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Background: Intermediate lesions (ILs) are challenging to treat. This study aimed to assess the impact of ILs on long-term clinical outcomes in patients with significant coronary lesions (SLs).Methods: This was a non-randomized, retrospective, single-center study. The study subjects were patients with SL (n=403, Men=249), followed up for 10 years (118.5±5.5 months), and divided into 2 groups according to the presence of IL (IL (-) and IL (+) groups with 192 and 211 patients, respectively). The primary outcome was the occurrence of major adverse cardiovascular events (MACE), which included all-cause death, myocardial infarction (MI), stroke, and revascularization (RVSC).Results: There were no significant differences in MACEs between the IL (-) and IL (+) groups (death, 7.8% vs. 12.3%; MI, 0.0% vs. 2.4%; stroke, 5.7% vs. 6.6%; and RVSC, 19.8% vs. 24.6%). However, the RVSC rate related to IL was lower (5.2% vs. 13.2%) than that related to stented lesions in all subjects. The important predictors for total MACEs in all subjects were the number of ILs and ejection fraction. The predictors of total RVSC events were IL location (right coronary artery [RCA]) and hypertension. The predictor of IL-related RVSC was the number of ILs.Conclusion: Ten-year clinical outcomes of IL were excellent and better than those of stented lesions in patients with SL. Thus, ILs can be managed with optimal medical treatment with acceptable clinical outcomes in patients with SL. The increased risk of MACE in patients with multiple ILs and ILS in the RCA should be carefully managed.

The natural history of intermediate coronary lesions (30 to 70% angiographic stenosis) and the prognostic predictors in predicting very long-term clinical outcomes is unknown.Patients (n = 82, mean 60 years old) with intermediate non-culprit coronary lesions (NCL, n = 86), evaluated by virtual histology-intravascular ultrasound (VH-IVUS), were followed for 10 years. Major adverse cardiovascular events (MACE; all-cause death, myocardial infarction, stroke, and revascularization) were collected over follow-up period and stratified by culprit lesion (CL)-related, NCL-related and indeterminate/unrelated to CL or NCL lesions. NCL-related MACE was further stratified into intermediate and minimal NCL-related events.Twenty two (25.6%) out of 86 intermediate NCL were associated with MACE in 20/82 (24.4%) study patients. Ten-year cumulative intermediate NCL-related MACE rate was twice (25.6% vs. 12.8%) compared to treated culprit lesion (CL)-related MACE. Ten-year cumulative revascularization rate of the intermediate NCL lesions was similar (17.4% vs. 15.1%) to those of CL, but higher than that of minimal (stenosed30% at baseline) NCL (8.1%). Important intermediate NCL VH-IVUS predictor for MACE was area stenosis ≥50%, and for revascularization were percent diameter stenosis, plaque burden ≥70%, and fibrofatty area.Ten-year MACE rate of intermediate NCL was double that of CL and ten-year revascularization rate of intermediate NCL was similar or slightly higher than that of CL. VH-IVUS may play an important role in determining the very long-term clinical outcomes in patients with intermediate NCL. This study suggests that Intermediate NCL can be safely followed up in terms of revascularization risk.

Patient: Female, 21-year-old Final Diagnosis: Toxocariasis-associated acute perimyocarditis with cardiogenic shock Symptoms: Dizziness • epigastric pain • headache • vomiting Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Rare disease Background: Toxocariasis is an infection due to ingestion of the helminth parasite larvae found in dogs (Toxocara canis) or cats (Toxocara cati). Symptoms vary from being asymptomatic to shock, depending on the organ invaded by the parasite. However, cardiac involvement with shock in toxocariasis is very rare. Case Report: A 21-year-old woman without any history of underlying conditions visited the Emergency Department because of epigastric pain, vomiting, headache, and dizziness. Her blood pressure was 80/60 mmHg. Computed tomography (CT) of the brain showed no abnormal lesions. The abdominal-pelvic CT with contrast showed right pleural effusion, pericardial effusion, and focal ascites in the pelvic cavity. Laboratory tests revealed an elevation of eosinophils (40%) and cardiac enzymes (creatinine kinase-MB 27.6 ng/mL, high-sensitive cardiac troponin T 1.21 ng/mL). The transthoracic echocardiogram showed left ventricular systolic dysfunction (ejection fraction 44%) and moderate pericardial effusion. She was presumptively diagnosed with hypereosinophilic perimyocarditis and admitted to the Intensive Care Unit for shock. The pericardial effusion increased during treatment; therefore, pericardiocentesis was performed. Analysis of the pericardial effusion showed eosinophilia (eosinophils 90%) and the serologic test for parasites was positive for Toxocara and Sparganum. A combination therapy of albendazole, praziquantel, and corticosteroid resolved the pericardial effusion and the peripheral blood eosinophil count normalized. She was discharged without any other complications. At Outpatient Clinic follow-ups and observations over the next 2 years there were no abnormal findings, including pericardial effusion or eosinophilia. Conclusions: Toxocariasis rarely causes perimyocarditis with cardiogenic shock. Patients who present with pericardial effusion and eosinophilia need to be evaluated for parasitic infection.

Background Despite the chronicled success of low-density lipoprotein cholesterol (LDLc)-lowering statin therapy, substantial residual cardiovascular (CV) disease risk remains a problem worldwide, highlighting the need to for combination therapies targeting non-LDLc factors, such as with fenofibrate. Methods/design The STAFENO trial is a prospective, randomized, open-label, multi-center trial to compare the effect of statin plus fenofibrate with statin alone on the reduction and stabilization of plaque in non-diabetic, combined dyslipidemia patients with non-intervened, intermediate coronary artery disease (CAD) using virtual histology-intravascular ultrasound at 12 months. A total of 106 eligible patients are planned to be randomized to receive either a combination therapy (rosuvastatin 10 mg plus fenofibrate 160 mg/day) or monotherapy (rosuvastatin 10 mg/day) for 12 months. The primary endpoint of this study is the percentage change in the necrotic core volume. Secondary endpoints include changes in tissue characteristics and 1-year major CV events, including all-cause mortality, CV mortality, nonfatal myocardial infarction, stroke, and revascularization of the intervened and non-intervened lesions. Discussion The STAFENO trial will address whether combination treatment of statin and fenofibrate has an additive beneficial effect compared to statin alone on the reduction and stabilization of plaque and CV events in non-diabetic, combined dyslipidemia patients with non-intervened intermediate CAD. Trial registration ClinicalTrials.gov, NCT02232360. Registered 9 February 2014. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0004ULE&selectaction=Edit&uid=U00023SZ&ts=2&cx=juppd2

Background: The mechanism of in-stent restenosis (ISR) is multifactorial, which includes biological, mechanical and technical factors. This study hypothesized that increased inflammatory reaction, which is known to be an important atherosclerotic process, at a culprit lesion may lead to higher restenosis rates. Methods: The study population consisted of 241 patients who had undergone percutaneous coronary intervention with virtual histology-intravascular ultrasound (VH-IVUS) and a 9-month follow-up coronary angiography. Compared herein is the coronary plaque composition between patients with ISR and those without ISR. Results: Patients with ISR (n = 27) were likely to be older (66.2 ± 9.5 years vs. 58.7 ± 11.7 years, p = 0.002) and have higher levels of high-sensitivity C-reactive protein (hs-CRP, 1.60 ± 3.59 mg/dL vs. 0.31 ± 0.76 mg/dL, p < 0.001) than those without ISR (n = 214). VH-IVUS examination showed that percent necrotic core volume (14.3 ± 8.7% vs. 19.5 ± 9.1%, p = 0.005) was higher in those without ISR than those with ISR. Multivariate analysis revealed that hs-CRP (odds ratio [OR] 3.334, 95% con­fidence interval [CI] 1.158–9.596, p = 0.026) and age (OR 3.557, 95% CI 1.242–10.192, p = 0.018) were associated with ISR. Conclusions: This study suggests that ISR is not associated with baseline coronary plaque composition but is associated with old age and increased expression of the inflammatory marker of hs-CRP. (Cardiol J 2018; 25, 1: 7–13)

Hypercholesterolemia is a major risk factor for atherosclerosis. Remaining challenges in the management of atherosclerosis necessitate development of animal models that mimic human pathophysiology. We characterized a novel mutant pig model with DNA transposition of D374Y gain-of-function (GOF) cDNA of chimp proprotein convertase subtilisin/kexin type-9 (PCSK9), and tested the hypothesis that it would develop peripheral vascular remodeling and target organ injury in the kidney. Wild-type or PCSK9-GOF Ossabaw miniature pigs fed a standard or atherogenic diet (AD) (n = 7 each) were studied in vivo after 3 and 6 months of diet. Single-kidney hemodynamics and function were studied using multidetector computed tomography and kidney oxygenation by blood oxygen level-dependent magnetic resonance imaging. The renal artery was evaluated by intravascular ultrasound, aortic stiffness by multidetector computed tomography, and kidney stiffness by magnetic resonance elastography. Subsequent ex vivo studies included the renal artery endothelial function and morphology of abdominal aorta, renal, and femoral arteries by histology. Compared with wild type, PCSK9-GOF pigs had elevated cholesterol, triglyceride, and blood pressure levels at 3 and 6 months. Kidney stiffness increased in GOF groups, but aortic stiffness only in GOF-AD. Hypoxia, intrarenal fat deposition, oxidative stress, and fibrosis were observed in both GOF groups, whereas kidney function remained unchanged. Peripheral arteries in GOF groups showed medial thickening and development of atheromatous plaques. Renal endothelial function was impaired only in GOF-AD. Therefore, the PCSK9-GOF mutation induces rapid development of atherosclerosis in peripheral vessels of Ossabaw pigs, which is exacerbated by a high-cholesterol diet. This model may be useful for preclinical studies of atherosclerosis.

Hypertension has been associated with atherosclerosis and cardiovascular disease. Carotid intima media thickness is increased in hypertensive patients. But, the correlation between carotid intima media thickness and antihypertensive agents is still uncertain. Therefore, we investigated carotid intima media thickness based on types of antihypertensive agents. 1809 patients were enrolled in this study and it showed that 1079 hypertensive patients had thicker carotid intima media thickness than non-hypertensive patients, with carotid intima media thicknesses of (0.72 ± 17 mm vs 0.64 ± 15 mm, P

We evaluated the relationship among BMI, carotid sonographic findings, and long-term (5 years) cardiovascular events in Asian patients with coronary artery disease (CAD).The study population consisted of 1342 consecutive patients with CAD, who were stratified into four groups according to weight status, as defined by the WHO for the Asian population: underweight (group I: BMI18.5 kg/m, n=38); normal weight (group II: 18.5≤BMI23.5 kg/m, n=352); overweight (group III: 23.5≤BMI27.5 kg/m, n=700); and obese (group IV: BMI≥27.5 kg/m, n=252). All patients underwent carotid ultrasonography. Multivariate analysis was performed to identify predictors of long-term mortality, and the results were expressed in terms of hazard ratio (HR) with 95% confidence interval (95% CI).Compared with the other groups, groups I and II included older patients and had a higher incidence of multivessel CAD, carotid plaque (group I: 42.1%; group II: 42.3%; group III: 27.9%; group IV: 24.6%; P=0.003), and major cardiovascular events including cardiac death, acute myocardial infarction, and stroke. In multivariate analysis, old age, lower ejection fraction, high carotid intima-media thickness, and presence of carotid plaque were positive independent predictors for mortality, whereas BMI was a negative independent predictor (group II: HR=0.28, 95% CI=0.14-0.57, P0.001; group III: HR=0.26, 95% CI=0.13-0.51, P0.001; group IV: HR=0.08, 95% CI=0.03-0.22, P0.001).In patients with CAD, underweight and normal-weight status was associated with higher long-term mortality rates and incidence of major cardiovascular events, suggesting that the obesity paradox is also manifested in Asian patients with CAD.

Background It is uncertain whether the coronary lesion with intermediate stenosis is more likely to cause cardiovascular events than a normal or minimal lesion. We conducted a single-center, prospective cohort study to identify long-term clinical outcomes of patients with untreated non-culprit intermediate lesion and evaluate its predictor of cardiovascular events by using virtual histology-intravascular ultrasound (VH-IVUS). Methods Subjects with non-culprit intermediate lesion underwent VH-IVUS were prospectively registered after percutaneous coronary intervention at the culprit lesion. Intermediate lesion was defined as 30 to 70% stenosis in coronary angiography and primary outcome was an occurrence of major adverse cardiovascular events (MACE) defined as all-cause death, intermediate lesion revascularization (InLR), minimal lesion revascularization (MnLR, unplanned revascularization elsewhere in the target vessel or in other coronary arteries which looked normal or minimal stenosis), cerebrovascular events, or non-fatal myocardial infarction (MI). The mean follow-up period was 4.2 years. Results Total 25 MACE, approximately 7% incidence annually, were identified during a follow-up period in 86 patients with 89 intermediate lesions. InLR (n = 13) was a most common event followed by MnLR (n = 6), non-fatal MI (n = 4), all-cause death (n = 3), and cerebrovascular events (n = 1). Diameter stenosis (OR 1.07, 95% CI 1.01–1.12, p = 0.015), plaque burden (PB, OR 1.07, 95% CI 1.00–1.15, p = 0.040), fibrofatty area (FFA, OR 1.61, 95% CI 1.10–2.38, p = 0.016), PB ≥ 70% (OR 3.93, 95% CI 1.28–12.07, p = 0.018), and area stenosis ≥ 50% (OR 2.94, 95% CI 1.01–8.56, p = 0.042) showed significant relationships with an occurrence of MACE. In multivariable Cox-proportional hazard analysis, FFA in intermediate lesion was an only independent predictor of MACE (HR 1.36, 95% CI 1.05–1.77, p = 0.019). Conclusions Untreated intermediate lesions had a significantly higher chance for requiring revascularization compared with a normal or minimal lesion. And also, a large FFA in intermediate lesion was a significant predictor of cardiovascular events and which finding was mainly driven by coronary-related events, in particularly intermediate lesion progression.

Background FFR of deferred PCI lesions can predict future cardiovascular events. However, the prognostic utility of FFR remains unclear in diabetic patients in view of the potential impact of the diffuse nature of vascular disease process. We aimed to study the relation between fractional flow reserve (FFR) values and long-term outcomes of diabetic and non-diabetic patients with deferred percutaneous coronary intervention (PCI). Methods Patients with FFR assessment and deferred PCI (n=630) were enrolled and stratified according to diabetes mellitus (DM) status and FFR values. Patients were followed over a median of 39months. Cox proportional hazard regression models were used to analyze the association between clinical endpoints and clinical factors such as DM and FFR. Results In non-diabetics (n=450), higher FFR values were associated with less cardiovascular events (hazard ratio (HR) for death and myocardial infarction (MI) [95% confidence interval (CI)], 0.61[0.44 to 0.86] per 0.1 increase in FFR, p=0.007; HR for revascularization [95%CI], 0.66[0.49 to 0.9] per 0.1 increase in FFR, p=0.006). In diabetics (n=180), there was no difference in death and MI across the range of FFR values. Among those patients with an FFR >0.85, diabetics had a more than two-fold higher risk of death and MI than non-diabetics (HR [95% CI], 2.20 [1.19 to 4.01], p=0.015). Conclusion Among non-diabetic patients with deferred PCI, a higher FFR was associated with lower rates of death, MI and revascularization. On the contrary in diabetic patients with deferred revascularization, FFR was not able to differentiate the risk of cardiovascular events.

It is uncertain whether the coronary lesion with intermediate stenosis is more likely to cause cardiovascular events than a normal or minimal lesion. We conducted a single-center, prospective cohort study to identify long-term clinical outcomes of patients with the untreated non-culprit intermediate

Aims The current study was designed to test that vasa vasorum (VV) plays a role in the progression of cardiac allograft vasculopathy (CAV) in patients with heart transplantation (HTX). Methods and results Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) were performed in the left anterior descending artery in 19 segments of 19 HTX patients (median 2.1 years from HTX). Each segment is composed of both the continuous lesions: (i) CAV area: intimal thickness >0.5 mm with 5 mm length and (ii) VV area: intimal thickness ≤0.5 mm with 5 mm length. The per cent VV volume (VV volume/vessel volume × 100, %VV) was evaluated in the VV area with OCT (in CAV area VV cannot be assessed because of limited penetration power of OCT). A year later, the association between the baseline %VV and the change in per cent plaque volume (plaque volume/vessel volume × 100, %PV) was evaluated with IVUS. To a normal distribution, Δ%PV (follow-up %PV–initial %PV) was undergone square root transformation. The correlations between the %VV at baseline study and square root-Δ%PV were significant both in the CAV area and in the VV area ( r = 0.787, P < 0.001 and r = 0.701, P < 0.001, respectively). In multivariable analysis, only the %VV was significantly correlated with square root-Δ%PV in both areas. Conclusion The current study demonstrated a significant association between the VV volume and the progression of plaque volume in both the CAV area and the VV area. Thus, VV may be a potential predictor and possible therapeutic target to attenuate CAV. [10.1093/ehjci/jev318][1] [1]: /lookup/doi/10.1093/ehjci/jev318

Endothelial dysfunction is a key step in the initiation and progression of atherosclerosis and subsequent cardiovascular complications. We examined whether peripheral endothelial function, as assessed by fingertip reactive hyperemia-peripheral arterial tonometry (RH-PAT), can provide additional clinical value to traditional risk factors for cardiovascular diseases in predicting coronary artery disease (CAD).We included 118 stable patients who were referred for coronary angiography for chest pain evaluation or due to abnormal stress test results. A natural logarithmic value of the RH-PAT index (Ln_RHI) was obtained before cardiac catheterization by an independent operator. Significant CAD was defined as luminal stenosis of at least 70% (≥50% at left main) and/or fractional flow reserve of up to 0.80 in one or more major coronary arteries or their major branches.Levels of Ln_RHI were significantly lower in patients with CAD (n=60) compared with patients without CAD (n=58; 0.69±0.29 vs. 0.88±0.27, P0.001). Ln_RHI was significantly associated with CAD independent from traditional risk factors (odds ratio for a 0.1 decrease in Ln_RHI=1.25, 95% confidence interval: 1.04-1.52, P=0.01). The net reclassification index was improved when Ln_RHI was added to traditional risk factors (0.62, 95% confidence interval: 0.27-0.97, P=0.001).Peripheral endothelial function, as assessed by RH-PAT, improved risk stratification when added to traditional risk factors. RH-PAT is potentially useful for identifying patients at high risk for CAD.

Ischemic heart disease is the leading cause of morbidity and mortality throughout the world. Many clinical trials have suggested that lifestyle and pharmacologic interventions are effective in attenuating atherosclerotic disease progression and events development. However, an individualized approach with careful consideration to comprehensive vascular health is necessary to perform successful intervention strategies. Endothelial dysfunction plays a pivotal role in the early stage of atherosclerosis and is also associated with plaque progression and occurrence of atherosclerotic complications. The assessment of endothelial function provides us with important information about individual patient risk, progress and vulnerability of disease, and guidance of therapy. Thus, the application of endothelial function assessment might enable clinicians to innovate ideal individualized medicine. In this review, we summarize the current knowledge on the impact of pharmacological therapies for atherosclerotic cardiovascular disease on endothelial dysfunction, and argue for the utility of non-invasive assessment of endothelial function aiming at individualized medicine.

Over the past decades, secondary prevention of cardiovascular (CV) disease has improved and considerably reduced mortality rates. However, there remains a high-rate of new or recurrent CV events in those with established atherosclerotic vascular diseases. Although most of the prevailing therapies target the conventional risk factors, there is notable interindividual heterogeneity in adaptation to risk factors and response to therapies, which affects efficacy. It is desirable to have a methodology for directly assessing the functional significance of atherogenesis, and for managing individual patients based on their comprehensive vascular health. Endothelial function plays a pivotal role in all stages of atherosclerosis, from initiation to atherothrombotic complication. Endothelial function reflects the integrated effect of all the atherogenic and atheroprotective factors present in an individual, and is therefore regarded as an index of active disease process and a significant risk factor for future CV events. Moreover, improvement in endothelial function is associated with decreased risk of CV events, even in the secondary prevention setting. The introduction of endothelial function assessment into clinical practice may trigger the development of a more tailored and personalized medicine and improve patient outcomes. In this review, we summarize current knowledge on the contribution of endothelial dysfunction to atherosclerotic CV disease in the secondary prevention setting. Finally, we focus on the potential of an endothelial function-guided management strategy in secondary prevention.

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.

Background: The associations between statin and coronary plaque compositional changes were re­ported according to the use of high dose or not. An evaluation of the impact of low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL by using real world dosages of statin on coronary plaque composition was undertaken. Methods: The study subjects consisted of 61 patients (mean 59.9 years old, 45 males) who underwent percutaneous coronary intervention, baseline and follow-up (F/U; mean 8.4 months) virtual histology- -intravascular ultrasound (VH-IVUS) examination. Change of plaque composition at peri-stent area, which was selected in order to measure the identical site at F/U study, was compared according to the F/U LDL-C level. Results: Body mass index, prevalence of dyslipidemia, baseline total cholesterol and baseline LDL-C were significantly lower in F/U LDL-C < 70 mg/dL group (14 segments in 10 patients) than F/U LDL-C ≥ 70 mg/dL group (79 segments in 51 patients). F/U high-density lipoprotein cholesterol (HDL-C, OR 1.06, 95% CI 1.00–1.11, p = 0.054) and F/U LDL-C < 70 mg/dL (OR 3.43, 95% CI 0.97–12.17, p = 0.056) showed strong tendency of regression of necrotic core volume (NCV) ≥ 10%. In multivariable logis­tic regression analysis, F/U HDL-C (OR 1.07, 95% CI 1.01–1.14, p = 0.020) and F/U LDL-C < 70 mg/dL (OR 8.02, 95% CI 1.58–40.68, p = 0.012) were the independent factors for regression of NCV ≥ 10%. Conclusions: Follow-up LDL-C level < 70 mg/dL with any types of statins and increase of HDL-C were associated with regression of NCV ≥ 10% in patients with coronary artery disease.

Images made from ultrasound are based on the transmission and reception of sound waves reflected from tissue. Ultrasound transducers use a piezoelectric crystal (usually a ceramic) to generate and receive ultrasound waves. The piezoelectric crystal material has the property of expanding its crystal size through electrical current. When an alternating electric current is applied, the crystal alternately compressed and expands, generating an ultrasound wave [1]. The frequency of sound wave depends on the nature and thickness of the piezoelectric material. When reflected ultrasound waves return to the transducer, an electric current is generated and converted into the image.

Takotsubo cardiomyopathy (TTC) is a syndrome characterized by transient regional systolic dysfunction of the left ventricle (LV). However, far fewer reports focused on the prevalence of left ventricular diastolic function (DF) and its impact on an adverse prognosis in TTC.From January 2005 to October 2014, 205 consecutive TTC patients (mean age, 70±12years; 95% female) were studied. The patients underwent transthoracic echocardiography at the acute phase and recovery phase (mean, 38±16days after admission).DF was labeled as normal, mild, moderate and severe. At the acute phase, Abnormal DF was present in 108 patients (53%), and left ventricular ejection fraction (LVEF)50% in 156 patients (76%). At the recovery phase, DF was unchanged for 104 patients (51%), 44 patients (21%) had worsened, 57 patients (28%) had improved in DF grade. 25 patients (12%) had an LVEF50%. During 2years of follow-up, 34 patients developed clinical adverse events. Kaplan-Meier analysis estimated that the subgroup with unimproved DF and LVEF50% at recovery phase had the worst 2-year survival. In multivariable analysis, unimproved DF with LVEF50% and heart rate (HR) remained predictors of clinical adverse events.The current study demonstrated that consideration of both change of DF and LVEF allows identification of subgroups with divergent long-term prognoses in patients with TTC, and may indicate the need for a different management in the high-risk TTC patients.

Background The present study investigated whether cilostazol can eliminate adverse smoking outcome after percutaneous coronary intervention (PCI). Methods and results A total of 914 patients with successful drug-eluting stent (DES) implantation were randomly assigned to dual antiplatelet therapy (DAT; aspirin and clopidogrel, n=457) or to triple antiplatelet therapy (TAT; DAT with cilostazol, n=457). The effect of smoking on 2-year major adverse cardio/cerebrovascular events (MACCE) in both the TAT and DAT groups was evaluated. Total MACCE were not significantly different between the 2 anti-platelet regimens (9.8% in TAT vs. 11.4% in DAT groups, P=0.45), but the adverse effects of smoking on clinical outcome were different between DAT vs. TAT. Current smokers had a higher prevalence of MACCE than non-smokers in the DAT group (16.7% vs. 9.5%, P=0.04). In the TAT group, however, the adverse effect of smoking was abolished (9.2% vs. 10.1%, P=0.85). Regarding the effects of smoking on the antiplatelet effects of DAT or TAT, post-treatment platelet reactivity (in P2Y12 reaction units; PRU) in current smokers was not significantly lower than that in non-smokers in the DAT group, whereas, in the TAT group, it was significantly lower than that of non-smokers (189±88 vs. 216±89 PRU, P=0.01). Conclusions Adverse clinical effects of smoking may be eliminated by the addition of cilostazol to DAT after DES implantation. This may be due to the stimulation of cilostazol's antiplatelet effects by smoking.

Vasospastic angina (VSA) is a variant form of angina in which chest pain typically appears without provocation, is accompanied by transient ST-segment elevation, and usually resolves spontaneously or with rapid-acting nitroglycerin. Although VSA usually occurs in angiographically normal or near

One of the leading causes of morbidity and mortality, acute coronary syndrome (ACS) often is caused by plaque rupture or erosion. It is, therefore, understandable that ongoing studies attempt to detect vulnerable plaque to understand the mechanism of plaque rupture and develop tools to predict

Background and Objectives It is unclear which plaque component is related with long-term clinical outcomes in patients with coronary artery occlusive disease (CAOD). We assessed the relationship between plaque compositions and long-term clinical outcomes in those patients. Subjects and Methods The study subjects consisted of 339 consecutive patients (mean 61.7±12.2 years old, 239 males) who underwent coronary angiogram and a virtual histology-intravascular ultrasound examination. Major adverse cardiac and cerebrovascular events (MACCE), including all-cause death, non-fatal myocardial infarction, cerebrovascular events, and target vessel revascularization were evaluated during a mean 28-month follow-up period. Results Patients with high fibrofatty volume (FFV, >8.90 mm3, n=169) had a higher incidence of MACCE (25.4% vs. 14.7%, p=0.015), male sex (75.7% vs. 65.3%, p=0.043), acute coronary syndrome (53.3% vs. 35.9%, p=0.002), multivessel disease (62.7% vs. 41.8%, p

Background The mechanisms of atrial fibrillation (AF) are highly divergent. The prevalence of AF increases significantly with age, and underling mechanisms might vary with age. Endothelial dysfunction may be associated with AF and atrial arrhythmia recurrence after catheter ablation. We tested the hypothesis that the impact of endothelial dysfunction on arrhythmia recurrence following catheter ablation is age dependent. Methods and Results This study enrolled 92 participants with AF undergoing catheter ablation. Endothelial function was assessed by peripheral arterial tonometry before ablation, and the natural logarithmic transformation of reactive hyperemia index was calculated. Endothelial dysfunction was defined as a natural logarithmic transformation of reactive hyperemia index P =0.029) and any atrial arrhythmia ( P =0.015), and the risk associated with endothelial dysfunction for arrhythmia recurrence was higher in younger versus older participants. Participants were divided into 2 age groups at a threshold of 60 years. Among participants aged ≤60 years, multivariate Cox proportional hazards analysis revealed the independent association between endothelial dysfunction and increased risk of arrhythmia recurrence (hazard ratio for AF 4.18 [95% CI 1.33–15.82], P =0.014, and for any atrial arrhythmia 3.62 [95% CI 1.29–11.81], P =0.014). Kaplan–Meier analysis showed that participants with endothelial dysfunction had significantly higher rates of recurrence of AF ( P =0.01) and any atrial arrhythmia ( P =0.002). Conclusions The risk associated with endothelial dysfunction for arrhythmia recurrence following catheter ablation was age dependent and was higher in younger participants.

Background The study compared downstream coronary and conduit disease progression in the left anterior descending coronary artery treated with coronary artery bypass grafting using the left internal mammary artery ( LIMA ) versus percutaneous coronary intervention with bare metal stent ( BMS ) or drug eluting stent ( DES ). Methods and Results A total of 12 301 consecutive patients underwent isolated primary coronary revascularization, of which 2386 met our inclusion criteria (Percutaneous coronary intervention, n=1450; coronary artery bypass grafting, n=936). Propensity score analysis matched 628 patients, of which 468 were treated to the left anterior descending with coronary artery bypass grafting with LIMA (n=314), percutaneous coronary intervention with BMS (n=94), and DES (n=60). Coronary angiograms were analyzed by quantitative coronary angiography ( QCA ; n=433). Cumulative downstream coronary and conduit disease progression were estimated by Kaplan–Meier method and effect of treatment type by Cox proportional hazard models. Patients treated with LIMA had significantly lower risk of downstream coronary disease progression at follow‐up angiogram compared with BMS and DES (hazard ratio [ HR ] [95% CI ], 0.34; [0.20–0.59]; P =0.0002; and HR [95% CI ], 0.39; [0.20–0.79]; P =0.01, respectively). LIMA was associated with a lower risk of conduit disease progression compared to BMS and DES ( HR [95% CI ], 0.18; [0.12–0.28]; P HR [95% CI ], 0.27; [0.16–0.46]; P BMS was associated with higher HR for downstream coronary and conduit disease progression compared with DES , but the difference did not reach statistical significance ( HR [95% CI], 1.13; [0.57–2.36]; P =0.73; and HR [95% CI ], 1.46; [0.88–2.50]; P =0.14, respectively). Conclusions LIMA grafting to left anterior descending is associated with significantly lower risk of downstream coronary and conduit disease progression compared to percutaneous coronary intervention with BMS and DES .

Coronary artery anomaly has been reported from 0.6% to 1.2% in routine angiographic series. Moreover, single coronary artery is one of the rarest anomalies among coronary anomalies. Although patients with coronary anomalies are usually asymptomatic, they may also be associated with myocardial ischemia, ventricular fibrillation, syncope, congestive heart failure, and sudden death. We report two similar cases of single coronary artery anomaly with right coronary artery (RCA) arising both from the proximal left anterior descending artery for proximal RCA and left circumflex artery for distal RCA.

Objective: We evaluated the impact of diabetes mellitus (DM) and DM control status on each layers of carotid artery in asymptomatic population. Methods: This is an observational cohort study consisted of 1,479 patients. The carotid images were sent to the Korea Research Institute of Standards and Science for core laboratory analysis using specialized software which can measure intima and media thickness respectively. Results: DM patients (n=634, 42.9%) were likely to be older, higher prevalence of male, hypertension and dyslipidemia, and higher creatinine level than non-DM patients (n=845, 57.1%). There was no significant demographic difference according to DM control status in DM patients. DM patients showed higher carotid intima-media thickness (CIMT, 0.70 ± 0.15 mm vs. 0.66 ± 0.16 mm, p

BackgroundEndothelial dysfunction plays a pivotal role in cardiovascular disease progression, and is associated with adverse events. The purpose of this systematic review and meta‐analysis was to i...

Objectives We aimed to test whether cilostazol has beneficial effects in the real-world patients treated with intracoronary drug-eluting stents (DES). Background The addition of cilostazol on the conventional dual antiplatelet therapy has been reported to reduce platelet reactivity and to improve clinical outcomes after percutaneous coronary intervention in previous studies. Methods In a randomized multicenter trial, we enrolled 960 patients who received DES. They were randomized to receive either dual antiplatelet therapy (DAT) (aspirin and clopidogrel) or triple antiplatelet therapy (TAT) (aspirin, clopidogrel, and cilostazol) for 6 months. Primary end point was the composite of cardiac death, nonfatal myocardial infarction, ischemic stroke, or target lesion revascularization (TLR). Secondary end points were P2Y 12 reaction unit (PRU) measured with the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) at discharge and at 6 months after the index procedure. All-cause death, stent thrombosis, and each component of the primary end point at 6 months were other secondary end points. Analysis was done on an intention-to-treat basis. Results At 6 months' follow-up, there was no difference in the primary end point between the 2 groups (8.5% in TAT vs. 9.2% in DAT, p = 0.74). In secondary end point analysis, the TAT group achieved lower PRU levels than the DAT group both at discharge (206.6 ± 90.3 PRU vs. 232.2 ± 80.3 PRU, p Conclusions Despite the greater reduction of platelet reactivity by addition of cilostazol to conventional DAT, TAT did not show superiority in reducing the composite of adverse cardiovascular outcomes after DES implantation. (The Efficacy of CILostazol ON Ischemic Complications After DES Implantation [CILON-T]; NCT00776828 )

Increased level of N-terminal pro-B type natriuretic peptide (NT-proBNP) is known to be associated with adverse outcome in patients with acute coronary syndrome. We evaluated early outcomes of patients with acute ST-elevated myocardial infarction (STEMI) according to the level of NT-proBNP as a substudy of Korean Acute Myocardial Infarction Registry (KAMIR).Study population consisted of 1052 consecutive patients (mean 61.3+/-12.8 years old, male 73.2%) with STEMI of onset12 h who underwent primary percutaneous coronary intervention (PCI) and who had baseline NT-proBNP level by electrochemiluminescence immnunoassay (ECLIA, NT-proBNP kit, Roche Diagnostics, Mannheim, Germany). The study subjects were divided into two groups according to the level of serum NT-proBNP.Patients with NT-proBNP level991 pg/mL (n=329, 57.1% male) had lower left ventricle ejection fraction (LVEF) (47.8+/-11.8% vs. 53.0+/-10.8%, p0.001), needed longer intensive care (3.7+/-3.6 days vs. 2.8+/-2.4 days, p0.001) and had higher in-hospital mortality (1.3% vs. 7.4%, p0.001) than those with NT-proBNP levelor=991 pg/mL (n=723, 80.5% male). Multiple logistic regression analysis revealed that the independent predictors of in-hospital mortality were LVEF45% (OR 5.43, 95% CI 1.71 to 17.29, p=0.004), elevated NT-proBNP (991 pg/mL) (OR 3.70, 95% CI 1.14 to 12.03, p=0.030), old age (or=70 years) (OR 4.71, 95% CI 1.43 to 15.52, p=0.011), advanced Killip class (1) (OR 4.96, 95% CI 1.58 to 15.53, p=0.006), male gender (OR 5.67, 95% CI 1.45 to 22.21, p=0.013) and TIMI flow 0 before PCI (OR 5.04, 95% CI 1.08 to 23.41, p=0.039).This study suggests that baseline NT-proBNP level is associated with short term mortality in patients with STEMI underwent primary PCI.

Objectives: Slow flow phenomenon is a serious complication of percutaneous coronary intervention (PCI) and is associated with a poor prognosis. We sought to evaluate the characteristics of lesions predisposing to the slow/no-reflow phenomenon during primary PCI in patients with acute myocardial infarction. Methods: The study subjects consisted of 57 consecutive patients (mean age 58.5 (SD 14.5) years, 45 males) who underwent primary PCI for acute myocardial infarction and intravascular ultrasound-virtual histology (IVUS-VH) examination. Slow flow was defined as ⩽ thrombolysis in myocardial infarction grade 2 after PCI. Results: Slow flow developed in 12 patients (eight males). Patients with slow flow were likely to be older (67.5 (13.8) years vs 56.2 (13.9) years, p = 0.015), had more cardiogenic shock (16.7% vs 2.2%, p = 0.046), larger fibrofatty volume over the entire lesion length (36.7 (25.5) mm 3 vs 18.0 (18.6) mm 3 , p = 0.006), higher remodelling index (1.10 (0.17) vs 0.99 (0.16), p = 0.043), larger plaque area (16.2 (5.4) mm 2 vs 12.5 (4.9) mm 2 , p = 0.025), fibrous area (8.0 (3.3) mm 2 vs 5.4 (3.0) mm 2 , p = 0.014) and fibrofatty area (2.7 (2.2) mm 2 vs 1.3 (1.6) mm 2 , p = 0.016) at the minimal lumen site than those without slow flow (37 males). Multivariate analysis revealed that the fibrofatty volume over the entire lesion length was the only independent factor (β = 0.359, 95% confidence interval 0.002 to 0.012, p = 0.006) for slow flow during primary PCI. Conclusions: This study suggests that slow flow may be dependent on the tissue characterisation (fibrofatty volume) of the underlying lesion at the time of the primary PCI for acute myocardial infarction.

Background Endothelial dysfunction plays a pivotal role in cardiovascular disease progression, and is associated with adverse events. The purpose of this systematic review and meta‐analysis was to investigate the prognostic magnitude of noninvasive peripheral endothelial function tests, brachial artery flow‐mediated dilation (FMD), and reactive hyperemia–‐peripheral arterial tonometry (RH‐PAT) for future cardiovascular events. Methods and Results Databases of MEDLINE, EMBASE, and the Cochrane Library were systematically searched. Clinical studies reporting the predictive value of FMD or RH‐PAT for cardiovascular events were identified. Two authors selected studies and extracted data independently. Pooled effects were calculated as risk ratio (RR) for continuous value of FMD and natural logarithm of RH‐PAT index (Ln_RHI) using random‐effects models. Thirty‐five FMD studies of 17 280 participants and 6 RH‐PAT studies of 1602 participants were included in the meta‐analysis. Both endothelial function tests significantly predicted cardiovascular events (adjusted relative risk [95% CI]: 1% increase in FMD 0.88 [0.84–0.91], P P Conclusions Noninvasive peripheral endothelial function tests, FMD and RH‐PAT, significantly predicted cardiovascular events, with similar prognostic magnitude. Further research is required to determine whether the prognostic values of these 2 methods are independent of each other and whether an endothelial function–guided strategy can provide benefit in improving cardiovascular outcomes.

Spontaneous coronary artery dissection (SCAD) is one of the underlying mechanisms of acute coronary syndrome and sudden cardiac death, especially in young women. Although hemorrhage from vasa vasorum (VV) has been suggested as a possible mechanism of SCAD [(1)][1], no study has evaluated the

Background Coronary microvascular dysfunction (CMD) is associated with cardiovascular events in type 2 diabetes mellitus (T2DM). Optimal glycaemic control does not always preclude future events. We sought to assess the effect of the current target of HBA1c level on the coronary microcirculatory function and identify predictive factors for CMD in T2DM patients. Methods We studied 100 patients with T2DM and 214 patients without T2DM. All of them with a history of chest pain, non-obstructive angiograms and a direct assessment of coronary blood flow increase in response to adenosine and acetylcholine coronary infusion, for evaluation of endothelial independent and dependent CMD. Patients with T2DM were categorized as having optimal (HbA1c < 7 %) vs. suboptimal (HbA1c ≥ 7 %) glycaemic control at the time of catheterization. Results Baseline characteristics and coronary endothelial function parameters differed significantly between T2DM patients and control group. The prevalence of endothelial independent CMD (29.8 vs. 39.6 %, p = 0.40) and dependent CMD (61.7 vs. 62.2 %, p = 1.00) were similar in patients with optimal vs. suboptimal glycaemic control. Age (OR 1.10; CI 95 % 1.04–1.18; p < 0.001) and female gender (OR 3.87; CI 95 % 1.45–11.4; p < 0.01) were significantly associated with endothelial independent CMD whereas glomerular filtrate (OR 0.97; CI 95 % 0.95–0.99; p < 0.05) was significantly associated with endothelial dependent CMD. The optimal glycaemic control was not associated with endothelial independent (OR 0.60, CI 95 % 0.23–1.46; p 0.26) or dependent CMD (OR 0.99, CI 95 % 0.43–2.24; p = 0.98). Conclusions The current target of HBA1c level does not predict a better coronary microcirculatory function in T2DM patients. The appropriate strategy for prevention of CMD in T2DM patients remains to be addressed. Keywords: Endothelial dysfunction; Diabetes mellitus; Coronary microcirculation Yes

Background Myocardial perfusion scintigraphy (MPS) is used widely to assess cardiovascular risk in patients with chest pain. The utility of carotid intima–media thickness (CIMT) and endothelial function as assessed by reactive hyperemia-peripheral arterial tonometry index (RHI) in risk stratifying patients with angina-like symptoms needs to be defined. We investigated whether the addition of CIMT and RHI to Framingham Cardiovascular Risk Score (FCVRS) and MPS improves comprehensive cardiovascular risk prediction in patients presenting with angina-like symptoms. Methods We enrolled 343 consecutive patients with angina-like symptoms suspected of having stable angina. MPS, CIMT, and RHI were performed and patients were followed for cardiovascular events for a median of 5.3years (range 4.4–6.2). Patients were stratified by FCVRS and MPS. Results During the follow-up, 57 patients (16.6%) had cardiovascular events. Among patients without perfusion defect, low RHI was significantly associated with cardiovascular events in the intermediate and high FCVRS groups (hazard ratio (HR) [95% confidence interval (CI)] of RHI≤2.11 was 6.99 [1.34–128] in the intermediate FCVRS group and 6.08 [1.08–114] in the high FCVRS group). Furthermore, although MPS did not predict, only RHI predicted hard cardiovascular events (cardiovascular death, myocardial infarction, and stroke) independent from FCVRS, and adding RHI to FCVRS improved net reclassification index (20.9%, 95% CI 0.8–41.1, p=0.04). Especially, RHI was significantly associated with hard cardiovascular events in the high FCVRS group (HR [95% CI] of RHI≤1.93 was 5.66 [1.54–36.4], p=0.007). Conclusions Peripheral endothelial function may improve discrimination in identifying at-risk patients for future cardiovascular events when added to FCVRS–MPS-based risk stratification.

Objective The ratio of basal distal intracoronary pressure (Pd) and aortic pressure (Pa) is a nonhyperemic index for the severity of coronary artery stenosis. The aim of the current study was to evaluate the clinical usefulness of a hybrid baseline Pd/Pa-fractional flow reserve (FFR) strategy in reducing the need for hyperemia. Methods In this study, 570 lesions from 527 consecutive patients who had both baseline Pd/Pa and FFR determined were evaluated retrospectively. To evaluate the hybrid baseline Pd/Pa-FFR approach, patients were categorized into treatment, deferral, and undetermined groups on the basis of their baseline Pd/Pa. Thereafter, patients in the undetermined group were assigned to FFR-guided treatment or deferral on the basis of an FFR cutoff value of 0.80 or lower. Major adverse cardiac events were evaluated in a median of 48.8 months (interquartile range, 35.0-66.4). Results A hybrid strategy using a deferral baseline Pd/Pa value of 1.00 (negative predictive value of 100%) and a treatment baseline Pd/Pa value of 0.86 or lower (positive predictive value of 100%), and limiting adenosine to a baseline Pd/Pa value between 0.87 and 0.99 would prevent the need for vasodilator drugs in 14.6% of lesions (14.0% patients), maintaining 100% agreement with an FFR-only strategy. However, adenosine-free lesions are increased to 59.6%, with 91% agreement. There was no difference in the major adverse cardiac event-free survival rate at 5 years between baseline Pd/Pa-guided and FFR-guided treatment patients (70.8 vs. 76.3%, P=0.63), or between baseline Pd/Pa-guided and FFR-guided deferral patients (71.3 vs. 82.4%, P=0.99). Conclusion The current study reports a range of baseline Pd/Pa values that can predict myocardial ischemia without the need for inducing hyperemia. Adoption of this hybrid baseline Pd/Pa-FFR approach can reduce the need for drug-induced hyperemia.

Objective— Endothelial dysfunction is an early manifestation of atherosclerosis. Inflammation and vasa vasorum play a pivotal role in the pathophysiology of plaque initiation, development, and complications. Optical coherence tomography allows high-resolution imaging of tissue microstructure. Therefore, the aim of this study was to test the hypothesis that segments with endothelial dysfunction show macrophages and vasa vasorum in patients with early coronary artery disease. Approach and Results— Optical coherence tomography images were obtained from 40 patients with mild coronary atherosclerosis who underwent coronary endothelial function assessment. Optical coherence tomography findings, including macrophages and microchannels, were evaluated in 76 coronary segments corresponding to those in endothelial response to acetylcholine. Coronary artery diameter change in response to acetylcholine was more severe in segments showing macrophages (−17.7±14.7% versus −6.3±13.9%; P P P P =0.02 for trend, respectively). In particular, segments with both macrophages and microchannels (n=12) tended to have worse endothelial function than those with macrophages alone (n=15) and microchannels alone (n=15; −22.1±14.6% versus −10.9±15.6% and −10.9±15.6%; P =0.07 and P =0.06, respectively). Conclusions— Epicardial endothelial dysfunction was associated with optical coherence tomography –identified macrophages and microchannels in mild coronary atherosclerosis. The current study further supports the role of inflammation and vasa vasorum proliferation in the early stage of coronary atherosclerosis.

Since Einthoven invented the string galvanometer for registering electrical activity of the heart in 1903, electrocardiography (ECG) became the most common and important medical examination. With this 12-lead surface ECG, we can diagnose arrhythmia, ischemic heart disease, or other heart disease.

Aim To compare the responsiveness to clopidogrel in patients who were prescribed two different types of statins, atorvastatin vs. rosuvastatin, following percutaneous coronary intervention. Methods A total of 915 patients were randomized according to the antiplatelet therapy strategy in the CILON-T trial. In this subgroup analysis, we included patients who took atorvastatin(20 mg/day, n=295) or rosuvastatin(10 mg/day, n=261) during the entire study period and underwent measurement of the P2Y12 reaction unit(PRU) values at both discharge and six months. We compared the P2Y12 reaction unit(PRU) values at six months and investigated the relationship between the genotypes of cytochrome P450(CYP) 3A4, 3A5 and 2C19 with the PRU values at six months in both groups. Results The baseline characteristics did not differ between the groups. There were no significant differences in the PRU values at discharge(atorvastatin 221.0±87.3 vs. rosuvastatin 217.1±84.7, p=0.59). However, the rosuvastatin group had higher PRU values than the atorvastatin group at six months(atorvastatin 226.4±79.3 vs. rosuvastatin 241.5±88.2, p=0.033). In the genotype analysis, the number of CYP2C19 loss-of-function (LOF) alleles((＊)2 or (＊)3) was positively associated with a higher PRU value in both statin groups, and there were no significant interactions regarding the PRU values between the number of CYP 2C19 LOF alleles and the type of statin(p for interaction=0.56). In the multivariate analysis, the use of rosuvastatin was a significant predictor of a PRU value of ＞273(the highest tertile)(OR 1.67, 95% confidence interval 1.05-2.65, p=0.031). Conclusions Rosuvastatin is associated with high on-treatment platelet reactivity compared with atorvastatin following the coadministration of clopidogrel for six months. Further studies are therefore warranted to clarify the mechanism underlying this relationship.