Effects of Nicorandil Administration on Infarct Size in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: The CHANGE Trial.

Background Nicorandil was reported to improve microvascular dysfunction and reduce reperfusion injury when administered before primary percutaneous coronary intervention. In this multicenter, prospective, randomized, double-blind clinical trial (CHANGE [Effects of Nicorandil Administration on Infarct Size in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention]), we investigated the effects of nicorandil administration on infarct size in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results A total of 238 patients with ST-segment-elevation myocardial infarction were randomized to receive intravenous nicorandil (n=120) or placebo (n=118) before reperfusion. Patients in the nicorandil group received a 6-mg intravenous bolus of nicorandil followed by continuous infusion at a rate of 6 mg/h. Patients in the placebo group received the same dose of placebo. The predefined primary end point was infarct size on cardiac magnetic resonance (CMR) imaging performed at 5 to 7 days and 6 months after reperfusion. CMR imaging was performed in 201 patients (84%). Infarct size on CMR imaging at 5 to 7 days after reperfusion was significantly smaller in the nicorandil group compared with the placebo (control) group (26.5±17.1 g versus 32.4±19.3 g; P=0.022), and the effect remained significant on long-term CMR imaging at 6 months after reperfusion (19.5±14.4 g versus 25.7±15.4 g; P=0.008). The incidence of no-reflow/slow-flow phenomenon during primary percutaneous coronary intervention was much lower in the nicorandil group (9.2% [11/120] versus 26.3% [31/118]; P=0.001), and thus, complete ST-segment resolution was more frequently observed in the nicorandil group (90.8% [109/120] versus 78.0% [92/118]; P=0.006). Left ventricular ejection fraction on CMR imaging was significantly higher in the nicorandil group than in the placebo group at both 5 to 7 days (47.0±10.2% versus 43.3±10.0%; P=0.011) and 6 months (50.1±9.7% versus 46.4±8.5%; P=0.009) after reperfusion. Conclusions In the present trial, administration of nicorandil before primary percutaneous coronary intervention led to improved myocardial perfusion grade, increased left ventricular ejection fraction, and reduced myocardial infarct size in patients with ST-segment-elevation myocardial infarction. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03445728.

Effects of nicorandil on myocardial infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: study design and protocol for the randomized controlled trial.

Previous studies have shown that nicorandil has a protective effect on cardiomyocytes. However, there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct size in patients with ST-segment elevation myocardial infarction (STEMI) compared to the current standard of percutaneous coronary intervention (PCI) regimen. The CHANGE (China-Admini stration of Nicorandil Group) study is a multicenter, prospective, randomized, double-blind and parallel-controlled clinical study of STEMI patients undergoing primary PCI in China, aiming to evaluate the efficacy and safety of intravenous nicorandil in ameliorating the myocar dial infarct size in STEMI patients undergoing primary PCI and provide evidence-based support for myocardial protection strategies of STEMI patients.

Sitagliptin attenuates the progression of coronary atherosclerosis in patients with coronary disease and type 2 diabetes.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for ASCVD, the aim of this study was to investigate the effects of a dipeptidyl peptidase-4 inhibitor, sitagliptin, on prevention of progression of coronary atherosclerosis assessed by three-dimensional quantitative coronary angiography (3D-QCA) in T2DM patients with coronary artery disease (CAD). METHODS: This was a prospective, randomized, double-center, open-label, blinded end point, controlled 18-month study in patients with CAD and T2DM. A total of 149 patients, who had at least 1 atherosclerotic plaque with 20%-80% luminal narrowing in a coronary artery, and had not undergone intervention during a clinically indicated coronary angiography or percutaneous coronary intervention, were randomized to sitagliptin group (n = 74) or control group (n = 75). Atherosclerosis progression was measured by repeat 3D-QCA examination in 88 patients at study completion. The primary outcome was changes in percent atheroma volume (PAV) from baseline to study completion measured by 3D-QCA. Secondary outcomes included change in 3D-QCA-derived total atheroma volume (TAV) and late lumen loss (LLL). RESULTS: The primary outcome of PAV increased of 1.69% (95%CL, -0.8%-4.2%) with sitagliptin and 5.12% (95%CL, 3.49%-6.74%) with the conventional treatment (p = 0.023). The secondary outcome of change in TAV in patients treated with sitagliptin increased of 6.45 mm3 (95%CL,-2.46 to 6.36 mm3) and 9.45 mm3 (95%CL,-4.52 to 10.14 mm3) with conventional treatment (p = 0.023), however, no significant difference between groups was observed (p = 0.175). Patients treated with sitagliptin had similar LLL as compared with conventional antidiabetics (-0.06, 95%CL, -0.22 to 0.03 vs. -0.08, -0.23 to -0.03 mm, p = 0.689). CONCLUSIONS: In patients with type 2 diabetes and coronary artery disease, treatment with sitagliptin resulted in a significantly lower rate of progression of coronary atherosclerosis compared with conventional treatment.

Intracoronary arterial retrograde thrombolysis with percutaneous coronary intervention: a novel use of thrombolytic to treat acute ST-segment elevation myocardial infarction.

BACKGROUND: Clearance of coronary arterial thrombosis is necessary in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing urgent percutaneous coronary intervention (PCI). There is currently no highly-recommended method of thrombus removal during interventional procedures. We describe a new method for opening culprit vessels to treat STEMI: intracoronary arterial retrograde thrombolysis (ICART) with PCI. METHODS & RESULTS: Eight patients underwent ICART. The guidewire was advanced to the distal coronary artery through the occlusion lesion. Then, we inserted a microcatheter into the distal end of the occluded coronary artery over the guidewire. Urokinase (5-10 wu) mixed with contrast agents was slowly injected into the occluded section of the coronary artery through the microcatheter. The intracoronary thrombus gradually dissolved in 3-17 min, and the effect of thrombolysis was visible in real time. Stents were then implanted according to the characteristics of the recanalized culprit lesion to achieve full revascularization. One patient experienced premature ventricular contraction during vascular revascularization, and no malignant arrhythmias were seen in any patient. No reflow or slow flow was not observed post PCI. Thrombolysis in myocardial infarction flow grade and myocardial blush grade post-primary PCI was 3 in all eight patients. No patients experienced bleeding or stroke. CONCLUSIONS: ICART was accurate and effective for treating intracoronary thrombi in patients with STEMI in this preliminary study. ICART was an effective, feasible, and simple approach to the management of STEMI, and no intraprocedural complications occurred in any of the patients. ICART may be a breakthrough in the treatment of acute STEMI.

Cutting-balloon angioplasty before drug-eluting stent implantation for the treatment of severely calcified coronary lesions.

BACKGROUND: Severely calcified coronary lesions respond poorly to balloon angioplasty, resulting in incomplete and asymmetrical stent expansion. Therefore, adequate plaque modification prior to drug-eluting stent (DES) implantation is the key for calcified lesion treatment. This study was to evaluate the safety and efficacy of cutting balloon angioplasty for severely calcified coronary lesions. METHODS: Ninety-two consecutive patients with severely calcified lesions (defined as calcium arc ≥ 180° calcium length ratio ≥ 0.5) treated with balloon dilatation before DES implantation were randomly divided into two groups based on the balloon type: 45 patients in the conventional balloon angioplasty (BA) group and 47 patients in the cutting balloon angioplasty (CB) group. Seven cases in BA group did not satisfactorily achieve dilatation and were transferred into the CB group. Intravascular ultrasound (IVUS) was performed before balloon dilatation and after stent implantation to obtain qualitative and quantitative lesion characteristics and evaluate the stent, including minimum lumen cross-sectional area (CSA), calcified arc and length, minimum stent CSA, stent apposition, stent symmetry, stent expansion, vessel dissection, and branch vessel jail. In-hospital, 1-month, and 6-month major adverse cardiac events (MACE) were reported. RESULTS: There were no statistical differences in clinical characteristics between the two groups, including calcium arc (222.2° ± 22.2° vs. 235.0° ± 22.1°, P = 0.570), calcium length ratio (0.67 ± 0.06 vs. 0.77 ± 0.05, P = 0.130), and minimum lumen CSA before PCI (2.59 ± 0.08 mm(2) vs. 2.52 ± 0.08 mm(2), P = 0.550). After stent implantation, the final minimum stent CSA (6.26 ± 0.40 mm(2) vs. 5.03 ± 0.33 mm(2); P = 0.031) and acute lumen gain (3.74 ± 0.38 mm(2) vs. 2.44 ± 0.29 mm(2), P = 0.015) were significantly larger in the CB group than that of the BA group. There were not statistically differences in stent expansion, stent symmetry, incomplete stent apposition, vessel dissection and branch vessel jail between two groups. The 30-day and 6-month MACE rates were also not different. CONCLUSIONS: Cutting balloon angioplasty before DES implantation in severely calcified lesions appears to be more efficacies including significantly larger final stent CSA and larger acute lumen gain, without increasing complications during operations and the MACE rate in 6-month.

Incomplete revascularization in the drug eluting stent era permits meaningful long-term (12-78 months) outcomes in patients ≥ 75 years with acute coronary syndrome.

OBJECTIVE: To compare long-term prognosis between complete revascularization (CR) and incomplete revascularization (IR) in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). METHODS: We prospectively enrolled patients ≥ 75 years with ACS and multi-lesion disease between January 2005 and December 2010 at our center (Institute of Geriatric Cardiology, Chinese PLA General Hospital). Baseline clinical characteristics, PCI parameters and long-term (12 to 78 months) outcomes including main adverse cardiac and cerebral events (MACCE) were compared between CR and IR groups. We used the Kaplan-Meier curve to describe the survival rates, and variables reported to be associated with prognosis were included in Cox regression. RESULTS: Of the 502 patients, 230 patients obtained CR, and the other 272 patients underwent IR. Higher SYNTAX score was an independent predictor of IR [Odds ratio (OR): 1.141, 95% confidence interval (95% CI): 1.066-1.221, P = 0.000]. A total of 429 patients (85.5%) were followed with a duration ranging from 12 months to 78 months. There were no significant differences in cumulative survival rates and event free survival rates between the two groups, even for patients with multi-vessel disease. Older age (OR: 1.079, 95% CI: 1.007-1.157, P = 0.032), prior myocardial infarction (OR: 1.440, 95% CI: 1.268-2.723, P = 0.001) and hypertension (OR: 1. 653, 95% CI: 1.010-2.734, P = 0.050) were significant independent predictors of long-term MACCE. CONCLUSIONS: Given that both clinical and coronary lesion characteristics are much more complex in patients ≥75 years with ACS and multi-lesion disease, IR may be an option allowing low risk hospital results and meaningful long-term (12 to 78 months) outcomes.

[Tirofiban improved the prognosis of senior acute coronary syndrome patients received percutaneous coronary intervention].

OBJECTIVE: To examine if tirofiban may improve the prognosis in aged acute coronary syndrome (ACS) patients received percutaneous coronary intervention (PCI). METHODS: Three hundred and twenty-five ACS patients (age ≥ 60 years), all received drug-eluting stents implantation, were assigned into tirofiban group (n = 210) to receive tirofiban+aspirin and clopidogrel and control group (n = 115) to received aspirin and clopidogrel only. The incidence of thrombolysis in myocardial infarction (TIMI) grade 3 after PCI, in-stent thrombosis, slight/severe bleeding, platelet decrease, myocardial infarction (MI) and target vessel revascularization (TVR) within 30 days and 12 months after PCI and 30 days and 12 months mortality post PCI. RESULTS: In comparison with the control group, the tirofiban group had significantly higher TIMI grade 3 flow after PCI (99.05% vs. 94.78%, P < 0.05), lower in-stent thrombosis (0.47% vs. 2.61%, P < 0.05), as well as lower mortality, MI, and TVR in 30 days and 12 months after PCI (30 days: 0, 0.47% and 0.47% vs. 2.61%, 3.48% and 2.61%; 12 months: 0, 0.47% and 0.47% vs. 2.61%, 5.22% and 5.22%, P < 0.05 or P < 0.01). No significant difference was found (both P > 0.05) in slight bleeding (7.14% vs. 4.35%) and severe bleeding (0 vs. 0) between tirofiban group and control group. A slight difference in thrombocytopenia was found between tirofiban group and control group (0.95% vs. 0), but it failed to reach the level of statistical significance (P > 0.05). CONCLUSIONS: Tirofiban may improve the TIMI grade flow in senior ACS patients after PCI. It also decreases the incidence of in-stent thrombosis, mortality, MI, and TVR in 30 days and 12 months after PCI, without causing increase in severe bleeding and platelet penia. Therefore, it may improve the short/long-term prognosis for these patients.

Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1-1639A/A.

BACKGROUND: Patients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin, and to have a greatly increased risk of bleeding. The experience for the dosing of warfarin in such extremely rare cases has been seldom reported. METHODS: Demographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA. The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium. RESULTS: Both cases (68-year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment, with target international normalized ratio (INR) 2 to 3. Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d. They needed more than 1 month to stabilize their anticoagulation. Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d. Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d. No concomitant medicine to increase or decrease the INR value was recorded for them. Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles -CYP2C9*3/*3 and VKORC1-1639 A/A. Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses. CONCLUSIONS: Two Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin. The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes, as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy.

Multisource image fusion method using support value transform.

With the development of numerous imaging sensors, many images can be simultaneously pictured by various sensors. However, there are many scenarios where no one sensor can give the complete picture. Image fusion is an important approach to solve this problem and produces a single image which preserves all relevant information from a set of different sensors. In this paper, we proposed a new image fusion method using the support value transform, which uses the support value to represent the salient features of image. This is based on the fact that, in support vector machines (SVMs), the data with larger support values have a physical meaning in the sense that they reveal relative more importance of the data points for contributing to the SVM model. The mapped least squares SVM (mapped LS-SVM) is used to efficiently compute the support values of image. The support value analysis is developed by using a series of multiscale support value filters, which are obtained by filling zeros in the basic support value filter deduced from the mapped LS-SVM to match the resolution of the desired level. Compared with the widely used image fusion methods, such as the Laplacian pyramid, discrete wavelet transform methods, the proposed method is an undecimated transform-based approach. The fusion experiments are undertaken on multisource images. The results demonstrate that the proposed approach is effective and is superior to the conventional image fusion methods in terms of the pertained quantitative fusion evaluation indexes, such as quality of visual information (Q(AB/F)), the mutual information, etc.