Abstract
BACKGROUND: The mortality rate of cardiogenic shock complicating acute myocardial infarction (AMI-CS) remains high and underscores an unmet clinical need for more effective therapeutic strategies in this space. Reducing myocardial O(2) consumption (MVO(2)) improves myocardial O(2) supply-demand balance, even in the presence of ongoing ischemia, and limits infarct size. METHODS: Using a comprehensive cardiovascular simulation, we aimed to examine the impact of mechanical unloading with a percutaneous left ventricular assist device (pVAD) combined with heart rate and contractility reduction, also referred to as pharmacologic chronotropic and inotropic unloading (mechano-ino-chronotropic unloading [MIC]), on MVO(2) and hemodynamic parameters in a model of AMI-CS. RESULTS: We found that MIC unloading is more effective at reducing MVO(2) than mechanical unloading alone, without adverse hemodynamic effects when adequate mechanical unloading is utilized. Furthermore, we show that the degree of mechanical unloading achieved by pVAD is enhanced at lower heart rates due to longer periods of outflow from the left ventricle during diastole; that is, pVAD and lower heart rate are synergistic with regards to unloading. CONCLUSIONS: Overall, these findings suggest that MIC unloading may be more effective than mechanical unloading in reducing infarct size in AMI-CS, potentially leading to greater short-term and long-term left ventricular recovery. Future clinical investigations of this therapeutic approach are encouraged.