Long-term outcome of percutaneous or surgical revascularization with and without prior stroke in patients with three-vessel disease.

OBJECTIVE: To determine whether high-risk patients with three-vessel disease (TVD) with and without prior stroke preferentially benefit from three strategies [percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical therapy (MT)]. METHODS: A total of 8943 patients with TVD were included in the study. Patients enrolled were stratified into two categories according to the presence or absence of prior stroke history. The primary endpoint was all-cause death. Secondary endpoints included stroke and major adverse cardiac and cerebrovascular event (MACCE), a composite of death, myocardial infarction (MI), unplanned revascularization and stroke. RESULTS: Prior stroke was present in 888 patients (9.9%). These patients were older and had higher rates of comorbidities. During a median follow-up of 7.5 years, patients with prior stroke were strongly associated with increased risks of all-cause death, cardiac death, stroke and MACCE, even after adjusting for confounding variables and results been consistent across either treatment subgroup (PCI, CABG and MT) (all adjusted P < 0.01). Notably, there was a significant interaction between prior stroke history and treatment strategies. Revascularization strategy (PCI or CABG) was associated with a lower incidence of all-cause death and MACCE compared with MT alone, and favorable rates of MACCE, MI and unplanned revascularization in the CABG group compared with the PCI group, but with similar rate of all-cause death regardless of prior stroke history. The prevalence of stroke was significantly higher after CABG when compared with PCI or MT in no prior stroke patients [hazard ratio (HR) = 1.429, 95% CI: 1.132-1.805 for CABG vs. MT; HR = 1.703, 95% CI: 1.371-2.116 for CABG vs. PCI]. CONCLUSIONS: Patients with TVD and prior stroke have poor clinical outcomes. It is essential to balance benefit and risk when determining the optimal treatment strategy for TVD with and without prior stroke.

Using machine learning to aid treatment decision and risk assessment for severe three-vessel coronary artery disease.

BACKGROUND: Three-vessel disease (TVD) with a SYNergy between PCI with TAXus and cardiac surgery (SYNTAX) score of ≥ 23 is one of the most severe types of coronary artery disease. We aimed to take advantage of machine learning to help in decision-making and prognostic evaluation in such patients. METHODS: We analyzed 3786 patients who had TVD with a SYNTAX score of ≥ 23, had no history of previous revascularization, and underwent either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) after enrollment. The patients were randomly assigned to a training group and testing group. The C4.5 decision tree algorithm was applied in the training group, and all-cause death after a median follow-up of 6.6 years was regarded as the class label. RESULTS: The decision tree algorithm selected age and left ventricular end-diastolic diameter (LVEDD) as splitting features and divided the patients into three subgroups: subgroup 1 (age of ≤ 67 years and LVEDD of ≤ 53 mm), subgroup 2 (age of ≤ 67 years and LVEDD of > 53 mm), and subgroup 3 (age of > 67 years). PCI conferred a patient survival benefit over CABG in subgroup 2. There was no significant difference in the risk of all-cause death between PCI and CABG in subgroup 1 and subgroup 3 in both the training data and testing data. Among the total study population, the multivariable analysis revealed significant differences in the risk of all-cause death among patients in three subgroups. CONCLUSIONS: The combination of age and LVEDD identified by machine learning can contribute to decision-making and risk assessment of death in patients with severe TVD. The present results suggest that PCI is a better choice for young patients with severe TVD characterized by left ventricular dilation.

Direct Bilirubin Levels Predict Long-Term Outcomes in Patients With Acute Coronary Syndrome Under Different Glucose Metabolism Status: A 6.5-Year Cohort Study of Three-Vessel Disease.

Background: There is controversy over the relationship between bilirubin and coronary artery disease. This study aimed to evaluate the predictive value of direct bilirubin (DB) in patients with complex acute coronary syndrome (ACS). Methods: From April 2004 to February 2011, 5,322 ACS patients presenting with three-vessel disease were consecutively enrolled. Disease severity and complexity were determined by SYNTAX score (SS) and SS II. The primary endpoint was all-cause death, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE). Stratification of normal glucose regulation, prediabetes, and diabetes was based on a previous diagnosis, hypoglycemic medications, fasting blood glucose, and hemoglobin A1c. Results: Subjects were divided into quartiles according to baseline DB (µmol/L): Q1 (0-1.6), Q2 (1.61-2.20), Q3 (2.21-2.80), and Q4 (>2.80). Multivariable logistic regression analysis showed that DB was an independent predictor of intermediate-high SS. During a median follow-up time of 6.5 years, elevated DB was associated with more all-cause death (p < 0.001) but not MACCE. DB remained to be predictive of all-cause death in the multivariable Cox regression model (Q2 vs. Q1: HR 1.043, 95% CI 0.829-1.312, p = 0.719; Q3 vs. Q1: HR 1.248, 95% CI 1.001-1.155, p = 0.048; Q4 vs. Q1: HR 1.312, 95% CI 1.063-1.620, p = 0.011). When subjects are stratified according to glucose metabolism regulation and treatment strategies, the predictivity of DB was only profound in patients with diabetes or with conservative treatment. Additionally, incorporating DB further improved the discrimination and reclassification abilities of SS II for risk prediction. Conclusion: DB is a potential biomarker for predicting lesion severity and long-term outcomes in ACS patients.

Differential Diagnosis, Clinical Characteristics, and Interventions of Braid-Like Coronary Artery: Case Series Analysis Based on Optical Coherence Tomography.

AIM: Based on optical coherence tomography (OCT), we aimed to determine the diagnosis, clinical characteristics, and interventions of braid-like coronary arteries, which are rare and tend to be diagnosed as a woven coronary artery (WCA) anomaly. METHODS AND RESULTS: We identified braid-like lesions on coronary angiography (CAG) in 7 patients (6 men; median age 47 years; age range 26 to 57 years). All patients were heavy smokers. Four patients were diagnosed with an old myocardial infarction and the other 3 with unstable angina. The braid-like lesions were located in the left anterior descending arteries in 2 patients and in the right coronary arteries in the other 5. TIMI grade 2 flow was observed in all involved vessels. OCT findings of all lesions were consistent with recanalization of organized thrombi, which consisted of septa that divided the lumen into multiple small cavities communicating with each other. No separate three-layered structure could be defined. Based on the significance of the stenosis and its related symptoms, drug-eluting stents were implanted in all of the lesions. All patients experienced symptomatic improvement after the intervention and were followed up event-free for 12 months. CONCLUSIONS: Braid-like coronary arteries are likely to undergo recanalization of organized thrombi rather than WCA according to our OCT findings. The majority of cases affect men who smoke heavily. Percutaneous stent implantation may be beneficial in selected patients when feasible.

Prognostic Values of Serum Chloride and Sodium Levels in Patients with Three-vessel Disease.

OBJECTIVE: Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD. METHODS: We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients. RESULTS: A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score. CONCLUSION: Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.

Association of CDKN2B-AS1 Polymorphisms with Premature Triple-vessel Coronary Disease and Their Sex Specificity in the Chinese Population.

OBJECTIVE: The aim of this study is to establish whether cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms are associated with premature triple-vessel disease (PTVD). METHODS: Nine single-nucleotide polymorphisms (rs1063192, rs10757274, rs1333042, rs1333049, rs2285327, rs3217986, rs3217992, rs4977574, and rs9632884) were genotyped in 884 PTVD patients and 907 control subjects (males ⪕ 50 years old and females ⪕ 60 years old) using the improved multiplex ligase detection reaction method. RESULTS: The allele frequencies of rs10757274 G, rs1333049 C, rs4977574 G (all P < 0.001), and rs3217986 G (P = 0.040) were significantly higher in the PTVD group than in the control group, but those of rs1063192 A, rs1333042 G, and rs9632884 C (all P < 0.001) were significantly lower in the former than in the latter. Logistic regression analysis revealed that homozygote AA of rs1333042 is associated with decreased risk for PTVD (OR = 0.42, 95% CI: 0.22-0.82, P = 0.011). In addition, the allele frequencies observed differed between genders. The G allele of rs3217986 was associated with increased risk for PTVD in male patients only (OR = 2.94, 95% CI: 1.27-6.80, P = 0.012) in the dominant model, and no positively mutated allele was found in female patients. CONCLUSION: Polymorphisms of the CDKN2B-AS1 gene are associated with the incidence of PTVD in the Chinese population. Furthermore, the frequencies of mutated alleles differed between genders.

Evaluation of CRUSADE and ACUITY-HORIZONS Scores for Predicting Long-term Out-of-Hospital Bleeding after Percutaneous Coronary Interventions.

BACKGROUND: There is scanty evidence concerning the ability of Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) and Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (ACUITY-HORIZONS) scores to predict out-of-hospital bleeding risk after percutaneous coronary interventions (PCIs) with drug-eluting stents (DES) in patients receiving dual antiplatelet therapy. We aimed to assess and compare the long-term prognostic value of these scores regarding out-of-hospital bleeding risk in such patients. METHODS: We performed a prospective observational study of 10,724 patients undergoing PCI between January and December 2013 in Fuwai Hospital, China. All patients were followed up for 2 years and evaluated through the Fuwai Hospital Follow-up Center. Major bleeding was defined as Types 2, 3, and 5 according to Bleeding Academic Research Consortium Definition criteria. RESULTS: During a 2-year follow-up, 245 of 9782 patients (2.5%) had major bleeding (MB). CRUSADE (21.00 [12.00, 29.75] vs. 18.00 [11.00, 26.00], P < 0.001) and ACUITY-HORIZONS (9.00 [3.00, 14.00] vs. 6.00 [3.00, 12.00], P < 0.001) risk scores were both significantly higher in the MB than non-MB groups. Both scores showed a moderate predictive value for MB in the whole study cohort (area under the receiver-operating characteristics curve [AUROC], 0.565; 95% confidence interval [CI], 0.529-0.601, P = 0.001; AUROC, 0.566; 95% CI, 0.529-0.603, P < 0.001, respectively) and in the acute coronary syndrome (ACS) subgroup (AUROC: 0.579, 95% CI: 0.531-0.627, P = 0.001; AUROC, 0.591; 95% CI, 0.544-0.638, P < 0.001, respectively). However, neither score was a significant predictor in the non-ACS subgroup (P > 0.05). The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup. CONCLUSIONS: CRUSADE and ACUITY-HORIZONS scores showed statistically significant but relatively limited long-term prognostic value for out-of-hospital MB after PCI with DES in a cohort of Chinese patients. The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup.

Comparison of Long-term Outcomes in Patients with Premature Triple-vessel Coronary Disease Undergoing Three Different Treatment Strategies: A Prospective Cohort Study.

BACKGROUND: Patients with premature triple-vessel disease (PTVD) have a higher risk of recurrent coronary events and repeat revascularization; however, the long-term outcome of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical therapy (MT) alone for PTVD patients is controversial. The aim of this study is to evaluate the long-term outcome of PTVD patients among these three treatment strategies, to find out the most appropriate treatment methods for these patients. METHODS: One thousand seven hundred and ninety-two patients with PTVD (age: men ≤50 years and women ≤60 years) were enrolled between 2004 and 2011. The primary end point was all-cause death. The secondary end points were cardiac death, myocardial infarction, stroke, or repeat revascularization. RESULTS: PCI, CABG, and MT alone were performed in 933 (52.1%), 459 (25.6%), and 400 (22.3%) patients. Both PCI and CABG were associated with lower all-cause death (4.6% vs. 4.1% vs. 15.5%, respectively, P < 0.01) and cardiac death (2.8% vs. 2.0% vs. 9.8%, respectively, P < 0.01) versus MT alone. The rate of repeat revascularization in the CABG group was significantly lower than those in the PCI and MT groups. After adjusting for baseline factors, PCI and CABG were still associated with similar lower risk of all-cause death and cardiac death versus MT alone (all-cause death: hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.23-0.53, P < 0.01 and HR: 0.35, 95% CI: 0.18-0.70, P = 0.003, respectively, and cardiac death: HR: 0.32, 95% CI: 0.19-0.54, P < 0.01 and HR: 0.36, 95% CI: 0.14-0.93, P = 0.03, respectively). CONCLUSIONS: PCI and CABG provided equal long-term benefits for all-cause death and cardiac death for PTVD patients. Patients undergoing MT alone had the worst long-term clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov; Identifier: NCT02634086. https://www.clinicaltrials.gov/ct2/show/record/NCT02634086?term=NCT02634086&rank=1.

Inhibitory effect of iron on in vitro proliferation of smooth muscle cells.

BACKGROUND: Iron is a biocorrodible metal that might be used in bioabsorbable stents. This study investigated the effects at the cellular and protein levels of soluble divalent iron (ferrous gluconate) and soluble trivalent iron (ferric chloride) on the proliferation of human aortic smooth muscle cell (HASMC) in vitro. METHODS: The water-soluble tetrazolium (WST-1) test was used to evaluate the effect of iron on proliferation of HASMC and Western blotting was used to measure the levels of signaling proteins involved in proliferative and apoptosis pathways. RESULTS: HASMC proliferation was inhibited in a concentration dependent manner after treatment with soluble divalent and trivalent iron at concentrations of 100-500 µmol/L. Western blotting analysis showed that the proliferating cell nuclear antigen (PCNA) expression following treatment with soluble divalent iron and trivalent iron at 100, 300 and 500 µmol/L was reduced compared to the control. The PCNA expression decreased with increasing iron concentration and to a greater extent with the trivalent iron than with the divalent iron treatment group. The p53 expression was markedly increased in a concentration dependent manner in both iron treatment groups. CONCLUSION: The soluble divalent iron and, to a greater degree trivalent iron, inhibited HASMC proliferation in a dosedependent manner, which may be attributed to reduction of PCNA expression and increase of p53 expression.

Dicycloplatin differentially inhibits proliferation of human aortic smooth muscle and endothelial cells: potential for use in drug-eluting stents.

BACKGROUND: Dicycloplatin is a relatively safe third generation platinum-complex anti-cancer drug. The present study focused on the effects of dicycloplatin on in vitro proliferation and apoptosis of human aortic smooth muscle cells (HASMC) and human aortic endothelial cells (HAEC). METHODS: Proliferation of HASMC and HAEC, DNA content, and cellular levels of proliferation- and apoptosis-related proteins were assessed using the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay, flow cytometry and Western blotting assays, respectively. RESULTS: Dicycloplatin at 10 ng/ml significantly inhibited HASMC proliferation, however, 10 µg/ml were required to significantly inhibit HAEC proliferation. Cell cycle analysis showed that dicycloplatin was a non-specific inhibitor of the cell cycle. Although dicycloplatin significantly decreased proliferating cell nuclear antigen (PCNA) expression in HASMC at all concentrations tested, it did not significantly affect PCNA expression in HAEC; Bax and p53 protein expression was upregulated in dicycloplatin groups. CONCLUSIONS: Dicycloplatin at nanogram concentrations significantly inhibits HASMC proliferation, although the effect is relatively weaker than that of sirolimus. In contrast, the effect of dicycloplatin on inhibition of HAEC proliferation is much less pronounced than that on HASMC. The latter characteristics point to the potential for use of dicycloplatin in drug-eluting stents.