Introduction: Myocardial infarction (MI) remains a leading cause of chronic heart failure (CHF). Presence of unsalvaged myocardium leads to cardiac remodeling and CHF. Reducing myocardial oxygen consumption (MVO2) in acute MI is known to reduce infarct size. We reported that the combination of LV mechanical unloading and chronotropic unloading (i.e., bradycardia) synergistically reduced MVO2 more than 60%. In this study, we examined if the combination therapy outperforms mechanical unloading alone in reducing MI size and preventing heart failure in the long-term. We used transvascular LV assist device (Impella) for mechanical unloading and If channel inhibitor (ivabradine, IVA) for chronotropic unloading.
Methods: In 18 anesthetized dogs, we ligated the coronary arteries for 180 min and then reperfused. We initiated Impella and/or IVA (1mg/kg, iv) 60 min after the onset of ischemia and continued the support until 60 min after reperfusion. We allocated animals into 3 groups, no treatment (IR, n=6), Impella (n=6) and Impella+IVA (n=6). Four weeks after MI, we compared LV function, heart failure parameters and infarct size.
Results: In the acute phase of MI, heart rate in Impella+IVA was by far lower than other groups (IR: 142±22 and Impella+IVA: 89±13 bpm, p<0.05). Four weeks after MI, as shown in Fig. 1, Impella+IVA normalized LV end-systolic elastance (Ees) (IR: 5.8±2.0 and Impella+IVA: 13.0+4.6 mmHg/ml, p<0.05) and markedly decreased LV end-diastolic pressure (IR: 7.7±4.3 and Impella+IVA: 2.5±2.4 mmHg, p<0.05) and NT-proBNP (IR: 2858±1412 and Impella+IVA: 889±499 pg/ml, p<0.05). Impella+IVA strikingly reduced the infarct size by nearly 80% (IR: 15.6±4.2 and Impella+IVA: 4.3±3.4%, p<0.05, Fig. 2).
Conclusion: Combination of LV mechanical unloading and bradycardic agent synergistically reduced infarct size and prevented subsequent heart failure. This “mechano-chronotropic unloading” may serve as a powerful therapeutic option to prevent CHF after MI.