Effectiveness of Integrative Medicine Therapy on Coronary Artery Disease Prognosis: A Real-World Study.

OBJECTIVE: To evaluate the effectiveness of integrative medicine (IM) on patients with coronary artery disease (CAD) and investigate the prognostic factors of CAD in a real-world setting. METHODS: A total of 1,087 hospitalized patients with CAD from four hospitals in Beijing, China were consecutively selected between August 2011 and February 2012. The patients were assigned to two groups based on the treatment: Chinese medicine (CM) plus conventional treatment, i.e., IM therapy (IM group); or conventional treatment alone (CT group). The endpoint was major adverse cardiac events [MACE; including cardiac death, myocardial infarction (MI), and revascularization]. RESULTS: A total of 1,040 patients finished the 2-year follow-up. Of them, 49.4% (514/1,040) received IM therapy. During the 2-year follow-up, the total incidence of MACE was 11.3%. Most of the events involved revascularization (9.3%). Cardiac death/MI occurred in 3.0% of cases. For revascularization, logistic stepwise regression analysis revealed that age ⩾ 65 years [odds ratio (OR), 2.224], MI (OR, 2.561), diabetes mellitus (OR, 1.650), multi-vessel lesions (OR, 2.554), baseline high sensitivity C-reactive protein level ⩾ 3 mg/L (OR, 1.678), and moderate or severe anxiety/depression (OR, 1.849) were negative predictors (P<0.05); while anti-platelet agents (OR, 0.422), ß-blockers (OR, 0.626), statins (OR, 0.318), and IM therapy (OR, 0.583) were protective predictors (P<0.05). For cardiac death/MI, age ⩾ 65 years (OR, 6.389) and heart failure (OR, 7.969) were negative predictors (P<0.05), while statin use (OR, 0.323) was a protective predictor (P<0.05) and IM therapy showed a beneficial tendency (OR, 0.587), although the difference was not statistically significant (P=0.218). CONCLUSION: In a real-world setting, for patients with CAD, IM therapy was associated with a decreased incidence of revascularization and showed a potential benefit in reducing the incidence of cardiac death or MI.

Effect of Kuanxiong Aerosol () on Patients with Angina Pectoris: A Non-inferiority Multi-center Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris. METHODS: Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina. RESULTS: The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01). CONCLUSIONS: KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).

[Effect and mechanism of recombinant hirudin on atherosclerotic plaques in apolipoprotein E knockout (ApoE(-/-)) mice].

OBJECTIVE: To explore the effect and mechanism of hirudin on atherosclerotic plaques in apolipoprotein E knockout (ApoE(-/-)) mice. METHODS: Totally 24 ApoE(-/-) mice, 7-8 weeks old were fed with high fat diets. They were randomly divided into the recombinant hirudin treatment group (drug group) and the model group according to body weight and different dens, 12 in each group. Twelve C57BL/6J mice, 7-8 weeks old fed with high fat diet were recruited as the normal control group. Recombinant hirudin (0.25 mg/kg) was intraperitoneally injected to mice in the drug group from the 10th week old once every other day for five successive weeks. Equal volume of normal saline was injected to mice in the model group. Mice in the normal control group received no treatment. All mice were sacrificed after fed with high fat diet until they were 20 weeks old. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), high-sensitive C-reactive protein (hs-CRP), E-selectin, interleukin-6 (IL-6), and stromal metalloproteinase-2 (MMP-2) were detected. The plaque/lumen area and extracellular lipid composition/ plaque area were analyzed by HE staining and morphometry. Changes of signaling molecules in store-operated calcium channels, including stromal interacting molecule 1 (STIM1), Orail protein, and transient receptor potential channel 1 (TRPC1) were determined by Western blot. Results Lipid plaque formed in the aorta vessel wall of 20-week old mice in the model group. Compared with the normal control group, serum levels of TC, TG and LDL increased (P<0.01), hs-CRP, E-selction, IL-6, and MMP-2 obviously increased (P<0.01, P<0.05) in the model group; expression levels of STIM1, TRPC1, and Orail significantly increased (P<0.01). Compared with the model group, the plaque/lumen area and the extracellular lipid composition/plaque area significantly decreased in the drug group (P<0.05, P<0.01); serum levels of TC and LDL, hs-CRP, E-selction, IL-6, and MMP-2 obviously decreased (P<0.05, P<0.01); expression levels of STIM1, TRPC1, and Orail were significantly down-regulated (P<0.05, P<0.01). CONCLUSION: Hirudin could significantly improve lipids and endothelial functions of ApoE(-/-) mice, down-regulate expression levels of STIM1, Orai1, and TRPC1, and thus delaying the occurrence and development of atherosclerosis.

Clinical impact of dual antiplatelet therapy use in patients following everolimus-eluting stent implantation: insights from the SEEDS study.

BACKGROUND: Studies have suggested that use of prolonged dual antiplatelet therapy (DAPT) following new generation drug-eluting stent implantation may increase costs and potential bleeding events. This study aimed to investigate the association of DAPT status with clinical safety in patients undergoing everolimus-eluting stent (EES) implantation in the SEEDS study (A Registry to Evaluate Safety and Effectiveness of Everolimus Drug-eluting Stent for Coronary Revascularization) at 2-year follow-up. METHODS: The SEEDS study is a prospective, multicenter study, where patients (n = 1900) with small vessel, long lesion, or multi-vessel diseases underwent EES implantation. Detailed DAPT status was collected at baseline, 6-month, 1- and 2-year. DAPT interruption was defined as any interruption of aspirin and/or clopidogrel more than 14 days. The net adverse clinical events (NACE, a composite endpoint of all-cause death, all myocardial infarction (MI), stroke, definite/probable stent thrombosis (ST), and major bleeding (Bleeding Academic Research Consortium II-V)) were investigated according to the DAPT status at 2-year follow-up. RESULTS: DAPT was used in 97.8% of patients at 6 months, 69.5% at 12 months and 35.4% at 2 years. It was observed that the incidence of NACE was low (8.1%) at 2 years follow-up, especially its components of all-cause death (0.9%), stroke (1.1%), and definite/probable ST (0.7%). DAPT was not an independent predictor of composite endpoint of all-cause death/MI/stroke (hazard ratio [HR]: 0.693, 95% confidence interval [CI]: 0.096-4.980, P = 0.715) and NACE (HR: 1.041, 95% CI: 0.145-7.454, P = 0.968). Of 73 patients who had DAPT interruption, no patient had ST at 12-month, and only 1 patient experienced ST between 1- and 2-year (1.4%). There was a high frequency of major bleeding events (53/65, 82.5%) occurred in patients receiving DAPT treatment. CONCLUSIONS: Prolonged DAPT use was not associated with improved clinical safety. The study emphasized that duration of DAPT needs to be shortened in Chinese patients following EES implantation (ClinicalTrials.gov identifier: NCT 01157455).

Validation of residual SYNTAX score with second-generation drug-eluting stents: one-year results from the prospective multicentre SEEDS study.

AIMS: The SYNTAX score has been proposed as a valuable tool to characterise coronary anatomy prospectively based on its complexity. This study evaluated the prognostic value on adverse outcomes of the residual SYNTAX score (rSS) in patients with complex lesions treated with an everolimus-eluting stent (EES). METHODS AND RESULTS: One thousand eight hundred and fifty-one patients with small vessel (reference diameter <2.75 mm), long lesion (length >25 mm), or multivessel (>2 target vessels) disease who underwent percutaneous coronary intervention (PCI) with EES in the prospective SEEDS (A Registry To Evaluate Safety And Effectiveness Of Everolimus Drug Eluting Stent For Coronary Revascularization) trial were categorised into low (<6), mid (>6-<12) and high (>12) baseline SYNTAX score (bSS) groups, and into low (=0), mid (>0-<5) and high (>5) rSS groups. Mean bSS and rSS were 10.87±7.26 and 2.18±3.97, respectively; 64% of patients had complete revascularisation (rSS=0). At 12 months the primary outcome of ischaemia-driven target vessel failure (TVF, composite of cardiac death, target vessel myocardial infarction and ischaemia-driven target vessel revascularisation) was significantly higher in the high bSS and rSS groups than in the respective lower groups (p<0.01 for both). In multivariable analysis, rSS was an independent predictor of TVF (hazard ratio: 1.403, 95% confidence interval: 1.081 to 1.820, p=0.01). CONCLUSIONS: Twelve-month TVF was significantly higher in the highest rSS group; rSS with a cut-off of 5 might therefore allow the risk stratification of patients with complex lesions treated with a second-generation drug-eluting stent (Clinical-Trials.gov identifier: NCT 01157455).

Combination of Chinese Herbal Medicines and Conventional Treatment versus Conventional Treatment Alone in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention (5C Trial): An Open-Label Randomized Controlled, Multicenter Study.

Aims. To evaluate the efficacy of Chinese herbal medicines (CHMs) plus conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods and Results. Participants (n = 808) with ACS who underwent PCI from thirteen hospitals of mainland China were randomized into two groups: CHMs plus conventional treatment group (treatment group) or conventional treatment alone group (control group). All participants received conventional treatment, and participants in treatment group additionally received CHMs for six months. The primary endpoint was the composite of cardiac death, nonfatal recurrent MI, and ischemia-driven revascularization. Secondary endpoint was the composite of readmission for ACS, stroke, or congestive heart failure. The safety endpoint involved occurrence of major bleeding events. The incidence of primary endpoint was 2.7% in treatment group versus 6.2% in control group (HR, 0.43; 95% CI, 0.21 to 0.87; P = 0.015). The incidence of secondary endpoint was 3.5% in treatment group versus 8.7% in control group (HR, 0.39; 95% CI, 0.21 to 0.72; P = 0.002). No major bleeding events were observed in any participant. Conclusion. Treatment with CHMs plus conventional treatment further reduced the occurrence of cardiovascular events in patients with ACS after PCI without increasing risk of major bleeding.

Long-term outcome of native artery versus bypass graft intervention in prior coronary artery bypass graft patients with ST-segment elevation myocardial infarction.

BACKGROUND: Patients with prior coronary artery bypass graft (CABG) have a poor outcome after acute myocardial infarction (AMI). Little is known about the treatment strategy and outcome of percutaneous coronary intervention (PCI) in these patients. The purpose of this study was to investigate the impact of graft versus native artery PCI on the outcomes of prior CABG patients with AMI. METHODS: Between September 2005 and October 2011, a total of 140 consecutive patients with previous CABG undergoing PCI for the treatment of AMI were included. Clinical/procedural characteristics and long-term clinical outcomes were compared between graft and native artery PCI patients. RESULTS: The mean time interval to prior CABG was (5.6 ± 4.2) years. Thirty patients received graft PCI, success rate being 90%. One hundred and ten patients received native artery PCI, success rate being 90.7% (P > 0.05). There were no significant differences in the basic characteristics between the two groups. All patients received drug eluting stents (DESs). Three patients died during hospitalization in the graft-PCI group (10% vs. native PCI 0, P < 0.05). After a median follow- up of two years, major adverse cardiac events (MACE) (myocardial infarction, target vessel revascularization, total death) were 20% with no significant difference between the two groups. Cox regression analysis showed that both diabetes mellitus (DM, HR 3.57, 95%CI 1.03 - 5.75, P < 0.05) and primary PCI (HR 5.932, 95%CI 1.91 - 18.4, P < 0.05) were independent predictors of MACE. CONCLUSIONS: More patients with prior CABG underwent native artery PCI for AMI. PCI to culprit graft vessels had higher in-hospital mortality. DM and primary PCI, but not graft PCI, were predictors for adverse long-term outcome.

[Analysis of the clinical data of patients with acute coronary syndrome complicated by hemorrhage during hospitalization].

OBJECTIVE: To investigate the clinical characteristics of patients with acute coronary syndrome suffering hemorrhage during hospitalization. METHODS: The clinical symptoms, diagnostic and therapeutic characteristics and in-hospital outcome of 3807 inpatients who were recruited into SINO-GRACE study in China due to acute coronary syndrome from March, 2001 to December, 2007 were collected. Statistical methods were adopted to compare the differences in clinical data between hemorrhage group and non-hemorrhage group. RESULTS: Hemorrhage had happened in 57 out of 3807 inpatients with the incidence of 1.50%. Five patients, which accounted for 9.6% of the overall hemorrhage cases, were fatal hemorrhage. Nine patients were intracranial hemorrhage with the incidence of 0.24%. There were 155 deaths among the 3807 patients, with an overall mortality rate of 4.1%. The mortality of hemorrhage accounted for 3.2% in overall mortality. Patients with one of the following factors were more apt to hemorrhage: > 70 years old, previous hemorrhage history, renal failure history, heart failure history and clopidogrel and glycoprotein (GP) IIb/IIIa receptor antagonist administration for coronary artery bypass grafting. Patients who developed hemorrhage might need prolonged hospitalization and were liable to develop heart-related adverse events, including re-infarction and sustained ventricular tachycardia/fibrillation after they were admitted in hospital over 24 hours. CONCLUSION: Patients with acute coronary syndrome who underwent coronary artery bypass grafting, with advanced age, previous hemorrhage history, renal failure history, heart failure history or treated with clopidogrel and GP IIb/IIIa receptor antagonist are more vulnerable to hemorrhage.

[Effects of Maixuekang Capsule on the platelet aggregation rate and its long-term prognosis of patients with acute coronary syndrome under percutaneous coronary intervention].

OBJECTIVE: To study the changes of adenosine diphosphate (ADP)-induced platelet aggregation rate, and evaluate the effects of Maixuekang Capsule (MC) on the platelet aggregation rate, high-sensitive C-reactive protein (hs-CRP) and the long-term prognosis in patients with acute coronary syndrome under percutaneous coronary intervention (PCI). METHODS: Totally 236 inpatients with acute coronary syndrome under PCI, who successively received PCI from July 2008 to June 2010, were randomly assigned to the routine treatment group (RTT, 120 cases) and the MC treatment group (MKT, 116 cases). Besides routine medication, patients in the MKT group additionally took MC, 12 capsules daily for 12 successive months. The ADP-induced platelet aggregation rate and hs-CRP concentration were determined before PCI, 12 h and 30 days after PCI. In the meantime, the incidence of adverse cardio-/cerebrovascular events was recorded during the twelve-month clinical follow-up. Results Compared with before PCI, ADP-induced platelet aggregation rate and the serum hs-CRP concentration were significantly higher 12 h after PCI (P < 0.05). They were significantly reduced after 30-day treatment of MC, showing statistical difference when compared with those in the RTT group (P < 0.05). In the 12-month follow-up, the incidence of adverse cardio-/cerebrovascular events was significantly lower in the MKT group than in the RTT group (6.9% vs 12.5%, P < 0.01). CONCLUSIONS: ADP-induced platelet aggregation function was significantly elevated after PCI, which was a predictive factor of poor coronary events. MC improved the long-term prognosis of patients with acute coronary syndrome possibly through inhibiting the platelet aggregation rate and the hs-CRP concentration.

[Cause of in-hospital death among acute myocardial infarction patients undergoing primary percutaneous coronary intervention in Beijing].

OBJECTIVE: To analyze the cause of in-hospital death among acute myocardial infarction patients undergoing primary percutaneous coronary intervention (PPCI) in Beijing area to evoke better individualized preventive approach. METHODS: In-hospital mortality and causes were analyzed based on database from Beijing percutaneous coronary intervention registry study (BJPCI Registry) in 2010. RESULTS: A total of 4660 PPCI patients from 48 hospitals were included. In-hospital mortality was 2.4% (n = 110). Cardiogenic shock (39.1%, 43/110), mechanical complications (28.2%, 31/110) and intervention-related complications [28.2%, 31/110: procedure related (n = 28), drug related (n = 3)] were the leading causes of in-hospital death. Five deaths was attributed to comorbidity related reason (4.5%, 5/110). The in-hospital mortality had no significant difference among hospitals of different grade or total annual PCI (all P > 0.05). In-hospital mortality was slightly higher in hospital with annual PPCI < 300 than in hospitals with annual PPCI ≥ 300 (2.9% vs. 1.8%, P < 0.05). CONCLUSION: Cardiogenic shock, mechanical complications and intervention-related complications are the main causes of in-hospital death among acute myocardial infarction patients receiving PPCI.

Combined effect of atorvastatin and probucol on plasma cystatin C levels and severity of coronary lesion in patients with borderline coronary lesion.

BACKGROUND: The plasma cystatin C concentration (PcyC) has been demonstrated to have prognostic value in acute coronary syndrome, but the study of PcyC in patients with borderline coronary lesions is limited. Moreover, the effects of atorvastatin and probucol on PcyC and the severity of coronary lesions are unknown. This study was to evaluate the effects of the combination of atorvastatin and probucol on PcyC and severity of coronary lesion in patients with borderline coronary lesions. METHODS: One hundred and thirty consecutive patients with borderline coronary lesions (40% to 60% isolated single stenosis assessed by quantitative coronary angiography) were enrolled into the borderline coronary lesion (BCL) group, and one hundred and thirty-six subjects without coronary lesions comprised the controls (CTR). The subjects in the BCL group were randomized into routine treatment (RTT, n = 60), and combined treatment with atorvastatin 20 mg plus probucol 1.0 g daily added to routine medication (CBT, n = 70), both groups were treated for 6 months continuously. The levels of PcyC, high-sensitive C-reactive protein (hs-CRP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were determined. One hundred and four subjects in the BCL group were rechecked by coronary angiography. RESULTS: PcyC levels were significantly higher in the BCL group than in the CTR group; (2003.26 ± 825.73) ng/ml vs. (1897.83 ± 664.46) ng/ml (P < 0.01). Compared with patients in the RTT group, the levels of PcyC, TC, LDL-C, TG and hs-CRP were significantly lower in the CBT group (P < 0.05). Moreover, there was a trend towards a slight decrease in the RTT patients, (54.38 ± 10.67)% vs. (50.29 ± 9.89)% (P > 0.05), and a significant decrease in the CBT patients, (53.65 ± 9.48%) vs. (40.38 ± 12.93)% (P < 0.05), in the mean percent stenosis of borderline coronary lesions before and after six months of treatment. CONCLUSIONS: Cystatin C played an important role in the development of coronary artery disease, and was associated with the severity of coronary lesions. The combination of atorvastatin and probucol decreased PcyC levels, and could be the treatment of choice.

Coronary stenting versus bypass surgery in heart failure patients with preserved ejection fraction.

BACKGROUND: The optimal revascularization strategy in patients with heart failure with preserved ejection fraction (HFPEF) remains unclear. The aim of the present study was to compare the effects of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with HFPEF. METHODS: From July 2003 through September 2005, a total of 920 patients with coronary artery disease (CAD) and HFPEF (ejection fraction ≥ 50%) underwent PCI (n = 350) or CABG (n = 570). We compared the groups with respect to the primary outcome of mortality, and the secondary outcomes of main adverse cardiac and cerebral vascular events (MACCE), including death, myocardial infarction, stroke and repeat revascularization, at a median follow-up of 543 days. RESULTS: In-hospital mortality was significantly lower in the PCI group than in the CABG group (0.3% vs. 2.5%, adjusted P = 0.016). During follow-up, there was no significant difference in the two groups with regard to mortality rates (2.3% vs. 3.5%, adjusted P = 0.423). Patients receiving PCI had higher MACCE rates as compared with patients receiving CABG (13.4% vs. 4.0%, adjusted P < 0.001), mainly due to higher rate of repeat revascularization (adjusted P < 0.001). Independent predictors of mortality were age, New York Heart Association (NYHA) class and chronic total occlusion. CONCLUSION: Among patients with CAD and HFPEF, PCI was shown to be as good as CABG with respect to the mortality rate, although there was a higher rate of repeat revascularization in patients undergoing PCI.

[Analysis of the risk factors of patients with acute coronary syndrome suffering hemorrhage during hospitalization].

OBJECTIVE: To analyze the risk factors related to in-hospital bleeding for patients with acute coronary syndrome (ACS). METHODS: Clinical and therapeutic data of 3807 patients who were registered with acute coronary syndrome in SINO-GRACE in China from March 2001 to December 2007 were reviewed. A total of 57 patients were grouped to bleeding group and 234 out of the remaining 3750 patients without bleeding were randomly chosen and served as non-bleeding group. Hemorrhage-related factors were screened and compared between the two groups. Unitary logistic regression analysis was performed to detect the possible factors related to hemorrhage. Factors with P < 0.1 were further analyzed by stepwise regression method and multivariate conditional logistic regression analyses. RESULTS: (1) Age, history of coronary artery bypass graft (CABG), previous hemorrhage, renal failure and heart failure as well incidence of acute coronary syndrome were significantly higher in bleeding group than in non-bleeding group (all P ≤ 0.05). Patients were more often treated with clopidogrel and glycoprotein (GP) IIb/IIIa receptor antagonist in bleeding group than in non-bleeding group. (2) Single factor logistic regression analysis showed that age > 70 years, history of previous bleeding, renal failure, heart failure, clopidogrel and GP IIb/IIIa receptor antagonists use, non-ST-segment elevation myocardial infarction, inferior wall, lateral myocardial infarction, CABG were risk factors for bleeding (all P < 0.05). (3) Multivariate logistic regression analysis showed that history of renal failure (OR = 19.77, 95%CI 4.38 - 89.18, P < 0.01) and clopidogrel (OR = 19.77, 95%CI 4.38 - 89.18, P < 0.01) and GPIIb/IIIa receptor antagonist (OR = 343.57, 95%CI 40.39 - 999.99, P < 0.01) use were the independent risk factors for bleeding. CONCLUSION: Our results show that renal failure history and clopidogrel and GPIIb/IIIa receptor antagonist use are independent risk factors for in-hospital bleeding in patients with acute coronary syndrome.

The union of anti-CD34 antibody can improve the performance of drug-eluting stents.

OBJECTIVES: The authors investigate whether the combination of anti-CD34 antibody with DES is win-win cooperation. BACKGROUND: DES may reduce the risk of restenosis compared to bare-metal stents (BMS), but they were found to inhibit the healing process of intima. METHODS: Fifteen BMS, 17 DES, and 16 combined anti-CD34 antibody and DES were randomly implanted in the coronary arteries of 22 minipigs. Ten minipigs were followed up to 2 weeks. The stenting coronary segments were examined by histological examination and scanning electron microscopy after in vivo coronary angiography and intracoronary optical coherence tomography (OCT) examinations. The other 12 minipigs were followed up to 3 months. Coronary angiography and intracoronary OCT examination were performed in vivo and histological examination was performed on the stenting coronary segments. RESULTS: After 2 weeks, the neointimal covering level of the DES was lower than that in BMS, but the covering level of the combined stents was even better than the BMS. After 3 months, neointimal hyperplasia was significant in the BMS, but not in the other two types of stents. The in-stent late lumen loss of the combined stents even showed a decreasing tendency when compared with the DES. CONCLUSION: The combination of anti-CD34 antibody and DES can not only well offset the short-term inhibitory effect on re-endothelialization but also slightly enhance the long-term antiproliferative effect.

Ultrasonic destruction of albumin microbubbles enhances gene transfection and expression in cardiac myocytes.

BACKGROUND: It has been proven that ultrasonic destruction of microbubbles can enhance gene transfection efficiency into the noncardiac cells, but there are few reports about cardiac myocytes. Moreover, the exact mechanisms are not yet clear; whether the characteristic of microbubbles can affect the gene transfection efficiency or not is still controversial. This study was designed to investigate whether the ultrasound destruction of gene-loaded microbubbles could enhance the plasmids carried reporter gene transfection in primary cultured myocardial cell, and evaluate the effects of microbubbles characteristics on the transgene expression in cardiac myocytes. METHODS: The ß-galactosidase plasmids attached to the two types of microbubbles, air-contained sonicated dextrose albumin (ASDA) and perfluoropropane-exposed sonicated dextrose albumin (PESDA) were prepared. The gene transfection into cardiac myocytes was performed in vitro by naked plasmids, ultrasound exposure, ultrasonic destruction of gene-loaded microbubbles and calcium phosphate precipitation, and then the gene expression and cell viability were analyzed. RESULTS: The ultrasonic destruction of gene-loaded microbubbles enhanced gene expression in cardiac myocytes compared with naked plasmid transfection ((51.95 ± 2.41) U/g or (29.28 ± 3.65) U/g vs. (0.84 ± 0.21) U/g, P < 0.01), and ultrasonic destruction PESDA resulted in more significant gene expression than ASDA ((51.95 ± 2.41) U/g vs. (29.28 ± 3.65) U/g, P < 0.05). Ultrasonic destruction of microbubbles during calcium phosphate precipitation gene transfection enhanced ß-galactosidase activity nearly 8-fold compared with calcium phosphate precipitation gene transfection alone ((111.35 ± 11.21) U/g protein vs. (14.13 ± 2.58) U/g protein, P < 0.01). Even 6 hours after calcium phosphate precipitation gene transfection, ultrasound-mediated microbubbles destruction resulted in more intense gene expression ((35.63 ± 7.65) U/g vs. (14.13 ± 2.58) U/g, P < 0.05). CONCLUSIONS: Ultrasonic destruction of microbubbles might be a promising method for the delivery of non-viral DNA into cardiac myocytes, and the gene tranfection is related to the characteristics of microbubbles.

Comparision of high sensitivity C-reactive protein and matrix metalloproteinase 9 in patients with unstable angina between with and without significant coronary artery plaques.

BACKGROUND: Inflammation within vulnerable coronary plaques may cause unstable angina by promoting rupture and erosion. C-reactive protein (CRP) is the most reliable and accessible test method for clinical use for identifying coronary artery disease event. Matrix metalloproteinase 9 (MMP-9) is highly over-expressed in the vulnerable regions of a plaque. Our aim was to evaluate the plasma levels of MMP-9 and hsCRP in subjects with both unstable angina and coronary plaques, as well as in those with unstable angina without coronary plaques. METHODS: Patients with newly diagnosed unstable angina pectoris from clinical presentation and ECG, who were undergoing coronary angiography from April 2007 to April 2009, were included in this study. A total of 170 subjects were enrolled in the study. Before angiography, the baseline clinical data (mainly including conventional risk factors) was collected. These patients were divided into two groups, a non-plaque group (G1) which included 55 patients with no significant stenosis or less than 20% stenosis in at least one of the major coronary artery branches, and a plaque group (G2) which included 115 patients with at least one of the major coronary artery branches unstable angina pectoris with at least 50% stenosis of one major coronary artery. The patients presenting with calcified nodules of a major coronary artery were excluded from this study. We examined the serum levels of MMP-9 for all cases by multi-effect enzyme-linked immunosorbent assay. RESULTS: There was a significant difference in the serum levels of MMP-9 between the two groups (P < 0.001). The percentage of patients with hypertension, diabetes and current smokers were significantly different between the two groups (P = 0.034, P = 0.031, and P = 0.044 respectively). The univariate Logistic regression analyses of risk factors showed that smoking was the main risk factor for angina in the non-plaque group with the OR being 1.95 (95%CI 1.02 - 3.75). Hypertension, diabetes mellitus were negatively related with the occurrence of angina in the non-plaque group with the ORs being 0.50, and 0.36, respectively (95%CI 0.26 - 0.96 and 0.14 - 0.94). The MMP-9 level was negatively related to the occurrence of angina in the non-plaque group with an OR of 0.59 (95%CI 0.47 - 0.81). CONCLUSIONS: There is a significantly difference in MMP-9 levels between the plaque and non-plaque groups. Current smoking has a significant influence on unstable angina patients without documented plaques. The serum MMP-9 level may be a significant biomarker which can help differentiate patients with unstable angina with plaques from those with unstable angina but without plaques.

[Evaluation on the relationship between pregnancy associated plasma protein-a and intravascular ultrasound detected culprit coronary plaque morphology in patients with unstable angina].

OBJECTIVE: To assess the relationship between pregnancy associated plasma protein-A (PAPP-A) and culprit coronary plaque morphology in patients with unstable angina (UA). METHODS: Sixty-eight UA patients undergoing diagnostic coronary angiography and intravascular ultrasound were included in this study. A sandwich enzyme-linked immunosorbent assay technique was used to assay the circulating PAPP-A. Plaque characteristics of culprit lesion were analyzed for UA patients with various PAPP-A levels. RESULTS: PAPP-A level was significantly higher in high-risk UA than in non-high-risk UA [(19.9 ± 20.1) mIU/L vs. (6.9 ± 5.7) mIU/L, P = 0.002]. Optimal threshold of PAPP-A to predict high-risk UA was determined as 11.0 mIU/L with a sensitivity of 78.6% and a specificity of 77.5%. Patients with higher PAPP-A level (≥ 11.0 mIU/L) was associated with larger external elastic membrane cross-sectional area, plaque area and more plaque burden compared with patients with lower PAPP-A level (all P < 0.01). Positive remodeling, attenuated plaque and plaque rupture were significantly more often in patients with higher PAPP-A than in patients with lower PAPP-A level (all P < 0.01). PAPP-A ≥ 11.0 mIU/L (OR = 5.921, P = 0.014) and attenuated plaque (OR = 7.541, P = 0.038) were independent risk predictors for high-risk UA. CONCLUSIONS: PAPP-A was associated with instability of culprit plaque in UA patients. PAPP-A ≥ 11.0 mIU/L and attenuated plaque were independent predictors for high-risk UA.

Successful treatment with biventricular pacing in a patient with hypertrophic obstructive cardiomyopathy.

We report the effects of biventricular pacing in a patient with hypertrophic obstructive cardiomyopathy (HOCM) refractory to medical therapy. A 58-year-old man with HOCM had suffered from dyspnea, chest pain and palpitation for 5 years. Cardiac catheterization showed a left ventricular outflow tract (LVOT) gradient of 80 mmHg. He refused septal myomectomy and the septal ablation was not available. Based on intraoperative pressure measurements, he was implanted with biventricular pacing and LVOT gradient decreased to 10 mmHg. During the follow-up period of 6 months, the patient's symptoms were markedly improved. Biventricular pacing may be an alternative therapy for patients with HOCM.

Comparison of drug eluting stent implantation with coronary artery bypass surgery in the treatment of patients with chronic total occlusion and multiple vessel disease.

BACKGROUND: In patients with chronic total occlusion (CTO) and multivessel coronary artery disease, the comparison of surgical and the percutaneous revascularization strategies has rarely been conducted. The aim of this study was to compare long term clinical outcomes of drug eluting stent (DES) implantation with coronary artery bypass surgery (CABG) in the patients with CTO and multivessel disease. METHODS: From a prospective registry of 6000 patients in our institution, we included patients with CTO and multivessel coronary artery disease who underwent either CABG (n = 679) or DES (n = 267) treatment. Their propensity risk score was used for adjusting baseline differences. RESULTS: At a median follow-up of three years, propensity score adjusted Cox regression analysis showed that the rate of major adverse cardiac cerebrovascular events (MACCE) was lower in CABG group (12.7% vs. 24.3%, hazard ratio (HR) 1.969, 95%CI 1.219 - 3.179, P = 0.006) mainly due to lower rate of target vessel revascularization in CABG group than in DES group (3.1% vs. 17.2%, HR 16.14, 95%CI 5.739 - 45.391, P < 0.001). The incidence of cardiac death or myocardial infarction (composite end point) was not significantly different between these two groups. On multivariate analysis, the significant predictors of MACCE were only the type of revascularization. Age, left ventricular ejection fraction (LVEF), and complete revascularization were identified as significant predictors of composite end points. CONCLUSIONS: Our study shows that in patients with CTO and multivessel coronary disease, DES can offer comparable long term outcomes in cardiac death and myocardial infraction free survival in comparison with CABG. However, there is an increased rate of MACCE which results from more repeat revascularizations. Obtaining a complete revascularization is crucial for decreasing adverse cardiac events.

Syntax score predicts clinical outcome in patients with three-vessel coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: The Syntax score was recently developed as a comprehensive, angiographic tool grading the complexity of coronary artery disease (CAD). It aims to assist in patient selection and risk stratification of patients with extensive CAD undergoing revascularization. However, the prognostic value of the Syntax score in patients undergoing percutaneous coronary intervention (PCI) has not been validated. The aim of this study was to evaluate its role in predicting long-term incidences of major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing PCI for 3-vessel disease. METHODS: Two hundred and three consecutive patients with de novo 3-vessel CAD undergoing PCI with sirolimus-eluting stents were studied. Their angiograms were scored according to the Syntax score. The patients were divided into tertiles according to the Syntax score: lowest Syntax score tertile (Syntax score ≤ 22), intermediate Syntax score tertile (Syntax score of 23 to 32), and the highest Syntax score tertile (Syntax score ≥ 33). During the 1-year follow-up, the MACCE-free survival curves were estimated by the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the relation between the Syntax score and the incidence of MACCE. Performance of the Syntax score was studied with respect to predicting the rate of MACCE by receiver operator characteristic (ROC) curves with an area under the curve. RESULTS: The overall Syntax score ranged from 6 to 66 with mean ± standard deviation of 27.9 ± 12.6 and a median of 26. At 1 year, the Syntax score significantly predicted the risk of MACCE (HR 1.07/U increase, 95%CI 1.04 to 1.11, P < 0.001). The rate of MACCE was significantly increased among patients in the highest Syntax score tertile (17.9%) as compared with those with the lowest Syntax score tertile (1.4%, P < 0.001) or intermediate Syntax score tertile (6.2%, P = 0.041). After the adjustment for all potential confounders, the Syntax score remained a significant predictor of the rate of MACCE (adjusted HR 1.12/U increase, 95%CI 1.05 to 1.20, P < 0.001). The Syntax score accurately predicted MACCE with an area under the receiver operator curve of 0.77 (95%CI 0.65 to 0.90, P < 0.001). A Syntax score of 29.5 was identified as the optimal cutoff to predict MACCE with a sensitivity of 82.4% and specificity of 65.6%. CONCLUSION: The Syntax score predicts the risk of MACCE in patients with 3-vessel disease undergoing PCI.