Long-term efficacy, safety and biocompatibility of a novel sirolimus eluting iron bioresorbable scaffold in a porcine model.

Iron is considered as an attractive alternative material for bioresorbable scaffolds (BRS). The sirolimus eluting iron bioresorbable scaffold (IBS), developed by Biotyx Medical (Shenzhen, China), is the only iron-based BRS with an ultrathin-wall design. The study aims to investigate the long-term efficacy, safety, biocompatibility, and lumen changes during the biodegradation process of the IBS in a porcine model. A total of 90 IBSs and 70 cobalt-chromium everolimus eluting stents (EES) were randomly implanted into nonatherosclerotic coronary artery of healthy mini swine. The multimodality assessments including coronary angiography, optical coherence tomography, micro-computed tomography, magnetic resonance imaging, real-time polymerase chain reaction (PCR), and histopathological evaluations, were performed at different time points. There was no statistical difference in area stenosis between IBS group and EES group at 6 months, 1year, 2 years and 5 years. Although the scaffolded vessels narrowed at 9 months, expansive remodeling with increased mean lumen area was found at 3 and 5 years. The IBS struts remained intact at 6 months, and the corrosion was detectable at 9 months. At 5 years, the iron struts were completely degraded and absorbed in situ, without in-scaffold restenosis or thrombosis, lumen collapse, aneurysm formation, and chronic inflammation. No local or systemic toxicity and abnormal histopathologic manifestation were found in all experiments. Results from real-time PCR indicated that no sign of iron overload was reported in scaffolded segments. Therefore, the IBS shows comparable efficacy, safety, and biocompatibility with EES, and late lumen enlargement is considered as a unique feature in the IBS-implanted vessels.

First-in-human evaluation of a novel ultrathin sirolimus-eluting iron bioresorbable scaffold: 3-year outcomes of the IBS-FIM trial.

BACKGROUND: The first-generation polymeric bioresorbable scaffolds resulted in higher than acceptable 3-year rates of device-related adverse outcomes. AIMS: We aimed to assess the intermediate-term safety and performance of a novel ultrathin-strut sirolimus-eluting iron bioresorbable scaffold (IBS) in non-complex coronary lesions. METHODS: The prospective, single-arm, open-label IBS first-in-human study enrolled 45 patients, each with a single de novo lesion. Enrolled patients were randomly assigned to 2 follow-up cohorts. Angiographic and imaging follow-up with intravascular ultrasound and optical coherence tomography (OCT) were conducted at 6 and 24 months in cohort 1 (n=30) and at 12 and 36 months in cohort 2 (n=15). Clinical follow-up was conducted at 1, 6 and 12 months, and annually thereafter up to 5 years. The coprimary outcomes were target lesion failure (TLF) and angiographic late lumen loss (LLL) at 6 months. RESULTS: A total of 45 patients were enrolled between April 2018 and January 2019. The mean age was 53.2 years, 77.8% were male, and 26.7% had diabetes. The TLF rates were 2.2% at 6 months and 6.7% at 3 years, which in all cases were due to clinically indicated target lesion revascularisation. No deaths, myocardial infarctions or stent thromboses occurred during 3-year follow-up. In-scaffold LLL was 0.33±0.27 mm at 6 months and 0.37±0.57 mm at 3 years. By OCT, the proportion of covered struts was 99.8% at 6 months and 100% after 1 year. The 3-year strut absorption rate was 95.4%. CONCLUSIONS: In this first-in-human experience, an ultrathin IBS was safe and effective for the treatment of de novo non-complex coronary lesions up to 3-year follow-up.

Two-Dimensional Shear Wave Elastography Evaluation of Post-transplantation Complications in Pediatric Receipt: A Retrospective Cohort.

Background: The 20-year survival rate in pediatric patients after liver transplantation (LT) was no more than 70%. Hepatic fibrosis is one of the principal factors affecting the long-term prognosis. Imaging evaluation was the first-line examination for pediatric liver graft assessment. However, the sensitivity and specificity were insufficient. Thus, two-dimensional shear wave elastography (2D-SWE) was performed to evaluate liver graft stiffness and complication in post-transplant pediatric receipt. Materials and Methods: In this retrospective cohort, 343 pediatric recipients who underwent liver graft biopsy in our tertiary LT center were recruited between June 2018 and December 2020. The 2D-SWE evaluation, laboratory examination, routine post-transplant biopsy, and hepatic pathological assessment were performed. Results: Ninety-eight of the 343 pediatric patients were included according to the protocol. The Liver Stiffness Measurements (LSM) value of 2D-SWE was significantly elevated in post-transplant fibrosis (p < 0.0001). The LSM value of patients with post-transplant biliary complications (p < 0.0001) and biopsy-proven rejection (BPR, p = 0.0016) also rose compared to regular recovery patients. Concerning the sensitivity and specificity of 2D-SWE in diagnosing liver graft fibrosis, the area under the ROC curve (AUC) was 88%, and the optimal cutoff value was 10.3 kPa. Conclusion: Pediatric LSM by 2D-SWE was efficient. Routine 2D-SWE evaluation could be optimal to predict significant liver graft fibrosis.

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.

Long-term safety and absorption assessment of a novel bioresorbable nitrided iron scaffold in porcine coronary artery.

This study aimed to investigate the long-term biocompatibility, safety, and degradation of the ultrathin nitrided iron bioresorbable scaffold (BRS) in vivo, encompassing the whole process of bioresorption in porcine coronary arteries. Fifty-two nitrided iron scaffolds (strut thickness of 70 µm) and 28 Vision Co-Cr stents were randomly implanted into coronary arteries of healthy mini-swine. The efficacy and safety of the nitrided iron scaffold were comparable with those of the Vision stentwithin 52 weeks after implantation. In addition, the long-term biocompatibility, safety, and bioresorption of the nitrided iron scaffold were evaluated by coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, energy dispersive spectrometry and histopathological evaluations at 4, 12, 26, 52 weeks and even at 7 years after implantation. In particular, a large number of struts were almost completely absorbed in situ at 7 years follow-up, which were first illustrated in this study. The lymphatic drainage pathway might serve as the potential clearance way of iron and its corrosion products.

Association of lipoprotein(a) with platelet aggregation and thrombogenicity in patients undergoing percutaneous coronary intervention.

This study aimed to evaluate the association of lipoprotein(a) levels with platelet aggregation and thrombogenicity in patients undergoing percutaneous coronary intervention (PCI), and to investigate the ischemic outcome on this population. Lipoprotein(a) and modified thrombelastography were measured in 6601 consecutive patients underwent PCI on dual antiplatelet therapy. Cox proportional regression analysis was applied to illustrate the ischemic events in a 2-year follow up. The mean levels of lipoprotein(a) were 29.0 mg/dl. Patients with higher lipoprotein(a) levels had significantly accelerated fibrin generation (lower K time and bigger α angle) and greater clot strength (higher maximum amplitude (MA)) than patients with lower lipoprotein(a) levels (P < .001). Moreover, the higher lipoprotein(a) group also exhibited significantly higher adenosine diphosphate (ADP) induced platelet aggregation (MAADP) by thrombelastography platelet mapping assay than lower lipoprotein(a) group. Cox regression analyzes revealed that patients with higher lipoprotein(a) levels had a 16% higher risk of major adverse cardiovascular and cerebrovascular events (HR 1.159, 95%CI: 1.005-1.337, P = .042) compared with patients with lower lipoprotein(a) levels. This association persisted after adjustment for a broad spectrum of risk factors (HR 1.174, 95%CI: 1.017-1.355, P = .028). High plasma lipoprotein(a) levels were associated with increased platelet aggregation and ischemic events in patients underwent PCI. Lipoprotein(a) might indicate the need for prolonged antiplatelet therapy.

Heart failure and left ventricular dysfunction in older patients with chronic kidney disease: the China Hypertension Survey (2012-2015).

BACKGROUND: Heart failure (HF) is a leading cause of hospitalization and mortality for older chronic kidney disease (CKD) patients. However, the epidemiological data is scarce. We aimed to determine the prevalence of left ventricular (LV) dysfunction and HF, and to explore the risk factors for HF among those patients. METHODS: This is a cross-sectional analysis of the China Hypertension Survey conducted between October 2012 and December 2015. A total of 5, 808 participants aged ≥ 65 years were included in the analysis. Self-reported history of HF and any other cardiovascular diseases was acquired. 2-D and Doppler echocardiography were used to assess LV dysfunction. CKD was defined as either estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2 or urinary albumin to creatinine ratio (ACR) ≥ 30 mg/g. RESULTS: Among CKD patients aged ≥ 65 years, the weighted prevalence of HF, heart failure with preserved ejection fraction (HFpEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF) was 4.8%, 2.5%, 0.8%, and 1.7%, respectively. The weighted prevalence of HF was 5.0% in patients with eGFR < 60 mL/min per 1.73 m2, and was 5.9% in patients with ACR ≥ 30 mg/g. The prevalence of LV systolic dysfunction was 3.1%, and while it was 8.9% for moderate/severe diastolic dysfunction. Multivariate analysis showed that smoking was significantly associated with the risk of HF. Furthermore, age, smoking, and residents in rural areas were significantly associated with a risk of LV diastolic dysfunction. CONCLUSIONS: The prevalence of HF and LV dysfunction was high in older patients with CKD, suggesting that particular strategies will be required.

Risk or Beneficial Factors Associated with Unplanned Revascularization Risk Following Percutaneous Coronary Intervention: A Large Single-Center Data.

OBJECTIVE: To analyze factors associated with unplanned revascularization (UR) risk in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). METHODS: A total of 10,640 cases with CAD who underwent PCI were analyzed. Multivariate COX regressions and competing risk regressions were applied. RESULTS: The patients who underwent UR following PCI in 30 days, 1, and 2 years accounted for 0.3%, 6.5%, and 8.7%, respectively. After multivariate adjustment, the number of target lesions [hazard ratio ( HR) = 2.320; 95% confidence interval ( CI): 1.643-3.277; P < 0.001], time of procedure ( HR= 1.006; 95% CI: 1.001-1.010; P = 0.014), body mass index ( HR= 1.104; 95% CI: 1.006-1.210; P = 0.036), incomplete revascularization (ICR) ( HR= 2.476; 95% CI: 1.030-5.952; P = 0.043), and age ( HR = 1.037; 95% CI: 1.000-1.075; P = 0.048) were determined as independent risk factors of 30-day UR. Factors, including low-molecular-weight heparin or fondaparinux ( HR= 0.618; 95% CI: 0.531-0.719; P < 0.001), second-generation durable polymer drug-eluting stent ( HR = 0.713; 95% CI: 0.624-0.814; P < 0.001), left anterior descending artery involvement ( HR= 0.654; 95% CI: 0.530-0.807; P < 0.001), and age ( HR= 0.992; 95% CI: 0.985-0.998; P = 0.014), were independently associated with decreased two-year UR risk. While, Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score ( HR= 1.024; 95% CI: 1.014-1.033; P < 0.001) and ICR ( HR= 1.549; 95% CI: 1.290-1.860; P < 0.001) were negatively associated with two-year UR risk. CONCLUSION: Specific factors were positively or negatively associated with short- and medium-long-term UR following PCI.

Strengthening effects of bone marrow mononuclear cells with intensive atorvastatin in acute myocardial infarction.

OBJECTIVE: To test whether intensive atorvastatin (ATV) increases the efficacy of transplantation with autologous bone marrow mononuclear cells (MNCs) in patients suffering from anterior ST-elevated myocardial infarction (STEMI). METHODS: This clinical trial was under a 2×2 factorial design, enrolling 100 STEMI patients, randomly into four groups of regular (RA) or intensive ATV (IA) with MNCs or placebo. The primary endpoint was the change of left ventricular ejection fraction (LVEF) at 1-year follow-up from baseline, primarily assessed by MRI. The secondary endpoints included other parameters of cardiac function, remodelling and regeneration determined by MRI, echocardiography, positron emission tomography (PET) and biomarkers. RESULTS: All the STEMI patients with transplantation of MNCs showed significantly increased LVEF change values than those with placebo (p=0.01) with only in the IA+MNCs patients group demonstrating significantly elevation of LVEF than in the IA+placebo group (+12.6% (95%CI 10.4 to 19.3) vs +5.0% (95%CI 4.0 to 10.0), p=0.001), pointing to a better synergy between ATV and MNCs (p=0.019). PET analysis revealed significantly increased viable areas of myocardium (p=0.015), while the scar sizes (p=0.026) and blood aminoterminal pro-B-type natriuretic peptide (p<0.034) reduced. All these above benefits of MNCs were also attributed to IA+MNCs instead of RA+MNCs group of patients with STEMI. CONCLUSIONS: Intensive ATV treatment augments the therapeutic efficacy of MNCs in patients with anterior STEMI at the convalescent stage. The treatment with the protocol of intensive ATV and MNC combination offers a clinically essential approach for myocardial infarction. TRIAL REGISTRATION NUMBER: NCT00979758.

Impact of high-sensitivity C-reactive protein on coronary artery disease severity and outcomes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Inflammation plays a pivotal role in coronary artery disease (CAD). Few data from large-size studies are available on the association of high-sensitivity C-reactive protein (hs-CRP) and severity of CAD. Our aim was to investigate their relationship as well as their impact on long-term outcomes in patients undergoing percutaneous coronary intervention. METHODS: In 2013, 10,020 patients were consecutively included. Patients were divided into three groups based on hs-CRP on admission: 0-3mg/L (n=6978, 69.6%), 3.01-10mg/L (n=1997, 19.9%), >10mg/L (n=1045, 10.4%). Disease severity was determined by SYNTAX score (SS). Their differences were assessed in SS and major adverse cardiovascular events (MACEs, including all-cause death, myocardial infarction, revascularization, and in-stent thrombosis) among groups. RESULTS: The mean follow-up period was 874 days. Patients with elevated hs-CRP were older, had more risk factors such as hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, and cigarette smoking. Multivariate regression analysis showed that hs-CRP >10mg/L (OR 1.49, 95% confidence interval 1.21-1.84, p<0.001), age, previous myocardial infarction, serum creatinine, and left ventricular ejection fraction were independent predictors of intermediate-high SS (>22). Subgroup analysis indicated that the relation between hs-CRP and SS was also consistent in acute coronary syndrome and its subtypes. Although elevated hs-CRP was positively associated with increased rates of MACEs (11.0% versus 12.1% versus 14.3%, p=0.006), death (1.0% versus 1.3% versus 3.0%, p<0.001), and revascularization (8.6% versus 10.4% versus 10.0%, p=0.032), it did not show any prognostic effect for adverse outcomes in multivariate regression analyses (all adjusted p> 0.05). While SS>22 remained independently predictive of MACEs and revascularization after adjusting confounders, the risks of which were increased by 56% and 68%, respectively. CONCLUSION: Serum hs-CRP could be a useful biomarker for indicating CAD severity and could aid in risk stratification.

Transplantation efficacy of autologous bone marrow mesenchymal stem cells combined with atorvastatin for acute myocardial infarction (TEAM-AMI): rationale and design of a randomized, double-blind, placebo-controlled, multi-center, Phase II TEAM-AMI trial.

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement ('fertilizing') for cell-based therapy. Clinical Trial Registration: NCT03047772.

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.

Preclinical Evaluation of a Novel Sirolimus-Eluting Iron Bioresorbable Coronary Scaffold in Porcine Coronary Artery at 6 Months.

OBJECTIVES: The aim of this study was to investigate the operability, 6-month efficacy, and safety of the novel sirolimus-eluting iron bioresorbable coronary scaffold (IBS) system compared with a cobalt-chromium everolimus-eluting stent (EES) (XIENCE Prime stent) in porcine coronary arteries. BACKGROUND: Bioresorbable scaffolds have been considered the fourth revolution in percutaneous coronary intervention. However, the first-generation bioresorbable scaffold showed suboptimal results. METHODS: Forty-eight IBS and 48 EES were randomly implanted into nonatherosclerotic swine. The operability, efficacy, and safety of the IBS and EES were evaluated using coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, and histopathologic evaluation at 7, 14, 28, 90, and 180 days after implantation. RESULTS: The operability of the ultrathin IBS (∼70 µm) was comparable with that of the EES, except for its visibility. There was no statistically significant difference in area stenosis between the IBS and EES from 28 to 180 days. The IBS maintained its integrity up to 90 days without corrosion, while corrosion was observed in a few struts in 2 of 10 IBS at 180 days. The percentage of endothelialization of IBS was higher than that of XIENCE Prime stents within 14 days after implantation. The fibrin score was higher in the IBS group at 28 days but comparable with the EES group at 90 and 180 days. No scaffold or stent thrombosis was seen in either group. No abnormal histopathologic changes in scaffolded or stented vessel segments and 5 main remote organs were observed in either group. CONCLUSIONS: Preclinical results suggest that the novel IBS has comparable operability, mid-term efficacy, and safety with the EES, and its corrosion profile in porcine coronary arteries is reasonable, which could support initial clinical study of the IBS.

Platelet reactivity in patients with chronic kidney disease undergoing percutaneous coronary intervention.

This study aimed to evaluate the platelet reactivity in real-world patients with different chronic kidney disease (CKD) stages after percutaneous coronary intervention (PCI), and to examine whether high residual platelet reactivity (HRPR) is associated with higher incidence of adverse cardiovascular events in a 2-year follow up. A total of 10 724 consecutive patients receiving DAPT with aspirin and clopidogrel after PCI throughout 2013 were enrolled. We applied modified thromboelastography (mTEG) in 6745 patients. Kaplan-Meier analysis and Cox proportional regression analysis were applied to illustrate end points for patients. The prevalence of HRPR for adenosine diphosphate (ADP) was higher in patients with CKD3-5 than patients with CKD1-2 (47.0% vs. 37.3%, p = 0.002), but not for arachidonic acid (AA). No significant difference was observed for MACCE between patients with or without HRPR for ADP (HR 1.004, 95%CI: 0.864-1.167, p = 0.954). Patients with HRPR for ADP was associated with less bleeding events than patients without HRPR for ADP (HR 0.795, 95%CI: 0.643-0.982, p = 0.034). In this large cohort of real-world patients after PCI, the deterioration of renal function was linked to HRPR for ADP. HRPR was not associated with MACCE in patients with CKD in a 2-year follow up. Bleeding risks were significantly lower in PCI patients with versus without HRPR for ADP.

Time trends regarding the etiology of renal artery stenosis: 18 years' experience from the China Center for Cardiovascular Disease.

The time trends regarding the etiology of renal artery stenosis (RAS) are changing, but few investigations have focused on these issues. This study aimed to analyze the time trends regarding the etiology of RAS in a large patient sample from the China Center for Cardiovascular Disease. Consecutive inpatients with RAS from January 1999 to December 2016 were enrolled in this study. The etiologic diagnosis of RAS was based on established criteria. We retrospectively analyzed the time trends regarding the etiology of RAS during an 18-year period. A total of 2905 patients with RAS were enrolled. There were 2393 (82.4%) patients with atherosclerosis (AS), 345 (11.9%) with Takayasu arteritis (TA), 126 (4.3%) with fibromuscular dysplasia (FMD), and 41 (1.4%) with other causes. Among all patients (n = 2905), patients aged ≤ 40 years (n = 450), patients aged >40 years (n = 2455), female patients (n = 1097), male patients (n = 1808), female patients aged >40 years (n = 808), and male patients aged >40 years (n = 1647), there were a gradual increase in the proportion of atherosclerotic RAS (P < 0.05), a gradual decrease in the proportion of RAS caused by TA (P < 0.05), and almost no change in the proportion of RAS caused by FMD during the 18-year period (P > 0.05). The data show that the primary causes of RAS are AS, TA, and FMD. The proportion of RAS caused by AS and TA gradually increased and decreased, respectively, over time, and the proportion of RAS caused by FMD showed no significant change.

Clinical outcomes and influencing factors of in-stent restenosis after stenting for symptomatic stenosis of the vertebral V1 segment.

OBJECTIVE: The objective of this study was to evaluate 30-day and long-term clinical outcomes and influencing factors of in-stent restenosis (ISR) after stenting for symptomatic stenosis of the vertebral V1 segment. METHODS: The clinical and follow-up data of 301 consecutive patients (mean age, 64 ± 8 years; 252 men) with symptomatic V1 stenosis who underwent stenting at the Fuwai Hospital between January 2010 and June 2016 were collected retrospectively. The 30-day and long-term follow-up of stroke and death after stenting and the recurrence of symptoms, ISR, and repeated revascularization were assessed. RESULTS: Technical success was 100%. The mean stenosis of lesions was reduced from 82.8% ± 7.6% to 4.4% ± 4.0% immediately after 312 stents (165 bare-metal stents [BMSs] and 147 drug-eluting stents) were implanted. The overall risk of combined any stroke and death was 1.0% (3/301) within 30 days after stenting. The rates of freedom from any stroke and death were 98.2%, 96.8%, and 91.4% at 1 year, 3 years, and 5 years, respectively. After a mean follow-up of 2.9 ± 1.5 years, 46 (15.8%) patients developed ISR, of whom 19 (6.5%) were symptomatic. Twenty-two (7.6%) patients with ISR underwent repeated revascularization. The primary and assisted patency rates were 90.0% and 95.4%, 82.6% and 90.3%, and 80.3% and 87.9% at 1 year, 3 years, and 5 years, respectively. BMS (hazard ratio, 2.02; 95% confidence interval, 1.01-4.06; P < .05) and diabetes (hazard ratio, 1.87; 95% confidence interval, 1.04-3.37; P = .04) were independently associated with an increased risk of ISR. CONCLUSIONS: Percutaneous stent placement for symptomatic V1 stenosis is safe and associated with a good long-term patency rate. BMS and diabetes are independent predictive factors of ISR.

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.

Impact of Proton-pump Inhibitors on the Pharmacodynamic Effect and Clinical Outcomes in Patients Receiving Dual Antiplatelet Therapy after Percutaneous Coronary Intervention: A Propensity Score Analysis.

BACKGROUND: Prior studies have reported controversial conclusions regarding the risk of adverse cardiovascular events in patients using proton-pump inhibitors (PPIs) combined with clopidogrel therapy, causing much uncertainty in clinical practice. We sought to evaluate the safety of PPIs use among high-risk cardiovascular patients who underwent percutaneous coronary intervention (PCI) in a long-term follow-up study. METHODS: A total of 7868 consecutive patients who had undergone PCI and received dual antiplatelet therapy (DAPT) at a single center from January 2013 to December 2013 were enrolled. Adenosine diphosphate (ADP)-induced platelet aggregation inhibition was measured by modified thromboelastography (mTEG) in 5042 patients. Propensity score matching (PSM) was applied to control differing baseline factors. Cox proportional hazards regression was used to evaluate the 2-year major adverse cardiovascular and cerebrovascular events (MACCEs), as well as individual events, including all-cause death, myocardial infarction, unplanned target vessel revascularization, stent thrombosis, and stroke. RESULTS: Among the whole cohort, 27.2% were prescribed PPIs. The ADP-induced platelet aggregation inhibition by mTEG was significantly lower in PPI users than that in non-PPI users (42.0 ± 30.9% vs. 46.4 ± 31.4%, t = 4.435, P < 0.001). Concomitant PPI use was not associated with increased MACCE through 2-year follow-up (12.7% vs. 12.5%, χ2 = 0.086, P = 0.769). Other endpoints showed no significant differences after multivariate adjustment, regardless of PSM. CONCLUSION: In this large cohort of real-world patients, the combination of PPIs with DAPT was not associated with increased risk of MACCE in patients who underwent PCI at up to 2 years of follow-up.

Impact of diabetes duration on 3-year clinical outcomes following coronary revascularization.

OBJECTIVE: The aim of this study was to evaluate the impact of diabetes duration on long-term clinical outcomes after drug-eluting stent (DES) implantation or coronary artery bypass grafting (CABG). METHODS: A total of 820 diabetic patients treated with initial DES (n=451) or CABG (n=369) were consecutively enrolled in this single-center follow-up study. The main outcomes included major adverse cardiac events and major adverse cardiac or cerebrovascular events (MACCEs). Cox regression analysis with propensity adjustment was used for data analysis. RESULTS: Three-year risks of major adverse cardiac events were significantly higher in the DES group compared with the CABG group irrespective of whether the diabetes durations were less or more than 5 years [hazard ratio (HR) 2.27, 95% confidence interval (CI) 1.19-4.31, P=0.01; HR 3.73, 95% CI 2.72-10.12, P<0.01; P for interaction=0.28]. A similar trend was observed for repeat revascularization. However, CABG was associated with increased risk of stroke, especially in the patients with diabetes duration of at least 5 years (HR 0.02, 95% CI 0.002-0.12, P<0.01). Three-year risk of MACCEs was significantly higher in the DES group in patients with diabetes duration of at least 5 years (HR 2.13, 95% CI 1.34-3.39, P<0.01), but not for those less than 5 years (HR 1.03, 95% CI 0.65-1.63, P=0.91). A statistically significant interaction between diabetes duration and treatment strategy was found for MACCEs (P for interaction=0.04). CONCLUSION: Short diabetes duration (<5 years) was associated with equal risk of MACCEs among stable coronary artery disease patients with DES and CABG, emphasizing the need to consider the duration of diabetes when determining the best strategy for patients undergoing coronary revascularization.

CYP2C19 genotyping combined with on-clopidogrel platelet reactivity in predicting major adverse cardiovascular events in Chinese patients with percutaneous coronary intervention.

INTRODUCTION: Both CYP2C19 genotyping and platelet function testing are used to predict major adverse cardiac events (MACEs) in Chinese patients treated with clopidogrel and undergoing stent implantation, but the most accurate prognostic technique is still debated. Here, we combine both techniques, to determine if a more accurate prognosis is possible. METHODS: Patients undergoing stent implantation (1104) were genotyped and assessed for platelet reactivity, with a 12-month follow-up. The CYP2C19*2 (rs4244285), and *3 (rs4986893) alleles were genotyped. High on treatment platelet reactivity was defined as adenosine diphosphate (ADP)-induced platelet inhibition ≤30%. MACEs included death, nonfatal myocardial infarction, target vessel revascularization, or stent thrombosis. RESULTS AND CONCLUSIONS: Hazard ratios (HRs) for cardiovascular ischemic outcomes based on the two testing methods are as follows. CYP2C19 genotyping: carriers of CYP2C19 loss-of-function alleles, HR: 2.515, 95% confidence interval (CI), 1.150-5.501, P=0.021; ADP-induced platelet inhibition ≤30%, HR: 1.992, 95% CI, 1.040-3.818, P=0.038. An ischemic risk score between zero and two was calculated. Compared with the group with a score of zero, HRs for adverse cardiovascular outcomes were 4.078 for those with a score of two (95% CI: 1.525-10.905, P=0.005). However, there was no significant difference between the group with the score of zero and the group with the score of one. CYP2C19 genotyping combined with platelet reactivity is an independent and additive predictor of 1-year MACE in Chinese patients undergoing stenting with clopidogrel treatment, which is better than either test alone.