Anisotropic Reinforcement Following Myocardial Infarction

Every 34 seconds, an American has a heart attack, or myocardial infarction (MI). Acutely, loss of muscle contraction leads to passive stretching of the infarct throughout the entire cardiac cycle, reducing the pumping capacity of the ventricle. In the long term, chronic hemodynamic changes can lead to pathological ventricular remodeling and heart failure, especially after a large MI. In an effort to prevent remodeling and progression to heart failure, numerous studies have explored the utility of mechanical restraint of the infarct or ventricle to limit post-MI ventricular dilation. Studies of both local and global reinforcement approaches have found that isotropic restraint (stiffening the infarct or ventricle similarly in all directions) can be used to reduce post-MI ventricular remodeling. However, both experimental and computational studies have failed to show improvements in acute, post-MI ventricular function with reinforcement. This dissertation explores the use of an optimized, local reinforcement strategy to determine its effects on both acute post-MI function and chronic ventricular remodeling.

A finite element model of the canine heart was used to predict the reinforcement approach that optimized acute, post-MI function: selective, anisotropic reinforcement in the longitudinal (apex-base) direction. We tested this model prediction in a canine model of acute MI, using an epicardial patch to generate longitudinal restraint of the infarct region. Unlike isotropic strategies, anisotropic reinforcement of the acute infarct led to immediate recovery of over 50% of the functional deficit in cardiac output caused by infarction. Using the same animal model and reinforcement approach, we then conducted a chronic trial to determine whether these acute improvements in function would translate into improvement in chronic function or attenuation of left ventricular (LV) dilation. Somewhat surprisingly, we did not observe any differences in global LV function, LV remodeling, or infarct scar structure at the conclusion of our 8-week chronic study. We hypothesized that dramatic compaction of the infarct scar during healing mechanically unloaded the tension in the epicardial patch, so that scars were no longer experiencing any restraint by 8 weeks post-MI.

We constructed a new finite element model of the canine left ventricle to examine the relationship between infarct restraint, scar compaction, and left ventricular function. We incorporated infarct remodeling by simulating varying degrees of longitudinal compaction, along with isotropic stiffening of the scar. Higher degrees of longitudinal scar compaction produced larger decreases in end-diastolic and end-systolic volume, although predicted stroke volumes across all chronic reinforcement models were similar. Consistent with our experimental hypothesis, end-systolic longitudinal stresses in the center of the patch transitioned from tensile to compressive with increasing magnitudes of scar compaction. This model forms a new foundation for the in silico evaluation of both acute and chronic effects of post-MI restraint therapies.