Routine Functional Testing or Standard Care in High-Risk Patients after PCI.

BACKGROUND: There are limited data from randomized trials to guide a specific follow-up surveillance approach after myocardial revascularization. Whether a follow-up strategy that includes routine functional testing improves clinical outcomes among high-risk patients who have undergone percutaneous coronary intervention (PCI) is uncertain. METHODS: We randomly assigned 1706 patients with high-risk anatomical or clinical characteristics who had undergone PCI to a follow-up strategy of routine functional testing (nuclear stress testing, exercise electrocardiography, or stress echocardiography) at 1 year after PCI or to standard care alone. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years. Key secondary outcomes included invasive coronary angiography and repeat revascularization. RESULTS: The mean age of the patients was 64.7 years, 21.0% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had diffuse long lesions, 38.7% had diabetes, and 96.4% had been treated with drug-eluting stents. At 2 years, a primary-outcome event had occurred in 46 of 849 patients (Kaplan-Meier estimate, 5.5%) in the functional-testing group and in 51 of 857 (Kaplan-Meier estimate, 6.0%) in the standard-care group (hazard ratio, 0.90; 95% confidence interval [CI], 0.61 to 1.35; P = 0.62). There were no between-group differences with respect to the components of the primary outcome. At 2 years, 12.3% of the patients in the functional-testing group and 9.3% in the standard-care group had undergone invasive coronary angiography (difference, 2.99 percentage points; 95% CI, -0.01 to 5.99), and 8.1% and 5.8% of patients, respectively, had undergone repeat revascularization (difference, 2.23 percentage points; 95% CI, -0.22 to 4.68). CONCLUSIONS: Among high-risk patients who had undergone PCI, a follow-up strategy of routine functional testing, as compared with standard care alone, did not improve clinical outcomes at 2 years. (Funded by the CardioVascular Research Foundation and Daewoong Pharmaceutical; POST-PCI ClinicalTrials.gov number, NCT03217877.).

Breast Arterial Calcification: A Potential Biomarker for Atherosclerotic Cardiovascular Disease Risk?

PURPOSE OF REVIEW: We aimed to summarize the current evidence regarding the association between breast arterial calcification (BAC) and atherosclerotic cardiovascular disease (ASCVD) in women and discuss the potential role of BAC in the risk stratification and preventive approaches for ASCVD. RECENT FINDINGS: BAC has emerged as a potential women-specific risk marker for ASCVD. Although BAC presents as a medial calcification of the arteries, notably different from the intimal atherosclerotic process, current evidence supports a correlation between BAC and ASCVD risk factors or subclinical and clinical ASCVD, such as coronary artery disease or stroke. As millions of women undergo mammograms each year, the potential clinical application of BAC in enhanced ASCVD risk estimation, with no additional cost or radiation, has tremendous appeal. Although further research regarding optimal risk assessment and management in women with BAC is required, the presence of BAC should prompt healthy cardiovascular lifestyle modifications.

Effect of Ticagrelor on Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction (HEALING-AMI).

OBJECTIVES: The aim of this study was to evaluate the effect of ticagrelor versus clopidogrel on left ventricular (LV) remodeling after reperfusion of ST-segment elevation myocardial infarction (STEMI) in humans. BACKGROUND: Animal studies have demonstrated that ticagrelor compared with clopidogrel better protects myocardium against reperfusion injury and improves remodeling after myocardial infarction. METHODS: In this investigator-initiated, randomized, open-label, assessor-blinded trial performed at 10 centers in Korea, patients were enrolled if they had naive STEMI successfully treated with primary percutaneous coronary intervention (PCI) and at least 6-month planned duration of dual-antiplatelet treatment. The coprimary endpoints were LV remodeling index (LVRI) (a relative change of LV end-diastolic volume) measured on 3-dimensional echocardiography and N-terminal pro-B-type natriuretic peptide level at 6 months. RESULTS: Among initially enrolled patients with STEMI (n = 336), 139 in each group completed the study. LVRI at 6 months was numerically lower with ticagrelor versus clopidogrel (0.6 ± 18.6% vs. 4.5 ± 16.5%; p = 0.095). Ticagrelor significantly reduced the 6-month level of N-terminal pro-B-type natriuretic peptide (173 ± 141 pg/ml vs. 289 ± 585 pg/ml; p = 0.028). These differences were prominent in patients with pre-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade 0. By multivariate analysis, ticagrelor versus clopidogrel reduced the risk for positive LV remodeling (LVRI >0%) (odds ratio: 0.56; 95% confidence interval: 0.33 to 0.95; p = 0.030). The LV end-diastolic volume index remained unchanged during ticagrelor treatment (from 54.7 ± 12.2 to 54.2 ± 12.2 ml/m2; p = 0.629), but this value increased over time during clopidogrel treatment (from 54.6 ± 11.3 to 56.4 ± 13.9 ml/m2; p = 0.056) (difference -2.3 ml/m2; 95% confidence interval: -4.8 to 0.2 ml/m2; p = 0.073). Ticagrelor reduced LV end-systolic volume index (from 27.0 ± 8.5 to 24.7 ± 8.4 ml/m2; p < 0.001), whereas no reduction was seen with clopidogrel (from 26.2 ± 8.9 to 25.6 ± 11.0 ml/m2; p = 0.366) (difference -1.8 ml/m2; 95% confidence interval: -3.5 to -0.1 ml/m2; p = 0.040). CONCLUSIONS: Ticagrelor was superior to clopidogrel for LV remodeling after reperfusion of STEMI with primary PCI. (High Platelet Inhibition With Ticagrelor to Improve Left Ventricular Remodeling in Patients With ST Segment Elevation Myocardial Infarction [HEALING-AMI]; NCT02224534).

Pragmatic trial comparing routine versus no routine functional testing in high-risk patients who underwent percutaneous coronary intervention: Rationale and design of POST-PCI trial.

BACKGROUND: Although the need to detect restenosis has diminished in the contemporary practice of percutaneous coronary intervention (PCI) with drug-eluting stents (DES), the surveillance of ischemia owing to restenosis or disease progression deserves attention in high-risk PCI settings. It is unknown whether follow-up strategy of routine noninvasive functional testing potentially reduces the risk of major cardiovascular events in high-risk PCI patients. METHODS: The POST-PCI study is an investigator-initiated, multicenter, prospective randomized trial comparing the effectiveness of two follow-up strategies in patients with high-risk anatomic or clinical characteristics who underwent PCI. Study participants were randomly assigned to either (1) the routine noninvasive stress testing (exercise electrocardiography, nuclear stress imaging, or stress echocardiography) at 12 months post-PCI or (2) the standard-care without routine testing. In the routine stress testing group, depending on the testing results, all clinical decisions regarding subsequent diagnostic or therapeutic procedures were at the treating physician's discretion. The primary endpoint was a composite outcome of death from any causes, myocardial infarction, or hospitalization for unstable angina at 2 years post-PCI. RESULTS: More than 1700 high-risk PCI patients have been randomized over 2.0 years at 11 major cardiac centers in Korea. CONCLUSION: This pragmatic POST-PCI trial will provide valuable clinical evidence on the effectiveness of follow-up strategy of routine noninvasive stress testing in high-risk PCI patients.

Breast Arterial Calcification is Associated with the Progression of Coronary Atherosclerosis in Asymptomatic Women: A Preliminary Retrospective Cohort Study.

We evaluated whether breast arterial calcification (BAC) is associated with the progression of coronary atherosclerosis in asymptomatic women. This retrospective observational cohort study analysed asymptomatic women from the BBC registry. In 126 consecutive women (age, 54.5 ± 7.0 years) who underwent BAC evaluation and repeated coronary computed tomography angiography (CCTA) examinations, the coronary arterial calcification score (CACS) and segment stenosis score (SSS) were evaluated to assess the progression of coronary arterial calcification (CAC) and coronary atherosclerotic plaque (CAP). CAC and CAP progression were observed in 42 (33.3%) and 26 (20.6%) women, respectively (median interscan time, 4.3 years), and were associated with the presence of BAC and a higher BAC score at baseline. Women with BAC demonstrated higher CAC and CAP progression rates and showed higher chances for CAC and CAP progression during follow-up (p < 0.001 for both). In multivariable analyses, the BAC score remained independently associated with both CAC and CAP progression rates after adjustment for clinical risk factors (ß = 0.087, p = 0.029; and ß = 0.020, p = 0.010, respectively) and with additional adjustment for baseline CACS (ß = 0.080, p = 0.040; and ß = 0.019, p = 0.012, respectively) or SSS (ß = 0.079, p = 0.034; and ß = 0.019, p = 0.011, respectively). Thus, BAC may be related to the progression of coronary atherosclerosis and its evaluation may facilitate decision-making.

Association of Plasma Marker of Oxidized Lipid with Histologic Plaque Instability in Patients with Peripheral Artery Disease.

BACKGROUND: The association between oxidized low-density lipoprotein (OxLDL) and plaque instability in coronary and carotid artery disease is well established. However, the association between OxLDL and the histologic changes of plaque in peripheral artery disease has not been clearly elucidated. This study aims to investigate the association between plasma OxLDL and histologic plaque instability in patients with peripheral artery disease. METHODS: Prospectively obtained plaques from 48 patients who underwent endovascular atherectomy (n = 20), surgical endarterectomy (n = 9), or bypass surgery (n = 19) for treatment of atherosclerotic femoropopliteal artery disease were evaluated for histologic fibrosis, sclerosis, calcification, necrosis, cholesterol cleft, and foamy macrophages using hematoxylin and eosin, oil red O, and immunohistochemical staining. Unstable plaques were defined as plaques that were positive for foamy macrophages and with lipid content of more than 10% of the total plaque area. Plasma OxLDL levels were measured using an enzyme-linked immunosorbent assay (Mercodia AB, Uppsala, Sweden). RESULTS: Of the 48 patients, 26 (54%) had unstable plaques. The unstable plaque group was younger, had fewer angiographic total occlusions, less calcification, and more CD68-positive and LOX-1-positive cells than the stable plaque group. Plasma OxLDL levels were significantly higher in the unstable plaque group than in the stable plaque group (57.4 ± 13.9 vs. 47.2 ± 13.6 U/L, P = 0.014). Multivariate analysis revealed that plasma OxLDL level, smoking, angiographic nontotal occlusion, and statin nonuse were independent predictors of unstable plaque. CONCLUSIONS: Among patients with peripheral artery disease, the histologic instability of femoropopliteal plaque was independently associated with high plasma OxLDL, smoking, nontotal occlusion, and statin nonuse. Further large-scale studies are necessary to evaluate the role of noninvasive OxLDL measurement for predicting plaque instability and future adverse vascular event.

Comparison of Minimally Invasive Direct Coronary Artery Bypass and Percutaneous Coronary Intervention Using Second-Generation Drug-Eluting Stents for Coronary Artery Disease　- Propensity Score-Matched Analysis.

BACKGROUND: Some studies comparing minimally invasive direct coronary artery bypass (MIDCAB) and percutaneous coronary intervention (PCI) have reported MIDCAB's superiority, but they did not investigate contemporary PCI with newer generation drug-eluting stents (DES). We compared clinical outcomes after MIDCAB with previously reported outcomes after PCI with second-generation DES.Methods and Results:We retrospectively reviewed the records of patients treated with MIDCAB. Baseline characteristics and clinical outcomes after MIDCAB were compared with those for left anterior descending artery disease treated via PCI. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), a composite of cardiovascular death, non-fatal myocardial infarction, ischemic stroke, and target vessel revascularization (TVR). A propensity score-matching (PSM) analysis was conducted to adjust for between-group differences in baseline characteristics. We analyzed 77 patients treated with MIDCAB and 2,206 treated with PCI. The MIDCAB group was older and had more severe coronary disease and a higher incidence of left ventricular dysfunction. Over a 3-year follow-up, the PCI group had favorable MACCE outcomes. After PSM, there were no between-group differences in MACCE (MIDCAB, 15.6% vs. PCI, 23.4%; hazard ratio [HR], 0.80; 95% CI: 0.38-1.68, P=0.548) or TVR (MIDCAB, 2.6% vs. PCI, 5.2%; HR, 0.51; 95% CI: 0.10-3.09, P=0.509). CONCLUSIONS: Clinical outcomes were similar between MIDCAB and PCI using second-generation DES over 3 years of follow-up.

Efficacy of IntraCoronary Erythropoietin Delivery BEfore Reperfusion-Gauging Infarct Size in Patients with Acute ST-segment Elevation Myocardial Infarction (ICEBERG).

Previous clinical studies have shown inconsistent results regarding the effect of erythropoietin in ST-segment elevation myocardial infarction (STEMI). This study investigated whether directed intracoronary infusion of darbepoetin-α into ischemic myocardium before reperfusion would reduce infarct size or post-infarct remodeling in STEMI patients.Eighty STEMI patients received one of the following treatments simultaneously with the first balloon inflation: intracoronary darbepoetin-α 300 µg (n = 40) or saline (n = 40), administered via the over-the-wire balloon system. The primary endpoint was infarct size estimated by serial cardiac enzyme levels after procedure. The secondary endpoints were (1) infarct size and proportion of salvaged myocardium measured with cardiac magnetic resonance (CMR) at baseline; (2) post-infarct remodeling (PIR), defined as an increase in left ventricular end-diastolic volume more than 20% at 4 months compared to the baseline on CMR; and (3) composite cardiovascular endpoints assessed at 4 months.The peak CK-MB [median 270.0 (interquartile range 139.8-356.3) versus 231.5 (131.0-408.5) ng/mL, P = 0.55] and troponin-I [128.5 (63.5-227.8) versus 109.0 (43.8-220.0) ng/mL, P = 0.52) ] did not differ between the darbepoetin-α and control group. Fifty-seven patients completed the baseline and 4-month follow-up CMR. There were no differences in infarct size [30.6 (18.1-49.8) versus 31.5 (22.5-47.3) cm3, P = 0.91), proportion of salvaged myocardium [26.7% (15.9-42.6%) versus 35.8% (22.4-48.8%), P = 0.12) or PIR (8.0% versus 6.7%, P = 0.62) between the two groups. Composite cardiovascular outcomes did not differ between the two groups.In conclusion, administration of intracoronary darbepoetin-α before reperfusion did not reduce infarct size or post-infarct remodeling in STEMI patients.

Clinical and Computed Tomography Angiographic Predictors of Coronary Lesions That Later Progressed to Chronic Total Occlusion.

OBJECTIVES: This study aimed to investigate clinical and coronary computed tomographic angiography (CTA) characteristics of lesions that progressed to chronic total occlusion (CTO). BACKGROUND: CTO is one of the most common reasons for referral to coronary artery bypass surgery. Prediction and adequate early management for future CTO lesions may be beneficial. METHODS: The study evaluated patients with at least 1 vessel with a diameter stenosis of ≥70% on invasive coronary angiography (ICA) who underwent previous coronary CTA >12 months before ICA, from 2006 to 2015. The study compared the baseline clinical and coronary CTA characteristics of the patients with future CTO lesions with those of the patients with future non-CTO lesions (patient-level analysis) and compared coronary CTA findings between the future CTO lesion with the most stenotic non-CTO lesion in each CTO patient (lesion-level analysis). RESULTS: Among the 216 patients, 32 (14.8%) had a CTO lesion on ICA. In patient-level analysis, no significant differences in clinical characteristics were found, whereas the coronary CTA culprit lesions of the CTO group had a smaller minimal lumen diameter (MLD) with more adverse plaque characteristics. In lesion-level analysis, future CTO lesions had a smaller MLD, a smaller reference segment diameter (RD), and longer lesion length. These lesions were more likely to be noncalcified plaques with a noneccentric cross-sectional distribution, and had a higher remodeling index, lower mean plaque attenuation (MPA), and more napkin-ring signs. In multivariate analysis and receiver-operating characteristic curve analysis, MLD of <2.0 mm, RD of <3.2 mm, and MPA of <50 Hounsfield units were independent predictors of future CTO lesions. The risk of CTO development in lesions with triple risk factors was 14-fold higher than that of the lesions with no risk factors. CONCLUSIONS: Lesions that progressed to CTO had more severe baseline coronary CTA features than non-CTO lesions. A small MLD, small RD, and low MPA were independent predictors of progression to CTO.

Prediction of Subclinical Coronary Artery Disease With Breast Arterial Calcification and Low Bone Mass in Asymptomatic Women: Registry for the Women Health Cohort for the BBC Study.

OBJECTIVES: This study sought to determine whether evaluations of breast arterial calcification (BAC) and low bone mass (LBM) could improve the ability to predict subclinical coronary artery disease (CAD) in asymptomatic women. BACKGROUND: An improved risk stratification strategy beyond the measurement of conventional risk factors is needed to identify women at high risk of CAD. METHODS: The BBC (Women Health Registry Study for Bone, Breast, and Coronary Artery Disease) enrolled 2,100 asymptomatic women who underwent dual-energy X-ray absorptiometry, digital mammography, and coronary computed tomography angiography. We assessed the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk and evaluated the presence and severity of BAC, LBM, coronary artery calcification (CAC), and coronary atherosclerotic plaque (CAP). RESULTS: CAC and CAP were found in 11.2% and 15.6% of participants, respectively. In women with CAC or CAP, increasing trends in the presence and severity of both BAC and LBM were observed. Both BAC and LBM were found to be associated with the presence of CAC (unadjusted odds ratios [OR]: 3.54 and 2.22, respectively) and CAP (unadjusted OR: 3.02 and 1.91, respectively). However, in multivariate analysis, only the presence of BAC and BAC score remained as independent predictors. For the prediction of CAC and CAP, addition of the BAC presence to the 10-year ASCVD risk significantly increased the areas under the curve (area under the curve: 0.71 to 0.72; p = 0.016; and area under the curve: 0.66 to 0.68; p = 0.010; respectively) and resulted in net reclassification index improvements (area under the curve: 0.304; p <0.001; and area under the curve: 0.245; p <0.001; respectively). CONCLUSIONS: The presence and severity of BAC and LBM were significantly associated with the risk of subclinical CAD in asymptomatic women. BAC evaluation especially provides an independent and incremental value over conventional risk algorithms. (Women Health Cohort for Breast, Bone and Coronary Artery Disease [BBC]; NCT03235622).

Breast Arterial Calcification: A Potential Surrogate Marker for Cardiovascular Disease.

Breast arterial calcifications (BAC), frequently observed on screening mammography, have been considered as an incidental finding without increased risk for breast cancer. They are medial calcifications and therefore, are indicative of arteriosclerosis. Previous studies indicated that the risk factors of BAC partly overlap with those of cardiovascular disease (CVD), and the presence of BAC is associated with prevalent and incident CVD. This suggests that medial arterial calcification might contribute to CVD through a pathway distinct from the intimal atherosclerotic process. A recent study showed that the presence and severity of BAC are associated with the presence of coronary artery calcification or plaques on coronary computed tomography angiography in asymptomatic women aged more than 40 years. In addition, BAC provided an independent and incremental predictive value over conventional risk factors. Given that population-based mammography screening is currently recommended in asymptomatic women, the evaluation of BAC may be helpful in identifying high-risk women without additional cost or radiation exposure.

Effect of tailored use of tirofiban in patients with Non-ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention: a randomized controlled trial.

BACKGROUND: We conducted a randomized controlled trial to investigate whether an additional platelet inhibition with tirofiban would reduce the extent of myocardial damage and prevent periprocedural myonecrosis in patients with Non-ST-elevation acute coronary syndrome (NSTE-ACS) with a high residual platelet activity (HPR). METHODS: Patients with an HPR, defined as P2Y12 reaction unit (PRU) > 230, were randomly assigned to group A (tirofiban treatment, n = 30) or C1 (n = 30) and patients without an HPR to C2 (n = 78). Periprocedural myocardial damage was assessed using the area under the curve (AUC) of serial cardiac enzyme levels from the time of the procedure to post-36 h. Periprocedural myonecrosis incidence was evaluated. RESULTS: The troponin I AUC was not different between the groups (197.2 [41.5395.7], 37.9 [8.9313.9], 121.3 [43.7481.8] h∙ng/mL; p = 0.088). The results did not change when the baseline levels were adjusted (365.3 [279.5, 451.1], 293.0 [207.1, 379.0], and 298.0 [244.7, 351.3] h∙ng/mL; p = 0.487). The rate of periprocedural myonecrosis was also not different between the groups (53.0% vs. 50.0% vs. 33.3%, p = 0.092). The CK-MB isoenzyme analysis showed similar results. No difference in complications was noted. CONCLUSION: Additional tirofiban administration was not beneficial to patients with NSTE-ACS even with an HPR. TRIAL REGISTRATION: Clinical trial no. NCT03114995 , registered 11 April, 2017, retrospectively.

The Effect of Cilostazol on the Angiographic Outcome of Drug-Eluting Coronary Stents Angiographic Analysis of the CILON-T (Influence of CILostazol-Based Triple Antiplatelet Therapy ON Ischemi Complication after Drug-Eluting StenT Implantation) Trial.

It is not clear if anti-restonotic effect of cilostazol is consistent for different types of drug-eluting stents (DES).The purpose of this study was to compare the anti-proliferative effect of cilostazol between DAT and TAT with consideration of confounding influences of DES type.Nine hundred and fifteen patients were randomized to either dual antiplatelet therapy (DAT; aspirin and clopidogrel) or triple antiplatelet therapy (TAT; aspirin, clopidogrel, and cilostazol) in the previous CILON-T trial. After excluding 70 patients who received both or neither stents, we analyzed 845 patients who received exclusively PES or ZES, and compared in-stent late loss at 6 months between both antiplatelet regimens (DAT versus TAT).Baseline angiographic and clinical characteristics were similar between the DAT (656 lesions in 425 patients) and the TAT group (600 lesions in 420 patients). The 6-month follow-up angiography was completed in 745 patients (88.2%). Quantitative coronary angiography showed that TAT significantly reduced in-stent late loss (DAT 0.62 ± 0.62 mm versus TAT 0.54 ± 0.49 mm, P = 0.015). Stent type, diabetes or lesion length did not interact with difference of late loss. However, reduction of late loss by cilostazol did not lead to a significant reduction in the rate of target lesion revascularization (TLR) (DAT 7.8% versus TAT 6.9%, P = 0.69) due to a nonlinear relationship found between late loss and TLR.The TAT group showed less in-stent late loss as compared to the DAT group. This was consistently observed regardless of DES type, lesion length, or diabetic status. However, reduction of late loss by cilostazol did not lead to a significant reduction in TLR.

Relation between secondhand smoke exposure and cardiovascular risk factors in never smokers.

OBJECTIVE: Secondhand smoke exposure (SHSE) in nonsmokers has been associated with premature cardiovascular mortality and ischemic heart disease. We conducted a cross-sectional, population-based study evaluating the relationship between SHSE, measured by subjective and objective methods, and conventional cardiovascular risks such as blood pressure, lipid profiles, and fasting glucose. METHODS: We extracted information on 7376 healthy adults who had never smoked, for whom there were available urine cotinine levels, from the Korea National Health and Nutrition Examination Survey 2008-2011. SHSE was defined using self-report questionnaires and urine cotinine levels. The main outcomes included SBP and DBP, serum lipid profiles, and fasting glucose. RESULTS: The mean age of the study population was 45.4 ±â€Š0.4 years and 75.2% were women. Self-reported SHSE had no significant association with study outcomes except for DBP, which had marginally positive relationships (P = 0.060). Unadjusted analysis showed higher cotinine levels were associated with lower SBP, total cholesterol, LDL cholesterol, and triglyceride. All associations lost statistical significance after multivariable adjustment. Fasting glucose had a positive relationship with urine cotinine in quartiles but not with logarithm-transformed cotinine. CONCLUSION: Although SHSE is associated with increased risk of cardiovascular mortality and morbidity, we did not find any consistent relationship among SHSE and blood pressure, lipid, or fasting glucose levels in this cross-sectional study. Using objective measurements of urine cotinine did not alter this relationship. Further long-term prospective studies are needed to evaluate the effect of SHSE as a cardiovascular risk factor.

A laboratory association between hemoglobin and VerifyNow P2Y12 reaction unit: A systematic review and meta-analysis.

BACKGROUND: VerifyNow P2Y12 assay is used widely to evaluate residual platelet reactivity in patients taking P2Y12 receptor antagonists. However, a laboratory association between VerifyNow P2Y12 reaction unit (PRU) and hemoglobin, which might lead to wrong interpretation of the data, is reported. We performed these systematic review and meta-analysis to clearly define the relationship between PRU and hemoglobin and to elucidate whether the relationship, if any, is a true biological association or is just a laboratory error. METHODS: Through a comprehensive electronic and manual search, 10 studies were selected for the cohort level meta-analysis. Among 10 studies, we were able to retrieve the raw data of 5 studies, and a patient-level meta-analysis was performed. Potential publication bias was searched by funnel plot analysis and was actively adjusted, if present, by trim and fill method. RESULTS: The pooled analysis revealed a significant inverse correlation between PRU and hemoglobin (r=-0.349; P<.001; 10 studies with 4,793 patients). VerifyNow P2Y12 base unit, which reflects off-drug platelet reactivity, was also inversely correlated with hemoglobin (r=-0.526; P<.001; 8 studies with 4,395 patients). % Inhibition (r=0.081; P=.059; 6 studies with 3,832 patients) and ΔPRU (r=-0.037; P=.188; 5 studies with 3,521 patients) were not associated with hemoglobin. A significant inverse association between PRU and hemoglobin was also observed in the patient-level meta-analysis (3,533 patients pooled from 5 studies; r=-0.335; P<.001). Light transmission aggregometry (r=0.160; P=.072; 4 studies with 1,144 patients) and multiple electrode platelet aggregometry (r=-0.029; P=.394; 3 studies with 7,645 patients) showed no significant association with hemoglobin. CONCLUSIONS: A significant inverse association was observed between PRU and hemoglobin which is likely to be a laboratory error. Clinicians should be aware that this association might lead to wrong interpretation of the data.

Long-Term Prognostic Value of Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With and Without Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting.

The value of late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) for the prediction of functional recovery after surgical revascularization has been previously established. However, the impact of LGE-MRI on the long-term prognosis after coronary artery bypass grafting (CABG) remains incompletely understood. Therefore, we aimed to evaluate the long-term prognostic value of LGE-MRI, based on the presence or absence of left ventricular (LV) dysfunction, in patients with coronary artery disease undergoing CABG. One hundred forty-six consecutive patients underwent cine- and LGE-MRI before CABG. Adverse cardiac events included cardiac death, nonfatal myocardial infarction, heart failure, and unstable angina. A 3-year landmark analysis of the primary end point was also performed for patients surviving beyond 3 years after CABG. During a median follow-up of 9.4 years, 44 patients (30%) experienced adverse cardiac events. Although a LV ejection fraction <50% was associated only with adverse cardiac events at 3 years after CABG, LGE was associated with a worse outcome both at and beyond 3 years after CABG. In the overall study population, LGE presence (adjusted hazard ratio [HR] 2.58; p = 0.027), score (adjusted HR 1.06; p <0.001), and extent (adjusted HR 1.08; p <0.001) were independent predictors of adverse cardiac events. Moreover, in both the LV ejection fraction <50% and ≥50% groups, the LGE extent was an independent predictor of adverse cardiac events. In conclusion, our qualitative and quantitative analyses of LGE-MRI provide long-term prognostic information after surgical revascularization. The LGE extent was a strong predictor of adverse cardiac events, independent of the LV function.

Cigarette Smoking Does Not Enhance Clopidogrel Responsiveness After Adjusting VerifyNow P2Y12 Reaction Unit for the Influence of Hemoglobin Level.

OBJECTIVES: The authors performed this analysis to examine whether the enhanced clopidogrel responsiveness in current smokers is maintained after adjusting the influence of hemoglobin on VerifyNow P2Y12 reaction unit (PRU). BACKGROUND: PRU is consistently reported to be lower in current smokers. However, PRU has a significant inverse relationship with hemoglobin level, and smokers have higher hemoglobin levels. Because the association between PRU and hemoglobin is likely to be an in vitro phenomenon, we hypothesized that the observed difference in PRU between nonsmokers and current smokers is the result of confounding effect of hemoglobin rather than true difference in platelet reactivity. METHODS: Three cohorts were combined for the analysis (SNUBH [Seoul National University Bundang Hospital], n = 459; CILON-T [influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation], n = 715; HOST-ASSURE [Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen], n = 1,357). The final combined cohort consisted of 1,314 patients who underwent percutaneous coronary intervention and had VerifyNow P2Y12 assay results. General linear model (analysis of covariance) was used to control the effect of hemoglobin on PRU. RESULTS: A significant inverse correlation was observed between PRU and hemoglobin (r = -0.389; p < 0.001). Current smokers showed a significantly higher hemoglobin level (13.5 ± 1.6 vs. 14.4 ± 1.5; p < 0.001) but lower PRU level (230.1 ± 90.7 vs. 212.2 ± 83.6; p < 0.001). After adjusting the influence of hemoglobin on PRU, there was no difference in PRU between nonsmokers and current smokers (224.1 [95% confidence interval: 218.7 to 229.5] vs. 225.3 [95% confidence interval: 217.2 to 233.3]; p = 0.813). CONCLUSIONS: The observed difference in PRU between nonsmokers and current smokers is largely attributable to the difference in hemoglobin level. Enhanced clopidogrel responsiveness in cigarette smokers is not confirmed in this study and the concept of the smokers' paradox needs further validation.

Physiological and clinical relevance of anomalous right coronary artery originating from left sinus of Valsalva in adults.

OBJECTIVE: To examine physiological and clinical relevance of an anomalous right coronary artery originating from left sinus of Valsalva (right ACAOS) with interarterial course in adults. METHODS AND RESULTS: For physiological assessment, fractional flow reserve (FFR) during dobutamine challenge was measured in 37 consecutive adult patients with lone right ACAOS with interarterial course. At baseline, mean FFR was 0.91±0.06, declining to 0.89±0.06 upon dobutamine infusion (p<0.001). Dobutamine stress FFR was significant (≤0.8) in three patients (8.1%), two of whom were surgically treated. Following surgery, dobutamine stress FFR rose from 0.76 to 0.94 and 0.76 to 0.98. Remodelling index (r=0.583, p=0.002), minimal lumen area (diastole: r=0.580, p=0.002; systole: r=0.0618, p<0.001) and per cent area stenosis (r=-0.550, p=0.004), measured by intravascular ultrasound, correlated with dobutamine stress FFR. To assess the clinical relevance, follow-up data of 119 patients with lone right ACAOS with interarterial course were analysed retrospectively. Two deaths occurred during a median follow-up period of 4 years, for a mortality rate of 0.34 per 100 person-year. No instances of myocardial infarction were recorded and one patient did undergo surgical revascularisation in the course follow-up. CONCLUSIONS: Most instances of lone right ACAOS with interarterial course discovered in adults were physiologically insignificant and ran benign clinical courses. Conservative management may thus suffice in this setting if no definitive signs of myocardial ischaemia are evident.

Impact of smoking status on clinical outcomes after successful chronic total occlusion intervention: Korean national registry of CTO intervention.

OBJECTIVES: We sought to evaluate the effect of cigarette smoking on long-term outcomes after successful percutaneous coronary intervention for chronic total occlusion (CTO) lesions. BACKGROUND: Cigarette smoking promotes the progression of atherosclerosis but enhances the antiplatelet effect of clopidogrel. METHODS: The Korea National Registry of CTO Intervention included 2,167 patients with CTO lesions from 26 centers who were successfully revascularized with drug-eluting stents from 2007 to 2009. Thrombotic events were defined as the composite of cardiac death, nonfatal myocardial infarction, and stent thrombosis. RESULTS: Current-smokers had more favorable baseline characteristics such as a younger age and lower prevalence of hypertension and diabetes mellitus. At 1 year, current-smokers had a significantly lower thrombotic event rate (1.1% vs. 2.7%, P = 0.034), but a significantly higher target vessel revascularization (TVR) rate (7.2% vs. 4.2%, P = 0.017) compared with never-smokers. After adjustment, current-smoking was independently associated with a 72% decreased risk for thrombotic events, and 73% increased risk for TVR. CONCLUSIONS: In patients with a revascularized CTO lesion, cigarette smoking is associated with fewer thrombotic events but with a higher incidence of TVR. Patients with CTO may benefit from smoking cessation to reduce TVR in conjunction with the use of new more potent antiplatelet agents whose effect is independent of cigarette smoking to improve thrombotic events. © 2015 Wiley Periodicals, Inc.