Optimal antithrombotic strategy in patients with atrial fibrillation beyond 1 year after drug-eluting stent implantation: Design and rationale of the randomized ADAPT AF-DES trial.

BACKGROUND: Both anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. METHODS: The ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. CONCLUSIONS: The ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04250116.

Long-term clinical outcomes in patients with untreated non-culprit intermediate coronary lesion and evaluation of predictors by using virtual histology-intravascular ultrasound; a prospective cohort study.

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.

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.

Lack of correlation between the optimal glycaemic control and coronary micro vascular dysfunction in patients with diabetes mellitus: a cross sectional study.

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.

Coronary endothelial dysfunction is associated with inflammation and vasa vasorum proliferation in patients with early atherosclerosis.

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<0.01) and microchannels (-15.9±15.9% versus -6.4±13.5%; P<0.01) than those without. There were increasing trends of the prevalence of macrophages and microchannels with endothelial dysfunction as stratified by quartiles of coronary artery diameter change (P<0.01 and 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.

Secondary prevention strategy of cardiovascular disease using endothelial function testing.

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.

Attenuation in peripheral endothelial function after continuous flow left ventricular assist device therapy is associated with cardiovascular adverse events.

BACKGROUND: Patients with heart failure (HF) have abnormal endothelial function. Although use of a continuous flow left ventricular assist device (CF-LVAD) results in significant hemodynamic improvement, the effects on systemic endothelial function are unclear. METHODS AND RESULTS: Eighteen HF patients with CF-LVAD implantation were included in this prospective observational study. We measured reactive hyperemia index (RHI) before and after CF-LVAD implantation to evaluate sequential changes in endothelial function. Patients were followed clinically for the occurrence of adverse cardiovascular events, a composite of death, thrombosis, bleeding, HF, renal failure, and arrhythmia. Preoperative RHI was 1.77±0.39. Early in the postoperative period (7-14 days after operation) RHI significantly decreased to 1.19±0.31 (P<0.001, compared with preoperative RHI). At first and second follow-up (4-6 weeks and 3-7 months after operation) RHI remained lower at 1.48±0.50 (P=0.030) and 1.26±0.37 (P=0.002), respectively, compared with preoperative RHI. The decrease in early postoperative RHI relative to preoperative RHI was significantly associated with adverse cardiovascular events after CF-LVAD (age-adjusted risk ratio for 0.25 decrease in RHI, 1.35; 95% confidence interval: 1.13-1.62, P=0.001). CONCLUSIONS: Peripheral endothelial function had a significant and persistent decline up to 5 months following implantation of CF-LVAD, and this decline was associated with adverse cardiovascular events. These findings may provide insight into some of the vascular complications following CF-LVAD in HF patients.

Cilostazol eliminates adverse smoking outcome in patients with drug-eluting stent implantation.

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.

A Rare Case of Stroke in a 76-Year-Old Woman: Left Atrial Papillary Fibroelastoma as the Culprit.

BACKGROUND Papillary fibroelastoma is the most common type of benign primary cardiac tumor and is usually asymptomatic. However, tumor fragments or surface thrombus can embolize and cause transient ischemic attacks, strokes, or myocardial infarction. This report describes a 76-year-old woman who presented with dysarthria and right-sided weakness due to a stroke associated with a left atrial papillary fibroelastoma. CASE REPORT A 76-year-old woman visited the Emergency Department because she had right-sided weakness and dysarthria from 12 h ago. Brain magnetic resonance image was done at the Emergency Department, showing multiple small embolic, acute infarction in left basal ganglia and fronto-temporo-parietal lobes. Transthoracic and transesophageal echocardiogram showed a hypermobile echogenic mass (0.8×1.5 cm) with villous surface on the orifice of left atrial appendage. Twenty-four-hour Holter monitoring was performed to evaluate the cause of cerebral infarction, and there was no paroxysmal atrial fibrillation. Thoracic computed tomography angiography also showed a sea anemone-shaped mass around the left atrial appendage. Cardiac tumor excision was done via a lower partial sternotomy. Histopathologic analysis showed multiple delicate fronds, and the avascular fibroelastic cores were lined by a single layer of CD31-positive endothelial cells. Histopathologic findings were consistent with papillary fibroelastoma. The patient was discharged without any other complications on day 30 of hospitalization. CONCLUSIONS This case highlights the importance of cardiac imaging in patients with acute stroke, including transthoracic and transesophageal echocardiography, which can show the typical imaging features of papillary fibroelastoma and other intracardiac sources of embolus.

Toxocariasis-Associated Acute Perimyocarditis with Cardiogenic Shock: A Case Report.

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.

Design and rationale of a randomized control trial testing the effectiveness of combined therapy with STAtin plus FENOfibrate and statin alone in non-diabetic, combined dyslipidemia patients with non-intervened intermediate coronary artery disease - STAFENO study.

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.

Ten-year clinical outcomes of an intermediate coronary lesion; prognosis and predictors of major adverse cardiovascular events.

AIMS: 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. METHODS: 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. RESULTS: 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 (stenosed <30% 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. CONCLUSIONS: 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.

Rationale of decreasing low-density lipoprotein cholesterol below 70 mg/dL in patients with coronary artery disease: A retrospective virtual histology-intravascular ultrasound study.

BACKGROUND: The associations between statin and coronary plaque compositional changes were re-ported 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 logis-tic 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.

Impact of different antihypertensives on carotid arterial wall thickness.

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 < .001), (0.31 ± 0.07 mm vs 0.30 ± 0.06 mm, P < .001), and (0.41 ± 0.13 mm vs 0.35 ± 0.12 mm, P < .001). Additionally, hypertensive patients on beta-blockers also had thicker carotid intima media thickness than the non-beta-blocker group, with carotid intima media thicknesses of (0.74 ± 0.18 mm vs 0.71 ± 0.16 mm, P = .018), (0.33 ± 0.09 mm vs 0.31 ± 0.07 mm, P = .029), and (0.43 ± 0.13 mm vs 0.40 ± 0.13 mm, P = .035). Multivariate analysis showed that carotid intima thickness was only correlated with beta-blockers (odds ratio = 2.489, confidence interval = 1.183-5.239, P = .016); however, this study showed that beta-blocker could be associated with increased carotid wall thickness as well.

In-stent restenosis-prone coronary plaque composition: A retrospective virtual histology-intravascular ultrasound study.

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% con-fidence 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).

Peripheral vascular atherosclerosis in a novel PCSK9 gain-of-function mutant Ossabaw miniature pig model.

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.

Body mass index, carotid plaque, and clinical outcomes in patients with coronary artery disease.

OBJECTIVES: We evaluated the relationship among BMI, carotid sonographic findings, and long-term (5 years) cardiovascular events in Asian patients with coronary artery disease (CAD). PATIENTS AND METHODS: 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: BMI<18.5 kg/m, n=38); normal weight (group II: 18.5≤BMI<23.5 kg/m, n=352); overweight (group III: 23.5≤BMI<27.5 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). RESULTS: 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, P<0.001; group III: HR=0.26, 95% CI=0.13-0.51, P<0.001; group IV: HR=0.08, 95% CI=0.03-0.22, P<0.001). CONCLUSION: 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.

Prevalence of diastolic function and clinical impact on long-term outcome in takotsubo cardiomyopathy.

BACKGROUND: 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. METHODS: 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). RESULTS: 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 LVEF <50%. During 2years of follow-up, 34 patients developed clinical adverse events. Kaplan-Meier analysis estimated that the subgroup with unimproved DF and LVEF <50% at recovery phase had the worst 2-year survival. In multivariable analysis, unimproved DF with LVEF <50% and heart rate (HR) remained predictors of clinical adverse events. CONCLUSIONS: 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.

Association between the vasa vasorum and the atherosclerotic changes in cardiac allograft vasculopathy: volumetric analysis.

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.