Valsartan treatment significantly preserved regional fractional area change (ipRFAC 34% vs 20%, p<0.01) in the remote non-infarcted myocardium of mice 4 weeks after induced myocardial infarction.
Does valsartan improve left ventricle regional fractional area change (RFAC) in a mouse model of myocardial infarction?
In a mouse model of MI, regional fractional area change (RFAC) by CMR effectively detected regional systolic dysfunction and protective effects of valsartan that were missed by global ejection fraction.
Absolute Event Rate: 34% vs 20%
p-value: p=<0.01
AIM: Left ventricle (LV) regional fractional area change (RFAC) measured by cardiac magnetic resonance (CMR) allows the non-invasive localization and quantification of the degree of myocardial infarction (MI), and could be applied to assess the effectiveness of pharmacological or regenerative therapies. Here we investigate the ability of RFAC to identify regional dysfunction and discriminate the effect of pharmacological treatment with valsartan, a selective antagonist of angiotensin II type 1 receptor, in a model of MI. METHODS AND RESULTS: C57BL/6N mice, undergoing coronary artery ligation, were divided into two groups: untreated (MI) or treated with valsartan (MI+Val). Sham-operated mice were used as a control. Cardiac dimensions and function were assessed at baseline, 24 hours, 1 and 4 weeks post surgery by CMR and echocardiography. At sacrifice histology and whole-genome gene expression profiling were performed. RFAC was able to detect significant differences between treatment groups whereas the global ejection fraction was not. RFAC showed greater loss of regional contraction in remote non-infarcted myocardium in MI group than in MI+Val group. Consistently, in the same region MI+Val mice showed reduced myocyte hypertrophy, fibroblast proliferation, and fibrosis and modulation of target genes; in addition, left atrium volumes, appendage length and duct contraction were preserved. CONCLUSION: In this study, RFAC effectively estimated the degree of systolic dysfunction and discriminated the regions preserved by pharmacological treatment. RFAC index is a promising tool to monitor changes in LV contraction and to assess the effectiveness of therapeutic regimens in clinical settings.
Castiglioni et al. (Thu,) conducted a other in Myocardial Infarction (n=60). Valsartan vs. Vehicle (untreated MI) was evaluated on Mean regional fractional area change of the inferior and posterior sectors (ipRFAC) at 4 weeks (p=<0.01). Valsartan treatment significantly preserved regional fractional area change (ipRFAC 34% vs 20%, p<0.01) in the remote non-infarcted myocardium of mice 4 weeks after induced myocardial infarction.