Spontaneous Variability of Left Ventricular Outflow Tract Gradient in Hypertrophic Obstructive Cardiomyopathy

BACKGROUND: Improvement in the left ventricular outflow tract (LVOT) gradient has been used as a means of assessing response to therapy in patients with hypertrophic obstructive cardiomyopathy (HOCM). To our knowledge, no data exist regarding the spontaneous day-to-day variability of the LVOT gradient in patients with HOCM. Defining the magnitude of such variability is critical to properly understand how much improvement in LVOT gradient must be present to invoke a therapeutic response. METHODS AND RESULTS: We studied the spontaneous variation in the continuous-wave, Doppler-derived pressure gradient on 5 consecutive days in 12 HOCM patients and 5 aortic stenosis control subjects. While in some patients the day-to-day variability in resting gradient was small, in others it varied markedly. The 95% confidence interval for attributing a change in LVOT gradient to factors other than random variation is +/-32 mm Hg for resting gradient and +/-50 mm Hg for provoked gradient. The mean coefficient of variation for gradient across 5 days for the group was 0.52+/-0.33 for resting gradient and 0.46+/-0.16 for provoked gradient. The day-to-day variability in pressure gradient could not be explained by changes in heart rate, blood pressure, or left ventricular end-diastolic dimension, each of which had a coefficient of variation <.11. Moreover, technical factors related to the performance or interpretation of the studies did not account for it because the coefficient of variation for gradient in aortic stenosis was <10% and interobserver and intraobserver agreement was excellent (r=.96 and .98, respectively). CONCLUSIONS: The LVOT pressure gradient varies considerably from day to day in stable patients with HOCM. A single measurement of pressure gradient is not adequate to define the severity of dynamic LVOT obstruction in HOCM.