Growth differentiation factor-15 is a prognostic marker in patients with intermediate coronary artery disease.

BACKGROUND: Growth differentiation factor-15 (GDF-15) is involved in multiple processes that are associated with coronary artery disease (CAD). However, little is known about the association between GDF-15 and the future ischemic events in patients with intermediate CAD. This study was conducted to investigate whether plasma GDF-15 constituted risk biomarkers for future cardiovascular events in patients with intermediate CAD. METHODS: A prospective study was performed based on 541 patients with intermediate CAD (20%-70%). GDF-15 of each patient was determined in a blinded manner. The primary endpoint was major adverse cardiac event (MACE), which was defined as a composite of all-cause death, nonfatal myocardial infarction, revascularization and readmission due to angina pectoris. RESULTS: After a median follow-up of 64 months, 504 patients (93.2%) completed the follow-up. Overall, the combined endpoint of MACE appeared in 134 patients (26.6%) in the overall population: 26 patients died, 11 patients suffered a nonfatal myocardial infarction, 51 patients underwent revascularization, and 46 patients were readmitted for angina pectoris. The plasma levels of GDF-15 (median: 1172.02 vs. 965.25 pg/mL, P = 0.014) were higher in patients with ischemic events than those without events. After adjusting for traditional risk factors, higher GDF-15 levels were significantly associated with higher incidence of the composite endpoint of MACE (HR = 1.244, 95% CI: 1.048-1.478, Quartile 4 vs. Quartile 1, P = 0.013). CONCLUSIONS: The higher level of GDF-15 was an independent predictor of long-term adverse cardiovascular events in patients with intermediate CAD.

Long-term outcomes of staged recanalization for concurrent chronic total occlusion in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

BACKGROUND: In patients with acute ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI), approximately 10% are concomitant with a chronic total occlusion (CTO) in a non-culprit vessel. However, the impact of staged CTO recanalization on prognosis in this cohort remains disputable. This study aimed to compare the long-term outcomes of staged CTO recanalization versus medical therapy in patients with STEMI after primary PCI. METHODS: Between January 2005 and December 2016, a total of 287 patients were treated with staged CTO-PCI (n = 91) or medical therapy (n = 196) after primary PCI in our center. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of all-cause death, nonfatal myocardial infarction (MI), stroke or unplanned revascularization. After propensity-score matching, 77 pairs of well-balanced patients were identified. RESULTS: The mean follow-up period was 6.06 years. Overall, the incidence of the primary endpoint of MACCE was significantly lower in staged CTO-PCI group than that in medical therapy group in both overall population (22.0% vs. 46.9%; hazard ratio (HR) = 0.48, 95% CI: 0.29-0.77) and propensity-matched cohorts (22.1% vs. 42.9%; HR: 0.48, 95% CI: 0.27-0.86). In addition, staged CTO-PCI was also associated with reduced risk of the composite of cardiac death, nonfatal MI or stroke compared with medical therapy in both overall population (9.9% vs. 26.5%; hazard ratio (HR) = 0.39, 95% CI: 0.19-0.79) and propensity-matched cohorts (9.1% vs. 22.1%; HR: 0.40, 95% CI: 0.16-0.96). After correction of the possible confounders, staged CTO-PCI was independently associated with reduced risks of MACCE (adjusted HR: 0.46, 95% CI: 0.28-0.75), the composite of cardiac death, nonfatal MI or stroke (adjusted HR: 0.45, 95% CI: 0.22-0.94) and all-cause mortality (adjusted HR: 0.32, 95% CI: 0.13-0.83). Moreover, the results of sensitivity analysis were almost concordant with the overall analysis. CONCLUSIONS: In patients with STEMI and a concurrent CTO who undergo primary PCI, successful staged recanalization of CTO in the non-culprit vessels is associated with better clinical outcomes during long-term follow-up.

Predictive Value of Electromechanical Activation Time for In-Hospital Major Cardiac Adverse Events in Heart Failure Patients.

OBJECTIVE: This prospective study aimed to evaluate the value of the cardiac cycle time-corrected electromechanical activation time (EMATc) measured at admission for predicting major cardiac adverse events (MACEs) in hospitalized patients with chronic heart failure (CHF). METHODS: CHF patients with a left ventricular ejection fraction (LVEF) lower than 50% (N = 145) were enrolled in this study. Documented clinical end-points (MACEs) included cardiogenic death, onset of acute HF as assessed with invasive and noninvasive mechanical ventilation, and cardiogenic shock. According to the different clinical end-points, patients were divided into two groups: a MACE group (n = 22) and a nonMACE group (n = 123). EMATc, LVEF, and circulating levels of B type natriuretic peptide (BNP) and Troponin I (TnI) were measured. Multivariate logistic regression analysis was used to examine the association between EMATc and MACEs. The parameters adjusted in the multivariable model included EMATc, BNP, and heart rate. The predictive value of EMATc was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Elevated EMATc was an independent risk factor for MACEs (odds ratio [OR] 1.1443, 95% confidence interval [CI] 1.016-1.286, P = 0.027). The area under the ROC curve for EMATc was 0.799 (95% CI 0.702-0.896, P < 0.001). The optimal cutoff EMATc value was >13.8% with a sensitivity of 81.8% and a specificity of 65.9%. CONCLUSIONS: We demonstrated that an elevated EMATc measured at admission is an independent risk factor for MACEs among hospitalized CHF patients. Acoustic cardiography measured at admission may provide a simple, noninvasive method for risk stratification of CHF patients. This trial is registered with ChiCTR1900021470.

Long term outcomes of drug-eluting stent versus coronary artery bypass grafting for left main coronary artery disease: a meta-analysis.

BACKGROUND: It is still controversial whether percutaneous coronary intervention with drug-eluting stent (DES) is safe and effective compared to coronary artery bypass graft surgery (CABG) for unprotected left main coronary artery (ULMCA) disease at long-term follow up (≥ 3 years). METHODS: Eligible studies were selected by searching PubMed, EMBASE, and Cochrane Library up to December 6, 2016. The primary endpoint was a composite of death, myocardial infarction (MI) or stroke during the longest follow-up. Death, cardiac death, MI, stroke and repeat revascularization were the secondary outcomes. RESULTS: Four randomized controlled trials and twelve adjusted observational studies involving 14,130 patients were included. DES was comparable to CABG regarding the occurrence of the primary endpoint (HR = 0.94, 95% CI: 0.86-1.03). Besides, DES was significantly associated with higher incidence of MI (HR = 1.56, 95% CI: 1.09-2.22) and repeat revascularization (HR = 3.09, 95% CI: 2.33-4.10) compared with CABG, while no difference was found between the two strategies regard as the rate of death, cardiac death and stroke. Furthermore, DES can reduce the risk of the composite endpoint of death, MI or stroke (HR = 0.80, 95% CI: 0.67-0.95) for ULMCA lesions with SYNTAX score ≤ 32. CONCLUSIONS: Although with higher risk of repeat revascularization, PCI with DES appears to be as safe as CABG for ULMCA disease at long-term follow up. In addition, treatment with DES could be an alternative interventional strategy to CABG for ULMCA lesions with low to intermediate anatomic complexity.

Drug-Eluting Balloon versus New-Generation Drug-Eluting Stent for the Treatment of In-Stent Restenosis: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Currently, drug-eluting balloon (DEB) appears to be an attractive alternative option for the treatment of in-stent restenosis (ISR). Nevertheless, the clinical outcomes of DEB have seldom been compared to those of new-generation drug-eluting stent (DES). Thus, this meta-analysis aimed to evaluate the safety and efficacy of DEB compared to those of new-generation DES in the treatment of ISR. METHODS: A comprehensive search of electronic databases including PubMed, EMBASE, and Cochrane Library up to November 2, 2017 was performed to identify pertinent articles comparing DEB to new-generation DES for the treatment of ISR. In addition, conference proceedings for the scientific sessions of the American College of Cardiology, American Heart Association, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, and EuroPCR were also searched. The primary endpoint was target lesion revascularization (TLR) at the longest follow-up. Dichotomous variables were presented as risk ratios (RR s) with 95% confidence intervals (CI s), while the overall RR s were estimated using the Mantel-Haenszel random-effects model. RESULTS: Five randomized controlled trials (RCTs) and eight observational studies involving 2743 patients were included in the present meta-analysis. Overall, DEB was comparable to new-generation DES in terms of TLR (RR = 1.24, 95% CI: 0.89-1.72, P = 0.21), cardiac death (RR = 1.55, 95% CI: 0.89-2.71, P = 0.12), major adverse cardiovascular event (RR = 1.21, 95% CI: 0.98-1.48, P = 0.07), myocardial infarction (RR = 1.12, 95% CI: 0.72-1.76, P = 0.62), and stent thrombosis (RR = 0.95, 95% CI: 0.38-2.42, P = 0.92). However, DEB was associated with higher risk of all-cause mortality than new-generation DES (RR = 1.65, 95% CI: 1.09-2.50, P = 0.02). This was especially true in the real-world observational studies (RR = 1.79, 95% CI: 1.12-2.88, P = 0.02). In RCTs, however, no significant difference was found between the two treatment strategies in the risk of all-cause mortality. CONCLUSIONS: The current meta-analysis showed that DEB and new-generation DES had comparable safety and efficacy for the treatment of ISR in RCTs. However, treatment with DEB was associated with higher risk of all-cause mortality in the real-world nonrandomized studies.

Long-term outcomes of PCI vs. CABG for ostial/midshaft lesions in unprotected left main coronary artery.

BACKGROUND: There are limited data on long-term (> 5 years) outcomes of drug-eluting stent (DES) implantation compared with coronary artery bypass grafting (CABG) for ostial/midshaft left main coronary artery (LMCA) lesions. METHODS: Of the 259 consecutive patients in Beijing Anzhen Hospital with ostial/midshaft LMCA lesions, 149 were treated with percutaneous coronary intervention (PCI) with DES and 110 were with CABG. The endpoints of the study were death, repeat revascularization, myocardial infarction (MI), stroke, the composite of cardiac death, and major adverse cardiac and cerebrovascular events (MACCE, the composite of cardiac death, MI, stroke or repeat revascularization).The duration of follow-up is 7.1 years (interquartile range 5.3 to 8.2 years). RESULTS: There is no significant difference between the PCI and CABG group during the median follow-up of 7.1 years (interquartile range: 5.3-8.2 years) in the occurrence of death (HR: 0.727, 95% CI: 0.335-1.578; P = 0.421), the composite endpoint of cardiac death, MI or stroke (HR: 0.730, 95% CI: 0.375-1.421; P = 0.354), MACCE (HR: 1.066, 95% CI: 0.648-1.753; P = 0.801), MI (HR: 1.112, 95% CI: 0.414-2.987; P = 0.833), stroke (HR: 1.875, 95% CI: 0.528-6.659; P = 0.331), and repeat revascularization (HR: 1.590, 95% CI: 0.800-3.161; P = 0.186). These results remained after multivariable adjusting. CONCLUSION: During a follow-up up to 8.2 years, we found that DES implantation had similar endpoint outcomes compared with CABG.

Comparison of the performance of the CRUSADE, ACUITY-HORIZONS, and ACTION bleeding scores in ACS patients undergoing PCI: insights from a cohort of 4939 patients in China.

BACKGROUND: The CRUSADE, ACTION and ACUITY-HORIZONS scores are commonly used for predicting in-hospital major bleeding events in patients with acute coronary syndrome (ACS), but the homogeneous nature of these models' population limits simple extrapolation to other local population. We aimed to compare the performance of the three risk models in Chinese patients. METHODS: We evaluated the performance of the three predicting scores for predicting in-hospital major bleeding events defined by thrombolysis in myocardial infarction (TIMI) serious (major and minor) episodes, in a cohort of Chinese ACS patients with either non-ST-elevation ACS (NSTE-ACS) or ST-elevation myocardial infarction (STEMI). Calibration and discrimination of the three risk models were evaluated by the Hosmer-Lemeshow test and C-statistic, respectively. We compared the predictive accuracy of the risk scores by the Delong non-parametric test. RESULTS: TIMI serious bleeding rate was 1.1% overall (1.9% and 0.86% for STEMI and NSTE-ACS, respectively). The CRUSADE, ACTION and ACUTIY-HORIZONS scores showed an adequate discriminatory capacity for major bleeding: in overall patients, the C-statistic was 0.80, 0.77, and 0.70, respectively; in NSTE-ACS patients, the C-statistic was 0.73, 0.72, and 0.64, respectively; in STEMI patients, the C-statistic was 0.91, 0.92, and 0.75, respectively. The C-statistic for the ACUITY-HORIZONS model was significantly lower than those of the CRUSADE and ACTION scores for the prediction of TIMI serious bleeding in overall patients (compared with CRUSADE, z = 3.83, P = 0.02; compared with ACTION, z = 3.51, P = 0.03); in NSTE-ACS patients (compared with CRUSADE, z = 2.37, P = 0.01; compared with ACTION, z = 2.11, P = 0.04), and in STEMI patients (compared with CRUSADE, z = 2.6.77, P = 0.02; compared with ACTION, z = 7.91, P = 0.002). No differences were observed when the CRUSADE and ACTION models were compared to each other, regardless of overall patients (z = 0.68, P = 0.31) and both of ACS types (NSTE-ACS, z = 0.52, P = 0.60), and STEMI patients (z = 0.36, P = 0.74). However, the three risk scores all overestimated the absolute major bleeding risk in each risk stratification in our study. For example, the predicted rate of CRUSADE score at high risk stratification was 11.9% vs. an actual rate of 5.3%. CONCLUSIONS: The CRUSADE and ACTION scores had a greater calibration and discrimination for in-hospital major bleeding compared with the ACUITY-HORIZONS score in Chinese patients with ACS undergoing PCI. However, they all overestimated the bleeding risk rate for Chinese populations. Calibration of these risk scores would be useful for the generalization in Chinese populations.

Stenting versus non-stenting treatment of intermediate stenosis culprit lesion in acute ST-segment elevation myocardial infarction: a multicenter randomized clinical trial.

BACKGROUND: The benefit/risk ratio of stenting in acute ST-segment elevation myocardial infarction (STEMI) patients with single vessel intermediate stenosis culprit lesions merits further study, therefore the subject of the present study. METHODS AND RESULTS: It was a prospective, multicenter, randomized controlled trial. Between April 2012 and July 2015, 399 acute STEMI patients with single vessel disease and intermediate (40%-70%) stenosis of the culprit lesion before or after aspiration thrombectomy and/or intracoronary tirofiban (15 µg/kg) were enrolled and were randomly assigned (1: 1) to stenting group (n = 201) and non-stenting group (n = 198). In stenting group, patients received pharmacologic therapy plus standard percutaneous coronary intervention (PCI) with stent implantation. In non-stenting group, patients received pharmacologic therapy and PCI (thrombectomy), but without dilatation or stenting. Primary endpoint was 12-month rate of major adverse cardiac and cerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction (MI), repeat revascularization and stroke. Secondary endpoints were 12-month rates of all cause death, ischemia driven admission and bleeding complication. Median follow-up time was 12.4 ± 3.1 months. At 12 months, MACCE occurred in 8.0% of the patients in stenting group, as compared with 15.2% in the non-stenting group (adjusted HR: 0.42, 95% CI: 0.19-0.89, P = 0.02). The stenting group had lower non-fatal MI rate than non-stenting group, (1.5% vs. 5.5%, P = 0.03). The two groups shared similar cardiac death, repeat revascularization, stroke, all cause death, ischemia driven readmission and bleeding rates at 12 months. CONCLUSIONS: Stent implantation had better efficacy and safety in reducing MACCE risks among acute STEMI patients with single vessel intermediate stenosis culprit lesions.

Association of single nucleotide polymorphism rs2076185 in chromosome 6P24.1 with premature coronary artery diseases in Chinese Han population.

OBJECTIVES: To study the association of single nucleotide polymorphism (SNP) rs2076185 in chromosome 6p24.1 with the premature coronary artery diseases (PCAD) in Chinese Han population. METHODS: A total of 1382 patients were divided into the PCAD group and the control group based on their coronary arteriography (CAG) results. Their SNP rs2076185 were analyzed by the mass-spectrometry. Their allele and genotype frequency in Hardy-Weinberg equilibrium were calculated for assessment. Logistic regression was employed to remove confounding factors and correlate SNP rs2076185 with PCAD. RESULTS: The allele and genotype frequencies of the control group were in Hardy-Weinberg equilibrium (P > 0.05). The frequencies of allele G of rs2076185 were 54.2% in the PCAD group and 49.5% in the control group. The difference was significant (P = 0.042). The genotype distribution of rs2076185 of the two groups was also significantly different. The univariate analysis showed that the rs2076185 polymorphisms were associated with the PCAD only in the additive model (OR: 0.828, 95% CI: 0.711-0.964, P = 0.014), and in the dominant model (OR: 0.753, 95% CI: 0.591-0.958, P = 0.021). After removing the confounding variables, the rs2076185 polymorphisms was associated with PCAD in the additive model (OR: 0.775, 95% CI: 0.648-0.928, P = 0.005), in the dominant model (OR: 0.698, 95% CI: 0.527-0.925, P = 0.012), and in the recessive model (OR: 0.804, 95% CI: 0.538-0.983, P = 0.038). CONCLUSION: Allele G of rs2076185 reduces the PCAD risks in Chinese Han population, therefore it could be a coronary artery diseases protective factor in Chinese Han population.

Prognostic performance of interleukin-10 in patients with chest pain and mild to moderate coronary artery lesions-an 8-year follow-up study.

BACKGROUND: Interleukin (IL)-10, IL-6 and their ratio (IL-6/IL-10) play an important role in the risk of developing coronary artery disease, and may correlate with its outcomes. Few clinical trials have investigated the prognostic impact of these factors on long-term cardiovascular events in patients presented with chest pain. METHODS: A prospective study was performed on 566 patients admitted with chest pain and identified mild to moderate coronary artery lesions. IL-10, IL-6 and IL-6/IL-10 were measured. RESULTS: A total of 511 patients completed the follow-up. The median follow-up time was 74 months. Kaplan-Meier analysis demonstrated a clear increase of the incidence of major adverse cardiac events during the follow-up period in patients with below-median levels of IL-10 (P = 0.006) and above-median levels of IL-6/IL-10 (P = 0.012). Multivariate Cox proportional hazards analysis indicated the IL-10 levels to be strong independent predictors after adjustment for underlying confounders. CONCLUSIONS: Elevated IL-10 levels are associated with a more favorable long-term prognosis in patients with chest pain and mild to moderate coronary artery lesions. IL-10 could be used for early risk assessment of long-term prognosis.

Very Long-term Outcomes and Predictors of Percutaneous Coronary Intervention with Drug-eluting Stents Versus Coronary Artery Bypass Grafting for Patients with Unprotected Left Main Coronary Artery Disease.

BACKGROUND: There are limited data on longer-term outcomes (>5 years) for patients with unprotected left main coronary artery (ULMCA) disease who underwent percutaneous coronary intervention (PCI) in the drug-eluting stents (DES) era. This study aimed at comparing the long-term (>5 years) outcomes of patients with ULMCA disease underwent PCI with DES and coronary artery bypass grafting (CABG) and the predictors of adverse events. METHODS: All consecutive patients with ULMCA disease treated with DES implantation versus CABG in our center, between January 2003 and July 2009, were screened for analyzing. A propensity score analysis was carried out to adjust for potential confounding between the two groups. RESULTS: Nine hundred and twenty-two patients with ULMCA disease were enrolled for the analyses (DES = 465 vs. CABG = 457). During the median follow-up of 7.1 years (interquartile range 5.3-8.2 years), no difference was found between PCI and CABG in the occurrence of death (P = 0.282) and the composite endpoint of cardiac death, myocardial infarction (MI) and stroke (P = 0.294). Rates of major adverse cardiac and cerebrovascular events were significantly higher in the PCI group (P = 0.014) in large part because of the significantly higher rate of repeat revascularization (P < 0.001). PCI was correlated with the lower occurrence of stroke (P = 0.004). Multivariate analysis showed ejection fraction (EF) (P = 0.012), creatinine (P = 0.016), and prior stroke (P = 0.031) were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age (P = 0.026) and EF (P = 0.002) were independent predictors in the CABG group. CONCLUSIONS: During a median follow-up of 7.1 years, there was no difference in the rate of death between PCI with DES implantation and CABG in ULMCA lesions in the patient cohort. CABG group was observed to have significantly lower rates of repeat revascularization but higher stroke rates compared with PCI. EF, creatinine, and prior stroke were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age and EF were independent predictors in the CABG group.

Prediction of risk of cardiovascular events in patients with mild to moderate coronary artery lesions using naïve Bayesian networks.

BACKGROUND: This prospective study integrated multiple clinical indexes and inflammatory markers associated with coronary atherosclerotic vulnerable plaque to establish a risk prediction model that can evaluate a patient with certain risk factors for the likelihood of the occurrence of a coronary heart disease event within one year. METHODS: This study enrolled in 2686 patients with mild to moderate coronary artery lesions. Eighty-five indexes were recorded, included baseline clinical data, laboratory studies, and procedural characteristics. During the 1-year follow-up, 233 events occurred, five patients died, four patients suffered a nonfatal myocardial infarction, four patients underwent revascularization, and 220 patients were readmitted for angina pectoris. The Risk Estimation Model and the Simplified Model were conducted using Bayesian networks and compared with the Single Factor Models. RESULTS: The area under the curve was 0.88 for the Bayesian Model and 0.85 for the Simplified Model, while the Single Factor Model had a maximum area under the curve of 0.65. CONCLUSION: The new models can be used to assess the short-term risk of individual coronary heart disease events and may assist in guiding preventive care.

Predictive Ability of the SYNergy Between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery Score II for Long-term Mortality in Patients with Three-vessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention Treated with Second-generation Drug-eluting Stents.

BACKGROUND: The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery Score II (SS-II) can well predict 4-year mortality in patients with complex coronary artery disease (CAD), and guide decision-making between coronary artery bypass graft surgery and percutaneous coronary intervention (PCI). However, there is lack of data regarding the utility of the SS-II in patients with three-vessel CAD undergoing PCI treated with second-generation drug-eluting stents (DES). The purpose of the present study was to evaluate the ability of the SS-II to predict long-term mortality in patients with three-vessel CAD undergoing PCI with second-generation DES. METHODS: Totally, 573 consecutive patients with de novo three-vessel CAD who underwent PCI with second-generation DES were retrospectively studied. According to the tertiles of the SS-II, the patients were divided into three groups: The lowest SS-II tertile (SS-II ≤20), intermediate SS-II tertile (SS-II of 21-31), and the highest SS-II tertile (SS-II ≥32). The survival curves of the different groups were estimated by the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the relationship between the SS-II and 5-year mortality. The performance of the SS-II with respect to predicting the rate of mortality was studied by calculating the area under the receiver operator characteristic (ROC) curve. The predictive ability of the SS-II for 5-year mortality was evaluated and compared with the SS alone. RESULTS: The overall SS-II was 27.6 ± 9.0. Among patients in the lowest, intermediate and the highest SS-II tertiles, the 5-year rates of mortality were 1.6%, 3.2%, and 8.6%, respectively (P = 0.003); the cardiac mortality rates were 0.5%, 1.9%, and 5.2%, respectively (P = 0.014). By multivariable analysis, adjusting for the potential confounders, the SS-II was an independent predictor of 5-year mortality (hazard ratio: 2.45, 95% confidence interval: 1.38-4.36; P = 0.002). The SS-II demonstrated a higher predictive accuracy for 5-year mortality compared with the SS alone (the area under the ROC curve was 0.705 and 0.598, respectively). CONCLUSION: The SS-II is an independent predictor of 5-year mortality in patients with three-vessel CAD undergoing PCI treated with second-generation DES, and demonstrates a superior predictive ability over the SS alone.