Diastolic dysfunction in the elderly--the interstitial issue

Diastolic dysfunction is increasingly recognized as a cause of congestive heart failure. Meta-analyses of earlier studies of this disorder suggest that 40%-50% of patients with the congestive heart failure syndrome have preserved left ventricular systolic function, with current estimates ranging up to 74%. Among patients >or=65 years of age with congestive heart failure, 55% of all subjects and 67% of women had normal systolic function. Histopathologic evaluation reveals a maladaptive remodeling of the interstitium associated with aging, resulting in an increase in interstitial collagen content. The interstitium normally plays a critical role in the generation of early diastolic suction. When there is a significant enough increase in myocardial collagen volume fraction, with its increased viscoelastic burden, this normal early diastolic suction is compromised and diastolic pressures increase. Left ventricular diastolic dysfunction ensues. Neurohumoral abnormalities associated with diastolic dysfunction include activation of the renin-angiotensin-aldosterone system, including increased elaboration of myocardial aldosterone. This excess of aldosterone appears to play a major role in the development of myocardial fibrosis. Recent observations in animal models and humans have demonstrated regression of interstitial collagen volume fraction in response to inhibition of the renin-angiotensin-aldosterone system by angiotensin-converting enzyme inhibitors and aldosterone inhibition, with improvement in diastolic function. Therapeutic implications of these observations suggest targeting the maladaptive remodeling of the interstitium via inhibition of the renin-angiotensin-aldosterone system.