Protective Effects of Salvianolate on Contrast-Induced Nephropathy after Primary Percutaneous Coronary Intervention: A Prospective Multicenter Randomized Controlled Trial.

OBJECTIVES: This study's aim was to evaluate the protective effects of salvianolate on contrast-induced nephropathy after primary percutaneous coronary intervention (PPCI) compared with normal saline (NS) hydration. METHODS: We enrolled patients with acute myocardial infarction who underwent PPCI in 3 centers in Shanghai. The patients were randomly assigned to the salvianolate group or the NS group. The incidence of CIN, the changes in renal function parameters, and the occurrence of adverse events after the procedure were compared between the 2 groups. We used a multivariate logistic regression analysis to determine the independent correlates of CIN after PPCI. RESULTS: A total of 484 patients were finally included in the statistical analysis. Compared with the control group, salvianolate reduced the incidence of CIN (9.1 vs. 16.3%, p = 0.018) after PPCI. The renal function parameters after PPCI in the salvianolate group were superior to those of the control group (p < 0.05). The composite adverse events rate was significantly lower in the salvianolate group within 1 month after the procedure (9.5 vs. 15.5%, p = 0.046). A higher peak of troponin I and loop diuretic therapy were the independent correlates of CIN after PPCI. CONCLUSIONS: Salvianolate reduces the incidence of CIN and protects renal function after PPCI, and the effects were superior to those of NS hydration.

Immune Cell Repertoire and Their Mediators in Patients with Acute Myocardial Infarction or Stable Angina Pectoris.

Background: To evaluate the natural innate and adaptive immunity through gene expression and cytology levels in peripheral blood mononuclear cells in patients with acute myocardial infarction (AMI), stable angina pectoris (SAP) and controls. Methods: 210 patients with AMI, 210 with SAP, and 250 clinical controls were recruited. Whole human genome microarray analysis was performed in 20 randomly chosen subjects per group were examined to detect the expressions of complement markers, natural killer cells, T cells and B cells. The quantity of these cells and related cytokines as well as immunoglobulin levels were measured in all subjects. Results: In AMI group, the mRNA expressions of late complement component, markers of natural killer cells, CD3+, CD8+ T cells and B cells were down-regulated, while those of early complement component and CD4+T cells were up-regulated (p<0.05). In both AMI and SAP patients, the quantity of natural killer cells, CD3+, CD8+ T cells, B cells, IgM and IgG were significantly lower than those of the controls. CD4+ T cells, CH50, C3, C4, IL-2, IL-4, IL-6 and IFN-γ were significantly higher (p<0.05). Conclusions: In AMI patients, both of gene expressions related to complement, natural killer cells, CD3+, CD8+ T cells, B cells and the quantity of these immune cells decreased while cell number reduced in SAP patients. Immune function in both AMI and SAP patients decreased especially in AMI patients with declined gene and protein levels. To improve the immune system is a potential target for medical interventions and prevention in AMI.

TBX20 loss-of-function mutation associated with familial dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of congestive heart failure, sudden cardiac death and cardiac transplantation. Aggregating evidence highlights the genetic origin of DCM. However, DCM is a genetically heterogeneous disorder, and the genetic components underlying DCM in most cases remain unknown. METHODS: The coding regions and splicing junction sites of the TBX20 gene were sequenced in 120 unrelated patients with idiopathic DCM. The available close relatives of the index patient carrying an identified mutation and 300 unrelated ethnically matched healthy individuals used as controls were genotyped for TBX20. The functional characteristics of the mutant TBX20 were assayed in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system. RESULTS: A novel heterozygous TBX20 mutation, p.F256I, was identified in a family with DCM transmitted in an autosomal dominant fashion, which co-segregated with DCM in the family with complete penetrance. The missense mutation was absent in 600 control chromosomes and the altered amino acid was completely conserved evolutionarily among various species. Functional assays revealed that the mutant TBX20 had significantly diminished transcriptional activity. Furthermore, the mutation markedly reduced the synergistic activation of TBX20 with NKX2-5 or GATA4. CONCLUSIONS: This study links TBX20 loss-of-function mutation to idiopathic DCM in humans for the first time, providing novel insight into the molecular mechanism underpinning DCM.

Pleiotropic effects of fenofibrate therapy on rats with hypertriglycemia.

BACKGROUND: Cardio-protective effect of fibrate therapy is controversial and current research is to evaluate the effect of fenofibrate therapy on rats with hypertriglycemia. METHODS: Rats with hypertriglycemia were produced by 10% fructose administration (10 ml daily) for 4 weeks. After model has been successfully produced as reflected by increased triglyceride level, different doses of fenofibrate, namely low dose (50 mg/kg body weight) and high dose (100 mg/kg body weight), were orally prescribed for 2 weeks. At baseline, 4 weeks of fructose administration and 2 weeks of fenofibrate therapy, parameters of interest were evaluated and compared. RESULTS: At baseline, no significant differences of parameter were observed between groups. After 4 weeks of fructose prescription, triglyceride level increased in company with high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) decreased. C-reactive protein (CRP) and malondialdehyde (MDA) levels were also elevated. Endothelial function was impaired as reflected by reduced nitric oxide (NO) production and elevated serum asymmetric dimethylarginine (ADMA) level. All these changes were significant as compared to the control group (P<0.05), suggesting that short-term of triglyceride elevation could potently initiate atherosclerosis. With 2 weeks of fenofibrate therapy, in comparison to un-treated group, triglyceride level was significantly reduced in parallel with HDL-C and ApoA1 elevation. Inflammation and oxidation were also profoundly ameliorated as reflected by CRP and MDA reduction. Notably, NO production was enhanced in company with serum ADMA level decrease. Overall, these improvements manifested in a dose-dependent manner, which was supported by multivariate regression analysis showing that after adjusted to other variables, the dose of fenofibrate therapy remained significantly associated with NO production and serum ADMA level, with OR of 1.042 (high-dose versus low-dose, 95% CI 1.028-1.055, P<0.05). CONCLUSIONS: Fenofibrate therapy not only could reduce triglyceride level but also confer pleiotropic effects in terms of endothelium-protection and amelioration of inflammation and oxidation in a dose-dependent manner.

The efficacy and safety of ivabradine hydrochloride versus atenolol in Chinese patients with chronic stable angina pectoris.

PURPOSE: The aim of this study was to assess the efficacy and safety of ivabradine (Iva) noninferiority to atenolol (Aten) in Chinese patients with chronic stable angina pectoris. METHODS: In this double-blind, double-dummy trial, patients with symptomatic angina pectoris and positive exercise tolerance test were randomized into the Iva [5 or 7.5 mg bis in die (BID)] or Aten group (12.5 or 25 mg BID) according to computer-generated random numbers for 12 weeks. RESULTS: One hundred and sixty-eight patients were randomized to the Iva group and 166 to the Aten group. In a full analysis set, increases in the total exercise duration (TED) were 54.3 ± 120.1 seconds with Iva 5 mg and 58.8 ± 114.7 seconds with Aten 12.5 mg at the fourth week, and at the 12th week, TED improved by 84.1 ± 130.5 seconds with Iva and 77.8 ± 126.6 seconds with Aten (95%CI: -21.4-34.1 seconds, p = 0.0011 for noninferiority). The analysis of per protocol set yielded similar results (95%CI: -31.4-33.0 seconds, p = 0.0131 for noninferiority). Heart rate was reduced in both groups at rest and during peak exercise. There were small, nonsignificant differences in the number of adverse events between the two groups (66 in Iva and 73 in Aten, p > 0.05). Nine patients (5.42%) were reported to develop phosphenes/luminous phenomena and blurred vision in the Iva group (p = 0.0035). CONCLUSIONS: Iva is effective in reducing heart rates and improving exercise capacity and noninferior to Aten in Chinese patients with chronic stable angina pectoris. Iva is well tolerated and safe.

Mutational spectrum of the NKX2-5 gene in patients with lone atrial fibrillation.

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia in humans and is responsible for substantial morbidity and mortality worldwide. Emerging evidence indicates that abnormal cardiovascular development is involved in the pathogenesis of AF. In this study, the coding exons and splice sites of the NKX2-5 gene, which encodes a homeodomain-containing transcription factor essential for cardiovascular genesis, were sequenced in 146 unrelated patients with lone AF as well as the available relatives of the mutation carriers. A total of 700 unrelated ethnically matched healthy individuals used as controls were genotyped. The disease-causing potential of the identified NKX2-5 variations was predicted by MutationTaster and PolyPhen-2. The functional characteristics of the mutant NKX2-5 proteins were analyzed using a dual-luciferase reporter assay system. As a result, two heterozygous NKX2-5 mutations, including a previously reported p.E21Q and a novel p.T180A mutation, were identified in two families with AF transmitted in an autosomal dominant pattern. The mutations co-segregated with AF in the families with complete penetrance. The detected substitutions, which altered the amino acids highly conserved evolutionarily across species, were absent in 700 control individuals and were both predicted to be causative. Functional analyses demonstrated that the NKX2-5 mutants were associated with significantly decreased transcriptional activity compared with their wild-type counterpart. The findings expand the spectrum of NKX2-5 mutations linked to AF and provide additional evidence that dysfunctional NKX2-5 may confer vulnerability to AF, suggesting the potential benefit for the early prophylaxis and personalized treatment of AF.

[Effect of catheter-based renal sympathetic denervation in pigs with rapid pacing induced heart failure].

OBJECTIVE: This study investigated the effect of catheter-based renal sympathetic denervation (RDN) in pigs with rapid pacing induced heart failure. METHODS: Heart failure was induced by rapid right ventricular pacing in 12 pigs and pigs were randomly divided into RDN group (n = 6): pacing+RDN at 7 days post pacing; control group (n = 6): pacing only. Echocardiography examination (LVEF, LVEDD and LVESD) was performed before pacing and at 1 and 2 weeks post pacing. Serum biochemical markers including renin, aldosterone and creatinine were also measured at baseline, 1 and 2 weeks after pacing. Repeated renal artery angiography was performed at 1 week after RDN. All pigs were sacrificed to examine the heart and renal pathology and renal artery sympathetic nerve staining at 2 weeks post pacing. RESULTS: LVEF decreased 1 week after rapid pacing from (60.5 ± 6.0)% to (35.3 ± 9.8)%. LVEF was significantly higher [(42.8 ± 5.9) % vs. (33.4 ± 9.7)%, P = 0.001 8] while LVESD was significantly lower [(28.4 ± 3.7) mm vs. (33.0 ± 2.0) mm, P = 0.001 6] in the RDN group than in the control group at 2 weeks post pacing. At 2 weeks after pacing, plasma concentrations of renin and aldosterone were significantly lower in RDN group compared to the control group (all P < 0.05) . Kidney function and blood pressure were comparable between the two groups at 2 weeks post pacing. There were no signs of renal damages such as renal artery stenosis, dissection and thrombus in all pigs after 2 weeks pacing. Sympathetic neurons of adventitia were injured in RND group. CONCLUSION: RDN could significantly improve cardiac function and attenuate left ventricular remodeling via inhibiting renin-angiotensin-aldosterone system in this pacing induced pig heart failure model.

The effect of PPARG gene polymorphisms on the risk of coronary heart disease: a meta-analysis.

The peroxisome proliferator-activated receptor-γ (PPARG) is a member of the nuclear hormone receptor superfamily that has attracted considerable attention as a candidate gene for coronary heart disease (CHD) based on its function as a key factor involved in the regulation of lipid and glucose metabolism. In the past decade, a number of case-control studies have been carried out to investigate the relationship between the PPARG polymorphisms and CHD. However, these studies have yielded contradictory results. To derive a more precise estimation of the relationship, a meta-analysis of 33 studies including a total of 12,340 cases and 17,471 controls on 3 PPARG polymorphisms (Pro12Ala, C161T and C1431T) was performed. In a combined analysis, the summary per-allele odds ratio for CHD was 1.02 (95 % CI: 0.93-1.13), 0.86 (95 % CI: 0.72-1.02), and 0.92 (95 % CI: 0.74-1.16) for PPARG 12Ala, 161T and 1431T alleles, respectively. No significant results were observed under dominant or recessive genetic models for these polymorphisms in almost all comparisons. In the stratified analyses according to ethnicity, sample size, CHD endpoints and HWE status, no evidence of any gene-disease association was obtained. Our results suggest that the Pro12Ala, C161T and C1431T polymorphisms of PPARG gene are not associated with CHD susceptibility.

[Effects of exercise therapy at the intensity of anaerobic threshold for exercise tolerance in patients with chronic stable coronary artery disease].

OBJECTIVE: To investigate the effects of exercise therapy at the intensity of anaerobic threshold (AT) for exercise tolerance in patients with chronic stable coronary artery disease. METHODS: Forty-three patients with chronic stable coronary artery disease (3 patients after coronary arterial bypass graft (CABG) surgery, 22 patients with old myocardial infarction and 18 unstable angina pectoris undergoing successful percutaneous coronary intervention (PCI) finished twice cardiopulmonary exercise test (CPET) and followed their rehabilitation program for 3 months. Thirty-two patients finished their aerobic exercise therapy based on their individual anaerobic thresholds while 11 patients had no exercise therapy. RESULTS: The heart rate at AT intensity (97 ± 9/min) was lower than their traditional minimal target heart rate (112 ± 7/min) and lower than heart rate (115 ± 11/min) at ischemic threshold post-CPET. The O(2) consumption (10.7 ± 2.4 to 12.6 ± 2.9 ml×min(-1)×kg(-1)) (P = 0.04) and workload (37 ± 18 to 47 ± 13 J/s) (P = 0.04) at AT level and the O(2) consumption (15.3 ± 3.1 to 20.6 ± 4.2 ml×min(-1)×kg(-1), P = 0.02) and workload(68 ± 12 and 87 ± 14 J/s, P = 0.01) at peak level markedly increased after 3 months in the exercise group. And the O(2) consumption (15.3 ± 2.9 to 16.2 ± 3.1 ml×min(-1)×kg(-1)) and workload (65 ± 13 to 73 ± 16 J/s) at peak level mild increased after 3 months in the non-exercise group, but their O(2) consumption (11.0 ± 2.7 to 11.3 ± 2.8 ml×min(-1)×kg(-1)) and workload (38 ± 11 to 37 ± 9 J/s) at AT level had no obvious change. CONCLUSION: AT exercise intensity was lower than ischemic threshold post-CPET. Exercise therapy at the intensity of anaerobic threshold can improve oxygen capacity and exercise tolerance.

[Effects of aerobic exercise on exercise tolerance in patients with chronic heart failure].

OBJECTIVE: To explore the effects of aerobic exercise on exercise tolerance in patients with chronic heart failure (CHF). METHODS: A total of 50 CHF patients with left ventricular ejection fraction (LVEF) < 49% by echocardiography were enrolled. And they were randomly divided into exercise group (n = 25) and non-exercise group (n = 25). Cardiopulmonary exercise testing (CPET) was performed. The patients of exercise group underwent an aerobic exercise program in which exercise intensity was decided by anaerobic threshold (AT) before 10 J/s while those of non-exercise group performed daily activities. After 6 sessions of supervised aerobic exercise, the home-based aerobic exercise training began. CPET was re-examined 3 months later. RESULTS: The VO(2) AT, VO(2) peak, Load AT, Load peak, peak VO(2)/HR and VE/VCO(2) slope at baseline were similar between exercise group and non-exercise group (P > 0.05). The VO(2) AT, VO(2) peak, Load AT, Load peak and peak VO(2)/HR in patients of exercise group were increased compared with baseline, The differences between baseline and 3 months later expressed as ΔVO(2) AT, ΔVO(2) peak, ΔLoad AT, ΔLoad peak, Δpeak VO(2)/HR and ΔVE/VCO(2) slope, The differences of ΔVO(2) AT, ΔVO(2) peak, ΔLoad AT, ΔLoad peak and Δpeak VO(2)/HR between two groups were statistically significant [ΔVO(2) AT: 2.8 (1.2 - 3.5) ml×kg(-1)×min(-1) vs -0.3 (-2.8 - 0.1) ml×kg(-1)×min(-1), P < 0.01; ΔVO(2) peak: 3.4 (1.8 - 4.6) ml×kg(-1)×min(-1) vs -0.5 (-1.4 - 0.3) ml×kg(-1)×min(-1), P < 0.01; ΔLoad AT:15.0 (2.5 - 22.5) J/s vs 0.5(-4.2 - 3.8) J/s, P < 0.01; ΔLoad peak: 15.0 (1.3 - 25.0) J/s vs 0.0 (-8.8 - 15.0) J/s, P < 0.05; Δpeak VO(2)/HR: 2.3 (0.0 - 4.0) ml×kg(-1)×beat(-1) vs -0.1 (-0.7 - 1.2) ml×kg(-1)×beat(-1), P < 0.01]. The difference of ΔVE/VCO(2) slope was not statistically significant [-2.3 (-12.2 - 1.8) vs 1.0 (-0.4 - 2.6), P > 0.05]. CONCLUSION: After 3 months of aerobic exercise, exercise capacity may improve in the CHF patients.

[The effects of aerobic exercise on cardiac output during exercise in patients with chronic heart failure].

OBJECTIVE: To observe the effects of aerobic exercise on cardiac output during exercise in patients with chronic heart failure (CHF). METHODS: A total of 50 CHF patients (echocardiography measured left ventricular ejection fraction < 0.49) were enrolled in the study and randomly divided into aerobic exercise group (n = 25) and control group (n = 25). Cardiopulmonary exercise testing (CPET) was performed. Patients of aerobic exercise group underwent aerobic exercise according to aerobic exercise prescription and exercise intensity is decided by anaerobic threshold before 10 J/s (1 minute before) of the oxygen consumption. After 6 supervised aerobic exercise training sessions in the hospital, patients were asked to perform the home-based aerobic exercise training. Patients in control group were required to maintain daily physical activities. CPET were reviewed 3 months later. RESULTS: Cardiac output (CO), peak CO, peak cardiac power output (peak CPO), resting heart rate (HR), heart rate at AT (HRAT), HR peak, resting mean arterial pressure (MAP), peak MAP at baseline were similar between aerobic exercise group and control [(4.2 ± 2.0) L/min vs. (3.3 ± 1.0) L/min, (6.2 ± 2.7) L/min vs. (5.2 ± 1.8) L/min, (1.8 ± 2.9) L/min vs. (2.0 ± 1.8) L/min, (1.3 ± 0.5) J/s vs. (1.2 ± 0.5) J/s, (76.8 ± 13.5) beats/min vs. (73.4 ± 11.9) beats/min, (91.5 ± 11.3) beats/min vs. (92.6 ± 12.4) beats/min, (106.0 ± 12.9) beats/min vs. (108.3 ± 17.4) beats/min, (80.8 ± 9.9) mm Hg (1 mm Hg = 0.133 kPa) vs. (87.6 ± 13.3) mm Hg, (98.8 ± 12.4) mm Hg vs. (102.7 ± 13.9) mm Hg, all P > 0.05]. Compared to baseline, CO, peak CO, peak CPO, HR, HRAT, HR peak, MAP, peak MAP after 3 months were similar between aerobic exercise group and control (all P > 0.05). The differences between baseline and 3 months later expressed as ΔCO, Δpeak CO, Δpeak CPO, ΔHR, ΔHRAT, ΔHR peak, ΔMAP, Δpeak MAP were also similar between aerobic exercise group and control group [(-0.7 ± 2.4) L/min vs. (0.7 ± 2.0) L/min, (1.1 ± 2.6) L/min vs. (1.4 ± 2.1) L/min, (0.1 ± 3.7) L/min vs. (-0.2 ± 2.5) L/min, (0.2 ± 1.0) J/s vs. (0.2 ± 0.5) J/s, (-0.4 ± 7.6) beats/min vs. (1.9 ± 9.9) beats/min, (3.4 ± 11.3) beats/min vs. (-2.8 ± 7.6) beats/min, (8.9 ± 14.5) beats/min vs. (3.7 ± 14.4) beats/min, (1.5 ± 12.8) mm Hg vs. (-1.3 ± 11.1) mm Hg, (6.4 ± 18.9) mm Hg vs. (1.3 ± 12.3) mm Hg, all P > 0.05]. CONCLUSION: Three months aerobic exercise training did not improve cardiac output and related parameters during exercise in this cohort patients with CHF.

Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Effects of granulocyte colony­stimulating factor on rabbit carotid and porcine heart models of chronic obliterative arterial disease.

Previous studies suggest that granulocyte colony­stimulating factor (G­CSF) can promote bone marrow derived progenitor cells to mediate cardiovascular repair, potentially reversing mechanical dysfunction in chronic ischaemic heart disease and post myocardial infarction. Two models were used in the present study both using a surgical ameroid constrictor to induce arterial stenosis. The first model used the carotid artery of rabbits. They were divided into high fat diet (inducing atherosclerosis) or normal fat diet (control) groups. Each was subdivided into surgical exposure group without constrictor, ameroid constrictor receiving normal saline or receiving G­CSF 15 µg/kg/day. Endothelial markers of endothelial nitric oxide synthase and endothelin 1 were increased by the use of ameroid constrictor in both atherosclerotic and non­atherosclerotic mice, however were not further altered by G­CSF. Scanning electron microscopy indicated that ameroid constrictor application altered endothelial morphology from an oval shape to a round shape and this was more prominent in the atherosclerotic compared with the non­atherosclerotic group. G­CSF injection increased the number of endothelial cells in all groups. The second model used the left coronary artery of pigs. They were equally divided into following groups, receiving normal saline (control), G­CSF 2.5 µg/kg/day (low dose), 5 µg/kg/day (medium dose) and 10 µg/kg/day (high dose) for 5 days. G­CSF at a low or high dose worsened intimal hyperplasia however at a medium dose improved it. In conclusion, G­CSF had no effect in a rabbit carotid artery model of atherosclerosis. Its effects on the porcine heart were dose­dependent; arterial disease worsened at a low or high dose, but improved at a medium dose.

Safety and efficacy of zotarolimus-eluting stents in the treatment of diabetic coronary lesions in Chinese patients: The RESOLUTE-DIABETES CHINA Study.

BACKGROUND: The RESOLUTE-DIABETES CHINA study was specifically designed to investigate the safety and efficacy of Resolute zotarolimus-eluting stents (ZES; Medtronic, Santa Rosa, CA, USA) in the treatment of diabetic coronary lesions in the Chinese population. METHODS: In all, 945 patients with de novo native coronary lesions and type 2 diabetes mellitus were recruited at 32 cardiac centers across the Chinese mainland and were implanted with Resolute ZES. The primary endpoint was target vessel failure (TVF); secondary endpoints were clinical outcomes, namely all-cause death, stroke, bleeding, target lesion revascularization (TLR), target vessel revascularization (TVR), non-TVR, and stent thrombosis (ST). The follow-up period for all endpoints was 12 months after the procedure. RESULTS: In all, 933 patients (98.73%) had clinical follow-up at 12 months. The rate of TVF was 11.60%, whereas the rate of occurrence of secondary endpoints was 5.47%, with four patients (0.43%) having subacute or late ST. There were no significant differences in TVF rates comparing patients with different HbA1c levels or receiving different glucose control treatments (all P > 0.05). Patients with multivessel lesions had higher TVF rates (95% confidence intervals) than those with single-vessel lesions (16.76% [12.10%-22.97%) vs 9.72% [7.79%-12.11%], respectively; P = 0.006). There were no significant differences in TVF rates in patients with or without small vessels, bifurcated lesions, or chronic total occlusions (all P > 0.05). [Correction added on 17 January 2019, after first online publication: in the second sentence of Results section, "TLF" was changed to "TVF".]. CONCLUSIONS: Resolute ZES may perform well in the Chinese diabetic population, especially in those with poor glucose control, complex lesions, and certain unfavorable clinical features. Further studies are needed to determine why ZES perform well in this population.

[Effects of early submaximal cardiopulmonary exercise test and cardiac rehabilitation for patients with acute myocardial infarction after percutaneous coronary intervention: a comparative study].

OBJECTIVE: To investigate the safety and effects of early submaximal cardiopulmonary exercise test (CPET) and cardiac rehabilitation for patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). METHODS: 94 patients with AMI after PCI were randomly divided into 2 groups: exercise group undergoing anaerobic rehabilitation training based on anaerobic threshold (AT) exercise prescription for 3 months, and control group, conducting exercise according to the needs of the patients themselves. Three months later, the exercise cardiopulmonary function was evaluated. RESULTS: In the first CPET 89 patients attained their anaerobic threshold (AT) and their heart rates were lower than their target heart rates following the exercise test. The oxygen consumption at the anaerobic threshold (VO2AT) 3 months later of the exercise group was [(12.6 +/- 2.9) ml x min(-1) x kg(1)], significantly greater and that before the exercise [(10.5 x 2.9) ml x min x kg(-1), P = 0.000]. The peak oxygen uptake (VO2 pea) 3 months of the exercise group was (20 +/- 4) ml x min(-1) x kg(-1), signficantly greater then that before exercise [(14 +/- 4) ml x min(-1) x kg(-1), P = 0.000]. The LAT 3 months of the exercise group was (42 +/- 16) J x s(-1), significantly higher than that before exercise p [(33 +/- 20) J x s(-1), P = 0.000]. The workload at peak level (Lpeak) 3 months of the exercise group was (89 +/- 14) J x s(-1) significantly greater than thatbefore exercise [(66 +/- 21) J x s(-1), P = 0.000]. And the VO2pea and Lpeak of 3 months later of the control group were [(19 +/- 4) ml x min(-l) x kg(-1)) and (80 +/- 14) J x s(-1)] respectively, both significantly higher than those before exercise [(14 +/- 4) ml x min(-1) x kg(-1) and (64 +/- 21) J x s(-1), both P = 0.000]. CONCLUSION: The early submaximal CPET and cardiac rehabilitation for patients with AMI after PCI are not only safe but also can improve their exercise capacity.

Circulating miR-21, miR-378, and miR-940 increase in response to an acute exhaustive exercise in chronic heart failure patients.

Congestive heart failure (CHF) is a major cause of hospitalizations, morbidity, and mortality in Western societies. In addition to optimal medical and device therapy, exercise training is an important adjunct treatment option for CHF patients. MicroRNAs (miRNAs, miRs) participate in a variety of physiological and pathological processes. Dynamic regulation of circulating miRNAs during exercise in healthy persons and athletes has recently been documented, however, the response of circulating miRNAs to exercise in CHF patients is undetermined. Twenty-eight CHF patients underwent a symptom-limited incremental cardiopulmonary exercise test on a bicycle ergometer using a standardized exercise protocol of revised Ramp10 programs at Shanghai Tongji Hospital. Blood samples were collected before and immediately after an acute exercise session. RNA was extracted from the serum and selected miRNAs were determined using quantitative polymerase chain reactions. Moreover, inflammatory and muscle damage markers were determined by enzyme linked immunosorbent assays. We found that serum miR-21, miR-378 and miR-940 levels were significantly up-regulated immediately following an acute exercise while the rest were not changed. In addition, no robust correlation was identified between changes of these miRNAs and exercise capacity, muscle damage or inflammation. In conclusion, serum miR-21, miR-378, and miR-940 increase in response to an acute exhaustive exercise in CHF patients. Further studies are needed to clarify the potential use of circulating miRNAs as biomarkers of exercise adaptation in CHF patients, and if they have any use as prognostic markers of cardiovascular outcomes.

Characteristics of B cell­associated gene expression in patients with coronary artery disease.

The current study aimed to identify differentially expressed B cell­associated genes in peripheral blood mononuclear cells and observe the changes in B cell activation at different stages of coronary artery disease. Groups of patients with acute myocardial infarction (AMI) and stable angina (SA), as well as healthy volunteers, were recruited into the study (n=20 per group). Whole human genome microarray analysis was performed to examine the expression of B cell­associated genes among these three groups. The mRNA expression levels of 60 genes associated with B cell activity and regulation were measured using reverse transcription­quantitative polymerase chain reaction. The mRNA expression of the B cell antigen receptor (BCR)­associated genes, CD45, NFAM, SYK and LYN, were significantly upregulated in patients with AMI; however, FCRL3, CD79B, CD19, CD81, FYN, BLK, CD22 and CD5 mRNA expression levels were significantly downregulated, compared with patients in the SA and control group. The mRNA levels of the T­independent B cell­associated genes, CD16, CD32, LILRA1 and TLR9, were significantly increased in AMI patients compared with SA and control patients. The mRNA expression of genes associated with T­dependent B cells were also measured: EMR2 and CD97 were statistically upregulated, whereas SLAMF1, LY9, CD28, CD43, CD72, ICOSL, PD1, CD40 and CD20 mRNAs were significantly downregulated in AMI group patients compared with the two other groups. Additionally the gene expression levels of B cell regulatory genes were measured. In patients with AMI, CR1, LILRB2, LILRB3 and VAV1 mRNA expression levels were statistically increased, whereas, CS1 and IL4I1 mRNAs were significantly reduced compared with the SA and control groups. There was no statistically significant difference in B cell­associated gene expression levels between patients with SA and the control group. The present study identified the downregulation of genes associated with BCRs, B2 cells and B cell regulators in patients with AMI, indicating a weakened T cell­B cell interaction and reduced B2 cell activation during AMI. Thus, improving B2 cell­mediated humoral immunity may be a potential target for medical intervention in patients with AMI.

Depletion of complement system immunity in patients with myocardial infarction.

The aim of the present study was to evaluate differences in the expression of complement system genes, and serum levels of CH50, C3 and C4 in peripheral blood mononuclear cells from patients with myocardial infarction (AMI), stable angina pectoris (SA) and controls. A total of 100 patients with AMI, 100 with SA and 100 clinical controls were recruited in the present study. In each group, 20 randomly selected individuals were examined using whole human genome microarray analysis to detect the expression of genes of the complement system. The serum levels of CH50, C3 and C4 were measured in all 300 subjects. In the patients with AMI, the expression levels of genes encoding C1qα, C1qß, C1qγ, C1r, Factor P, C5a (complement component), CR1, integrin αM, integrin αX, integrin ß2, C5aR, CRIg (complement receptors) and CD46, CD55 and CD59 (complement regulators) were significantly higher, compared with the respective genes in the SA patients and controls (P<0.05), whereas the mRNA levels of C1s, C7, C8ß and C9 were the lowest in this group (P<0.05). No statistically significant differences were found in the gene expression levels of complement components or regulators between the SA and control groups. The serum levels of CH50, C3 and C4 were significantly increased in the AMI and SA groups, compared with the controls. In the AMI and SA groups, the complement system was activated. However, the differential mRNA expression of complement components, receptors and regulators in the AMI group suggested the dysfunction of the C5b-9 complex. The depression of complement system immunity in the patients with AMI may be associated with the pathogenesis of AMI.

The Prognostic Value of Peak Cardiac Power Output in Chinese Patients with Chronic Heart Failure.

BACKGROUND: Cardiopulmonary exercise testing has been widely used to risk stratify patients with chronic heart failure (CHF). Peak oxygen consumption (peakVO2) was regarded as a powerful predictor of survival, as it is a surrogate for peak cardiac output (CO), which by most is considered the "true" measure of heart failure. Therefore, it is reasonable to hypothesize that CO is an even stronger predictor than peak VO2. The present study is aimed to investigate the prognostic value of peak cardiac power output (peak CPO) in comparison with peakVO2 in Chinese patients with CHF. METHODS: Participants provided written informed consent to participate in this study. Totally 129 patients with CHF underwent symptom-limited cardiopulmonary exercise testing (CPET), with mean age 59.1 ± 11.4 years, 87.6% male, 57.4% ischemic etiology, body mass index (BMI) 24.7 ± 3.7 kg/m(2) and LVEF 38 ± 9%. CO was measured using an inert gas rebreathing method. The primary endpoints are cardiac deaths. RESULTS: Over median 33.7-month follow-up, 19 cardiac deaths were reported. Among peak VO2,VE/VCO2 slope and Peak CPO, their area under ROC were 0.64, 0.67, 0.68, respectively (Ρ<0.05).The optimal thresholds for predicting cardiac deaths were peak VO2 ≤ 13.4 ml.kg(-1).min(-1), and VE/VCO2 slope ≥ 39.3 and peak CPO≤ 1.1 respectively by ROC analysis. Finally, in patients with a peak VO2 ≤ 13.4 ml.kg(-1).min(-1) those with peak CPO>1.1W had better survival than those with peak CPO ≤ 1.1W. However, by multivariate analysis adjusted for age, sex, BMI, resting heart rate, LVMI, LVEF, Peak CPO was not an independent predictor of cardiac deaths (P> 0.05). CONCLUSIONS: Peak CPO was not a predictor of cardiac death in Chinese CHF patients.