Copyright © 1990 by the European Society of Cardiology.
© 1990 The European Society of Cardiology
Left ventricular function as an end-point of thrombolytic therapy
Green Lane Hospital and University of Auckland School of Medicine Auckland, New Zealand
Correspondence to: Professor R. M. Norris, C/- Coronary Care Unit, Green Land Hospital, Auckland 3, New Zealand
For clinical prognosis, LV function is best described in terms of ejection fraction (EF) or end-systolic volume (ESV). Because deterioration of LV function is the most important adverse prognostic factor for patients after recovery from myocardial infarction, any agent which improves function should improve long-term survival.
Clinical trials in which LV function has been measured have shown that early administration of all the presently available thrombolytic drugs improves LV function. There is, however, no evidence that one drug is better than another for preservation of LV function. Indeed in our double-blind comparison of streptokinase (SK) with tissue plasminogen activator (tPA) in which intervention was made at 2·5 ± 0·6 h after onset, EF at 3 weeks after infarction was 58 ± 12% for SK (n = 116) vs 58 ± 12% for tPA (n = 124). The 95% confidence limit for the difference was 0 ± 37%. Patency rates on the infarct-related artery at 3 weeks were similar in the two groups (75% SK, 76% tPA).
Besides refleting infarct size, LV function is also influenced by healing of the infarct, infarct expansion and LV remodelling. Two clincal trials have shown that captopril treatment started at 1–4 weeks after infarction and continuing for 1 year can prevent progressive LV dilatation in patient who have not received thrombolysis. One possible explanation for our own finding of similar effects of SK and tPA on LV function at three weeks after infarction, despite presumably more rapid reperfusion in patients given tPA, is that later reperfusion with SK prevented infarct expansion.
LV function is a legitimate surrogate end-point for mortality for trials aiming to fine tune the thrombolytic regimen. Our finding that ESV is superior to EF for prediction of long-term survival for patients who did not receive thrombolysis suggests that ESV rather than EF should be the end-point for thrombolysis trials. However, ESV requires contrast ventriculography for accurate measurement and even using contrast ventriculography the range of values for ESV is wider than for EF requiring greater trial numbers for stahtical power. Of the two trials of captopril (above) one showed the major beneficial effect on ESV and the other on end-diastolic volume (EDV).
Evidence is already available which tends to confirm the expectation that improvement in LV function following thrombolysis is associated with improved survival for up to 4 years after completion of myocardial infarction.
Key Words: Ejection fraction • end-systolic volume • thrombolysis