The efficacy of the figure-of-eight suture technique in the treatment of tunnel bleeding of the femoral artery route after percutaneous coronary intervention or angiography.

OBJECTIVE: To evaluate the efficacy of the figure-of-eight (FOE) suture technique in the treatment of tunnel bleeding after femoral artery puncture compared with manual compression (MC). METHODS: This prospective, randomized, controlled study enrolled patients that had received transfemoral coronary artery angiography or percutaneous coronary intervention and then developed tunnel bleeding. They were randomly assigned into two groups: FOE suture group (ES group) and manual compression group (MC group). Total treatment time, performance frequency, performance time, rate of deep vein thrombosis (DVT) and in-hospital time after the procedure were compared. RESULTS: A total of 152 patients were enrolled in the study (ES group, n = 63; MC group, n = 89). Compared with the MC group, the total treatment time (mean ± SD: ES 22.3 ± 5.4 h versus MC 26.8 ± 6.8 h), performance frequency (mean ± SD: ES 2.1 ± 0.7 versus MC 2.6 ± 1.1), performance time (mean ± SD: ES 8.9 ± 2.5 min versus MC 12.3 ± 4.1 min), in-hospital time after the procedure (mean ± SD: ES 3.5 ± 1.2 days versus MC 4.8 ± 2.1 days) and DVT rate (ES 0.0% versus MC 6.7%) were significantly lower in the ES group. CONCLUSION: The FOE suture technique effectively treated tunnel bleeding after femoral artery puncture.

Interaction between platelet-derived microRNAs and CYP2C19*2 genotype on clopidogrel antiplatelet responsiveness in patients with ACS.

BACKGROUND: Both platelet-derived microRNAs and the genotype of CYP2C19*2 were implicated for the variability of clopidogrel antiplatelet responsiveness. However, their interaction on the antiplatelet responsiveness of clopidogrel in patients with acute coronary syndrome (ACS) remains unknown. METHODS: Consecutive clopidogrel-treated patients with ACS were recruited, with their antiplatelet responsiveness evaluated by the relative platelet inhibition (RI), as measured by light transmittance aggregometry (LTA) at baseline and 5days' after the maintenance treatment of clopidogrel. Extreme cases were selected according to the octiles of RI value. Expression of the microRNAs targeting the mRNAs of P2RY12 was analyzed in the platelet of the extreme cases. Genotyping of CYP2C19*2 was performed for each extreme case. RESULTS: Among the included 272 ACS patients, 21 cases were screened as the extremely high-responders with RI>84%, and 18 as the extremely low-responders with RI<10%. Bioinformatics tools predicted the candidate microRNAs of miR-223, miR-221, and miR-21 could bind directly to the mRNA of P2RY12. Compared with the extremely low-responders, the expression of miR-223, miR-221, and miR-21 was significantly higher in the extremely high-responders (miR-223: 7.18±2.95 vs. 0.99±0.64, p=0.022; miR-221: 3.60±2.54 vs. 1.14±0.81, p=0.004; miR-21: 4.36±3.33 vs. 2.31±1.69, p=0.01). ROC curve showed ideal discriminatory power of the platelet-derived miRNAs for the prediction of clopidogrel antiplatelet responsiveness (c-index=0.70 for miR-223; c-index=0.76 for miR-221; c-index=0.79 for miR-21). After stratified by the carrier status of CYP2C19*2, the association between platelet-derived miRNAs and clopidogrel antiplatelet responsiveness could be found only in CYP2C19*2 carriers, but not in non-carriers. CONCLUSIONS: Platelet-derived miRNAs (miR-223, miR-221 and miR-21) are independently associated with clopidogrel antiplatelet responsiveness in ACS patients. However, the association could be influenced by the interaction with CYP2C19*2 genotype.

Hypotensive effects of renal denervation in spontaneously hypertensive rat based on ultrasonic contrast imaging.

BACKGROUND: Sympathetic nerves-fire rate is generally enhanced in some types of hypertension models. Renal sympathetic denervation(RSD) by the radiofrequency ablation was used to treat the hypertension has achieved curative effect.HTN-1 and HTN-2 trial reported catheter-based renal denervation may cause substantial and sustained blood-pressure reduction in patients with resistant hypertension. However, recent controlled HTN-3 trial questioned the BP lowering effect of Renal denervation treatment. The controversial results maybe arised from the incompleted RSD which implemented inside the renal artery. Now renal denervation therapy for resistant hypertension is in attractive and controversial status. Our aim is to define the hyotensive value of complete renal denervation in adult spontaneous hypertensive rats. METHODS: Male spontaneous hypertensive rats(SHR) aged 12 weeks were randomly selected for either unilateral renal artery sympathetic nerves ablation (URSNA), or conventional technique of renal denervation (CRD), or bilateral renal artery sympathetic nerves ablation (BRSNA) and sham operation. Blood pressure, sodium and water balance,serum reninangiotensin II and Norepinephrine concentration were measured during 20 weeks after renal denervation operation. Internal diameters of renal arteries and renal blood flow rate was tested by ultrasonic contrast imaging. RESULTS: The continued increased blood pressure in SHR was delayed and significantly reduced by conventional renal denervation over a period of 8 weeks. Both the bilateral and unilateral renal sympathetic nerve ablation procedure did not prevent the development of hypertension in SHR. The attenuation of hypertension was accompanied with the increase of urinary sodium excretion and depression of rennin angiotensin system (RAS). CONCLUSIONS: We concluded that renal denervation may not be an effective therapeutic method in the long-term control of hypertension in adult SHR.

Additional manual thrombus aspiration for ST-segment elevation myocardial infarction during percutaneous coronary intervention: an updated meta-analysis.

BACKGROUND: The clinical efficacy and safety of adjunctive thrombus aspiration (TA) in patients with ST-segment elevation myocardial infarction (STEMI) during percutaneous coronary intervention (PCI) remain controversial. METHODS: Twenty five eligible randomized controlled trials were included to compare the use of thrombus aspiration (TA) with PCI and PCI-only for STEMI. The primary endpoint was all-cause mortality and death. The secondary endpoints were major adverse cardiac events (MACE), recurrent infarction (RI), target vessel revascularization (TVR), stent thrombosis (ST), perfusion surrogate markers and stroke. RESULTS: TIMI flow grade 3 and MBG 2-3 were significantly increased in the TA plus PCI arm compared with the PCI-only arm [relative risk (RR): 1.05, 95% confidence intervals (CI): 1.02-1.09, P = 0.004] and (RR: 1.68, 95% CI: 1.40-2.00, P < 0.001), respectively. There were no significant differences in all-cause mortality, MACEs, TVR and ST rates between the two groups. The RI rate was lower in the TA plus PCI arm than that in the PCI-only arm with short-term follow-up duration (RR: 0.60, 95% CI: 0.38-0.96, P = 0.03), but there was no significant difference in RI incidence over the medium- or long-term follow-up periods (RR: 1.00, 95% CI: 0.77-1.29, P = 0.98), and (RR: 0.96, 95% CI: 0.81-1.15, P = 0.69), respectively. There were statistically significant differences in the rates of crude stroke and stroke over the medium- or long-term follow-up periods and the crude stroke rate in the TA plus PCI (RR: 1.60, 95% CI: 1.08-2.38, P = 0.02) and (RR: 1.43, 95% CI: 1.03-1.98, P = 0.03), respectively; this was not observed between the two arms during the short-term follow-up period (RR: 1.47, 95% CI: 0.97-2.21, P = 0.07). CONCLUSIONS: Routine TA-assisted PCI in STEMI patients can improve myocardial reperfusion and get limited benefits related to the clinical endpoints, which may be associated with stroke risk.

Electrophysiological Characteristics of the LQT2 Syndrome Mutation KCNH2-G572S and Regulation by Accessory Protein KCNE2.

Mutations in hERG cause long QT syndrome type 2 which is characterized by a prolonged QT interval on electrocardiogram and predisposition to life-threatening ventricular tachyarrhythmia, syncope, and sudden death. hERG-G572S induces trafficking defects of hERG channel protein from Golgi to the plasma membrane and results in a dominant negative suppression of hERG current density. As an accessory ß subunit, KCNE2 promotes hERG migration from Golgi to cellular membrane. In this study, we investigated the rescue effect of KCNE2 in a G572S mutation of hERG. Transfection was performed into HEK293 cells. Patch clamp technique, western blotting analyses and confocal microscopic examination were used. Results showed that KCNE2 had a significantly enhanced effect on G572S mutation current. The increase of current was largest at KCNH2:KCNE2 of 1:3. Confocal images showed co-expressing G572S and KCNE2 could cause a substantial up-regulated membrane protein (155 kDa) expression. Expression of membrane protein accumulated markedly with increasing ratio of KCNH2:KCNE2. G572S defective mutant could be restored by both KCNE2 and lower temperature (27°C), which suggested that the lower temperature could be the favorable circumstances for the rescue function of KCNE2. In this study, we successfully set up "the action potential" on the HEK 293 cells by genetically engineered to express Kir2.1, Nav1.5, and Kv11.1, wherein on reaching over an excitation threshold by current injection. The results suggested that KCNE2 could shorten action potential duration which was prolonged by G572S. These findings described electrophysiological characteristics of the LQT2 syndrome mutation KCNH2-G572S and regulation by accessory protein KCNE2, and provided a clue about LQT2 and relative rescue mechanism.

Effects of sleep deprivation on action potential and transient outward potassium current in ventricular myocytes in rats.

BACKGROUND: Sleep deprivation contributes to the development and recurrence of ventricular arrhythmias. However, the electrophysiological changes in ventricular myocytes in sleep deprivation are still unknown. MATERIAL AND METHODS: Sleep deprivation was induced by modified multiple platform technique. Fifty rats were assigned to control and sleep deprivation 1, 3, 5, and 7 days groups, and single ventricular myocytes were enzymatically dissociated from rat hearts. Action potential duration (APD) and transient outward current (Ito) were recorded using whole-cell patch clamp technique. RESULTS: Compared with the control group, the phases of APD of ventricular myocytes in 3, 5, and 7 days groups were prolonged and APD at 20% and 50% level of repolarization (APD20 and APD50) was significantly elongated (The APD20 values of control, 1, 3, 5, and 7 days groups: 5.66±0.16 ms, 5.77±0.20 ms, 8.28±0.30 ms, 11.56±0.32 ms, 13.24±0.56 ms. The APD50 values: 50.66±2.16 ms, 52.77±3.20 ms, 65.28±5.30 ms, 83.56±7.32 ms, 89.24±5.56 ms. P<0.01, n=18). The current densities of Ito significantly decreased. The current density-voltage (I-V) curve of Ito was vitally suppressed downward. The steady-state inactivation curve and steady-state activation curve of Ito were shifted to left and right, respectively, in sleep deprivation rats. The inactivation recovery time of Ito was markedly retarded and the time of closed-state inactivation was markedly accelerated in 3, 5, and 7 days groups. CONCLUSIONS: APD of ventricular myocytes in sleep deprivation rats was significantly prolonged, which could be attributed to decreased activation and accelerated inactivation of Ito.

Novel completed biodegradable polymer sirolimus-eluting stent versus durable polymer sirolimus-eluting stent in de novo lesions: nine-month angiographic and three-year clinical outcomes of HOPE trial.

BACKGROUND: Drug-eluting stents (DES) with durable polymer have significantly reduced restenosis and target vessel revascularization compared with bare metal stents. Durable polymer has been linked with persistent inflammation of vessel wall and delayed endothelial healing that may increase the risk of late and very late stent thrombosis. This study sought to evaluate the efficacy and safety of HELIOS completed biodegradable polymer sirolimus-eluting stent (SES) in de novo coronary lesions. METHODS: Totally, 287 patients with one or two de novo coronary lesions (lesion length ≤ 38 mm and reference vessel diameter 2.5-4.0 mm) were enrolled in the HOPE study, a prospective, multicenter, randomized, non-inferiority trial. Patients were randomized to treatment either with HELIOS completed biodegradable polymer SES (n = 142) or PARTNER durable polymer SES (n = 145). The primary endpoint was angiographic in-stent late lumen loss (LLL) at 9-month follow-up. The secondary endpoint included stent thrombosis and major adverse cardiac events including cardiac death, myocardial infarction (MI) and target lesion revascularization (TLR). RESULTS: The 9-month in-stent LLL in the HELIOS group was similar to the PARTNER group, (0.16 ± 0.22) mm vs. (0.19 ± 0.30) mm (P = 0.28). The difference and 95% confidence interval were -0.03 (-0.09, 0.04), and the P value for non-inferiority <0.01. Major adverse cardiovascular event (MACE) occurred in 7.9% vs. 8.2%, MI in 2.4% vs. 3.0%, TLR in 5.5% vs. 3.0%, and stent thrombosis in 0 vs. 1.5%; and events were comparable between the HELIOS group and PARTNER group at three-year follow-up (all P > 0.05). The three-year cardiac death was lower in the HELIOS group, but with no significant difference, 0 vs. 3.0% (P = 0.12). CONCLUSIONS: In the HOPE trial, the novel completed biodegradable polymer SES HELIOS was non-inferior to the durable polymer SES PARTNER with respect to nine-month in-stent LLL in de novo coronary lesions. The incidence of other clinical endpoints was low for both of the stents in three-year follow-up.

Systematic study of the effects of lowering low-density lipoprotein-cholesterol on regression of coronary atherosclerotic plaques using intravascular ultrasound.

BACKGROUND: Conflicting results currently exist on the effects of LDL-C levels and statins therapy on coronary atherosclerotic plaque, and the target level of LDL-C resulting in the regression of the coronary atherosclerotic plaques has not been settled. METHODS: PubMed, EMBASE, and Cochrane databases were searched from Jan. 2000 to Jan. 2014 for randomized controlled or blinded end-points trials assessing the effects of LDL-C lowering therapy on regression of coronary atherosclerotic plaque (CAP) in patients with coronary heart disease by intravascular ultrasound. Data concerning the study design, patient characteristics, and outcomes were extracted. The significance of plaques regression was assessed by computing standardized mean difference (SMD) of the volume of CAP between the baseline and follow-up. SMD were calculated using fixed or random effects models. RESULTS: Twenty trials including 5910 patients with coronary heart disease were identified. Mean lowering LDL-C by 45.4% and to level 66.8 mg/dL in the group of patients with baseline mean LDL-C 123.7 mg/dL, mean lowering LDL-C by 48.8% and to level 60.6 mg/dL in the group of patients with baseline mean LDL-C 120 mg/dL, and mean lowering LDL-C by 40.4% and to level 77.8 mg/dL in the group of patients with baseline mean LDL-C 132.4 mg/dL could significantly reduce the volume of CAP at follow up (SMD -0.108 mm3, 95% CI -0.176 ~ -0.040, p = 0.002; SMD -0.156 mm3, 95% CI -0.235 ~ -0.078, p = 0.000; SMD -0.123 mm3, 95% CI -0.199 ~ -0.048, p = 0.001; respectively). LDL-C lowering by rosuvastatin (mean 33 mg daily) and atorvastatin (mean 60 mg daily) could significantly decrease the volumes of CAP at follow up (SMD -0.162 mm3, 95% CI: -0.234 ~ -0.081, p = 0.000; SMD -0.101, 95% CI: -0.184 ~ -0.019, p = 0.016; respectively). The mean duration of follow up was from 17 ~ 21 months. CONCLUSIONS: Intensive lowering LDL-C (rosuvastatin mean 33 mg daily and atorvastatin mean 60 mg daily) with >17 months of duration could lead to the regression of CAP, LDL-C level should be reduced by >40% or to a target level <78 mg/dL for regressing CAP.

PON1 Q192R genotype influences clopidogrel responsiveness by relative platelet inhibition instead of on-treatment platelet reactivity.

BACKGROUND: paraoxonase-1 (PON1) was recently identified as the crucial enzyme for clopidogrel bioactivation, with PON1 Q192R (rs662) polymorphism determining the clopidogel antiplatelet efficacy. However, subsequent studies showed controversies over the findings. This study aimed to evaluate the impact of PON1 Q192R in parallel to that of CYP2C19*2 (rs4244285) on clopidogrel responsiveness in a cohort of Chinese patients with unstable angina pectoris. MATERIAL AND METHODS: One hundred and eighty Chinese-Han patients diagnosed with unstable angina pectoris and treated with clopidogrel were consecutively recruited. Clopidogrel responsiveness, measured by relative platelet inhibition {RI=[(pretreatment aggregation-posttreatment aggregation at 5days)/(pretreatment aggregation)] x100%}, was assessed in relation to PON1 Q192R and CYP2C19*2 genotypes. RI values were stratified into four quartiles, with patients in quartile 1 defined as individuals of clopidogrel non-responsiveness. The contributions of PON1 Q192R and CYP2C19*2 to on-treatment platelet reactivity (OTPR) at 5days maintenance dose of clopidogrel were also evaluated. RESULTS: For PON1 Q192R genotypes, RI values were significantly lower in patients with QR and RR alleles than in patients with QQ alleles (p=0.01). OTPR values at 5days maintenance dose of clopidogrel were similar across all the PON1 Q192R genotypes (p=0.41). PON1 192 QR and RR conferred increased risks for clopidogrel non-responsiveness [OR 3.64; 95% CI (1.21-10.92), p=0.02]. For CYP2C19*2 genotypes, compared to CYP2C19*1/*1 wild type carriers, CYP2C19*2 carriers showed a significantly higher OTPR (p=0.009), and a trend for lower RI values (p=0.06). An increased risk for clopidogrel non-responsiveness was found in patients with CYP2C19*2 genotype [OR 2.02; 95% CI (1.03-3.96), p=0.04]. CONCLUSIONS: Both PON1 Q192R and CYP2C19*2 genotypes influence clopidogrel responsiveness, with the impact of PON1 Q192R mainly on relative platelet inhibition instead of OTPR of clopidogrel.

Influence of CYP2C9 and VKORC1 genotypes on the risk of hemorrhagic complications in warfarin-treated patients: a systematic review and meta-analysis.

BACKGROUND: The main challenge for warfarin anticoagulation is the risk for hemorrhagic complications. Although certain pharmacogenetic factors may explain the individual variabilities about the therapeutic warfarin dose requirement, the genetic factors to warfarin hemorrhagic complications due to over-anticoagulation are largely unknown. To interpret the potential role of warfarin-related genotypes on over-anticoagulation and hemorrhagic complications, we conducted a meta-analysis based on 22 published studies. METHODS: A comprehensive search was applied to the reports on over-anticoagulation and hemorrhagic complications published prior to December 31, 2012 in PubMed and EMBASE. References were identified by strict inclusion and exclusion criteria, with additional information obtained by consulting with the authors of primary studies. The roles of genotypes in CYP2C9 and VKORC1 on over-anticoagulation (INR > 4) and hemorrhagic complications were analyzed by Revman 5.0.2 software. RESULTS: A total of 6272 patients in 22 reports were included in the meta-analysis, including studies of 18 from Caucasians (3 from both Caucasian and African-American), 3 from Asians, and 1 from Brazilians. Compared to CYP2C9 wild genotype (CYP2C9*1), both CYP2C9*2 (rs 1799853, c. 430 C > T, p. Arg144Cys) and *3 (rs 1057910, c. 1075 A >C, p. Ile359Leu) confer significantly higher risk for warfarin over-anticoagulation and hemorrhagic complications. After stratification by CYP2C9 allele status, significantly higher risk for hemorrhagic complications was found only in carriers of at least 1 copy of CYP2C9*3 [For total hemorrhages: *1/*3 HR: 2.05 (1.36-3.10), p < 0.001; *3/*3 HR: 4.87 (1.38-17.14), p = 0.01; For major hemorrhages: *1/*3 HR: 2.43 (1.17-5.06), p = 0.02; *3/*3 HR: 4.81 (0.95-24.22), p = 0.06]. Furthermore, similar susceptibility of total hemorrhage by CYP2C9 genotypes was observed in Caucasians and Asians. After stratification by the occurrence time, both CYP2C9*2 and *3 are risk factors for over-anticoagulation within 30 days of warfarin treatment [*2 HR: 1.64 (1.11-2.43), p = 0.01; *3 HR: 2.48 (1.56-3.96), p < 0.001], and only CYP2C9*3 showed higher risk for over-anticoagulation after 30 days [HR: 1.86 (1.08-3.20), P = 0.03]. For VKORC1 c. -1639G > A (rs 9923231) genotypes, GA and AA contributed significantly higher risk for over-anticoagulation within 30 days [HR: 2.14 (1.75-2.62), p < 0.001], but not for over-anticoagulation after 30 days [HR:0.78 (0.46-1.33), p = 0.36]. No significant association was found between VKORC1 genotypes and hemorrhagic complications. CONCLUSIONS: Both CYP2C9 and VKORC1 genotypes are associated with an increased risk for warfarin over-anticoagulation, with VKORC1 c. -1639G > A more sensitive early in the course of anticoagulation. CYP2C9*3 is the main genetic risk factor for warfarin hemorrhagic complications.

Genetic determinants of high on-treatment platelet reactivity in clopidogrel treated Chinese patients.

INTRODUCTION: Cytochrome P450 (CYP), ATP-binding cassette transporters (ABCB1), and paraoxonase-1 (PON1) play crucial roles in clopidogel absorption and bioactivation. Genetic polymorphisms in these genes have been associated with the variability of the response to clopidogrel, however their contribution to high on-treatment platelet reactivity (HPR) in clopidogrel treated Chinese patients is less known. MATERIALS AND METHODS: Five-hundred Chinese-Han patients treated with clopidogrel for acute coronary syndrome (ACS) were consecutively recruited from the Department of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army, from September 2010 to September 2012. We assessed the relations of CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*17 (rs12248560), PON1Q129R (rs662) and ABCB1C3435T (rs1045642) to the platelet aggregation after 5 days maintenance dose of clopidogrel administration, and the risk for HPR. The cutoff of HPR was defined as 20 µmol/L adenosine diphosphate (ADP)-induced platelet aggregation>50%. RESULTS: Both CYP2C19*2 and *3 alleles were significantly associated with higher platelet aggregation after 5 days maintenance dose of clopidogrel administration (P<0.00001 and P=0.042, respectively). The platelet aggregation in carriers of at least one CYP2C19 loss-of-function allele (*2 or *3, accounted for 58% of the study population) was obviously higher than that in non-carriers (P<0.00001). Patients with the CYP2C19*2 allele had a higher risk of HPR than those with the CYP2C19 wild-type genotype [adjusted hazard ratio (HR), 1.56; 95% confidence interval(CI), 1.04-2.33, P=0.03]. The carriers of at least one CYP2C19 loss-of-function allele could also predict significantly greater risk of HPR compared with non-carriers (adjusted HR1.79,95% CI: 1.33-2.4,P=0.003). However, the carriage of CYP2C19*3 alone could not predict the risk of HPR significantly (adjusted HR, 1.5; 95% CI: 0.83-3, P=0.16). Significant relation of CYP2C19*17, PON1Q129R and ABCB1C3435T to the platelet aggregation was not found. CONCLUSION: In clopidogrel treated Chinese patients with ACS, carriers of at least one CYP2C19 loss-of-function allele could predict greater risk of HPR, with the impact mainly attributing to CYP2C19*2. Neither ABCB1 nor PON1 genotype could influence the antiplatelet response of clopidogrel in the cohort of Chinese patients.

Effectiveness of percutaneous coronary intervention within 12 hours to 28 days of ST-elevation myocardial infarction in a real-world Chinese population.

OBJECTIVES: Percutaneous coronary intervention( PCI) for ST-elevation myocardial infarction (STEMI) has been widely accepted for patient who come within 12 hours, but for those who come to the hospital late (12 hours to 28 days) the long-term data and possible predictors are limited regarding 'hard' endpoints in 'real world'. METHODS: The registry data of all 5523 consecutive patients admitted due to an incident STEMI (12 hours to 28 days) in our center were analyzed. Patients were divided into 3 age groups (age<65; age = 65-74; age ≥75) and two therapeutic groups including conservative and PCI group. The primary endpoints included 30-day mortality and 1-year mortality. RESULTS: The clinical characteristics include female gender; history of diabetes mellitus, previous myocardial infarction, cerebral vascular disease, chronic renal failure, atrial fibrillation, hypertension, anemia, gastric bleeding; presentation of ventricular tachycardia/ventricular fibrillation, pneumonia, heart failure, multiple organ failure and cardiogenic shock. The ratio of all the above factors increased with the age getting older (all p<0.05), while that of the PCI decreased significantly with ageing (53.9%, 36.3% and 21.7%). Except hypertension, all the other factors were less seen in the PCI group than in the conservative group (p<0.01). Pooled estimates, based on type of therapy and age groups, PCI resulted in significantly lower 30-day and 1-year mortality. Cox analysis showed the positive predictors for 30 days and 1 year mortality were heart failure, cerebral vascular disease, chronic renal failure, ventricular tachycardia/ventricular fibrillation, age, female, gastric intestinal bleeding, cardiogenic shock, multiple organ failure, while PCI was a negative predictor. ROCs analysis showed AUCs were always higher for PCI group. CONCLUSIONS: The elderly have more comorbidities and higher rates of mortality, mandating thorough evaluation before acceptance for PCI. PCI between 12 hours to 28 days in all ages of patients including the elderly with STEMI is significantly more effective than conservative therapy.

Influence of warfarin dose-associated genotypes on the risk of hemorrhagic complications in Chinese patients on warfarin.

This study was designed to evaluate the effect of the warfarin dose-associated genotypes, CYP2C9*3 (rs1057910), VKORC1 -1639 G/A (rs9923231), and CYP4F2 1347 C/T (rs2108622), on hemorrhagic complications in Han Chinese patients. Consecutively recruited patients requiring more than 1 year of warfarin treatment were followed from the initiation of warfarin anticoagulation for at least 3 months. CYP2C9*3, VKORC1 -1639 G/A, and CYP4F2 1347 C/T were genotyped by sequencing. The association between genotypes and warfarin hemorrhagic complications was evaluated using Cox proportional hazard regression, adjusted for demographic and clinical factors. Of 312 eligible patients obtaining stable warfarin anticoagulation in 3 months, 11 major and 69 minor hemorrhages occurred over 147 person-years. The CYP2C9*3 genotype conferred an increased risk of all [hazard ratio (HR) 3.07, 95 % confidence interval (CI) 1.57-6.01] and minor hemorrhage (HR 3.28, 95 % CI 1.62-6.65), but not major hemorrhage (HR 0.44, 95 % CI 0.04-4.72). CYP2C9*3 also conferred an increased risk of over-anticoagulation with international normalization ratio (INR) ≥4 (HR 2.92, 95 % CI 1.08-7.85). VKORC1 -1639 G/A, and CYP4F2 rs2108622 did not confer significant increase in risk for hemorrhage or over-anticoagulation. Kaplan-Meier curves showed that time to all hemorrhagic events was significantly shorter for patients with CYP2C9*3 genotype than non-carriers (P = 0.001), but not for patients with VKORC1 -1639 G/A or CYP4F2 rs2108622 genotype (P = 0.3 and 0.2). CYP2C9*3 may be the main genetic factor in hemorrhagic complications in Chinese patients under warfarin anticoagulation.

Estimation of the warfarin dose with a pharmacogenetic refinement algorithm in Chinese patients mainly under low-intensity warfarin anticoagulation.

Pharmacogenetic (PG) dosing algorithms have been confirmed to predict warfarin therapeutic dose more accurately; however, most of them are based on standard intensity of warfarin anticoagulation, and their utility outside this range is limited. This study was designed to develop and validate a PG refinement algorithm in Chinese patients mainly under low-intensity warfarin anticoagulation. Consented Chinese-Han patients (n=310) under stable warfarin treatment were randomly divided into a derivation (n=207) and a validation cohort (n=103), with 83% and 80% of the patients under low-intensity anticoagulation, respectively. In the derivation cohort, a PG algorithm was constructed on the basis of genotypes (CYP2C9*3 and VKORC1-1639A/G) and clinical data. After integrating additional covariates of international normalised ratio (INR) values (INR on day 4 of therapy and target INR) and genotype of CYP4F2 (rs2108622), a PG refinement algorithm was established and explained 54% of warfarin dose variability. In the validation cohort, warfarin dose prediction was more accurate (p < 0.01) with the PG refinement algorithm than with the PG algorithm and the fixed dose approach (3 mg/day). In the entire cohort, the PG refinement algorithm could accurately identify larger proportions of patients with lower dose requirement (≤2 mg/day) and higher dose requirement (≥4 mg/day) than did the PG algorithm. In conclusion, PG refinement algorithm integrating early INR response and three genotypes (CYP2C9*3, VKORC1-1639A/G, CYP4F2 rs2108622) improves the accuracy of warfarin dose prediction in Chinese patients mainly under low-intensity anticoagulation.

Using optogenetics to translate the "inflammatory dialogue" between heart and brain in the context of stress.

Inflammatory processes are an integral part of the stress response and are likely to result from a programmed adaptation that is vital to the organism's survival and well-being. The whole inflammatory response is mediated by largely overlapping circuits in the limbic forebrain, hypothalamus and brainstem, but is also under the control of the neuroendocrine and autonomic nervous systems. Genetically predisposed individuals who fail to tune the respective contributions of the two systems in accordance with stressor modality and intensity after adverse experiences can be at risk for stress-related psychiatric disorders and cardiovascular diseases. Altered glucocorticoid (GC) homeostasis due to GC resistance leads to the failure of neural and negative feedback regulation of the hypothalamic-pituitary-adrenal axis during chronic inflammation, and this might be the mechanism underlying the ensuing brain and heart diseases and the high prevalence of co-morbidity between the two systems. By the combined use of light and genetically-encoded light-sensitive proteins, optogenetics allows cell-type-specific, fast (millisecond-scale) control of precisely defined events in biological systems. This method is an important breakthrough to explore the causality between neural activity patterns and behavioral profiles relevant to anxiety, depression, autism and schizophrenia. Optogenetics also helps to understand the "inflammatory dialogue", the inflammatory processes in psychiatric disorders and cardiovascular diseases, shared by heart and brain in the context of stress.

Comparative performance of warfarin pharmacogenetic algorithms in Chinese patients.

INTRODUCTION: Multiple warfarin pharmacogenetic algorithms have been confirmed to predict warfarin dose more accurately than clinical algorithm or the fixed-dose approach. However, their performance has never been objectively evaluated in patients under low intensity warfarin anticoagulation, which is optimal for prevention of thromboembolism in Asian patients. MATERIAL AND METHODS: We sought to compare the performances of 8 eligible pharmacogenetic algorithms in a cohort of Chinese patients (n=282) under low intensity warfarin anticoagulation with target international normalized ratio (INR) ranged from 1.6 to 2.5. The performance of each algorithm was evaluated by calculating the percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) between each predicted dose and actual stable dose. RESULTS: In the entire cohort, the pharmacogenetic algorithms could predict warfarin dose with the average MAE of 0.87 ± 0.17 mg/day (0.73-1.17 mg/day), and the average percentage within 20% of 43.8% ± 8.1% (29.1% - 52.1%). By pairwise comparison, warfarin dose prediction was significantly more accurate with the algorithms derived from Asian patients (48.6% - 50.0%) than those from Caucasian patients (29.1% - 39.7%; odds ratio [OR]: 1.61-3.36, p ≤ 0.02). Algorithms with additional covariates of INR values or CYP4F2*3 performed better than those without the covariates (adding INR: OR: 1.71 (1.08-2.72), p =0.029; adding CYP4F2*3: OR: 2.67(1.41-5.05), p =0.004). When the patients were stratified according to the dose range, the algorithms from Caucasian and racially mixed populations tended to perform better in higher dose group (≥ 4.5mg/day), and algorithms from Asian populations performed better in intermediate dose group (1.5-4.5mg/day). None of the algorithms performed well in lower dose group (≤ 1.5mg/day). CONCLUSIONS: No eligible pharmacogenetic algorithm could perform the best for all dosing range in the Chinese patients under low intensity warfarin anticoagulation. Construction of a refinement pharmacogenetic algorithm integrating 3 genotypes (CYP2C9, VKORC1 and CYP4F2) and INR data should be warranted to improve the warfarin dose prediction in such patients.

Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia guided by magnetic navigation system: a prospective randomized comparison with conventional procedure.

BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) is one of the most common paroxysmal supraventricular tachyarrhythmias. The aim of the study was to prospectively compare the characteristics of radiofrequency catheter ablation of AVNRT guided by a magnetic navigation system with the conventional procedure. METHODS: Patients with AVNRT diagnosed by electrophysiological tests were randomized into two groups. In the conventional technique group (CMT), a common 4-mm-tip quadrapolar temperature-controlled ablation catheter was used. In the magnetic navigation system guidance group (MNS), a magnetic 4-mm-tip quadrapolar temperature-controlled ablation catheter was used. The following parameters were collected and compared between the two groups: ablation procedure time, patient fluoroscopy time, operator fluoroscopy time, energy delivery numbers, maximal energy per deployment, success rate, complication rate and operative cost. RESULTS: Forty patients were enrolled and randomized into CMT and MNS groups. The age, gender, tachycardia history and basic cardiovascular diseases of the two groups were comparable (P > 0.05). All procedures were conducted successfully without complications. No tachycardia recurred during the follow-up period of (9.3 ± 2.6) months. In the MNS group, the patient and operator fluoroscopy times ((11.5 ± 4.3) min, (4.2 ± 1.5) min), energy delivery numbers (3.2 ± 0.9), and maximal energy per deployment ((16.9 ± 3.4) W) were shorter or lower than those of the CMT group ((14.3 ± 6.2) min, (13.6 ± 3.5) min, 6.3 ± 2.1, (23.7 ± 1.3) W, respectively) (P < 0.05). But the operative cost for the MNS group was higher than that of the CMT group (P < 0.01). CONCLUSION: Magnetic navigation system guided radiofrequency catheter ablation of AVNRT has the advantages of shorter fluoroscopy time and lower energy delivery numbers and maximal energy per deployment compared to the present conventional ablation technique.