J-shaped relationship between serum creatinine and mortality in Korean patients with acute heart failure.

BACKGROUND: Cachexia and sarcopenia are common among heart failure (HF) patients and are linked to poor outcomes. As serum creatinine levels are influenced by both renal function and muscle mass, our study aimed to investigate the relationship between serum creatinine levels and mortality in acute HF patients. METHODS: We enrolled 5198 consecutive acute HF patients from the Korea Acute Heart Failure (KorAHF) registry, excluding those on renal replacement therapy. Patients were categorized into five groups based on their discharge serum creatinine levels: low (< 0.6 mg/dL), reference (0.6-0.89 mg/dL), upper normal (0.9-1.19 mg/dL), high (1.2-1.49 mg/dL), and very high (≥ 1.5 mg/dL). The primary endpoint was post-discharge all-cause mortality. RESULTS: The mean creatinine level was 1.20 ± 0.88 mg/dL. Notably, 335 (6.4%) patients had serum creatinine levels < 0.6 mg/dL. These patients were younger (mean age, 67 years) and more likely to have a low BMI (< 18.5 kg/m2) compared to the reference group (15.3% vs. 6.4%). Over a median follow-up of 975 days, 1743 (34.8%) patients died. We observed a J-shaped relationship between serum creatinine levels and mortality, with both low and high levels associated with increased mortality. After adjusting for covariates, including age, sex, body mass index, diabetes, hypertension, smoking, malignancy, atrial fibrillation on electrocardiography, levels of C-reactive protein, sodium, hemoglobin, albumin, brain natriuretic peptide, de novo heart failure, use of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists, patients with serum creatinine levels < 0.6 mg/dL had a 33% higher risk of all-cause mortality (HR, 1.33; 95% CI, 1.06 to 1.66) compared to those with levels of 0.6-0.89 mg/dL. However, BUN, which is not affected by muscle metabolism, exhibited a linear relationship with mortality. CONCLUSIONS: Among acute HF patients, there exists a J-shaped relationship between discharge serum creatinine levels and mortality, highlighting the increased mortality risk in individuals with very low serum creatinine levels.

Anatomical study to determine a new approach to treat benign masses located in the anterior condyle region: a case report.

A 22-year-old male patient presented to the clinic with severe pain in the preauricular area with an inability to completely occlude the jaw. Facial computed tomography and magnetic resonance imaging revealed a well-defined lesion that was tentatively diagnosed as a benign tumor or cystic mass. Surgical approach of a lesion in the condyle is delicate and problematic as many vulnerable anatomical structures are present. There are several methods for surgery in this area. Typically, an extraoral approach is dangerous because of potential injuries to nerves and arteries. The intraoral approach also presents difficulties due to the lack of visibility and accessibility. On occasion, coronoidectomy may be performed. The goal here was to determine an easier and safer new surgical approach to the condyle. We reached the anterior part of the pterygoid plate in the same method as in Le Fort I surgery. From this point, through the external pterygoid muscle, approaching the anterior aspect of the condyle is relatively easy and safe, with minimal damage to the surrounding tissues. Pus was drained at the site, and the lesion was diagnosed as an abscess. Pain and inability to close the mouth resolved without recurrence.

Efficacy and safety of standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg in primary hypertension: A randomized, double-blind, active-controlled, multicenter phase 3 trial.

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are -19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and -11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.

Iron Deficiency in Korean Patients With Heart Failure.

BACKGROUND: Although iron deficiency (ID) is an important and treatable risk factor for heart failure (HF), data on ID are scarce in Asian patients with HF. Therefore, we sought to determine the prevalence and clinical characteristics of ID in hospitalized Korean patients with HF. METHODS: In this prospective, multicenter cohort study, 461 patients with acute HF seen at five tertiary centers from January to November 2019 in Korea were enrolled. ID was defined as serum ferritin < 100 µg/L or ferritin 100-299 µg/L in combination with transferrin saturation < 20%. RESULTS: The patients' mean age was 67.6 ± 14.9 years, and 61.8% were male. Among total 461 patients, ID was present in 248 patients (53.8%). The prevalence of ID was significantly higher in women than in men (65.3% vs. 47.3%, P < 0.001). In a multivariable logistic regression analysis, the independent predictors of ID were female sex (odds ratio [OR], 2.19; 95% confidence interval [CI], 1.47-3.30), valvular heart disease (OR, 2.10; 95% CI, 1.10-4.17), higher heart rate (OR, 1.10; 95% CI, 1.01-1.21), anemia (OR, 1.60; 95% CI, 1.07-2.40), and the use of clopidogrel (OR, 1.56; 95% CI, 1.00-2.45). Among women, the prevalence of ID did not significantly differ between younger and older women (< 65 years: 73.7% vs. ≥ 65 years: 63.0%, P = 0.222), those with low and high body mass index (BMI < 25 kg/m²: 66.2% vs. BMI ≥ 25 kg/m²: 69.6%, P = 0.703), or those with low and high natriuretic peptide (NP) levels (NP < median: 69.8% vs. NP ≥ median: 61.1%, P = 0.295). Only 0.2% patients with acute HF received intravenous iron supplementation in Korea. CONCLUSION: The prevalence of ID is high in hospitalized Korean patients with HF. Because ID cannot be diagnosed by clinical parameters, routine laboratory examinations are necessary to identify patients with ID. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04812873.

Neutrophil-to-lymphocyte ratio as a predictor of in-hospital complications and overall mortality in Takotsubo syndrome preceded by physical triggers.

BACKGROUND: Takotsubo syndrome (TTS) with physical triggers has worse short- and long-term clinical courses than those with emotional triggers. However, predictive factors associated with poor outcomes of TTS with physical triggers are unknown. METHODS: We included 231 patients identified as TTS preceded by physical triggers at two tertiary referral hospitals from 2010 to 2019. In-hospital complications (IHC)-a composite of malignant arrhythmia, need for mechanical circulatory support or mechanical ventilation, and in-hospital death-and overall mortality were retrospectively reviewed. The associations with clinical features were evaluated by multivariable logistic and Cox regression analyses. RESULTS: The mean age was 69.3 ± 11.6 years, and 85 (36.8%) were male. The in-hospital complications rate was 46.8%. During a median follow-up of 883 days, 96 (41.6%) had died, and overall mortality was 13.6% per patient-year. Higher neutrophil-to-lymphocyte ratio (NLR) was associated with a higher risk of IHC (area under the receiver operating characteristic curve = 0.73; positive and negative predictive value = 60.9% and 67.2% for NLR ≤ 12); odds ratio (OR) with 95% confidence interval (CI) was 1.03 (1.01-1.05), p = 0.010. Subsequently, higher NLR was also related to a greater risk of overall mortality; patients with high NLR (NLR > 12) exhibited poor long-term survival than those with low NLR (NLR ≤ 5): hazard ratio (95% CI), 3.70 (1.72-7.94) with p < 0.001. CONCLUSIONS: A high NLR at initial presentation is associated with an increased risk of IHC and overall mortality in TTS preceded by physical triggers. Given that the treatment of TTS is mainly supportive, intensive monitoring with careful follow-up would be warranted in patients with high NLR.

Dummy run quality assurance study in the Korean Radiation Oncology Group 19 - 09 multi-institutional prospective cohort study of breast cancer.

BACKGROUND: The Korean Radiation Oncology Group (KROG) 19 - 09 prospective cohort study aims to determine the effect of regional nodal irradiation on regional recurrence rates in ypN0 breast cancer patients. Dosimetric variations between radiotherapy (RT) plans of participating institutions may affect the clinical outcome of the study. We performed this study to assess inter-institutional dosimetric variations by dummy run. METHODS: Twelve participating institutions created RT plans for four clinical scenarios using computed tomography images of two dummy cases. Based on a reference structure set, we analyzed dose-volume histograms after collecting the RT plans. RESULTS: We found variations in dose distribution between institutions, especially in the regional nodal areas. Whole breast and regional nodal irradiation (WBI + RNI) plans had lower inter-institutional agreement and similarity for 95% isodose lines than WBI plans. Fleiss's kappa values, which were used to measure inter-institutional agreement for the 95% isodose lines, were 0.830 and 0.767 for the large and medium breast WBI plans, respectively, and 0.731 and 0.679 for the large and medium breast WBI + RNI plans, respectively. There were outliers in minimum dose delivered to 95% of the structure (D95%) of axillary level 1 among WBI plans and in D95% of the interpectoral region and axillary level 4 among WBI + RNI plans. CONCLUSION: We found inter-institutional and inter-case variations in radiation dose delivered to target volumes and organs at risk. As KROG 19 - 09 is a prospective cohort study, we accepted the dosimetric variation among the different institutions. Actual patient RT plan data should be collected to achieve reliable KROG 19 - 09 study results.

Smoking may be more harmful to vasospastic angina patients who take antiplatelet agents due to the interaction: Results of Korean prospective multi-center cohort.

BACKGROUND: The interaction between smoking and the use of antiplatelet agents on the prognosis of vasospastic angina (VA) is rarely investigated. METHODS: VA-Korea is a nation-wide multi-center registry with prospective design (n = 1812). The primary endpoint was the composite occurrence of acute coronary syndrome (ACS), symptomatic arrhythmia, and cardiac death. Log-rank test and Cox proportional hazard model were for statistical analysis. Also, we conducted interaction analysis in both additive and multiplicative scales between smoking and antiplatelet agents among VA patients. For additive scale interaction, relative excess risk due to interaction (RERI) was calculated and for multiplicative scale interaction, the ratio of hazard ratio (HR) was calculated. All statistical analysis conducted by Stata Ver 16.1. RESULTS: Patients who were smoking and using antiplatelet agents had the highest incidence rate in the primary composite outcome. The incidence rate was 3.49 per 1,000 person-month (95% CI: 2.30-5.30, log-rank test for primary outcome p = 0.017) and HR of smoking and using antiplatelet agents was 1.66 (95%CI: 0.98-2.81). The adjusted RERI of smoking and using antiplatelet agents was 1.10 (p = 0.009), and the adjusted ratio of HR of smoking and using antiplatelet agents was 3.32 (p = 0.019). The current study observed the interaction between smoking and using antiplatelet agents in both additive and multiplicative scales. CONCLUSIONS: Smoking was associated with higher rates of unfavorable clinical outcomes among VA patients taking antiplatelet agents. This suggested that VA patients, especially those using antiplatelet agents should quit smoking.

Practical guidance for P2Y12 inhibitors in acute myocardial infarction undergoing percutaneous coronary intervention.

AIMS: Potent P2Y12 inhibitors for dual antiplatelet therapy (DAPT) is crucial for managing acute myocardial infarction; however, the selection of drugs is based on limited clinical information such as age and body weight. The current study sought to develop and validate a new risk scoring system that can be used to guide the selection of potent P2Y12 inhibitors by balancing ischaemic benefit and bleeding risk. METHODS AND RESULTS: Derivation cohort of 10 687 patients who participated in the Korea Acute Myocardial Infarction Registry-National Institutes of Health study was used to construct a new scoring system. We combined the ischaemic and bleeding models to establish a simple clinical prediction score. Among the low score group (n = 1764), the observed bleeding risk (8.7% vs. 4.4%, P < 0.001) due to potent P2Y12 inhibitors exceeded ischaemic benefit (1.3% vs. 2.2%, P = 0.185) during 12 months. Conversely, the high score group (n = 1898) showed an overall benefit from taking potent P2Y12 inhibitors from the standpoint of observed ischaemic (17.1% vs. 8.6%, P < 0.001) and bleeding events (10.1% vs. 6.8%, P = 0.073). The performance of ischaemic [integrated area under the curve (iAUC) = 0.809] and bleeding model (iAUC = 0.655) was deemed to be acceptable. CONCLUSION: The new scoring system is a useful clinical tool for guiding DAPT by balancing ischaemic benefit and bleeding risk, especially among Asian populations. Further validation studies with other cohorts will be required to verify that the new system meets the needs of real clinical practice.

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.

Coronary artery bypass graft versus percutaneous coronary intervention in acute heart failure.

OBJECTIVE: Myocardial ischaemia is a leading cause of acute heart failure (AHF). However, optimal revascularisation strategies in AHF are unclear. We aimed to compare two revascularisation strategies, coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), in patients with AHF. METHODS: Among 5625 consecutive patients enrolled prospectively in the Korean Acute Heart Failure registry from March 2011 to February 2014, 717 patients who received CABG or PCI during the index hospitalisation for AHF were included in this analysis. We compared adverse outcomes (death, rehospitalisation for HF aggravation or cardiovascular causes, ischaemic stroke and a composite outcome of death and rehospitalisation for HF aggravation or cardiovascular causes) with the use of propensity score matching. RESULTS: For the propensity score-matched cohort with 190 patients, CABG had a lower risk of all-cause mortality than PCI (83 vs 147 deaths per 1000 patient-years; HR 0.57, 95% CI 0.34 to 0.96, p=0.033) during the median follow-up of 4 years. There was also a trend towards lower rates of rehospitalisation due to cardiovascular events or HF aggravation. Subgroup analysis revealed that the adverse outcomes were significantly lower in the CABG group than in PCI group, especially in patients with old age, three-vessel diseases, significant proximal left anterior descending artery disease and those without left main vessel disease or chronic total occlusion. CONCLUSIONS: Compared with PCI, CABG is associated with significant lower all-cause mortality in patients with AHF. Further studies should evaluate proper revascularisation strategies in AHF. CLINICAL TRIAL REGISTRATION: NCT01389843; Results.

Fimasartan for Remodeling after Myocardial Infarction.

An angiotensin receptor blocker (ARB) mitigates cardiac remodeling after myocardial infarction (MI). Here, we investigated the effect of fimasartan, a new ARB, on cardiac remodeling after MI. Sprague⁻Dawley rats were assigned into 3 groups: surgery only (sham group, n = 7), MI without (MI-only group, n = 13), and MI with fimasartan treatment (MI + Fima group, n = 16). MI was induced by the permanent ligation of the left anterior descending artery. Treatment with fimasartan (10 mg/kg) was initiated 24 h after MI and continued for 7 weeks. Rats in the MI + Fima group had a higher mean ejection fraction (66.3 ± 12.5% vs. 51.3 ± 14.8%, P = 0.002) and lower left ventricular end-diastolic diameter (9.14 ± 1.11 mm vs. 9.91 ± 1.43 mm, P = 0.045) than those in the MI-only group at 7 weeks after MI. The infarct size was lower in the MI + Fima than in the MI group (P < 0.05). A microarray analysis revealed that the expression of genes related to the lipid metabolism and mitochondrial membrane ion transporters were upregulated, and those involved in fibrosis and inflammation were downregulated by fimasartan. Fimasartan attenuates cardiac remodeling and dysfunction in rats after MI and may prevent the progression to heart failure after MI.

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.

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.

Association of potent P2Y12 blockers with ischemic and bleeding outcomes in non-ST-segment elevation myocardial infarction.

BACKGROUND: Potent P2Y12 blockers are preferred in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). However, the risk of bleeding remains a major concern. We assessed the association of potent P2Y12 blockers with ischemic and bleeding outcomes in patients with NSTEMI. METHODS: From the Korea Acute Myocardial Infarction Registry-National Institute of Health database, 4927 patients with NSTEMI receiving drug-eluting stents (DES) were divided into potent P2Y12 blocker (ticagrelor or prasugrel, n=901) and clopidogrel (n=3180) groups. Propensity-matched 12-month ischemic and bleeding events were compared. Patients who received anticoagulants or who discontinued P2Y12 blockers or switched between potent P2Y12 blockers and clopidogrel were excluded. RESULTS: In the overall population, patients at higher ischemic and bleeding risks more often received clopidogrel. After propensity matching (n=901 in each group), 12-month rates of major adverse cardiac and cerebrovascular events were lower (7.3% vs. 10.1%, p=0.038), but Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were higher (5.9% vs. 2.2%, p<0.001) with potent P2Y12 blockers. Twelve-month rates of death from any cause, MI, stroke, or TIMI major bleeding were not different. On multivariate analysis, 12-month risk of TIMI major or minor bleeding was higher with B2 or C lesion, potent P2Y12 blocker use, body weight <60kg, and lower with time to PCI <12h and radial artery access. CONCLUSIONS: In patients with NSTEMI receiving DES, potent P2Y12 blockers were associated with reduced ischemic but increased bleeding risk with similar net clinical benefits.

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.

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.

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.

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.

The effects of erythropoiesis stimulating therapy for anemia in chronic heart failure: A meta-analysis of randomized clinical trials.

BACKGROUND: Although anemia is common in chronic heart failure (CHF), the use of erythropoiesis stimulating agents (ESAs) in CHF patients remains controversial. In this meta-analysis, we sought to clarify the efficacy and safety of ESAs in anemic patients with CHF. METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, the U.S. National Institutes of Health registry of clinical trials. We included 13 randomized clinical trials (RCTs) in the meta-analysis. The co-primary outcome was all-cause mortality and rehospitalization. The safety analysis outcome was thromboembolic events. RESULTS: Preliminary analysis showed that ESA-treatment did not have any effect for all-cause mortality and rehospitalization. However, we revealed a significant small-study bias, and used the trim-and-fill method to reduce this bias. The summary effect of ESA-treatment was insignificant for all-cause mortality (risk ratio [RR] 0.91, 95% confidence interval [CI] 0.59-1.42, p=0.69) and for rehospitalization (RR 0.91, 95% CI 0.67-1.23, p=0.53). Regarding symptoms, ESA-treatment improved dyspnea (NYHA grade improvement: 1.63, 95% CI 0.65-2.62, p<0.001) and quality-of-life measured by subjective questionnaires. However, in safety analysis, ESAs increased the over-all risk for thromboembolic events (RR 1.28, 95% CI 1.03-1.58, p=0.026), however, no specific increase was observed in severe thromboembolic events. Subgroup analysis showed no difference in ESA-treatment according to the type of ESAs (darbepoetin vs. erythropoietin) and between studies of different follow-up durations (<6months or ≥6months). CONCLUSION: Among CHF patients with anemia, ESA-treatment has a neutral effect on all-cause mortality and rehospitalization and improves symptoms, but has harmful effects on thromboembolic events.