Efficacy and safety comparison between pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction / 中华心血管病杂志

Objective: To compare the efficacy and safety of pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction (STEMI). Methods: STEMI patients, who received intravenous thrombolytic therapy in Henan STEMI registry between September 2016 and August 2018, were eligible for this study. A total of 5479 patients from 66 hospitals were screened and patients were divided into pro-urokinase group (n=638) and reteplase group (n=702) according to thrombolytic drugs. Data including patient demographics, risk factors, medical histories, patient information at admission, in-hospital treatment, time delays, and clinical events were collected. The clinical recanalization rate, in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital main adverse cardiovascular and cerebrovascular events (MACCE, death or treatment withdrawal, congestive heart failure, reinfarction and ischemic stroke) and post-thrombolysis bleeding were compared between the two groups. Bleeding events were evaluated with Bleeding Academic Research Consortium (BARC) criteria. Results: The median age [61.8 (53.2, 69.0) vs. 62.6 (52.1, 69.8), P=0.833] or the proportion of women [23.0% (147/638) vs. 25.1% (176/702), P=0.385] were similar between the pro-urokinase and reteplase groups. Clinical recanalization rates were similar between the pro-urokinase and reteplase groups [82.1% (524/638) vs. 84.9% (596/702), P=0.172], and there was no difference in the median time from onset to thrombolysis [194.5 (135.0,290.0) min vs. 190 (126.0,292.0) min, P=0.431] and the median recanalization time [95 (67.5,120.0) min vs. 95 (71.0,119.0) min, P=0.561] between the two groups. There was no significant difference in in-hospital mortality [5.5% (35/638) vs. 5.1% (36/702), P =0.770], in-hospital all-cause mortality, treatment withdrawal [8.9% (57/638) vs.7.7% (54/702), P=0.410], and in-hospital MACCE [13.0% (83/638) vs. 10.4% (73/702), P=0.137] between pro-urokinase and reteplase groups. However, the incidence of post-thrombolysis bleeding was significantly higher in reteplase group than in pro-urokinase group [7.8% (55/702) vs. 3.8% (24/638), P=0.002]. Further analysis found that the incidence of oral bleeding and the BARC grades 1-2 bleeding were significantly higher in reteplase group than in pro-urokinase group, whereas the incidence of cerebral hemorrhage was similar between the two groups [0.6% (4/638) vs. 0.4% (3/702), P=0.715]. The comparison of efficacy and safety outcomes between the two groups after adjusting for baseline characteristics using general linear mixed models was consistent with those before the adjustment. There was no significant difference in in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital MACCE after adjusting for baseline characteristics and post-thrombolysis bleeding between the two groups. Conclusions: Pro-urokinase and reteplase have similar clinical efficacy in the treatment of STEMI. In terms of safety, the incidence of cerebral hemorrhage is similar, while the incidence of BARC grades 1-2 bleeding and oral bleeding is higher in reteplase group than in pro-urokinase group, which has no impact on in-hospital outcomes.

Efficacy and safety of tirofiban use after successful percutaneous coronary intervention for patients with moderate to high risk non-ST segment elevation acute coronary syndromes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of tirofiban use immediately after successful percutaneous coronary intervention (PCI) in patients with moderate to high risk non-ST segment elevation acute coronary syndromes (NSTE-ACS).</p><p><b>METHODS</b>NSTE-ACS patients undergoing successful PCI (n = 246) were randomized by the envelope method to tirofiban group (n = 122, 10 µg/kg bolus within 3 min followed by 0.10-0.15 µg×kg(-1)×min(-1) for 36 h i.v.) or control group (n = 124, saline i.v. for 36 h). The primary efficacy composite end point was death, myocardial infarction, target vascular revascularization or ischemic stroke at 30 days. The second end point was the occurrence of composite end point at 7 days or 6 months. Key safety end points were bleeding and thrombocytopenia 3 days after PCI.</p><p><b>RESULTS</b>Baseline characteristics were well-balanced between the two groups (P > 0.05). The primary end point occurred in 0.9% (1/117) patients in the tirofiban group and 3.3% (4/123) patients of those in the control group (P = 0.40). There was no significant difference in the composite end point at 7 days [0.8% (1/122) vs. 3.2% (4/124), P = 0.38] between the groups, however, there was a trend towards lower composite efficacy end points at 6 months in tirofiban group compared to control group [0.9% (1/117) vs. 5.9% (7/118), P = 0.07]. The probability of survival free of composite end point was significantly higher in the tirofiban group than that in the control group (99.2% vs. 94.2%, log-rank test, P = 0.03). There was no GUSTO severe or moderate bleeding or severe thrombocytopenia within 3 days post-PCI. There was no significant difference in mild bleeding [13.1% (16/122) vs. 7.3% (9/124), P = 0.13] or mild thrombocytopenia [0.8% (1/122) vs. 0.8% (1/124), P = 1.00] between the groups.</p><p><b>CONCLUSION</b>Tirofiban use after successful PCI can improve 6-month event-free survival without increasing the risk of bleeding for patients with moderate to high risk NSTE-ACS.</p>

Comparative study on the efficacy of intracoronary infusion with various types of autologous bone marrow stem cells for patients with dilated cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the effects of intracoronary infusion of mononuclear stem cells (MNCs) or mesenchymal stem cells (MSCs) in patients with dilated cardiomyopathy (DCM).</p><p><b>METHODS</b>DCM patients with left ventricular ejection fraction(LVEF) < 40% were randomized to intracoronary infusion of MNCs [(5.1 ± 2.0) × 10(8), n = 16] or MSCs [(4.9 ± 1.7) × 10(8), n = 17] or equal volume normal saline (n = 20) through the guiding catheter. Changes of left ventricular end-diastolic diameter (LVEDd), LVEF and myocardium perfusion defects were assessed before and at (30 ± 3) days and (90 ± 7) days after the procedure. Malignant cardiovascular events were also recorded.</p><p><b>RESULTS</b>(1) One month after the procedure, LVEF in transplantation groups significantly increased compared to before procedure (all P < 0.05), and significant increase of LVEF was observed only in MSCs transplantation group compared to control group (P < 0.05). However, absolute changes of LVEDd and perfusion defects of myocardium were similar among and within groups (P > 0.05). (2) Comparing with before procedure and control group, LVEF in transplantation groups increased significantly in three months after the procedure (P < 0.05), but there were no significant differences between transplantation groups (P > 0.05). LVEDd and myocardium perfusion defects in transplantation groups improved significantly compared with that of before procedure (P < 0.05), while significant decrease of myocardium perfusion defects was only observed in patients treated with MSCs compared with control group at three months after procedure (P < 0.05). (3) There were no significant differences in major cardiovascular events between transplantation group and control during follow-up (P > 0.05).</p><p><b>CONCLUSIONS</b>Intracoronary bone marrow stem cells transplantation is safe and effective for DCM patients while the efficacy of MSCs and MNCs transplantation is comparable.</p>

Angiotensin(1-7) attenuates left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of Angiotensin(1-7) [Ang(1-7)] on left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy (ADR-DCM).</p><p><b>METHODS</b>Weight-matched adult male Wistar rats were randomly divided into 3 groups: (1) the ADR-DCM group (n = 25), in which 2.5 mg/kg of ADR was weekly intravenously injected for 10 weeks. (2) Ang(1-7) group (n = 25), in which ADR rats were simultaneously treated with angiotensin-(1-7) (24 µg×kg(-1)×h(-1), ip.) for 12 weeks. (3) normal control group (n = 10). Hemodynamics and echocardiography examination were performed at 12 weeks. The malondialdehyde (MDA) was measured by TBA methods. The plasma concentration of AngII was determined by immunoradiometric assay. The pathological change was analyzed by histological hematoxylin-eosin staining. Myocardial apoptosis was assessed by TUNEL method. The protein expression of pro-apoptotic protein caspase-3, Bax and anti-apoptotic protein Bcl-xl in cardiomyocytes were detected by Western blot.</p><p><b>RESULTS</b>Mortality was significantly lower in Ang(1-7) group than in ADR-DCM group (16% vs. 40%, P < 0.01). Compared to the control group, left ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD) and left ventricular end-diastolic pressure (LVEDP) were significantly increased in ADR-DCM group (all P < 0.01) while fractional shorting (FS), +dp/dtmax and -dp/dtmax were significantly reduced in ADR-DCM group (all P < 0.01). LVEDD, LVESD and LVEDP were significantly reduced while FS, +dp/dtmax and -dp/dtmax were significantly higher in Ang(1-7) group compared to the ADR-DCM group, but still higher than the control group (all P < 0.01). The concentrations of AngII and MDA were higher in the ADR-DCM group than in the control group (P < 0.01), which were significantly reduced by Ang(1-7) treatment (P < 0.01). The TUNEL-positive cells and apoptosis index, the expression of pro-apoptotic protein caspase-3 and Bax were significantly higher while the expression of anti-apoptotic protein Bcl-xl was significantly lower in the ADR-DCM group than in the control group (all P < 0.01) which could all be partially reversed by Ang(1-7) treatment (all P < 0.01).</p><p><b>CONCLUSION</b>Ang(1-7) could significantly attenuate left ventricular dysfunction and myocardial apoptosis in this model by downregulating pro-apoptotic protein caspase-3 and Bax and upregulating anti-apoptotic protein Bcl-xl expression.</p>

Predictive value of corrected QT interval, corrected Tp-e interval and Tp-e/QT ratio on malignant arrhythmia events in acute ST-segment elevation myocardial infarction patients undergoing thrombolysis / 中华心血管病杂志

<p><b>OBJECTIVE</b>The prognostic value of corrected QT interval (QTc), corrected Tp-e interval (Tp-ec) and Tp-e/QT ratio on occurrence of malignant arrhythmia events (MAE) in acute ST-segment elevation myocardial infarction (STEMI) patients underwent successful thrombolysis was explored and the potential association of these indices with MAE was analyzed.</p><p><b>METHODS</b>Fifty-seven STEMI patients underwent successful thrombolytic therapy within 6 hours after admission and conservative medical treatment were included. QTc, Tp-ec, Tp-e/QT ratio were obtained and calculated in infarct-related electrocardiograph leads and non-infarct-related leads before thrombolysis, (7±1) days and (30±3) days after thrombolysis respectively, and incidence of MAE up to 30 days after thrombolysis was analyzed. Sixty age and gender matched normal subjects served as control group.</p><p><b>RESULTS</b>(1) QTc, Tp-ec, Tp-e/QT in infarct-related and non-infarct-related leads in STEMI group before thrombolysis were significantly higher than those in control group (all P<0.05), and values from the infarct-related leads were significantly higher than those from non-infarct-related leads in STEMI group (all P<0.05). QTc, Tp-ec and Tp-e/QT all significantly and continuously reduced from 7 days and at 30 days post thrombolysis compared the before thrombolysis (P<0.05 vs. before thrombolysis). (2) Tp-ec≥100 ms and Tp-e/QT ratio≥0.25 before thrombolysis in infarct-related leads were linked with higher incidence of MAE within 30 days post thrombolysis in this patient cohort [28.1% (9/32) vs. 40% (1/25), 27.8% (10/36) vs.0, respectively, all P<0.05].</p><p><b>CONCLUSION</b>QTc, Tp-ec and Tp-e/QT values decreased post successful thrombolysis in STEMI patients and higher Tp-ec and Tp-e/QT values before thrombolysis in STEMI patients were related with higher MAE incidence up to 30 days post successful thrombolysis in this patient cohort.</p>

Association between smoking status at follow-up and clinical outcomes in patients undergoing successful percutaneous coronary intervention / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess the association between smoking status at follow-up and clinical outcomes in patients undergoing successful percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>The smoking status at follow-up was investigated in 592 patients undergoing successful PCI between Jan. 2003 and Nov. 2006. The patients were divided into three groups on the basis of their smoking status at follow-up: non-smokers (n = 272), quitters (n = 215) and current smokers (n = 105). Major adverse cardiac events were recorded.</p><p><b>RESULTS</b>The average follow-up time was 19.0 months. At follow-up, current smokers were significantly younger (P < 0.01), more likely to be male (P < 0.01) than non-smokers and had more favorable clinical and angiographic characteristics: lower prevalence of hypertension (P < 0.05) and diabetes (P < 0.05), fewer diseased vessels (P < 0.05) and fewer implanted coronary stents (P < 0.01), larger target vessel diameter (P < 0.01). However, the incidence of non-fatal myocardial infarction (MI) in quitters (1.40%) was significantly higher than in nonsmokers (0.37%, P < 0.05), the incidence of nonfatal MI in current smokers (4.76%) was significantly higher than quitters (1.40%, P < 0.05) and nonsmokers (0.37%, P < 0.01). After adjustments for age, gender, hypertension, diabetes, dyslipidaemia, target vessel diameter, the number of diseased vessels, the kind and number of implanted stents, and the follow-up time, multi-variables logistic regression analysis showed that current smoking was a independent predictive factor for non-fatal MI (beta = 1.28, wald chi2 = 6.91, P < 0.01).</p><p><b>CONCLUSIONS</b>Smokers, especially current smokers, were at increased risk for non-fatal MI post successful PCI. Therefore, all patients underwent PCI should be encouraged to stop smoking.</p>

Effects of telmisartan on voltage-gated Kv1.3 and Kv1.5 potassium channels expressed in Xenopus oocytes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effects of telmisartan on Kv1.3 and Kv1.5 potassium channels expressed in Xenopus oocytes.</p><p><b>METHODS</b>Kv1.3 and Kv1.5 potassium channel currents expressed in Xenopus oocytes were recorded and observed in the absence and presence of telmisartan using standard two-microelectrode voltage clamp techniques.</p><p><b>RESULTS</b>Telmisartan resulted in a concentration- and voltage-dependent inhibition effect on Kv1.3 channel current (IC(50) 2.05 micromol/L)and on Kv1.5 channel current (IC(50) 2.37 micromol/L).</p><p><b>CONCLUSIONS</b>Telmisartan blocks open-state Kv1.3 channel which could be one of the mechanisms related to its immunomodulatory and anti-atherosclerosis effect. Telmisartan also blocks open-state Kv1.5 channel which might partly account for its effect on reducing the incidence of atrial fibrillation.</p>

Psychological stress status in patients with acute coronary syndrome and stable angina pectoris / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the psychological stress status in patients with acute coronary syndrome (ACS) and stable angina pectoris (SA).</p><p><b>METHODS</b>The intensity of social psychological stress and the serum levels of IL-6, CRP and ICAM-1 were determined in patients with ACS (n = 67) and SA (n = 33).</p><p><b>RESULTS</b>(1) The percentage of patients with psychological stress was significantly higher in ACS than that in SA group (78.8% vs. 21.2%, P < 0.01). (2) The serum levels of CRP [(14.82 +/- 5.07) g/L vs. (8.78 +/- 4.34) g/L], IL-6 [(101.7 +/- 22.2) ng/L vs. (71.1 +/- 23.5) ng/L] and sICAM-1 [(1.41 +/- 0.47) mg/L vs. (0.82 +/- 0.37) mg/L] were significantly higher in psychological stress group than those in non-psychological stress group (all P < 0.05). Serum CRP [(18.91 +/- 3.12) g/L vs. (6.20 +/- 2.46) g/L], IL-6 [(114.6 +/- 15.2) ng/L vs. (56.4 +/- 15.8) ng/L] and sICAM-1 [(1.67 +/- 0.39) mg/L vs. (0.63 +/- 0.28) mg/L] levels in ACS group were significantly higher than those in SA group (all P < 0.01).</p><p><b>CONCLUSION</b>Higher psychological stress was associated with higher risk of ACS and increased serum inflammatory cytokines.</p>

Changes of blood lipids in colorectal cancer patients with coronary heart disease and value of lipid-lowering therapy with statins / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes of blood lipid in patients with colorectal cancer complicated by coronary heart disease (CHD) and the effect of lipid-lowering therapy with statins in these patients.</p><p><b>METHODS</b>In 32 pathologically confirmed colorectal cancer patients with CHD, the concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and lipoprotein (a) (Lp(a)) were detected at the baseline, before and after the operation, and at 6 months of postoperative atorvastatin treatment. Thirty patients with TC over 5.70 mmol/L and established coronary artery disease served as the control group.</p><p><b>RESULTS</b>TC, TG and LDL-C in the 30 control patients were significantly decreased after 6 months of 20 mg atorvastatin treatment, and even further decreased till 12 months (P<0.01), but no significant changes occurred in HDL-C and Lp(a). The baseline level of TC, TG, LDL-C and HDL-C were significantly decreased (P<0.01), while Lp(a) increased (P<0.05) in the 32 cancer patients with CHD. Continuing atorvastatin treatment further decreased TC, TG and LDL-C (P<0.05) and increased HDL-C (P<0.05) without affecting Lp(a). The cancer patients had significantly lower TC and LDL-C levels than the control group (P<0.05), but had significantly increased Lp(a) (P<0.05). Six months of atorvastatin treatment further decreased LDL-C and HDL-C in the cancer patients (P<0.05), while TC and Lp(a) had no significant changes.</p><p><b>CONCLUSIONS</b>Increased Lp(a) in colorectal cancer patients can be associated with its anti-tumor effect. Alterations in the blood lipid profile raises a new issue concerning the safety of lipid-lowering therapy in colorectal cancer patients complicated by CHD.</p>

Effects of intracoronary autologous bone marrow mononuclear cells transplantation in patients with dilated cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of intracoronary autologous bone marrow mononuclear cells (BM-MNCs) transplantation in patients with dilated cardiomyopathy (DCM).</p><p><b>METHODS</b>On top of standard therapy, DCM patients received BM-MNCs transplantation (n = 71) or saline injection (n = 187). The baseline clinical characteristics of two groups were comparable. Data on echocardiography, Holter, six-minute-walk test, cardiac SPECT and annual hospital days were obtained in all patients at baseline, 1, 3, 6, 12 and 24 months after transplantation.</p><p><b>RESULTS</b>Six-minute-walk distance was significantly longer at one month [(345 +/- 76) m vs. (286 +/- 104) m, P < 0.05] and thereafter (all P < 0.05) in BM-MNCs group compared with saline group. Left ventri ocular ejection fraction (LVEF) at one month in BM-MNCs group was significantly higher compared with saline group [(41.5 +/- 9.4)% vs. (37.3 +/- 6.6)%, P < 0.05] and with pre-transplantation value [(41.5 +/- 9.4)% vs. (32.4 +/- 8.5)%, P < 0.05] while LVEF was similar at 24 months after transplantation between the two groups [(43.6 +/- 6.3)% vs. (43.2 +/- 6.0)%, P > 0.05]. Three months after transplantation, the number of ischemic segments of BM-MNCs group was significantly reduced compared with that of saline group (2.0 +/- 1.0 vs. 3.1 +/- 1.4, P < 0.05) and with baseline (2.0 +/- 1.0 vs. 3.1 +/- 1.2, P < 0.05) while the number of necrotic segments were similar in both groups during the follow-up. There were no significant difference in survival between two groups during 2 years follow-up (95.4% vs. 94.9%, P > 0.05) but the annual hospitalization days of BM-MNCs group was significantly lower than that of saline group [(23.6 +/- 13.4) d vs. (33.0 +/- 14.0) d, P > 0.05].</p><p><b>CONCLUSIONS</b>Intracoronary transplantation of autologous BM-MNCs was safe and could increase LVEF and the six-minute-walk distance and reduce hospitalization days for patients with dilated cardiomyopathy.</p>