碎片状QRS波群在冠心病心肌缺血中的意义
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摘要
背景和目的：
常规12导联平静心电图中碎片状QRS复合波(Fragrnented QRS Complexes；fQRSs)的出现，包括各种不同形式的RSR’波形(具体图形如下)，排除典型的束支传导阻滞，被认为具有诊断无症状性陈旧性心肌梗死的意义，且与Q波相比有着更高的敏感性和阴性预测值。在本次研究中，我们发现fQRS波不仅可见于心肌梗死患者，同样也可出现在心绞痛、心肌缺血、确诊或可疑冠心病、高血压左心室肥厚等患者的心电图中，我们认为平静心电图中fQRS波的出现同局部区域性的心肌缺血所造成的电生理改变有关。我们知道，QRS波群是左右心室除极的综合心电向量，任何影响心室除极向量改变的因素都将导致QRS波群振幅和时限的变化。心室肌细胞间除极的扩布速度、心脏特殊传导系统的传导速度、有效除极心室肌细胞的数量是QRS波群形成的主要影响因素，这些因素受到心肌供血、炎症、退行性改变、心脏自主神经等多重因素的影响，因此，我们推测碎片状QRS波群的出现或许是提示心肌缺血存在的一种新的有用标志。为了验证这一假说，我们做相关研究分析。
临床工作中我们早期较倾向于使用非侵入性的方法来诊断冠心病心肌缺血，它们包括：常规12导联平静心电图(ECG)、平板运动试验、心脏彩色多普勒超声心动图(UCG)、24h动态心电图(DCG)以及一些生化指标等，它们均能在一定程度上反映并提示心肌缺血。尤其常规12导联平静心电图，它历史悠久，检查方便，经济，无创伤，可随时多次重复检查，且检测导联多，是发现心肌缺血的重要手段，是目前临床工作中最常用的方法，但ST-T段的分析诊断心肌缺血的敏感性和特异性均较低，为此需要与其他各种辅助检查综合分析来评估心肌缺血的存在。而探索更多简便、无创的诊断方法是我们临床工作者们的主要目标和任务。
方法和对象：
回顾性调查研究1000份心电图和200名患者。
一、研究对象：第一步，随机抽取1000份南方医院心血管内科门诊或住院患者的12导联平静心电图，排除存在典型束支传导阻滞或起搏心律的共61份心电图(其中不完全性右束支传导阻滞22份，完全性右束支传导阻滞17份，左前分支传导阻滞9份，完全性左束支传导阻滞5份，起搏心律8份)。剩余939份心电图，即939名患者，作为我们的研究对象。按照其心电图中是否存在fQRS波将这939名患者分成两组，并研究两组人群在性别、年龄、心血管事件发生情况等方面有无差异，其差异是否具有统计学意义等。第二步，随机选取我院心血管内科同时接受平板运动试验、选择性冠状动脉造影检查(CAG)的患者200名(有心肌梗死病史、存在高血压左心室肥厚、心电图存在上述传导阻滞的患者直接排除研究之外)。分别以平板运动试验阳性、CAG阳性、平板运动或CAG结果任一阳性为诊断冠心病心肌缺血的标准，并依此来评估fQRS波在诊断冠心病心肌缺血方面的价值。
二、诊断标准
(一)、心电图检查：所有入选病例均获取常规12导联平静心电图(GE，Marquette；Mac 5000；filter range，0．16 to 100Hz；走纸速度为25mm／s；标准电压为10mm／mv)，在QRS波群时限<120ms，且在≥1个连续导联中，对应于主要的冠状动脉供血区域，出现附加的R波(R’)或在S波的底部出现顿挫，或者出现>1 R’的不规则QRS波形等，这些不规则的QRS波群统称为碎片状QRS波群(fQRS)(如上图所示)。典型的束支传导阻滞(QRS时限≥120ms)、室内传导阻滞、不完全右束支传导阻滞、起搏心律等在我们本次研究中被排除在外。V_1～V_5导联中出现fQRS波提示前壁或者前降支供血区域心肌缺血；Ⅰ、aVL、V_5、V_6导联中出现fQRS波提示侧壁或者回旋支支配区域心肌缺血；Ⅱ、Ⅲ、aVF导联中出现fQRS波提示下壁或者右冠状动脉支配区域的心肌缺血。所有心电图由两名经验医师在不知道对象临床资料的前提下阅片，心电图一致性为99．5％。
(二)、选择性冠状动脉造影检查：采用德国西门子AXIOM Artis dTA血管造影系统，行冠状动脉造影，记录冠状动脉情况。采用Judkins法，行股动脉穿刺，插入Judkins左、右冠脉造影导管，分别行左、右冠脉造影。投照体位以常规体位及根据造影所见情况，选择能充分暴露病变段血管的最佳位置进行。冠状动脉狭窄的严重程度用其内径缩小的百分比来表示，其内径狭窄程度≥50％被认为血管存在有意义的病变，其内径狭窄程度≥75％被认为冠状动脉病变显著，或存在多支血管病变，可确诊冠心病。
(三)、平板运动试验：采用西门子MEGACART运动心电图机，与之相配套的运动平板是美国BURDICK公司出产的T600。平板运动试验是诊断冠心病心肌缺血常用的无创性检查，平板运动试验基本原理是通过运动增加心脏负荷，增加心肌耗氧量以揭示冠脉灌注不足的表现，从而辅助诊断冠心病。其阳性标准判断：①运动中或运动后出现典型心绞痛。②以R波为主的导联运动中或运动后出现ST段水平或下斜型下移>0．1mV，持续时间2min以上。③除aVR导联外，运动中或运动后ST段弓背型上移>0．1mV。④运动中或运动后出现T波正常化。判定标准为原T波倒置的导联出现T波直立，振幅达1．5mm以上。⑤运动中或运动后出现室早、室速、束支传导阻滞等心律失常。
(四)、超声心动图和平静心电图对左心室肥厚的定义标准：使用美国Acuson Sequoia 512彩色多普勒超声现象仪，探头频率为2～4MHz。按国际心脏协会和WHO推荐方法，在胸骨旁左心室长轴切面获得二尖瓣腱索水平的M型图像，于舒张末期测量室间隔厚度(IVSd)、左室后壁厚度(LVPWd)、左心室内径(LVD)。根据美国超声学会推荐，运用Devereux公式算出左室质量指数(LVMI)，LVMI(g／m~2)={0．8×1．04[(IVSd+LVPWd+LVD)~3-LVD~3]+0．6}／体表面积，以LVMI男性≥116g／m~2，女性≥104g／m~2作为左心室肥厚的诊断标准；平静心电图中，QRS波时间与(RaVL+SV_3)的乘积>2440 mm·ms(女性>2446 mm·ms)或者(SV_1+RV_(5／6))>38 mm是被用来评估存在左心室肥厚的标准。在我们的研究中，超声心动图和平静心电图中任一结果达到上述标准，我们即认为患者存在高血压左心室肥厚。
(五)、fQRS波诊断价值的评估：心肌缺血即为患者存在典型心绞痛症状并且(或)同时有心肌缺血客观证据的一种病理状态。造成心肌缺血的原因有很多，如冠状动脉狭窄或痉挛、心肌肥厚、心率增快等等，但临床上我们最为关注的是由冠状动脉狭窄引起的心肌缺血，即冠心病心肌缺血。临床上诊断冠心病心肌缺血的方法有很多，最常用的也最有价值的一项无创性检查即为平板运动试验，但其假阳性率较高，尤其在女性患者，容易导致误诊；最具诊断价值的一项检查即为选择性冠状动脉造影(CAG)，但其有创性及昂贵的价格，限制了其早期及普遍使用。为了较好的客观的评估fQRS波在诊断冠心病心肌缺血时的价值，我们将之同临床上最常用也最有价值的这两种方法比较，即分别以平板运动试验阳性、CAG阳性、平板运动或CAG任一结果阳性为诊断冠心病心肌缺血的标准并依此来分别描述fQRS波诊断的敏感性、特异性、阴性预测值等指标。
三、统计分析：计量资料(年龄)数据用均数±标准差((?)±s)表示；两组患者性别构成的比较采用两样本χ~2检验；两组患者平均年龄的比较采用独立样本t检验：两组之间心血管疾病发生率的比较采用两样本χ~2检验。差异性检验水准为0．05(双侧)，P<0．05被认为具有统计学意义。应用SPSS13．0软件进行统计分析。
结果：
fQRS组和无fQRS组之间心血管疾病发生率的比较采用两样本χ~2检验，经检验，χ~2值为：136．101，P<0．001，即两组人群心血管事件的发生率存在显著性差异，fQRS波组中心绞痛的发生率为18．5％，无fQRS波组中心绞痛的发生率为6．7％；fQRS波组中高血压左心室肥厚(LVH)的发生率为34．7％，无fQRS波组中LVH的发生率为12．9％；fQRS波组中急性心肌梗死的发生率为7．2％，无fQRS波组中急性心肌梗死的发生率为4．5％；fQRS波组中陈旧性心肌梗死(OMI)的发生率为3．3％，无fQRS波组中OMI的发生率为2．0％；fQRS波组中相对正常的人群占35．2％，无fQRS波组中相对正常的人群占72．4％。
我们如以平板运动试验阳性为诊断冠心病心肌缺血的标准，那么，fQRS波诊断心肌缺血的敏感性为46．0％，特异性为68．0％，阴性预测值为94．9％；如以选择性冠状动脉造影(CAG)检查阳性(即造影下冠状动脉狭窄程度≥75％或存在多支血管病变)为诊断冠心病心肌缺血的标准，那么，fQRS波诊断心肌缺血的敏感性为55．4％，特异性为86．9％，阴性预测值为96．7％；如平板运动试验和CAG两项检查结果任一阳性即认为存在心肌缺血，那么，fQRS波诊断心肌缺血的敏感性为45．1％，特异性为74．1％，阴性预测值为95．3％。
结论：
第一步研究结果说明，心电图中出现fQRS波的人群较之心电图中无fQRS波的人群，其心绞痛、心肌梗死、左心室肥厚、无症状型冠心病等心血管事件的发生率显著增高(P<0．001)，可知fQRS波的出现同心血管事件的发生是有一定关系的。fQRS波组心肌缺血的发生率显著高于无fQRS波组，且我们知道高血压左心室肥厚亦会导致心肌缺血，故fQRS波的出现同心肌缺血的存在是有一定关系的。
第二步研究结果发现，fQRS波诊断心肌缺血的特异性和阴性预测值较高，尤其阴性预测值。说明fQRS的出现能够预测心肌缺血的存在，而不存在fQRS波则意味着患者发生心肌缺血的可能性较小。fQRS波的出现可能提示心肌血液灌注和功能的异常，局限导联fQRS的出现与局部区域性心肌缺血的存在相关。为平静心电图ST-T改变诊断冠心病心肌缺血提供了新的标准，是平板运动试验和选择性冠状动脉造影的一项很好的补充性检查，能够更准确、更早的发现心肌缺血，及早干预，降低冠心病的死亡率及显著改善患者预后。
Background and Objective:
The appearance of a fragmented QRS complexes (fQRS) on a resting 12-lead electrocardiogram (ECG) which include various RSR' patterns without a typical bundle-branch block was regarded as a marker of a prior silent MI (some types of different fQRS are shown below). And the fQRS on a 12-lead ECGhas a substantially higher sensitivity and negative predictive value compared with Q wave.
In our study, we find that the fQRS was not only appears in patients with MI, but also in patients with angina cordis, asymptomatic coronary artery disease (CAD), and left ventricular hypertrophy (LVH). We, therefore, postulate that the fQRS (RSR' pattern or its all variants) may be a useful sign of myocardial ischemia. We know that QRS waves is the comprehend vector of double ventricle depolarization, any factors which change the ventricle depolarization will lead to the change of vibration and the change of latitude of QRS. The speed of depolarization between ventricle cells and conduction of specific conduction system of the heart, the amount of depolarization ventricle cells in effect are the main influential factors of the formative of QRS, and these are influenced by the blood-supply of the myocardium, the inflammation, the change of retrogression and the autonomic nerve of the heart. We, therefore, postulate that the fQRS (RSR' Pattern or its all variants) may be a useful sign of myocardial ischemia. We tend to use the noninvasive methods to diagnose myocardial ischemia clinically, such as resting 12-leads electrocardiograms (ECG), exercise treadmill test, echocardiograms, dynamic electrocardiogram (DCG) and some biochemical indicators. These methods all can indicate myocardial ischemia at some distant, especially the ECG, which is convenient and economical, can be easily accepted by patients and was the most widely used method to help diagnose the myocardial ischemia of coronary artery disease, but the sensitivity and specificity of ST-segment analysis were low, so the main destination of our clinicians was to find more noninvasive methods can indicate the myocardial ischemia.
Methods:
Retrospective review was performed on ECGs of 1000 patients and 200 patients undergoing coronary angiography (CAG) and exercise treadmill test.
Study population
1000 patients who were referred for ECG at Nan Fang hospital, Guang Zhou, China were included in our first study stage. 61(6%) patients were excluded from our analysis because of incomplete right bundle-branch block (n=22), complete right bundle-branch block (n=17), left anterior bundle-branch block (n=9), complete left bundle-branch block (n=5), and paced rhythm (n=8). The data for the final cohort of 939 patients were analyzed in this study. According to the appearance of the fQRS in electrocardiogram or not, a useful scheme is to consider 2 groups, and the difference between them on sex, age, cardiovascular history was evaluated. It can be seen from the result that there was no difference on sex and age, but there was a significant difference on cardiovascular history (P <0.001). The incidence of angina, MI, asymptomatic CAD and left ventricular hypertrophy (LVH) in the group with fQRS on the ECG was higher than the other group, and the difference has the statistical significance. ECGs in 200 patients undergoing CAG and exercise treadmill test at our hospital were included in our second study stage, and the patients with bundle-branch block above were excluded from the group when we selecting study population. We use the exercise treadmill test positive, CAG positive, and exercise treadmill test and/or CAG positive separately as the criteria of myocardial ischemia, and according to this the value of fQRS in diagnosing myocardial ischemia can be evaluated.
Diagnostic criteria
ECG criteria
The resting 12-lead ECG (GE, Marquette, Wis; model Mac 5000; filter range, 0.16 to 100 Hz; AC filter, 60Hz, 25mm/s, 10mm/mv) was analyzed by 2 independent experienced technicians blinded to the patients' clinical information. There was 99.5% concordance for the ECG signs. The RSR' pattern includes various morphologies of the QRS interval (QRS duration<120ms). It was defined by the presence of an additional R wave(R' ) or notching in the nadir of the S wave, or the presence of >1 R' (fragmentation) in≥1 leads, corresponding to a major coronary artery territory (Figure 1). Typical bundle-branch block pattern (QRS≥120ms), intraventricular conduction delay, and incomplete right bundle-branch block were excluded from our analysis. The presence of an fQRS in≥1 anterior leads ( V1 to V5) was assigned to myocardial ischemia in anterior segments or in the left anterior descending artery (LAD) territory. The presence of an fQRS in≥1 lateral leads (I, aVL, V5 and V6) was assigned to lateral segments or left circumflex artery (LCx) territory myocardial ischemia. Similarly, the presence of an fQRS in≥1 inferior leads (Ⅱ,Ⅲ, and aVF) was assigned to myocardial ischemia in the inferior segments or in the right coronary artery (RCA) territory.
Coronary angiography
Coronary angiography (CAG) testing was performed with a digital flat angiography system (AXIOM Artis dTA, germany Siemens) by using Seldinger technique and Judkins catheters, and acquiring images in multiple projections, The severity of the stenosis was expressed as a percentage reduction of the internal diameter, a reduction of 75% or more in the luminal diameter was considered significant, the CAD can be diagnosed definitely and myocardium dominated by it was ischemic probably.
Exercise treadmill test
The test was performed by the exercise electrocardiography (MEGACART, Siemens) and the motion flat plate (T600, BURDICK, America). The test was considered positive when:①the angina occurred during or after the exercise test.②the presence of > 0.1 mv horizontal or downsloping ST-segment depression in R waves leads and the time last more than 2 minutes.③the presence of >0.1mv ST-segment elevation in all leads except aVR lead.④the abnormal T waves tend to normal during or after the exercise test.⑤ventricular tachycardia, premature ventricular and bundle branch block occurred during or after the exercise test. UCG and ECG Criteria for LVH
Comprehensive 2D and Doppler echocardiography was performed. Left ventricular dimensions (interventricular septal thickness [IVS], posterior wall thickness [PW], and left ventricular end-diastolic diameter [LVEDD]) were measured at end of diastole with M-mode by using the leading-edge-to-leading-edge convention. Left ventricular mass was determined by using the Troy formula according to the recommendations of the American Society of Echocardiography: left ventricular mass(g)=1.05[(LVEDD+IVS+PW) -LVEDD]. Left ventricular mass was divided with body surface area to obtain the left ventricular mass index (LVMI). LVMI limits used to establish LVH were 116g/m~2 for male and 104g/m~2 for females. The product of QRS duration times Cornell voltage (RaVL+SV3, with 6 mm added in women) >2440 mm·ms or Sokolow-Lyon voltage (SV1+RV5/6) >38 mm on ECG was used to identify LV hypertrophy.
Evaluation of the diagnostic significance of fQRS
Myocardial ischemia was one pathologic state with patients have typical angina or significant myocardial ischemia symptoms and also have some objective evidences for myocardial ischemia. The reasons for myocardial ischemia were many, for example, the coronary artery stenosis or spasm, myocardium hypertrophy, tachycardia and so on. But we mostly care about the coronary artery stenosis clinically. In clinically, there are many methods can diagnose the myocardial ischemia. The most commonly used and valuable noninvasive method was exercise treadmill test, but the false positive rate was high, the most valuable method for diagnose the CAD was CAG, but it was a invasive method and the price of it was high, so it cannot be widely used and easily accepted. We use the exercise treadmill test positive, CAG positive, and exercise treadmill test and/or CAG positive separately as the criteria of myocardial ischemia, and according to this the value of fQRS in diagnosing myocardial ischemia can be evaluated well.
Statistical analysis
Categorical data are presented by mean±S.D ( x±s); comparison of average age between the two groups adopted independent-samples T Test; comparison of interclass-rate adoptedχ~2-test; Sensitivities were defined as the number of true-positive tests divided by the total number of patients with myocardial ischemia evaluated by our standard, Specificities were defined as the number of true-negative tests divided by the total number of patients without myocardial ischemia evaluated by our criteria. For all tests, a probability value<0.05 was considered significant. SPSS 13.0 was used for analysis.
Results:
The cohort with fQRS demonstrated a significantly higher cardiovascular disease incidence compared with the non-fQRS cohort (P <0.001). In the fQRS group, the incidence of angina was 18.5%, the incidence of LVH was 34.7%, the incidence of acute myocardial infarction (AMI) was 7.2%, the incidence of old myocardial infarction (OMI) was 3.3%, and 35.2% patients was relatively normal. In the no fQRS group, the incidence of angina was 6.7%, the incidence of LVH was 12.9%, the incidence of AMI was 4.5%, the incidence of OMI was 2.0%, and 73.5% patients was relatively normal. The fQRS, when compared with exercise treadmill test, the sensitivity, specificity, and the negative predictive value of it for myocardial ischemia were 46.0%, 68.0%, and 94.9%; when compared with CAG, the sensitivity, specificity, and the negative predictive value of it were 55.4%, 86.9%, and 96.7%; when compared with exercise treadmill test and/or CAG, the sensitivity, specificity, and negative predictive value of it were 45.1%, 74.1%, and 95.3%.
Conclusions:
The cohort with fQRS demonstrated a significantly higher incidence of angina, MI, LVH, and asymptomatic CAD compared with the non-fQRS cohort (P <0.001). From the result we know that the presence of fQRS was associated with the cardiovascular disease, especially for the myocardial ischemia.
The fQRS has the high specificity and negative predictive value for myocardial ischemia. The presence of fQRS may denote the existence of myocardial ischemia, if there were no fQRS, the possibility of the patients have myocardial ischemia was small. The fQRS may be associated with the myocardial perfusion and function abnormalities, and regional fQRS patterns may denote the presence of focal regional myocardial ischemia. The fQRS in the ECG was a useful supplementary method for the two methods above.
常规12导联平静心电图中碎片状QRS复合波(Fragrnented QRS Complexes；fQRSs)的出现，包括各种不同形式的RSR’波形(具体图形如下)，排除典型的束支传导阻滞，被认为具有诊断无症状性陈旧性心肌梗死的意义，且与Q波相比有着更高的敏感性和阴性预测值。在本次研究中，我们发现fQRS波不仅可见于心肌梗死患者，同样也可出现在心绞痛、心肌缺血、确诊或可疑冠心病、高血压左心室肥厚等患者的心电图中，我们认为平静心电图中fQRS波的出现同局部区域性的心肌缺血所造成的电生理改变有关。我们知道，QRS波群是左右心室除极的综合心电向量，任何影响心室除极向量改变的因素都将导致QRS波群振幅和时限的变化。心室肌细胞间除极的扩布速度、心脏特殊传导系统的传导速度、有效除极心室肌细胞的数量是QRS波群形成的主要影响因素，这些因素受到心肌供血、炎症、退行性改变、心脏自主神经等多重因素的影响，因此，我们推测碎片状QRS波群的出现或许是提示心肌缺血存在的一种新的有用标志。为了验证这一假说，我们做相关研究分析。
临床工作中我们早期较倾向于使用非侵入性的方法来诊断冠心病心肌缺血，它们包括：常规12导联平静心电图(ECG)、平板运动试验、心脏彩色多普勒超声心动图(UCG)、24h动态心电图(DCG)以及一些生化指标等，它们均能在一定程度上反映并提示心肌缺血。尤其常规12导联平静心电图，它历史悠久，检查方便，经济，无创伤，可随时多次重复检查，且检测导联多，是发现心肌缺血的重要手段，是目前临床工作中最常用的方法，但ST-T段的分析诊断心肌缺血的敏感性和特异性均较低，为此需要与其他各种辅助检查综合分析来评估心肌缺血的存在。而探索更多简便、无创的诊断方法是我们临床工作者们的主要目标和任务。
方法和对象：
回顾性调查研究1000份心电图和200名患者。
一、研究对象：第一步，随机抽取1000份南方医院心血管内科门诊或住院患者的12导联平静心电图，排除存在典型束支传导阻滞或起搏心律的共61份心电图(其中不完全性右束支传导阻滞22份，完全性右束支传导阻滞17份，左前分支传导阻滞9份，完全性左束支传导阻滞5份，起搏心律8份)。剩余939份心电图，即939名患者，作为我们的研究对象。按照其心电图中是否存在fQRS波将这939名患者分成两组，并研究两组人群在性别、年龄、心血管事件发生情况等方面有无差异，其差异是否具有统计学意义等。第二步，随机选取我院心血管内科同时接受平板运动试验、选择性冠状动脉造影检查(CAG)的患者200名(有心肌梗死病史、存在高血压左心室肥厚、心电图存在上述传导阻滞的患者直接排除研究之外)。分别以平板运动试验阳性、CAG阳性、平板运动或CAG结果任一阳性为诊断冠心病心肌缺血的标准，并依此来评估fQRS波在诊断冠心病心肌缺血方面的价值。
二、诊断标准
(一)、心电图检查：所有入选病例均获取常规12导联平静心电图(GE，Marquette；Mac 5000；filter range，0．16 to 100Hz；走纸速度为25mm／s；标准电压为10mm／mv)，在QRS波群时限<120ms，且在≥1个连续导联中，对应于主要的冠状动脉供血区域，出现附加的R波(R’)或在S波的底部出现顿挫，或者出现>1 R’的不规则QRS波形等，这些不规则的QRS波群统称为碎片状QRS波群(fQRS)(如上图所示)。典型的束支传导阻滞(QRS时限≥120ms)、室内传导阻滞、不完全右束支传导阻滞、起搏心律等在我们本次研究中被排除在外。V_1～V_5导联中出现fQRS波提示前壁或者前降支供血区域心肌缺血；Ⅰ、aVL、V_5、V_6导联中出现fQRS波提示侧壁或者回旋支支配区域心肌缺血；Ⅱ、Ⅲ、aVF导联中出现fQRS波提示下壁或者右冠状动脉支配区域的心肌缺血。所有心电图由两名经验医师在不知道对象临床资料的前提下阅片，心电图一致性为99．5％。
(二)、选择性冠状动脉造影检查：采用德国西门子AXIOM Artis dTA血管造影系统，行冠状动脉造影，记录冠状动脉情况。采用Judkins法，行股动脉穿刺，插入Judkins左、右冠脉造影导管，分别行左、右冠脉造影。投照体位以常规体位及根据造影所见情况，选择能充分暴露病变段血管的最佳位置进行。冠状动脉狭窄的严重程度用其内径缩小的百分比来表示，其内径狭窄程度≥50％被认为血管存在有意义的病变，其内径狭窄程度≥75％被认为冠状动脉病变显著，或存在多支血管病变，可确诊冠心病。
(三)、平板运动试验：采用西门子MEGACART运动心电图机，与之相配套的运动平板是美国BURDICK公司出产的T600。平板运动试验是诊断冠心病心肌缺血常用的无创性检查，平板运动试验基本原理是通过运动增加心脏负荷，增加心肌耗氧量以揭示冠脉灌注不足的表现，从而辅助诊断冠心病。其阳性标准判断：①运动中或运动后出现典型心绞痛。②以R波为主的导联运动中或运动后出现ST段水平或下斜型下移>0．1mV，持续时间2min以上。③除aVR导联外，运动中或运动后ST段弓背型上移>0．1mV。④运动中或运动后出现T波正常化。判定标准为原T波倒置的导联出现T波直立，振幅达1．5mm以上。⑤运动中或运动后出现室早、室速、束支传导阻滞等心律失常。
(四)、超声心动图和平静心电图对左心室肥厚的定义标准：使用美国Acuson Sequoia 512彩色多普勒超声现象仪，探头频率为2～4MHz。按国际心脏协会和WHO推荐方法，在胸骨旁左心室长轴切面获得二尖瓣腱索水平的M型图像，于舒张末期测量室间隔厚度(IVSd)、左室后壁厚度(LVPWd)、左心室内径(LVD)。根据美国超声学会推荐，运用Devereux公式算出左室质量指数(LVMI)，LVMI(g／m~2)={0．8×1．04[(IVSd+LVPWd+LVD)~3-LVD~3]+0．6}／体表面积，以LVMI男性≥116g／m~2，女性≥104g／m~2作为左心室肥厚的诊断标准；平静心电图中，QRS波时间与(RaVL+SV_3)的乘积>2440 mm·ms(女性>2446 mm·ms)或者(SV_1+RV_(5／6))>38 mm是被用来评估存在左心室肥厚的标准。在我们的研究中，超声心动图和平静心电图中任一结果达到上述标准，我们即认为患者存在高血压左心室肥厚。
(五)、fQRS波诊断价值的评估：心肌缺血即为患者存在典型心绞痛症状并且(或)同时有心肌缺血客观证据的一种病理状态。造成心肌缺血的原因有很多，如冠状动脉狭窄或痉挛、心肌肥厚、心率增快等等，但临床上我们最为关注的是由冠状动脉狭窄引起的心肌缺血，即冠心病心肌缺血。临床上诊断冠心病心肌缺血的方法有很多，最常用的也最有价值的一项无创性检查即为平板运动试验，但其假阳性率较高，尤其在女性患者，容易导致误诊；最具诊断价值的一项检查即为选择性冠状动脉造影(CAG)，但其有创性及昂贵的价格，限制了其早期及普遍使用。为了较好的客观的评估fQRS波在诊断冠心病心肌缺血时的价值，我们将之同临床上最常用也最有价值的这两种方法比较，即分别以平板运动试验阳性、CAG阳性、平板运动或CAG任一结果阳性为诊断冠心病心肌缺血的标准并依此来分别描述fQRS波诊断的敏感性、特异性、阴性预测值等指标。
三、统计分析：计量资料(年龄)数据用均数±标准差((?)±s)表示；两组患者性别构成的比较采用两样本χ~2检验；两组患者平均年龄的比较采用独立样本t检验：两组之间心血管疾病发生率的比较采用两样本χ~2检验。差异性检验水准为0．05(双侧)，P<0．05被认为具有统计学意义。应用SPSS13．0软件进行统计分析。
结果：
fQRS组和无fQRS组之间心血管疾病发生率的比较采用两样本χ~2检验，经检验，χ~2值为：136．101，P<0．001，即两组人群心血管事件的发生率存在显著性差异，fQRS波组中心绞痛的发生率为18．5％，无fQRS波组中心绞痛的发生率为6．7％；fQRS波组中高血压左心室肥厚(LVH)的发生率为34．7％，无fQRS波组中LVH的发生率为12．9％；fQRS波组中急性心肌梗死的发生率为7．2％，无fQRS波组中急性心肌梗死的发生率为4．5％；fQRS波组中陈旧性心肌梗死(OMI)的发生率为3．3％，无fQRS波组中OMI的发生率为2．0％；fQRS波组中相对正常的人群占35．2％，无fQRS波组中相对正常的人群占72．4％。
我们如以平板运动试验阳性为诊断冠心病心肌缺血的标准，那么，fQRS波诊断心肌缺血的敏感性为46．0％，特异性为68．0％，阴性预测值为94．9％；如以选择性冠状动脉造影(CAG)检查阳性(即造影下冠状动脉狭窄程度≥75％或存在多支血管病变)为诊断冠心病心肌缺血的标准，那么，fQRS波诊断心肌缺血的敏感性为55．4％，特异性为86．9％，阴性预测值为96．7％；如平板运动试验和CAG两项检查结果任一阳性即认为存在心肌缺血，那么，fQRS波诊断心肌缺血的敏感性为45．1％，特异性为74．1％，阴性预测值为95．3％。
结论：
第一步研究结果说明，心电图中出现fQRS波的人群较之心电图中无fQRS波的人群，其心绞痛、心肌梗死、左心室肥厚、无症状型冠心病等心血管事件的发生率显著增高(P<0．001)，可知fQRS波的出现同心血管事件的发生是有一定关系的。fQRS波组心肌缺血的发生率显著高于无fQRS波组，且我们知道高血压左心室肥厚亦会导致心肌缺血，故fQRS波的出现同心肌缺血的存在是有一定关系的。
第二步研究结果发现，fQRS波诊断心肌缺血的特异性和阴性预测值较高，尤其阴性预测值。说明fQRS的出现能够预测心肌缺血的存在，而不存在fQRS波则意味着患者发生心肌缺血的可能性较小。fQRS波的出现可能提示心肌血液灌注和功能的异常，局限导联fQRS的出现与局部区域性心肌缺血的存在相关。为平静心电图ST-T改变诊断冠心病心肌缺血提供了新的标准，是平板运动试验和选择性冠状动脉造影的一项很好的补充性检查，能够更准确、更早的发现心肌缺血，及早干预，降低冠心病的死亡率及显著改善患者预后。
Background and Objective:
The appearance of a fragmented QRS complexes (fQRS) on a resting 12-lead electrocardiogram (ECG) which include various RSR' patterns without a typical bundle-branch block was regarded as a marker of a prior silent MI (some types of different fQRS are shown below). And the fQRS on a 12-lead ECGhas a substantially higher sensitivity and negative predictive value compared with Q wave.
In our study, we find that the fQRS was not only appears in patients with MI, but also in patients with angina cordis, asymptomatic coronary artery disease (CAD), and left ventricular hypertrophy (LVH). We, therefore, postulate that the fQRS (RSR' pattern or its all variants) may be a useful sign of myocardial ischemia. We know that QRS waves is the comprehend vector of double ventricle depolarization, any factors which change the ventricle depolarization will lead to the change of vibration and the change of latitude of QRS. The speed of depolarization between ventricle cells and conduction of specific conduction system of the heart, the amount of depolarization ventricle cells in effect are the main influential factors of the formative of QRS, and these are influenced by the blood-supply of the myocardium, the inflammation, the change of retrogression and the autonomic nerve of the heart. We, therefore, postulate that the fQRS (RSR' Pattern or its all variants) may be a useful sign of myocardial ischemia. We tend to use the noninvasive methods to diagnose myocardial ischemia clinically, such as resting 12-leads electrocardiograms (ECG), exercise treadmill test, echocardiograms, dynamic electrocardiogram (DCG) and some biochemical indicators. These methods all can indicate myocardial ischemia at some distant, especially the ECG, which is convenient and economical, can be easily accepted by patients and was the most widely used method to help diagnose the myocardial ischemia of coronary artery disease, but the sensitivity and specificity of ST-segment analysis were low, so the main destination of our clinicians was to find more noninvasive methods can indicate the myocardial ischemia.
Methods:
Retrospective review was performed on ECGs of 1000 patients and 200 patients undergoing coronary angiography (CAG) and exercise treadmill test.
Study population
1000 patients who were referred for ECG at Nan Fang hospital, Guang Zhou, China were included in our first study stage. 61(6%) patients were excluded from our analysis because of incomplete right bundle-branch block (n=22), complete right bundle-branch block (n=17), left anterior bundle-branch block (n=9), complete left bundle-branch block (n=5), and paced rhythm (n=8). The data for the final cohort of 939 patients were analyzed in this study. According to the appearance of the fQRS in electrocardiogram or not, a useful scheme is to consider 2 groups, and the difference between them on sex, age, cardiovascular history was evaluated. It can be seen from the result that there was no difference on sex and age, but there was a significant difference on cardiovascular history (P <0.001). The incidence of angina, MI, asymptomatic CAD and left ventricular hypertrophy (LVH) in the group with fQRS on the ECG was higher than the other group, and the difference has the statistical significance. ECGs in 200 patients undergoing CAG and exercise treadmill test at our hospital were included in our second study stage, and the patients with bundle-branch block above were excluded from the group when we selecting study population. We use the exercise treadmill test positive, CAG positive, and exercise treadmill test and/or CAG positive separately as the criteria of myocardial ischemia, and according to this the value of fQRS in diagnosing myocardial ischemia can be evaluated.
Diagnostic criteria
ECG criteria
The resting 12-lead ECG (GE, Marquette, Wis; model Mac 5000; filter range, 0.16 to 100 Hz; AC filter, 60Hz, 25mm/s, 10mm/mv) was analyzed by 2 independent experienced technicians blinded to the patients' clinical information. There was 99.5% concordance for the ECG signs. The RSR' pattern includes various morphologies of the QRS interval (QRS duration<120ms). It was defined by the presence of an additional R wave(R' ) or notching in the nadir of the S wave, or the presence of >1 R' (fragmentation) in≥1 leads, corresponding to a major coronary artery territory (Figure 1). Typical bundle-branch block pattern (QRS≥120ms), intraventricular conduction delay, and incomplete right bundle-branch block were excluded from our analysis. The presence of an fQRS in≥1 anterior leads ( V1 to V5) was assigned to myocardial ischemia in anterior segments or in the left anterior descending artery (LAD) territory. The presence of an fQRS in≥1 lateral leads (I, aVL, V5 and V6) was assigned to lateral segments or left circumflex artery (LCx) territory myocardial ischemia. Similarly, the presence of an fQRS in≥1 inferior leads (Ⅱ,Ⅲ, and aVF) was assigned to myocardial ischemia in the inferior segments or in the right coronary artery (RCA) territory.
Coronary angiography
Coronary angiography (CAG) testing was performed with a digital flat angiography system (AXIOM Artis dTA, germany Siemens) by using Seldinger technique and Judkins catheters, and acquiring images in multiple projections, The severity of the stenosis was expressed as a percentage reduction of the internal diameter, a reduction of 75% or more in the luminal diameter was considered significant, the CAD can be diagnosed definitely and myocardium dominated by it was ischemic probably.
Exercise treadmill test
The test was performed by the exercise electrocardiography (MEGACART, Siemens) and the motion flat plate (T600, BURDICK, America). The test was considered positive when:①the angina occurred during or after the exercise test.②the presence of > 0.1 mv horizontal or downsloping ST-segment depression in R waves leads and the time last more than 2 minutes.③the presence of >0.1mv ST-segment elevation in all leads except aVR lead.④the abnormal T waves tend to normal during or after the exercise test.⑤ventricular tachycardia, premature ventricular and bundle branch block occurred during or after the exercise test. UCG and ECG Criteria for LVH
Comprehensive 2D and Doppler echocardiography was performed. Left ventricular dimensions (interventricular septal thickness [IVS], posterior wall thickness [PW], and left ventricular end-diastolic diameter [LVEDD]) were measured at end of diastole with M-mode by using the leading-edge-to-leading-edge convention. Left ventricular mass was determined by using the Troy formula according to the recommendations of the American Society of Echocardiography: left ventricular mass(g)=1.05[(LVEDD+IVS+PW) -LVEDD]. Left ventricular mass was divided with body surface area to obtain the left ventricular mass index (LVMI). LVMI limits used to establish LVH were 116g/m~2 for male and 104g/m~2 for females. The product of QRS duration times Cornell voltage (RaVL+SV3, with 6 mm added in women) >2440 mm·ms or Sokolow-Lyon voltage (SV1+RV5/6) >38 mm on ECG was used to identify LV hypertrophy.
Evaluation of the diagnostic significance of fQRS
Myocardial ischemia was one pathologic state with patients have typical angina or significant myocardial ischemia symptoms and also have some objective evidences for myocardial ischemia. The reasons for myocardial ischemia were many, for example, the coronary artery stenosis or spasm, myocardium hypertrophy, tachycardia and so on. But we mostly care about the coronary artery stenosis clinically. In clinically, there are many methods can diagnose the myocardial ischemia. The most commonly used and valuable noninvasive method was exercise treadmill test, but the false positive rate was high, the most valuable method for diagnose the CAD was CAG, but it was a invasive method and the price of it was high, so it cannot be widely used and easily accepted. We use the exercise treadmill test positive, CAG positive, and exercise treadmill test and/or CAG positive separately as the criteria of myocardial ischemia, and according to this the value of fQRS in diagnosing myocardial ischemia can be evaluated well.
Statistical analysis
Categorical data are presented by mean±S.D ( x±s); comparison of average age between the two groups adopted independent-samples T Test; comparison of interclass-rate adoptedχ~2-test; Sensitivities were defined as the number of true-positive tests divided by the total number of patients with myocardial ischemia evaluated by our standard, Specificities were defined as the number of true-negative tests divided by the total number of patients without myocardial ischemia evaluated by our criteria. For all tests, a probability value<0.05 was considered significant. SPSS 13.0 was used for analysis.
Results:
The cohort with fQRS demonstrated a significantly higher cardiovascular disease incidence compared with the non-fQRS cohort (P <0.001). In the fQRS group, the incidence of angina was 18.5%, the incidence of LVH was 34.7%, the incidence of acute myocardial infarction (AMI) was 7.2%, the incidence of old myocardial infarction (OMI) was 3.3%, and 35.2% patients was relatively normal. In the no fQRS group, the incidence of angina was 6.7%, the incidence of LVH was 12.9%, the incidence of AMI was 4.5%, the incidence of OMI was 2.0%, and 73.5% patients was relatively normal. The fQRS, when compared with exercise treadmill test, the sensitivity, specificity, and the negative predictive value of it for myocardial ischemia were 46.0%, 68.0%, and 94.9%; when compared with CAG, the sensitivity, specificity, and the negative predictive value of it were 55.4%, 86.9%, and 96.7%; when compared with exercise treadmill test and/or CAG, the sensitivity, specificity, and negative predictive value of it were 45.1%, 74.1%, and 95.3%.
Conclusions:
The cohort with fQRS demonstrated a significantly higher incidence of angina, MI, LVH, and asymptomatic CAD compared with the non-fQRS cohort (P <0.001). From the result we know that the presence of fQRS was associated with the cardiovascular disease, especially for the myocardial ischemia.
The fQRS has the high specificity and negative predictive value for myocardial ischemia. The presence of fQRS may denote the existence of myocardial ischemia, if there were no fQRS, the possibility of the patients have myocardial ischemia was small. The fQRS may be associated with the myocardial perfusion and function abnormalities, and regional fQRS patterns may denote the presence of focal regional myocardial ischemia. The fQRS in the ECG was a useful supplementary method for the two methods above.
引文
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[3] Jo Mahenthiran, Bilal R. Khan, Stephen G Sawada, et al. Fragmented QRScomplexes not typical of a bundle branch block: A marker of greater myocardialperfusion tomography abnormalities in coronary artery disease [J]. J Nucl Cardiol,2007,14: 347-53.
[4] Reddv CV, Cheriparambill K, Saul B, et al. Fragmented Left Sided QRS inAbsence of Bundle Branch Block: Sign of left ventricular Aneurysm [J]. AnnNoninvasive Electrocardiol, 2006,11(2): 132-8.
[5] Cohn PF, Fox KM, Daly C. Silent myocardial ischemia[J]. Circulation,2003,108(10): 1263-77.
[6]龙曼云，骆瑗．心电图及动态心电图对冠心病诊断价值的临床研究[J]．右江民族医学院学报，2001，(6)：891-2．
[7] Escolar E, Weigold G, Fuisz A, et al. New imaging techniques for diagnosing coronary artery disease[J]. CMAJ, 2006,174(4): 487-95.
[8]刘康桐，石磊，雷长城等．平板运动、超声心动图对冠心病的诊断价值[J]．衡阳医学院学报，2000，28(2)：147-8．
[9]袁冬冬，许明强．西门子运动心电图机配套平板的改进[J]．医疗卫生装备，2000，(5)：44．
[10]赵小平，王兴． 12导联动态心电图与平板运动试验诊断冠心病心肌缺血??的比较[J]．临床心电学杂志，2006，15(4)：269-71．
[11]田森，文亚红，许勇等．不典型胸痛患者平板运动试验和冠状动脉造影检查结果分析[J]．四川医学，2007，28(6)：608-9．
[12] Moore RB, Shapiro LM, Gibson DG Relation between electrocardiographic replolarisation changes and mechanical events in left ventricular hypertrophy[J]. Br Heart J, 1984, 52(5):516-23.
[13]农盛雄，宾建平，吴平生左室肥厚与左心室舒张功能不全相关性的研究临床超声医学杂志2006年第6期
[14] Sundstrom J, Lind L, Arnlov J, et al. Echocardiographic and electrocardiographicdiagnoses of left ventricular hypertrophy predict mortality independently of eachother in a population of elderly men[J]. Circulation, 2001,103(19):2346-51.
[15] Hildick-Smith DJ, Shapiro LM. Echocardiographic differentiation ofpathological and physiological left ventricular hypertrophy[J]. Heart, 2001,85(6):615-9.
[16]杨旭明，李小彩，闰文泰等．心肌缺血时QRS波群中切迹的物理特性[J]．中国心脏起搏与心电生理杂志，1999，13(2)：105-7．
[17] Abboud S, Zlochiver S. High-frequency QRS electrocardiogram for diagnosingand monitoring ischemic heart disease[J]. J Electrocardiol, 2006, 39(1):82-6.
[18] Rubart M, Zipes DP. Mechanisms of sudden cardiac death[J]. J Clinic invest,2005,115(9): 2305-15.
[19] Lander P, Gomis P, Warren S, et al. Abnormal intra-QRS potentials associatedwith percutaneous transluminal coronary angiography-induced transient myocardialischemia [J]. J Electrocardiol, 2006,39(3):282-9.
[20] Katagiri T, Toba K, Takeyama Y, et al. Morphologic and biochemical studies onthe experimental chronic ischemic myocardium with the Ameroid constrictor [J]. JpnCirc J, 1978,42(3):345-52.
[21] Vanoverschelde JL, Wijns W, Depre C, et al. Mechanisms of chronic regionalpostischemic dysfunction in humans. New insights from the study of noninfarctedcollateral-dependent myocardium[J]. Circulation, 1993, 87(5):1513-23.
[22] Pullan AJ, Buist ML, Sands GB, et al. Cardiac electrical activity-from heart to body surface and back again[J]. J Electrocardiol, 2003,36(Suppl):63-7.
[23] Sapoznikov D, Tzivoni D, Weiman J, et al. High fidelity ECG in the diagnosis of occult coronary artery disease: a study of patients with normal conventional ECG[J].J Electrocardiol, 1977,10(2): 137-48.
[24] Rubulis A, Jensen J, Lundahl G. Ischemia induces aggravation of baseline repolarization abnormalities in left ventricular hypertrophy: a deleterious interaction.J Appl Physiol. 2006,101(1):102-10.
[25] Hauser M, Bengel FM, Hager A, et al. Impaired myocardial blood flow and coronary flow reserve of the anatomical right systemic ventricle in patients with congenitally corrected transposition of the great arteries. Heart, 2003, 89(10):1231-5.
[26] Pietrasik G, Goldenberq I, Zdzienicka J, Moss AJ, Zareba W. Prognostic significance of fragmented QRS complex for predicting the risk of recurrent cardiac events in patients with Q-wave myocardial infarction. Am J Cardiol 2007;(4):583-586.
[1] Cohn PF, Fox KM, Daly C. Silent myocardial ischemia[J]. Circulation, 2003, 108(10): 1263-77.
[2]龙曼云，骆瑗．心电图及动态心电图对冠心病诊断价值的临床研究[J]．右江民族医学院学报，2001，(6)：891-2．
[3] Wolf E, Tzivoni D, Stern S. Comparison of exercise tests and 24-hour ambulatory electrocardiographic monitoring in detection of ST-T changes [J]. Br Heart J, 1974, 36(1):90-5.
[4]李俊峡，崔俊玉．心电图在冠心病诊断中的价值[J]．临床误诊误治，2007，20(8)：1-4．
[5]刘康桐，石磊，雷长城等．平板运动、超声心动图对冠心病的诊断价值[J]．衡阳医学院学报，2000，28(2)：147-8．
[6]赵小平，王兴．12导联动态心电图与平板运动试验诊断冠心病心肌缺血的比较[J]．临床心电学杂志，2006，15(4)：269-71．
[7]田森，文亚红，许勇等．不典型胸痛患者平板运动试验和冠状动脉造影检查结果分析[J]．四川医学，2007，28(6)：608-9．
[8]刘秋莎，袁良俊，赵继先等．80例中老年女性平板运动试验假阳性原因分析中国老年保健医学杂志2007，5(3)：40-1．
[9]冯晓霞，林碧珠．12导联动态心电图对冠心病心肌缺血的诊断价值[J]．广东医学院学报，2007，25(3)：281-2．
[10]王红，吕桂芬，谢剑等．冠状动脉造影检查评价三种无创方法对冠心病的诊断价值[J]．广西医学，2001，23(4)：776-7．
[11]王瑞莉．冠心病诊断技术的发展及临床应用评价[J]．陕西中医学院学报，??2001，24(5)：7-8．
[12]王春柳，吴扬，吕岩等．脉冲多普勒组织成像早期定量诊断冠心病心肌缺血的临床研究[J]．中国老年学杂志，2006，26(3)：297-8．
[13]唐红，解俊敏，张嬿等 冠心病患者心肌声学造影定量分析的初步研究[J]．生物医学工程学杂志，2007，24(5)：1036-9．
[2] Van Campen CM, Visser FC, Visser CA. The QRS score: a promising newexercise score for detecting coronary artery disease based on exercise-inducedchanges of Q-, R- and S-waves: a relationship with myocardial ischemia [J]. EurHeart J, 1996,17(5): 699-708.
[3] Jo Mahenthiran, Bilal R. Khan, Stephen G Sawada, et al. Fragmented QRScomplexes not typical of a bundle branch block: A marker of greater myocardialperfusion tomography abnormalities in coronary artery disease [J]. J Nucl Cardiol,2007,14: 347-53.
[4] Reddv CV, Cheriparambill K, Saul B, et al. Fragmented Left Sided QRS inAbsence of Bundle Branch Block: Sign of left ventricular Aneurysm [J]. AnnNoninvasive Electrocardiol, 2006,11(2): 132-8.
[5] Cohn PF, Fox KM, Daly C. Silent myocardial ischemia[J]. Circulation,2003,108(10): 1263-77.
[6]龙曼云，骆瑗．心电图及动态心电图对冠心病诊断价值的临床研究[J]．右江民族医学院学报，2001，(6)：891-2．
[7] Escolar E, Weigold G, Fuisz A, et al. New imaging techniques for diagnosing coronary artery disease[J]. CMAJ, 2006,174(4): 487-95.
[8]刘康桐，石磊，雷长城等．平板运动、超声心动图对冠心病的诊断价值[J]．衡阳医学院学报，2000，28(2)：147-8．
[9]袁冬冬，许明强．西门子运动心电图机配套平板的改进[J]．医疗卫生装备，2000，(5)：44．
[10]赵小平，王兴． 12导联动态心电图与平板运动试验诊断冠心病心肌缺血??的比较[J]．临床心电学杂志，2006，15(4)：269-71．
[11]田森，文亚红，许勇等．不典型胸痛患者平板运动试验和冠状动脉造影检查结果分析[J]．四川医学，2007，28(6)：608-9．
[12] Moore RB, Shapiro LM, Gibson DG Relation between electrocardiographic replolarisation changes and mechanical events in left ventricular hypertrophy[J]. Br Heart J, 1984, 52(5):516-23.
[13]农盛雄，宾建平，吴平生左室肥厚与左心室舒张功能不全相关性的研究临床超声医学杂志2006年第6期
[14] Sundstrom J, Lind L, Arnlov J, et al. Echocardiographic and electrocardiographicdiagnoses of left ventricular hypertrophy predict mortality independently of eachother in a population of elderly men[J]. Circulation, 2001,103(19):2346-51.
[15] Hildick-Smith DJ, Shapiro LM. Echocardiographic differentiation ofpathological and physiological left ventricular hypertrophy[J]. Heart, 2001,85(6):615-9.
[16]杨旭明，李小彩，闰文泰等．心肌缺血时QRS波群中切迹的物理特性[J]．中国心脏起搏与心电生理杂志，1999，13(2)：105-7．
[17] Abboud S, Zlochiver S. High-frequency QRS electrocardiogram for diagnosingand monitoring ischemic heart disease[J]. J Electrocardiol, 2006, 39(1):82-6.
[18] Rubart M, Zipes DP. Mechanisms of sudden cardiac death[J]. J Clinic invest,2005,115(9): 2305-15.
[19] Lander P, Gomis P, Warren S, et al. Abnormal intra-QRS potentials associatedwith percutaneous transluminal coronary angiography-induced transient myocardialischemia [J]. J Electrocardiol, 2006,39(3):282-9.
[20] Katagiri T, Toba K, Takeyama Y, et al. Morphologic and biochemical studies onthe experimental chronic ischemic myocardium with the Ameroid constrictor [J]. JpnCirc J, 1978,42(3):345-52.
[21] Vanoverschelde JL, Wijns W, Depre C, et al. Mechanisms of chronic regionalpostischemic dysfunction in humans. New insights from the study of noninfarctedcollateral-dependent myocardium[J]. Circulation, 1993, 87(5):1513-23.
[22] Pullan AJ, Buist ML, Sands GB, et al. Cardiac electrical activity-from heart to body surface and back again[J]. J Electrocardiol, 2003,36(Suppl):63-7.
[23] Sapoznikov D, Tzivoni D, Weiman J, et al. High fidelity ECG in the diagnosis of occult coronary artery disease: a study of patients with normal conventional ECG[J].J Electrocardiol, 1977,10(2): 137-48.
[24] Rubulis A, Jensen J, Lundahl G. Ischemia induces aggravation of baseline repolarization abnormalities in left ventricular hypertrophy: a deleterious interaction.J Appl Physiol. 2006,101(1):102-10.
[25] Hauser M, Bengel FM, Hager A, et al. Impaired myocardial blood flow and coronary flow reserve of the anatomical right systemic ventricle in patients with congenitally corrected transposition of the great arteries. Heart, 2003, 89(10):1231-5.
[26] Pietrasik G, Goldenberq I, Zdzienicka J, Moss AJ, Zareba W. Prognostic significance of fragmented QRS complex for predicting the risk of recurrent cardiac events in patients with Q-wave myocardial infarction. Am J Cardiol 2007;(4):583-586.
[1] Cohn PF, Fox KM, Daly C. Silent myocardial ischemia[J]. Circulation, 2003, 108(10): 1263-77.
[2]龙曼云，骆瑗．心电图及动态心电图对冠心病诊断价值的临床研究[J]．右江民族医学院学报，2001，(6)：891-2．
[3] Wolf E, Tzivoni D, Stern S. Comparison of exercise tests and 24-hour ambulatory electrocardiographic monitoring in detection of ST-T changes [J]. Br Heart J, 1974, 36(1):90-5.
[4]李俊峡，崔俊玉．心电图在冠心病诊断中的价值[J]．临床误诊误治，2007，20(8)：1-4．
[5]刘康桐，石磊，雷长城等．平板运动、超声心动图对冠心病的诊断价值[J]．衡阳医学院学报，2000，28(2)：147-8．
[6]赵小平，王兴．12导联动态心电图与平板运动试验诊断冠心病心肌缺血的比较[J]．临床心电学杂志，2006，15(4)：269-71．
[7]田森，文亚红，许勇等．不典型胸痛患者平板运动试验和冠状动脉造影检查结果分析[J]．四川医学，2007，28(6)：608-9．
[8]刘秋莎，袁良俊，赵继先等．80例中老年女性平板运动试验假阳性原因分析中国老年保健医学杂志2007，5(3)：40-1．
[9]冯晓霞，林碧珠．12导联动态心电图对冠心病心肌缺血的诊断价值[J]．广东医学院学报，2007，25(3)：281-2．
[10]王红，吕桂芬，谢剑等．冠状动脉造影检查评价三种无创方法对冠心病的诊断价值[J]．广西医学，2001，23(4)：776-7．
[11]王瑞莉．冠心病诊断技术的发展及临床应用评价[J]．陕西中医学院学报，??2001，24(5)：7-8．
[12]王春柳，吴扬，吕岩等．脉冲多普勒组织成像早期定量诊断冠心病心肌缺血的临床研究[J]．中国老年学杂志，2006，26(3)：297-8．
[13]唐红，解俊敏，张嬿等 冠心病患者心肌声学造影定量分析的初步研究[J]．生物医学工程学杂志，2007，24(5)：1036-9．