Circulation, Vol 88, 92-100, Copyright © 1993 by American Heart Association
TC Andrews, T Fenton, N Toyosaki, SP Glasser, PM Young, G MacCallum, RS Gibson, TL Shook and PH Stone
BACKGROUND. Identification of whether episodes of ambulatory ischemia are
caused by increases in myocardial oxygen demand or to episodic coronary
vasoconstriction in patients with stable coronary disease may be important
to guide selection of optimal anti-ischemic therapy and to gain insight
into mechanisms responsible for adverse cardiac events. METHODS AND
RESULTS. Mean minute heart rate activity during ambulatory ECG (AECG)
monitoring was determined for 50 patients treated with propranolol,
diltiazem, nifedipine, or placebo in a randomized, double- blind, crossover
trial. Periods of heart rate increases of various magnitudes and durations
and starting at various baseline heart rates on each therapy were
identified throughout each 48-hour AECG recording, and the proportion of
these periods associated with an ischemic episode was determined. The
circadian variation of ischemic episodes categorized by the presence or
absence of an increase in heart rate was analyzed. Eighty-one percent of
ischemic episodes were preceded by an increase in heart rate > or = 5
beats per minute. The likelihood of developing ischemia associated with a
heart rate increase was proportional to the magnitude and duration of the
heart rate increase and the baseline heart rate before the increases in
heart rate: likelihood ranged from 4% when the heart rate increased 5-9
beats per minute and lasted < 10 minutes to 60% when the heart rate
increased > or = 20 beats per minute and lasted > or = 40 minutes.
The likelihoods of developing ischemia based on changes in the heart rate
variables were similar for each of the therapies. Propranolol therapy
significantly reduced the magnitude and duration of heart rate increase and
the baseline heart rate compared with therapy with placebo, diltiazem, or
nifedipine (P < .001). Ischemic episodes associated with a heart rate
increase displayed a daytime peak, whereas ischemia occurring without a
heart rate increase occurred evenly throughout the day. Propranolol reduced
the proportion of heart rate-related ischemic episodes and increased the
proportion of non-heart rate-related episodes compared with placebo (P <
.02), and nifedipine exerted the opposite effect (P = .005). Multivariate
analysis indicated that the probability of developing ischemia was strongly
associated with heart rate variables and was unaffected by time of day.
CONCLUSIONS. Most episodes of ambulatory ischemia are associated with a
preceding period of increased heart rate. The likelihood of developing
ischemia is predicted by heart rate variables and unaffected by time of
day. Anti- ischemic efficacy is generally a result of the medication's
efficacy in reducing heart rate variables. A minority of ischemic episodes
are not associated with preceding periods of increased heart rate, may be
caused by episodic coronary vasoconstriction, and are more effectively
reduced by nifedipine than propranolol.
ARTICLES
Subsets of ambulatory myocardial ischemia based on heart rate activity. Circadian distribution and response to anti-ischemic medication. The Angina and Silent Ischemia Study Group (ASIS)
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
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