Factors excercising an influence on recovery of hibernating myocardium after coronary artery bypass grafting

Abstract

Objective: Coronary artery bypass grafting (CABG) in patients with endstage coronary disease (CAD) significantly improves symptoms and prolongs life expectancy. Left ventricular function is also improved in some patients, but not in others. Factors which influence functional recovery of hibernating myocardium after revascularization are at present under investigation.

Methods: From 3/2000 to 8/2002, we analyzed 41 patients with an ejection fraction (EF) of < or =30%, who underwent CABG, prospectively. All patients received low-dose dobutamine echocardiography (DE), dobutamine myocardial scintigraphy with SPECT, dobutamine magnetic resonance tomography (MRI), contrast-enhanced MRI and, when necessary, positron emission tomography (PET). Hibernating myocardium (area of interest) was identified with these diagnostic tools preoperatively and biopsy samples were taken intraoperatively.

Results: All patients received complete coronary revascularization. Early mortality was 2.4%. Three patients died during follow-up. Six months after the operation DE, MRI and SPECT were repeated. EF increased in 23 patients (group I) by at least >or =5%, and in 14 patients (group II) it did not improve. The wall motion score in the area of interest had increased during preoperative DE in group I significantly. The score did not change in group II. In addition the diastolic-systolic wall thickness increase in the area of interest rose >15% during DE in group I preoperatively; the increase was < or =15% in group II. MRI hyperenhancement of the left ventricle was significantly lower in group I compared to group II preoperatively. SPECT showed myocardial viability in the area of interest in all 37 patients. There were no significant differences between group I and II seen in SPECT. When the area of interest was located in the anterior wall the patients more frequently showed ventricular improvement postoperatively than patients with an area of interest located in the inferior, lateral or posterior wall. Light microscopy showed more severe myocardial cell hypertrophy (>19 microm) and less severe destruction of myocardial cell architecture in biopsies of group I compared to group II (myocardial cell hypertrophy < or =17 microm). Electron microscopy showed mitochondrial abnormalities in size and shape, lack of contractile material and large areas containing nonspecified cytoplasm, lipid droplets, and large glycogen-filled regions, but no significant differences between the two groups. Gene expresssion of the pro-apoptotic genes BAK and BAX was lowered compared to expression in 'normal' myocardium. The anti-apoptotic gene BCL-XL was significantly more expressed in the 'area of interest' of group II patients than in group I patients.

Conclusions: We conclude that in patients with endstage CAD myocardial recovery after coronary revascularization can be predicted using DE and MRI preoperatively. Myocardial regions without any potential of functional recovery show less adaptation (less pronounced myocardial cell hypertrophy), a more severe degree of myocardial architecture destruction and a higher degree of anti-apoptotic gene expression. We recommend a myocardial biopsy when DE and MRI are not favorable in a patient with end stage coronary artery disease referred to us with the option of heart transplantation or coronary bypass.