Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: Rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial.

BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

Down-regulation of lncRNA MALAT1 alleviates vascular lesion and vascular remodeling of rats with hypertension.

OBJECTIVE: Recently, the effect of long non-coding RNAs (lncRNAs) in hypertension (HTN) has been identified. This study aims to explore the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HTN and its role in vascular lesion and remodeling of HTN rats. RESULTS: LncRNA MALAT1 expression was up-regulated in HTN patients, and lncRNA MALAT1 could be an effective index of HTN diagnosis. Down-regulated MALAT1 and inhibited Notch-1 could reduce relative factor expression, including inflammation-related factors, endothelial function-related factors and oxidative stress-related factors, and inhibit apoptosis of aortic endothelial cells of HTN rats. METHODS: LncRNA MALAT1 expression in HTN patients and healthy controls was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Angiotensin II (Ang II)-induced HTN rat models were injected with MALAT1-siRNA, empty lentivirus vector, Notch pathway inhibitor (DAPT) and dimethyl sulphoxide (DMSO) via caudal vein. After three-week treatment, changes of blood pressure, inflammatory factor levels, endothelial function-related factors, oxidative stress indices and apoptosis of vascular endothelial cells were determined by a series of assays. CONCLUSION: This study revealed that down-regulated lncRNA MALAT1 could alleviate the vascular lesion and remodeling of HTN rats, the mechanism may be related to the inhibited activation of Notch signaling pathway.

Effects of adrenomedullin on the cell numbers and apoptosis of endothelial progenitor cells.

PURPOSE: To investigate the effect of adrenomedullin on the cell numbers and apoptosis of endothelial progenitor cells (EPCs). METHODS: Mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation. The cells were stimulated with adrenomedullin, before and after the treatment of adrenomedullin-receptor antagonist, adrenomedullin 22-52, or a PI3K inhibitor LY294002. RESULTS: Adrenomedullin dose-dependently increased the number of EPCs (P < 0.05). Adrenomedullin also significantly decreased apoptosis rate of EPCs in a concentration-dependent manner (P < 0.05). In the isolated human mononuclear cells pretreated with adrenomedullin 22-52 or LY294002, adrenomedullin failed to increase the number of EPCs or to reduce the level of apoptosis. CONCLUSIONS: Adrenomedullin increases the number of EPCs and decreases their apoptosis. These actions are likely mediated by PI3K signaling pathways. The clinical importance of these favourable effects on EPCs remains to be determined.

Integrin alpha5beta1 suppresses rBMSCs anoikis and promotes nitric oxide production.

BACKGROUND: Cell based therapy has been heralded as a novel, promising therapeutic strategy for cardiovascular diseases including pulmonary arterial hypertension (PAH). However, the low survival rate after transplantation due to cell death via anoikis is a major obstacle in stem cell therapy. Cells adhesion via Integrin alpha5beta1 (ITGA5B1) has a tendency to exert higher maximum forces. The present study aimed to evaluate the potential protective effect of ITGA5B1 on rat bone marrow mesenchymal stem cells (rBMSCs) from anoikis. METHODS: Mononuclear cells were isolated by density gradient centrifugation with Ficoll, and rBMSCs cell surface markers were evaluated by flow cytometry. Osteogenic and adipocyte differentiation was determined by Alizarin Red S and Oil Red O staining respectively. The expression of Integrin A5 (ITGA5), Integrin B1 (ITGB1), eNOS and actived-caspase-3 mRNA or protein was confirmed by qPCR and western-blot. Cell adhesion, cell viability, anoikis and the migration of rBMSCs were also evaluated. Nitric oxide (NO) production was detected by the greiss assay. RESULTS: Co-infected with Integrin A5 and B1 lentivirus to rBMSCs increased ITGA5 and ITGB1 mRNA and protein expression. ITGA5B1 enhanced the cell adhesion, cell viability, cell migration and NO production but reduced the cell anoikis in rBMSCs/ITGA5B1 groups. CONCLUSION: Transduction of rat rBMSCs with ITGA5B1 lentivirus could prevent cell anoikis and increase NO production.

Relationship between platelet-leukocyte aggregation and myocardial perfusion in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

OBJECTIVE: To explore the relationship between inflammation, oxidative stress and poor myocardial perfusion in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). BACKGROUND: Risk factors and mechanisms of poor reperfusion in patients with STEMI after primary PCI remain unclear. METHODS: A total of 143 patients who underwent primary PCI after STEMI were divided into good and poor perfusion groups according to sum-ST-segment resolution (sumSTR) and TIMI myocardial perfusion grade (TMP) results. Aortic sinus arterial blood was collected after primary PCI. The platelet-leukocyte aggregation (PLA), platelet-neutrophil aggregation (PNA), platelet-monocyte aggregation (PMA) and platelet-lymphocyte aggregation (PLyA) were measured by flow cytometry. The malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured by chemical colorimetry. RESULTS: The leukocyte count, neutrophil ratio and high-sensitivity C-reactive protein were significantly higher in the poor perfusion group than the good perfusion group (p < 0.05). Multiple linear regression analysis showed that neutrophil ratio was an independent risk factor of sumSTR in STEMI patients after primary PCI (p < 0.01). The poor myocardial perfusion group had higher levels of PLA, PNA, PMA and MDA (p < 0.05). There were no differences in PLyA and SOD levels between the good and poor myocardial perfusion groups (p > 0.05). CONCLUSION: Inflammation and oxidative stress were related to poor myocardial perfusion in patients with STEMI after primary PCI.

Treatment of left main coronary artery stenosis with drug-eluting stent following heart transplantation.

Cardiac allograft vasculopathy is the leading cause of death after the first year of heart transplantation. The optimal treatment for unprotected left main coronary artery disease in orthotopic heart transplantation (OHT) patients is unknown. Two OHT patients with left main disease following heart transplantation underwent percutaneous coronary intervention (PCI). Technical success was achieved in the patients with drug-eluting stents inserted to cover the lesions in the left main coronary artery. After 16 months follow-up, one patient died of multiorgan failure, the other was alive and free from myocardial infarction or target vessel revascularization. We conclude that the unprotected PCI for the left main coronary artery stenosis in transplanted heart is feasible.

L-carnitine as an adjunct therapy to percutaneous coronary intervention for non-ST elevation myocardial infarction.

OBJECTIVES: To evaluate the effects of L: -carnitine as an adjunct therapy to percutanenous coronary intervention (PCI) for non-ST elevation acute coronary syndrome (NSTEMI). MATERIALS AND METHODS: Ninety-six consecutive patients with NSTEMI were randomized into treatment group (L: -carnitine 5 g IV bolus followed by 10 g/day IV infusion for 3 days), and control group. All patients also underwent PCI within 24 h from the onset of chest pain. The peak values of creatine kinase-MB and troponin-I before and after PCI were observed. RESULTS: In the treatment group, the peak values of creatine kinase-MB were significantly lower than the control group at 12 h and 24 h after PCI (P < 0.01). The peak values of troponin-I in the treatment group were also lower than the control group at 8 h after PCI (P < 0.01). Multivariate regression analysis showed that L: -carnitine therapy was an independent predictor for the reduction of creatine kinase-MB (r = 0.596, P < 0.001) or troponin-I (r = 0.633, P < 0.001). CONCLUSION: L: -carnitine adjunct therapy appears to be associated with a reduced level of cardiac markers in patients with NSTEMI. These results support a larger clinical trial to investigate the effect of L: -carnitine on cardiac events following PCI.

A new approach for transseptal catheterization in patients undergoing percutaneous balloon mitral valvuloplasty.

AIMS: To evaluate the safety and efficacy of a new approach for transseptal catheterization in patients undergoing percutaneous balloon mitral valvuloplasty (PBMV). METHODS: One hundred and two patients with rheumatic mitral stenosis were randomized into two groups. In the study group (RA approach), an imaginary horizontal line was drawn from the top end of the tricuspid valve under anteroposterior fluoroscopic view. The intersection of the horizontal line and the right edge of the corresponding thoracic vertebra was defined as the upper border of the Fossa ovalis. The atrial septum was punctured from a point 0.5 cm below the upper border of the Fossa ovalis. In the control group (LA approach), an imaginary horizontal line was drawn between the upper and middle third of the left atrium, and the intersection of this horizontal line and the right edge of the corresponding thoracic vertebra was used as an atrial septum puncture point. RESULTS: Atrial septum puncture succeeded in all patients in the study group and in 72.6% of the patients in the control group (p < 0.01). The average fluoroscopy times for transseptal catheterization in the study and the control groups were 2.0 +/- 0.5 and 3.0 +/- 1.0 min, respectively (p < 0.01). Transseptal catheterization was subsequently achieved using the RA approach in the 14 patients from the control group in whom the LA approach failed. CONCLUSIONS: The RA approach is a safe and effective means for transseptal catheterization in patients undergoing PBMV.