Gi Byoung Nam

Mutations in SCN10A Are Responsible for a Large Fraction of Cases of Brugada Syndrome

BACKGROUNDnBrS is an inherited sudden cardiac death syndrome. Less than 35% of BrS probands have genetically identified pathogenic variants. Recent evidence has implicated SCN10A, a neuronal sodium channel gene encoding Nav1.8, in the electrical function of the heart.nnnOBJECTIVESnThe purpose of this study was to test the hypothesis that SCN10A variants contribute to the development of Brugada syndrome (BrS).nnnMETHODSnClinical analysis and direct sequencing of BrS susceptibility genes were performed for 150 probands and family members as well as >200 healthy controls. Expression and coimmunoprecipitation studies were performed to functionally characterize the putative pathogenic mutations.nnnRESULTSnWe identified 17 SCN10A mutations in 25 probands (20 male and 5 female); 23 of the 25 probands (92.0%) displayed overlapping phenotypes. SCN10A mutations were found in 16.7% of BrS probands, approaching our yield for SCN5A mutations (20.1%). Patients with BrS who had SCN10A mutations were more symptomatic and displayed significantly longer PR and QRS intervals compared with SCN10A-negative BrS probands. The majority of mutations localized to the transmembrane-spanning regions. Heterologous coexpression of wild-type (WT) SCN10A with WT-SCN5A in HEK cells caused a near doubling of sodium channel current compared with WT-SCN5A alone. In contrast, coexpression of SCN10A mutants (R14L and R1268Q) with WT-SCN5A caused a 79.4% and 84.4% reduction in sodium channel current, respectively. The coimmunoprecipitation studies provided evidence for the coassociation of Nav1.8 and Nav1.5 in the plasma membrane.nnnCONCLUSIONSnOur study identified SCN10A as a major susceptibility gene for BrS, thus greatly enhancing our ability to genotype and risk stratify probands and family members.

J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge

The J-wave syndromes (JWSs), consisting of the Brugada syndrome (BrS) and early repolarization syndrome (ERS), have captured the interest of the cardiology community over the past 2 decades following the identification of BrS as a new clinical entity by Pedro and Josep Brugada in 1992.[1][1] The

J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge☆☆☆

J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge Charles Antzelevitch, PhD, FHRS, Gan-Xin Yan, MD, PhD, Michael J. Ackerman, MD, PhD, Martin Borggrefe, MD, Domenico Corrado, MD, PhD, Jihong Guo, MD, Ihor Gussak, MD, PhD, Can Hasdemir, MD, Minoru Horie, MD, Heikki Huikuri, MD, Changsheng Ma, MD, Hiroshi Morita, MD, PhD, Gi-Byoung Nam, MD, PhD, Frederic Sacher, MD, PhD, Wataru Shimizu, MD, PhD, Sami Viskin, MD, Arthur A.M. Wilde, MD, PhD, FHRS

A Case of Helicobacter cinaedi Bacteremia in an Asplenic Patient

Helicobacter cinaedi is an enterohepatic species. It can cause bacteremia, gastroenteritis, and cellulitis, particularly in immunocompromised individuals, such as those with acquired immunodeficiency syndrome, malignancy, or alcoholism. There are no previous reports of H. cinaedi infection in Korea. A 71-yr-old man was admitted to the emergency room because of dyspnea on November 9, 2011. He had undergone splenectomy 3 yr ago because of immune hemolytic anemia. Chest plain radiography revealed bilateral pleural effusion. He developed fever on hospital day (HD) 21. Three sets of blood cultures were taken, and gram-negative spiral bacilli were detected in all aerobic vials. The isolate grew in tiny colonies on chocolate agar after 3-day incubation under microaerophilic conditions. This organism tested positive for catalase and oxidase, and negative for urease. The 16S rRNA gene sequence of this isolate exhibited 99.8% homology with the published sequence of H. cinaedi CCUG 18818T (GenBank accession no. ABQT01000054) and 98.5% homology with the sequence of Helicobacter bilis Hb1T (GenBank accession no. U18766). The patient was empirically treated with piperacillin/tazobactam and levofloxacin, and discharged with improvement on HD 31. To our knowledge, this is the first report of H. cinaedi bacteremia in an asplenic patient. Asplenia appears to be a risk factor for H. cinaedi bacteremia.

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.

Conduction disturbance after isolated surgical aortic valve replacement in degenerative aortic stenosis

Objective: Conduction disturbances are common in patients with aortic stenosis. We investigated the incidence, reversibility, and prognosis of conduction disorders requiring permanent pacemaker implantation in patients with degenerative aortic stenosis after isolated aortic valve replacement. Methods: This was a retrospective study conducted at a tertiary care center. We evaluated the incidence of conduction disturbances in patients who underwent isolated surgical aortic valve replacement for aortic stenosis between January 2005 and May 2015. Relevant clinical information was obtained from the patients medical records. Results: We reviewed results of 663 patients with pathologically proven degenerative aortic stenosis (bicuspid aortic valve, n = 285 [43.0%]) who underwent isolated aortic valve replacement (mechanical valve, n = 310 [46.8%]). Patients mean age was 67.1 ± 8.1 years, and 362 were male (54.6%). Immediate postoperative intraventricular conduction disorders occurred in 56 patients (8.4%), and atrioventricular block occurred in 68 patients (10.3%). Ten patients with symptomatic second‐degree or third‐degree atrioventricular block underwent permanent pacemaker implantation within 30 days of aortic valve replacement. During the mean follow‐up period of 1288 ± 1122 days, 64 patients (9.7%) developed irreversible conduction disorders (bundle branch block n = 24 and first‐degree atrioventricular block n = 42). Of the 10 patients requiring permanent pacemakers, 4 remained depend on the permanent pacemaker during follow‐up. Beyond 30 days after aortic valve replacement, 1 patient underwent permanent pacemaker implantation for de novo conduction disturbance 44 months postoperatively. Conclusions: After isolated aortic valve replacement, permanent pacemaker implantation for conduction disturbance is rare (n = 10/663, 1.5%). Isolated aortic valve replacement for degenerative aortic stenosis has a low risk of conduction disturbances during long‐term follow‐up.

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.

Restoration of Atrial Mechanical Function after Successful Radio - Frequency Catheter Ablation of Atrial Flutter

Background: Atrial mechanical dysfunction and its recovery time course after successful radiofrequency ablation of chronic atrial flutter (AFL) has been largely unknown. We serially evaluated left atrial function by echocardiography after successful ablation of chronic atrial flutter. Methods: In 13 patients with chronic AFL, mitral E wave A wave, and the ratio of A/E velocity were measured at 1 day, 1 month, 3 months and 6–12 months after successful radiofrequency (RF) ablation. Doppler tissue imaging (DTI) technique was also used to avoid load-dependent variation in the flow velocity pattern. Results: Left atrial mechanical function, assessed by A wave velocity and the annular motion, was depressed at 1 day, but improved significantly at 1 month and maintained through 6–12 months after the ablation. Left atrial size did not change significantly. Conclusion: Left atrial mechanical function was depressed immediately after successful RF ablation of chronic AFL, but it improved significantly after 1 month and was maintained over one year.