LONGITUDINAL ASSOCIATION OF POST-INFARCT LIPOMATOUS METAPLASIA AND MALIGNANT ARRHYTHMIA

Myocardial infarction (MI) from coronary artery obstruction affects more than 1 million people annually in the United States resulting in symptoms, reduced quality of life, and substantially increased risk of heart failure and sudden death. Rapid diagnosis on electrocardiography and treatment with percutaneous intervention (PCI) are essential to minimize the risk and size of permanent myocardial injury as well as the risks of ischemia or reperfusion triggered malignant arrhythmia. Ironically, restoration of blood flow to infarcting myocardium can result in reperfusion injury and expand infarct size. Recent data from animal studies suggest that reperfusion injury may promote lipomatous metaplasia (LM) or intra-myocardial fat deposition. LM has been shown to associate with negative cardiac remodeling, leading to worsening heart function and higher chances for congestive heart failure. We have shown that LM is prevalent but highly variable in distribution among patients with prior MI and ubiquitous among those presenting with ventricular tachycardia (VT). We have also shown that corridors critical to VT circuitry traverse infarcted tissue through or near LM. The latter association appears to be mediated by prolonged local action potential duration, reduced conduction velocity, as well as increased regional resistance and reduced current loss as impulses traverse corridors adjacent to LM. In prior studies, we have also shown that reperfusion injury, the apparent precursor to LM, can be quantified by cardiac magnetic resonance (CMR) as pathologic iron deposition, and is present in most patients despite nominally successful reperfusion. However, the association of reperfusion injury with LM incidence and progression in humans have not yet been defined. Additionally, no prospective study has evaluated the longitudinal evolution of scar, LM, and viable tissue architecture with the incidence of VT. Thus, we propose a prospective observational study of 175 patients <2 months since PCI for acute ST elevation MI (STEMI) that undergo CMR at baseline, and at 1- and 2-years’ follow-up. Using data from this cohort we will test the following premises: 1. That LM incidence occurs early post STEMI and that its volumetric progression is associated with time since reperfusion; 2. That the extent of LM is associated with reperfusion injury following PCI for STEMI; and 3. That LM precedes and predicts the incidence of sustained VT following MI. Our group has extensive experience with STEMI and VT management, image acquisition and analysis, epidemiology, and biostatistics. The findings of this study will have wide applicability to our mechanistic understanding and management of cardiac remodeling and VT.