Abstract 1117: Aldosterone Receptor Blockade Does Not Reduce Atrial Collagen Levels with Atrial Fibrillation
Background: Atrial fibrillation (AF) is associated with increased fibrosis within the left atrial (LA) myocardium. Antagonism of aldosterone receptors (ALDOBLOCK) can affect fibrosis through associated changes in levels of the matrix metalloproteinases (MMPs) and tissue inhibitors of the MMPs (TIMPs). However, the effects of ALDOBLOCK on LA fibrosis in the setting of AF are unknown.
Methods and Results: LA samples were obtained from dilated cardiomyopathy patients (DCM, n=43) at transplantation. AF was present in 23 pts (duration 1– 84 months). ALDOBLOCK (either spironolactone 12.5–25 mg, or eplerenone 25–50 mg) was used in 9/20 non-AF and 7/23 AF patients, where age (55±10 years), gender (70% male), and LA size (5.2±0.8 cm) were equivalent. LA myocardial MMP-9 (zymography, pixels), TIMP-1 (immu-noblotting, pixels), and total collagen content (COLL, μg COLL/μg protein/g tissue) were measured. Compared to non-AF values, MMP-9 (5137±1095 vs 11890±3010, p<0.05) and COLL (1.03±0.17 vs 1.58±0.15, p<0.05) were increased with AF, but TIMP-1 levels were unchanged (345±89 vs 487±77, p=NS). MMP-9 was unaffected by ALDOBLOCK regardless of AF status. However, TIMP-1 and COLL were reduced with ALDOBLOCK in the non-AF group, but not in the AF group (Figure⇓).
Conclusion: ALDOBLOCK at therapeutic dosages reduced TIMP-1 and COLL in non-AF pts, but did not provide similar effects with AF. These findings provide further evidence that current pharmacological modalities in the setting of AF and DCM fail to alter key determinants of atrial remodeling in AF patients.