In the report by Heffernan et al, the investigators stated that left ventricular outflow tract gradient (LVOTG) was assessed during exercise in patients with hypertrophic cardiomyopathy (HC), as previously described by Maron et al. In that study, LVOTG was measured not during exercise but after exercise, when changing from upright to supine position was responsible for delayed LVOTG measurement. In Heffernan et al’s study, from the same institution, although abnormal blood pressure response to exercise was analyzed during exercise in an upright position, LVOTG was measured not simultaneously with exercise but with some delay after exercise in a different (supine) position (according to the method described in the previous report ).

In a pioneering study from the National Institutes of Health published in 1966, Mason et al stated that cardiac symptoms were noted most commonly in patients when they were in the erect position, and these symptoms also tended to occur during or immediately after exertion. Accordingly, we would like to reemphasize the many advantages of LVOTG measurement during exercise in the upright over the supine position in patients with HC: (1) Verification of LVOTG in the upright position before exercise is essential, because in some studies, rapid increases in LVOTG were reported after passive orthostatic stress testing only, and in such circumstances, exercise provocation is not needed or is even contraindicated (because of risk for syncope). (2) In the assessment of abnormal blood pressure response, exercise LVOTG should be measured in upright exercise. (3) Exercise in the supine position is nonphysiologic: in supine bicycle (ergometry) exercise, left ventricular preload is greater than in the upright position, resulting in less LVOTG provocability and greater exercise-related diastolic dysfunction and pulmonary hypertension (milder LVOTG and faster exercise intolerability), and the standing position during exercise (especially in stress testing using the “more natural” treadmill rather than the “less natural” bicycle for patients with HC) reflects a more physiologic condition during everyday activity than bicycle ergometry, whether supine or upright. (4) LVOTG is more easily provoked using double-stressor testing (active exercise combined with upright position). (5) There is increased safety of monitoring LVOTG during exercise. (6) Additional psychological stress for patients is associated with fast movement from a treadmill to an examining table for echocardiography to compare the peak exercise upright and postexercise supine results. (7) The upright position is also important during the recovery period, because rapid postexercise preload reduction in upright position gives an opportunity to detect further LVOTG increase and/or the development of new LVOTG. (8) In everyday life, patients remain upright (or sit down) after exercise rather than being rapidly placed in a supine position.

There are additional advantages of LVOTG measurement in treadmill versus bicycle ergometry: (1) Walking is a much more physiologic exercise than cycling. Some patients may have problems with muscle fatigue when trying to ride a bicycle. (2) Cycling more effectively pumps blood from the legs to the heart and “artificially” increases left ventricular preload, thus blunting the inducible LVOTG.

Several other stress tests, such as the Valsalva maneuver, amyl nitrite inhalation, isoproterenol infusion, and so on, are nonphysiologic and non-natural. The practical significance of LVOTG provoked by non-natural stimuli remains controversial, because these maneuvers are difficult to standardize in routine clinical practice and do not reproduce the physiologic conditions in which obstruction occurs during daily life. Currently, several HC centers across Europe and the United States are testing various exercise protocols of LVOTG provocation for methodologic standardization and optimization.