Ae-Young Her

Effect of Intravascular Ultrasound–Guided vs Angiography-Guided Everolimus-Eluting Stent Implantation: The IVUS-XPL Randomized Clinical Trial

IMPORTANCE Use of intravascular ultrasound (IVUS) promotes better clinical outcomes for coronary intervention in complex coronary lesions. However, randomized data demonstrating the clinical usefulness of IVUS are limited for lesions treated with drug-eluting stents. OBJECTIVE To determine whether the long-term clinical outcomes with IVUS-guided drug-eluting stent implantation are superior to those with angiography-guided implantation in patients with long coronary lesions. DESIGN, SETTING, AND PARTICIPANTS The Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions (IVUS-XPL) randomized, multicenter trial was conducted in 1400 patients with long coronary lesions (implanted stent ≥28 mm in length) between October 2010 and July 2014 at 20 centers in Korea. INTERVENTIONS Patients were randomly assigned to receive IVUS-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. MAIN OUTCOMES AND MEASURES Primary outcome measure was the composite of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction, or ischemia-driven target lesion revascularization at 1 year, analyzed by intention-to-treat. RESULTS One-year follow-up was complete in 1323 patients (94.5%). Major adverse cardiac events at 1 year occurred in 19 patients (2.9%) undergoing IVUS-guided and in 39 patients (5.8%) undergoing angiography-guided stent implantation (absolute difference, -2.97% [95% CI, -5.14% to -0.79%]) (hazard ratio [HR], 0.48 [95% CI, 0.28 to 0.83], P = .007). The difference was driven by a lower risk of ischemia-driven target lesion revascularization in patients undergoing IVUS-guided (17 [2.5%]) compared with angiography-guided (33 [5.0%]) stent implantation (HR, 0.51 [95% CI, 0.28 to 0.91], P = .02). Cardiac death and target lesion-related myocardial infarction were not significantly different between the 2 groups. For cardiac death, there were 3 patients (0.4%) in the IVUS-guided group and 5 patients (0.7%) in the angiography-guided group (HR, 0.60 [95% CI, 0.14 to 2.52], P = .48). Target lesion-related myocardial infarction occurred in 1 patient (0.1%) in the angiography-guided stent implantation group (P = .32). CONCLUSIONS AND RELEVANCE Among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at 1 year. These differences were primarily due to lower risk of target lesion revascularization. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01308281.

Prediction of Left Atrial Fibrosis With Speckle Tracking Echocardiography in Mitral Valve Disease: A Comparative Study With Histopathology

Background and Objectives Left atrial (LA) fibrosis is a main determinant of LA remodeling and development of atrial fibrillation. However, non-invasive prediction of LA fibrosis is challenging. We investigated whether preoperative LA strain as measured by speckle tracking echocardiography could predict the degree of LA fibrosis and LA reverse remodeling after mitral valve (MV) surgery. Subjects and Methods Speckle tracking echocardiography and LA volume measurements were performed in 50 patients one day before MV surgery. LA tissues were obtained during the surgery, and the degrees of their interstitial fibroses were measured. LA volume measurements were repeated within 30 days after surgery (n=50) and 1-year later (n=39). Results Left atrial global strain was significantly correlated with the degree of LA fibrosis (r=-0.55, p<0.001), and its correlation was independent of age, underlying rhythm, presence of rheumatic heart disease and type of predominant MV disease (B=-1.37, 95% confidence interval -2.32 - -0.41, p=0.006). The degree of LA fibrosis was significantly correlated with early (r=-0.337, p=0.017) and 1-year (r=-0.477, p=0.002) percent LA volume reduction after MV surgery, but LA global strain was not significant. Conclusion Left atrial strain as measured by speckle tracking echocardiography might be helpful for predicting the degree of LA fibrosis in patients with MV disease.

Combined Usefulness of the Platelet-to-Lymphocyte Ratio and the Neutrophil-to-Lymphocyte Ratio in Predicting the Long-Term Adverse Events in Patients Who Have Undergone Percutaneous Coronary Intervention with a Drug-Eluting Stent

Objectives The aim of this study was to investigate the combined usefulness of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in predicting the long-term adverse events in patients who have undergone percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). Methods 798 patients with stable angina, unstable angina and non-ST elevated myocardial infarction (NSTEMI) who underwent elective successful PCI with DES were consecutively enrolled. The value of PLR and NLR in predicting adverse coronary artery disease (CAD) events and the correlations between these markers and adverse events (all-cause mortality, cardiac death, and nonfatal myocardial infarction) were analyzed. Results The follow-up period was 62.8 ± 28.8 months. When patients were classified into four groups according to the optimal cut-off values for the PLR and NLR on receiver operating characteristic analysis, patients with a high PLR (>128) and high NLR (>2.6) had the highest occurrence of adverse events among the groups. On Cox multivariate analysis, the NLR >2.6 [hazard ratio (HR) 2.352, 95% confidence interval (CI) 1.286 to 4.339, p = 0.006] and the PLR >128 (HR 2.372, 95% CI 1.305 to 3.191, p = 0.005) were independent predictors of long-term adverse events after adjusting for cardiovascular risk factors. Moreover, both a PLR >128 and a NLR >2.6 were the strongest predictors of adverse events (HR 2.686, 95% CI 1.452 to 4.970, p = 0.002). Conclusion High pre-intervention PLR and NLR, especially when combined, are independent predictors of long-term adverse clinical outcomes such as all-cause mortality, cardiac death, and myocardial infarction in patients with unstable angina and NSTEMI who have undergone successful PCI with DES.

Effects of Atorvastatin 20 mg, Rosuvastatin 10 mg, and Atorvastatin/Ezetimibe 5 mg/5 mg on Lipoproteins and Glucose Metabolism:

The aim of this study was to compare the effects of 3 different statin regimens that have equivalent low-density lipoprotein cholesterol (LDL-C) lowering efficacy on the apolipoprotein B/A1 ratio and glucose metabolism. After a 4-week dietary lead-in, 90 hypercholeserolemic patients were randomly assigned to 1 of 3 treatment groups for 8 weeks: atorvastatin 20 mg, rosuvastatin 10 mg, or atorvastatin/ezetimibe 5 mg/5 mg. At drug treatment week 8, we compared the percentage changes in lipid parameters, apolipoprotein B/A1 ratio, hemoglobin A1c, and homeostasis model assessment-insulin resistance (HOMA-IR) from baseline. Seventy-six patients completed the study and the percentage changes in LDL-C were comparable among the groups. However, the percentage reduction in the apolipoprotein B/A1 ratio was significantly greater in the rosuvastatin group (—47% ± 14%, P = .04) and the combination group (—46% ± 8%, P = .05) than in the atorvastatin group (—39% ± 11%). The percentage increase in hemoglobin A1c was small but significantly greater in the atorvastatin group compared to the combination group (3.0% ± 5.2% and —0.4% ± 4.0%, P = .03). The effect of rosuvastatin on hemoglobin A1c was not different from those of the other 2 regimens. The effects of 3 statin regimens were similar on HOMA-IR. In conclusion, 3 statin regimens have differential effect on apolipoprotein B/A1 and glycemic control after comparable LDL-C reduction.

Left Atrial Strain Assessed by Speckle Tracking Imaging Is Related to New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting

BACKGROUND Left atrial (LA) dysfunction was recently proposed as an important factor in the development of postoperative atrial fibrillation (POAF). LA strain analysis by 2-dimensional (2D) speckle tracking imaging is emerging as a new tool to evaluate LA function. We aimed to evaluate the correlation of LA dysfunction assessed by 2D speckle tracking imaging with the occurrence of POAF after coronary artery bypass grafting (CABG). METHODS In this study, 53 patients (mean age 66 ± 9 years) undergoing elective isolated CABG were enrolled. Conventional transthoracic echocardiography and 2D speckle tracking strain analysis were performed before surgery. POAF was detected with continuous electrocardiography monitoring throughout hospitalization (mean duration 17 ± 10 days). RESULTS POAF occurred in 13 of 53 patients (24%). Patients with POAF were significantly older than patients with normal sinus rhythm after surgery (71 ± 5 vs 64 ± 10 years, P = 0.026). Compared with patients with normal sinus rhythm, patients with POAF had a significantly larger LA volume index (32.6 ± 5.1 vs 27.3 ± 7.2 mL/m(2), P = 0.018), lower value of LA global strain (25.4 ± 10.4 vs 36.8 ± 7.6%, P = 0.001), and strain rate (1.2 ± 0.6 vs 1.6 ± 0.8 seconds, P = 0.024). By multivariate logistic regression analysis, only LA global strain (odds ratio, 1.12; 95% confidence interval, 1.00-1.24; P = 0.040) was an independent predictor of POAF after CABG. CONCLUSIONS Preoperative LA global strain measured by 2D speckle tracking strain analysis is associated with the development of POAF after CABG.

Relationship between aspirin/clopidogrel resistance and intra-stent thrombi assessed by follow-up optical coherence tomography after drug-eluting stent implantation

AIMS No data exist regarding the relationship between aspirin/clopidogrel resistance and intra-stent thrombi on follow-up optical coherence tomography (OCT) after drug-eluting stent (DES) implantation. The purpose of this study was to evaluate the relationship between aspirin/clopidogrel resistance and intra-stent thrombi on the follow-up OCT in DES-treated patients. METHODS AND RESULTS A total of 308 DES-treated patients who underwent follow-up OCT and simultaneous measurement of aspirin reaction unit (ARU) and P2Y12 reaction unit (PRU) using the VerifyNow assay system were selected for the study. Aspirin and clopidogrel resistance were defined as ARU ≥550 and PRU ≥275, respectively. Intra-stent thrombi were detected in 29 patients (9.4%). The mean time interval from DES implantation to OCT was 195 ± 133 days (202.9 ± 103.0 days for patients with intra-stent thrombi vs. 194.7 ± 136.0 days for patients without intra-stent thrombi; P = 0.750). There were no significant differences between patients with and without intra-stent thrombi with regard to the incidence of aspirin resistance (13.8 vs. 11.1%, respectively; P = 0.630) or clopidogrel resistance (72.4 vs. 50.5%, respectively; P = 0.056). The percentage of uncovered struts was 17.9 ± 15.8% in patients with intra-stent thrombi and 12.7 ± 17.3% in patients without intra-stent thrombi (P = 0.098). Stent length was significantly longer in patients with intra-stent thrombi (22.9 ± 6.0 vs. 19.4 ± 5.0 mm, P = 0.006). Multivariate logistic regression analysis showed that stent length (odds ratio = 1.152, 95% confidential interval 1.025-1.295; P = 0.017) was the only independent risk factor for the presence of intra-stent thrombi on OCT. CONCLUSION This OCT study suggested that the presence of intra-stent thrombi may not be associated with aspirin/clopidogrel resistance in DES-treated patients.

Prognostic Utility of Neutrophil-to-Lymphocyte Ratio on Adverse Clinical Outcomes in Patients with Severe Calcific Aortic Stenosis.

Background Inflammation is an important factor in the pathogenesis of calcific aortic stenosis (AS). We aimed to evaluate the association between an inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) and major adverse cardiovascular events (MACE) in patients with severe calcific AS. Methods A total of 336 patients with isolated severe calcific AS newly diagnosed between 2010 and 2015 were enrolled in this study. Using Cox proportional hazards (PH) regression models, we investigated the prognostic value of NLR adjusted for baseline covariates including logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE-I) and undergoing aortic valve replacement (AVR). We also evaluated the clinical relevance of NLR risk groups (divided into low, intermediate, high risk) as categorized by NLR cutoff values. MACE was defined as a composite of all-cause mortality, cardiac death and non-fatal myocardial infarction during the follow-up period. Results The inflammatory marker NLR was an independent prognostic factor most significantly associated with MACE [hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.04–1.09; p-value <0.001]. The goodness-of-fit and discriminability of the model including EuroSCORE-I and AVR (loglikelihood difference, 15.49; p-value <0.001; c-index difference, 0.035; p-value = 0.03) were significantly improved when NLR was incorporated into the model. The estimated Kaplan-Meier survival rates at 5 years for the NLR risk groups were 84.6% for the low risk group (NLR ≤ 2), 67.7% for the intermediate risk group (2 < NLR ≤ 9), and 42.6% for the high risk group (NLR > 9), respectively. Conclusion The findings of the present study demonstrate the potential utility of NLR in risk stratification of patients with severe calcific AS.

Gender differences in risk factors and clinical outcomes in young patients with acute myocardial infarction.

Background There are limited data on the influence of gender on risk factors and clinical outcomes in young patients with acute myocardial infarction (AMI). Methods This prospective study stratified outcomes according to gender in patients of age ≤50 years with a diagnosis of AMI, and who were enrolled in the nationwide registry of the Korea Working Group of Myocardial Infarction. The end point was the incidence of major adverse cardiovascular events (MACEs) defined as the composite of cardiac death, recurrent myocardial infarction (MI), and repeat revascularisation at 30 days and 1 year after admission. Results The registry enrolled 30 001 patients with AMI, of whom 5200 met the study inclusion criteria; 4805 patients were male and 395 were female. Current smoking was significantly higher in men, while hypertension and diabetes mellitus were significantly more common in women. Women underwent less coronary revascularisation, and were less likely to be on optimal medical therapy compared with men despite having a higher Killip class at presentation and higher risk angiographic findings. Although women had higher rates of MACEs (3.8% vs 1.8%, p=0.018 at 30 days and 7.8% vs 4.7%, p=0.004 at 1-year follow-up) compared with men, female gender was not an independent predictor of MACEs after adjusting for propensity score. Conclusions There were significant gender differences in the risk factors for coronary artery disease and the short-term and long-term clinical outcomes of young patients with AMI. Continued preventive strategies should be focused on gender-different risk factor reduction in these young patients.

High-intensity Statin Treatments in Clinically Stable Patients on Aspirin Monotherapy 12 Months After Drug-eluting Stent Implantation: A Randomized Study

INTRODUCTION AND OBJECTIVES Current guidelines on the treatment of blood cholesterol recommend continuous maintenance of high-intensity statin treatment in drug-eluting stent (DES)-treated patients. However, high-intensity statin treatment is frequently underused in clinical practice after stabilization of DES-treated patients. Currently, the impact of continuous high-intensity statin treatment on the incidence of late adverse events in these patients is unknown. We investigated whether high-intensity statin treatment reduces late adverse events in clinically stable patients on aspirin monotherapy 12 months after DES implantation. METHODS Clinically stable patients who underwent DES implantation 12 months previously and received aspirin monotherapy were randomly assigned to receive either high-intensity (40mg atorvastatin, n = 1000) or low-intensity (20mg pravastatin, n = 1000) statin treatment. The primary endpoint was adverse clinical events at 12-month follow-up (a composite of all death, myocardial infarction, revascularization, stent thrombosis, stroke, renal deterioration, intervention for peripheral artery disease, and admission for cardiac events). RESULTS The primary endpoint at 12-month follow-up occurred in 25 patients (2.5%) receiving high-intensity statin treatment and in 40 patients (4.1%) receiving low-intensity statin treatment (HR, 0.58; 95%CI, 0.36-0.92; P = .018). This difference was mainly driven by a lower rate of cardiac death (0 vs 0.4%, P = .025) and nontarget vessel myocardial infarction (0.1 vs 0.7%, P = .033) in the high-intensity statin treatment group. CONCLUSIONS Among clinically stable DES-treated patients on aspirin monotherapy, high-intensity statin treatment significantly reduced late adverse events compared with low-intensity statin treatment. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01557075.

Plaque characteristics and inflammatory markers for the prediction of major cardiovascular events in patients with ST-segment elevation myocardial infarction

To investigate the clinical utility of culprit plaque characteristics and inflammatory markers for the prediction of future cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI) with successful drug-eluting stent (DES) implantation. We evaluated 172 STEMI patients with successful primary percutaneous coronary intervention (PCI) with DES using pre-PCI high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR) and pre-PCI intravascular ultrasound virtual histology (IVUS-VH) of culprit lesions. The incidence of major adverse cardiovascular events (MACE) including all-cause mortality, non-fatal MI, stroke and late revascularization were recorded during hospitalization and follow-up. During follow-up (median 41 months), the incidence of MACE did not significantly differ among patients with or without all 3 high-risk plaque features on IVUS-VH (15.1 vs. 16.2%; p = 0.39). In contrast, patients with elevated hs-CRP and NLR levels were at significant risk for MACE [32.7 vs. 5.8%; hazard ratio (HR) 7.85; p < 0.001 and 43.9 vs. 6.9%; HR 8.44; p < 0.001, respectively]. High-risk plaque features had no incremental usefulness to predict future MACE. However, the incorporation of hs-CRP and NLR into a model with conventional clinical and procedural risk factors significantly improved the C-statistic for the prediction of MACE (0.76–0.89; p = 0.04). High-risk plaque features identified by IVUS-VH in culprit lesions were not associated with future MACE in patients with STEMI receiving DES. However, elevated hs-CRP and NLR levels were significantly associated with poorer outcomes and had incremental predictive values over conventional risk factors.