PROGNOSTIC VALUE AND PHYSIOLOGICAL CORRELATES OF HEART-RATE-VARIABILITY IN CHRONIC SEVERE MITRAL REGURGITATION

Background. A variety of measures of heart rate variability have been devised to measure high-frequency (0.15-0.40 Hz), low-frequency (0.04- 0.15 Hz), or ultralow-frequency (<0.0033 Hz) fluctuations in sinus cyc le length. Although measures of low-frequency and ultralow-frequency h eart rate variability have been shown to correlate with prognosis in s everal populations with ischemic heart disease, their relevance to pat ients with primary valvular heart disease remains to be determined. Me thods and Results. Thirty-eight patients with nonischemic causes of ch ronic severe mitral regurgitation who were in sinus rhythm underwent 2 4-hour ambulatory electrocardiography as part of a prospective study o f the natural history of regurgitant valvular heart disease. Patients were followed for as long as 9.2 years, and end points of mortality, p rogression to mitral valve surgery, and development of chronic atrial fibrillation were tabulated. Time- and frequency-domain measurements o f high-frequency, low-frequency, and ultralow-frequency heart rate var iability were computed and compared with resting ventricular function by radionuclide cineangiography and outcome. The standard deviation of the 5-minute mean RR intervals (SDANN), a measure of ultralow-frequen cy heart rate variability, was correlated with left ventricular ejecti on fraction (r=0.49, p=0.002) and right ventricular ejection fraction (r=0.43, p=0.007), whereas low-frequency and high-frequency heart rate variabilities were not. Heart rate, ultralow-frequency heart rate var iability, and, to a lesser extent, high-frequency heart rate variabili ty exhibited significant diurnal variation, but low-frequency heart ra te variability did not. Heart rate and ultralow-frequency, low-frequen cy, and combined low- and high-frequency heart rate variability predic ted mortality and total events. The most powerful predictor of subsequ ent events was SDANN. Patients with reduced SDANN were significantly m ore likely to develop end-point events (p<0.001) with increased progre ssion to mitral valve surgery (p<0.001) as well as increased early mor tality (p=0.02). In a multivariate proportional hazards model, SDANN r etained independent predictive power (p=0.001). Likewise, SDANN was th e only variable that was significantly associated with the subsequent development of atrial fibrillation (relative risk, 3.1; p=0.03). Concl usions. Ultralow-frequency heart rate variability, as measured by SDAN N, correlates with right and left ventricular performance and predicts development of atrial fibrillation, mortality, and progression to val ve surgery in patients with chronic severe mitral regurgitation.