Systolic dysfunction of the ventricle in congestive heart failure: pathophysiology, diagnosis, and therapy

Investigations into the pathophysiology and treatment of the failing left ventricle have yielded impressive results over the past three decades. Patients with systolic dysfunction have abnormalities of the molecular machinery and signaling of contraction which may be in-born or acquired, and result in the characteristic mechanical abnormalities associated with this condition. Correlation of these ultrastructural contractile abnormalities with the mechanical dysfunction observed clinically is complicated by alterations of preload and afterload which accompany systolic failure. The systemic consequences of contractile failure result in a cascade of neuroendocrine and cytokine activation which perpetuates a cycle of further myocardial dysfunction and systemic humoral response. Based on this neuroendocrine paradigm, pharmacologic intervention trials have yielded promising gains in survival and symptom status in patients with systolic dysfunction, particularly with the ACE inhibitors and the beta-adrenergic blockers. For patients with acute systolic failure the inotropic agents continue to be useful in short term support but chronic administration with these agents should be avoided because of enhanced mortality observed in virtually all placebo controlled trials. Finally, long-term mortality rates remain high in patients with systolic dysfunction despite current therapy, thus offering an opportunity for the novel approaches currently under investigation to substantially impact on patient outcomes. (c)1999 by CHF, Inc.