Clinical Outcome after Everolimus-Eluting Stent Implantation for Small Vessel Coronary Artery Disease: XIENCE Asia Small Vessel Study.

There are limited data on outcomes after implantation of everolimus-eluting stents (EES) in East Asian patients with small vessel coronary lesions. A total of 1,600 patients treated with XIENCE EES (Abbott Vascular, CA, USA) were divided into the small vessel group treated with one ≤2.5 mm stent (n=119) and the non-small vessel group treated with one ≥2.75 mm stent (n=933). The primary end point was a patient-oriented composite outcome (POCO), a composite of all-cause death, myocardial infarction (MI), and any repeat revascularization at 12 months. The key secondary end point was a device-oriented composite outcome (DOCO), a composite of cardiovascular death, target-vessel MI, and target lesion revascularization at 12 months. The small vessel group was more often female, hypertensive, less likely to present with ST-elevation MI, and more often treated for the left circumflex artery, whereas the non-small vessel group more often had type B2/C lesions, underwent intravascular ultrasound, and received unfractionated heparin. In the propensity matched cohort, the mean stent diameter was 2.5±0.0 mm and 3.1±0.4 mm in the small and non-small vessel groups, respectively. Propensity-adjusted POCO at 12 months was 6.0% in the small vessel group and 4.3% in the non-small vessel group (p=0.558). There was no significant difference in DOCO at 12 months (small vessel group: 4.3% and non-small vessel group: 1.7%, p=0.270). Outcomes of XIENCE EES for small vessel disease were comparable to those for non-small vessel disease at 12-month clinical follow-up in real-world Korean patients.

Clinical Outcomes of Elderly Patients with Non ST-Segment Elevation Myocardial Infarction Undergoing Coronary Artery Bypass Surgery.

The aim of this study is to investigate the clinical outcomes of the elderly patients with Non ST-segment elevation myocardial infarction (NSTEMI) undergoing coronary artery bypass surgery (CABG) compared to non-elderly patients. Patients with NSTEMI and undergoing CABG (n=451) who were registered in the Korea Acute Myocardial Infarction Registry between December 2003 and August 2012 were divided into two groups.; the non-elderly group (<75 years, n=327) and the elderly group (≥75 years, n=124). In-hospital mortality was higher in the elderly group (4.9% vs. 11.3%, p=0.015), but cardiac death, myocardial infarction, and major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, percutaneous revascularization, and redo-CABG after a one-year follow up were not different between the two groups. Predictors of in-hospital mortality in patients with NSTEMI undergoing CABG were left ventricular (LV) dysfunction (ejection fraction ≤40%) [hazard ratio (HR): 2.76, 95% confidence interval (CI): 1.16-6.57, p=0.022] and age (HR: 1.05, 95% CI: 1.01-1.10, p=0.047). So elderly NSTEMI patients should be considered for CABG if appropriate, but careful consideration for surgery is required, especially if the patients have severe LV systolic dysfunction.

Safety and Efficacy of the Endeavor Resolute® Stent in Patients with Multivessel Disease: The HEART (Honam EndeAvor ResoluTe) Prospective, Multicenter Trial.

The Endeavor Resolute® (ER) is a zotarolimus-eluting stent (ZES) with a biocompatible BioLinx polymer. This study prospectively compared the clinical outcomes of 2 versions of ZES, ER and Endeavor Sprint® (ES), in patients with multivessel disease. A total of 488 patients who underwent multivessel percutaneous coronary intervention (PCI) were divided into 2 groups the ER group (n=288) and the ES group (n=200). The primary endpoint was a composite of major adverse cardiac events (MACE) consisting of death, myocardial infarction, and target vessel revascularization after 12 months. In all patients, the prevalence of diabetes was higher in the ER group (42.7% vs. 31.0%, p=0.009). The rate of post-PCI Thrombolysis in Myocardial Infarction flow grade 3 was higher in the ER group (100.0% vs. 98.0%, p=0.028). There were no between-group differences in the in-hospital, 1-month and 12-month clinical outcomes. In the propensity score matched cohort (n=200 in each group), no differences were observed in the baseline and procedural characteristics. There were no statistical differences in the rates of in-hospital, 1-month and 12-month events (12-month MACE in the ER and ES groups: 6.0% vs. 3.5%, p=0.240, respectively). The safety and efficacy of both versions of ZES were comparable in patients with multivessel disease during a 12-month clinical follow-up.

Hydrogen Peroxide-Responsive Nanoparticle Reduces Myocardial Ischemia/Reperfusion Injury.

BACKGROUND: During myocardial ischemia/reperfusion (I/R), a large amount of reactive oxygen species (ROS) is produced. In particular, overproduction of hydrogen peroxide (H2O2) is considered to be a main cause of I/R-mediated tissue damage. We generated novel H2O2-responsive antioxidant polymer nanoparticles (PVAX and HPOX) that are able to target the site of ROS overproduction and attenuate the oxidative stress-associated diseases. In this study, nanoparticles were examined for their therapeutic effect on myocardial I/R injury. METHODS AND RESULTS: The therapeutic effect of nanoparticles during cardiac I/R was evaluated in mice. A single dose of PVAX (3 mg/kg) showed a significant improvement in both cardiac output and fraction shortening compared with poly(lactic-coglycolic acid) (PLGA) particle, a non-H2O2-activatable nanoparticle. PVAX also significantly reduced the myocardial infarction/area compared with PLGA (48.7±4.2 vs 14.5±2.1). In addition, PVAX effectively reduced caspase-3 activation and TUNEL-positive cells compared with PLGA. Furthermore, PVAX significantly decreased TNF-α and MCP-1 mRNA levels. To explore the antioxidant effect of PVAX by scavenging ROS, dihydroethidium staining was used as an indicator of ROS generation. PVAX effectively suppressed the generation of ROS caused by I/R, whereas a number of dihydroethidium-positive cells were observed in a group with PLGA I/R. In addition, PVAX significantly reduced the level of NADPH oxidase (NOX) 2 and 4 expression, which favors the reduction in ROS generation after I/R. CONCLUSIONS: Taken together, these results suggest that H2O2-responsive antioxidant PVAX has tremendous potential as a therapeutic agent for myocardial I/R injury.

Energy Calibration of a CdTe Photon Counting Spectral Detector with Consideration of its Non-Convergent Behavior.

Fast and accurate energy calibration of photon counting spectral detectors (PCSDs) is essential for their biomedical applications to identify and characterize bio-components or contrast agents in tissues. Using the x-ray tube voltage as a reference for energy calibration is known to be an efficient method, but there has been no consideration in the energy calibration of non-convergent behavior of PCSDs. We observed that a single pixel mode (SPM) CdTe PCSD based on Medipix-2 shows some non-convergent behaviors in turning off the detector elements when a high enough threshold is applied to the comparator that produces a binary photon count pulse. More specifically, the detector elements are supposed to stop producing photon count pulses once the threshold reaches a point of the highest photon energy determined by the tube voltage. However, as the x-ray exposure time increases, the threshold giving 50% of off pixels also increases without converging to a point. We established a method to take account of the non-convergent behavior in the energy calibration. With the threshold-to-photon energy mapping function established by the proposed method, we could better identify iodine component in a phantom consisting of iodine and other components.

p-Hydroxybenzyl alcohol-containing biodegradable nanoparticle improves functional blood flow through angiogenesis in a mouse model of hindlimb ischemia.

Therapeutic angiogenesis has achieved promising results for ischemic diseases or peripheral artery disease in preclinical and early-phase clinical studies. We examined the therapeutic angiogenic effects of HPOX, which is biodegradable polymer composing the antioxidant p-hydroxybenzyl alcohol (HBA), in a mouse model of hindlimb ischemia. HPOX effectively stimulated blood flow recovery, compared with its degraded compounds HBA and 1,4-cyclohexendimethanol, via promotion of capillary vessel density in the ischemic hindlimb. These effects were highly correlated with levels of angiogenic inducers, vascular endothelial cell growth factor (VEGF), heme oxygenase-1 (HO-1), and Akt/AMPK/endothelial nitric oxide synthase (eNOS) in ischemic mouse hindlimb muscle. Blood perfusion and neovascularization induced by HPOX were reduced in eNOS(-/-) and HO-1(+/-) mice. HPOX also elevated the endothelial cell markers VEGF receptor-2, CD31, and eNOS mRNAs in the ischemic hindlimb, indicating that HPOX increases endothelial cell population and angiogenesis in the ischemic muscle. However, this nanoparticle suppressed expression levels of several inflammatory genes in ischemic tissues. These results suggest that HPOX significantly promotes angiogenesis and blood flow perfusion in the ischemic mouse hindlimb via increased angiogenic inducers, along with suppression of inflammatory gene expression. Thus, HPOX can be used potentially as a noninvasive drug intervention to facilitate therapeutic angiogenesis.

Tissue Cancellation in Dual Energy Mammography Using a Calibration Phantom Customized for Direct Mapping.

An easily implementable tissue cancellation method for dual energy mammography is proposed to reduce anatomical noise and enhance lesion visibility. For dual energy calibration, the images of an imaging object are directly mapped onto the images of a customized calibration phantom. Each pixel pair of the low and high energy images of the imaging object was compared to pixel pairs of the low and high energy images of the calibration phantom. The correspondence was measured by absolute difference between the pixel values of imaged object and those of the calibration phantom. Then the closest pixel pair of the calibration phantom images is marked and selected. After the calibration using direct mapping, the regions with lesion yielded different thickness from the background tissues. Taking advantage of the different thickness, the visibility of cancerous lesions was enhanced with increased contrast-to-noise ratio, depending on the size of lesion and breast thickness. However, some tissues near the edge of imaged object still remained after tissue cancellation. These remaining residuals seem to occur due to the heel effect, scattering, nonparallel X-ray beam geometry and Poisson distribution of photons. To improve its performance further, scattering and the heel effect should be compensated.

A unified statistical framework for material decomposition using multienergy photon counting x-ray detectors.

PURPOSE: Material decomposition using multienergy photon counting x-ray detectors (PCXD) has been an active research area over the past few years. Even with some success, the problem of optimal energy selection and three material decomposition including malignant tissue is still on going research topic, and more systematic studies are required. This paper aims to address this in a unified statistical framework in a mammographic environment. METHODS: A unified statistical framework for energy level optimization and decomposition of three materials is proposed. In particular, an energy level optimization algorithm is derived using the theory of the minimum variance unbiased estimator, and an iterative algorithm is proposed for material composition as well as system parameter estimation under the unified statistical estimation framework. To verify the performance of the proposed algorithm, the authors performed simulation studies as well as real experiments using physical breast phantom and ex vivo breast specimen. Quantitative comparisons using various performance measures were conducted, and qualitative performance evaluations for ex vivo breast specimen were also performed by comparing the ground-truth malignant tissue areas identified by radiologists. RESULTS: Both simulation and real experiments confirmed that the optimized energy bins by the proposed method allow better material decomposition quality. Moreover, for the specimen thickness estimation errors up to 2 mm, the proposed method provides good reconstruction results in both simulation and real ex vivo breast phantom experiments compared to existing methods. CONCLUSIONS: The proposed statistical framework of PCXD has been successfully applied for the energy optimization and decomposition of three material in a mammographic environment. Experimental results using the physical breast phantom and ex vivo specimen support the practicality of the proposed algorithm.

Automatic registration between 3D intra-operative ultrasound and pre-operative CT images of the liver based on robust edge matching.

The registration of a three-dimensional (3D) ultrasound (US) image with a computed tomography (CT) or magnetic resonance image is beneficial in various clinical applications such as diagnosis and image-guided intervention of the liver. However, conventional methods usually require a time-consuming and inconvenient manual process for pre-alignment, and the success of this process strongly depends on the proper selection of initial transformation parameters. In this paper, we present an automatic feature-based affine registration procedure of 3D intra-operative US and pre-operative CT images of the liver. In the registration procedure, we first segment vessel lumens and the liver surface from a 3D B-mode US image. We then automatically estimate an initial registration transformation by using the proposed edge matching algorithm. The algorithm finds the most likely correspondences between the vessel centerlines of both images in a non-iterative manner based on a modified Viterbi algorithm. Finally, the registration is iteratively refined on the basis of the global affine transformation by jointly using the vessel and liver surface information. The proposed registration algorithm is validated on synthesized datasets and 20 clinical datasets, through both qualitative and quantitative evaluations. Experimental results show that automatic registration can be successfully achieved between 3D B-mode US and CT images even with a large initial misalignment.

Clinical effects of hypertension on the mortality of patients with acute myocardial infarction.

The incidence of ischemic heart disease has been increased rapidly in Korea. However, the clinical effects of antecedent hypertension on acute myocardial infarction have not been identified. We assessed the relationship between antecedent hypertension and clinical outcomes in 7,784 patients with acute myocardial infarction in the Korea Acute Myocardial Infarction Registry during one-year follow-up. Diabetes mellitus, hyperlipidemia, cerebrovascular disease, heart failure, and peripheral artery disease were more prevalent in hypertensives (n=3,775) than nonhypertensives (n=4,009). During hospitalization, hypertensive patients suffered from acute renal failure, shock, and cerebrovascular event more frequently than in nonhypertensives. During follow-up of one-year, the incidence of major adverse cardiac events was higher in hypertensives. In multi-variate adjustment, old age, Killip class > or =III, left ventricular ejection fraction <45%, systolic blood pressure <90 mmHg on admission, post procedural TIMI flow grade < or =2, female sex, and history of hypertension were independent predictors for in-hospital mortality. However antecedent hypertension was not significantly associated with one-year mortality. Hypertension at the time of acute myocardial infarction is associated with an increased rate of in-hospital mortality.

Three-dimensional blood vessel quantification via centerline deformation.

It is clinically important to quantify the geometric parameters of an abnormal vessel, as this information can aid radiologists in choosing appropriate treatments or apparatuses. Centerline and cross-sectional diameters are commonly used to characterize the morphology of vessel in various clinical applications. Due to the existence of stenosis or aneurysm, the associated vessel centerline is unable to truly portray the original, healthy vessel shape and may result in inaccurate quantitative measurement. To remedy such a problem, a novel method using an active tube model is proposed. In the method, a smoothened centerline is determined as the axis of a deformable tube model that is registered onto the vessel lumen. Three types of regions, normal, stenotic, and aneurysmal regions, are defined to classify the vessel segment under-analyzed by use of the algorithm of a cross-sectional-based distance field. The registration process used on the tube model is governed by different region-adaptive energy functionals associated with the classified vessel regions. The proposed algorithm is validated on the 3-D computer-generated phantoms and 3-D rotational digital subtraction angiography (DSA) datasets. Experimental results show that the deformed centerline provides better vessel quantification results compared with the original centerline. It is also shown that the registered model is useful for measuring the volume of aneurysmal regions.

Gastrointestinal stromal tumor in ileal neobladder.

Gastrointestinal stromal tumor (GIST) is a recently described mesenchymal tumor that can develop in any portion of the gastrointestinal tract. The occurrence of a GIST in the urinary tract is rare, but GIST can present as tumor of the urinary tract or invade the urinary tract. This is the first reported case of GIST in the ileal neobladder, which presented as a submucosal tumor. The patient underwent an open exploration and partial resection of the neobladder pouch.

A new path planning algorithm for maximizing visibility in computed tomography colonography.

In virtual colonoscopy, minimizing the blind areas is important for accurate diagnosis of colonic polyps. Although useful for describing the shape of an object, the centerline is not always the optimal camera path for observing the object. Hence, conventional methods in which the centerline is directly used as a path produce considerable blind areas, especially in areas of high curvature. Our proposed algorithm first approximates the surface of the object by estimating the overall shape and cross-sectional thicknesses. View positions and their corresponding view directions are then jointly determined to enable us to maximally observe the approximated surface. Moreover, by adopting bidirectional navigations, we may reduce the blind area blocked by haustral folds. For comfortable navigation, we carefully smoothen the obtained path and minimize the amount of rotation between consecutive rendered images. For the evaluation, we quantified the overall observable area on the basis of the temporal visibility that reflects the minimum interpretation time of a human observer. The experimental results show that our algorithm improves visibility coverage and also significantly reduces the number of blind areas that have a clinically meaningful size. A sequence of rendered images shows that our algorithm can provide a sequence of centered and comfortable views of colonography.

Impact of preinterventional arterial remodeling on in-stent neointimal hyperplasia and in-stent restenosis after coronary stent implantation.

BACKGROUND: Patterns of arterial remodeling during the course of plaque development have been shown to play an important role in both the progression of de novo atherosclerosis and in the restenotic process following coronary intervention. The aim of the present prospective study was to evaluate the effect of pre-interventional arterial remodeling on in-stent neointimal hyperplasia (NIH) and in-stent restenosis (ISR) after stenting. METHODS AND RESULTS: Pre-interventional arterial remodeling was assessed in 85 native coronary lesions by using intravascular ultrasound (IVUS). The remodeling index (RI) was 1.09+/-0.20 in the positive remodeling (PR)/intermediate remodeling (IR) group and 0.84+/-0.12 in the negative remodeling (NR) group. The plaque plus media cross sectional area (P&M CSA) at pre-intervention and NIH CSA at follow-up in the minimal lumen CSA were significantly larger in the PR/IR group (9.2+/-2.9 mm2 vs 6.2+/-1.8 mm2, 3.3+/-1.2 mm2 vs 1.5+/-0.9 mm2; p = 0.001, p = 0.001, respectively). On 3-dimensional analysis of IVUS images at follow-up, the lumen volume was significantly smaller in the PR/IR group than that in the NR group (62+/-15 mm3 vs 75 +/-20 mm3; p = 0.001), and neointima hyperplasia volume was significantly larger in the PR/IR group than that in the NR group (46+/-15 mm3 vs 26+/-10 mm3; p = 0.001). A significant positive correlation was found between pre-interventional RI and follow-up NIH CSA (r = 0.25, p = 0.022). The incidence of ISR and repeat intervention was significantly higher in the PR/IR group (30.8% vs 18.2%, 28.8% vs 15.2%; p = 0.032, 0.035, respectively). CONCLUSION: Measuring pre-interventional arterial remodeling patterns by IVUS may be helpful to stratify lesions at high-risk of ISR.

Prognostic significance of simvastatin therapy in patients with ischemic heart failure who underwent percutaneous coronary intervention for acute myocardial infarction.

We prospectively followed 202 patients with ischemic heart failure who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (left ventricular [LV] ejection fraction <40%). Patients were divided into 2 groups: groups I (simvastatin group, n = 106, aged 60.8 +/- 10.3 years, men 71.7%) and II (non-simvastatin group, n = 96, aged 60.9 +/- 10.4 years, men 78.1%). During 1-year clinical follow-up, simvastatin therapy was associated with a significant reduction in mortality (1.9% vs 7.5%, p = 0.048), restenosis rate (25.7% vs 43.1%, p = 0.033), and repeat PCI rate (25.7% vs 43.1%, p = 0.033), and with significant improvement in LV ejection fraction (31% to 42% vs 32% to 39%, p = 0.042). The event-free survival rate was higher in group I than in group II (79.8% vs 57.0%, p = 0.001). In conclusion, simvastatin therapy improves LV systolic function and decreases mortality, restenosis, and repeat PCI rate in patients with ischemic heart failure who underwent PCI for acute myocardial infarction.

Predictive factors of major adverse cardiac events in acute myocardial infarction patients complicated by cardiogenic shock undergoing primary percutaneous coronary intervention.

BACKGROUND: The aim of this study was to assess in-hospital mortality and major adverse cardiac events (MACE) during long-term clinical follow-up of patients who developed cardiogenic shock (CS) after acute myocardial infarction (AMI) and who underwent primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: The data from 147 patients with CS after AMI (61.7 +/-10.4 years, M:F =156:99) who underwent primary PCI at Chonnam National University Hospital between January 1999 and December 2002 were analyzed: clinical characteristics, coronary angiographic findings and mortality during admission, and MACE during a 1-year clinical follow-up. Of the enrolled patients, 121 patients survived (group I, M:F =94:27) and 26 died (group II, M:F =14:12) during admission. By binary logistic regression analysis, in-hospital death was associated with low Thrombolysis In Myocardial Infarction (TIMI) flow after coronary revascularization (p=0.02, odds ratio (OR) =1.3). Eighty-nine patients (60.5%) survived without MACE during the 1-year clinical follow-up and MACE was associated with a C-reactive protein (CRP) of more than 1 mg/dl (p=0.002, OR =6.3) and low TIMI flow after coronary revascularization (p<0.001, OR =7.8). CONCLUSIONS: Primary PCI achieving TIMI 3 flow reduces in-hospital death in AMI with CS. High concentration of CRP and low TIMI flow are associated with MACE during long-term clinical follow-up.

Effect of combined intracoronary adenosine and nicorandil on no-reflow phenomenon during percutaneous coronary intervention.

BACKGROUND: This study aimed to clarify the effect of intracoronary administration of combined adenosine and nicorandil on the no-reflow phenomenon. METHODS AND RESULTS: Fifty patients (67+/-10 years, 30 male) with acute myocardial infarction (AMI) who developed no-reflow phenomenon during primary percutaneous coronary intervention (PCI) between June 2001 and May 2003 comprised the study group, which was divided into 2 groups: group I [25 patients, 67+/-10 years, 13 male; adenosine (24 microg/ml) alone in addition to nitrate] and group II [25 patients, 66+/-9 years, 17 male; combined intracoronary administration of adenosine and nicorandil (2 mg/ml) in addition to nitrate]. In-hospital and 6-month major adverse cardiac events (MACE) after PCI were compared between the 2 groups. Risk factors of coronary disease, left ventricular ejection fraction and wall motion score were not significantly different between the 2 groups (p=NS). Time interval from the onset of chest pain to PCI, number of involved vessels, lesion type according to ACC/AHA classification and TIMI flow grade (TFG) were not significantly different in both groups (p=NS). Incidence of thrombosis or dissection after balloon angioplasty, diameter and length of stent, and use of Reopro during PCI were not significantly different. TFG after PCI (2.0+/-0.9 vs 2.6+/-0.6, p=0.024), DeltaTFG (1.5+/-1.1 vs 2.2+/-1.0, p=0.033) and difference in TIMI frame count (TFC) before and after PCI (DeltaTFC) were greater in group II than group I (45.2+/-24.5 vs 63.6+/-23.2, p=0.014). Myocardial blush score 3 was obtained more frequently in group II than group I (44% vs 76%, p=0.014). In-hospital death did not occur in any of group II, but 4 patients of group I died (p=0.043). Two cases of MACE developed in each group and heart failure occurred in 3 (12%) of group I and 1 (4%) of group II patients during the 6-month follow-up (p=NS). CONCLUSIONS: Intracoronary administration of adenosine combined with nicorandil may improve both the occurrence of no-reflow in patients during PCI for AMI and short-term clinical outcome, compared with adenosine alone.