Clinical and therapeutic implications of chronic left ventricular dysfunction in coronary artery disease

Abstract

In patients with myocardial ischemia, left ventricular dysfunction (LV) may arise from irreversible damage (cell death), myocardial stunning (postischemic dysfunction), or myocardial hibernation (persistent myocardial dysfunction at rest due to underperfusion). Chronic LV dysfunction usually refers to hibernating myocardium. However, stunning might also become chronic, producing persistent myocardial dysfunction. Clinical studies have demonstrated that many patients with coronary artery disease have subsequent recurring ischemic (symptomatic or silent) episodes at short intervals in the same area and that each episode may be followed by myocardial stunning. In these patients the myocardium may not recover fully between episodes and function may remain reversibly depressed for long periods or may even be clinically depressed. The recognition of both stunning and hibernation is very important clinically and therapeutically, since chronic LV dysfunction may have a negative effect on mortality and morbidity in patients with coronary artery disease. Moreover, both clinical states are potentially correctable. Pharmacologic intervention with β blockers, angiotensin-converting enzyme inhibitors, or calcium antagonists might improve or protect hibernating myocardium. The acute hemodynamic effects of the dihydropyridine calcium antagonist nisoldipine have been investigated in patients with chronic LV dysfunction probably arising from hibernating myocardium. Nisoldipine was found to improve both left ventricular systolic and diastolic function without activating the adrenergic system. The improvement in systolic function may be due to a redistribution of coronary blood flow and to a slight reduction in afterload induced by nisoldipine. On the other hand, nisoldipine may improve diastolic function in these patients by an intrinsic mechanism, reducing intracellular calcium overload or balancing intracellular calcium homeostasis in the ischemic areas. However, when chronic LV dysfunction is due to hibernating myocardium, the “gold standard” of therapy in these patients is restoration of normal blood flow by mechanical or surgical revascularization. In the chronically stunned myocardium drug treatment is aimed at preventing ischemic episodes and restoring normal function. Calcium antagonists have been shown to be effective both in preventing ischemia and in attenuating postischemic stunning. In a previous study we observed that myocardial stunning was prevented when nisoldipine was given before ischemia induced by balloon inflation during coronary angioplasty. Further clinical studies are needed to differentiate between ischemic, stunned, and hibernating myocardium and to determine when each of these conditions leads to chronic LV dysfunction. Moreover, the optimal therapeutic interventions in these conditions need to be well defined.