The China Patient-Centred Evaluative Assessment of Cardiac Events (China PEACE)-Prospective Study of 3-Vessel Disease: rationale and design.

INTRODUCTION:Complex coronary artery disease (left main and three-vessel disease) carries high risks of adverse events and cost burden. However, in China, little is known about which patients are directed toward which treatment strategies and what outcomes are being achieved.METHODS AND ANALYSIS:Using the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) research network, this prospective study of three-Vessel Disease, the China PEACE-3VD study, has a plan to consecutively register over 4000 patients with a diagnosis of 3VD and/or left-main disease by elective coronary angiography at 24 large cardiovascular centres in China. We centrally conducted medical record abstraction and SYNTAX Score calculation for all registered patients. The sites invited patients to the prospective cohort, and conducted 1-year follow-up on major events, including cardiac events, symptoms, secondary prevention and quality of life. The estimated entire sample size of eligible patients of 4000 was determined based on both feasibility and consideration of adequate statistical precision for describing the treatment decisions, guidelines adherence and appropriateness of treatment for patients with complex coronary artery diseases. The study is designed to investigate patient, clinician and hospital factors associated with each treatment strategy (percutaneous coronary intervention, coronary artery bypass grafting or medical therapy) as well as appropriateness of treatment choice, current guideline compliance and patient-reported outcomes for patients with complex coronary artery disease in large cardiovascular centres in China, as a foundation for enhanced knowledge in the field and to assist quality improvement initiatives.ETHICS AND DISSEMINATION:The study protocol was approved by the ethics committee at the China National Center for Cardiovascular Diseases. Findings will be shared with participating hospitals, policymakers and the academic community, to promote quality monitoring, quality improvement and the efficient allocation, and use of coronary revascularisation procedures in China.TRIAL REGISTRATION NUMBER:NCT01625312; Pre-results.

Response to Letters Regarding Article, "Efficacy of Long-Term β-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery".

The Chinese Cardiac Surgery Registry: Design and Data Audit.

BACKGROUND:In light of the burgeoning volume and certain variation of in-hospital outcomes of cardiac operations in China, a large patient-level registry was needed. We generated the Chinese Cardiac Surgery Registry (CCSR) database in 2013 to benchmark, continuously monitor, and provide feedback of the quality of adult cardiac operations. We report on the design of this database and provide an overview of participating sites and quality of data.METHODS:We established a network of participating sites with an adult cardiac surgery volume of more than 100 operations per year for continuous web-based registry of in-hospital and follow-up data of coronary artery bypass grafting (CABG) and valve operations. After a routine data quality audit, we report the performance and quality of care back to the participating sites.RESULTS:In total, 87 centers participated and submitted 46,303 surgical procedures from January 2013 to December 2014. The timeliness rates of the short-list and in-hospital data submitted were 73.6% and 70.2%, respectively. The completeness and accuracy rates of the in-hospital data were 97.6% and 95.1%, respectively. We have provided 2 reports for each site and 1 national report regarding the performance of isolated CABG and valve operations.CONCLUSIONS:The newly launched CCSR with a national representativeness network and good data quality has the potential to act as an important platform for monitoring and improving cardiac surgical care in mainland China, as well as facilitating research projects, establishing benchmarking standards, and identifying potential areas for quality improvements (ClinicalTrials.gov No. NCT02400125).

Efficacy of Long-Term β-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery.

BACKGROUND:Conflicting results from recent observational studies have raised questions concerning the benefit of β-blockers for patients undergoing coronary artery bypass grafting (CABG). Furthermore, the efficacy of long-term β-blocker therapy in CABG patients after hospital discharge is uncertain.METHODS AND RESULTS:The study included 5926 consecutive patients who underwent CABG and were discharged alive. The prevalence and consistency of β-blocker use were determined in patients with and without a history of myocardial infarction (MI). β-Blockers were always used in 1280 patients (50.9%) with and 1642 patients (48.1%) without previous MI after CABG. Compared with always users (n=2922, 49.3%), the risk of all-cause death was significantly higher among inconsistent β-blocker users (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.50-2.57), and never using β-blockers was associated with increased risk of both all-cause death (HR, 1.42; 95% CI, 1.01-2.00) and the composite of adverse cardiovascular events (HR, 1.29; 95% CI, 1.10-1.50). In the cohort without MI, the HR for all-cause death was 1.70 (95% CI, 1.17-2.48) in inconsistent users and 1.23 (95% CI, 0.76-1.99) in never users. In the MI cohort, mortality was higher for inconsistent users (HR, 2.14; 95% CI, 1.43-3.20) and for never users (HR, 1.59; 95% CI, 1.07-2.63). Consistent results were obtained in equivalent sensitivity analyses.CONCLUSIONS:In patients with or without previous MI undergoing CABG, the consistent use of β-blockers was associated with a lower risk of long-term mortality and adverse cardiovascular events. Strategies should be developed to understand and improve discharge prescription of β-blockers and long-term patient adherence.

Safety and efficacy of everolimus-eluting stent versus zotarolimus-eluting stent: A meta-analysis of randomized controlled clinical trials and observational studies.

BACKGROUND:The safety and efficacy of everolimus-eluting stent (EES) versus zotarolimus-eluting stent (ZES) are controversial both in randomized controlled clinical trials (RCTs) and observational studies. The aim of this study was to assess the safety and efficacy of EES versus ZES.METHODS:Pubmed, Embase, Cochrane database and www.clinicaltrials.gov updated to Mar 2014 with safety [major adverse cardiac events (MACE)], all-cause mortality, non-fatal myocardial infarction (MI), stent thrombosis (ST) and efficacy [target vessel revascularization (TVR), target lesion revascularization (TLR), target vessel failure (TVF), target lesion failure (TLF)] endpoints and follow-up of ≥12 months were identified.RESULTS:Data from 11,778 patients in 8 RCTs and 34,850 patients in 26 observational studies were included. In RCT studies, no evidence indicating that EES was safer or more efficacious than ZES. In observational studies, EES associated with a significantly lower risk for MACE (RR: 0.56, 95% CI: 0.46-0.69), ST (RR: 0.59, 95% CI: 0.45-0.78), TVR (RR: 0.61, 95% CI: 0.47-0.79), TLR (RR: 0.57, 95% CI: 0.38-0.83) and TLF (RR: 0.69, 95% CI: 0.50-0.93). The pooled data of RCTs and observational studies showed that compared to ZES, EES associated with a significant lower risk for MACE (RR: 0.65, 95% CI: 0.54-0.78), ST (RR: 0.66, 95% CI: 0.52-0.83), TVR (RR: 0.72, 95% CI: 0.58-0.89), TLR (RR: 0.63, 95% CI: 0.49-0.82) and TLF (RR: 078, 95% CI: 0.62-1.00).CONCLUSIONS:In RCTs, EES and ZES showed comparable safety and efficacy, while in observational studies or pooled data, EES was safer and more efficacious than ZES.

Polymorphisms of VEGF, TGFβ1, TGFβR2 and conotruncal heart defects in a Chinese population.

Genetic variants may determine susceptibility of congenital heart disease (CHD). To evaluate the impact of transforming growth factor-β1 (TGFβ1), TGFβ receptor II (TGFβR2) and vascular endothelial growth factor (VEGF) polymorphisms on conotruncal heart defects susceptibility, we genotyped six functional polymorphisms TGFβ1 rs1800469 C>T, TGFβR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T in a hospital based case-control study of 244 conotruncal heart defects cases and 136 non-CHD controls in a Chinese population. Logistic regression analyses revealed that if the TGFβ1 rs1800469 CC homozygote genotype was used as the reference group, subjects carrying the CT variant heterozygote had a significant 0.48-fold decreased risk of conotruncal heart defects [odds ratio (OR) = 0.52; 95% confidence interval (CI) = 0.30-0.88], subjects carrying the TT variant homozygote had a significant 0.47-fold decreased risk of conotruncal heart defects (OR 0.53; 95% CI 0.28-1.00). In stratification analyses, the TGFβ1 rs1800469 C>T genotype was associated with a decreased risk for tetralogy of fallot in homozygote comparisons (OR 0.47; 95% CI 0.22-0.99), a decreased risk for transposition of great artery in the dominant genetic model (OR 0.49; 95 % CI 0.28-0.87) and heterozygote comparisons (OR 0.45; 95% CI 0.24-0.83). Our findings suggest that TGFβ1 rs1800469 C>T polymorphism was significantly associated with decreased risk of conotruncal heart defects. TGFβR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T polymorphisms may not play a role in the susceptibility of conotruncal heart defects.

Cardiomyocyte cytokinesis score: a potential method for cardiomyocyte proliferation.

One of the most important indicators of myocardial regeneration is cardiomyocyte proliferation. However, it is difficult to distinguish cardiomyocytes in the regenerating stage from binucleated or multinucleated myocytes by conventional morphometric techniques. As cell cycle progression (CCP) scores have been successfully applied to the evaluation of the proliferation of cancer cells, we sought to establish a multi-gene score to evaluate cardiomyocyte proliferation in this study. Given the disturbances of nuclear division without cell division that occurs in cardiomyocytes, ten cytokinesis-correlated genes (Anln, Aurkb, Cenpa, Kif4, Kif23, Prc1, RhoA, Spin1, TACC2, and CDC42) were chosen to establish the cardiomyocyte cytokinesis score (CC-Score). The expression levels of these genes in H9C2 rat cardiomyoblast cells, the proliferation of which were stimulated or inhibited, were detected using qRT-PCR. To confirm the feasibility of the CC-Score system, four conventional methods for evaluating cardiomyocyte proliferation, including the MTT assay, BrdU assay, immunofluorescence, and flow cytometry analysis, were used in each group. The results of the CC-Score in the assessment of the proliferation of H9C2 cells were consistent with those of four commonly used proliferative assay methods. We conclude that the CC-Score can be used to assess the proliferation status of H9C2 cells, and suggest that the CC-Score may be a potential method for the assessment of cardiomyocyte proliferation in myocardial regeneration. However, validation studies utilizing primary cultured rat cardiomyocytes and heart tissue are warranted.

[Cytocompatibility of PBS/PLA blend as the sternal fixation material].

UNLABELLED:To evaluate biocompatibility and cytotoxicity of PBS/PLA blend as the material for sternal fixation.METHODS:L929 cell line was used to assess the cytotoxicity and cytocompatibility of PBS/PLA blend by incubation of the cells with the aqueous extract of the material for 3 days. The cytocompatibility of the material was evaluated by observing the proliferation of the cells cultured on the surface of the material. The proliferation of the cells cultured on the surface of the material was compared with that of the cells cultured on medical polyethylene and polyvinyl chloride to assess the cytotoxicity of the material.RESULTS:L929 cells showed no morphological changes after a 3-day incubation with the aqueous extract of the material. The cells cultured on the surface of the blend material exhibited better proliferative activity than those cultured on medical polyethylene and polyvinyl chloride, demonstrating no obvious cytotoxicity of the material.CONCLUSION:PBS/PLA blend material possesses excellent cytocompatibility and can be a promising biodegradable polymer for sternal fixation.

The China Patient-Centred Evaluative Assessment of Cardiac Events (China PEACE)-Prospective Study of 3-Vessel Disease: rationale and design.

INTRODUCTION:Complex coronary artery disease (left main and three-vessel disease) carries high risks of adverse events and cost burden. However, in China, little is known about which patients are directed toward which treatment strategies and what outcomes are being achieved.METHODS AND ANALYSIS:Using the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) research network, this prospective study of three-Vessel Disease, the China PEACE-3VD study, has a plan to consecutively register over 4000 patients with a diagnosis of 3VD and/or left-main disease by elective coronary angiography at 24 large cardiovascular centres in China. We centrally conducted medical record abstraction and SYNTAX Score calculation for all registered patients. The sites invited patients to the prospective cohort, and conducted 1-year follow-up on major events, including cardiac events, symptoms, secondary prevention and quality of life. The estimated entire sample size of eligible patients of 4000 was determined based on both feasibility and consideration of adequate statistical precision for describing the treatment decisions, guidelines adherence and appropriateness of treatment for patients with complex coronary artery diseases. The study is designed to investigate patient, clinician and hospital factors associated with each treatment strategy (percutaneous coronary intervention, coronary artery bypass grafting or medical therapy) as well as appropriateness of treatment choice, current guideline compliance and patient-reported outcomes for patients with complex coronary artery disease in large cardiovascular centres in China, as a foundation for enhanced knowledge in the field and to assist quality improvement initiatives.ETHICS AND DISSEMINATION:The study protocol was approved by the ethics committee at the China National Center for Cardiovascular Diseases. Findings will be shared with participating hospitals, policymakers and the academic community, to promote quality monitoring, quality improvement and the efficient allocation, and use of coronary revascularisation procedures in China.TRIAL REGISTRATION NUMBER:NCT01625312; Pre-results.

Response to Letters Regarding Article, "Efficacy of Long-Term β-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery".

The Chinese Cardiac Surgery Registry: Design and Data Audit.

BACKGROUND:In light of the burgeoning volume and certain variation of in-hospital outcomes of cardiac operations in China, a large patient-level registry was needed. We generated the Chinese Cardiac Surgery Registry (CCSR) database in 2013 to benchmark, continuously monitor, and provide feedback of the quality of adult cardiac operations. We report on the design of this database and provide an overview of participating sites and quality of data.METHODS:We established a network of participating sites with an adult cardiac surgery volume of more than 100 operations per year for continuous web-based registry of in-hospital and follow-up data of coronary artery bypass grafting (CABG) and valve operations. After a routine data quality audit, we report the performance and quality of care back to the participating sites.RESULTS:In total, 87 centers participated and submitted 46,303 surgical procedures from January 2013 to December 2014. The timeliness rates of the short-list and in-hospital data submitted were 73.6% and 70.2%, respectively. The completeness and accuracy rates of the in-hospital data were 97.6% and 95.1%, respectively. We have provided 2 reports for each site and 1 national report regarding the performance of isolated CABG and valve operations.CONCLUSIONS:The newly launched CCSR with a national representativeness network and good data quality has the potential to act as an important platform for monitoring and improving cardiac surgical care in mainland China, as well as facilitating research projects, establishing benchmarking standards, and identifying potential areas for quality improvements (ClinicalTrials.gov No. NCT02400125).

Efficacy of Long-Term β-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery.

BACKGROUND:Conflicting results from recent observational studies have raised questions concerning the benefit of β-blockers for patients undergoing coronary artery bypass grafting (CABG). Furthermore, the efficacy of long-term β-blocker therapy in CABG patients after hospital discharge is uncertain.METHODS AND RESULTS:The study included 5926 consecutive patients who underwent CABG and were discharged alive. The prevalence and consistency of β-blocker use were determined in patients with and without a history of myocardial infarction (MI). β-Blockers were always used in 1280 patients (50.9%) with and 1642 patients (48.1%) without previous MI after CABG. Compared with always users (n=2922, 49.3%), the risk of all-cause death was significantly higher among inconsistent β-blocker users (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.50-2.57), and never using β-blockers was associated with increased risk of both all-cause death (HR, 1.42; 95% CI, 1.01-2.00) and the composite of adverse cardiovascular events (HR, 1.29; 95% CI, 1.10-1.50). In the cohort without MI, the HR for all-cause death was 1.70 (95% CI, 1.17-2.48) in inconsistent users and 1.23 (95% CI, 0.76-1.99) in never users. In the MI cohort, mortality was higher for inconsistent users (HR, 2.14; 95% CI, 1.43-3.20) and for never users (HR, 1.59; 95% CI, 1.07-2.63). Consistent results were obtained in equivalent sensitivity analyses.CONCLUSIONS:In patients with or without previous MI undergoing CABG, the consistent use of β-blockers was associated with a lower risk of long-term mortality and adverse cardiovascular events. Strategies should be developed to understand and improve discharge prescription of β-blockers and long-term patient adherence.

Safety and efficacy of everolimus-eluting stent versus zotarolimus-eluting stent: A meta-analysis of randomized controlled clinical trials and observational studies.

BACKGROUND:The safety and efficacy of everolimus-eluting stent (EES) versus zotarolimus-eluting stent (ZES) are controversial both in randomized controlled clinical trials (RCTs) and observational studies. The aim of this study was to assess the safety and efficacy of EES versus ZES.METHODS:Pubmed, Embase, Cochrane database and www.clinicaltrials.gov updated to Mar 2014 with safety [major adverse cardiac events (MACE)], all-cause mortality, non-fatal myocardial infarction (MI), stent thrombosis (ST) and efficacy [target vessel revascularization (TVR), target lesion revascularization (TLR), target vessel failure (TVF), target lesion failure (TLF)] endpoints and follow-up of ≥12 months were identified.RESULTS:Data from 11,778 patients in 8 RCTs and 34,850 patients in 26 observational studies were included. In RCT studies, no evidence indicating that EES was safer or more efficacious than ZES. In observational studies, EES associated with a significantly lower risk for MACE (RR: 0.56, 95% CI: 0.46-0.69), ST (RR: 0.59, 95% CI: 0.45-0.78), TVR (RR: 0.61, 95% CI: 0.47-0.79), TLR (RR: 0.57, 95% CI: 0.38-0.83) and TLF (RR: 0.69, 95% CI: 0.50-0.93). The pooled data of RCTs and observational studies showed that compared to ZES, EES associated with a significant lower risk for MACE (RR: 0.65, 95% CI: 0.54-0.78), ST (RR: 0.66, 95% CI: 0.52-0.83), TVR (RR: 0.72, 95% CI: 0.58-0.89), TLR (RR: 0.63, 95% CI: 0.49-0.82) and TLF (RR: 078, 95% CI: 0.62-1.00).CONCLUSIONS:In RCTs, EES and ZES showed comparable safety and efficacy, while in observational studies or pooled data, EES was safer and more efficacious than ZES.

Polymorphisms of VEGF, TGFβ1, TGFβR2 and conotruncal heart defects in a Chinese population.

Genetic variants may determine susceptibility of congenital heart disease (CHD). To evaluate the impact of transforming growth factor-β1 (TGFβ1), TGFβ receptor II (TGFβR2) and vascular endothelial growth factor (VEGF) polymorphisms on conotruncal heart defects susceptibility, we genotyped six functional polymorphisms TGFβ1 rs1800469 C>T, TGFβR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T in a hospital based case-control study of 244 conotruncal heart defects cases and 136 non-CHD controls in a Chinese population. Logistic regression analyses revealed that if the TGFβ1 rs1800469 CC homozygote genotype was used as the reference group, subjects carrying the CT variant heterozygote had a significant 0.48-fold decreased risk of conotruncal heart defects [odds ratio (OR) = 0.52; 95% confidence interval (CI) = 0.30-0.88], subjects carrying the TT variant homozygote had a significant 0.47-fold decreased risk of conotruncal heart defects (OR 0.53; 95% CI 0.28-1.00). In stratification analyses, the TGFβ1 rs1800469 C>T genotype was associated with a decreased risk for tetralogy of fallot in homozygote comparisons (OR 0.47; 95% CI 0.22-0.99), a decreased risk for transposition of great artery in the dominant genetic model (OR 0.49; 95 % CI 0.28-0.87) and heterozygote comparisons (OR 0.45; 95% CI 0.24-0.83). Our findings suggest that TGFβ1 rs1800469 C>T polymorphism was significantly associated with decreased risk of conotruncal heart defects. TGFβR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T polymorphisms may not play a role in the susceptibility of conotruncal heart defects.

Cardiomyocyte cytokinesis score: a potential method for cardiomyocyte proliferation.

One of the most important indicators of myocardial regeneration is cardiomyocyte proliferation. However, it is difficult to distinguish cardiomyocytes in the regenerating stage from binucleated or multinucleated myocytes by conventional morphometric techniques. As cell cycle progression (CCP) scores have been successfully applied to the evaluation of the proliferation of cancer cells, we sought to establish a multi-gene score to evaluate cardiomyocyte proliferation in this study. Given the disturbances of nuclear division without cell division that occurs in cardiomyocytes, ten cytokinesis-correlated genes (Anln, Aurkb, Cenpa, Kif4, Kif23, Prc1, RhoA, Spin1, TACC2, and CDC42) were chosen to establish the cardiomyocyte cytokinesis score (CC-Score). The expression levels of these genes in H9C2 rat cardiomyoblast cells, the proliferation of which were stimulated or inhibited, were detected using qRT-PCR. To confirm the feasibility of the CC-Score system, four conventional methods for evaluating cardiomyocyte proliferation, including the MTT assay, BrdU assay, immunofluorescence, and flow cytometry analysis, were used in each group. The results of the CC-Score in the assessment of the proliferation of H9C2 cells were consistent with those of four commonly used proliferative assay methods. We conclude that the CC-Score can be used to assess the proliferation status of H9C2 cells, and suggest that the CC-Score may be a potential method for the assessment of cardiomyocyte proliferation in myocardial regeneration. However, validation studies utilizing primary cultured rat cardiomyocytes and heart tissue are warranted.

[Cytocompatibility of PBS/PLA blend as the sternal fixation material].

UNLABELLED:To evaluate biocompatibility and cytotoxicity of PBS/PLA blend as the material for sternal fixation.METHODS:L929 cell line was used to assess the cytotoxicity and cytocompatibility of PBS/PLA blend by incubation of the cells with the aqueous extract of the material for 3 days. The cytocompatibility of the material was evaluated by observing the proliferation of the cells cultured on the surface of the material. The proliferation of the cells cultured on the surface of the material was compared with that of the cells cultured on medical polyethylene and polyvinyl chloride to assess the cytotoxicity of the material.RESULTS:L929 cells showed no morphological changes after a 3-day incubation with the aqueous extract of the material. The cells cultured on the surface of the blend material exhibited better proliferative activity than those cultured on medical polyethylene and polyvinyl chloride, demonstrating no obvious cytotoxicity of the material.CONCLUSION:PBS/PLA blend material possesses excellent cytocompatibility and can be a promising biodegradable polymer for sternal fixation.