Kyoung-Ha Park

Randomized Comparison of Everolimus-Eluting Stent Versus Sirolimus-Eluting Stent Implantation for De Novo Coronary Artery Disease in Patients With Diabetes Mellitus (ESSENCE-DIABETES) Results From the ESSENCE-DIABETES Trial

Background— Drug-eluting stents significantly improved angiographic and clinical outcomes compared with bare metal stents in diabetic patients. However, a comparison of everolimus-eluting stents and sirolimus-eluting stents in diabetic patients has not been evaluated. Therefore we compared effectiveness of everolimus-eluting stents and sirolimus-eluting stents in patients with diabetes mellitus. Methods and Results— This prospective, multicenter, randomized study compared everolimus-eluting stent (n=149) and sirolimus-eluting stent (n=151) implantation in diabetic patients. The primary end point was noninferiority of angiographic in-segment late loss at 8 months. Clinical events were also monitored for at least 12 months. Everolimus-eluting stents were noninferior to sirolimus-eluting stents for 8-month in-segment late loss (0.23±0.27 versus 0.37±0.52 mm; difference, −0.13 mm; 95% confidence interval, −0.25 to −0.02; upper 1-sided 95% confidence interval, −0.04; P<0.001 for noninferiority), with reductions in in-stent restenosis (0% versus 4.7%; P=0.029) and in-segment restenosis (0.9% versus 6.5%; P=0.035). However, in-stent late loss (0.11±0.26 versus 0.20±0.49 mm; P=0.114) was not statistically different between the 2 groups. At 12 months, ischemia-driven target lesion revascularization (0.7% versus 2.6%; P=0.317), death (1.3% versus 3.3%; P=0.448), and myocardial infarction (0% versus 1.3%; P=0.498) were not statistically different between the 2 groups. Major adverse cardiac events, including death, myocardial infarction, and ischemia-driven target lesion revascularization (2.0% versus 5.3%; P=0.218), were also not statistically different between the 2 groups. Conclusions— Everolimus-eluting stents were noninferior to sirolimus-eluting stents in reducing in-segment late loss and reduced angiographic restenosis at 8 months in patients with diabetes mellitus and coronary artery disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00997763.

A Randomized, Double-Blind, Multicenter Comparison Study of Triple Antiplatelet Therapy With Dual Antiplatelet Therapy to Reduce Restenosis After Drug-Eluting Stent Implantation in Long Coronary Lesions: Results From the DECLARE-LONG II (Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients with Long Coronary Lesions) Trial

OBJECTIVESnThe purpose of this study was to determine whether cilostazol reduces intimal hyperplasia in patients undergoing long zotarolimus-eluting stent implantation (stent length: ≥ 30 mm) for native long coronary lesions (length: ≥ 25 mm).nnnBACKGROUNDnRestenosis after drug-eluting stent implantation remains a significant clinical problem in long coronary lesions.nnnMETHODSnPatients (n = 499) were assigned randomly to triple (aspirin, clopidogrel, and cilostazol, triple group: n = 250) or dual antiplatelet therapy (aspirin and clopidogrel and placebo, dual group: n = 249) for 8 months after long zotarolimus-eluting stent implantation. The primary end point was in-stent late loss at the 8-month angiography according to the intention-to-treat principle.nnnRESULTSnThe 2 groups had similar baseline characteristics. The in-stent (0.56 ± 0.55 mm vs. 0.68 ± 0.59 mm, p = 0.045) and in-segment (0.32 ± 0.54 mm vs. 0.47 ± 0.54 mm, p = 0.006) late loss were significantly lower in the triple versus dual group, as were 8-month in-stent restenosis (10.8% vs. 19.1%, p = 0.016), in-segment restenosis (12.2% vs. 20.0%, p = 0.028), and 12-month ischemic-driven target lesion revascularization (5.2% vs. 10.0%, p = 0.042) rates. At 12 months, major adverse cardiac events including death, myocardial infarction, and ischemic-driven target lesion revascularization tended to be lower in the triple group than the dual group (7.2% vs. 12.0%, p = 0.07). Percent intimal hyperplasia volume by volumetric intravascular ultrasound analysis was reduced from 27.1 ± 13.2% for the dual group to 22.1 ± 9.9% for the triple group (p = 0.017).nnnCONCLUSIONSnPatients receiving triple antiplatelet therapy after long zotarolimus-eluting stent implantation had decreased extent of late luminal loss, percent intimal hyperplasia volume, and angiographic restenosis, resulting in a reduced risk of 12-month target lesion revascularization compared with patients receiving dual antiplatelet therapy. (Triple Versus Dual Antiplatelet Therapy after ABT578-Eluting Stent; NCT00589927).

Comparison of the effectiveness of sirolimus‐ and paclitaxel‐eluting stents for small coronary artery lesions

Background: The sirolimus‐eluting stent (SES) and the paclitaxel‐eluting stent (PES) reduce restenosis in small coronary artery lesions. However, it is not clear which of these stents is superior in terms of clinical outcomes. Methods: The authors retrospectively examined 197 patients with 245 de novo small coronary artery lesions (≤≤2.75 mm) that were treated with either the SES (156 lesions) or the PES (89 lesions). Six‐month angiographic restenosis rates and the 9‐month target lesion revascularization (TLR) rates were compared between the two groups. Results: In terms of baseline clinical and angiographic parameters, the two groups well matched together. Six‐month angiographic follow‐up was performed on 170 patients (86.3%), comprising 135 SES lesions (86.5%) and 76 PES lesions (85.4%). At 6‐month angiographic follow‐up, the late lumen loss was less in the SES group than in the PES group (0.29 ± 0.42 vs. 0.69 ± 0.63 mm, P < 0.01). Therefore, the SES group showed a lower rate of angiographic restenosis than the PES group (6.7% vs. 27.7%, P < 0.01). At 9 months there were no deaths or myocardial infarctions in either group. The 9‐month TLR rate was lower in the SES group than in the PES group (3.3% vs. 14.4%, P < 0.01). The Kaplan‐Meier estimate of freedom from TLR at 9 months was 96.7% for the SES patients and 86.5% for the PES patients (P < 0.01). Conclusions: The SES treatment may be superior to the PES treatment in terms of long‐term clinical and angiographic outcomes in patients with small coronary artery lesions.

Alterations in arterial function after high-voltage electrical injury

IntroductionThe aim of this study was to evaluate the functional changes of the arterial endothelium and smooth muscle after a high-voltage electrical injury (HVEI), using flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD).MethodsTwenty-five male patients injured in the upper extremities by current due to contact with more than 20,000 volts were enrolled in the study. FMD and NMD were measured on the brachial artery within 48 hours after HVEI, and follow-up FMD and NMD were evaluated six weeks later. In addition, we enrolled an age, sex and body mass index matched healthy control group consisting of 25 individuals. Including FMD and NMD, all the variables of the control group were investigated one time and compared with the initial and six week follow-up data of the HVEI group.ResultsA significantly lower initial FMD was seen in the HVEI group compared with the control group (2.1 ± 1.2% versus 13.6 ± 3.4%, P < 0.01). At the six week follow-up, the FMD of the HVEI group had significantly improved compared to the initial FMD (2.1 ± 1.2% versus 5.1 ± 2.1%, P < 0.01), but it was still lower than the FMD of the control group (5.1 ± 2.1% versus 13.6 ± 3.4%, P < 0.01). A significantly lower NMD was seen both initially and at the six week follow-up compared with the NMD of the control group (7.3 ± 4.7% versus 20.4 ± 4.1%, P < 0.01 and 11.4 ± 6.7% versus 20.4 ± 4.1%, P < 0.01, respectively). The FMD study of the contralateral arm which was uninjured by HVEI was available in six patients. In those patients, the six week follow-up FMD was significantly improved in the HVEI arm compared with the initial FMD (1.8 ± 0.6% versus 4.4 ± 1.6%, P < 0.01). However, in the contralateral uninjured arm, there was no difference between the initial and the six week follow-up FMDs (5.5 ± 1.4% versus 6.9 ± 2.2%, P = 0.26).ConclusionsAfter HVEI, the endothelial and smooth muscle functions of the brachial artery were significantly decreased for at least six weeks. Long term cautious care might be needed for all victims of HVEI, because there is a chance of increased risk of thrombosis or stenosis in the injured arm.

Alterations of carotid arterial mechanics preceding the wall thickening in patients with hypertension

BACKGROUND AND AIMSnCarotid intima-media thickness (cIMT) is an established surrogate marker of atherosclerosis. However, cIMT may not reflect the whole arterial changes occurring in various pathologic conditions, such as hypertension. The aim of this study was to evaluate whether vascular properties of carotid artery (CA) in patients with hypertension differ from those of patients with diabetes and controls before the progression of cIMT.nnnMETHODSnVascular properties of CA were assessed in 402 consecutive asymptomatic subjects who have normal cIMT (131 with hypertension, 151 with diabetes mellitus, and 120 controls). Conventional carotid stiffness indices calculated from vessel diameter and blood pressure, and parameters from velocity-vector imaging (VVI), including vessel area, fractional area change (FAC), radial velocity, circumferential strain, and strain rate were measured to assess the differences between the groups.nnnRESULTSnIn univariate analysis, both patients with hypertension and diabetes showed higher elastic modulus, lower distensibility coefficients and FAC of VVI than those of controls. However, when adjusting for baseline covariates, only FAC (odds ratio [OR]xa0=xa00.82, 95% confidence interval [CI]xa0=xa00.70-0.97, pxa0=xa00.025) and vessel area (ORxa0=xa02.84, 95% CIxa0=xa01.64-4.91, pxa0<xa00.001) discriminated CA of patients with hypertension from those of controls. Also, patients with hypertension showed larger vessel area than diabetes (ORxa0=xa02.58, 95% CIxa0=xa01.75-3.80, pxa0<xa00.001) independent of baseline covariates. No significant vascular parameter was found to discriminate patients with diabetes from controls after adjustments.nnnCONCLUSIONnDespite normal cIMT, the CA of hypertensive patients was stiffer than those of controls and positive remodeling preceded the wall thickening independent of baseline covariates.

Functional recovery of regional myocardial deformation in patients with takotsubo cardiomyopathy

BACKGROUNDnTakotsubo cardiomyopathy (TC) is acute, but completely reversible in the absence of significant coronary artery disease. This study aims to assess the functional recovery of regional myocardial deformation in patients with TC using 2-dimensional (2D) speckle tracking echocardiography.nnnMETHODSnThirty-three patients diagnosed with TC (mean age 63 years, 26 female) prospectively underwent serial 2D echocardiography on day 1 (initial presentation), day 4 [the middle, interquartile range (IQR), 2-5 days], and day 21 (recovery, IQR 13-32 days). Twenty-one (64%) patients showed classical type of TC with akinesis of mid-left ventricular (LV) and apical segments and 12 (36%) of patients presented with mid-LV variant with apical sparing. Myocardial deformations were serially assessed using 2D strain analysis. All echocardiographic values on day 21 were compared with the corresponding values from 30 controls of similar age and gender.nnnRESULTSnLV ejection fraction (EF) gradually improved at follow-up (32±8% on day 1 vs. 62±4% on day 21, p<0.001). Despite no difference in LVEF between the patients with complete recovery (LVEF >60% on day 21) and controls, the patients showed significantly lower global longitudinal strain than controls. On regional analysis of the mid-LV segments, both longitudinal and circumferential strains of patients with TC were similarly diminished on day 1. During recovery, longitudinal strain showed more delayed recovery than circumferential strain compared to the values of controls. In LV apex of controls, circumferential strain normally presented higher value than longitudinal strain. In LV apex of patients with classical TC, the reduced circumferential strain on day 1 rapidly increased with a wide variation to maintain augmented circumferential shortening.nnnCONCLUSIONSnQuantifying LV myocardial deformation in patients with TC is informative in the detection of persistent subtle LV dysfunction and improves our understanding of regional myocardial mechanics during recovery.

The Heart Valve Society. 2nd Annual Meeting, March 17-19, 2016, New York City, N.Y., USA: Abstracts

s Cardiology 2016;134:136–310 DOI: 10.1159/000444511 147 Remodeling of Tissue-Engineered Heart Valves during a One-Year Follow-Up Period in Sheep – A Computational-Experimental Analysis Sandra Loerakker1, Bart Sanders1, Boris Schmitt2, Petra E. Dijkman3, Hendrik Spriestersbach2, Anita Driessen-Mol1, Emanuela S. Fioretta1, Marco Bartosch2, Laura Frese3, Simon P. Hoerstrup3, Felix Berger2, Frank P.T. Baaijens 1Eindhoven University of Technology, Eindhoven, Netherlands; 2Deutsches Herzzentrum Berlin, Berlin, Germany; 3University and University Hospital Zurich, Zurich, Switzerland Objective: The functionality of tissue-engineered heart valves (TEHVs) often decreases over time due to leaflet retraction. Since mechanical factors play an important role in the remodeling process of cardiovascular tissues, understanding the interplay between mechanics and remodeling is crucial for developing TEHVs with long-term functionality. Previously, we suggested a valve design that could prevent or minimize leaflet shortening after implantation. The goal of the present study was to investigate the in vivo remodeling process with this new design and understand and predict the (robustness of the) remodeling process using computational models. Methods: TEHVs with the new design were implanted in the pulmonary position of sheep (n = 3) for a period of a full year. Valve functionality was monitored every four weeks via cMRI, and tissue composition and organization after remodeling were investigated in the explants. Based on the initial geometry and material properties of the valves before implantation, a computational model was used to predict and understand (the robustness of) the in vivo remodeling process. This model included cell contractility, cell-mediated collagen contraction, and strain-dependent collagen remodeling. Results: For the first time, all TEHVs preserved their functionality throughout the complete implantation period. The collagen fibers appeared to remodel from an initially random distribution towards a circumferentially oriented collagen network. Furthermore, the contractility of the cells in the valve appeared to be low. Our computational model was able to quantitatively predict the remodeling response of the valves when cell contractility was assumed to be low. Variations in cell contractility and initial leaflet thickness in the model demonstrated that valve functionality after remodeling is most sensitive to cell contractility, whereas the collagen architecture appeared to be quite insensitive to changes in cell contractility or leaflet thickness. Conclusions: Our combined computational-experimental efforts confirmed that TEHVs can maintain their functionality during a oneyear follow-up period when the initial valve design is chosen carefully. Computational models were essential in defining a rational design, and predicting the most important determinants in the remodeling process. We gratefully acknowledge the support of the EU ([FP7/2007–2013], grant agreement no. 242008), and the Netherlands CardioVascular Research Initiative (CVON2012-01). A New Fluid-Structure Interaction Model for Bicuspid

Endothelial Function and Cardiovascular Autonomic Activity in Neurally Mediated Syncope

Objectives: The aim of this study was to investigate endothelial function and cardiovascular autonomic activity in patients with neurally mediated syncope (NMS). Methods: Patients with a typical history of NMS were divided according to the result of a head-up tilt (HUT) test. There were 25 patients each in the HUT-positive (HUT+), HUT-negative (HUT-) and control groups. Flow-mediated dilation (FMD) and 24-hour ambulatory electrocardiography (AECG) were performed before the HUT tests. Results: The HUT+ group had a significantly higher FMD than that of the HUT- group and the control group (8.8 ± 3.3 vs. 6.4 ± 2.9%, p = 0.006, and 8.8 ± 3.3 vs. 5.7 ± 2.2%, p = 0.001, respectively). On a 24-hour AECG, the parasympathetic indexes of time domain, such as rMSSD and the pNN50, were significantly higher in the HUT+ group than in the HUT- group (39.0 ± 9.6 vs. 31.6 ± 9.6 ms, p = 0.016, and 16.5 ± 8.1 vs. 10.2 ± 7.2%, p = 0.002, respectively) and the control group (39.0 ± 9.6 vs. 28.9 ± 9.6%, p = 0.001 and 16.5 ± 8.1 vs. 8.7 ± 6.7%, p = 0.001, respectively). High-frequency spectra (parasympathetic activity) of the frequency domain showed similar results. Conclusions: Not only parasympathetic activity, but also endothelial function may affect the results of HUT tests in patients with NMS.

Functional changes of the myocardium in survivors of high-voltage electrical injury

IntroductionThere are limited long-term follow-up data on functional changes in the myocardium after high-voltage electrical injury (HVEI).MethodsTwenty-three patients who had been exposed to HVEI (>20,000 volts) and preserved left ventricular ejection fraction (≥55%) were enrolled in the study. Echocardiographic parameters, including peak systolic strain (S) and strain rate (SR), were evaluated at baseline, six weeks and six months later. These data were compared with a healthy control group who were matched in terms of age, sex and body mass index.ResultsThe systolic and diastolic blood pressure and the heart rate were significantly higher in the HVEI group compared with the control group at baseline and at six weeks, but not at the six-month follow-up. Conventional echocardiographic data showed no differences between the groups during the study period. In contrast to the S, the baseline and six weeks, SR was significantly increased in the HVEI group compared with the control group. However, at the six-month follow-up, there was no difference in the SR between the groups. Among the 23 patients with HVEI, 17 of the patients had vertical current injury, and 6 patients had horizontal current injury. There was no difference in terms of the conventional echocardiography, S and SR between the patients with vertical injury and those with horizontal injury at baseline and at the six-month follow-up.ConclusionsThe long-term contractile performance of the myocardium is preserved when patient do not experience left ventricular dysfunction in the early stages after HVEI.

Combined Treatment With Dichloroacetic Acid and Pyruvate Reduces Hippocampal Neuronal Death After Transient Cerebral Ischemia

Transient cerebral ischemia (TCI) occurs when blood flow to the brain is ceased or dramatically reduced. TCI causes energy depletion and oxidative stress, which leads to neuronal death and cognitive impairment. Dichloroacetic acid (DCA) acts as an inhibitor of pyruvate dehydrogenase kinase (PDK). Additionally, DCA is known to increase mitochondrial pyruvate uptake and promotes glucose oxidation during glycolysis, thus enhancing pyruvate dehydrogenase (PDH) activity. In this study, we investigated whether the inhibition of PDK activity by DCA, which increases the rate of pyruvate conversion to adenosine triphosphate (ATP), prevents ischemia-induced neuronal death. We used a rat model of TCI, which was induced by common carotid artery occlusion and hypovolemia for 7u2009min while monitoring the electroencephalography for sustained isoelectric potential. Male Sprague-Dawley rats were given an intraperitoneal injection of DCA (100u2009mg/kg) with pyruvate (50u2009mg/kg) once per day for 2u2009days after insult. The vehicle, DCA only or pyruvate on rats was injected on the same schedule. Our study demonstrated that the combined administration of DCA with pyruvate significantly decreased neuronal death, oxidative stress, microglia activation when compared with DCA, or pyruvate injection alone. These findings suggest that the administration of DCA with pyruvate may enhance essential metabolic processes, which in turn promotes the regenerative capacity of the post-ischemic brain.