Model-based design of mechanical therapies for myocardial infarction

The mechanical properties of healing myocardial infarcts are a critical determinant of pump function and the transition to heart failure. Recent reports suggest that modifying infarct mechanical properties can improve function and limit ventricular remodeling. However, little attempt has been made to identify the specific infarct material properties that would optimize left ventricular (LV) function. We utilized a finite-element model of a large anteroapical infarct in a dog heart to explore a wide range of infarct mechanical properties. Isotropic stiffening of the infarct reduced end-diastolic (EDV) and end-systolic (ESV) volumes, improved LV contractility, but had little effect on stroke volume. A highly anisotropic infarct, with high longitudinal stiffness but low circumferential stiffness coefficients, produced the best stroke volume by increasing diastolic filling, without affecting contractility or ESV. Simulated infarcts in two different locations displayed different transmural strain patterns. Our results suggest that there is a general trade-off between acutely reducing LV size and acutely improving LV pump function, that isotropically stiffening the infarct is not the only option of potential therapeutic interest, and that customizing therapies for different infarct locations may be important. Our model results should provide guidance for design and development of therapies to improve LV function by modifying infarct mechanical properties.