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Cardiac fibrosis as a cause of diastolic dysfunction
1Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Insights
Diastolic dysfunction, a cause of heart failure, involves cardiac fibrosis. Treatments targeting the renin-angiotensin-aldosterone system can prevent and reverse fibrosis, improving heart function.
Area of Science:
- Cardiology
- Cardiovascular Physiology
- Pathology
Background:
- Diastolic dysfunction is a significant cause of heart failure (HF), particularly in patients with preserved left ventricular systolic function.
- Common causes include hypertensive heart disease and ischemic cardiomyopathy.
- Cardiac fibrosis, an adverse accumulation of fibrillar collagen, underlies these conditions.
Purpose of the Study:
- To investigate the role of cardiac fibrosis in diastolic dysfunction.
- To explore the potential of targeting the renin-angiotensin-aldosterone system for treating diastolic dysfunction.
Main Methods:
- Review of experimental studies on cardiac fibrosis and diastolic dysfunction.
- Analysis of pharmacologic interventions targeting the renin-angiotensin-aldosterone system (ACE inhibition and AT receptor antagonism).
Main Results:
- Cardiac fibrosis impairs diastolic function by increasing tissue viscoelasticity.
- Pharmacologic inhibition of the renin-angiotensin-aldosterone system prevents fibrosis and preserves diastolic function.
- ACE inhibition and AT receptor antagonism can induce regression of established cardiac fibrosis.
Conclusions:
- Diastolic dysfunction is linked to cardiac fibrosis.
- Interference with the renin-angiotensin-aldosterone system offers a cardioprotective and cardioreparative strategy.
- Diastolic dysfunction may be a reversible condition through antifibrotic therapies.
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.