Rusticali G, Di Clemente D, Ruggeri A, Borghi A, Bugiardini R
Istituto di Patologia Speciale Medica e Metodologia Clinica, Università degli Studi di Bologna.
G Ital Cardiol. 1995 Sep;25(9):1161-70.
Although patients with syndrome X (angina and normal coronary arteries, in absence of coronary spasm, cardiomyopathy or valvulopathy) and those with stable angina as well as documented coronary artery disease share a similar clinical presentation (effort related symptoms, positive exercise stress testing and reversible perfusion defects), their prognosis is markedly different. Coronary atherosclerosis is usually progressive relative to morbidity and mortality. Conversely prognosis both in terms of persistence of pain and mortality appears to be benign in syndrome X. Most cardiologists favor proceeding with coronary angiography in all patients presenting with exercise induced ST depression and reversible perfusion defects. However, it should not be assumed that this strategy will remain the preferred one. The aim of this study was to assess whether non invasive testing could identify underlying coronary artery anatomy, thus prognosis in the above subset of patients. The approach was selected on a clearly stated objective of how isosorbide dinitrate and verapamil may influence coronary flow reserve, thus exercise stress testing in syndrome X. Nitrates have been shown to reduce coronary flow reserve during stress tachycardia. The opposite occurs with calcium blockers.
We studied 48 patients with effort angina referred to our laboratory for diagnostic evaluation. All patients underwent two separate sessions at one-day interval. Each session consisted of exercise stress testing before and after isosorbide dinitrate (s.l.; 5-10 mg) or verapamil (i.v.; 10 mg), given in a randomized crossover fashion. Angiography was performed within 3 months from testing. Efficacy of drugs in terms of exercise capacity was assessed by using the following criteria: 1) prevention of significant (> or = 0.1 mV) ST depression while reaching same workload levels attained during baseline testing; 2) improvement in the ischemic thresholds, that is an increase in: time to 0.1 mV ST depression > or = 120 sec., with heart rate (> or = 10 bpm) and rate pressure product (> or = 2 U x 1000) greater than those attained during baseline testing; 3) increase in time to peak exercise (> or = 120 sec).
In syndrome X, both drugs resulted ineffective in one patient, one patient showed a favourable response to isosorbide dinitrate whereas the remaining 13/15 patients improved exercise capacity following verapamil, but not isosorbide dinitrate. The opposite occurred in coronary artery disease patients: both isosorbide dinitrate and verapamil were effective in 21/33 patients, and ineffective in 8/33 patients. The remaining 4 patients responded to isosorbide dinitrate but not to verapamil.
虽然X综合征患者(心绞痛且冠状动脉正常,无冠状动脉痉挛、心肌病或瓣膜病)以及稳定型心绞痛患者和已确诊冠状动脉疾病患者有相似的临床表现(劳力相关症状、运动负荷试验阳性及可逆性灌注缺损),但其预后明显不同。冠状动脉粥样硬化通常与发病率和死亡率相关且呈进行性发展。相反,X综合征在疼痛持续和死亡率方面的预后似乎较好。大多数心脏病专家倾向于对所有出现运动诱发ST段压低和可逆性灌注缺损的患者进行冠状动脉造影。然而,不应认为这一策略仍将是首选策略。本研究的目的是评估非侵入性检查能否识别潜在的冠状动脉解剖结构,从而判断上述患者亚组的预后。该方法基于一个明确阐述的目标,即硝酸异山梨酯和维拉帕米如何影响冠状动脉血流储备,进而对X综合征患者进行运动负荷试验。硝酸盐已被证明会在应激性心动过速期间降低冠状动脉血流储备。钙通道阻滞剂则相反。
我们研究了48例因劳力性心绞痛前来我们实验室进行诊断评估的患者。所有患者在一天的间隔内进行了两个独立的阶段。每个阶段包括在硝酸异山梨酯(舌下含服;5 - 10毫克)或维拉帕米(静脉注射;10毫克)给药前后进行运动负荷试验,采用随机交叉方式。在试验后3个月内进行冠状动脉造影。通过以下标准评估药物在运动能力方面的疗效:1)在达到基线试验期间达到的相同工作量水平时,预防显著(≥0.1毫伏)ST段压低;2)改善缺血阈值,即以下指标增加:出现0.1毫伏ST段压低的时间≥120秒,心率(≥10次/分钟)和心率血压乘积(≥2×1000)大于基线试验期间达到的值;3)运动高峰时间增加(≥120秒)。
在X综合征患者中,两种药物对1例患者均无效,1例患者对硝酸异山梨酯有良好反应,而其余13/15例患者在使用维拉帕米后运动能力改善,但使用硝酸异山梨酯后未改善。在冠状动脉疾病患者中情况相反:硝酸异山梨酯和维拉帕米对21/33例患者均有效,对8/33例患者无效。其余4例患者对硝酸异山梨酯有反应,但对维拉帕米无反应。
1)维拉帕米而非硝酸异山梨酯可改善X综合征患者的运动能力;2)这不适用于稳定型心绞痛患者;3)对维拉帕米而非硝酸异山梨酯有良好反应是识别心绞痛且冠状动脉正常患者的敏感(86%)且特异(100%)的方法;4)非侵入性检查可筛选出那些需要直接进行冠状动脉造影的劳力性心绞痛患者;5)一些劳力相关心绞痛患者可能无需进一步检查。