Seil Oh

Mobilized Endothelial Progenitor Cells by Granulocyte-Macrophage Colony-Stimulating Factor Accelerate Reendothelialization and Reduce Vascular Inflammation After Intravascular Radiation

Background—Endothelial progenitor cells (EPCs) play a pivotal role in repair and regeneration of damaged vessels. We investigated the role of mobilized EPCs in the healing process after intravascular radiation therapy. Methods and Results—One iliac artery of hypercholesterolemic rabbits was subjected to balloon injury and intravascular radiation with a Re-188 balloon and the contralateral iliac artery to balloon injury only. Rabbits received granulocyte-macrophage colony-stimulating factor (recombinant human GM-CSF) (60 &mgr;g/d subcutaneously) daily for 1 week, either 7 days before the angioplasty or at the time of angioplasty. Control rabbits received human albumin. GM-CSF significantly increased the double-positive (CD31+ and KDR+) fraction in peripheral blood monocytes and showed a higher number of EPCs than albumin after culture and, furthermore, enhanced migration and incorporation of EPCs. In the albumin group, intravascular radiation therapy reduced neointimal hyperplasia but delayed reendothelialization and aggravated monocyte infiltration. GM-CSF treatment significantly accelerated the reendothelialization and inhibited monocyte infiltration (reendothelialization index, 81±13% in the GM-CSF radiation [n=7] versus 30±11% in the control radiation [n=9] at 2 weeks, P <0.01). GM-CSF treatment produced an additional significant reduction in neointimal formation at 14 and 28 days after injury in the intravascular radiation groups (intima to media ratio, 0.14±0.11 in the GM-CSF radiation [n=5] versus 0.36±0.07 in the control radiation [n=5] at 4 weeks, P <0.01). Conclusions—GM-CSF treatment mobilizes EPCs, accelerates reendothelialization, and reduces monocytes infiltration after intravascular radiation therapy, suggesting that stem cell mobilization is a promising strategy for enhancing the vascular healing process after cytotoxic angioplasty.

Novel robotic catheter remote control system: feasibility and safety of transseptal puncture and endocardial catheter navigation

Objectives: The aims of this study were to demonstrate the safety and the feasibility of the robotic catheter remote control system (CCS) in endocardial navigation in all cardiac chambers, as well as facilitation of the transseptal puncture.

Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation.

Objective We studied evolving antithrombotic therapy patterns in patients with newly diagnosed non-valvular atrial fibrillation (AF) and ≥1 additional stroke risk factor between 2010 and 2015. Methods 39 670 patients were prospectively enrolled in four sequential cohorts in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF): cohort C1 (2010–2011), n=5500; C2 (2011–2013), n=11 662; C3 (2013–2014), n=11 462; C4 (2014–2015), n=11 046. Baseline characteristics and antithrombotic therapy initiated at diagnosis were analysed by cohort. Results Baseline characteristics were similar across cohorts. Median CHA2DS2-VASc (cardiac failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65–74 and sex category (female)) score was 3 in all four cohorts. From C1 to C4, the proportion of patients on anticoagulant (AC) therapy increased by almost 15% (C1 57.4%; C4 71.1%). Use of vitamin K antagonist (VKA)±antiplatelet (AP) (C1 53.2%; C4 34.0%) and AP monotherapy (C1 30.2%; C4 16.6%) declined, while use of non-VKA oral ACs (NOACs)±AP increased (C1 4.2%; C4 37.0%). Most CHA2DS2-VASc ≥2 patients received AC, and this proportion increased over time, largely driven by NOAC prescribing. NOACs were more frequently prescribed than VKAs in men, the elderly, patients of Asian ethnicity, those with dementia, or those using non-steroidal anti-inflammatory drugs, and current smokers. VKA use was more common in patients with cardiac, vascular, or renal comorbidities. Conclusions Since NOACs were introduced, there has been an increase in newly diagnosed patients with AF at risk of stroke receiving guideline-recommended therapy, predominantly driven by increased use of NOACs and reduced use of VKA±AP or AP alone. Trial registration number NCT01090362; Pre-results.

Chronic Atrioventricular Nodal Vagal Stimulation First Evidence for Long-Term Ventricular Rate Control in Canine Atrial Fibrillation Model

Background— We have previously demonstrated that selective atrioventricular nodal (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during atrial fibrillation (AF) in acute experiments. However, it is not known whether this approach could provide a long-term treatment in conscious animals. Thus, this study reports the first observations on the long-term efficacy and safety of this novel approach to control ventricular rate during AF in chronically instrumented dogs. Methods and Results— In 18 dogs, custom-made bipolar patch electrodes were sutured to the epicardial AVN fat pad for delivery of selective AVN-VS by a subcutaneously implanted nerve stimulator (pulse width 100 &mgr;s or 1 ms, frequency 20 or 160 Hz, amplitude 6 to 10 V). Fast-rate right atrial pacing (600 bpm) was used to induce and maintain AF. ECG, blood pressure, and body temperature were monitored telemetrically. One week after the induction of AF, AVN-VS was delivered and maintained for at least 5 weeks. It was found that AVN-VS had a consistent effect on ventricular rate slowing (on average 45±13 bpm) over the entire period of observation. Echocardiography showed improvement of cardiac indices with ventricular rate slowing. AVN-VS was well tolerated by the animals, causing no signs of distress or discomfort. Conclusions— Beneficial long-term ventricular rate slowing during AF can be achieved by implantation of a nerve stimulator attached to the epicardial AVN fat pad. This novel concept is an attractive alternative to other methods of rate control and may be applicable in a selected group of patients.

Effects of acute hyperglycemia on endothelium-dependent vasodilation in patients with diabetes mellitus or impaired glucose metabolism.

Although impaired endothelial function is well known in patients with diabetes mellitus (DM), the precise mechanism and the factors that contribute to this dysfunction remain to be clarified. The authors examined the effect of acute hyperglycemia on endothelium-dependent vasodilation in patients with DM or impaired glucose metabolism in vivo by plethysmography. In eight patients with diabetes mellitus or impaired glucose metabolism, the vasodilatory response to acetylcholine at infusion rates of 7.5, 15, and 30 microg/min was studied in the fasting state and at two levels of hyperglycemia, which were achieved by the infusion of glucose, insulin, and somatostatin. The vasodilatory response to acetylcholine was measured by calculating the forearm blood flow ratio (FBFR), defined as the measured forearm blood flow at a specific acetylcholine infusion rate divided by the baseline forearm blood flow without acetylcholine infusion. The induction of hyperglycemia resulted in a significant reduction in FBFR for all rates of acetylcholine infusion. The FBFR at an acetylcholine infusion rate of 7.5 microg/min was 1.13 +/- 0.07 and 1.19 +/- 0.06 for stages 1 and 2, respectively, compared with 1.36 +/- 0.08 for stage 3 (p < .05). In addition, at an acetylcholine infusion rate of 30 microg/min, the reduction in FBFR was associated with the degree of hyperglycemia (3.72 +/- 0.51, 2.98 +/- 0.42, 2.42 +/- 0.32 for stages 1, 2, and 3 glucose levels, respectively, at an acetylcholine infusion rate of 30 microg/min, p < .05 by analysis of variance [ANOVA]). The results show that the induction of hyperglycemia results in a significant attenuation of endothelial function, and suggests the importance of hyperglycemia in the development of endothelial dysfunction observed in patients with DM or impaired glucose metabolism.

Does Sex Affect Anticoagulant Use for Stroke Prevention in Nonvalvular Atrial Fibrillation? The Prospective Global Anticoagulant Registry in the FIELD-Atrial Fibrillation

Background—Among patients with atrial fibrillation (AF), women are at higher risk of stroke than men. Using prospective cohort data from a large global population of patients with nonvalvular AF, we sought to identify any differences in the use of anticoagulants for stroke prevention in women and men. Methods and Results—This was a prospective multicenter observational registry with 858 randomly selected sites in 30 countries. A total of 17 184 patients with newly diagnosed (⩽6 weeks) nonvalvular AF and ≥1 additional investigator-defined stroke risk factor(s) were recruited (March 2010 to June 2013). The main outcome measure was the use of anticoagulants (vitamin K antagonists, factor Xa inhibitors, and direct thrombin inhibitors) for stroke prevention at AF diagnosis. Of 17 184 patients enrolled, 43.8% were women. More women than men were at moderate-to-high risk of stroke (CHADS2 score ≥2: 65.1% versus 54.7%). Rates of anticoagulant use were not different overall (60.9% of men versus 60.8% of women) and in patients with a CHADS2 score ≥2 (adjusted odds ratio for women versus men, 1.00; 95% confidence interval, 0.92–1.09). In patients at low risk (CHA2DS2-VASc of 0 in men and 1 in women), 41.8% of men and 41.1% of women received an anticoagulant. In patients at high risk (CHA2DS2-VASc score ≥2), 35.4% of men and 38.4% of women did not receive an anticoagulant. Conclusions—These contemporary global data show that anticoagulant use for stroke prevention is no different in men and women with nonvalvular AF. Thromboprophylaxis was, however, suboptimal in substantial proportions of men and women, with underuse in those at moderate-to-high risk of stroke and overuse in those at low risk. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

Esophageal Luminal Temperature Measurement Underestimates Esophageal Tissue Temperature During Radiofrequency Ablation Within the Canine Left Atrium: Comparison Between 8 mm Tip and Open Irrigation Catheters

Introduction: Evaluation of luminal temperature during left atrial ablation is used clinically; however, luminal temperature does not necessarily reflect temperature within the esophageal wall and poses a risk of atrioesophageal fistula. This animal study evaluates luminal esophageal temperature and its relation to the temperature of the external esophageal tissue during left atrial lesions using the 8 mm solid tip and the open irrigated tip catheters (OIC).

Functional polymorphism in the promoter region of the gelatinase B gene in relation to coronary artery disease and restenosis after percutaneous coronary intervention.

AbstractThe matrix metalloproteinases appear to play an important role in the development and progression of atherosclerotic lesions. We studied the C-1562T polymorphism of the gelatinase B promoter in relation to coronary artery disease and restenosis after a percutaneous coronary intervention (PCI) in Koreans. To determine the frequency of the C-1562T allele, we examined 63 patients with coronary artery disease who underwent both PCI and 6-month follow-up coronary angiograms (CAGs), and 67 control patients with a normal CAG with respect to their clinical data and genotype. Frequencies of the C/C homozygotes and the non-C/C heterozygotes and homozygotes (C/T and T/T) were 94% and 6% in the normal CAG group, and 76.2% and 23.8% in the patient group, respectively. This gave a relative risk of 0.203 (95% CI: 0.063–0.651, P = 0.005) for coronary artery disease when the C/C genotype was compared with the non-C/C genotype. In the patient groups, the allele frequencies of the C/C and non-C/C were 80% and 20% in the nonrestenotic subgroup, and 71.4% and 28.6% in the restenotic subgroup (P = 0.554). No T/T homozygote was found in any of the groups. We conclude that C/C homozygosity is a potential genetic protective factor for coronary artery disease in Koreans.

The association of cholesteryl ester transfer protein polymorphism with high-density lipoprotein cholesterol and coronary artery disease in Koreans

Cholesteryl ester transfer protein (CETP) is a key protein involved in high‐density lipoprotein cholesterol (HDL‐C) metabolism. It is known to affect plasma HDL‐C levels, and its genetic regulation may be involved in the development of coronary artery disease (CAD). The aim of this study was to determine the frequency of the CETP Taq1B polymorphism in Koreans, and to investigate its relationship with plasma HDL‐C levels and CAD. One‐hundred and nineteen patients with significant CAD and 106 controls were examined with respect to their genotypes, lipid profiles and other risk factors of CAD. The genotype frequencies of B1B1:B1B2:B2B2 in males and females were 35.5%:50%:14.5% and 34.7%:42.6%:22.7%, respectively, which is comparable to previous reports in other ethnic groups. The B1B1 homozygote was associated with significantly lower HDL‐C levels in females (p = 0.049) and non‐smoking males (p = 0.037). After controlling for gender, body mass index (BMI) and smoking, the TaqIB polymorphism was still significantly associated with HDL‐C levels (p = 0.046) and explained 5.4% of the HDL‐C variation in this study. By univariate analysis, the B1B1 homozygote was a significant predictor of CAD (p = 0.043), and this was confirmed by multivariate analysis with traditional risk factors, i.e. the B1B1 homozygote was an independent predictor of CAD (p = 0.026, odds ratio = 1.97, 95% confidence interval: 1.08–3.57). In conclusion, the B1B1 homozygote of the CETP Taq1B polymorphism is associated with low HDL‐C levels in females and non‐smoking males, and may be an independent genetic risk factor of CAD in the Korean population.

Association of endothelial constitutive nitric oxide synthase gene polymorphism with acute coronary syndrome in Koreans

Objective: To examine the effects of two polymorphisms of the endothelial constitutive nitric oxide synthase (ecNOS) gene, 4a/4b(A:B) located in intron 4 and Glu298Asp(G:T) located in exon 7, on the development of acute coronary syndromes (ACS). Methods: 164 patients with ACS and 142 control participants were investigated for genotype and conventional risk factors. Genotype was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. Results: Genotype and allele frequencies of the A:B polymorphism in the ACS group (0.15:0.85 for AA+AB:BB, 0.09:0.91 for A:B) differed from those in the control group (0.26:0.74 for AA+AB:BB, 0.15:0.85 for A:B). However, genotype and allele frequencies of the G:T polymorphism in the ACS group (0.22:0.78 for TT+TG:GG, 0.11:0.89 for T:G) were similar to those in the control group (0.17:0.83 for TT+TG:GG, 0.09:0.91 for T:G). Multiple logistic regression analysis showed that the non-BB (AA+AB) and the non-BB+GG genotypes were significant protective factors against ACS (odds ratios 0.49 and 0.34, 95% confidence intervals 0.26 to 0.93 and 0.14 to 0.83, respectively). In addition, linear association analysis showed that the percentage of ACS patients was significantly lower in the genotype group non-BB+GG than in the genotype group BB+non-GG (39.6% v 62.7%, p  =  0.01). Conclusions: The non-BB genotype of the ecNOS 4a/4b gene polymorphism is a protective factor against the development of ACS. The GG genotype of the ecNOS Glu298Asp polymorphism exerts a benefit in addition to the non-BB genotype in the Korean population.