Relation of ultra-low frequency heart rate variability to the clinical course of chronic aortic regurgitation.

We examined the relation of the standard deviation of the 5-minute mean RR intervals over 24 hours (SDANN), a measure of ultra-low frequency heart rate variability (HRV) (<0.0033 Hz), and other measures of HRV to clinical outcome events in 50 asymptomatic or minimally symptomatic patients with chronic severe aortic regurgitation (AR) who underwent ambulatory electrocardiography as part of a prospective study of the natural history of regurgitant valvular diseases. At entry, all patients were in sinus rhythm and had New York Heart Association functional class I or minimal II congestive heart failure, with left ventricular (LV) ejection fraction > or = 45% and LV end-diastolic dimension > or = 5.5 cm in women and > or = 5.9 cm in men. End points were defined as progression to aortic valve replacement (n = 19) or sudden cardiac death (n = 1) during the mean follow-up period of 8.1 +/- 3.8 years. With the median SDANN of 145 ms as a partition value, the average annual risk of end-point events in patients with low SDANN was significantly greater than the event rate in patients with high SDANN (11%/year vs 2%/year, p <0.0003). In multivariate analysis, reduced SDANN was associated with end-point events independent of LV function, LV end-systolic dimension, and symptom status (p = 0.001). We conclude that reduced ultra-low frequency HRV measured as SDANN is strongly related to progression to valve surgery in asymptomatic and minimally symptomatic patients with chronic AR.