Thrombolysis in Acute Myocardial Infarction: An Electrocardiographic Study

[摘要] The value of thrombolytic therapy in the treatment of acute myocardial infarction is now unchallenged following the publication of large scale clinical trials showing an impressive reduction in mortality. Intravenous administration of a thrombolytic agent in the early hours of myocardial infarction is established practice in all hospitals, from district generals to specialized cardiac centres. The aim is to obtain a patent artery, improve left ventricular function and decrease mortality. The effectiveness of intravenous therapy obviates the need for acute angiography and intracoronary administration, but a definitive statement concerning whether reperfusion has occurred cannot be made. The 12 lead ECG undergoes well recognised dynamic changes in the early phase of myocardial infarction. Successful lysis, either induced or spontaneous, will modify these changes. Whether these modifications can be quantified and used as simple non invasive tests of reperfusion, myocardial salvage and infarct size has caused much speculation. To have such a simple, widely available, reproducible and inexpensive tool would be highly desirable in a clinical setting. This thesis has addressed these questions. The first study demonstrated the rapid fall in ST segment elevation occurring in response to thrombolysis, and introduced a measurement which expresses this fall as a proportion of the admission value. This is termed the Fractional Change and can be applied to either 24 hour tape recordings or to the 12 lead ECG. A Fractional Change Value > 0.5 occurring by 2-3 hours following therapy is highly specific and sensitive for reperfusion. The next study examined whether an electrocardiographic marker of infarct size, the QRS score, was attenuated in patients achieving successful reperfusion compared with a historical cohort of patients with infarctions given no therapy other than simple analgesia. Only patients with anterior infarcts were studied, and although both groups had similar areas of myocardium at jeopardy on admission, the group of patients achieving successful reperfusion had a significant reduction in the QRS score at 48 hours compared to the control group. These initial studies showed that dynamic changes in the ECG can reflect both reperfusion and myocardial salvage, but are limited in that they were performed in relatively small numbers, and the ECG measurements were made and tabulated manually. A method for digitizing 12 lead ECG's with subsequent computer storage of data for comparative analysis has been developed, and incorporates an automatic QRS scoring system. The developmental work involved in setting this system up and its subsequent validation with inter- and intra-observer variation studies is presented in Chapter 5. This system was then used to follow the sequential ECG changes in a prospective angiographically controlled, double blind randomised trial of 128 patients comparing anistreplase with streptokinase. The 90 minute patency rates for both drugs were found to be the same (anistreplase 55%, streptokinase 53%) . Coronary angiography performed at 90 minutes post therapy allowed a detailed correlation between ECG changes on admission and acute coronary anatomy. The findings of this particular study showed that the height of ST segment elevation does not bear any relation to the age of the infarct, that there is a high incidence of reciprocal change early in the course of infarction, and that this is not related to coexisting disease or remote ischaemia, but is likely to be an electrocardiographic mirror phenomenon. Examining the resolution of ST segment elevation and depression showed that it was the rate of fall which discriminates patent from non patent arteries, and that using a Fractional Change Value of 0. 5 to detect reperfusion, calculated at 2 hours post treatment from a single lead showing maximal ST segment elevation, gave the best sensitivity (81%) and specificity (60%), when compared with a number of different parameters. In addition, it appears that the presence of collaterals supplying the infarct area could result in a high Fractional Change Value despite no antegrade perfusion. This study also confirmed that achievement of a patent artery early (i.e. before 90 minutes) significantly attenuated Q wave development, R wave loss and the QRS score in anterior infarction, but did not affect electrocardiographic markers of infarct size when applied to inferior infarcts. In summary, this thesis provides a detailed study of the electrocardiographic changes taking place in acute myocardial infarction, especially as a consequence of treating with thrombolysis, quantitates these changes and shows where they may be used in a clinical setting as non-invasive tests to aid patient management.

[发布机构] University:University of Glasgow

[关键词] Medicine