Elevated end-diastolic wall stress after acute myocardial infarction predicts adverse cardiovascular outcomes and longer hospital length of stay.

BACKGROUND: Acute myocardial infarction (MI) leads to ventricular remodeling in response to oxygen demand. Such changes include left ventricular (LV) dilatation and increased myocardial wall stress. Prior studies showed that wall stress is a vital parameter of cardiac remodeling. However, outcome data are lacking. We aim to investigate wall stress post-MI in relation to biomarkers of cardiac remodeling and cardiovascular outcomes. METHODS: Patients presenting with ST-elevation MI (STEMI) requiring primary percutaneous intervention (PCI) were enrolled prospectively. LVEF and volume-based end-diastolic (EDWS) and end-systolic (ESWS) wall stress were measured from predischarge echocardiograms. Serum samples were collected for measurement of serum biomarkers. We identified 81 patients meeting inclusion criteria (64% men, 36% women) with a mean age of 61. The primary outcome was major adverse cardiovascular events (MACE) defined as 1-year composite endpoint of cardiac mortality, recurrent MI, revascularization, or stroke. Length of hospitalization (LOH) was recorded. RESULTS: Major adverse cardiovascular events-positive patients (n = 12) had significantly higher EDWS levels (15.87 vs 12.33, P = 0.045), and galectin-3 levels (19.07 vs 11.75, P = 0.015), and lower LVEF (40.0% vs 48.4%, P = 0.023) compared to MACE-negative patients. Patients with LOH > 72 hours (n = 33) had significantly higher EDWS, galectin-3, and peak troponin, and lower LVEF compared to patients with LOH < 72 hours. EDWS positively correlated with LOH and galectin-3. EDWS was an independent predictor of MACE by binomial regression analysis. CONCLUSION: End-diastolic walls tress is a potential prognostic tool for risk stratifying STEMI patients, providing an assessment of the functional consequences of myocardial remodeling. It is predictive of MACE independent of LVEF, associated with longer hospitalizations, and correlates with galectin-3, a biomarker of cardiac remodeling.

The Therapeutic Potential of Blocking Galectin-3 Expression in Acute Myocardial Infarction and Mitigating Inflammation of Infarct Region: A Clinical Outcome-Based Translational Study.

INTRODUCTION: Increased galectin-3 is associated with ischemic cardiomyopathy, although its role in early remodeling post-myocardial infarction (MI) has not been fully elucidated. There are no data demonstrating that blocking galectin-3 expression would have an impact on the heart and that its relationship to remodeling is not simply an epiphenomenon. The direct association between galectin-3 and myocardial inflammation, dysfunction, and adverse cardiovascular outcomes post-MI was examined using clinical and translational studies. METHODS: We performed expression analysis of 9753 genes in murine model of acute MI. For galectin-3 loss of function studies, homozygous galectin-3 knock-out (KO) mice were subjected to coronary artery ligation procedure to induce acute MI (MI, N = 6; Sham, N = 6). For clinical validation, serum galectin-3 levels were measured in 96 patients with ST-elevation MI. Echocardiographic and angiographic parameters of myocardial dysfunction and 3-month composite outcome including mortality, recurrent MI, stroke, and heart failure hospitalization were measured. RESULTS: In the infarct regions of murine models, galectin-3 was a robustly expressed gene. Elevated galectin-3 expression strongly correlated with macrophage-mediated genes. Galectin-3 KO mice showed reduced myocardial macrophage infiltration after acute MI. Galectin-3 levels were higher in patients with early systolic dysfunction, and predicted 3-month major adverse cardiovascular events (area under the curve [AUC]: 0.917 ± 0.063; P = .001). CONCLUSIONS: Galectin-3 is directly associated with early myocardial inflammation post-MI and may represent a potential target for therapeutic inhibition.