Cardiac fibrosis as a cause of diastolic dysfunction

Abstract

Background: Diastolic dysfunction is increasingly recognized as a cause of symptomatic heart failure, including the clinical syndrome congestive heart failure (CHF). Meta-analyses of earlier studies of this disorder suggest 40-50% of patients with congestive heart failure have preserved left ventricular systolic function. Conditions associated with diastolic dysfunction are diverse and most commonly include ischemic cardiomyopathy with previous myocardial infarction(s) and hypertensive heart disease.

Pathophysiology: An underlying histopathologic finding in each of these entities is an adverse accumulation and structural remodeling of the heart's fibrillar collagen matrix expressed as cardiac fibrosis. In ventricular tissue fibrosis serves to impose a viscoelastic burden that compromises all of diastole, including the rate of relaxation, diastolic suction and passive stiffness. Various factors contribute to the abnormal accumulation of this fibrillar matrix. Of particular importance are effector hormones of the renin-angiotensin-aldosterone system.

Treatment: In experimental studies, pharmacologic interference with each of these circulating hormones, either through ACE inhibition or respective receptor antagonism, proves cardioprotective by preventing fibrosis while preserving diastolic function. Additionally, a regression of established cardiac fibrosis by its presumptive proteolytic digestion induced by ACE inhibition or AT receptor antagonism has been demonstrated. This cardioreparative strategy improves tissue stiffness and suggests diastolic dysfunction is reversible.