De-jia Huang

Telehealth interventions versus center-based cardiac rehabilitation of coronary artery disease: A systematic review and meta-analysis

Background Cardiac rehabilitation (CR) is an evidence-based recommendation for patients with coronary artery disease (CAD). However, CR is dramatically underutilized. Telehealth interventions have the potential to overcome barriers and may be an innovative model of delivering CR. This review aimed to determine the effectiveness of telehealth intervention delivered CR compared with center-based supervised CR. Method Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library and the Chinese BioMedical Literature Database (CBM), were searched to April 2014, without language restriction. Existing randomized controlled trials, reviews, relevant conference lists and gray literature were checked. Randomized controlled trials that compared telehealth intervention delivered CR with traditional center-based supervised CR in adults with CAD were included. Two reviewers selected studies and extracted data independently. Main clinical outcomes including clinical events, modifiable risk factors or other endpoints were measured. Results Fifteen articles reporting nine trials were reviewed, most of which recruited patients with myocardial infarction or revascularization. No statistically significant difference was found between telehealth interventions delivered and center-based supervised CR in exercise capacity (standardized mean difference (SMD) –0.01; 95% confidence interval (CI) –0.12–0.10), weight (SMD –0.13; 95% CI –0.30–0.05), systolic and diastolic blood pressure (mean difference (MD) –1.27; 95% CI –3.67–1.13 and MD 1.00; 95% CI –0.42–2.43, respectively), lipid profile, smoking (risk ratio (RR) 1.03; 95% CI 0.78–1.38), mortality (RR 1.15; 95% CI 0.61–2.19), quality of life and psychosocial state. Conclusions Telehealth intervention delivered cardiac rehabilitation does not have significantly inferior outcomes compared to center-based supervised program in low to moderate risk CAD patients. Telehealth intervention offers an alternative deliver model of CR for individuals less able to access center-based cardiac rehabilitation. Choices should reflect preferences, anticipation, risk profile, funding, and accessibility to health service.

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.

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.

Meta-Analysis of Relation Between Oral β-Blocker Therapy and Outcomes in Patients With Acute Myocardial Infarction Who Underwent Percutaneous Coronary Intervention

The aim of the present review was to investigate the association between the use of oral β-blockers and prognosis in patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) treatment. A systematic literature search was conducted in Pubmed (from inception to September 27, 2014) and Embase (Ovid SP, from 1974 to September 29, 2014) to identify studies that compared the outcome of patients with AMI taking oral β-blockers with that of patients not taking after PCI. Systematic review and meta-analysis were performed with random-effects model or fixed-effects model. Ten observational studies with a total of 40,873 patients were included. Use of β-blockers was associated with a reduced risk of all-cause death (unadjusted relative risk 0.58, 95% confidential interval 0.48 to 0.71; adjusted hazard ratio 0.76, 95% confidential interval 0.62 to 0.94). The potential benefit of β-blockers in preventing all-cause death was not similar in all population but was restricted to those with reduced ejection fraction, with low use proportion of other secondary prevention drugs or with non-ST-segment elevation myocardial infarction. The association between the use of β-blockers and improved survival rate was significant in ≤1-year follow-up duration. Rates of cardiac death, myocardial infarction, and heart failure readmission in patients using β-blockers were not significantly different from those in patients without β-blocker therapy. In conclusion, there is lack of evidence to support routine use of β-blockers in all patients with AMI who underwent PCI. Further trials are urgently needed to address the issue.

Nitrates for stable angina: A systematic review and meta-analysis of randomized clinical trials

OBJECTIVE To assess the effect (harms and benefits) of nitrates for stable angina. METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Randomized controlled trials with both parallel and crossover design were included. The following outcome measures were evaluated: number of angina attacks weekly and nitroglycerin consumption, quality of life, total exercise duration, time to onset of angina and time to 1 mm ST depression. RESULTS Fifty-one trials with 3595 patients meeting inclusion criteria were analyzed. Both intermittent and continuous regimens of nitrates lengthened exercise duration significantly by 31 and 53 s respectively. The number of angina attacks was significantly reduced by 2.89 episodes weekly for continuous administration and 1.5 episodes weekly for intermittent administration. With intermittent administration, increased dose provided with 21 s more length of exercise duration. With continuous administration, exercise duration was pronged more in low-dose group. Quality of life was not improved by continuous application of GTN patches and was similar between continuous and intermittent groups. In addition, 51.6% patients receiving nitrates complained with headache. CONCLUSION Long-term administration of nitrates was beneficial for angina prophylaxis and improved exercise performance but might be ineffective for improving quality of life. With continuous regimen, low-dose nitrates were more effective than high-dose ones for improving exercise performance. By contrast, with intermittent regimen, high-dose nitrates were more effective. In addition, intermittent administration could bring zero-hour effect.

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.