication, which thus far had been lacking, should be stipulated.

Methodology

The specific preparation for exercise test for echocardiographic monitoring has been described in detail by Cotrim et al. [2]. Also, the echocardiographic technology in upright position has been precisely demonstrated in this publications. At the present moment, we would like to propose a standardized stress echocardiographic protocol for LVOTG provocation in HCM in accordance with several previous studies exploring not only HCM but also other cardiac conditions (Table 1, Scheme 1). Mechanisms predisposing to LVOT induction are summarized in Scheme 2. The Doppler-echocardiographic approach is from the apical view.

Protocol	Comments, references
1. Period of 12-h fasting before exercise	[7]
2. Physiological exercise test for LVOTG provocation
A/ Pre-exercise stage – echocardiography first in supine position and then in upright position	In some patients rapid emergence or increase in LVOTG has been reported after mere standing prior to orthostatic stress testing; under such circumstances, exercise provocation is not only unnecessary but even contraindicated, because of the risk of syncope.
B/ Position during exercise – upright
C/ Exercise gradient monitoring – continuous
D/ Moment of gradient measurement by Doppler echocardiography – peak exercise
E/ Mode of exercise – treadmill	bicycle can be confidently used to acquire peak images, but peak O2 consumption is lower than that achieved by treadmill, which might lead to lower sensitivity. In addition, in contrast to treadmill, leg discomfort or lack of leg strength is a common reason for terminating prematurely the bicycling test.
F/ Termination of test – symptom-limited;	alternatively, pre-specified heart rate/workload (or combination).
G/ Post-exercise recovery – continuous monitoring of LVOTG in upright position
Full protocol in treadmill 2A-G [8–13]

Investigation centers/cardiac diseases

In transaortic valve level, normal values for healthy subjects during upright bicycle exercise in 24 adult healthy male endurance athletes from rest to peak exercise (at a heart rate of 160 bpm) are as follows:, the maximum aortic flow velocity almost doubled (1,14 vs 2,20 m/s) and the maximum transmitral flow velocity more than doubled (0,62 vs 1,43 m/s) [17]. The transaortic velocities with the similar increases were achieved in untrained adolescent boys (1,36 vs 2,08 m/s) and girls (1,08 vs 1,96 m/s) [18]. Maximal upright exercise transaortic gradient should be peaked below 20 mmHg in bicycle exercise.

We would like to emphasize that (sub)valvular gradient measurement during and after exercise may be diagnostically useful also in other diseases/conditions than HCM. Therefore, a standardized exercise protocol is of paramount importance for universal application in the practice of cardiology (Table 2), (Figures 1, 2, 3, 4 and 5), (Additional file 1, Additional file 2, and Additional file 3). In Table 2, we have included studies with at least Items B and D from Table 1. A significant number of studies on upright bicycle exercise was used; thus our analysis is heterogeneous. Items 1 and 2 in Table 2 described our own experiences.

Limitation of method and learning curves

Elderly patients may not exercise well in supine positions [29]. On the other hand, treadmill exercise may predispose to syncope [30]; however, particularly in patients with a history of syncope, we should assess hemodynamic changes during treadmill exercise as potential risk factors. An additional advantage of treadmill exercise is the fact that patients usually can achieve higher workload.

The main limitation of exercise stress echocardiography is the presence of a poor acoustic window in some patients [31, 32]. Furthermore, only apical view is imaginable. However, in Doppler-gradient examination feasibility is high and success rate may be achieved in more than 90% of the cases. The subvalvular LVOT gradient is easier to measure than the transvalvular gradient in aortic valvular stenosis [33]. In some clinical situation (hemodialysis room) only passive (non-exercise) orthostatic test may be applicable [34].

Imaging acquisition during exercise echocardiography is more difficult than during pharmacological stress, due to the greater increase in both heart and respiratory rates with exercise. Pharmacological stress echocardiography requires less skills than exercise stress echocardiography. On the other hand, most physicians and fellows in training acquire the necessary expertise to perform peak exercise studies on a treadmill with confidence after 100 cases.

Advantages of method

The low cost, safety [35], diagnostic accuracy, possibility of evaluation of functional capacity and lack of radiation exposure should make exercise stress echocardiography an attractive procedure for patients with hypertrophic subvalvular or valvular aortic stenosis. The possibility of evaluation of Doppler data during and after exercise in orthostatic position in patients with LVOT obstruction provides very practical and useful information. Despite its limitations we believe that this test when standardized is suitable for use in every institution around the world.