Changes in Wall Motion in Patients Treated for Unstable Angina: A Suggestion of the Stunned and Hibernating Myocardium in Humans

Abstract

A double-blind, placebo-controlled study using anistreplase was performed in 159 patients with unstable angina. All patients had a history of unstable angina combined with typical ECG changes and without evidence of a previous, recent, or ongoing myocardial infarction. The purpose of the present study was to analyze the relationship between the patency of the culprit artery and the behavior of the ischemia-related regional left ventricular (LV) wall motion. On entry to the study, all patients received conventional drug therapy: i.v. nitroglycerin therapy, an oral beta-blocking agent, and a calcium antagonist. Baseline angiography was carried out within 3 h after randomization, a mean of 4.2 +/- 3.0 h (range, 1 to 17 h) after the last attack of chest pain. Treatment with trial medication was withheld in 33 cases. Sixty-five patients with coronary artery disease received anistreplase (30 U/5 min)/heparin and 61 patients heparin-only therapy. Angiography was repeated 20.6 +/- 4.6 h (mean +/- SD; range, 12 to 39 h) after the baseline angiographic study. To assess changes in regional myocardial wall motion, the LV wall was divided into seven segments. The ischemia-related coronary artery stenosis was calculated quantitatively and related to the quantitatively assessed mean regional left ventricular ejection fraction (RLVEF) of the ischemia-related segments. In 118 of 126 patients who received trial medication, we found that anistreplase/heparin therapy leads to a significantly (p < 0.01) greater reduction in coronary artery diameter stenosis than heparin-only therapy (n = 63, mean +/- SD, 11 +/- 22, vs n = 55, mean +/- SD, 3 +/- 11%). Anistreplase/heparin therapy was related to a larger significant improvement of the ischemia-related RLVEF than heparin-only therapy, although the latter association was not statistically significant (n = 63, mean +/- SD, 7 +/- 15, vs n = 55, mean +/- SD, 5 +/- 14%). The effects of change of coronary artery stenosis on regional LV wall motion were also determined. A paradoxical finding was that a persistently occluded vessel or a vessel showing an increase in coronary artery stenosis was associated with a greater improvement of the ischemia-related RLVEF than a reopened vessel or a vessel with a reduction in coronary artery stenosis (n = 15, mean +/- SD, 7 +/- 11, vs n = 41, mean +/- SD, 8 +/- 13, vs n = 15, mean +/- SD, 1 +/- 12, vs n = 47, mean +/- SD, 5 +/- 16%, NS). One day after the last attack of chest pain, the regional LV wall motion was still abnormal in about 20% of patients. In these patients with unstable angina, the LV wall motion improved both in the treated and the control group at follow-up angiography 1 day later. Improved coronary arterial anatomy was associated with a lesser improvement of the LV contractile function than when worsening of the coronary angiographic appearance occurred. There is no rational explanation of these results. This is a beginning of an effort to elucidate the clinical significance of the stunned and hibernating myocardium in humans.