Hongning Song

Improving the efficacy of therapeutic angiogenesis by UTMD-mediated Ang-1 gene delivery to the infarcted myocardium

This study aimed to verify the feasibility and efficacy of ultrasound-targeted microbubble destruction (UTMD)-mediated angiopoietin-1 (Ang-1) gene delivery into the infarcted myocardium. Microbubbles carrying anti-intercellular adhesion molecule-1 (ICAM-1) antibody were prepared and identified. The microbubbles carrying anti-ICAM-1 antibody selectively adhered to the interleukin (IL)-1β-stimulated ECV304 cells and to the ischemic vascular endothelium, and the infarct area was examined to evaluate the targeting ability of ICAM-1 microbubbles in vitro and in vivo. The intravenous administration of the Ang-1 gene was carried out by UTMD in rabbits with acute myocardial infarction (AMI). The rabbits were divided into the control (no treatment), non-targeted microbubble destruction (non-TMB) and the ICAM-1 TMB (TMB) group. Gene delivery by direct intramyocardial injection (IMI) served as a reference. Two weeks later, regional myocardial perfusion and cardiac function were evaluated by echocardiography, and Ang-1 gene-mediated angiogenesis was assessed histologically and biochemically. The results revealed that the ICAM-1-targeted microbubbles selectively adhered to the IL-1β-stimulated ECV304 cells in vitro and to the ischemic vascular endothelium in the infarct area of the rabbits with AMI. Two weeks after the delivery of the Ang-1 gene, compared with the non-TMB group, left ventricular function and myocardial perfusion at the infarct area had improved in the TMB and IMI group (p<0.01). Ang-1 gene expression was detectable in the non-TMB, TMB and IMI group, while its expression was higher in the latter 2 groups (all p<0.01). The microvascular density (MVD) of the infarct area in the non-TMB, TMB and IMI group was 65.6±4.4, 96.7±2.1 and 100.7±3.6, respectively (p<0.01). The findings of our study indicate that UTMD-mediated gene delivery may be used to successfully deliver the Ang-1 gene to the infarcted myocardium, thus improving the efficacy of therapeutic angiogenesis. This may provide a novel strategy for future gene therapy.

Prediction for Improvement and Remodeling in First-Onset Myocardial Infarction by Speckle Tracking Echocardiography: Is Global or Regional Selection Better?

Cardiac function improvement and chamber remodeling after the onset of acute myocardial infarction (AMI) is crucial as it is closely related to the outcomes of patients. We sought to investigate the predictive value of left ventricular (LV) global and region of interest (ROI) assessment for prognosis of AMI patients by speckle tracking echocardiography (STE). We prospectively enrolled 81 first-onset AMI patients for baseline and 6-mo follow-up analysis. The echocardiography-derived parameters were compared in receiver operator characteristics (ROC) analysis for prediction of LV remodeling (LVR) (a minimum 20% increase of LV end-diastolic volume) and cardiac function improvement (a minimum 5% increase of LV ejection fraction). The ROI strain was selected by wall motion score index (WMSI) scores ≥2. The time of whole analysis process was recorded. Cut-off values of -9.92% for global circumferential strain (CS) and -5.53% for ROI CS predicted LVR. Cut-off values of -10.40% for global longitudinal strain (LS) and -5.33% for ROI LS predicted cardiac function improvement. Areas under curves of global and ROI parameters were comparable in ROC analysis (p > 0.05, all). The time of global analysis was less than the time of ROI analysis (p < 0.05) and the reproducibility of global analysis was slightly better than the ROI analysis. Our results demonstrated that STE was valuable for the prediction of LVR and cardiac function improvement after AMI. Compared with ROI parameters, global parameters were more integral and efficient as predictive factors with high predictive power, less analysis time and better reproducibility.

Evaluating the morphology of the left atrial appendage by a transesophageal echocardiographic 3-dimensional printed model

Abstract The novel 3-dimensional printing (3DP) technique has shown its ability to assist personalized cardiac intervention therapy. This study aimed to determine the feasibility of 3D-printed left atrial appendage (LAA) models based on 3D transesophageal echocardiography (3D TEE) data and their application value in treating LAA occlusions. Eighteen patients with transcatheter LAA occlusion, and preprocedure 3D TEE and cardiac computed tomography were enrolled. 3D TEE volumetric data of the LAA were acquired and postprocessed for 3DP. Two types of 3D models of the LAA (ie, hard chamber model and flexible wall model) were printed by a 3D printer. The morphological classification and lobe identification of the LAA were assessed by the 3D chamber model, and LAA dimensions were measured via the 3D wall model. Additionally, a simulation operative rehearsal was performed on the 3D models in cases of challenging LAA morphology for the purpose of understanding the interactions between the device and the model. Three-dimensional TEE volumetric data of the LAA were successfully reprocessed and printed as 3D LAA chamber models and 3D LAA wall models in all patients. The consistency of the morphological classifications of the LAA based on 3D models and cardiac computed tomography was 0.92 (P < .01). The differences between the LAA ostium dimensions and depth measured using the 3D models were not significant from those measured on 3D TEE (P > .05). A simulation occlusion was successfully performed on the 3D model of the 2 challenging cases and compared with the real procedure. The echocardiographic 3DP technique is feasible and accurate in reflecting the spatial morphology of the LAA, which may be promising for the personalized planning of transcatheter LAA occlusion.