OBJECTIVE To evaluate the effects of ivabradine on vascular endothelial function in patients with coronary artery disease. METHODS PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang Data， VIP and CBM databases were retrieved to collect randomized controlled trials （RCTs） about ivabradine （intervention group） versus placebo or β-blocker （control group） from the inception to Mar. 20th 2023. The meta-analysis was performed by using RevMan 5.4 software after literature screening， data extraction and quality evaluation. RESULTS A total of 12 RCTs were included， involving 1 206 patients. The results of meta-analysis showed that the levels of flow-mediated dilation （FMD） [MD＝1.71， 95%CI （0.96， 2.46）， P＜0.000 01] and nitric oxide （NO） [MD＝5.80， 95%CI （5.02， 6.59）， P＜0.000 01] in the intervention group were significantly higher than control group， while endothelin-1（ET-1） level was significantly lower than control group [MD＝－7.45， 95%CI （－8.42， －6.47）， P＜0.000 01]. There was no statistical significance in nitroglycerin-mediated dilation （NMD） level between 2 groups [MD＝0.13， 95%CI（－0.74， 1.00）， P＝0.77]. Subgroup analyses based on the different medications and intervention time in the control group showed better improvement in FMD level of patients receiving ivabradine， compared with placebo （P＜0.05）； compared with placebo and β-blocker， the level of NO in patients receiving ivabradine was improved significantly （P＜0.05）， while ET-1 level was decreased significantly （P＜0.05）. Regardless of the duration of the intervention， the levels of FMD， NO， and ET-1 in the intervention group were significantly improved compared to the control group （P＜0.01）， while the difference in NMD was not statistically significant （P＞0.05）. CONCLUSIONS Ivabradine can improve vascular endothelial function in patients with coronary artery disease.

OBJECTIVE To develop a standard of hierarchical management for patients with chronic obstructive pulmonary disease （COPD） from the perspective of pharmacists. METHODS The triangle hierarchical management model was used as the framework. Through literature research， the indicators of the hierarchical management standard for COPD patients were preliminarily compiled. A questionnaire was designed and administered to 18 experts， and Delphi method was conducted in two rounds to determine the contents of the standard. RESULTS The response rates for both rounds of expert consultation were 100%， with both authority coefficients of experts of 0.903 and Kendall coordination coefficiens of 0.279 and 0.189 for each indicator. The final established standard of hierarchical management for COPD patients included 25 stratified indicators and 17 pharmaceutical hierarchical management indicators. There were 9， 8 and 8 indicators in the high-risk， medium-risk， and stable layers， respectively， considering three aspects： disease， medication， and self-management level. The corresponding first-level， second- level， and third-level pharmaceutical management included 6， 6 and 5 indicators， respectively， including inhalation technical guidance， medication adherence guidance， treatment monitoring， and follow-up， etc. CONCLUSIONS The standard of hierarchical management for COPD patients established by Delphi method is scientific and reliable， which can provide a reference for pharmacists to carry out hierarchical management of COPD patients in China.

OBJECTIVE To evaluate the cost-effectiveness of ivabradine in the treatment of chronic heart failure （CHF） in the context of “Quadruple Therapy” from the perspective of the health system. METHODS Based on real-world cohort data， the Markov model was constructed according to the natural progression of CHF， with a cycle time of 3 months， a study timeframe of 20 years， and a discount rate of 5%. Using quality-adjusted life year （QALY） and incremental cost-effectiveness ratios （ICER） as the output indexes， the cost-utility analysis was used to evaluate the cost-effectiveness of ivabradine in combination with the “Quadruple Therapy” regimen， compared with the “Quadruple Therapy” regimen for the treatment of CHF， and the robustness of the results of the base analysis was verified by univariate sensitivity analysis and probabilistic sensitivity analysis. RESULTS The results of the base analysis showed that the ICER of ivabradine combined with the “Quadruple Therapy” regimen was 165 065.54 yuan/QALY， compared with the “Quadruple Therapy” regimen， which was lower than the willingness-to-pay （WTP） threshold （257 094 yuan/QALY） based on 3 times of China’s gross domestic product （GDP） per capita in 2022. The results of the univariate sensitivity analysis showed that the discount rate had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the probability that the ivabradine combined with the “Quadruple Therapy” regimen was cost-effective under the WTP threshold in this study was 59.50%. CONCLUSIONS When using 3 times China’s 2022 GDP per capita （257 094 yuan/ QALY） as the WTP threshold， the combination of ivabradine and the “Quadruple Therapy” regimen for treating CHF is cost- effective.

Objectives:To assess the effectiveness and safety of ivabradine for the treatment of chronic heart failure in the context of the new quadruple combination. Methods:Clinical data of 656 chronic heart failure patients hospitalized in Nanjing Drum Tower Hospital from March 2021 to June 2022 were retrospectively collected,and the patients were divided into control group(n=361)and observation group(n=295)according to ivabradine use,and both groups were treated with the new quadruple drug therapy.Propensity score matching was performed,268 patients in the observation group and 268 patients in the control group were successfully matched.The effectiveness(primary endpoint was the composite endpoint of cardiovascular death and rehospitalisation for worsening heart failure within 1 year of discharge;secondary endpoints were rehospitalisation for worsening heart failure,all-cause rehospitalisation,cardiovascular death,and all-cause death)and safety outcome measures(including bradycardia,atrial fibrillation,blurred vision,renal impairment,and hypertension)were compared between the two groups at 1 year after treatment. Results:After matching,there were no statistically significant differences at baseline characteristics between the two groups.Kaplan-Meier survival curve showed that the occurrence rates of primary endpoints(P=0.031),readmission for worsening heart failure(P=0.020),and all-cause readmission(P=0.036)were lower in the observation group than in the control group.Multivariate Cox proportional hazard regression analysis showed that the occurrence rates of primary endpoint events(P=0.045)and readmission for heart failure worsening(P=0.028)were lower in the observation group than in the control group. Conclusions:The ivabradine use on top of the new quadruple therapy regimen in patients with chronic heart failure is beneficial to improve one-year prognosis with favorable safety profile.

OBJECTIVETo summarize the experience with surgical correction of tetralogy of Fallot in adults over 40 years of age.

METHODSFrom November 1985 to July 2008, 9 male and 11 female patients aged 41-53 years (mean 46.3±3.5 years) underwent total surgical correction for tetralogy of Fallot. Twelve patients had preoperative NYHA class III cardiac function. The common comorbidities included infective endocarditis, cerebral abscess, cerebral infarction, renal dysfunction, and tricuspid insufficiency. Surgical corrections were carried out at the anatomical or physiological level.

RESULTSNineteen patients received right ventriculotomy to relieve right ventricular outflow obstruction and for ventricular septal defect closure, and 1 patient had Fontan operation. Two patients died after the surgery for heart failure and ventricular fibrillation. The average cardiopulmonary bypass time, aortic clamp time, and postoperative ventilation time was 142.9±36.3 min, 89.9±25.1 min, and 72.0±17.5 h, respectively. Postoperative low cardiac output syndrome occurred in 5 cases, septic shock in 1 case, secondary renal failure in 1 case, and bleeding in 2 cases. Echocardiography showed a significant postoperative reduction of the mean right ventricular outflow tract velocity from 4.29±1.36 m/s to 2.13±0.83 m/s (P<0.01); the right ventricular longitudinal dimension exhibited no significant changes postoperatively (57.1±6.7 mm vs 55.1±7.0 mm, P=0.65).

CONCLUSIONSSurgical correction of the tetralogy of Fallot in patients over 40 years is highly risky and requires appropriate management of cardiac failure, careful myocardial protection, and thorough intracardiac lesion correction to decrease surgical complications.

Objective Background and objective The Cox maze Ⅲ procedure has been considered the gold standard for the surgical treatment of atrial fibrillation (AF) and the modified Cox maze use bipolar radiofrequency ablation instead of the cut-and-sew technique,while also reducing the connecting lines in left atrium.This study was to understand whether completely isolation the posterior left atrium by increasing left atrium ablation lines can enhance the survival after modified Cox maze procedure.Methods From Jan 2009 to Dec 2009,all the patients underwent the Cox maze procedure,following the same examination,were divided into two groups (case-control): box lesion group (n =60),which is means the right and lefi pulmonary vein lesions were connected inferiorly by adding ablation lines,thereby completely isolating the posterior left atrium and the non-box lesion group (n =60).Similar interventions were given during the perioperative periods.Comparing the risk factors before surgeries,then follow-up was 100％ complete,and the mean follow-up was 9 ± 8.4 months.Results Except the box lesion had long time of extracorporeal circulation,the characteristics of the 2 groups were similar because there were no differences in age,AF duration,left atrial diameter,left ventricular ejection fraction or homochronous operation between the groups and there was no operative death.No patient was lost to follow-up.In the mean follow-up duration,a patient was died of intracerebral hemorrhage at 2 months postoperationly in the box lesion group and a patient suffered from stroke at 12 months postoperationly in the non-box lesion.The overall freedom from AF recurrence was higher in the box lesion group at 1 (70％ vs 51.2％,P =0.039) and 3 (78.3％ vs 60％,P =0.030) months.While it was 80％ vs 71.7％ (P =0.286) at 6 months.Eight patients wrere readmitted because of the recurrence of AF,4 and 2 patients underwent catheter ablation in box and non-box group respectively,one patient in each group underwent electrical conversion.After treatment,all of the patients were recovered to sinus rhythm and continued to take cordarone.Conclusion Compared to the single connecting between right and left pulmonary vein,isolating the entire posterior left atrium by creating a box lesion showed higher freedom from AF in the earlier months (1-3months).However,half a year after the surgery,there were no significant differences between the two groups.

Objective Konno-Rastan procedure is one option to cope with complex multilevel left ventricular outflow tract obstruction (LVOTO),which continues to pose a serious challenge to cardiac surgeons.The aim of this study is to retrospectively analyse indications for Konno-Rastan procedure,and to review the safeguards and pitfalls.Methods Between January 1996 and August 2012,totally 13 children with multilevel LVOTO underwent Konno-Rastan procedure.There were 8 boys and 5 girls.Age at surgeries ranged from 5 to 13 years,and weight from 12 to 51 kg with median of 21 kg.The pathology of this cohort includes:8 cases of congenital aortic valvular stenosis,3 cases of congenital aortic valvular stenosis combined with supravalvular stenosis,1 case of congenital aortic stenosis combined with VSD,coarctation and RVOT obstruction,1 case of aortic stenosis s/p percutaneous balloon aortic valvuloplasty.All patients have secondary diffuse tunnel LVOTO.Diameter of aortic ring ranges from 12.0 to 16.4 mm,and pressure gradient across the stenotic region ranges from 90-151 mm Hg.8 cases were implanted with St.Jude AG19 while 5 cases implanted with St.Jude AG17.Results All 13 cases survived.The 4th patient was implanted permanent epicardial pacemaker for transient Ⅲ AVB.The 4th and 5th patients were found residual ventricular septal repture at the nadir of ventricular incision,one underwent redo procedure while another is being followed up.All cases take cumadine to sustain INR at 1.8-2.5.No death emerges during follow-up period.The motality is 0％,the incidence rate of B is 7.7％,residual VSD 15.4％ and endocarditis 7.7％.Conclusion Konno-Rastan procedure is a promising techi.to relieve LVOTO.However,this complex procedure may lead to several fetal complications.Success of the surgery demands perfect operations.

Objective To validate of the Chinese system for cardiac operative risk evaluation (SinoSCORE) in Cantonese surgery patients. Methods Data from Guangdong Cardiovascular Institute in the period January 2004 through December 2008 were analyzed on 2462 Cantonese heart surgery patients. First, compared risk factors of this series and database of SinoSCORE, and then calculated the additive score of each patients and evaluate the discrimination and calibration of sinoSCORE in Cantonese patients. Results There were some differences between the risk factors of patients from two groups. The gender,smoking, diabetes, hyperlipemia, hypertension, chronic pulmonary diseases, stroke, cardiovascular surgery history, left main disease, atrial fibrillation/atrial flutter, pulmonary arterial hypertension, concomitant coronary surgery and concomitant valve surgery in Cantonese patients were different between two groups. However, The SinoSCORE was able to predict the in-hospital mortality of senior patients with good discrimination ( Hosmer-Lemeshow test, P = 0. 34 ) and calibration ( the area under the receiver operating characteristic curve, 0.84, P ＜ 0.01 ). Conclusion SinoSCORE was able to predict the in-hospital mortality of Cantonese heart surgery patients.

[Objective] To study the apoptosis after long time of heart preservation,and the barrier of caspase (Ac-DEVD-CHO) in prolonged heart transplantation.To improve the techniques on the preservation of donor heart.[Methods] Donor rat hearts were subjected to group A (non-Ac-DEVD-CHO-treated),group B (Ac-DEVD-CHO-treated) of hypothermic storage,after 9 hours of heart preservation,then performed heterotopic heart transplantation,followed by 60 min of normothermic reperfusion (n ＝ 6 in each group).[Results] After 60 min reperfusion,compared with group A,① a significant improvement in the percent recovery of HR was observed in group B (P ＜ 0.05);② Caspase-3 activity was decreased in group B (P ＜ 0.01);③ an apparent decline in the expression of infarct area was observed in group B (P ＜ 0.01);④ an apparent decline in the expression of TUNEL-positive cardiomyocyte was observed in group B (P ＜ 0.01);⑤ Group B shows the least disease.[Conclusion] ① After preservation and reperfusion,cardiomyocyte apoptosis was observe evidently,which led to irreversible heart dysfunction.② The administration of caspase-3 inhibition after reperfusion attenuates ischemia-reperfusion injury by suppressing apoptosis in heart transplantation.Furthermore,the use of caspase inhibition was investigated as a strategy for the preservation donor heart in transplantation.③ The relationship of dose-response and time-effect is still unknown.

Objective: To evaluate the phenomenon of post-coronary artery bypass graft (CABG) supply-dependent oxygen consumption and the critical level of oxygen delivery. Methods: 53 patients undergoing CABG were randomized selected for this study. The oxygen delivery, oxygen consumption, and oxygen extraction were studied 1,4,12,24, and 48 hours post-operatively. Data were analyzed by SPSS. Results: The oxygen delivery of post-op 1 hour was the lowest (363.88ml?min -1 ?m -2 ). The 4th and 12th hour post-operatively oxygen deliveries were 396.02 ml?min -1 ?m -2 and 412.92 ml?min -1 ?m -2 respectively, lowers than that post-op 24 hour. After post-op 24 hour, the oxygen delivery was relatively stable, and the value was 468.78 ml?min -1 ?m -2 . The oxygen consumption of post-op 12 hour was the highest (143.02 ml?min -1 ?m -2 ), which closed to the normal value. The oxygen extraction of post-op 1 hour was the highest (35.6%). The oxygen extraction of post-op 12 hour was 32.6%, slightly lower than that post-op 1 hour. The oxygen extraction of after post-op 24 decreases obviously to be relatively stable, the value was 30.2%. Conclusion: 1, Postoperative 1 to 4 hour of CABG, hypoxia exists and oxygen delivery should be increased by maintain a higher pulmonary capillary wedge pressure and cardiac index. 2,There is a pathologic oxygen supply dependency for critical patients of post-CABG, the patients is still in hypoxia post-CABG 48 hour. Therefore, it is very important to keep oxygen supply and decrease oxygen consumption. It is better that the assistant ventilation is kept about 24 hours postoperatively. The pulmonary complications should be controlled as soon as possible. 3, The critical level of oxygen delivery is between 363.88 ml?min -1 ?m -2 and 396.02 ml?min -1 ?m -2 .