Key result
Trans-valvular LV unloading before reperfusion cuts infarct size ~55% vs reperfusion alone in swine AMI.
Why the study?
New approaches to limit myocardial infarct size and progression to heart failure after STEMI are needed. Whether mechanically unloading the left ventricle before coronary reperfusion improves myocardial energy substrate utilization and preserves mitochondrial structure and function compared with immediate reperfusion was unknown.
Does mechanical left ventricular unloading with a trans-valvular pump before coronary reperfusion reduce infarct size, improve myocardial energy substrate utilization, and preserve mitochondrial structure and function compared to immediate reperfusion or veno-arterial ECMO in acute myocardial infarction?
Does mechanical left ventricular unloading with a trans-valvular pump before coronary reperfusion reduce infarct size, improve myocardial energy substrate utilization, and preserve mitochondrial structure and function compared to immediate reperfusion or veno-arterial ECMO in acute myocardial infarction?
Absolute Event Rate: 27.3% vs 60.1%
p-value: p=<0.001
Trans-valvular left ventricular unloading prior to coronary reperfusion limits ischemic injury, preserves mitochondrial cardiolipin content and Complex I function, and reduces infarct size in acute myocardial infarction, whereas veno-arterial ECMO exacerbates mitochondrial dysfunction and infarct size.
Background: Myocardial damage due to acute ST-segment elevation myocardial infarction (STEMI) remains a significant global health problem. New approaches to limit myocardial infarct size and reduce progression to heart failure after STEMI are needed. Mechanically reducing left ventricle workload (LV unloading) before coronary reperfusion is emerging as a potential approach to reduce infarct size. Objective: Given the central importance of mitochondria in reperfusion injury, we hypothesized that compared to immediate reperfusion (IR), LV unloading before reperfusion improves myocardial energy substrate utilization and preserves mitochondrial structure and function. Methods: To explore the effect of LV unloading duration on infarct size, we analyzed data from the STEMI-Door to Unload pilot trial and then tested the effect of LV unloading on ischemia and reperfusion injury, cardiac metabolism and mitochondrial function in swine models of acute myocardial infarction. Results: The duration of LV unloading before reperfusion was inversely associated with infarct size in patients with large anterior STEMI. In preclinical models, LV unloading reduced expression of hypoxia-sensitive proteins and myocardial damage due to ischemia alone. LV unloading with a trans-valvular pump (TV-P), but not with veno-arterial extracorporeal membrane oxygenation (ECMO) reduced infarct size. Using unbiased and blinded metabolic profiling, TV-P improved myocardial energy substrate utilization and preserved mitochondrial structure including cardiolipin content after reperfusion compared to IR or ECMO. Functional testing in mitochondria isolated from the infarct zone showed intact mitochondrial structure including cardiolipin content, preserved activity of the electron transport chain including mitochondrial Complex I, and reduced oxidative stress with TV-P supported reperfusion, but not with IR or ECMO. Conclusion: These novel findings identify that trans-valvular unloading limits ischemic injury before reperfusion, improves myocardial energy substrate utilization and preserves mitochondrial structure and function after reperfusion.
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Swain et al. (2020) studied Acute myocardial infarction / ST-segment elevation myocardial infarction (STEMI) (n=38). Trans-valvular left ventricular unloading pump (Impella CP) before reperfusion vs. Immediate reperfusion (IR) alone or veno-arterial extracorporeal membrane oxygenation (ECMO; 7,500 RPM) before reperfusion was evaluated on Myocardial infarct size (% of area at risk) after 210 minutes of LAD occlusion and 120 minutes of reperfusion (p=<0.001). Trans-valvular LV unloading before reperfusion reduced myocardial infarct size compared to reperfusion alone (27.3% vs 60.1%, p<0.001) and preserved mitochondrial function in swine AMI.
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