Abstract 8449: Evaluation of Atrial Remodeling and Fibrillation Vulnerability Using Molecular Imaging of Matrix Metalloproteinases

Abstract

INTRODUCTION: Heart failure after myocardial infarction (MI) leads to atrial remodeling and fibrosis, thereby increasing vulnerability to atrial fibrillation (AF). While matrix metalloproteinase (MMP) activity is known to be an important mediator of left ventricular (LV) remodeling after MI, atrial MMP activation in this setting has not been well studied. HYPOTHESIS: We hypothesized that atrial structural remodeling and fibrillation vulnerability occurring early after MI can be noninvasively assessed using targeted molecular imaging of MMP activation. METHODS: In vivo and ex vivo SPECT/CT images were obtained in control pigs (n=7) and in pigs 1 week (n=2) or 4 weeks (n=6) after surgical induction of MI. Hybrid 64-slice SPECT/CT scans were performed at 2 hours after intravenous injection of a Tc99m-labeled radiotracer targeted to activated MMPs (RP805; Lantheus Medical Imaging, North Billerica, MA). Myocardial RP805 retention was quantified by gamma well counting after sacrifice. AF vulnerability was assessed in control pigs (n=3) and in pigs 4 weeks post-MI (n=4) using atrial burst pacing for 10 seconds with cycle lengths ranging from 300 to 180 ms. RESULTS: SPECT/CT images demonstrated increased uptake in the MI region and both atria compared to control pigs. In vivo images at 1 week post-MI are shown. RP805 retention at 1 week post-MI was 762±75% in the MI region compared to normal LV and 339±52% in the left atrium (LA) compared to normal LA (p<0.01 each). At 4 weeks post-MI, these values were 351±51% in the MI region and 174±27% in the LA (p<0.01 each). AF was inducible in 4 of 4 post-MI pigs and 0 of 3 controls (p=0.03). CONCLUSIONS: MMP-targeted SPECT/CT imaging may provide valuable noninvasive assessment of atrial remodeling and allow early identification of arrhythmogenic substrates prior to the onset of irreversible fibrosis. This approach may have significant implications regarding AF risk stratification as well as preventive and interventional AF treatment.