Correlation between cardiac resynchronization response and pulmonary artery hemodynamic parameters. / å¿ƒè„å†åŒæ­¥åŒ–æ²»ç–—ååº”æ€§å’Œè‚ºåŠ¨è„‰è¡€æµåŠ¨åŠ›å­¦å‚æ•°çš„ç›¸å ³æ€§.

OBJECTIVES: To evaluate the response to cardiac resynchronization therapy (CRT) and the correlation between CRT and pulmonary artery hemodynamic parameters. METHODS: The patients with chronic heart failure indicator for CRT were enrolled. The left ventricular end-systolic volume (LVESV) was measured by echocardiography and New York Heart Association (NYHA) classification was evaluated between one week before and six months after CRT. Mean pulmonary artery pressure (mPAP), pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were measured by right heart catheterization. Left ventricular reverse remodeling (LVRR) is defined as a decrease of 15% or more in LVESV at the 6th month after CRT; Clinical response is defined as a decrease of NYHA classification at or above grade 1 at the 6th month after CRT. Pulmonary hypertension (PH) was defined as mPAP≥25 mmHg. According to the response, patients were divided into 3 groups: group A (LVRR+clinical response), group B (no LVRR+clinical response) and group C (no LVRR+no clinical response). The changes of NYHA classification, echocardiographic and pulmonary hemodynamic parameters were observed in the 3 groups. The Kaplan-Meier survival curve was used to analyze the differences in all-cause mortality, combined end-point events of death or re-hospitalization due to heart failure among different groups. RESULTS: A total of 45 patients with CRT implantation [aged (63.27±9.55) years, 36 males] were included. The average follow-up period was (33.76±11.50) months. Thirty-one patients (68.89%) were in group A, 9 of whom with PH. Eight patients (17.78%) were in group B, 7 of whom with PH. Six patients were in group C, all with PH. Cardiac function including NYHA classification, echocardiographic and pulmonary hemodynamic parameters had been significantly improved in group A after CRT implantation (P<0.05). In group B, NYHA classification and pulmonary hemodynamic parameters were decreased significantly (P<0.05), but echocardiographic parameters did not change obviously (P>0.05). There were no significant changes in NYHA classification, echocardiographic and pulmonary hemodynamic parameters in group C (P>0.05). Compared with group C, group A and group B had lower all-cause mortality (P=0.005) and lower incidence of composite endpoint events (P=0.001). CONCLUSIONS: Patients with LVRR and clinical response after CRT have a good prognosis. Patients with clinical response but without LVRR have a better prognosis than those without clinical response and LVRR, which may be related to the decrease of pulmonary hemodynamic parameters such as mPAP and TPG.

Cilostazol Promotes Angiogenesis and Increases Cell Proliferation After Myocardial Ischemia-Reperfusion Injury Through a cAMP-Dependent Mechanism.

PURPOSE: Previous study indicated the protective role of cilostazol in ischemia-reperfusion (I/R) injury. Here, we aimed to explore the function of cilostazol in myocardial I/R injury and the underlying mechanism. METHODS: The myocardial I/R injury rat model was constructed, and the expression levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor receptor b (PDGF-B) and the number of new blood vessels were measured by qRT-PCR and immunohistochemistry. VSMC and HUVEC cells were treated with hypoxia to induce in vivo I/R injury model. The protein expression of AKT, endothelial nitric oxide synthase (eNOS) and apoptosis-related protein levels were detected by western blotting. Besides, the positive staining rate and cell viability were tested by 5-bromo-2-deoxyuridine (Brdu)/4',6-diamidino-2-phenylindole (DAPI) or DAPI/TdT-mediated dUTP Nick-End Labeling (TUNEL) staining and MTT assay. RESULTS: Cilostazol promoted angiogenesis by increasing the number of new blood vessels and up-regulating the expression of VEGF, HGF, bFGF and PDGF-B in myocardial I/R-injury rat model. The in vitro experiments showed that cilostazol increased the level of eNOS and AKT, and also enhanced cell proliferation in hypoxia-treated VSMC and HUVEC cells. Furthermore, after 8-Br-cAMP treatment, VEGF, HGF, bFGF, PDGF-B, p-AKT and p-eNOS expression were up-regulated, while cleaved-caspase 3 and cleaved-PARP expression were down-regulated. In addition, the effects of cilostazol on cell viability and apoptosis were aggravated by 8-Br-cAMP and attenuated after KT-5720 treatment. CONCLUSION: Cilostazol could promote angiogenesis, increase cell viability and inhibit cell apoptosis, consequently protecting myocardial tissues against I/R-injury through activating cAMP.

Complete versus culprit-only revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease: a meta-analysis of randomized trials.

BACKGROUND: The best strategy for the treatment of the non-infarct artery in patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) undergoing primary percutaneous coronary intervention (PCI) is not yet defined. METHODS: We searched the literature for randomized controlled trials (RCTs) that compared complete revascularization (CR) with infarct-related coronary artery (IRA) only revascularization in hemodynamically stable patients with STEMI. Random effect risk ratios (RRs) were calculated for clinical outcomes. RESULTS: Nine RCTs with 2989 patients were included. No significant difference in all-cause mortality emerged between CR and IRA-only groups (relative risk [RR] = 0.74; 95% confidence interval [CI]: 0.52 to 1.04; p = 0.08). Compared with IRA-only, CR was associated with significantly lower rates of major adverse cardiac events (MACE) (RR = 0.53; 95% CI: 0.41 to 0.68; p < 0.001), cardiac death (RR = 0.48; 95% CI: 0.29 to 0.79; p = 0.004) and repeat revascularization (RR = 0.38; 95% CI: 0.30 to 0.47; p < 0.001). In subgroups analysis, immediate complete revascularization (ICR) reduced the risk of all-cause mortality (RR = 0.62; 95% CI: 0.39 to 0.97; p = 0.04), whereas staged complete revascularization (SCR) did not show any significant benefit in all-cause mortality (RR = 0.92; 95% CI: 0.46 to 1.86; p = 0.82). Stroke, contrast-induced nephropathy and major bleeding were not different between CR and IRA-only. CONCLUSIONS: For patients with STEMI and multivessel disease undergoing primary PCI, complete revascularization did not decrease the risk of all-cause mortality in current evidence from randomized trials. When feasible, immediate complete revascularization might be considered in patients with STEMI and multivessel disease.

Cilostazol protects against myocardial ischemia and reperfusion injury by activating transcription factor EB (TFEB).

Although cilostazol was proved to have antitumor biological effects, its function in myocardial ischemia and reperfusion (I/R) injury and the underlying mechanisms were not fully illustrated yet. In this study, a rat model of I/R injury was constructed and quantitative real-time PCR, Western blot, and immunofluorescence (IF) assay were performed. Our results showed that cilostazol increased LC3 II/LC3 I ratio, reduced p62 abundance, and promoted the expressions of LAMP1, LAMP2, cathepsin B, and cathepsin D, indicating that cilostazol could activate autophagy and elevated lysosome activation. Following analysis showed that cilostazol enhanced nuclear protein expression of transcription factor EB (TFEB), an important regulator of autophagy-lysosome pathway. Furthermore, CCI-779, an inhibitor of TFEB, could reverse the effects of cilostazol on autophagic activity and lysosome activation. Importantly, cilostazol suppressed I/R injury-induced apoptosis by decreasing the cleavage of caspase 3 and PARP. Enzyme-linked immunosorbent assay showed that cilostazol reduced the serum levels of CTn1 and CK-MB and decreased infract size caused by I/R injuries. Altogether this study suggested that cilostazol protects against I/R injury by regulating autophagy, lysosome, and apoptosis in a rat model of I/R injury. The protective mechanism of cilostazol was partially through increasing the transcriptional activity of TFEB.

Early Change in Global Longitudinal Strain is an Independent Predictor of Left Ventricular Adverse Remodelling in Patients With Right Ventricular Apical Pacing.

BACKGROUND: Right ventricular apical (RVA) pacing is related to adverse left ventricular (LV) remodelling. This study assessed changes in global longitudinal strain (GLS) after permanent RVA pacing, and investigated whether GLS at one month can predict later LV ejection fraction (LVEF) decline. METHODS: The study enrolled 68 patients with normal LVEF (≥50%) who underwent dual chamber pacemaker implantation for third-degree atrioventricular block. Global strains and LVEF were assessed using three-dimensional (3D) speckle tracking strain echocardiography (STE). RESULTS: At one month, GLS was significantly lower in those patients who developed pacing-induced LV dysfunction (PIVD), which was defined as a reduction in LVEF ≥5 percentage points at 12 months, than those who did not (-14.9±1.8 vs -16.1±1.7, p=0.014), although GLS was similar at baseline. In patients who developed PIVD, only GLS was significantly reduced at one month compared to baseline (-14.9±1.8 vs -16.6±1.2, p=0.022) whereas LVEF was not. Global longitudinal strain at one month was the only independent predictor for PIVD at 12 months on multivariate analysis (OR, 1.623; 95% CI, 0.986-2.210; p=0.009). Receiver operating characteristic (ROC) analysis showed that GLS at one month had a high predictive accuracy for the development of PIVD at 12 months, with an area under curve (AUC) of 0.88, 94% sensitivity, and 70% specificity. CONCLUSIONS: Global longitudinal strain at one month after pacemaker implantation had high predictive accuracy for identifying subsequent development of PIVD. Global longitudinal strain may be an invaluable parameter to predict LV adverse remodelling following permanent RVA pacing.

Berberine treatment reduces atherosclerosis by mediating gut microbiota in apoE-/- mice.

BACKGROUND: Berberine (BBR) has long been used for treating bacterial diarrhea due to its antimicrobial effect and is currently used to treat obesity, diabetes, hyperlipemia and atherosclerosis. Given the poor oral bioavailability of BBR, the mechanisms through which BBR mediates metabolic disorders are not well understood. The present study was designed to explore the role of BBR-induced gut microbiota modulation in the development of atherosclerosis. METHODS: Male apoE-/- mice were fed a high-fat diet (HFD) with or without the intragastric administration of BBR. Because mice are coprophagic and can transfer their gut microbiota to each other, we cohoused BBR-treated HFD-mice with non-BBR-treated HFD-fed mice. RESULTS: After 12 weeks of HFD feeding, compared with non-BBR-treated HFD-fed mice, BBR-treated HFD-fed mice exhibited a significant reduction in both atherosclerosis development and inflammatory cytokine expression. In addition, cohousing BBR-treated HFD-fed mice with non-BBR-treated HFD-fed mice decreased atherosclerosis development and inflammatory cytokine expression. The denaturing gradient gel electrophoresis and principal component analyses showed that the gut microbial profiles of BBR-treated HFD-fed mice were significantly different from those of HFD-fed mice but were similar to those of cohoused mice. The abundances ofFirmicutes and Verrucomicrobia in cohoused and BBR-treated mice were different from those in HFD-fed and normal chow-fed mice. Moreover, BBR reduced hepatic FMO3 expression and serum trimethylamine N-oxide levels. CONCLUSION: The antiatherosclerotic effect of BBR is related to alterations in gut microbiota compositions, indicating the potential therapeutic value of pharmacological approaches that may modulate the gut microbiota in treating atherosclerosis.

Antithrombotic therapy strategies for atrial fibrillation patients undergoing percutaneous coronary intervention: A systematic review and network meta-analysis.

OBJECTIVE: The aim of this systematic review and network meta-analysis was to evaluate the comparative efficacy and safety of antiplatelet agents, vitamin K antagonist (VKA) and non-VKA oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify clinical trials comparing antiplatelet drugs with VKA and NOACs or their combination in AF patients undergoing PCI with a mean/median follow-up of at least 12 months. A network meta-analysis was conducted to directly and indirectly compare the efficacy and safety of competitive antithrombotic regimens with a Bayesian random-effects model. Results were presented as relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: A total of 15 studies enrolling 13,104 patients were included. Among 5 regimens, rivaroxaban 15 mg daily plus P2Y12 inhibitor treatment demonstrated significant superiority over dual- and triple-antiplatelet therapies (DAPT, TT) in reducing thromboembolic events (0.64 [0.38, 0.95] and 0.68 [0.43, 0.98], respectively) but showed the maximum possibility of major bleeding risk, while VKA plus single antiplatelet therapy (SAPT) seemed the safest. Significantly less risk of major bleeding was seen in DAPT group than that in TT group (0.63 [0.39, 0.99]). CONCLUSIONS: The present study suggests that combination of VKA and SAPT is the best choice for AF patients undergoing PCI considering both efficacy and safety. Rivaroxaban 2.5 mg twice daily plus DAPT treatment owns the highest probability to be the optimal alternative to VKA plus SAPT for these patients.

Early Right Ventricular Apical Pacing-Induced Gene Expression Alterations Are Associated with Deterioration of Left Ventricular Systolic Function.

The chronic high-dose right ventricular apical (RVA) pacing may have deleterious effects on left ventricular (LV) systolic function. We hypothesized that the expression changes of genes regulating cardiomyocyte energy metabolism and contractility were associated with deterioration of LV function in patients who underwent chronic RVA pacing. Sixty patients with complete atrioventricular block and preserved ejection fraction (EF) who underwent pacemaker implantation were randomly assigned to either RVA pacing (n = 30) group or right ventricular outflow tract (RVOT) pacing (n = 30) group. The mRNA levels of OPA1 and SERCA2a were significantly lower in the RVA pacing group at 1 month's follow-up (both p < 0.001). Early changes in the expression of selected genes OPA1 and SERCA2a were associated with deterioration in global longitudinal strain (GLS) that became apparent months later (p = 0.002 and p = 0.026, resp.) The altered expressions of genes that regulate cardiomyocyte energy metabolism and contractility measured in the peripheral blood at one month following pacemaker implantation were associated with subsequent deterioration in LV dyssynchrony and function in patients with preserved LVEF, who underwent RVA pacing.

Cilostazol protects mice against myocardium ischemic/reperfusion injury by activating a PPARγ/JAK2/STAT3 pathway.

Myocardial ischemia/reperfusion (MIR) injury causes severe arrhythmias and a high lethality. The present study is designed to investigate the effect of cilostazol on MIR injury and the underlying mechaism. We measured the effects of cilostazol on heart function parameters in a mouse model of MIR. Proinflammatory cytokines and apoptosis proteins in the myocardium were examined to investigate the anti-inflammatory and anti-apoptosis ability of cilostazol. The participation of PPARγ/JAK2/STAT3 pathway was investigated. Results showed that the impairment of hemodynamic parameters caused by MIR was attenuated by cilostazol. The IL-6, IL-1ß and TNF-a levels were all decreased by cilostazol. Cilostazol also significantly inhibited Bax and cleaved caspase-3 levels and restored the Bcl-2 levels. PPARγ, JAK2 and STAT3 were all activated by cilostazol. Treatment of inhibitors of them abolished the protective effects of cilostazol on cardiac function, myocardial inflammation and apoptosis. In summary, cilostazol alleviated the cardiac function impairment, myocardial inflammation and apoptosis induced by MIR. The results present a novel signaling mechanism that cilostazol protects MIR injury by activating a PPARγ/JAK2/STAT3 pathway.

Clinical Research on Brain Natriuretic Peptide Guiding the Application of ß1 Receptor Blocker in Patients with Moderate to Severe Heart Failure.

BACKGROUND: This study aimed to explore the feasibility of guiding the application of metoprolol succinate in patients with moderate to severe heart failure (HF) through monitoring plasma brain natriuretic peptide (BNP) levels. METHODS: A total of 195 patients with moderate to severe HF (NYHA Functional Class III to IV) were selected and randomized into two groups: an observation group and a BNP group. The groups were established to observe the clinical conditions and establish plasma BNP levels to guide the application of metoprolol succinate. The average start-up of metoprolol succinate and average dose of metoprolol succinate after one month, as well as the recurrence rate and mortality of HF during hospital stay were compared between the two groups. RESULTS: Start-up of metoprolol succinate was shorter in the BNP group than in the observation group [(5.89 ± 1.76) d vs. (7.03 ± 2.08) d, p < 0.01], but no significant differences in recurrence rate (26.60% vs. 23.91%, p > 0.05) and mortality (6.38% vs. 5.43%, p > 0.05) of HF were observed between the two groups. The average dose of metoprolol succinate after one month was higher in the BNP group compared with that of the observation group [(47.65 ± 13.09) mg/d vs. (35.08 ± 11.08) mg/d, p < 0.01]. CONCLUSIONS: Although monitoring plasma BNP might have limited the clinical impact on the change of left ventricular ejection fraction, recurrence of HF or mortality within 1 month, it could safely facilitate early use and up-titration of the metoprolol succinate in patients with moderate to severe HF. KEY WORDS: BNP; Heart failure; ß receptor blocker.

[The predictive value of plasma cystatin C for non-ST-elevation acute coronary syndrome treated with percutaneous coronary intervention].

OBJECTIVE: To evaluate the prognosis value of plasma cystatin C in predicting adverse cardiac events after percutaneous coronary intervention (PCI) for non-ST-elevation acute coronary syndrome (NSTEACS). METHODS: A total of 277 patients (212 male, mean age 59 ± 12 years) with NSTEACS underwent successful PCI. The patients were then divided into MACE group and non-MACE group. Patients were divided into 4 groups according to the level of cystatinC : Q1 (<0.78 mg/L), Q2 (0.78-0.93 mg/L), Q3 (0.94-1.11 mg/L), and Q4 ( ≥ 1.12 mg/L) . Risk factors for MACE were analyzed by Cox regression analysis. RESULTS: The plasma Cys-C level were higher in MACE group than in non-MACE group(P < 0.05). The areas under ROC curve of Cys-C, cTnI, hsCRP an CK-MB to predict cardiac event were 0.737,0.630,0.692 and 0.650 respectively. After a follow-up of 1 year, the MACE in the Q2, Q3, and Q4 groups was higher than in the Q1 group (Logrank = 23.751, P < 0.01). Multivariate Cox regression analysis showed that cystatin C elevation was an independent predictor of major adverse cardiac events (P < 0.01). CONCLUSION: High plasma cystatin C concentration is an independent predictor of major adverse cardiac events in patients with NSTEACS treated with PCI.