Shaofeng Guan

Meta-analysis of the effect of percutaneous coronary intervention on chronic total coronary occlusions

Background and purposeCoronary chronic total occlusion (CTO) is the last stage of coronary artery atherosclerosis. Percutaneous coronary intervention (PCI) is a therapeutic procedure used to recanalize vessels with total occlusion. However, successful recanalization of CTO is still not optimal, and the key influence factors are still uncertainty. Therefore, a scientific evaluation on the effective of PCI for CTO treatment is necessary.MethodsRelevant studies of PCI treatment for CTO were examined. Data were extracted and assessed by two independent clinical experts. Embase, PubMed and Medline et al. were used as database. The main research key words include “CTO”, “PCI”, “Stent”, “Reopen”, “long-term”, “follow-up” and “outcome”. Quality assessment was carried out according to the Cochrane Handbook. The selected data were pooled and analyzed using fixed-effect model and random-effect model. Heterogeneity was assessed using the I2 test, Q test, L’abbe and Galbraith. Comprehensive Meta -Analysis 2.0 and Metanalysis 1.0 were used for statistics analysis in this research.ResultsA total of 16 articles involving 6695 cases in successful CTO recanalization (CTO success group) and 2370 cases in failed CTO recanalization(CTO failure group) were included in this research. Low CTO success was associated with elder age, previous coronary artery bypass graft surgery (CABG) history, multi-vessel diseases and right coronary artery disease lesion. Six follow-up variables including major adverse cardiac events (MACE), recurrent myocardial infarction (MI), all-cause death, incidence of angina, subsequent CABG and cumulative survival rate were found significantly reduced associated with CTO success.ConclusionsClinical baseline characteristics such as age, previous CABG history and lesion baseline characteristics such as lesion length, multi-vessel diseases might be important factors influencing the successful rate of CTO recanalization. Compared to CTO failure patients, all six follow-up variables showed advantage for CTO success patients.

Associations between pentraxin 3 and severity of coronary artery disease

Objective To investigate the associations between plasma levels of pentraxins 3 (PTX3) and C reactive protein (CRP) and the severity of coronary artery lesions. Design and methods 60 patients with coronary heart disease (CHD) who underwent coronary angiography (CAG) in our hospital were included. Plasma was collected during CAG. The coronary Gensini score was used to evaluate the severity of coronary artery lesions. Associations between Gensini scores and plasma levels of PTX3 and CRP were analysed. Patients with estimated glomerular filtration rate <60 mL/min/1.73 m2 were included in the chronic renal dysfunction subgroup. Results A linear correlation was observed between PTX3 and the Gensini score (r=0.513, p<0.001). One-way analysis of variance showed that PTX3 levels were significantly higher in patients with Gensini scores >90 compared with patients with scores of 46–90 or <45 (0–45:4.8±0.8, 46–90:6.7±1.2, >90:7.7±2.0, p<0.001). Stepwise multiple linear regression showed that PTX3 levels were significantly associated with Gensini score in patients with chronic renal dysfunction (p=0.012), while no significant association was found for CRP. Conclusions PTX3 levers were positively associated with the severity of coronary artery lesions. PTX3 is closely associated with the severity of coronary artery stenosis in patients with chronic renal dysfunction.

Targeting AMPK signalling pathway with natural medicines for atherosclerosis therapy: an integration of in silico screening and in vitro assay

An integration of virtual screening and kinase assay was reported to identify AMPK kinase inhibitors from various natural medicines.The activation of AMP-activated protein kinase (AMPK) signalling pathway plays a central role in the pathologic progression of atherosclerosis (AS). Targeting the AMPK is thus considered as a potential therapeutics to attenuate AS. Here, we report the establishment of a synthetic pipeline that integrates in silico virtual screening and in vitro kinase assay to discover new lead compounds of AMPK inhibitors. The screening is performed against a large-size pool of structurally diverse natural products, from which a number of compounds are inferred as promising candidates, and few of them are further tested in vitro by using a standard kinase assay protocol to determine their inhibitory potency against AMPK. With this scheme we successfully identify five potent AMPK inhibitors with IC50 values at micromolar level. We also examine the structural basis and molecular mechanism of nonbonded interaction network across the modelled complex interface of AMPK kinase domain with a newly identified natural medicine.

Acute and chronic myocardial infarction in a pig model: Utility of multi-slice cardiac computed tomography in assessing myocardial viability and infarct parameters

OBJECTIVES The aim of this study was to determine the feasibility of multi-slice computed tomography (MSCT) biphasic imaging in assessing myocardial viability and infarct parameters in both acutely and chronically infarcted pig models. MATERIALS AND METHODS Seven pigs underwent ligation of the distal left anterior descending artery. Imaging was performed on the day of infarction and 3 months post-infarct, with contrast infusion followed by MSCT scan acquisition at different time-points. Left ventricular ejection fractions (LVEFs) were obtained by left ventriculography (LVG) after 3 months. Infarcted locations found using MSCT were compared with those obtained using SPECT. Infarcted areas were also analysed histopathologically and compared with the findings from MSCT. RESULTS Chronic phase images had perfusion defects with lower CT values relative to normal myocardium (43±10HU vs. 156±13HU, p=0.001) on the early images but no residual defects on delayed images. However, we found hyperenhancing regions on delayed images (244±20HU vs. 121±25HU, p=0.001), and good correlation between MSCT- and LVG-derived LVEFs (60.56±7.56%). The areas identified by MSCT corresponded to the location of (201)Tl SPECT-/pathologic staining-derived regions in all models. Infarct size was in good agreement with MSCT and pathological analyses of chronic phase models. CONCLUSIONS Necrotic myocardium in different stages after infarction could be qualitatively and quantitatively assessed using MSCT biphasic imaging, as could the status of microcirculation formation. MSCT-measured LVEFs matched well with other modalities, and hence MSCT is a useful tool in assessing post-infarct cardiac function.

AMPK/NF-κB signaling pathway regulated by ghrelin participates in the regulation of HUVEC and THP1 Inflammation

Endothelial inflammation and monocyte plays an essential role in the initiation and progression of atherosclerosis. Ghrelin is beneficial for atherosclerosis progression. However, the detailed and precise molecular mechanisms of how ghrelin regulates endothelial inflammation are not clear. In this study, we investigated the regulation mechanism of ghrelin on TNF-α-activated endothelial inflammation and monocyte adhesion. It was found that TNF-α-induced monocyte adhesion on HUVEC was significantly attenuated by ghrelin. Furthermore, we found that ghrelin effectively suppressed TNF-α-induced inflammatory factors’ (including ICAM-1, VCAM-1, MCP-1, and IL-1β) expression through inhibiting AMPK phosphorylation and p65 expression both in HUVEC and THP-1. This phenomenon was further demonstrated by using AMPK agonist AICAR and inhibitor compound C, respectively. Our findings suggest that ghrelin may mediate TNF-α-induced endothelial inflammation and monocyte adhesion, in part via AMPK/NF-κB signaling pathway. These novel anti-inflammatory and immunoregulatory actions of ghrelin may play a certain role in understanding the formation and development of atherosclerosis.

Clinical significance of a single multi-slice CT assessment in patients with coronary chronic total occlusion lesions prior to revascularization.

Accurate assessment of coronary chronic total occlusion (CTO) lesion is essential to design an appropriate procedural strategy before revascularization. The present study aims to evaluate the significance of a single multislice computed tomography (MSCT) examination in patients with CTO lesion. We retrospectively analyzed the clinical data of 23 CTO lesions in twenty patients underwent computed tomography coronary angiography (CTCA) and SPECT. The CTCA was more powerful and sensitive to determine the CTO lesion length (100% v.s 47.8%) and to identify the length and location of calcification in occluded vessels compared with the coronary angiography (CAG). The LVEF measured by MSCT was comparable to that from the gated SPECT. Myocardial perfusion imaging showed that the location of the early defect region identified by MSCT was corresponded to the nuclide filling defect on the stressed 201thallium-SPECT imaging. The late hyperenhancement on MSCT was presented as incomplete nuclide filling on the 99mTc-MIBI imaging. The results suggested that a single MSCT examination in previous myocardial infarction without revascularization facilitates to provide some valuable information on the nature of the occluded lesion, myocardial perfusion and globe cardiac function, which would be helpful to design appropriate revascularization strategy in these subjects.

Efficacy and safety of a novel multi-electrode radiofrequency ablation catheter for renal sympathetic denervation in pigs.

Objective To investigate the safety and efficacy of a self-developed novel multi-electrode radiofrequency ablation catheter (Spark) for catheter-based renal denervation (RDN). Methods A total of 14 experimental miniature pigs were randomly divided into four groups (55°& 5-watt, 55°& 8-watt, 65°& 5-watt, and 65° & 8-watt groups). Spark was used for left and right renal artery radiofrequency ablation. Blood samples collected from renal arteries and veins as well as renal arteriography were performed on all animals before, immediately after, and three months after procedure to evaluate the effects of Spark on the levels of plasma renin, aldosterone, angiotensin I, and angiotensin II as well as the pathological changes of renal arteries. Results One pig died of an anesthetic accident, 13 pigs successfully underwent the bilateral renal artery ablation. Compared with basic measurements, pigs in all the four groups had significantly decreased mean arterial pressure after procedure. Histopathological analysis showed that this procedure could result in intimal hyperplasia, significant peripheral sympathetic nerve damage in the renal arteries such as inflammatory cell infiltration and fibrosis in perineurium, uneven distribution of nerve fibers, tissue necrosis, severe vacuolization, fragmented and unclear nucleoli myelin degeneration, sparse axons, and interruption of continuity. In addition, the renal artery radiofrequency ablation could significantly reduce the levels of plasma renin, aldosterone, angiotensin I, and angiotensin II in pigs. Conclusions The results suggest that this type of multi-electrode catheter-based radiofrequency ablation could effectively remove peripheral renal sympathetic nerves and reduce the activity of systemic renin-angiotensin system in pigs, thus facilitating the control of systemic blood pressure in pigs.

Utility of 64-MSCT in assessing acute non-reperfused myocardial infarct size

Objective To evaluate the utility of multi-slice computed tomography (MSCT) in assessing acute non-reperfused myocardial infarct size. Methods Seven domestic pigs (mean weight 17.3 ± 1.9 kg) underwent ligation of the distal left anterior descending artery to establish a model of acute myocardial infarction (MI). MSCT and triphenyltetrazolium chloride (TTC) staining were performed two hours later. The following data were acquired and analyzed: MI volume (%), CT values of the infarcted region, left ventricular cavity and normal cardiac tissue at various scanning time-points (1, 5, 10, 15, 20 min after contrast injection). Results Using MSCT, the overall MI volume showed a time-dependent decrease, with a reduction of 28.87% after 20 min. The greatest reduction occurred at the 5 min time-point. In TTC staining, MI volume was 9.87% ± 2.44%. When MI size, as determined by MSCT, was compared with that by TTC staining in Bland-Altman plots, there was a better agreement at 5, 10, and 15 min time-points at 1 and 20 min. Conclusions The study indicates that double-phase scanning examination using MSCT is a useful tool to assess MI size, and the optimal late-phase scanning time-point set within 5–15 min of contrast injection.

Retraction Note: Meta-analysis of the effect of percutaneous coronary intervention on chronic total coronary occlusions

Coronary chronic total occlusion (CTO) is the last stage of coronary artery atherosclerosis. Percutaneous coronary intervention (PCI) is a therapeutic procedure used to recanalize vessels with total occlusion. However, successful recanalization of CTO is still not optimal, and the key influence factors are still uncertainty. Therefore, a scientific evaluation on the effective of PCI for CTO treatment is necessary. Relevant studies of PCI treatment for CTO were examined. Data were extracted and assessed by two independent clinical experts. Embase, PubMed and Medline et al. were used as database. The main research key words include “CTO”, “PCI”, “Stent”, “Reopen”, “long-term”, “follow-up” and “outcome”. Quality assessment was carried out according to the Cochrane Handbook. The selected data were pooled and analyzed using fixed-effect model and random-effect model. Heterogeneity was assessed using the I 2 test, Q test, L’abbe and Galbraith. Comprehensive Meta -Analysis 2.0 and Metanalysis 1.0 were used for statistics analysis in this research. A total of 16 articles involving 6695 cases in successful CTO recanalization (CTO success group) and 2370 cases in failed CTO recanalization(CTO failure group) were included in this research. Low CTO success was associated with elder age, previous coronary artery bypass graft surgery (CABG) history, multi-vessel diseases and right coronary artery disease lesion. Six follow-up variables including major adverse cardiac events (MACE), recurrent myocardial infarction (MI), all-cause death, incidence of angina, subsequent CABG and cumulative survival rate were found significantly reduced associated with CTO success. Clinical baseline characteristics such as age, previous CABG history and lesion baseline characteristics such as lesion length, multi-vessel diseases might be important factors influencing the successful rate of CTO recanalization. Compared to CTO failure patients, all six follow-up variables showed advantage for CTO success patients.