Abstract 13798: Differential Plasma Profiles of Matrix Metalloproteinases and Tissue Inhibitors of the Metalloproteinases with Atrial Fibrillation: Relation to Recurrence Following Cardioversion

Abstract

Background: A common intervention for persistent atrial fibrillation (AF) is electrical cardioversion (EC), but a high rate of recurrence occurs with this procedure. The present study tested the hypothesis that alterations in the underlying structural / molecular processes, such as matrix metalloproteinases (MMPs) and tissue inhibitors of the MMPs (TIMPs) likely contribute — and may be predictive of patients in whom AF recurs post-EC.

Methods/Results: Pre-EC plasma samples were obtained from patients with persistent AF (n=25, 65±1 yrs). A cohort of age, sex, and weight-matched patients in sinus rhythm (n=10, 62±2 yrs) were used as referent controls. Plasma MMP (8 MMP types) and TIMP (all 4 TIMP types) levels were measured a using high-sensitivity multiplex assay. Plasma MMP-1 levels were lower (1034±188 vs. 2215±271 pg/mL, p<0.05) and MMP-9 levels were higher (12327±2113 vs. 5336±1138 pg/mL, p<0.05) with AF compared to control. Plasma TIMP-1 (17714±1319 vs. 22456±2073 pg/mL, p<0.05) and TIMP-3 (1987±573 vs. 4119±701 pg/mL, p<0.05) levels were lower while TIMP-4 levels (2010±216 vs. 1202±138 pg/mL, p<0.05) were higher with AF. Changes in plasma levels of MMPs/TIMPs were expressed as a percentage difference of the average value from control subjects (Figure). EC was successful in restoring sinus rhythm in all patients, but 12 (48%) reverted to AF ("AF Recurred", Figure) within 1 month. Pre-EC plasma MMP-9 levels were higher and TIMP-4 levels lower (Figure) in the AF Recurred group. Using a cutoff of 2000 pg/mL for TIMP-4, there was a 93% sensitivity and 57% specificity for predicting maintenance of sinus rhythm at one month.

Conclusions: These findings indicate that circulating levels of MMPs and TIMPs are altered with AF and that differential changes in the levels of certain MMPs and TIMPs may be predictive of AF recurrence. Thus, plasma levels of MMPs and TIMPs may be used to develop a novel biomarker "signature" to guide AF therapy.