Hua Chai

Sex-Related Differences in Outcomes After Transcatheter Aortic Valve Implantation A Systematic Review and Meta-analysis

Background—There were considerable discrepancies with regard to sex-related differences in complications and prognosis after transcatheter aortic valve implantation. Methods and Results—The Cochrane library and PubMed online databases were searched. Articles reporting sex-specific post–transcatheter aortic valve implantation complications and mortality were identified. Two authors selected studies and extracted data independently. Random- and fixed-effects models were used depending on between-study heterogeneity. There were 27 articles, a total of 9118 patients, enrolled in our systematic review and meta-analysis, including 4176 men and 4942 women. Pooled analyses suggested considerable sex-related differences in complications and early as well as midterm outcomes after transcatheter aortic valve implantation. The difference in the risk for heart block requiring permanent pacemaker implantation was noted to be significant only in the subgroup of the CoreValve-dominating studies (pooled risk ratio [RR, men versus women], 1.29; 95% confidence interval [CI], 1.13–1.47). Although men had significantly lower risks for major/life-threatening bleeding (pooled RR, 0.81; 95% CI, 0.68–0.96) and major vascular complications (pooled RR, 0.49; 95% CI, 0.37–0.66), they had poorer prognosis. In fact, male sex was associated with significantly higher risks for deaths at both 30 days (RR, 1.37; 95% CI, 1.07–1.76) and 1 year (RR, 1.30; 95% CI, 1.14–1.49). Conclusions—Although men had lower risks for major/life-threatening bleeding and major vascular complications after transcatheter aortic valve implantation, they had less favorable short-term and midterm survival.

Impact of Renal Dysfunction on Mid-Term Outcome after Transcatheter Aortic Valve Implantation: A Systematic Review and Meta-Analysis

Background There is conflicting evidence regarding the impact of preexisting renal dysfunction (RD) on mid-term outcomes after transcatheter aortic valve implantation (TAVI) in patients with symptomatic aortic stenosis (AS). Methods and results Forty-seven articles representing 32,131 patients with AS undergoing a TAVI procedure were included in this systematic review and meta-analysis. Pooled analyses were performed with both univariate and multivariate models, using a fixed or random effects method when appropriate. Compared with patients with normal renal function, mid-term mortality was significantly higher in patients with preexisting RD, as defined by the author (univariate hazard ratio [HR]: 1.69; 95% confidence interval [CI]: 1.50–1.90; multivariate HR: 1.47; 95% CI: 1.17–1.84), baseline estimated glomerular filtration rate (eGFR) (univariate HR: 1.65; 95% CI: 1.47–1.86; multivariate HR: 1.46; 95% CI: 1.24–1.71), and serum creatinine (univariate HR: 1.69; 95% CI: 1.48–1.92; multivariate HR: 1.65; 95% CI: 1.36–1.99). Advanced stage of chronic kidney disease (CKD stage 3–5) was strongly related to bleeding (univariate HR in CKD stage 3: 1.30, 95% CI: 1.13–1.49; in CKD stage 4: 1.30, 95% CI: 1.04–1.62), acute kidney injure (AKI) (univariate HR in CKD stage 3: 1.28, 95% CI: 1.03–1.59; in CKD stage 4: 2.27, 95% CI: 1.74–2.96), stroke (univariate HR in CKD stage 4: 3.37, 95% CI: 1.52–7.46), and mid-term mortality (univariate HR in CKD stage 3: 1.57, 95% CI: 1.26–1.95; in CKD stage 4: 2.77, 95% CI: 2.06–3.72; in CKD stage 5: 2.64, 95% CI: 1.91–3.65) compared with CKD stage 1+2. Patients with CKD stage 4 had a higher incidence of AKI (univariate HR: 1.70, 95% CI: 1.34–2.16) and all-cause death (univariate HR: 1.60, 95% CI: 1.28–1.99) compared with those with CKD stage 3. A per unit decrease in serum creatinine was also associated with a higher mortality at mid-term follow-up (univariate HR: 1.24, 95% CI: 1.18–1.30; multivariate HR: 1.19, 95% CI: 1.08–1.30). Conclusions Preexisting RD was associated with increased mid-term mortality after TAVI. Patients with CKD stage 4 had significantly higher incidences of peri-procedural complications and a poorer prognosis, a finding that should be factored into the clinical decision-making process regarding these patients.

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.

The impact of smoking on clinical efficacy and pharmacodynamic effects of clopidogrel: a systematic review and meta-analysis

Context Previous findings regarding the relationship between smoking and clopidogrel effects were considerably discrepant. Objective To assess the impact of smoking on clinical and pharmacodynamic response to clopidogrel. Data sources Medline, EMBASE and the Cochrane Library through January 2013 were searched. Reference lists of pertinent literatures and abstracts of major cardiovascular conferences were screened. Study selection Clinical and laboratory studies, which reported major adverse cardiovascular events and on-clopidogrel platelet reactivity categorised by smoking status respectively, were selected. Data extraction Descriptive and quantitative data were extracted. The main analyses were performed under a random-effects model. For clinical studies, HR estimates were synthesised according to smoking status; for laboratory studies, standardised mean difference (SMD) of on-clopidogrel platelet reactivity and OR for high on-clopidogrel platelet reactivity were pooled. Heterogeneity was quantified by computing I2 statistic. Results Of the 1869 citations retrieved, seven clinical studies and 12 laboratory studies involving 111 132 patients with established cardiovascular disease and 6658 patients with acute coronary syndrome and/or stent deployment, respectively, were included for meta-analysis. Pooled clinical results showed that an intensified antiplatelet regimen involving clopidogrel was associated with 10% reduced risk for major adverse cardiovascular events among non-current smokers (HR 0.90; 95% CI 0.85 to 0.96), while this clinical benefit was enhanced by 2.9-fold among current smokers (HR 0.71; 95% CI 0.62 to 0.80). Pooled analysis of laboratory studies revealed that current smokers had significantly lower on-clopidogrel platelet reactivity (SMD −0.30; 95% CI −0.46 to −0.15) but, notably, there was considerable inter-study heterogeneity (I2 76.2%; p=0.000). The analysis based on four studies (n=1423) suggested a significantly lower odds of high on-clopidogrel platelet reactivity among current smokers than those among never smokers (OR 0.33; 95% CI 0.22 to 0.43). Conclusions Smoking appears to positively modify the relative clinical efficacy and pharmacodynamic effects of clopidogrel.

Subclassification of left ventricular hypertrophy based on dilation stratifies coronary artery disease patients with distinct risk.

A new 4‐tired classification of left ventricular hypertrophy (LVH) based on LV concentricity and dilation has been proposed; however, the association between the new categorization of LV geometry and outcomes in patients with coronary artery disease (CAD) is still unknown.

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.

Heparin is Not Inferior to Bivalirudin in Percutaneous Coronary Intervention—Focusing on the Effect of Glycoprotein IIb/IIIa Inhibitor Use A Meta-Analysis

Our aim was to compare the efficacy and safety of bivalirudin (Biv) versus heparin (Hep) with or without similar usage rate of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI). The PubMed and EMbase were searched. Randomized trials comparing Biv versus Hep were eligible for inclusion. With imbalanced GPI use, Biv had significantly lower major bleeding (pooled risk ratio [RR], 0.67; 95% confidence interval [CI], 0.54-0.83) without difference in mortality (pooled RR, 0.95; 95% CI, 0.80-1.14). With comparable GPI use, no significant difference was observed in major bleeding (pooled RR, 0.95; 95% CI, 0.82-1.10) and mortality (pooled RR, 1.13; 95% CI, 0.85-1.50). With no GPI use, Biv was associated with numerically higher mortality (pooled RR, 1.17; 95% CI, 0.83-1.65) without significant difference in major bleeding (pooled RR, 0.81; 95% CI, 0.64-1.02). In conclusion, when comparing different anticoagulants during PCI, the effect of GPIs should not be underestimated. Heparin as such was found noninferior to Biv.

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.

Inhibition of Receptor Interacting Protein Kinases Attenuates Cardiomyocyte Hypertrophy Induced by Palmitic Acid.

Palmitic acid (PA) is known to cause cardiomyocyte dysfunction. Cardiac hypertrophy is one of the important pathological features of PA-induced lipotoxicity, but the mechanism by which PA induces cardiomyocyte hypertrophy is still unclear. Therefore, our study was to test whether necroptosis, a receptor interacting protein kinase 1 and 3 (RIPK1 and RIPK3-) dependent programmed necrosis, was involved in the PA-induced cardiomyocyte hypertrophy. We used the PA-treated primary neonatal rat cardiac myocytes (NCMs) or H9c2 cells to study lipotoxicity. Our results demonstrated that cardiomyocyte hypertrophy was induced by PA treatment, determined by upregulation of hypertrophic marker genes and cell surface area enlargement. Upon PA treatment, the expression of RIPK1 and RIPK3 was increased. Pretreatment with the RIPK1 inhibitor necrostatin-1 (Nec-1), the PA-induced cardiomyocyte hypertrophy, was attenuated. Knockdown of RIPK1 or RIPK3 by siRNA suppressed the PA-induced myocardial hypertrophy. Moreover, a crosstalk between necroptosis and endoplasmic reticulum (ER) stress was observed in PA-treated cardiomyocytes. Inhibition of RIPK1 with Nec-1, phosphorylation level of AKT (Ser473), and mTOR (Ser2481) was significantly reduced in PA-treated cardiomyocytes. In conclusion, RIPKs-dependent necroptosis might be crucial in PA-induced myocardial hypertrophy. Activation of mTOR may mediate the effect of necroptosis in cardiomyocyte hypertrophy induced by PA.

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.