[An angiographic trial to evaluate the efficacy and safety of tenecteplase in Chinese patients with acute myocardial infarction].

OBJECTIVE: In this randomized, open-label, multicenter, angiographic trial, we compared the efficacy and safety of tenecteplase (TNK-tPA) with alteplase (rt-PA) in Chinese patients with acute myocardial infarction. METHOD: Patients with acute ST-elevation myocardial infarction and pain to hospital time within 6 hours from October 2002, to March 2004 were randomly assigned a body weight-adjusted bolus of TNK-tPA (0.53 mg/kg over more than 10 s, n = 58) or front loaded rt-PA (< or = 100 mg, n = 52). Coronary angiography was performed at 90 min after initiating study drugs. All patients received aspirin and heparin (target activated partial thromboplastin time: 50-70 s). The primary end point of the trial was the rate of TIMI grade 3 flow at 90 minutes. Other end points included the rate of TIMI grade 2/3 flow at 90 minutes, all cause mortality at 30 days, the moderate/severe hemorrhage without intracranial hemorrhage (ICH) and ICH within 30 days. RESULTS: TIMI grade 3 flow at 90 minutes (68.4% vs. 66.7%, P = 1.00), TIMI grade 2 or 3 at 90 minutes (89.5% vs. 80.4%, P = 0.278), total mortality at 30 days (13.8% vs. 9.6%, P = 0.565), the rate of moderate/severe hemorrhage (8.6% vs. 5.8%, P = 0.72) and incidence of ICH (3.5% vs. 1.9%, P = 1.00) were all similar in TNK-tPA treated patients compared to rt-PA treated patients. CONCLUSION: The efficacy of single-bolus, weight-adjusted TNK-tPA fibrinolytic regimen is equivalent to front-loaded alteplase in terms of the rates of TIMI grade 3 flow, TIMI 2 or 3 flow. Incidences of moderate/severe hemorrhage, ICH and 30-days mortality were similar in TNK-tPA and rt-PA treated patients.

Therapeutic effect of urapidil on myocardial perfusion in patients with ST-elevation acute coronary syndrome.

OBJECTIVES: To evaluate the effect of urapidil on myocardial perfusion, and ventricular function in patients with ST-elevation acute coronary syndrome (ACS) treated with primary percutaneous coronary intervention (PCI). METHODS: Fifty-four patients were randomized into urapidil (12.5 mg, ic, n=27) or control group. Infarct related artery (IRA) was targeted with PCI following urapidil administration. TIMI blood flow, corrected TIMI frame count (cTFC), myocardial blush grade (MBG), ST resolution (STR) on ECG, creatine kinase MB (CK-MB) and cardiac troponin T (cTnT) were measured before, and after PCI. RESULTS: cTFC (18.38+/-3.30 vs 21.44+/-4.26, P=0.005), in the treatment group was lower than the placebo group, whereas MBG was higher (P=0.04). More patients in the urapidil group achieved significant STR following PCI (93% vs 70%, P=0.04). Left ventricular ejection fraction (LVEF), measured with echocardiography, in the urapidil group was higher than the control group 30 days after PCI (0.58+/-0.06 vs 0.54+/-0.06, P=0.04). Peak CK-MB and peak cTnT in the urapidil group was lower than the control group (P<0.01). Myocardial nitric oxide concentration in the urapidil group was higher than that of the control group (P<0.01). Following PCI, the endothelin-1 level did not change in the urapidil group (P>0.05) but it was increased in the control group (P<0.05). CONCLUSIONS: Urapidil treatment improves coronary flow, myocardial perfusion and left ventricular function following PCI in patients with ST-elevation ACS. These beneficial effects are associated with an enhanced biosynthesis of nitric oxide.

[Primary risk factors in Chinese patients with first acute myocardial infarction].

OBJECTIVE: To analyze the primary risk factors of patients with first ST elevation acute myocardial infarction (FSTEMI) in Beijing and Shenyang area between 2004--2005. The Attributable risk percentage (ARP) and population attributable risk percentage (PARP) of every risk factor were determined. METHOD: A total of 426 consecutive FSTEMI patients and 426 gender and age matched healthy controls were included in this 1:1 matched case-control study. RESULT: Multivariate logistic regression analysis showed that following 8 primary risk factors were associated with FSTEMI: heavy smoking (OR = 3.170), diabetes (OR = 2.835), positive family history (OR = 2.243), lack of soybeans intake (OR = 2.243), higher psychological stress (OR = 2.138), lack of fish intake (OR = 1.740), lower education level (OR = 1.572) and recent adverse life events (< 6 months before FSTEMI, OR = 1.515). The ARP are 71.53%, 58.33%, 54.05%, 40.81%, 56.85%, 41.53%, 48.62%, 54.00%; the PARP are 38.79%, 10.40%, 4.69%, 33.72%, 36.03%, 24.96%, 29.56%, 14.83%, respectively. CONCLUSION: In this patient cohort, the harmful risk factors responsible for the development of FSTEMI in Beijing and Shenyang areas during 2004--2005 are heavy smoking, higher psychological stress, lack of soybeans intake, lower education level, lack of fish intake, recent adverse life events, diabetes and positive family history.

[Clinical study of trimetazidine for myocardial protection in acute myocardial infarction].

OBJECTIVE: To assess the effect of trimetazidine as an adjunctive treatment to reperfusion therapy in acute myocardial infarction. METHODS: Sixty patients with acute myocardial infarction were randomized to receive trimetazidine (a loading dose of 60 mg followed by 20 mg 3 times daily) for 2 weeks (n = 32) or to be controls (n = 28). The loading dose was started early before the reperfusion therapy. Patients received intermittent ST-segment monitoring to assess the resolution of ST-segment deviation one hour after reperfusion therapy. Venous blood samples for measurement of malondialdehyde (MDA) and endothelin (ET-1) were taken immediately on admission and 1, 4, 8, 24 and 48 hours as well as 7 days after reperfusion. In-hospital and 3-months major adverse cardiac events were recorded. RESULTS: Blinded ST-segment analysis showed that there was a more marked return towards baseline one hour after reperfusion therapy in the trimetazidine group, than in the control group [change (7.14 +/- 3.50) mm vs (3.79 +/- 1.32) mm, P = 0.041]. The measurement of plasma MDA showed that, there was a significantly lower level in the trimetazidine group 4, 8, 24, 48 hours and 7 days after reperfusion (P < 0.05). The level of plasma ET-1 was significantly lower in the trimetazidine group 8 hours and 7 days after reperfusion (P < 0.05). There was no side effect due to trimetazidine. Clinical outcomes were similar between the two groups. CONCLUSIONS: Trimetazidine is effective for the resolution of ST-segment elevation. The effect of trimetazidine against malondialdehyde and ET-1 formation suggested that it might be the mechanism of the myocardial protection.

Double-blind, multicenter, active-controlled, randomized clinical trial to assess the safety and efficacy of orally administered nicorandil in patients with stable angina pectoris in China.

BACKGROUND: The efficacy and safety of nicorandil were evaluated in Chinese patients with stable angina pectoris (AP) in a double-blind, multicenter, active-controlled, randomized clinical trial. METHODS AND RESULTS: After a 2-week washout period, 232 patients with stable AP were randomized to receive either nicorandil (5 mg tid; 115 patients) or isosorbide mononitrate (ISMN: 20 mg bid; 117 patients) for 2 weeks. Exercise capacity, number of weekly anginal attacks, nitroglycerin (NTG) consumption, and safety were evaluated. Nicorandil and ISMN significantly prolonged the time to 1 mm ST-segment depression in an exercise tolerance test. Both drugs improved the total exercise time and the time to onset of chest pain. There was no significant difference between the 2 groups. Nicorandil significantly decreased the number of anginal attacks and NTG consumption. ISMN decreased the number of anginal attacks significantly; however, there was no significance in NTG consumption, and the ratio of anginal attack reduction was at least 50% was significantly higher with nicorandil. Nicorandil was well tolerated and there was no safety profile difference compared with ISMN. Thus, nicorandil may have equivalent or better antianginal effect than ISMN. CONCLUSIONS: Nicorandil is beneficial as treatment for AP.

[The relationship between high sensitivity C-reactive protein level at admission and myocardial perfusion after primary percutaneous intervention in patients with acute myocardial infarction].

OBJECTIVE: This study was designed to investigate the relationship between high sensitivity C-reactive protein (hs-CRP) level at admission and myocardial perfusion after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction. METHODS: The study population consisted of 197 patients (154 men, mean age 60.94 +/- 11.62 years) who were admitted to our hospital with first acute myocardial infarction and underwent primary PCI in the infarct-related artery. Myocardial perfusion was evaluated by Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade (TMPG). Patients were divided into two groups according to TMPG after PCI. Group 1 consisted of 39 patients with TMPG 0 - 1 and group 2 consisted of 158 patients with TMPG 2 - 3. Serum hs-CRP levels at admission were measured. RESULTS: hs-CRP level at admission was significantly higher in group 1 than that in group 2 (P = 0.026). CONCLUSIONS: Higher hs-CRP level at admission in patients with acute myocardial infarction is related to poorer myocardial perfusion post primary PCI.

[Valsartan eluting-stents inhibited neointimal hyperplasia by decreasing collagen deposition in rabbits].

OBJECTIVE: To assess the effect of valsartan eluting-stents on restenosis and collagen deposition in neointima hyperplasia in rabbits. METHODS: Valsartan eluting-stents and the carrier eluting-stents were made with patented multi-layers coating techniques. Bare stents (n = 8), carrier eluting-stents (n = 8) and valsartan eluting-stents (n = 10) were implanted into rabbit abdominal aortas, respectively. Quantitive angiography (QA) was performed before, immediately post and 3 months after stents implantations to determine the diameter of aortas. Rabbits were killed 3 months post stents implantation and the cross sections of the stented vessels were analyzed for neointimal formation: luminal area (LA), neointimal area (NIA), inner elastic lumina area (IELA), the maximal inner-membrane thickness (MIT) and percent stenosis. MASSON and picrosirius red staining were performed to observe the collagen deposition in neointima analyzed. RESULTS: The mean aortic diameters measured by QA at different time points were similar between the groups. LA was significantly larger (5 016 269 microm(2) +/- 207,934 microm(2) vs. 4,345,548 microm(2) +/- 125,822 microm(2) and 4,302,061 microm(2) +/- 167,952 microm(2), P < 0.01 vs. valsartan stents) while NIA (441,577 microm(2) +/- 74,099 microm(2) vs. 1,119,635 microm(2) +/- 163,503 microm(2) and 1,135,636 microm(2) +/- 136,555 microm(2)) and MIT (116 microm +/- 12 microm vs. 240 microm +/- 30 microm and 192 microm +/- 21 microm) as well as percent stenosis (8% +/- 2% vs. 20% +/- 2% and 21% +/- 2%) were significantly reduced in valsartan eluting-stents group compared to bare and carrier stents groups. MASSON and picrosirius red staining revealed rich type III collagen deposition in neointima and spare type I collagen patched around stents struts in bare and carrier stents groups and collagen deposition was rarely seen in neointima and stents struts in valsartan eluting-stents group. CONCLUSION: Valsartan eluting-stents inhibited neointimal hyperplasia by decreasing collagen deposition.

[Glucose level on admission and outcome after primary percutaneous coronary intervention in patients with acute myocardial infarction].

OBJECTIVE: To investigate the influence of elevated glucose level on epicardial/microvascular flow and survival in patients with acute ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). METHODS: A total of 308 patients with STEMI underwent primary PCI were divided into 3 groups according to the glucose level on admission: group 1, < 7.8 mmol/L; group 2, 7.8-11.0 mmol/L, and group 3, > or = 11.0 mmol/L. RESULTS: Compared with group 1, patients in the group 2 and 3 were older, had higher triglycerides levels and more 2-vessel or 3-vessel diseases. Although TIMI flow after PCI were similar among groups (89.7%, 86.0% and 86.3%, P = > 0.05), corrected TIMI frame count (CTFC) in group 2 and group 3 were higher than that in group 1. Moreover, TIMI myocardial perfusion grade (TMPG) 0-1 grade rate post PCI was higher in group 2 and 3 (30.3% and 29.0%) than that of group 1 (17.3%, P < 0.05). There was less frequently complete ST-segment resolution (56.7%) and early T wave inversion (58.3%) in group 3 than that of group 1 after PCI (72.0% and 73.4% respectively, P < 0.05). Mortality rate at 30 days post PCI was significantly higher in the group 3 (10.4%) than that in the group 1 (2.6%, P < 0.05). CONCLUSION: Elevated glucose level on admission in ST-segment elevation myocardial infarction patients treated with primary PCI is associated with reduced myocardial microvascular flow. Abnormal myocardial microvascular flow might contribute to the poor outcomes observed in patients with hyperglycemia on admission.

Prognosis of unprotected left main coronary artery stenting and the factors affecting the outcomes in Chinese.

BACKGROUND: The long term prognosis of unprotected left main coronary artery (LMCA) stenting is controversial. This study was conducted to evaluate the immediate and long term outcomes of LMCA stenting in Chinese patients and to determine which factors affect the outcomes. METHODS: From May 1997 to March 2003, 224 patients in 23 hospitals underwent elective unprotected LMCA stenting with bare metal stents. Their clinical records were analysed to ascertain immediate and long term outcomes of LMCA stenting as well as factors influencing the prognosis. RESULTS: Stents were implanted into LMCA successfully in 223 cases (99.6 %). One death (0.5%) and one case of non-Q wave nonfatal myocardial infarction (MI) occurred in hospital. The mean follow-up time was (15.6 +/- 12.3) months. Cardiac death developed in 10 cases (4.5%), noncardiac death in 2 cases (0.9%), nonfatal MI in 4 cases (1.8%), target lesion revascularization (TLR) of LMCA in 26 cases (11.7%) and TLR of nonLMCA in 37 cases (16.5%). Univariate analysis showed that cardiac death correlated with left ventricular ejection fraction (LVEF < 40%), female gender and LMCA combined with multivessel disease; that major adverse cardiac events (MACE) correlated with LVEF < 40%, bifurcation lesion and incomplete revascularization. Logistic regression analysis revealed that LVEF < 40% and female gender were independent predictors of cardiac death and MACE. Follow-up angiography was performed in 102 cases (45.7%). The restenosis rate was 31.4%. CONCLUSIONS: Long-term outcomes of stenting for selected patients with unprotected LMCA stenosis is acceptable. It should be performed in inoperable or low risk patients with LVEF > or = 40% and isolated LMCA disease or LMCA combined with multivessel diseases in whom complete revascularization can be obtained.

The influence of admission glucose on epicardial and microvascular flow after primary angioplasty.

BACKGROUND: Patients with elevated admission glucose levels may be at increased risk of death after myocardial infarction, independent of other baseline risk factors and more severe coronary artery disease. However, data regarding admission glucose and epicardial and microvascular flow after primary angioplasty is limited. METHODS: Angioplasty was performed in 308 ST-segment elevated myocardial infarction patients. Patients were divided into 3 groups on the basis of admission glucose level: group 1, < 7.8 mmol/L; group 2, (7.8 - 11.0) mmol/L; and group 3, >or= 11.0 mmol/L. RESULTS: Compared with group 1, patients in group 2 and group 3 were more often female and older. Triglycerides (TG) in group 3 were significantly higher than group 1. At angiography, they more frequently had 2-vessel or 3-vessel disease. In the infarct-related artery, there was no relationship between hyperglycemia and thrombolysis in myocardial infarction (TIMI) 3 flow after percutaneous coronary intervention (PCI) (89.7%, 86.0% and 86.3%, P = NS). However, corrected TIMI frame count (CTFC) in group 2 and group 3 were more than group 1. TIMI myocardial perfusion grade (TMPG) 0 - 1 grade among patients with hyperglycemia after PCI were more frequent (30.9% and 29.0% vs 17.3%, P < 0.05). There was less frequent complete ST - segment resolution (STR) and early T wave inversion among patients with hyperglycemia after PCI. CONCLUSION: Elevated admission glucose levels in ST - segment elevation myocardial infarction patients treated with primary PCI are independently associated with impaired microvascular flow. Abnormal microvascular flow may contribute at least in part to the poor outcomes observed in patients with elevated admission glucose.

[Effects of C-reactive protein and tumor necrosis factor-alpha on mRNA expression of pregnancy-associated plasma protein-A in monocytes].

OBJECTIVE: Serum pregnancy-associated plasma protein A (PAPP-A) is increased in acute coronary syndrome patients and related to prognosis. We investigated the effects of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-alpha) on PAPP-A mRNA expression in monocytes. METHODS: Monocytes were isolated by Ficoll density gradient centrifugation from blood of healthy volunteers. The PAPP-A expressions at mRNA level post CRP or rhTNF-alpha stimulation were measured by RT-PCR. RESULTS: PAPP-A mRNA expression in peripheral blood monocytes increased 2 hours (0.2128 +/- 0.0136) and peaked 24 hours (0.6837 +/- 0.1360) after CRP (20 mg/L) stimulation compared with control group (0.1842 +/- 0.0101). PAPP-A mRNA expression increased rapidly, peaked 2 hours (1.2546 +/- 0.0866) and remained elevated up to 24 hours (0.8203 +/- 0.0413) after rhTNF-alpha (100 ng/ml) stimulation. The effects of CRP and TNF-alpha were dose-dependent. PAPP-A mRNA expression of monocytes were 0.2544 +/- 0.0611, 0.4177 +/- 0.1200, 0.5828 +/- 0.0152, 0.6837 +/- 0.1360 after stimulated with CRP (1, 5, 10, 20 mg/L), and 0.2424 +/- 0.1378, 0.3335 +/- 0.0196, 0.5742 +/- 0.0131, 0.6913 +/- 0.0219 and 0.8203 +/- 0.0413 after stimulated with rhTNF-alpha (5, 10, 25, 50 and 100 ng/ml). Actinomycin D, the DNA-directed RNA polymerase inhibitor, completely blocked CRP and TNF-alpha induced PAPP-A expression. CONCLUSIONS: PAPP-A mRNA expression could be stimulated by CRP and TNF-alpha in human peripheral blood monocytes which might be responsible for the increased serum PAPP-A level in patients with acute coronary syndromes.

[Clinical research of heart rate turbulence on predictive value in patients with acute myocardial infarction].

OBJECTIVE: To assess the predictive value of heart rate turbulence (HRT) in patients with acute myocardial infarction. METHODS: One hundred and twenty-five patients with acute myocardial infarction were enrolled in this study. During the period from 6 to 21 days after onset of acute myocardial infarction, they were undergone 24-hour Holter recordings to collect the mean RR interval and heart rate variability (HRV) SDNN. The Holter files were processed with software of "HRT! View V0.60-1" to obtain the value of Turbulence Onset (TO) and Turbulence Slope (TS) and the value of "heart rate variability (HRV) SDNN". LVEF and EDD were measured by Ultrasonic Cardiography. Endpoint of follow-up was cardiac death. According to the results, patients were divided into two groups (the "survivors" and the "nonsurvivors"). The predictive value for high-risk patients with acute myocardial infarction was assessed by variables between the two groups. RESULTS: In the period of follow-up (mean 225.4 +/- 99.8 days), 14 patients died and 111 patients survived. In the univariate Cox regression analysis, "TS" was a strong univariate predictor of mortality (hazard ratio 11.46, P < 0.01); "TO" was a relatively weak predictor and the hazard ratio was 2.76 (P > 0.05). Combination of abnormal TO and abnormal TS was the strongest mortality predictor (hazard ratio 26.70, P < 0.01); in the multivariate Cox regression analysis, TS < or = 2.5 ms/RR and EDD > or = 5.6 cm were the independent predictors of mortality with hazard ratios 9.49 (P < 0.01) and 3.64 (P < 0.05), respectively. CONCLUSIONS: The absence of the heart rate turbulence after ventricular premature beats is a very potent post-infarction risk predictor which is independent of and stronger than other known risk predictors.

[Analysis of spontaneous reperfusion in acute myocardial infarction and its effect on short-term prognosis].

OBJECTIVE: To analyse the clinical and angiographic characteristics of spontaneous reperfusion (SR) in AMI, and to evaluate its effect on short-term prognosis. METHODS: 112 consecutive AMI patients without intravenous thrombolytic therapy received emergent coronary angiography and primary PCI. The patients were divided into SR group (antegrade TIMI grade 2-3 flow) and non-SR group (antegrade TIMI grade 0-1 flow). The clinical, angiographic and prognostic features of the patients were analyzed. RESULTS: 31 patients (27.7%) were in SR group, and there was no significant difference in base-line clinical characteristics between the two groups. Compared with non-SR group, peak values of CK and CK-MB, Ventricular wall motion abnormality and mortality were lower in SR group, ejection fraction was higher in SR group. Logistic regression analysis showed that there was good correlation between SR and peak value of CK, collaterals, ventricular wall motion abnormality and pre-dilation in PCI. CONCLUSION: SR decreased infarction size, improved heart function and reduced 30-day mortality.

[The studies of risk factors and early intervention in patients with acute coronary syndromes without ST-segment elevation].

OBJECTIVE: To investigate the risk factors and the values of early invasive intervention in patients with acute coronary syndromes (ACS) without ST-segment elevation. METHODS: Five hundred and forty-five patients of ACS without ST-segment elevation were randomly assigned to an early conservative strategy or early invasive strategy who had been admitted to hospitals consecutively from Oct. 2001 to Oct. 2003. The combined cardiovascular events (a combination of cardiac death, nonfatal myocardial infarction, nonfatal heart failure and re-hospital admission due to recurrent ischemia angina) within 30 days and 6 months were analyzed and the primary high risk factors for combined cardiovascular events were evaluated by means of multivariate logistic regression analysis among baseline clinical characteristics and laboratory data, meanwhile, the effects of an early conservative strategy or early invasive strategy on outcomes were also investigated. RESULTS: The incidences of combined cardiovascular events within 30 days and 6 months among 513 cases were 14.0% and 25.7% respectively. Multivariate logistic regression analysis implied ST-segment depression, elevation of troponin I level, increased C-reactive protein, lower ejection fraction of left ventricular and higher TIMI risk scores were all associated with an increases in cardiovascular events within 6 months, and they were respectively independent predictive factor for the increases of cardiovascular events. Early invasive strategy was associated with a lower rate of re-hospital admission due to recurrent ischemia angina within 30 days and a decreased incidences of combined cardiovascular events within 30 days and 6 months compared with early conservative strategy (all P < 0.05). CONCLUSIONS: ST-segment depression, elevation of troponin I level, increased C-reactive protein, lower ejection fraction of left ventricular and higher TIMI risk scores are high risk factors for patients with ACS without ST-segment elevation, and early invasive strategy can have a substantial impact in reducing combined cardiovascular events.

[The safety and efficacy of pre-treatment with enoxaparin (Clexane) in acute coronary syndrome patients undergoing percutaneous coronary intervention].

OBJECTIVE: The purpose of the study is to prospectively investigate the safety and efficacy of anticoagulation with enoxaparin (Clexane) in UA/NQMI patients undergoing PCI procedures. METHODS: UA/NQMI patients received Clexane 1 mg/kg, subcutaneously, q12h for at least 48 hours, the coronary angiography was immediately followed by PCI when indicated and is performed within 8 h after the morning injection. No additional UFH or LMWH was used during or after PCI. Blood samples were taken for further measurement of the anti-Xa activity in 176 patients. RESULTS: 507 UA/NQMI patients were included in the study. 176 patients (93.2%) of the average anti-Xa activity value was > 0.5 IU/ml. During follow-up within 30 days, 3.2% of the patients experienced AMI and 6.7% of the patients recurrent UAP. One patient (0.2%) received revascularization and another died of duodenum perforation. The rate of minor hemorrhage was 4.7% (24 patients). In 30-days follow up, one experienced NQMI and 1 recurrent UA among angiography patients. CONCLUSION: Subcutaneous Enoxaparin given at least for 48 hours before PCI with out additional UFH or LMWH during or after PCI was both safe and effective in high risk UA/NQMI patients.