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Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (EF, HFrEF) have experienced partial or complete recovery of EF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in hospitalized HFrEF patients with type 2 diabetes mellitus (T2DM).A total of 463 hospitalized T2DM patients with HFrEF were consecutively enrolled. Follow-up echocardiogram was performed after around 12 months. Patients who had an absolute EF improvement ≥10% and a second EF 40% were classified into HFrecEF, and those who did not meet these criteria were defined as persistent HFrEF.During the 12-month follow-up, 44.5% of T2DM patients developed HFrecEF. Patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.5% [IQR 5.8% ∼ 7.2%] vs. 6.7% [IQR 6.1% ∼ 7.8%], P = 0.003), especially in HF of an ischemic etiology. HbA1c levels were inversely correlated with changes in EF during follow-up. After multivariate adjustment, every 1% increase in HbA1c conferred a 17.4% (OR: 0.826 [95% CI 0.701-0.968]) lower likelihood of HFrecEF. Compared to patients with good glycemic control (HbA1c ≤ 6.2%), those with poor glycemic control (HbA1c 7.1%) had a 52.0% (OR: 0.480 [95% CI 0.281-0.811] decreased likelihood of HFrecEF.This study demonstrates that uncontrolled HbA1c level is associated with compromised development of HFrecEF in T2DM patients with HF, especially in those with an ischemic etiology.

Background Because of advances in medical treatments, a substantial proportion of patients with heart failure (HF) have experienced recovery of ejection fraction (EF), termed HF with recovered EF (HFrecEF). Insulin resistance (IR) is prevalent in HF and tightly related with prognosis. This study investigates the relationship between IR and the incidence of HFrecEF in patients who are nondiabetic. Methods and Results A total of 262 patients with HF with reduced EF (HFrEF) who were nondiabetic were consecutively enrolled. Patients were classified into HFrecEF (follow‐up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. IR was estimated by an updated homeostasis model assessment for IR (HOMA2‐IR). The median HOMA2‐IR level was 1.05 (interquartile range [IQR], 0.67–1.63) in our cohort of patients with HF who were nondiabetic. During follow‐up, 121 (odds ratio [OR], 46.2% [95% CI 40.2–52.2]) patients developed HFrecEF. Compared with patients with HFrEF, patients with HFrecEF had significantly lower HOMA2‐IR levels (0.92 [IQR, 0.61–1.37] versus 1.14 [IQR, 0.75–1.78], P =0.007), especially in nonischemic HF. Log 2 ‐transformed HOMA2‐IR was inversely correlated to improvements in EF (Pearson's r =−0.25, P Conclusions This study reveals that IR is independently associated with compromised development of HFrecEF in patients who are nondiabetic.

Background. Left ventricular (LV) diastolic dysfunction (LVDD) is the defining feature of heart failure with preserved ejection fraction (HFpEF) and predicts subsequent incident heart failure (HF) and all-cause mortality. Mounting evidence reveals that cardiometabolic risk factors play critical roles in the development of LVDD. In this study, we sought to investigate the relation between serum uric acid (SUA) level and the progression of LVDD in apparently healthy patients. Methods. A total of 1082 apparently healthy subjects without diagnosed cardiovascular disease and LVDD were consecutively enrolled. SUA levels were measured, and repeat echocardiography and tissue Doppler imaging (TDI) were performed at baseline and during 1-year follow-up. Results. By dividing the study population based on quartiles of SUA, we found subjects in higher quartiles had greater increases in TDI-derived early diastolic velocity (e ′ ) and E (peak LV filling velocity)/e ′ ratios during 1-year follow-up. After multivariate adjustment, high SUA persisted to be an independent predictor for the subsequent worsening of LVDD (odds ratio: 1.351 [95% CI 1.125~1.625], per 100 μmol/L SUA). Subgroup analysis suggested that the association between SUA and LVDD development was more pronounced in subjects without other cardiometabolic risk factors involved. Factor analysis demonstrated that high SUA was the major cardiometabolic attribute in patients with LVDD progression. Conclusion. Our findings suggest that high SUA is an independent cardiometabolic risk factor for the progression of LVDD in apparently healthy subjects.

Background The formation of advanced glycation end-products (AGEs) is a crucial risk factor for the pathogenesis of cardiovascular diseases in diabetes. We investigated whether N-epsilon-carboxymethyllysine (CML), a major form of AGEs in vivo, was associated with poor coronary collateral vessel (CCV) formation in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) of coronary artery. Methods This study consisted of 242 T2DM patients with coronary angiographically documented CTO. Blood samples were obtained and demographic/clinical characteristics were documented. The coronary collateralization of these patients was defined according to Rentrop or Werner classification. Serum CML levels were evaluated using ELISA assay. Receiver operating characteristic curve and multivariable regression analysis were performed. Results 242 patients were categorized into poor CCV group or good CCV group (107 vs. 135 by the Rentrop classification or 193 vs. 49 by the Werner classification, respectively). Serum CML levels were significantly higher in poor CCV group than in good CCV group (110.0 ± 83.35 vs. 62.95 ± 58.83 ng/ml by the Rentrop classification and 94.75 ± 78.29 ng/ml vs. 40.37 ± 28.69 ng/ml by Werner classification, both P Conclusions This study suggests that higher serum CML level is associated with poor collateralization in T2DM patients with CTO.

Background Patients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit HbA1c variability is a potential predictor of ISR in diabetic patients after stent implantation. Methods We consecutively enrolled type 2 diabetic patients who underwent successful elective percutaneous coronary intervention and performed follow-up coronary angiography after around 12 months. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of HbA1c variability for ISR. Results From September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8 ± 1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P = 0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9 ± 16.8%, 0.42 ± 0.88 mm and 1.66 ± 0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P

BACKGROUND Anatomic hepatectomy and wide resection margin may improve surgical outcome of patients with hepatocellular carcinoma (HCC), but not everyone gain survival benefit. It remains unclear what kind of patients would benefit from those surgical methods. We investigated the factors affecting survival of patients with HCC, with special attention paid to the surgical methods and pathological factors. METHODS A retrospective analysis was conducted on 231 patients with hepatitis B-related HCC who underwent surgery from August 2011 to November 2013 in authors' institute. The survival analysis included the following variables: gender, age, viral load, alpha-fetoprotein, des-γ-carboxy prothrombin, tumour size, cirrhosis, blood transfusion, complications, resection method, resection margin, microvascular invasion (mVI), peritumoural satellite nodule, recurrence time and recurrent burden. RESULTS The median follow-up time was 59 months. A total of 196 patients (84.9%) recurred and 151 patients (65.4%) deceased due to the disease. Multivariate analysis showed that cirrhosis, mVI and periturmoral satellite nodules were independent risk factors affecting overall survival after operation. The comparison between anatomic resection and local resection, and wide resection margin and narrow resection margin showed no significant differences for recurrence-free survival and overall survival, respectively (P = 0.089 and 0.068, 0.108 and 0.122). Stratified analysis revealed that anatomic resection and wide resection margin surgery improved survival when mVI or peritumoural satellite existed. CONCLUSION Anatomic resection and wide resection margin are effective methods to improve the surgical outcome of HCC with periturmoral micrometastasis, although tumour characteristics affect patients' survival more than surgical techniques.

Purpose To assess the accuracy of magnetic resonance (MR) imaging-based differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in a cohort of patients with focal liver lesions and cirrhosis. Materials and Methods This study was institutional review board approved, and the requirement for informed consent was waived. Between January 2009 and December 2014, a cohort of cirrhotic patients, including 71 with ICC and 612 with HCC, underwent unenhanced T1- and T2-weighted MR imaging, gadolinium-based contrast material-enhanced dynamic phase imaging, and partial hepatectomy. Results of pathologic examinations were obtained for all patients. Clinical, radiologic, and pathologic results in these patients were analyzed and compared comprehensively. Differences in signal intensity on baseline and contrast material-enhanced images and dynamic enhancement patterns were evaluated and compared by using the χ(2) test or the Fisher exact test. Results The preoperative diagnoses of 517 of 683 lesions were confirmed pathologically. Five ICCs and 481 HCCs displayed contrast material washout in delayed phases (P < .001). Thirty-six ICCs and 23 HCCs displayed a progressive enhancement pattern (P < .001). Twenty-six ICCs and 63 HCCs displayed a stable enhancement pattern (P < .001). ICCs displayed significantly different enhancement patterns according to size (P = .022). Conclusion The accurate discrimination of small ICCs from HCCs in the setting of cirrhosis at MR imaging is difficult, as substantial proportions of ICCs and HCCs have similar enhancement patterns. Absence of contrast material washout at MR imaging is not a factor that prevents the misdiagnosis of HCC. (©) RSNA, 2016 Online supplemental material is available for this article.

Background: Angiotensin type 1 receptor (AT 1 R) antagonists are extensively used for blood pressure control in elderly patients with hypertension. This study aimed to investigate the inhibitory effects of AT 1 R antagonist valsartan on platelet aggregation and the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension. Methods: Two-hundred and ten patients with hypertension and aged > 60 years were randomized to valsartan (n = 140) or amlodipine (n = 70) on admission. The primary endpoint was platelet aggregation rate (PAR) induced by arachidonic acid at discharge, and the secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up. Human aortic endothelial cells (HAECs) were stimulated by angiotensin II (Ang II, 100 nmol/L) with or without pretreatment of valsartan (100 nmol/L), and relative expression of cyclooxygenase-2 (COX-2) and thromboxane B 2 (TXB 2 ) and both p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kB (NF-kB) activities were assessed. Statistical analyses were performed by GraphPad Prism 5.0 software (GraphPad Software, Inc., California, USA). Results: PAR was lower after treatment with valsartan (11.49 ± 0.69% vs. 18.71 ± 2.47%, P < 0.001), associated with more reduced plasma levels of COX-2 (76.94 ± 7.07 U/L vs. 116.4 ± 15.89 U/L, P < 0.001) and TXB 2 (1667 ± 56.50 pg/ml vs. 2207 ± 180.20 pg/ml) (all P < 0.001). Plasma COX-2 and TXB 2 levels correlated significantly with PAR in overall patients (r = 0.109, P < 0.001). During follow-up (median, 18 months), there was a significantly lower thrombotic event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002). Relative expression of COX-2 and secretion of TXB 2 with concordant phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L). Conclusions: AT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

Background Uptake of oxidized low-density lipoprotein (oxLDL) by macrophages is recognized as a crucial step in the development of atherosclerosis, whereas the precise molecular mechanisms involving it remain to be elucidated. Methods and results This study focused on determining the role of toll-like receptor 4 (TLR4) and Src kinase in macrophage lipid accumulation. oxLDL significantly enhanced Src kinase activity and intracellular lipid contents in RAW264.7 macrophages, whereas the small interference RNA-mediated knockdown of TLR4 and Src or chemical inhibition of Src activity blocked oxLDL-induced lipid accumulation. Immunoprecipitation and immunofluorescence studies demonstrated that TLR4 was associated with Src on the plasma membrane upon oxLDL stimulation. Conclusions The results of the present study suggest an essential role of TLR4-Src signaling in macrophages in the pathogenesis of atherosclerosis.

Objective: In this paper, we review the previous classic research paradigms of a mass casualty incident (MCI) systematically and reflect the medical response to the Wenchuan earthquake and Hangzhou bus fire, in order to outline and develop an improved research paradigm for MCI management. Methods: We searched PubMed, EMBASE, China Wanfang, and China Biology Medicine (CBM) databases for relevant studies. The following key words and medical subject headings were used: ‘mass casualty incident’, ‘MCI’, ‘research method’, ‘Wenchuan’, ‘earthquake’, ‘research paradigm’, ‘science of surge’, ‘surge’, ‘surge capacity’, and ‘vulnerability’. Searches were performed without year or language restriction. After searching the four literature databases using the above listed key words and medical subject headings, related articles containing research paradigms of MCI, 2008 Wenchuan earthquake, July 5 bus fire, and science of surge and vulnerability were independently included by two authors. Results: The current progresses on MCI management include new golden hour, damage control philosophy, chain of survival, and three links theory. In addition, there are three evaluation methods (medical severity index (MSI), potential injury creating event (PICE) classification, and disaster severity scale (DSS)), which can dynamically assess the MCI situations and decisions for MCI responses and can be made based on the results of such evaluations. However, the three methods only offer a retrospective evaluation of MCI and thus fail to develop a real-time assessment of MCI responses. Therefore, they cannot be used as practical guidance for decision-making during MCI. Although the theory of surge science has made great improvements, we found that a very important factor has been ignored—vulnerability, based on reflecting on the MCI response to the 2008 Wenchuan earthquake and July 5 bus fire in Hangzhou. Conclusions: This new paradigm breaks through the limitation of traditional research paradigms and will contribute to the development of a methodology for disaster research.

Background Sirolimus-eluting stents (SES) with a biodegradable polymer coating have demonstrated promising results but have not been compared to SES with a durable polymer in high-risk patients. We compared the efficacy of these 2 stent types in patients with acute myocardial infarction (STEMI). Methods One thousand one hundred ninety-two STEMI patients were randomized to receive SES coated with biodegradable (n = 596) or durable polymer (n = 596). The study end-point was the composite of major adverse cardiac events (MACE) including all-cause death, recurrent myocardial infarction (MI), or target lesion revascularization (TLR) at 1-year follow-up. Secondary end-points included individual components of primary end-point and stent thrombosis. Results Compared with durable polymer SES, the noninferiority of SES with biodegradable polymer coating was established by an absolute risk difference of 0.9% in the primary end-point (12.4% vs. 13.3%, P = 0.67) and an upper limit of one-sided 95% confidence interval (CI) of 2.96% (P for noninferiority = 0.001). Rate of death, recurrent MI, and TLR were 7.9% and 8.6% (HR: 0.92; 95% CI: 0.61–1.38, P = 0.67), 2.9% and 3.5% (HR: 0.80; 95% CI: 0.42–1.54, P = 0.51), and 2.0% and 3.2% (HR: 0.62; 95% CI: 0.30–1.30, P = 0.20) in the biodegradable polymer SES and durable polymer SES group at 1-year clinical follow-up, respectively. Despite similar rates of 30-day ARC definite/probable stent thrombosis, late stent thrombosis (stent thrombosis occurring beyond 30 days) was lower with biodegradable polymer SES (0.7% vs. 2.2%, P = 0.028). Conclusions In patients undergoing primary PCI for STEMI, the use of biodegradable polymer SES was associated with noninferior 1-year rates of MACE compared with durable polymer SES. (J Interven Cardiol 2014;27:131–141)

Objective— In a previous study, we established diabetic and nondiabetic minipig models with coronary artery in-stent restenosis (ISR). Mass spectrometry showed that high-mobility group box (HMGB) 2 level was higher in ISR than in non-ISR tissue from diabetic minipigs. We here investigated whether serum HMGB2 levels were related to ISR in coronary artery disease patients. The effect of HMGB2 was evaluated in mice with femoral artery wire injury and in human aortic smooth muscle cells. Approach and Results— From 2513 patients undergoing coronary artery intervention and follow-up angiography at ≈1 year, 262 patients were diagnosed with ISR, and 298 patients with no ISR were randomly included as controls. Serum HMGB2 levels were significantly higher in patients with ISR than in those without ISR and were associated with ISR severity. Multivariable logistic regression analysis showed that HMGB2 level was independently associated with ISR. In experiments, HMGB2 expression was increased in vascular tissue after injury. Perivascular HMGB2 administration promoted injury-induced neointimal hyperplasia in C57Bl/6 mice compared with in the control, whereas such pathophysiological features were attenuated in Hmgb2 –/– mice. Mechanistically, HMGB2 enhanced neointimal hyperplasia in mice and proliferation and migration in human aortic smooth muscle cells by inducing reactive oxygen species through increased p47phox phosphorylation. Knocking down p47phox, however, inhibited HMGB2-induced effects in human aortic smooth muscle cells. Finally, HMGB2-induced effects were significantly declined in receptor of advanced glycation end products knockdown or deficient cells, but not in Toll-like receptor 4 knockdown or deficient cells. Conclusions— Serum HMGB2 levels were associated with ISR in patients. HMGB2 promoted neointimal hyperplasia in mice with arterial wire injury through reactive oxygen species activation.

The regulation of inflammatory responses by innate immune receptors is recognized as a crucial step in the development of atherosclerosis, although the precise molecular mechanisms remain to be elucidated. This study focused on illustrating the roles of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)- and Toll-like receptor 4 (TLR4)-regulated inflammatory responses in macrophages. We found that DC-SIGN expression levels were increased in macrophages of atherosclerotic plaques. Oxidized low-density lipoprotein (oxLDL) significantly enhanced DC-SIGN protein expression levels after a short-term exposure. Knockdown of DC-SIGN decreased expression and secretion of interleukin 1-β (IL1-β), monocyte chemo-attractant protein 1 (MCP-1), tumor necrosis factor-α (TNFα) and matrix metalloproteinase-9 (MMP-9). Immunofluorescence studies demonstrated that DC-SIGN and TLR4 co-localized in regions of the plaques. Moreover, DC-SIGN was co-expressed with TLR4 on the plasma membrane after oxLDL stimulation. The presence of an endogenous interaction and the results of the in vitro pull-down assays revealed that DC-SIGN binds directly with TLR4. We also present evidence that DC-SIGN mediates TLR4-regulated NFκB activation but not activation of p38 and JNK. Our results suggest an essential role of DC-SIGN/TLR4 signaling in macrophages in the pathogenesis of atherosclerosis.

Background— Traditional reperfusion options for patients with acute ST-segment elevation myocardial infarction (STEMI) presenting to non-primary percutaneous coronary intervention (PPCI)-capable hospitals generally include onsite fibrinolytics or emergency transfer for PPCI. A third option, involving interventionalist transfer, was examined in the REVERSE-STEMI study. Methods and Results— A total of 334 patients with acute STEMI who presented to 5 referral hospitals with angiographic facilities but without interventionalists qualified for PPCI were randomized to receive PPCI with either an interventionalist- (n=165) or a patient-transfer (n=169) strategy. The primary end point of door-to-balloon (D2B) time and secondary end points of left ventricular ejection fraction and major adverse cardiac events (MACE) at 1-year clinical follow-up were compared between the 2 groups. Compared with the patient-transfer strategy, the interventionalist-transfer strategy resulted in a significantly shortened D2B time (median, 92 minutes versus 141 minutes; P P P P =0.019). Multivariate Cox proportional hazards modeling revealed that the interventionalist-transfer strategy was an independent factor for reduced risk of composite MACE (hazard ratio, 0.63; 95% CI, 0.45 to 0.88; P =0.003). Conclusions— The interventionalist-transfer strategy for PPCI may be effective in improving the care of patients with STEMI presenting to a non-PPCI-capable hospital, particularly in a congested cosmopolitan region where patient transfers could be prolonged. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00713557.

We sought to examine if polymorphisms in the promoter region of YKL-40 gene (CHI3L1) are associated with serum YKL-40 levels and coronary artery disease (CAD) in Chinese patients.Three single nucleotide polymorphisms (SNPs) (-329GA, rs10399931; -247CT, rs10399805; -131GC, rs4950928) in the CHI3L1 promoter were determined in 213 consecutive patients with angiographically documented CAD (luminal diameter stenosis ≥50%) and 248 normal controls. Coronary cumulative obstruction score and number of diseased vessels represent the severity of CAD. Serum YKL-40 levels were assessed using an ELISA kit.Patients with CAD had remarkably higher serum YKL-40 levels compared to controls (p0.001). There was no difference in the allele, genotype and haplotype distribution of these three SNPs between controls and CAD patients. The minor alleles of CHI3L1-329GA and -131GC were significantly associated with decreased serum YKL-40 levels in both controls (p = 0.001 and p0.001, respectively) and CAD patients (p = 0.007 and p0.001, respectively), whereas CHI3L1-247CT had no appreciable effect. None of these genetic variants and haplotypes was associated with severity of angiographic CAD.CHI3L1-329GA and -131GC polymorphisms are associated with serum YKL-40 levels, but not with the prevalence or severity of CAD.

Excessive formation of advanced glycation end products (AGE) and lipid accumulation in macrophages play a pivotal role in the progression of atherosclerosis in diabetes mellitus. This study aimed to determine the molecular link between AGE-induced fatty acid binding protein 4 (FABP4) expression and macrophage lipid accumulation. AGE-BSA markedly increased macrophage FABP4 expression via engagement of RAGE, a 35-kDa transmembrane receptor that is able to bind extracellular AGE and responsible for the corresponding signal transduction, whereas knockdown of RAGE significantly reversed the FABP4 up-regulation. This effect was further paralleled with elevated intracellular total cholesterol and triacylglycerol levels. Finally, administration of FABP4 inhibitor totally abolished the increased lipid contents in response to AGE-BSA. These results indicate that FABP4 up-regulation is responsible for the enhanced macrophage lipid accumulation by AGE, which may underlie the accelerated formation of foam cells and development of atherosclerotic cardiovascular diseases in diabetic patients.

BACKGROUND: This study sought to examine whether circulatory levels of endothelial dysfunction biomarkers [vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1), sE-selectin, von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1)] are associated with occurrence of late or very late stent thrombosis (ST) after percutaneous coronary intervention with sirolimus-eluting stent implantation, and to assess the possible influence of genetic variants of these proteins on ST. METHODS: Serum levels of sVCAM-1, sICAM-1, sE-selectin, vWF, t-PA and PAI-1 were measured, and polymorphisms of vWF (-1234C/T, -1185A/G and -1051G/A), t-PA (insertion/deletion) and PAI-1 genes (4G/5G) were determined in 41 patients who experienced at least one episode of late or very late ST. Eighty-two patients without ST randomly selected from the same study period served as controls. RESULTS: Serum levels of vWF, sVCAM-1 and sICAM-1 were significantly increased in patients with ST than in controls (all P

We sought to investigate whether numbers and activity of circulating endothelial progenitor cells (EPCs) correlate with severity of coronary stenosis as well as cardiovascular risk factors in patients with stable coronary artery disease (CAD). Number of circulating EPCs was analyzed in 104 consecutive patients with proven or clinically suspected CAD. Adhesive and migratory activity was also determined. The number of EPCs was lower in patients with a single diseased coronary artery (Group II, n=35, p

Background: Our previous study suggested that heart-type fatty acid-binding protein (HFABP) levels were greatly elevated in the conditioned medium of explant culture of in-stent restenosis (ISR) tissue from diabetic minipigs compared with those of non-ISR tissue. We here verified this result in animal tissues and investigated the impact of HFABP overexpression in human aortic smooth muscle cells (hASMCs). Methods and Results: In Western blot and real-time RT-PCR, HFABP protein and mRNA levels were significantly higher in ISR than in non-ISR tissues from minipigs, and higher in the ISR tissue from diabetic minipigs than that from nondiabetic minipigs. The mRNA microarray and cellular effects of hASMC retroviral overexpression of HFABP and vector was analyzed. Compared with vector, HFABP transduction activates multiple signaling pathways (e.g. adipokine, TGF-β, Toll-like receptor, Wnt, Hedgehog, ErbB and Notch) and promotes inflammation, growth and migration in hASMCs whereas the knockdown of HFABP by small hairpin RNA attenuates these effects. Conclusion: HFABP expression is significantly higher in ISR tissue than in non-ISR tissue from diabetic and nondiabetic minipigs. Overexpression of HFABP induces multiple pathway-related promotion of inflammation, growth and migration in vascular SMCs, suggesting a potential role in coronary artery ISR.

There is increasing interest in percutaneous coronary intervention (PCI) for chronic total occlusions (CTO). Periprocedural myocardial injury (PMI) post CTO PCI is not uncommon, but true incidence and implications of PMI are not well understood.This study aimed to investigate risk factors for PMI post CTO PCI and its implications for the 1-year clinical outcome of a Chinese population.Baseline characteristics, procedure features, and major adverse cardiac events (MACE) at 1 year were assessed in 629 consecutive patients who underwent CTO PCI. PMI was diagnosed as an elevation of creatine kinase MB ≥3 times ULN 12-24 hr post procedure. Multivariate analysis was performed to determine the correlates of PMI and MACE at 1-year follow-up.In total, PMI was detected in 115 patients (18.3%). Compared with patients without PMI, those with PMI had a higher percentage of previous coronary artery bypass grafting (CABG), right coronary occlusion and side branch occlusion, and technical success was lower in the PMI group (90.4% vs. 96.7%, P = 0.003). One-year MACE-free survival was reduced in the PMI group (87.8% vs. 95.9%, P = 0.001). The final TIMI flow 0-1 (OR 2.23, 95%CI 1.06-4.87, P = 0.02), side branch occlusion (OR 2.67, 95%CI 1.19-7.11, P = 0.009), retrograde PCI (OR 1.35, 95%CI 1.10-2.74, P = 0.04), and history of prior CABG (OR 2.41, 95%CI 1.38-5.91, P = 0.01) were independent risk factors for the occurrence of PMI.In this unique Chinese cohort, PMI post CTO PCI was associated with several clinical and angiographic factors and exerts an adverse effect on 1-year clinical outcomes.

Background Pulmonary embolism (PE) is a potentially life-threatening condition. Although computed tomography pulmonary angiography (CTPA) is the reference standard for diagnosis, its early diagnosis remains a challenge, and the concerns about the radiation exposures further limit the general use of CTPA. The primary aim of this meta-analysis was to evaluate the overall diagnostic accuracy of transthoracic lung ultrasound (TLS) in the diagnosis of PE. Methods PubMed, Web of science, OvidSP, ProQuest, EBSCO, Cochrane Library and Clinicaltrial.gov were searched systematically. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and hierarchical summary receiver operating characteristic (HSROC) curves were used to examine the TS performance. The Bayes analysis was used to calculate the post-test probability of PE. Publication bias was assessed with Deeks funnel plot. Results The results indicated that the sensitivity, specificity, PLR and NLR were 0.85 (95% confidence interval (CI), 0.78 to 0.90), and 0.83 (95% CI, 0.73 to 0.90). And the DOR and HSROC were 28.82 (95% CI, 17.60 to 47.21), 0.91(95% CI, 0.88, 0.93). Conclusions The present meta-analysis suggested that transthoracic lung ultrasonography is helpful in diagnosing pulmonary embolism. Although the application of transthoracic lung ultrasound may change some patients’ diagnostic processes, it is inappropriate to generally use transthoracic ultrasonography in diagnosing pulmonary embolism currently.

OBJECTIVE We investigated whether and to what extent blood pressure (BP) affects coronary collateralization in type 2 diabetic and nondiabetic patients with stable angina and chronic total occlusion. METHODS Brachial BP was measured using an inflatable cuff manometer in 431 diabetic and 287 nondiabetic patients with stable angina and angiographic total occlusion of at least one major coronary artery. They were classified according to the SBP (

Patients are at risk of developing periprocedural myonecrosis after percutaneous coronary intervention (PCI). We investigated whether the use of the platelet glycoprotein (GP) IIb/IIIa receptor inhibitor tirofiban could reduce periprocedural myocardial infarction (PMI) in patients with stable coronary artery disease undergoing elective PCI with overlapping stent implantation for long lesions.A total of 748 stable angina patients with long lesions (≥ 40 mm in length) treated with overlapping stent implantation were randomly assigned to receive tirofiban (tirofiban group; n = 373) or conventional therapy (control group; n = 375). Intravenous tirofiban was initiated before PCI and maintained for 12 hr after the procedure. The primary endpoint was PMI, defined as an elevation in CK-MB3 times the upper limit of normal 12 hr after the index procedure. The secondary endpoint was major adverse cardiac events (MACE), including cardiac death, target vessel revascularization, and recurrent MI (re-MI), at one-year of clinical follow-up. The safety end-points included Thrombolysis in Myocardial Infarction (TIMI) major bleeding and stent thrombosis.Despite comparable angiographic and procedural characteristics, in the intention-to-treatment analysis, the primary endpoint was significantly reduced in the tirofiban group (4.0% vs. 11.5%, P0.001). Multivariate analysis revealed that the adjunctive use of tirofiban was the only negative predictor of PMI (OR 0.41, 95% CI 0.28-0.81, P0.01). At one-year of clinical follow-up, the overall occurrence of MACE was significantly lower in the tirofiban group (13.4% vs. 22.7%, P = 0.001). The rate of TIMI major bleeding and stent thrombosis did not differ significantly between the two groups.Our results show that the adjunctive use of tirofiban reduces the occurrence of PMI and MACE at one year in stable coronary artery disease patients undergoing elective PCI for long lesions with overlapping stent implantation.

Eph receptor (Eph)‐ephrin signaling plays an important role in organ development and tissue regeneration. Bidirectional signaling of EphB4–ephrinB2 regulates cardiovascular development. To assess the role of EphB4–ephrinB2 signaling in cardiac lineage development, we utilized two GFP reporter systems in embryonic stem (ES) cells, in which the GFP transgenes were expressed in Nkx2.5+ cardiac progenitor cells and in α‐MHC+ cardiomyocytes, respectively. We found that both EphB4 and ephrinB2 were expressed in Nkx2.5‐GFP+ cardiac progenitor cells, but not in α‐MHC‐GFP+ cardiomyocytes during cardiac lineage differentiation of ES cells. An antagonist of EphB4, TNYL‐RAW peptides, that block the binding of EphB4 and ephrinB2, impaired cardiac lineage development in ES cells. Inhibition of EphB4–ephrinB2 signaling at different time points during ES cell differentiation demonstrated that the interaction of EphB4 and ephrinB2 was required for the early stage of cardiac lineage development. Forced expression of human full‐length EphB4 or intracellular domain‐truncated EphB4 in EphB4‐null ES cells was established to investigate the role of EphB4‐forward signaling in ES cells. Interestingly, while full‐length EphB4 was able to restore the cardiac lineage development in EphB4‐null ES cells, the truncated EphB4 that lacks the intracellular domain of tyrosine kinase and PDZ motif failed to rescue the defect of cardiomyocyte development, suggesting that EphB4 intracellular domain is essential for the development of cardiomyocytes. Our study provides evidence that receptor‐kinase‐dependent EphB4‐forward signaling plays a crucial role in the development of cardiac progenitor cells. J. Cell. Biochem. 116: 467–475, 2015. © 2014 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.

Treatment of multiple hepatocellular carcinoma (HCC) remains a critical issue. In addition, the prognosis and prognostic factors of multiple HCC after hepatic resection are rarely prospectively documented.The clinicopathologic and follow-up data of 81 patients who underwent curative resection of HCC between January 2008 and January 2009 were prospectively collected. Patients were categorized according to the size of the largest tumor: group A (n = 40, two or three HCCs with maximum tumor diameter3 cm andor = 5 cm) and group B (n = 41, two or three HCCs with maximum tumor diameteror = 3 cm). The two groups were compared for clinicopathologic data and survival results.The 1-, 2-, 3-, and 4-year survival rates of group A were 75.0%, 58.0%, 50.0%, and 44.0%, respectively, while the survival rates of group B were 93.0%, 80.0%, 66.0%, and 47.0%, respectively. The 1-, 2-, 3-, and 4-year disease-free survival rates of group A were 43.0%, 30.0%, 23.0%, and 15.0%, respectively, comparing to 71.0%, 54.0%, 44.0%, and 36.0% in group B, respectively. The median overall cumulative survival time of group A and group B were 36.0 and 44.5 months, respectively (P = 0.322). The median disease-free survival time of group A was 10.0 months and was significantly shorter than that of group B (30.0 months, P = 0.011).Resection may provide comparative survival benefits even for patients with multiple HCCs with maximum tumor diameter3 cm andor = 5 cm.

A comprehensive meta-analysis was performed to evaluate the comparative benefits of coronary artery bypass grafting (CABG) versus drug-eluting stents (DES) in patients with diabetes mellitus and severe coronary artery disease (CAD).A comprehensive literature search of PubMed, Embase, and ScienceDirect was undertaken. References cited with the papers were also checked to identify relevant articles.In all, four randomized controlled trials, two prospective registries, and 11 retrospective studies were identified for review. Pooled analysis demonstrated that DES was associated with lower all-cause mortality at Day 30. However, there was no significant difference between CABG and DES in mortality at 12 months and at maximum follow-up. Furthermore, DES was associated with lower overall and major adverse cardiac and cerebrovascular events (MACCE)-free survival, as well as a higher incidence of myocardial infarction and repeat revascularization. In contrast, CABG was associated with an increased risk of stroke.For patients with diabetes mellitus and severe CAD, CABG is superior to DES in that it significantly improves overall and MACCE-free survival and reduces the incidence of myocardial infarction and repeat revascularization in the long term, although it is associated with greater perioperative risk and a higher incidence of stroke. Therefore, CABG should remain the gold standard for these patients.

To evaluate whether glycation of high-density lipoprotein (HDL) increases cardiovascular risk in patients with type 2 diabetes mellitus by altering its anti-atherogenic property.Data cited in this review were obtained mainly from Pubmed and Medline in English from 2000 to 2013, with keywords "glycation", "HDL", and "atherosclerosis". Study selection Articles regarding glycation of HDL and its role in atherogenesis in both humans and experimental animal models were identified, retrieved and reviewed.Glycation alters the structure of HDL and its associated enzymes, resulting in an impairment of atheroprotective functionality and increased risks for cardiovascular events in type 2 diabetic patients.Glycation of HDL exerts a deleterious effect on the development of cardiovascular complications in diabetes.

To determine whether the prosthesis-patient mismatch has a deleterious impact on survival after mitral valve replacement.A comprehensive literature search of PubMed, Embase, and ScienceDirect was carried out. References and cited papers of relevant articles were also checked.All articles published after January 1980 was initially considered. Non-English and non-human studies, case reports, and reviews were excluded from the initial search. References and cited papers of relevant articles were also checked.A total of 8 retrospective cohort studies were identified for this review. The overall incidence of prosthesis-patient mismatch (1.3 to1.2 cm(2)/m(2)) after mitral valve replacement ranged from 3.7% to 85.9% (moderate prosthesis-patient mismatch (0.9 to 1.2 cm(2)/m(2)) in 37.4% to 69.5%, severe prosthesis-patient mismatch (0.9 cm(2)/m(2)) in 8.7% to 16.4%). Four studies demonstrated an association of prosthesis-patient mismatch with reduced long-term survival, but the other four studies found no significant deleterious impact of prosthesis-patient mismatch after mitral valve replacement. No definite conclusion could be derived from these conflicting results.Current evidence is insufficient to derive a definite conclusion whether mitral prosthesis-patient mismatch affects long-term survival because of the biases and confounding factors that interfere with late clinical outcomes. Goodquality prospective studies are warranted to evaluate the impact of mitral prosthesis-patient mismatch after mitral valve replacement in the future.

No randomized trial has been performed to compare the efficacy of an intracoronary bolus of tirofiban versus urokinase during primary percutaneous coronary intervention (PCI). We investigated whether the effects of adjunctive therapy with an intracoronary bolus of urokinase was noninferior to the effects of an intracoronary bolus of tirofiban in patients with ST-elevation myocardial infarction (STEMI) undergoing PCI.A total of 490 patients with acute STEMI undergoing primary PCI were randomized to an intracoronary bolus of tirofiban (10 µg/kg; n = 247) or urokinase (250 kU/20 ml; n = 243). Serum levels of P-selectin, von Willebrand factor (vWF), CD40 ligand (CD40L), and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary drug administration. The primary endpoint was the rate of complete ( ≥ 70%) ST-segment resolution (STR) at 90 minutes after intervention, and the noninferiority margin was set to 15%.In the intention-to-treat analysis, complete STR was achieved in 54.4% of patients treated with an intracoronary bolus of urokinase and in 60.6% of those treated with an intracoronary bolus of tirofiban (adjusted difference: -7.0%; 95% confidence interval: -15.7% to 1.8%). The corrected TIMI frame count of the infarct-related artery was lower, left ventricular ejection fraction was higher, and the 6-month major adverse cardiac event-free survival tended to be better in the intracoronary tirofiban group. An intracoronary bolus of tirofiban resulted in lower levels of P-selectin, vWF, CD40L, and SAA in the coronary sinus compared with an intracoronary bolus of urokinase after primary PCI (P0.05).An intracoronary bolus of urokinase as an adjunct to primary PCI for acute STEMI is not equally effective to an intracoronary bolus of tirofiban with respect to improvement in myocardial reperfusion assessed by STR. This may be caused by less reduction in coronary circulatory platelet activation and inflammation.

To study the clinical value of total hemihepatic vascular exclusion (THHVE) in liver resection for patients with hepatocellular carcinoma (HCC) and impaired liver function.The data of 70 patients who underwent liver resection for HCC with impaired liver function between January 2009 and October 2011 were analyzed retrospectively. THHVE was applied in 38 patients (THHVE group), Pringle maneuver in 25 patients (Pringle group) and no vascular occlusion in 7 patients. In the THHVE group, 36 patients were male, 2 were female, average age was (54 ± 9) years. And in Pringle group, 23 patients were male, 2 were female, average age was (53 ± 10) years. Total intraoperative blood loss, blood transfusion rate, clamping time, postoperative complication rate, postoperative hospital stay and postoperative liver function were compared between the THHVE and Pringle group.Total blood loss ((317 ± 186) ml vs. (506 ± 274) ml, t = -3.025, P = 0.004) and transfusion rate (10.5% vs. 32.0%, χ(2) = 4.509, P = 0.034) were significantly lower in the THHVE group than in the Pringle group. Although the clamping time was longer ((21 ± 5) minutes vs. (17 ± 5) minutes, t = 3.209, P = 0.002), the total bilirubin levels on postoperative day 3 and 7 and ALT levels on postoperative day 1, 3, 7 were significantly lower in the THHVE group than in the Pringle group, and the pre-albumin level on postoperative day 7 was higher in the THHVE group than in the Pringle group. Total complication rate (26.3% vs. 52.0%, χ(2) = 4.291, P = 0.038) and major complication rate (7.9% vs. 28.0%, χ(2) = 4.565, P = 0.033) were lower in the THHVE group than in the Pringle group. And postoperative hospital stay duration was shorter in the THHVE group than in the Pringle group ((14.0 ± 2.6) d vs. (16.4 ± 4.0) d, t = -2.625, P = 0.012).THHVE is a safe and effective technique in liver resection for patients with HCC and impaired liver function. It is associated with less blood loss, lower transfusion requirements, better postoperative liver function recovery, lower postoperative complication rate and shorter postoperative hospital stay.

Transradial access has been increasingly used during primary percutaneous coronary intervention (PCI) for patients with acute ST-segment elevation myocardial infarction (STEMI) in last decade. Clinical benefits of upstream use of tirfiban therapy in STEMI patients treated by primary PCI have been reported. We investigated the merits of transradial vs. transfemoral access in primary PCI for STEMI patients with upstream use of tirofiban.Patients with STEMI treated with tirofiban between December 2006 and October 2012 then by primary PCI were compared between transradial (n = 298) and transfemoral (n = 314) access. Baseline demographics, angiographic and PCI features and primary endpoint of major adverse cardiac events (MACE) at 30-day clinical follow-up were recorded.Baseline and procedural characteristics were comparable between the two groups, apart from more patients in transradial group had hypertension and were treated by thrombus aspiration during primary PCI. Significantly fewer MACE occurred in the transradial group (5.4%) compared with the transfemoral group (9.9%) at 30-day clinical follow-up. Major bleeding events at 30-day clinical follow-up were 0 in transradial group and in 2.9% of transfemoral group. Multivariate analysis confirmed transradial approach as an independent negative predictor of 30-day MACE (HR 0.68; 95%CI 0.35 - 0.91; P = 0.03).Using transradial approach in primary PCI for acute STEMI infarction patients treated with tirofiban was clearly beneficial in reducing bleeding complications and improving 30-day clinical outcomes.

Transcatheter aortic valve implantation (TAVI) has emerged as the treatment choice for non-operable patients with severe symptomatic aortic stenosis (AS) and may be a good alternative to surgery for those at very high or prohibitive surgical risk. We performed a meta-analysis to evaluate the comparative benefits of TAVI versus surgical aortic valve replacement (SAVR) in patients with severe AS.A comprehensive literature search of PubMed, Embase, ScienceDirect and Cochrane Central Register of Controlled trials was performed, and randomized trials as well as cohort studies with propensity score analysis were included.One randomized trial (n = 699) and six retrospective cohort studies (n = 781) were selected for meta-analysis. Mortality at 30-day and 1-year follow-up was comparable between TAVI and SAVR. Despite similar incidences of stroke, myocardial infarction, re-operation for bleeding, and renal failure requiring dialysis, TAVI was associated with a lower occurrence rate of new-onset atrial fibrillation (OR 0.51, 95%CI 0.33 - 0.78) and shorter procedural time (mean difference -67.50 minutes, 95%CI -87.20 to -47.81 minutes). Post-operative aortic regurgitation and permanent pacemaker implantation were more common in patients after TAVI than in those with SAVR (OR 5.53, 95%CI 3.41 - 8.97; OR 1.71, 95%CI 1.02 - 2.84, respectively).In patients with severe symptomatic AS, TAVI and SAVR did not differ with respect to short- and mid-term survival, but the incidence of permanent pacemaker implantation and post-procedural aortic regurgitation remain relatively high after TAVI.

Objectives This study sought to evaluate the safety and efficacy of rosuvastatin in preventing contrast-induced acute kidney injury (CI-AKI) in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). Background CI-AKI is an important complication after contrast medium injection. While small studies have shown positive results with statin therapy, the role of statin therapy in prevention of CI-AKI remains unknown. Methods We randomized 2,998 patients with type 2 DM and concomitant CKD who were undergoing coronary/peripheral arterial angiography with or without percutaneous intervention to receive rosuvastatin, 10 mg/day (n = 1,498), for 5 days (2 days before, and 3 days after procedure) or standard-of-care (n = 1,500). Patients' renal function was assessed at baseline, 48 h, and 72 h after exposure to contrast medium. The primary endpoint of the study was the development of CI-AKI, which was defined as an increase in serum creatinine concentration ≥0.5 mg/dl (44.2 μmol/l) or 0.25% above baseline at 72 h after exposure to contrast medium. Results Patients randomized to the rosuvastatin group had a significantly lower incidence of CI-AKI than controls (2.3% vs. 3.9%, respectively; p = 0.01). During 30 days' follow-up, the rate of worsening heart failure was significantly lower in the patients treated with rosuvastatin than that in the control group (2.6% vs. 4.3%, respectively; p = 0.02). Conclusions Rosuvastatin significantly reduced the risk of CI-AKI in patients with DM and CKD undergoing arterial contrast medium injection. (Rosuvastatin Prevent Contrast Induced Acute Kidney Injury in Patients With Diabetes [TRACK-D]; NCT00786136 )

MicroRNAs are important regulators of gene expression, including those involving electrical remodeling in atrial fibrillation (AF). Recently, KCNN3, the gene that encodes the small-conductance calcium-activated potassium channel 3 (SK3), was found to be strongly associated with AF.To evaluate the changes in atrial myocardial microRNAs in patients with permanent AF and to determine the role of microRNA on the regulation of cardiac SK3 expression.Atrial tissue obtained during cardiac surgery from patients (4 sinus rhythm and 4 permanent AF) was analyzed by using microRNA arrays. Potential targets of microRNAs were predicted by using software programs. The effects of specific microRNAs on target gene expression were evaluated in HL-1 cells from a continuously proliferating mouse hyperplastic atrial cardiomyocyte cell line. Interactions between microRNAs and targets were further evaluated by using luciferase reporter assay and by using Argonaute pull-down assay.Twenty-one microRNAs showed significant (2-fold) changes in AF. MicroRNA 499 (miR-499) was upregulated by 2.33-fold (P.01) in AF atria, whereas SK3 protein expression was downregulated by 46% (P.05). Transfection of miR-499 mimic in HL-1 cells resulted in the downregulation of SK3 protein expression, while that of miR-499 inhibitor upregulated SK3 expression. Binding of miR-499 to the 3' untranslated region of KCNN3 was confirmed by luciferase reporter assay and by the increased presence of SK3 mRNA in Argonaute pulled-down microRNA-induced silencing complexes after transfection with miR-499.Atrial miR-499 is significantly upregulated in AF, leading to SK3 downregulation and possibly contributing to the electrical remodeling in AF.

There is a paucity of studies investigating the clinical and biochemical characteristics of pain in chronic heart failure (CHF) patients. This study aimed to determine the clinical and biochemical characteristics and outcomes in Chinese patients with CHF and symptoms of pain.Sociodemographics, serum levels of creatinine, NT-proBNP, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10, and two-dimensional echocardiographic left ventricular ejection fraction (LVEF) were determined in 305 patients with CHF. A questionnaire packet including the Brief Pain Inventory (BPI) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used to assess the degree of pain rated on a 0 - 10 scale and the quality of life (QOL). A six-minute walking test was performed during routine clinic visits. Major adverse cardiac events (MACE) were recorded; including all-cause or cardiac mortality and rehospitalization because of myocardial infarction, worsening heart failure or stroke at follow-up.Pain occurred in 25.6% of CHF patients, and was more common when the New York Heart Association (NYHA) functional class was worse. More patients with pain were female in gender, and had more co-morbidities, lower LVEF, and shorter distance during the 6-minute walking test. Despite similar serum levels of creatinine, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), IL-6 and IL-10, the TNF-α levels were higher and MLHFQ scores were greater in CHF patients with pain. At follow-up, CHF patients with moderate to severe pain (≥ 4 scale) had higher rates of all-cause and cardiac mortality and rehospitalization because of myocardial infarction, worsening heart failure or stroke. Multivariate regression analysis revealed that the presence of pain was an independent risk factor for MACE and reduced QOL in CHF patients.Pain occurs in all stages of the CHF trajectory, and its incidence increases as clinical functional status is worsened. The presence of pain exerts a negative impact on clinical outcome and QOL in patients with CHF.

Weight gain following smoking cessation increases cardiovascular risk, but its effects on prognosis after percutaneous coronary intervention (PCI) remain unclear. This study aimed to investigate the relationship between weight gain post smoking cessation and one-year clinical outcome in patients who underwent PCI with drug-eluting stent (DES).A total of 895 consecutive male smoking patients were divided into quitters (n = 437) and continuers (n = 458) according to their smoking status after PCI. Weight gain, major adverse cardiac events (MACE, including cardiac deaths, myocardial infarction and revascularization), and recurrent angina were recorded during follow-up for one year.Average weight gain in quitters was more than that in continuers (1.5 kg vs. -0.03 kg, P0.001). Weight was unchanged or increased by more than 1.5 kg in 78.17% of continuers, while 50.57% of quitters had a weight gain of less than 1.5 kg. Compared with continuers, MACE in quitters was significantly reduced after PCI (6.12% vs. 4.81%, P = 0.049), especially recurrent angina (13.97% in continuers vs. 9.84% in quitters, P = 0.027). After adjusting for weight gain and other factors, smoking cessation was independently associated with a lower risk of MACE and recurrent angina (OR = 0.73, P = 0.035). However, weight gain1.5 kg (OR = 1.55, P = 0.026) could curtail the benefits from smoking cessation.Weight gain may reduce the benefits of smoking cessation after PCI with DES implantation. Thus, although smoking cessation is recommended after PCI, weight control should also be highly encouraged for these patients.

The clinical significance of ischemic chest pain before acute ST-elevation myocardial infarction (STEMI) remains an interesting issue of investigation particularly in the era of percutaneous coronary intervention (PCI). This study aimed to assess the impact of angina prior to STEMI on short-term clinical outcomes in patients with acute STEMI undergoing primary PCI.Among a total of 875 consecutive patients with STEMI undergoing primary PCI, 292 had episodes of angina within 24 hours of STEMI (PA group) and the remaining 583 were free of anginal symptoms (non-PA group). Clinical characteristics, angiographic and procedural features, and in-hospital and 30-day outcomes were compared between the two groups.Diabetes was less common (17.5% vs. 23.3%, P = 0.04) and symptom-to-door time was shortened ((191.6 ± 96.8) minutes vs. (357.2 ± 341.9) minutes, P0.001) in the PA group than in the non-PA group. Patients with angina prior to STEMI had fewer totally or nearly totally occluded infarct-related artery (TIMI flow grade 0 - 1) at initial angiography (75.0% vs. 90.7%, P0.001), and achieved more TIMI flow grade 3 after primary PCI (84.2% vs. 78.2%, P = 0.04). These were associated with higher rates of overall procedural success (95.9% vs. 91.8%, P = 0.02) and of complete ST-segment resolution at 90 minutes after the procedure (51.7% vs. 40.3%, P = 0.001). During a 30-day clinical follow-up, the left ventricular ejection fraction was significantly improved ((53.0 ± 8.6)% vs. (51.1 ± 9.7)%, P = 0.002) and the primary endpoint of major adverse cardiac events was reduced in the PA group (7.2% vs. 12.7%, P = 0.01).Presence of angina prior to acute STEMI is associated with better outcome at a 30-day clinical follow-up in patients undergoing primary PCI.

This study aimed to compare the value of serum glycated albumin (GA) level versus glycated hemoglobin A(1c) (HbA(1c)) for evaluating the presence and severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM).Serum GA and blood HbA(1c) levels were measured in 829 consecutive T2DM patients with or without angiographically documented significant CAD (≥70% diameter stenosis).Serum GA levels were higher in diabetic patients with significant CAD than in those without (20.57 ± 4.23 vs. 19.00 ± 4.48%; p0.001), but HbA(1c) was similar in the two groups (7.74 ± 1.34 vs. 7.51 ± 1.37% p0.05). Compared to HbA(1c), GA correlated more closely with the sum of significant stenotic lesions (r = 0.275, p0.001 and r = 0.092, p = 0.019) and the extent index (r = 0.375, p0.001 and r = 0.091, p = 0.019). The area under the curve of GA was larger than that of HbA(1c) for detecting the presence of significant CAD (0.637 vs. 0.568; p = 0.046) and 3-vessel disease (0.620 vs. 0.536; p = 0.039). GA, but not HbA(1c), was independently associated with significant CAD.Serum GA level is a better indicator than HbA(1c) for evaluating the presence and severity of CAD and predicting major adverse cardiac events in patients with T2DM.

Potentially lethal ventricular arrhythmias (PLVAs) occur frequently in survivors after acute myocardial infarction and are increasingly recognized in other forms of structural heart diseases. This study investigated the prevalence and prognostic significance of PLVAs in patients with chronic heart failure (CHF).Data concerning demographics, etiology of heart failure, NYHA functional class, biochemical variables, electrocardiographic and echocardiographic findings, and medical treatments were collected by reviewing hospital medical records from 1080 patients with NYHA II-IV and a left ventricular (LV) ejection fraction ≤ 45%. PLVAs were defined as multi-focal ventricular ectopy (30 beats/h on Holter monitoring), bursts of ventricular premature beats, and nonsustained ventricular tachycardia. All-cause mortality, sudden death, and rehospitalization due to worsening heart failure, or cardiac transplantation during 5-year follow-up after discharge were recorded.The occurrence rate of PLVAs in CHF was 30.2%, and increased with age; 23.4% in patients45 years old, 27.8% in those between 45 - 65 years old, and 33.5% in patients65 years old (P = 0.033). Patients with PLVAs had larger LV size and lower ejection fraction (both P0.01) and higher all-cause mortality (P = 0.014) during 5-year follow-up than those without PLVAs. Age (OR 1.041, 95%CI 1.004 - 1.079, P = 0.03) and LV end-diastolic dimension (OR 1.068, 95%CI 1.013 - 1.126, P = 0.015) independently predicted the occurrence of PLVAs. And PLVA was an independent factor for all-cause mortality (RR 1.702, 95%CI 1.017 - 2.848, P = 0.031) and sudden death (RR 1.937, 95%CI 1.068 - 3.516, P = 0.030) in patients with CHF.PLVAs are common and exert a negative impact on long-term clinical outcome in patients with CHF.

The accuracy and reliability of two-dimensional monoplane and multiplane transesophageal echocardiography (TEE) in the quantitation of aortic valve area were compared in 54 patients with aortic stenosis. Fifty patients had aortic valve area calculated by the continuity equation and transthoracic Doppler echocardiography (TTE); 25 underwent cardiac catheterization. Two-dimensional echocardiograms adequate for quantitation of aortic valve area were obtained in 21 (39%) patients with monoplane TEE and in 51 (94%) with multiplane TEE. The mean aortic valve area determined by both TEE methods did not differ significantly from that derived from TTE and catheterization. The mean difference of aortic valve area measurements between monoplane TEE and TTE was -0.045 +/- 0.11 cm2; that between multiplane TEE and TTE was 0.001 +/- 0.11 cm2. Multiplane TEE provided a better correlation of aortic valve area measurements with either TTE (y = 0.97 x + 0.03; r = 0.96; SEE = 0.11 cm2) or catheterization (y = 0.84 x + 0.11; r = 0.90; SEE = 0.12 cm2) than the monoplane TEE (y = 0.88 x + 0.13; r = 0.83; SEE = 0.15 cm2 and y = 0.41 x + 0.42; r = 0.81; SEE = 0.15 cm2). Severe aortic stenosis with valve orifice area ofor = 0.75 cm2 during TTE examination was found by multiplane TEE with a sensitivity of 96% and a specificity of 96%. Thus aortic valve area can be directly and reliably measured by two-dimensional multiplane TEE in majority of patients with aortic stenosis.

To investigate the relationship between smoking and insulin resistance in non-obese male patients with CAD.414 consecutive non-obese male patients with angiographically-documented CAD (luminal diameter narrowing50%) were recruited, including 113 nonsmokers and 301 smokers. With 99 mild smokers (400 packs/year), 95 medium smokers (400 - 799 packs/year) and 107 heavy smokers (≥ 800 packs/year). Insulin resistance index (IRI) was expressed by homeostasis model assessment for insulin resistance (HOMA-IR) calculated by the formula of [fasting serum glucose (mmol/L) × fasting plasma insulin (mU/L)]/22.5. IRI ≥ 2.69 was defined as insulin resistance, while IRI2.69 was insulin sensitive. Fasting glucose, fasting insulin and IRI were recorded and odds ratio for the incidence of insulin resistance was calculated.Fasting glucose was higher in heavy smokers (5.86 mmol/L) than that in nonsmokers (5.51 mmol/L, P = 0.037) and mild smokers (5.33 mmol/L, P = 0.014). Fasting insulin and IRI were also significantly higher in heavy smokers (10.25 mU/L) than those in non-smokers (8.72 mU/L, P = 0.0231, respectively) and mild smokers (8.67 mU/L, P = 0.0231). Compared with nonsmokers, the odds ratio for the incidence of insulin resistance was 1.53 (95%CI 0.55 - 2.94; P = 0.027) in medium smokers and 1.89 (95%CI 0.49 - 3.14; P = 0.018) in heavy smokers.The relationship between smoking and insulin resistance is highly dose dependent in non-obese male patients with CAD.

This study aimed to evaluate the impact of vascular response assessed by intravascular ultrasound (IVUS) imaging on clinical outcomes in elderly patients (≥ 75 years) undergoing percutaneous coronary intervention (PCI) for de novo lesions with sirolimus-eluting stent (SES) implantation. Repeat coronary angiography with IVUS was performed 1 year after SES-based PCI for de novo lesions in 136 elderly patients (≥ 75 years) and 427 younger counterparts (75 years) (219 lesions and 635 lesions, respectively). Major adverse cardiac events (MACE) including cardiac death, non-fatal myocardial infarction, and target lesion revascularization (TLR) during 2-year follow-up were recorded. Despite similar angiographic in-stent restenosis and TLR and IVUS-detected incomplete stent apposition (ISA), absolute intimal hyperplasia and percentage of volumetric obstruction were lower in elderly than in younger patients. At 2-year follow-up, cumulative survival freedom from composite death and myocardial infarction or MACE was significantly reduced in elderly patients, but very late stent thrombosis was similar in the two groups. Cox proportional hazards model identified age, diabetes, left ventricular ejection fraction, lesion length,minimal stent cross-sectional area and plaque progression as independent predictors of non-fatal myocardial infarction or mortality. In elderly patients undergoing SES-based PCI, despite similar TLR, neointimal hyperplasia was significantly lower than in younger patients. IVUS measurements except for minimal stent cross-sectional area did not correlate with stent thrombosis and clinical outcomes at 2 years.

Primary percutaneous coronary intervention (PCI) has been clearly identified as the first therapeutic option for patients with acute ST-segment elevation myocardial infarction (STEMI). The importance of reducing door-to-balloon (D2B) time has gained increased recognition. This study aimed to assess the feasibility, safety and efficacy of the strategy of direct ambulance transportation of patients with acute STEMI to catheterization lab to receive primary PCI.The study population included 141 consecutive patients with chest pain and ST-segment elevation who were admitted to the catheterization laboratory directly by the ambulance and underwent primary PCI (DIRECT group). Another 145 patients with STEMI randomly selected from the PCI database, were served as control group (conventional group); they were transported to catheterization laboratory from emergency room (ER). The primary endpoint of D2B time, and secondary endpoint of in-hospital and 30-day major adverse cardiac events (MACE, including death, non-fatal reinfarction, and target vessel revascularization) were compared.Baseline and procedural characteristics between the two groups were comparable, except more patients in the DIRECT group presented TIMI 0-1 flow in culprit vessel at initial angiogram (80.1% and 73.8%, P = 0.04). Comparing to conventional group, the primary endpoint of D2B time was reduced ((54 ± 18) minutes and (112 ± 55) minutes, P0.0001) and the percentage of patients with D2B90 minutes was increased in the DIRECT group (96.9% and 27.0%, P0.0001). The success rate of primary PCI with stent implantation with final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was significantly higher in the DIRECT group (93.8% and 85.2%, P = 0.03). Although no significant difference was found at 30-day MACE free survival rate between the two groups (95.0% and 89.0%, P = 0.06), a trend in improving survival status in the DIRECT group was demonstrated by Kaplan-Meier analysis.Direct ambulance transport of STEMI patients to the catheterization laboratory could significantly reduce D2B time and improve success rate of primary PCI and 30-day clinical outcomes.

Susceptibility to coronary artery disease (CAD) and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways.Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin A(1c) (HbA(1c)), insulin, high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-6 were also measured, and compared with each patient's genotype.The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic (OR: 1.270, P = 0.044) and non-diabetic (OR: 1.369, P = 0.011) patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics (P = 0.019), but not in non-diabetics (P = 0.126). Among diabetic patients, CC genotype carriers had an increased risk of early-onset CAD (OR: 2.367, P = 0.008) and greater cumulative atherosclerotic burden compared with non-CC genotype carriers (Gensini score: 31.80 ± 17.20 vs. 23.09 ± 21.63, P = 0.039). No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbA(1c), or inflammatory cytokines for diabetic or non-diabetic patients with CAD.This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabetic patients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabetic patients through a novel biological pathway unrelated to glucose metabolism or inflammation.

Although thrombolytic therapy with rescue percutaneous coronary intervention (PCI) is a common treatment strategy for ST-segment elevation acute myocardial infarction (STEMI), scant data are available on its efficacy relative to primary PCI, and comparison was therefore the aim of this study.This multicenter, open-label, randomized, parallel trial was conducted in 12 hospitals on patients (ageor = 70 years) with STEMI who presented within 12 hours of symptom onset (mean interval3 hours). Patients were randomized to three groups: primary PCI group (n = 101); recombinant staphylokinase (r-Sak) group (n = 104); and recombinant tissue-type plasminogen activator (rt-PA) group (n = 106). For all patients allocated to the thrombolytic therapy arm, coronary angiography was performed at 90 minutes after drug therapy to confirm infarct-related artery (IRA) patency; rescue PCI was performed in cases with TIMI flow gradeor = 2. Bare-metal stent implantation was planned for all patients.After randomization it required an average of 113.4 minutes to start thrombolytic therapy (door-to-needle time) and 141.2 minutes to perform first balloon inflation in the IRA (door to balloon time). Rates of IRA patency (TIMI flow grade 2 or 3) and TIMI flow grade 3 were significantly lower in the thrombolysis group at 90 minutes after drug therapy than in the primary PCI group at the end of the procedure (70.5% vs. 98.0%, P0.0001, and 53.0% vs. 85.9%, P0.0001, respectively). Rescue PCI with stenting was performed in 117 patients (55.7%) in the thrombolytic therapy arm. Rates of patency and TIMI flow grade 3 were still significantly lower in the rescue PCI than in the primary PCI group (88.9% vs. 97.9%, P = 0.0222, and 68.4% vs. 85.0%, P = 0.0190, respectively). At 30 days post-therapy, mortality rate was significantly higher in the thrombolysis combined with rescue PCI group than in primary PCI group (7.1% vs. 0, P = 0.0034). Rates of death/MI and bleeding complications were significantly higher in the thrombolysis with rescue PCI group than in the primary PCI group (10.0% vs. 1.0%, P = 0.0380, and 28.10% vs. 8.91%, P = 0.0001, respectively).Thrombolytic therapy with rescue PCI was associated with significantly lower rates of coronary patency and TIMI flow grade 3, but with significantly higher rates of mortality, death/MI and hemorrhagic complications at 30 days, as compared with primary PCI in this group of Chinese STEMI patients with late presentation and delayed treatments.