Km. Stein et al., PROGNOSTIC VALUE AND PHYSIOLOGICAL CORRELATES OF HEART-RATE-VARIABILITY IN CHRONIC SEVERE MITRAL REGURGITATION, Circulation, 88(1), 1993, pp. 127-135
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.