Early and midterm outcomes of transcatheter aortic-valve replacement with balloon-expandable versus self-expanding valves: A meta-analysis.

BACKGROUND: Current guidelines provide recommendation for transcatheter aortic-valve replacement (TAVR) in severe aortic stenosis without emphasis on valve systems. The comparative performances of balloon-expandable valves (BEV) and self-expanding valves (SEV) remain unclear. We aim to compare the early (30-day) and midterm (1-year) mortality and cardiovascular outcomes of BEV with SEV. METHODS: PubMed, CENTRAL, and EMBASE were searched from inception to February 13, 2020 for randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. Odds ratios (ORs) for binary outcomes and mean differences for continuous outcomes were pooled using random-effect models (DerSimonian-Laird method) with Hartung-Knapp-Sidik-Jonkman variance correction. Primary outcomes were early and midterm all-cause mortality. RESULTS: We included 3 RCTs (1418 patients) and 12 PSM studies (36,540 patients). Compared with SEV, BEV was associated with significantly lower mortality at 30 days (OR 0.76, 95% CI 0.67-0.85, p < 0.001, I2 = 0) and 1 year (OR 0.87, 95% CI 0.77-0.99, p = 0.04, I2 = 20.4%) in PSM studies, but not RCTs with insufficient power. Similar findings were found in subgroups analysis based on valve generations and SEV types. The 30-day and 1-year cardiovascular mortality, 30-day incidences of moderate to severe paravalvular leak, procedural contrast agent volume, and procedure time were lower, but transvalvular pressure gradient was higher in BEV than SEV in PSM studies. The 30-day incidences of permanent pacemaker implantation (PPI), acute kidney injury, stroke, major bleeding, major vascular complications, and rehospitalization were not statistically different between BEV and SEV. Early-generation SEV was associated with a higher 30-day PPI risk than corresponding BEV comparators. PPI risk was lower in ACURATE neo (Boston Scientific, Natick, MA) but higher in Evolut R SEV (Medtronic Inc., Minneapolis, MN), both compared with SAPIEN 3 BEV (Edwards Lifesciences, Irvine, CA). CONCLUSIONS: PSM studies suggest lower early and midterm mortality in BEV than SEV, but the contribution of unmeasured confounders cannot be excluded. Results from adequately powered RCTs with long-term follow-up are critically needed to confirm these findings.

Intensive vs non-intensive statin pretreatment before percutaneous coronary intervention in Chinese patients: A meta-analysis of randomized controlled trials.

BACKGROUND: The results of intensive statin pretreatment before percutaneous coronary intervention (PCI) is inconsistent between Chinese and Western populations, and there are no corresponding meta-analyses involving hard clinical endpoints in the available published literature. AIM: To evaluate the efficacy and safety of high-dose statin loading before PCI in Chinese patients through a meta-analysis. METHODS: Relevant studies were identified by searching the electronic databases of PubMed, Embase and Cochrane's Library to December 2019. The outcomes included an assessment of major adverse cardiovascular event (MACE), non-fatal myocardial infarction (MI), cardiac death, target vessel revascularization (TVR), myalgia /myasthenia and abnormal alanine aminotransferase (ALT) in all enrolled patients. Random effect model and fixed effect model were applied to combine the data, which were further analyzed by χ 2 test and I 2 test. The main outcomes were then analyzed through the use of relative risks (RR) and its 95% confidence interval (95%CI). RESULTS: Eleven studies involving 3123 individuals were included. Compared with patients receiving placebo or no statin treatment before surgery, intensive statin treatment was associated with a clear reduction of risk of MACE (RR = 0.44, 95%CI: 0.31-0.61, P < 0.00001). However, compared with the patients receiving moderate-intensity statin before surgery, no advantage to intensive statin treatment was seen (RR = 1.04, 95%CI: 0.82-1.31, P = 0.74). In addition, no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR (RR = 0.43, 95%CI: 0.18-1.02, P = 0.06) , myalgia /myasthenia (RR = 1.35, 95%CI: 0.30-5.95, P = 0.69) and abnormal alanine aminotransferase (RR = 1.47, 95%CI: 0.54-4.02, P = 0.45) except non-fatal MI (RR = 0.54, 95%CI: 0.33-0.88, P = 0.01). CONCLUSION: Compared with placebo or no statin pretreatment, intensive statin before PCI displayed reduced incidence of MACE. However, there was no significant benefit between high and moderate-intensity statin. In addition, no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR, myalgia/myasthenia and abnormal alanine aminotransferase except non-fatal MI.

HMGB1-Promoted Neutrophil Extracellular Traps Contribute to Cardiac Diastolic Dysfunction in Mice.

Background Heart failure with preserved ejection fraction (HFpEF) remains an increasing public health problem with substantial morbidity and mortality but with few effective treatments. A novel inflammatory mechanism has been proposed, but the inflammatory signals promoting the development of HFpEF remain greatly unknown. Methods and Results Serum of patients with HFpEF was collected for measurement of circulating neutrophils and markers of neutrophil extracellular traps (NETs). To induce HFpEF phenotype, male C57BL/6 mice underwent uninephrectomy, received a continuous infusion of d-aldosterone for 4 weeks, and maintained on 1.0% sodium chloride drinking water. Heart tissues were harvested, immune cell types determined by flow cytometry, NETs formation by immunofluorescence, and western blotting. Differentiated neutrophils were cultured to investigate the effect of HMGB1 (high mobility group protein B1) and SGLT2 (sodium-glucose cotransporter-2) inhibitor on NETs formation in vitro. Circulating neutrophils and NETs markers are elevated in patients with HFpEF, as are cardiac neutrophils and NETs formation in HFpEF mice. NETs inhibition with deoxyribonuclease 1 in experimental HFpEF mice reduces heart macrophages infiltration and inflammation and ameliorates cardiac fibrosis and diastolic function. Damage-associated molecular pattern HMGB1 expression is elevated in cardiac tissue of HFpEF mice, and HMGB1 inhibition reduces heart neutrophil infiltration and NETs formation and ameliorates diastolic function. Lastly, SGLT2 inhibitor empagliflozin down-regulates heart HMGB1 expression, attenuates NETs formation and cardiac fibrosis, and improves diastolic function in HFpEF mice. Conclusions NETs contribute to the pathogenesis of HFpEF, which can be ameliorated by HMGB1 inhibition and SGLT2 inhibitors. Thus, HMGB1 and NETs may represent novel therapeutic targets for the treatment of HFpEF.

3D bioprinting of an electroactive and self-healing polysaccharide hydrogels.

Polysaccharide hydrogels including alginate, agarose, hyaluronic acid, and chitosan have been widely used as scaffolds in 3D bio-printing field. Konjac glucomannan (KGM) exhibits excellent properties of water solubility, biocompatibility, and biodegradability. Herein composite hydrogels were prepared via Schiff-base reaction between the aldehyde group of oxidized konjac glucomannan (OKGM) and the amino group of branched polyethyleneimine (PEI). The OKGM/PEI composite hydrogel displayed self-healing ability and pH sensitivity and showed shear thinning capability, which is suitable for 3D bio-printing technology. Furthermore, the OKGM/PEI electroactive composite hydrogel was obtained by adding carbon nanotubes (CNTs). Then the rheological behavior and morphology of OKGM/PEI electroactive hydrogels were thoroughly characterized. The conductivities of OKGM/PEI electroactive composite hydrogels increased with increasing the content of CNTs. The rheological behavior and 3D bio-printability of OKGM/PEI electroactive hydrogels were also tested. It was found that CNTs can also improve the bio-printability of OKGM/PEI electroactive hydrogels. Thus, the OKGM/PEI electroactive hydrogels could be employed as scaffolds for muscle and cardiac nerve tissue regeneration.

Off-Label Under- and Overdosing of Direct Oral Anticoagulants in Patients With Atrial Fibrillation: A Meta-Analysis.

BACKGROUND: Prescriptions of off-label under- and overdosing of direct oral anticoagulants (DOACs) are common for patients with atrial fibrillation, but their efficacy and safety remain unknown. METHODS: Databases were searched for randomized controlled trial or adjusted observational study that compared an off-label versus on-label dosing of DOACs through June 15, 2021. The primary efficacy outcome was ischemic stroke/system embolism (IS/SE), and primary safety outcome was major bleeding. Net clinical outcome was generally defined as the composite of IS/SE, major bleeding, and all-cause death. Hazard ratios (HRs) with 95% CIs were pooled with random-effects models with Hartung-Knapp-Sidik-Jonkman method for adjustment. RESULTS: Sixteen studies with 130 609 patients were included. Compared with on-labeling dosing, off-label underdosing of DOACs was associated with a higher risk of IS/SE (HR, 1.22 [95% CI, 1.05-1.42], P=0.01). The incidence of major bleeding was similar (HR, 0.95 [95% CI, 0.82-1.11], P=0.48). Off-label underdosing was associated with a higher risk of net clinical outcome (HR, 1.19 [95% CI, 1.04-1.40], P=0.04) and all-cause death (HR, 1.24 [95% CI, 1.04-1.48], P=0.02). Stratified analysis of off-label underdosing of DOACs for IS/SE showed subgroup differences among different DOAC types and study regions. Limited data showed that off-label overdosing was associated with a higher risk of IS/SE (HR, 1.26 [95% CI, 1.11-1.43], P=0.003) and major bleeding (HR, 1.30 [95% CI, 1.04-1.62], P=0.025). CONCLUSIONS: Compared with on-label dosing, off-label underdosing of DOACs increased the risk of thromboembolic events but did not decrease the risk of bleeding. Limited data for off-label overdosing showed higher risks of thromboembolic and bleeding. Further studies are warranted to confirm the results of off-label overdosing DOACs and subgroup results of underdosing DOACs.

Long-term and Temporal Outcomes of Transcatheter Versus Surgical Aortic-valve Replacement in Severe Aortic Stenosis: A Meta-analysis.

OBJECTIVE: To determine the 5-year and temporal performance of TAVR versus SAVR. BACKGROUND: TAVR has become a valuable treatment for severe aortic stenosis but the long-term safety and efficacy remain unclear. METHODS: Databases were searched until October 6, 2019 for randomized trials with ≥5 years' follow-up. Primary outcome was all-cause mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled with random-effects models. RESULTS: We included 4 trials with 3,758 patients. TAVR was associated with a significantly higher 5-year all-cause mortality than SAVR (OR, 1.19; 95% CI, 1.03-1.37; P = 0.02). Landmark analysis showed no significant difference within 2 years (OR, 0.92; 95% CI, 0.79-1.08; P = 0.33) but a statistically higher mortality in TAVR between 2 and 5 years (OR, 1.32; 95% CI, 1.14-1.52; P = 0.0002), with significant difference between these 2 temporal phases (P for interaction = 0.001). Similar interaction was found for cardiovascular mortality and several other outcomes. Rates of all-cause mortality or disabling stroke, permanent pacemaker implantation, aortic-valve rehospitalization, and reintervention were higher, but rates of major bleeding and new-onset fibrillation were lower in TAVR at 5 years. The incidences of myocardial infarction, stroke, and transient ischemic attack were not statistically different between TAVR and SAVR. CONCLUSIONS: TAVR was associated with a significantly higher all-cause mortality at 5 years compared with SAVR. Of note, all-cause mortality presented a characteristic temporal pattern showing increased risk between 2 and 5 years but not within 2 years. Longer-term follow-up data are warranted.

Genetic Basis and Genotype-Phenotype Correlations in Han Chinese Patients with Idiopathic Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure. A large proportion of genetic cause remains unexplained, especially in idiopathic DCM. We performed target next-generation sequencing of 102 genes which were known causes or candidate genes for cardiomyopathies and channelpathies in 118 prospectively recruited Han Chinese patients with idiopathic DCM. 41 of the 118 patients carried 40 pathogenic or likely pathogenic variants, providing a molecular diagnosis in 34.7% of patients. 32 of these variants were novel. TTN truncating variants were predominant, with a frequency of 31.0%, followed by variants of LMNA (14.3%), RBM20 (4.8%), and NEXN (4.8%). These 4 genes accounted for over half variants identified. No significant difference in clinical characteristics or rates of reaching the composite end point (cardiac transplantation and death from cardiac causes) between pathogenic or likely pathogenic variant carriers and noncarriers (hazard ratio 1.11, 95% CI: 0.41 to 3.00), or between patients with TTN truncating variants or without (hazard ratio 0.49, 95% CI: 0.36 to 6.10). In our prospective study, we first determined the overall genetic profiles and genotype-phenotype correlations in Han Chinese idiopathic DCM patients, which could provide insight for genetic diagnosis of DCM in this population.

Association Between Baseline, Achieved, and Reduction of CRP and Cardiovascular Outcomes After LDL Cholesterol Lowering with Statins or Ezetimibe: A Systematic Review and Meta-Analysis.

Background Several lipid-lowering therapies reduce CRP (C-reactive protein) independently of LDL-C (low-density lipoprotein cholesterol) reduction, but the association between CRP parameters and benefits from more-intensive LDL-C lowering is inconclusive. We aimed to determine whether the benefits of more- versus less-intensive LDL-C lowering on cardiovascular events related to baseline, achieved, or magnitude of reduction in CRP concentrations. Methods and Results PubMed, EMBASE, and Cochrane were searched through July 2, 2018. We included randomized controlled cardiovascular outcome trials of LDL-C lowering with statins or ezetimibe. Two reviewers independently extracted study data and rated study quality. Data were analyzed using meta-analysis and metaregression analysis. Rate ratios of mortality and cardiovascular outcomes associated with baseline, achieved, and magnitude reduction of CRP concentration were calculated. Twenty-four trials were included, with 171 250 patients randomly assigned to more- or less-intensive LDL-C-lowering treatments. Median follow-up duration was 4.2 years. More-intensive LDL-C lowering resulted in a significant reduction in incidences of all outcomes. Compared with less-intensive LDL-C lowering, more-intensive LDL-C lowering was associated with less reductions in myocardial infarction with a higher baseline CRP concentration (change in rate ratios per 1-mg/L increase in log-transformed CRP, 1.12 [95% CI, 1.04-1.22; P=0.007]), but not other outcomes. Similar risk reductions occurred for more- versus less-intensive LDL-C-lowering therapy regardless of the magnitude of CRP reduction or the achieved CRP level for all outcomes. Conclusions Baseline CRP concentrations might be associated with the benefits of LDL-C lowering on myocardial infarction, but no other outcomes, whereas the achieved and magnitude of reduction in CRP did not seem to have an important association.

Development of an underivatized LC-MS/MS method for quantitation of 14 neurotransmitters in rat hippocampus, plasma and urine: Application to CUMS induced depression rats.

Sensitive and comprehensive measurement of systemic metabolites of tryptophan, phenylalanine and glutamate metabolism in biological samples is effective for understanding the pathogenesis of depression and other neurological diseases. Therefore, this study developed an underivatized liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous monitoring the 3 components of glutamate metabolism in rat hippocampus and 11 components of tryptophan and phenylalanine metabolism in rat hippocampus, plasma and urine, and applied it to investigate their changes in rats induced by chronic unpredictable mild stress (CUMS). The investigated analytes are as follows: tryptophan, serotonin, 5-hydroxyindoleacetic acid, kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, quinolinic acid, phenylalanine, tyrosine, tyramine, glutamate, glutamine and gamma-aminobutyric acid. The method was verified to be sensitive and effective with satisfactory linearity, accuracies in the range of 78.2%-120.4%, and precisions less than 17.8% for all identified analytes. A series of significant changes in CUMS-induced rats can be detected: tryptophan, serotonin and tyrosine levels decreased and quinolinic acid increased in both hippocampus and plasma. In addition, the kynurenine/tryptophan ratios increased in hippocampus and plasma, the kynurenic acid/quinolinic acid ratios of plasma and urine were significantly reduced. These findings demonstrated that the CUMS procedure could lead to the central and peripheral imbalances of tryptophan and phenylalanine metabolism. In conclusion, a LC-MS/MS method for simultaneous measurement of several neurotransmitters in rat hippocampus, plasma and urine was developed and successfully applied to investigation of the central and peripheral changes in CUMS-induced rats. The method would be expected to provide applicability to the study of the mechanisms of depression and other related diseases associated with these neurotransmitters.

Downregulation of microRNA­182 inhibits cell viability, invasion and angiogenesis in retinoblastoma through inhibition of the PI3K/AKT pathway and CADM2 upregulation.

Retinoblastoma (RB) is a well­vascularized tumor dependent on angiogenesis. The present study aimed to explore whether microRNA (miR)­182 regulates cell viability, invasion and angiogenesis in RB via the phosphatidylinositol­3­OH kinase (PI3K)/protein kinase B (AKT) signaling pathway and by targeting cell adhesion molecule 2 (CADM2). The expression levels of miR­182 and CADM2 were initially detected in RB tissues from patients with RB who underwent ophthalmectomy, and normal retinal tissues collected from other trauma patients who underwent eye enucleation. To determine whether CADM2 was targeted by miR­182, a dual luciferase reporter assay was conducted. Subsequently, Y79 and WERI­Rb­1 RB cells were transfected with a miR­182 mimic or miR­182 inhibitor, or small interfering RNA against CADM2, in order to investigate the effects of miR­182 on viability and invasion, which were detected using MTT and Transwell assays, respectively. In addition, to determine whether the regulatory mechanism underlying the effects of miR­182 was associated with the PI3K/AKT signaling pathway, the expression levels of associated genes were detected by reverse transcription­quantitative polymerase chain reaction and western blot analysis. A xenograft tumor model in nude mice was also established, in order to evaluate the effects of miR­182 on tumor growth and angiogenesis. The results indicated that miR­182 expression was increased and CADM2 expression was reduced in RB tissues; CADM2 was confirmed to be targeted and negatively regulated by miR­182. When the expression of miR­182 was downregulated, cell viability, invasion, tumor volume and angiogenesis were significantly decreased. Furthermore, the expression levels of PI3K/AKT signaling pathway­associated genes were increased in response to miR­182 overexpression or CADM2 silencing. Taken together, these results suggested that inhibition of miR­182 may suppress cell viability, invasion and angiogenesis in RB through inactivation of the PI3K/AKT pathway and CADM2 upregulation. This mechanism may reveal a novel potential therapeutic target.

Percutaneous closure versus medical therapy for stroke with patent foramen Ovale: a systematic review and meta-analysis.

BACKGROUND: Patent foramen ovale (PFO) closure has emerged as a secondary prevention option in patients with PFO and cryptogenic stroke. However, the comparative efficacy and safety of percutaneous closure and medical therapy in patients with cryptogenic stroke and PFO remain unclear. METHODS: Randomized controlled trials (RCTs) and comparative observational studies that compared PFO closure against medical therapy, each with a minimal of 20 patients in the closure arm and 1-year follow-up were included. RESULTS: We analyzed 6961 patients from 20 studies (5 RCTs and 15 observational studies) with a median follow-up of 3.1 years. Moderate-quality evidence showed that PFO closure was associated with a significantly lower incidence of the composite outcome of ischemic stroke, transient ischemic attack (TIA), or all-cause death (odds ratio [OR]: 0.57; 95% confidence interval [CI]: 0.38 to 0.85; P = 0.006), mainly driven by lower incidence of stroke (OR: 0.39; 95% CI: 0.24 to 0.63; P < 0.001). The numbers needed to treat were 43 and 39 for the composite outcome and recurrent ischemic stroke respectively. PFO closure increased the risks for atrial fibrillation or atrial flutter (OR: 5.74; 95% CI: 3.08 to 10.70; P < 0.001; high-quality evidence) and pulmonary embolism (OR: 3.03; 95% CI: 1.06 to 8.63; P = 0.038; moderate-quality evidence), with the numbers needed to harm being 30 and 143 respectively. The risks for TIA, all-cause death, and major bleeding were not statistically different. Analyses limited to RCTs showed similar findings, as did a series of other subgroup analyses. CONCLUSION: In conclusion, PFO closure reduced the incidences of stroke and the composite outcome of ischemic stroke, TIA, or all-cause death, but increased risks for atrial fibrillation or atrial flutter and pulmonary embolism compared with medical therapy.

Comparative safety and efficacy of insulin degludec with insulin glargine in type 2 and type 1 diabetes: a meta-analysis of randomized controlled trials.

AIMS: To determine the safety and efficacy of insulin degludec versus glargine in patients with type 1 (T1D) and type 2 (T2D) diabetes mellitus. METHODS: Databases were searched until July 5, 2017. We included randomized controlled trials comparing degludec with glargine in diabetic patients, each with a minimum of 16 weeks of follow-up. RESULTS: Eighteen trials with 16,791 patients were included. Degludec was associated with a statistically significant reduction in risk for all confirmed hypoglycemia at the maintenance treatment period [estimated rate ratio (ERR) 0.81; 95% confidence interval (CI) 0.72‒0.92; P = 0.001], nocturnal confirmed hypoglycemia at the entire (ERR 0.71; 95% CI 0.63‒0.80; P < 0.001) and maintenance treatment period (ERR 0.65; 95% CI 0.59‒0.71; P < 0.001), all irrespective of the pooled diabetic populations and follow-up durations. The differences in the rate of hypoglycemia were more pronounced in nocturnal period and maintenance period and in T2D than T1D patients. Degludec reduced the incidence of severe hypoglycemia in T2D [ERR 0.65; (0.52; 0.89); P = 0.005] but not T1D patients. HbA1c concentration was slightly higher in degludec over glargine but was not clinically relevant [estimated treatment difference (ETD) 0.03; 95% CI - 0.00 to 0.06%; P = 0.06]. Fasting plasma glucose level was lower in degludec-treated patients (ETD - 0.28 mmol/L; 95% CI - 0.44 to - 0.11 mmol/L; P = 0.001). Several subgroup analyses showed largely consistent findings. The rates of adverse events including total mortality and cardiovascular events were not significantly different between two treatment strategies. CONCLUSIONS: Insulin degludec appears to have better safety in reducing hypoglycemic events with similar efficacy compared with insulin glargine.

Cardiovascular Safety, Long-Term Noncardiovascular Safety, and Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systemic Review and Meta-Analysis With Trial Sequential Analysis.

BACKGROUND: The cardiovascular and long-term noncardiovascular safety and efficacy of SGLT2 (sodium-glucose cotransporter 2) inhibitors have not been well documented. METHODS AND RESULTS: For cardiovascular outcomes, we performed a meta-analysis with trial sequential analysis of randomized controlled trials and adjusted observational studies, each with a minimum of 26 weeks and 2000 patient-years of follow-up. For long-term noncardiovascular safety and efficacy outcome analyses, we included only randomized controlled trials with at least 2 years and 1000 patient-years of follow-up. Five studies with 351 476 patients were included in cardiovascular outcomes analysis. Meta-analyses showed that SGLT2 inhibitors significantly reduced the risks of major adverse cardiac events (hazard ratio [HR]: 0.80; 95% confidence interval [CI], 0.69-0.92; P=0.002), all-cause mortality (HR: 0.67; 95% CI, 0.54-0.84; P<0.001), cardiovascular mortality (HR: 0.77; 95% CI, 0.60-0.98; P=0.03), nonfatal myocardial infarction (HR: 0.86; 95% CI, 0.76-0.98; P=0.02), hospitalization for heart failure (HR: 0.62; 95% CI, 0.55-0.69; P<0.001), and progression of albuminuria (HR: 0.68; 95% CI, 0.58-0.81; P<0.001). No significant difference in nonfatal stroke was found. Analyses limited to randomized controlled trials showed similar findings. Trial sequential analysis provided firm evidence of a 20% reduction in major adverse cardiac events, all-cause mortality, and hospitalization for heart failure with SGLT2 inhibitors, but evidence remains inconclusive for cardiovascular mortality. Nine randomized controlled trials contributed to long-term noncardiovascular and efficacy analyses. SGLT2 inhibitors reduced incidence of hypoglycemia and acute kidney injury but increased the risks of urinary tract and genital infections. CONCLUSIONS: SGLT2 inhibitors showed remarkable cardiovascular- and renal-protective effects and good long-term noncardiovascular safety with sustained efficacy.

Mid- and Long-Term Outcome Comparisons of Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus-Eluting Metallic Stents: A Systematic Review and Meta-analysis.

BACKGROUND: Percutaneous coronary interventions to implant bioresorbable vascular scaffolds (BVSs) were designed to reduce the late thrombotic events that occur with metallic stents. PURPOSE: To estimate the incidence of scaffold thrombosis after BVS implantation and compare everolimus-eluting BVSs with everolimus-eluting metallic stents (EESs) in terms of safety and efficacy at mid- and long-term follow-up in adults who had a percutaneous coronary intervention. DATA SOURCES: PubMed, EMBASE, the Cochrane Library, conference proceedings, and relevant Web sites from inception until 20 May 2017, without language restriction. STUDY SELECTION: 7 randomized trials and 38 observational studies (each with a minimum of 6 months and 100 patient-years of follow-up) in adults with coronary artery disease who had a BVS or an EES and reported scaffold or stent thrombosis (main outcome) or other secondary outcomes (such as death, myocardial infarction, or revascularization). DATA EXTRACTION: 2 reviewers independently extracted study data, rated study quality, and assessed strength of evidence. DATA SYNTHESIS: The pooled incidence of definite or probable scaffold thrombosis after BVS implantation was 1.8% (95% CI, 1.5% to 2.2%) at a median follow-up of 1 year (41 studies, 21 884 patients) and 0.8% (CI, 0.5% to 1.3%) beyond 1 year (14 studies, 4688 patients). Seven trials involving 5578 patients that directly compared BVSs with EESs showed an increased risk for definite or probable scaffold thrombosis (odds ratio [OR], 3.40 [CI, 2.01 to 5.76]) with BVSs at a median follow-up of 25 months. Increased risks were present at early (prominently subacute), late, and very late stages, and odds beyond 1 year were almost double those seen within 1 year. Bioresorbably vascular scaffolds increased risks for myocardial infarction (OR, 1.63 [CI, 1.26 to 2.10]), target lesion revascularization (OR, 1.31 [CI, 1.03 to 1.67]), and target lesion failure (OR, 1.37 [CI, 1.12 to 1.66]); the odds for these 3 end points also increased over time. The incidences of all-cause, cardiac, and noncardiac death and of target vessel and any revascularization did not differ. LIMITATION: Quality of observational studies was unclear, and some data were unpublished. CONCLUSION: Compared with EESs, BVSs increased the risks for scaffold thrombosis and other thrombotic events at mid- and long-term follow-up, and risks increased over time. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.

Percutaneous intervention versus coronary artery bypass graft surgery in left main coronary artery stenosis: a systematic review and meta-analysis.

BACKGROUND: The optimal revascularization technique in patients with left main coronary artery disease (CAD) remains controversial. We aimed to compare the long-term performance of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery in treatment of left main CAD. METHODS: PubMed, EMBASE, and the Cochrane Library were searched until November 16, 2016. RESULTS: Six randomized controlled trials and 22 matched observational studies including 22,487 patients and 90,167 patient-years of follow-up were included. PCI was associated with an overall higher risk for the major adverse cardiac and cerebrovascular events (hazard ratio (HR), 1.42; 95% confidence interval (CI), 1.14-1.77), mainly driven by higher rates of myocardial infarction (HR, 1.69; 95% CI, 1.22-2.34) and revascularization (HR, 2.80; 95% CI, 1.86-4.22). The overall risks for all-cause death (HR, 1.05; 95% CI, 0.93-1.20), cardiac death (HR, 1.05; 95% CI, 0.69-1.59), stroke (HR, 0.64; 95% CI, 0.33-1.24), and the composite safety endpoint of death, myocardial infarction, or stroke (HR, 1.06; 95% CI, 0.97-1.16) were similar between PCI and CABG. Stratified analysis based on stent types showed that the increased risk for myocardial infarction associated with PCI was only evident in patients with bare-metal stents or early-generation drug-eluting stents (DES), but not newer-generation DES. Stratified analyses based on study designs showed largely similar findings with the overall analyses, except for a significantly higher incidence of myocardial infarction in adjusted studies (HR, 2.01; 95% CI, 1.64-2.45) but a trend toward higher incidence in randomized trials (HR, 1.39; 95% CI, 0.85-2.27) associated with PCI. CONCLUSIONS: Compared with CABG, PCI with newer-generation DES might be a safe alternative revascularization strategy for treatment of left main CAD, but is associated with more repeat revascularization.

Prognostic Significance of Frontal QRS-T Angle in Patients with Idiopathic Dilated Cardiomyopathy.

BACKGROUND: Current risk stratification of idiopathic dilated cardiomyopathy (IDC) lacks sufficient sensitivity and specificity. The objective of this study was to investigate the predictive role of frontal QRS-T angles in IDC. METHODS: A prospective study with 509 IDC patients was performed from February 2008 to December 2013 in the Affiliated Drum Tower Hospital, Nanjing University School of Medicine. Baseline values and changes in QRS-T angles were recorded. Follow-up was conducted every 6 months. Analyses by Cox Proportional Hazards model were performed to evaluate the association between QRS-T angle and outcomes. The primary outcome of interest was all-cause mortality. RESULTS: During a median follow-up of 34 months, 90 of 316 patients with QRS-T angles >90° died compared to 31 of 193 patients with QRS-T angles ≤90° (hazard ratio [HR] =2.4, P < 0.001). Cardiac death was more prevalent in patients with a wide QRS-T angle (HR = 2.4, P < 0.001), similar to heart failure rehospitalization (HR = 2.5, P < 0.001). After adjustment for potential prognostic factors, the QRS-T angle was independently associated with all-cause mortality (HR = 2.5, P < 0.05), cardiac mortality (HR = 1.9, P < 0. 05), and heart failure rehospitalization (HR = 2.3, P < 0.01). Optimized therapy significantly narrowed the frontal QRS-T angle (100.9 ± 53.4° vs. 107.2 ± 54.4°, P < 0.001). The frontal QRS-T angle correlated well with established risk factors, such as left ventricular ejection fraction, brain natriuretic peptide, and New York Heart Association functional class. CONCLUSIONS: The frontal QRS-T angle is a powerful predictor of all-cause mortality, cardiac mortality, and worsening heart failure in IDC patients, independent of well-established prognostic factors. Optimized therapy significantly narrows the QRS-T angle, which might be an indicator of medication compliance, but this requires further investigation.

Periostin expression induced by oxidative stress contributes to myocardial fibrosis in a rat model of high salt-induced hypertension.

Periostin is an extracellular matrix protein involved in fibrosis. The present study investigated the importance of periostin in hypertension­induced myocardial fibrosis. Rats were randomly divided into either the normal group (0.4% NaCl diet; n=8) or hypertension group (8% NaCl diet; n=8). For 36 weeks, the blood pressure and heart rate of the rats were monitored. At week 36, the hearts were extracted for further analysis. Masson's staining and western blotting were performed to determine the levels of periostin protein expression, oxidative stress and fibrosis. In addition, fibroblasts were isolated from adult rats and cultured in vitro, and following treatment with angiotensin II (Ang II) and N-acetyl-L-cysteine (NAC), western blotting, immunofluorescence and 2',7' dichlorodihydrofluorescin staining were performed to examine reactive oxygen species production, and periostin and α­smooth muscle actin (α­SMA) expression levels. The results demonstrated that periostin expression and oxidative stress were increased in hypertensive hearts compared with normal hearts. The in vitro experiments demonstrated that Ang II upregulated the expression levels of periostin and α­SMA compared with the control, whereas, pretreatment with NAC inhibited oxidative stress, periostin and α­SMA expression in fibroblasts. In conclusion, the results of the current study suggested that oxidative stress­induced periostin is involved in myocardial fibrosis and hypertension. The present study demonstrated that periostin inhibition may be a promising approach for the inhibition of hypertension-induced cardiac remodeling.