OBJECTIVE: The purpose of this study was to prospectively investigate the value of the myocardial extracellular volume fraction (ECV) in predicting myocardial functional outcome after revascularization of coronary chronic total occlusion (CTO). MATERIALS AND METHODS: Thirty patients with CTO underwent cardiovascular magnetic resonance (CMR) before and 6 months after revascularization. Three baseline markers of functional outcome were evaluated in the dysfunctional segments assigned to the CTO vessels: ECV, transmural extent of infarction (TEI), and unenhanced rim thickness (RIM). At the global level, the ECV values of the whole myocardium with and without a hyperenhanced region (global and remote ECV) were respectively measured. RESULTS: In per-segment analysis, ECV was superior to TEI and RIM in predicting functional recovery (area under receiver operating characteristic curve [AUC]: 0.86 vs. 0.75 and 0.73, all p values < 0.010), and it emerged as the only independent predictor of regional functional outcome (odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.77–0.89; p < 0.001) independent of collateral circulation. In per-patient analysis, global baseline ECV was indicative of ejection fraction (EF) at the follow-up examination (β = −0.61, p < 0.001) and changes in EF (β = −0.57, p = 0.001) in multivariate regression analysis. A patient with global baseline ECV less than 30.0% (AUC, 0.93; sensitivity 94%, specificity 80%) was more likely to demonstrate significant EF improvement (OR: 0.38; 95% CI: 0.17–0.85; p = 0.019). CONCLUSION: Extracellular volume fraction obtained by CMR may provide incremental value for the prediction of functional recovery both at the segmental and global levels in CTO patients, and may facilitate the identification of patients who can benefit from revascularization.
Collateral Circulation ; Coronary Vessels* ; Follow-Up Studies ; Humans ; Infarction ; Magnetic Resonance Imaging* ; Myocardial Infarction ; Myocardial Ischemia ; Myocardium ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity

Objective Myocardial functional outcome after revascularization of coronary chronic total occlusion (CTO) was prospectively predicted using extracellular volume fraction (ECV) based on cardiovascular magnetic resonance (CMR). Methods Thirty patients with CTO underwent CMR before and 6 months after percutaneous coronary intervention (PCI) were enrolled. The CMR scan protocol included cine, pre?contrast and post?contrast T1 mapping and late gadolinium enhancement (LGE). Ejection fraction (EF) and segmental wall thickening (SWT) were calculated using CVI 42 software. SWT less than 45% indicated myocardial segment dysfunction. According to the American Heart Association (AHA) scientific statement, the dysfunctional segments assigned to CTO vessel were selected, and three baseline imaging markers, ECV, transmural extent of infarction (TEI) and unenhanced rim thickness (RIM) were respectively evaluated. The myocardial segments were divided into two subgroups, group with well?developed collaterals and group with poorly?developed collaterals, based on the collateral circulation using Rentrop classification. Baseline and follow?up values of SWT and EF were evaluated using paired Student′s t?test. Using an increase in SWT>10% as standard reference, ROC analysis was conducted to describe the predictive performance of baseline markers. A mixed linear model was used to probe the relationship between collateral circulation and SWT. Stepwise logistic regression analysis was used to determine the independent predictors of regional functional recovery. The differences of EF between poorly?developed and well?developed collaterals were compared by Student t test. Results The baseline mean segmental wall thickening (SWT) of the dysfunctional segments increased from 21.6% (9.7%, 33.3%) to 38.4% (19.0%, 51.2%) after PCI (Z=-6.869, P<0.001), and EF was also significantly higher compared with baseline (54.5%±8.5 % vs. 50.7%± 6.6%, t=-5.706, P<0.001). ECV showed good performance in predicting functional recovery with cutoff value 34.7%, area under ROC curve (AUC) 0.86, sensitivity 91%, and specificity 66%. The AUC of ECV was superior to TEI and RIM (AUC: 0.75 and 0.73, all P value<0.01). The segments with well?developed collaterals were associated with a higher SWT at follow?up [46.6% (36.6%, 64.2%) vs. 33.5% (12.8%, 47.8%),F=5.791, P=0.02]. Logistic regression analysis demonstrated that mean segmental ECV was the only independent predictors of regional functional outcome after PCI (OR=0.83, 95% confidence interval: 0.77—0.89; P<0.001). Conclusions ECV by CMR may provide incremental value for the prediction of regional functional recovery in CTO patients, and baseline collateral circulation correlates with the regional systolic function after revascularization.

OBJECTIVETo explore the effect and mechanism of rosuvastatin on tumor necrosis factor-α induced human mesenchymal stem cells (MSCs) apoptosis.

METHODHuman MSCs were treated as follows: (1) culture medium; (2) TNF-α (20 µg/ml) for 6 h; (3) rosuvastatin (20 µmol/L) for 24 h; (4) rosuvastatin (20 µmol/L) for 24 h followed by TNF-α (20 µg/ml) for 6 h; (5) TNF-α+rosuvastatin+50 nmol/L antago-miRNA; (6) TNF-α+rosuvastatin+100 nmol/L antago-miRNA. Cell survival and apoptosis were determined by MTT, TUNEL and caspase-3 activity assay. The changes of miRNA-210 in each group were detected with quantitative PCR.

RESULTTNF-α significantly induced human MSCs apoptosis in a concentration-dependent manner, and pretreatment with rosuvastatin significantly reduced MSCs apoptosis (caspase-3 assay: TNF-α+Statin group vs. TNF-α group: (1.63 ± 0.25) vs. (2.05 ± 0.36), P < 0.05). Meanwhile, TNF-α progressively reduced the expression of miRNA-210 in human MSCs in a dose-dependent manner, while the miRNA-210 expression was significantly upregulated in TNF-α+Statin group (P < 0.05). The protective effect of rosuvastatin on TNF-α induced MSCs apoptosis was largely abolished by co-treatment with 100 nmol/L antago-miRNA (TUNEL:TNF-α + Statin + antago-miR group vs. TNF-α + Statin group: (42.58 ± 6.71) % vs. (16.87 ± 9.27) %, P < 0.05).

CONCLUSIONPretreatment with rosuvastatin can significantly improve the viability of human MSCs after TNF-α injury, the protective mechanism of rosuvastatin is partly mediated through miRNA-210 up-regulation.

Apoptosis ; drug effects ; Caspase 3 ; Cell Survival ; Fluorobenzenes ; pharmacology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Mesenchymal Stromal Cells ; drug effects ; MicroRNAs ; pharmacology ; Pyrimidines ; pharmacology ; Rosuvastatin Calcium ; Sulfonamides ; pharmacology ; Tumor Necrosis Factor-alpha ; drug effects ; Up-Regulation

Cell Cycle Proteins ; Microtubule-Associated Proteins