Expanding the Paradigm

Cardiogenic shock (CS) is theleading cause of death for pa-tients with acute myocardial infarction (MI) who reach the hospital alive. Its incidence has remained con-stant for 20 years.1,2 Rapidly re-establishing infarct-related artery (IRA) blood flow is essential in the management of patients with shock due to right ventricular or left ventric-ular (LV) failure. A strategy of early revascularization is superior to initial aggressive medical therapy.3–5 Despite the advantages of early percutaneous coronary intervention (PCI) or coro-nary artery bypass graft surgery (CABG), once shock is diagnosed, the mortality rate remains high (50%) despite intervention, and half of the deaths occur within the first 48 hours.6–8 This may be caused by irre-versible extensive myocardial or vital-organ damage. New evidence sug-gests, however, that a systemic inflammatory response, complement activation, release of inflammatory cy-tokines, expression of inducible nitric oxide (NO) synthase (iNOS), and in-appropriate vasodilation may play an important role not only in the genesis of shock but also in outcome after shock. New insights and therapies are needed. Classic Shock Paradigm The underlying pathophysiology of CS is profound depression of myocardial contractility, resulting in a vicious spi-ral of reduced cardiac output (CO), low blood pressure, further coronary insufficiency, and further reduction in contractility and CO. The classic par-adigm predicts that compensatory sys-temic vasoconstriction with high sys-temic vascular resistance (SVR) should occur in response to the depres-sion of CO (Figure 1).9 Autopsy studies have shown that the pathological basis of CS is extensive MI. Varying pathological stages of infarction confirm the stuttering and progressive nature of the myocardial necrosis as a corollary of the vicious spiral. Combined new and old infarc-tions consistently involve at least 40% of the LV myocardium in these au-topsy specimens.1