You Ho Kim

Overexpression of Uncoupling Protein 2 in THP1 Monocytes Inhibits β2 Integrin-Mediated Firm Adhesion and Transendothelial Migration

Objective—Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and regulates production of reactive oxygen species in macrophages. Previous studies have shown that selective genetic disruption of UCP2 in bone marrow cells results in excess accumulation of monocytes/macrophages in the vascular wall of hypercholesterolemic low-density lipoprotein receptor-deficient (LDLR−/−) mice. Here we investigated whether UCP2 regulates expression of genes involved in monocyte recruitment. Methods and Results—UCP2 overexpression in THP1 monocytes, which induced a 10-fold increase in mitochondrial UCP2 protein levels, reduced steady-state level of intracellular reactive oxygen species (ROS) and H2O2-induced ROS production. THP1 monocytes with UCP2 overexpression showed lower intracellular calcium levels and less H2O2-triggered intracellular calcium mobilization, and less protein and mRNA levels of β2 integrins, most notably CD11b. UCP2 overexpression reduced β2 integrin-mediated firm adhesion of monocytes to either tumor necrosis factor-α (TNF-α)–stimulated human aortic endothelial cell (HAEC) monolayers or to plates coated with intercellular adhesion molecule-1, not vascular cell adhesion molecule-1. UCP2 overexpression also inhibited cell spreading and actin polymerization in monocytes treated with TNF-α and monocyte chemoattractant protein-1 (MCP-1), and reduced MCP-1–induced transmigration of monocytes through HAEC monolayers. Conclusions—Mitochondrial UCP2 in circulating monocytes may prevent excessive accumulation of monocytes/macrophages in the arterial wall, thereby reducing atherosclerotic plaque formation.

A prospective longitudinal study evaluating the usefulness of a T-cell-based assay for latent tuberculosis infection in kidney transplant recipients.

We evaluated whether ELISPOT assay can predict tuberculosis (TB) development in kidney‐transplantation (KT) recipients with a negative tuberculin skin test (TST). All adult patients admitted to a KT institute between June 2008 and December 2009 were enrolled; TB development after KT was observed between June 2008 and December 2010. Isoniazid (INH) was given to those patients with positive TST or clinical risk factors for latent TB infection (LTBI). ELISPOT assay was performed on all patients, and TB development after KT was observed by a researcher blinded to the results of ELISPOT. A total of 312 KT recipients including 242 (78%) living‐donor KT were enrolled. Of the 312 patients, 40 (13%) had positive TST or clinical risk factors for LTBI and received INH; none developed TB after KT. Of the remaining 272 patients, 4 (6%) of 71 with positive ELISPOT assay developed TB after KT, whereas none of the 201 patients with negative (n = 171) or indeterminate ELISPOTs (n = 30) developed TB after KT (rate difference between positive and negative/indeterminate ELISPOT, 3.3 per 100 person‐years [95% CI 1.4–5.1, p<0.001]). Positive ELISPOT results predict subsequent development of TB in KT recipients in whom LTBI cannot be detected by TST or who lack clinical risk factors for LTBI.

Lysophosphatidylcholine up-regulates CXCR4 chemokine receptor expression in human CD4 T cells

Oxidized low‐density lipoprotein (OxLDL) is an inflammatory modulator in the atherosclerotic plaque. We examined the effect of lysophosphatidylcholine (lysoPC), a main phospholipid component of OxLDL, on inflammatory responses in human CD4 T cells. We found that lysoPC dose‐ and time‐dependently increased expression of CXCR4, the chemokine receptor on CD4 T cells. This increase was inhibited by caffeic acid phenethyl ester or SN50, nuclear factor‐κB inhibitors, and also by suppression of G2A expression, the specific receptor for lysoPC, using antisense oligonucleotide. lysoPC enhanced CD4 T cell chemotaxis in response to stromal cell‐derived factor‐1 (SDF‐1), the exclusive ligand for CXCR4. lysoPC also enhanced SDF‐1‐stimulated production of inflammatory cytokines interleukin‐2 and interferon‐γ by CD4 T cells activated by anti‐CD3 immunoglobulin G. In conclusion, this study demonstrates that lysoPC directly modulates inflammatory responses in human CD4 T cells. The data suggest that the presence of lysoPC and SDF‐1 in atherosclerotic lesions may trigger inflammatory responses mediated by CD4 T cells, which may play an important role in progression of atherosclerosis.

Increased incidence of herpes zoster in the setting of cytomegalovirus preemptive therapy after kidney transplantation.

Herpes zoster (HZ) is a common infectious disease after kidney transplantation (KT). The incidence of HZ may increase during cytomegalovirus (CMV) preemptive therapy. We therefore evaluated the incidence, risk factors, and clinical outcomes of HZ after KT, according to the type of CMV prophylaxis used.

Cytomegalovirus infection after acute rejection therapy in seropositive kidney transplant recipients

Acute rejection (AR) after solid organ transplantation has been known to be a risk factor for cytomegalovirus (CMV) infection. However, data regarding the risk for CMV infection during and after anti‐rejection therapy are limited. This study investigated whether the risk of CMV infection and disease within 6 months of kidney transplantation (KT) increases in CMV‐seropositive KT recipients who develop AR.

Benefit of implantable cardioverter-defibrillator therapy after generator replacement in patients with Brugada syndrome

BACKGROUND An implantable cardioverter-defibrillator (ICD) is the only proven effective therapeutic strategy for patients with Brugada syndrome (BS). However, it is controversial whether the device should be replaced even in patients who had never experienced appropriate ICD therapy until the time of generator replacement. METHODS AND RESULTS This was a nationwide, multicenter retrospective study that enrolled patients who were diagnosed with BS and had an ICD implantation between January 1998 and April 2014. Appropriate ICD therapies administered for ventricular tachyarrhythmia were evaluated during follow-up. A total of 117 patients (age 43 ± 12 years, male 115 [98.3%]) were enrolled, and the mean follow-up duration was 6.0 ± 4.1 years. Thirty-seven (31.6%) patients had experienced appropriate ICD therapy during follow-up. Of all patients, 46 underwent replacement of the device. After the first generator replacement, the incidence of appropriate ICD therapy remained as high as 65.2% in patients who previously experienced appropriate ICD therapy before generator replacement. In 30 patients who did not experience any cardiac events until the first generator change, two (8.7%) had an episode of appropriate ICD therapy afterwards. CONCLUSIONS No episode of ICD therapy before generator replacement could not guarantee a safe clinical course. ICD generator replacement should be considered even in patients without ICD therapy before.

Prognosis after Implantation of Cardioverter-Defibrillators in Korean Patients with Brugada Syndrome

Purpose Our study aims to analyze prognosis after implantable cardioverter-defibrillator (ICD) implantation in Korean patients with Brugada syndrome (BrS). Materials and Methods This was a retrospective study of BrS patients implanted with an ICD at one of four centers in Korea between January 1998 and April 2012. Sixty-nine patients (68 males, 1 female) were implanted with an ICD based on aborted cardiac arrest (n=38, 55%), history of syncope (n=17, 25%), or induced ven tricular tachyarrhythmia on electrophysiologic study in asymptomatic patients (n=14, 20%). A family history of sudden cardiac death and a spontaneous type 1 electrocardiography (ECG) were noted in 13 patients (19%) and 44 patients (64%), respectively. Results During a mean follow-up of 59±46 months, 4.6±5.5 appropri ate shocks were delivered in 19 patients (28%). Fourteen patients (20%) experienced 5.2±8.0 inappropriate shocks caused by supraventricular arrhythmia, lead failure, or abnormal sensing. Six patients were admitted for cardiac causes during follow-up, but no cardiac deaths occurred. An episode of aborted cardiac arrest was a significant predictor of appropriate shock, and the composite of cardiac events in the Cox pro portional hazard model [hazard ratio (95% confidence interval) was 11.34 (1.31-97.94) and 4.78 (1.41-16.22), respectively]. However, a spontaneous type 1 ECG was not a predictor of cardiac events. Conclusion Appropriate shock (28%) and inappropriate shock (20%) were noted during a mean follow-up of 59±46 months in Korean BrS patients implanted with an ICD. An episode of aborted cardiac ar rest was the most powerful predictor of cardiac events.

Transvenous Lead Extraction via the Inferior Approach Using a Gooseneck Snare versus Simple Manual Traction

Background and Objectives The number of patients with cardiac implantable electronic devices needing lead extraction is increasing for various reasons, including infections, vascular obstruction, and lead failure. We report our experience with transvenous extraction of pacemaker and defibrillator leads via the inferior approach of using a gooseneck snare as a first-line therapy and compare extraction using a gooseneck snare with extraction using simple manual traction. Subjects and Methods The study included 23 consecutive patients (43 leads) who underwent transvenous lead extraction using a gooseneck snare (group A) and 10 consecutive patients (17 leads) who underwent lead extraction using simple manual traction (group B). Patient characteristics, indications, and outcomes were analyzed and compared between the groups. Results The dwelling time of the leads was longer in group A (median, 121) than in group B (median, 56; p=0.000). No differences were noted in the overall procedural success rate (69.6% vs. 70%), clinical procedural success rate (82.6% vs. 90%), and lead clinical success rate (86% vs. 94.1%) between the groups. The procedural success rates according to lead type were 89.2% and 100% for pacing leads and 66.7% and 83.3% for defibrillator leads in groups A and B, respectively. Major complications were noted in 3 (mortality in 1) patients in group A and 2 patients in group B. Conclusion Transvenous extraction of pacemaker leads via an inferior approach using a gooseneck snare was both safe and effective. However, stand-alone transvenous extraction of defibrillator leads using the inferior approach was suboptimal.

Tachyarrhythmia Cycle Length in Appropriate versus Inappropriate Defibrillator Shocks in Brugada Syndrome, Early Repolarization Syndrome, or Idiopathic Ventricular Fibrillation

Background and Objectives Implantable cardioverter–defibrillators (ICDs) are indicated in patients with Brugada syndrome (BS), early repolarization syndrome (ERS), or idiopathic ventricular fibrillation (IVF) who are at high risk for sudden cardiac death. The optimal ICD programming for reducing inappropriate shocks in these patients remains to be determined. We investigated the difference in the mean cycle length of tachyarrhythmias that activated either appropriate or inappropriate ICD shocks in these three patient groups to determine the optimal ventricular fibrillation (VF) zone for minimizing inappropriate ICD shocks. Subjects and Methods We selected 41 patients (35 men) (mean age±standard deviation=42.6±13.0 year) who received ICD shocks between April 1996 and April 2014 to treat BS (n=24), ERS (n=9), or IVF (n=8). Clinical and ICD interrogation data were retrospectively collected and analyzed for all events with ICD shocks. Results Of the 244 episodes, 180 (73.8%) shocks were appropriate and 64 (26.2%) were inappropriate. The mean cycle lengths of the tachyarrhythmias that activated appropriate and inappropriate shocks were 178.9±28.7 ms and 284.8±24.4 ms, respectively (p<0.001). The cutoff value with the highest sensitivity and specificity for discriminating between appropriate and inappropriate shocks was 235 ms (sensitivity, 98.4%; specificity, 95.6%). When we programmed a single VF zone of ≤270 ms, inappropriate ICD shocks were reduced by 70.5% and appropriate shocks were missed in 1.7% of these patients. Conclusion Programming of a single VF zone of ≤270 ms in patients with BS, ERS, or IVF could reduce inappropriate ICD shocks, with a low risk of missing appropriate shocks.

Complications of Cardiac Perforation and Lead Dislodgement with an MRI-Conditional Pacing Lead: a Korean Multi-Center Experience

Medtronic CapSureFix MRI 5086 pacing lead (5086; Medtronic, Inc., Minneapolis, MN, USA) has been reported to be associated with increased cardiac perforation and lead dislodgement. This study aimed to compare the incidence of cardiac perforation and lead dislodgement within 30 days after pacemaker implantation between 5086 MRI lead and previous Medtronic CapSureFix Novus 5076 non-MRI pacing lead. This was a nationwide, multicenter retrospective study in which we compared the incidence of adverse events between 277 patients implanted with 5086 lead and 205 patients implanted with 5076 lead between March 2009 and September 2014. Cardiac perforation within 30 days of pacemaker implantation occurred in 4 patients (1.4%) with the 5086 lead and in no patient with the 5076 lead (P = 0.084). Lead dislodgement occurred in 8 patients (2.9%) with the 5086 lead and in 5 patients (2.4%) with the 5076 lead (P = 0.764). On multivariate logistic regression analysis, age was significantly associated with cardiac perforation. Congestive heart failure and implantation of right atrial (RA) lead at RA free wall or septum were significant factors for the incidence of lead dislodgement and lead revision. The incidence of cardiac perforation and lead dislodgement were not statistically different between the patients with 5086 lead and the patients with 5076 lead. However, careful attention for cardiac perforation may be needed when using the 5086 MRI lead, especially in elderly patients.