Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
Status:
Completed
Trial end date:
2012-11-01
Target enrollment:
Participant gender:
Summary
Hypertrophic Cardiomyopathy (HCM) is the most common genetic cardiomyopathy and remains the
leading cause of sudden cardiac death in young people and an important cause of heart failure
symptoms and death at any age. In HCM, pathological remodeling of the left ventricle
involving myocardial fibrosis is likely a major contributor to cardiac dysfunction and also a
nidus for the generation of ventricular arrhythmias. Serum markers of collagen turnover have
been shown to reliably reflect the magnitude of myocardial fibrosis in a variety of
cardiovascular diseases. In addition, aldosterone antagonist drugs have been shown to
decrease fibrous tissue formation in the myocardium in certain pathologic cardiovascular
states in which aldosterone production is increased. In HCM, aldosterone production is
up-regulated and has been implicated in the formation of myocardial fibrosis.
Therefore, the specific aims of this proposal are to:
1. assess serum markers of collagen turnover at baseline and correlate these findings with
a variety of clinical and morphologic disease parameters
2. examine the effects of a 12-month treatment with the aldosterone antagonist
spironolactone on magnitude of fibrosis as measured by serum markers of collagen
turnover as well as changes in clinical and morphologic disease parameters.
3. explore the effects of a 12-month treatment with aldosterone antagonist spironolactone
on heart failure status, diastolic function, arrhythmic burden, and total LV mass and
quantity of fibrosis by CMR.
The results of this proposal will offer important insights into the clinical significance of
myocardial fibrosis in this primary genetic cardiomyopathy. The demonstration that
spironolactone decreases fibrosis and improves clinical course would provide the rational for
a larger multicenter clinical trial evaluating this novel therapy for improving clinical
outcome in patients with HCM.