Yuan-Ning Xu

A meta-analysis of impact of proton pump inhibitors on antiplatelet effect of clopidogrel

Previous mechanistic studies have suggested a possible interaction between proton pump inhibitor (PPIs) and clopidogrel. However, the results of clinical trials about the effects of PPIs on safety and efficacy of clopidogrel are controversial. The study sought to estimate the impact of PPIs on antiplatelet effect of clopidogrel. The study performed a meta-analysis of comparative concomitant use of clopidogrel with PPIs versus clopidogrel without PPIs studies published or presented to October 2010. Cardiovascular death, readmission for myocardial infarction/readmission for acute coronary syndrome, and nonfatal stroke were set as clinical endpoints. In randomized control trials (RCTs), the clinical endpoints risk ratio for clopidogrel with PPIs versus clopidogrel without PPIs was 1.20 (P= 0.34) in the random-effects model and 1.03 (P= 0.63) in the fixed-effects model. In observational studies, the risk ratio for the clinical endpoints for clopidogrel with PPI versus clopidogrel without PPI was 1.40 (P < 0.001) in the random-effects model and 1.49 (P < 0.001) in the fixed-effects model. Different assay methods showed that coadministration of clopidogrel with PPIs was associated with attenuation of clopidogrels antiplatelet effect in vitro. This meta-analysis indicated an obvious discrepancy between RCTs and observational studies with respect to the interaction between PPIs and clopidogrel.

Causes of Death Following Transcatheter Aortic Valve Replacement: A Systematic Review and Meta‐Analysis

Background Transcatheter aortic valve replacement (TAVR) is an effective alternative to surgical aortic valve replacement in patients at high surgical risk. However, there is little published literature on the exact causes of death. Methods and Results The PubMed database was systematically searched for studies reporting causes of death within and after 30 days following TAVR. Twenty-eight studies out of 3934 results retrieved were identified. In the overall analysis, 46.4% and 51.6% of deaths were related to noncardiovascular causes within and after the first 30 days, respectively. Within 30 days of TAVR, infection/sepsis (18.5%), heart failure (14.7%), and multiorgan failure (13.2%) were the top 3 causes of death. Beyond 30 days, infection/sepsis (14.3%), heart failure (14.1%), and sudden death (10.8%) were the most common causes. All possible subgroup analyses were made. No significant differences were seen for proportions of cardiovascular deaths except the comparison between moderate (mean STS score 4 to 8) and high (mean STS score >8) -risk patients after 30 days post-TAVR (56.0% versus 33.5%, P=0.005). Conclusions Cardiovascular and noncardiovascular causes of death are evenly balanced both in the perioperative period and at long-term follow-up after TAVR. Infection/sepsis and heart failure were the most frequent noncardiovascular and cardiovascular causes of death. This study highlights important areas of clinical focus that could further improve outcomes after TAVR.

Association between cytochrome P450 2C19 polymorphism and clinical outcomes in Chinese patients with coronary artery disease

BACKGROUND Cytochrome P450 (CYP)2C19 is expressed in vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which play a key role in regulating vascular tone. The aim of this study was to investigate whether the genetic functional variant 681G>A (*2) of cytochrome CYP2C19 is associated with adverse cardiovascular outcomes in Chinese patients with coronary artery disease (CAD). METHODS Between July 2008 and September 2009, 654 consecutive patients with CAD were enrolled in this study. All participants underwent CYP2C19 genotyping. The primary study endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Secondary endpoints included the components of the primary endpoint, death from any cause, and recurrent revascularization. RESULTS The baseline characteristics were well-balanced between carriers (heterozygous *1/*2, n=291; homozygous *2/*2, n=57) and non-carriers (n=306) of the CYP2C19*2 variant. During the follow-up period (11.42±4.23 months), the primary endpoint occurred more frequently in homozygous *2/*2 than in non-carriers (n=306) of CYP2C19*2 variant (12.28% versus 3.27%; adjusted hazard ratio [HR]=5.191; 95% confidence interval [CI]=1.936-13.917; P=0.001); however, no such increase was evident in heterozygous *1/*2 patients (4.12% versus 3.27%; adjusted HR=1.208; 95% CI 0.517-2.822; P=0.662). CONCLUSIONS The homozygous CYP2C19*2/*2 genotype is an independent determinant of adverse vascular events in Chinese patients with CAD.

COMPARISON OF THE SORTING EFFICIENCY AND INFLUENCE ON CELL FUNCTION BETWEEN THE STERILE FLOW CYTOMETRY AND IMMUNOMAGNETIC BEAD PURIFICATION METHODS

Currently, flow cytometry and immunomagnetic bead purification are the most commonly used cell sorting methods. We performed this study because there are few reports that directly compare the sorting efficiency and influence on cell functions of these two methods. The in vitro cultured third-generation bone marrow mesenchymal cells from newborn Sprague-Dawley rats were sorted and purified using sterile flow cytometry and immunomagnetic beads to obtain CXCR4-positive bone marrow mesenchymal stem cells (CXCR4+-MSCs). The yield and purity (detected by flow cytometry), in vitro viability (detected by the MTT method), and in vitro chemotactic capacity (detected by stromal cell-derived factor-1α [SDF-1α] induction) of sorted target cells using these two methods were compared. The purity of CXCR4+-MSCs obtained using sterile flow cytometry was higher than that using immunomagnetic bead purification. The MTT method and growth curves showed that the viability of cells was lower and that the amplification rate of cells decreased using sterile flow cytometry, whereas the cell viability was higher after cells were sorted using immunomagnetic beads (p < 0.01). The number of CXCR4+-MSCs cells that underwent chemotactic migration induced by SDF-1α after sorting using sterile flow cytometry was smaller than that using immunomagnetic bead purification (15.60 ± 1.14 vs. 26.40 ± 1.67, p < 0.01). Although the purity of CXCR4+-MSCs sorted by the immunomagnetic bead purification method was lower than that by sterile flow cytometry, the influence on cell activity of the former was smaller, including improved cell viability and improved SDF-1α -induced chemotactic migration in vitro.

Predictors and outcome of acute kidney injury after transcatheter aortic valve implantation-- a systematic review and meta-analysis.

AIMS The aim of this systematic review and meta-analysis was to investigate the predictors and outcome of acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS There were 35 articles recruiting 13,256 patients included in our study. Hypertension (odds ratio [OR] 1.92, 95% CI: 1.44 to 2.56), diabetes mellitus (OR 1.33, 95% CI: 1.20 to 1.47), peripheral artery disease (OR 1.28, 95% CI: 1.14 to 1.45) and a left ventricular ejection fraction <40% (OR 1.50, 95% CI: 1.19 to 1.88) were identified as significant independent predictors of AKI. In addition to the aforementioned comorbidities, procedure-related/post-TAVI factors such as transapical access (OR 1.68, 95% CI: 1.44 to 1.97), major bleeding (OR 1.82, 95% CI: 1.37 to 2.40) and transfusion (OR 1.30, 95% CI: 1.12 to 1.51) were also associated with a higher risk of AKI. Importantly, the risk of short-term all-cause death increased progressively with the aggravating severity of AKI (OR, 30 days: stage 1: 3.41; stage 2: 4.0; stage 3: 11.02; one year: stage 1: 1.95; stage 2: 2.82; stage 3: 7.34), as determined by a univariate analysis. After eliminating confounders, AKI remained linked to a higher risk for both short-term (30 days: HR 2.12, 95% CI: 1.59 to 2.83) and long-term (≥3 years: HR 1.37, 95% CI: 1.27 to 1.48) all-cause mortality. CONCLUSIONS The reason for the occurrence of AKI was multifactorial, including baseline characteristics, procedure-related and post-TAVI factors. It appeared that even stage 1 AKI exerted detrimental effects on survival within one year, and AKI was also independently linked to mortality beyond three years.

The relationship between chronic obstructive pulmonary disease and transcatheter aortic valve implantation--A systematic review and meta-analysis.

The present study was performed to investigate the relationship between chronic obstructive pulmonary disease (COPD) and transcatheter aortic valve implantation (TAVI). Background: Controversies regarding the relationship between COPD and TAVI have intensified. Methods: A literature review of the PubMed online database was performed, and articles published between January 1, 2002 and March 20, 2015 were analyzed. Random‐effect and fixed‐effect models were used, depending on the between‐study heterogeneity. Results: A total of 28 studies, involving 51,530 patients, were identified in our review. The burden of COPD ranged from 12.5% to 43.4%, and COPD negatively impacted both short‐term and long‐term all‐cause survival (30 days: odds ratio [OR], 1.43, 95% CI, 1.14–1.79; >2 years: hazard ratio [HR], 1.34, 95% CI, 1.12–1.61). COPD was also associated with increased short‐term and mid‐term cardiac‐cause mortality (30 days: OR, 1.29, 95% CI, 1.02–1.64; 1 year: HR: 1.09, 1.02–1.17). Moreover, COPD (OR, 1.97, 95% CI, 1.29–3.0) predicted post‐TAVI acute kidney disease. Importantly, chronic kidney disease (CKD) (HR, 1.2, 95% CI, 1.1–1.32) and the distance of the 6 minute walk test (6MWT) (HR, 1.16, 1.06–1.27) predicted TAVI futility in patients with COPD. Conclusion: COPD is common among patients undergoing TAVI, and COPD impacts both short‐ and long‐term survival. COPD patients, who had a lower BMI, shorter distance of 6MWT and CKD, were at higher risk for TAVI futility.

A Predictive Study of the Dynamic Development of the P‐Wave Terminal Force in Lead V1 in the Electrocardiogram in Relation to Long‐Term Prognosis in Non–ST‐Segment Elevation Acute Coronary Syndrome Patients during Hospitalization

Changes in the ECG indicator PtfV1 reflect left atrial pressure and left ventricular diastolic function in NSTE‐ACS patients during hospitalization. The value of PtfV1 in the evaluation of long‐term prognosis in NSTE‐ACS is still not clear. The purpose of this study was to investigate the relationship between the dynamic changes in P‐wave terminal force in lead V1(PtfV1) in the ECG of non–ST‐segment elevation acute coronary syndrome (NSTE‐ACS) patients during hospitalization and the long‐term major adverse cardiovascular events (MACEs) of patients.

Admission Serum Calcium Levels Improve the GRACE Risk Score Prediction of Hospital Mortality in Patients With Acute Coronary Syndrome.

The Global Registry of Acute Coronary Events (GRACE) risk score has been extensively validated to predict risk during hospitalization in patients with acute coronary syndrome (ACS). Recently, serum calcium has been suggested as an independent predictor for in‐hospital mortality in patients with ST‐segment elevation myocardial infarction; however, the relationship between the 2 has not been evaluated.

Transcatheter aortic valve implantation with the self‐expandable venus A‐Valve and CoreValve devices: Preliminary Experiences in China

Transcatheter aortic valve implantation (TAVI) has been demonstrated to be an effective alternative to surgical aortic valve replacement (SAVR) in patients with aortic stenosis who are deemed high risk or inoperable. Currently, TAVI procedures in China mostly make use of the domestic Venus A‐Valve and the CoreValve; however, there is no data on their comparative performance.

The Value of Combining CYP2C19*2 Polymorphism with Classic Risk Factors in Prediction of Clinical Prognosis in Acute Coronary Syndrome Patients

Objectives: To assess the impact of different CYP2C19*2 polymorphisms on clinical outcomes and the effects of CYP2C19*2 polymorphism on predicting clinical outcomes in association with classic risk factors in patients with acute coronary syndromes (ACS). Methods: Between July 2008 and September 2009, 497 consecutive patients with ACS who were admitted to the West China Hospital of Sichuan University were enrolled and underwent CYP2C19*2 determination. The clinical outcomes were the composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. Results: Baseline characteristics were balanced between noncarrier, heterozygous and homozygous groups of the CYP2C19*2 variant. The clinical endpoint occurred more frequently in the homozygous group (HR 4.86, CI 1.62–14.56, p = 0.005). After multivariable analysis, the CYP2C19*2 genetic variant was an independent predictor of cardiovascular events (HR 5.96, CI 1.77–20.03, p = 0.0039) as well as GRACE score and Killip class. The combination of CYP2C19*2 with GRACE score and Killip class increases the potential to predict adverse outcomes. Conclusions: Homozygosity (A/A) for CYP2C19*2 mutant is an independent determinant of prognosis in patients with ACS. The combination of CYP2C19*2 polymorphism with classic risk factors may be a useful tool to predict the risk of cardiovascular events.