Andrews T C, Fenton T, Toyosaki N, Glasser S P, Young P M, MacCallum G, Gibson R S, Shook T L, Stone P H
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Circulation. 1993 Jul;88(1):92-100. doi: 10.1161/01.cir.88.1.92.
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.
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.
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.
对于稳定性冠心病患者，明确动态缺血发作是由心肌需氧量增加还是由间歇性冠状动脉血管收缩引起，对于指导选择最佳抗缺血治疗以及深入了解导致不良心脏事件的机制可能具有重要意义。
在一项随机、双盲、交叉试验中，对50例接受普萘洛尔、地尔硫䓬、硝苯地平或安慰剂治疗的患者进行动态心电图（AECG）监测，测定平均每分钟心率活动。在每次48小时的AECG记录中，识别出各种幅度和持续时间且起始于每种治疗不同基线心率的心率增加期，并确定这些时期中与缺血发作相关的比例。分析按心率是否增加分类的缺血发作的昼夜变化。81%的缺血发作之前心率增加≥5次/分钟。与心率增加相关的发生缺血的可能性与心率增加的幅度、持续时间以及心率增加前的基线心率成正比：当心率增加5 - 9次/分钟且持续<10分钟时，可能性为4%；当心率增加≥20次/分钟且持续≥40分钟时，可能性为60%。每种治疗基于心率变量变化发生缺血的可能性相似。与安慰剂、地尔硫䓬或硝苯地平治疗相比，普萘洛尔治疗显著降低了心率增加的幅度和持续时间以及基线心率（P<.001）。与心率增加相关的缺血发作呈现白天高峰，而无心率增加时发生的缺血在一天中分布均匀。与安慰剂相比，普萘洛尔降低了与心率相关的缺血发作比例，增加了非心率相关发作的比例（P<.02），而硝苯地平则产生相反的效果（P =.005）。多因素分析表明，发生缺血的概率与心率变量密切相关，且不受一天中时间的影响。
大多数动态缺血发作与之前的心率增加期相关。发生缺血的可能性由心率变量预测，且不受一天中时间的影响。抗缺血疗效通常是药物降低心率变量疗效的结果。少数缺血发作与之前的心率增加期无关，可能由间歇性冠状动脉血管收缩引起，硝苯地平比普萘洛尔更有效地减少此类发作。
