Efficacy of Endocardial Ablation of Drug-Resistant Ventricular Fibrillation in Brugada Syndrome: Long-Term Outcome.

Background Both endocardial trigger elimination and epicardial substrate modification are effective in treating ventricular fibrillation (VF) in Brugada syndrome. However, the primary approach and the characteristics of patients who respond to endocardial ablation remain unknown. Methods Among 123 symptomatic Brugada syndrome patients (VF, 63%; syncope, 37%), ablation was performed in 21 VF/electrical storm patients, the majority of whom were resistant to antiarrhythmic drugs. Results Careful endocardial mapping revealed that 81% of the patients had no specific findings, whereas 19% of the patients, who experienced the most frequent VF episodes with notching of the QRS in lead V1, had delayed low-voltage fractionated endocardial electrograms. Ablation of VF triggers followed by endocardial substrate modification was performed in the right ventricular outflow tract in 85% of the cases and in the right ventricle in 15%. VF triggers could not be completely eliminated in 1 patient and VF became noninducible in 14 (88%) patients among 16 patients who underwent VF induction with normalization of Brugada-type ECG in 3. During follow-up (56.14±36.95 months), VF recurrence was observed in 7 patients. Importantly, all patients who had nothing of QRS in lead V1 did not respond to endocardial ablation despite presence of VF-triggering ectopic beats during ablation. Conclusions With careful documentation of VF-triggering ectopic beats and detailed endocardial mapping, endocardial VF trigger elimination followed by endocardial substrate modification has an excellent long-term outcome, whereas presence of QRS notching in lead V1 was associated with high VF recurrence suggesting epicardial substrate ablation as effective initial approach.

Effectiveness of laparoscopic stomach-partitioning gastrojejunostomy for patients with gastric outlet obstruction caused by advanced gastric cancer.

BACKGROUND: Distal advanced gastric cancer (AGC) occasionally causes gastric outlet obstruction (GOO). We developed a laparoscopic stomach-partitioning gastrojejunostomy (LSPGJ) to restore the ability of food intake. METHODS: This was a retrospective study performed at a single institution. Of consecutive 78 patients with GOO caused by AGC between 2006 and 2012, 43 patients who underwent LSPGJ were enrolled. The procedure was performed in an antiperistaltic Billroth II fashion, and the afferent loop was elevated and fixed along the staple line of the proximal partitioned stomach. Then, patients for whom R0 resection was planned received chemotherapy prior to laparoscopic gastrectomy. The primary end point was food intake at the time of discharge, which was evaluated using the GOO scoring system (GOOSS). Short- and long-term outcomes were assessed as secondary end points. Overall survival was estimated and compared between the groups who received neoadjuvant chemotherapy followed by surgery (NAC group), definitive chemotherapy followed by curative resection (Conversion group), and best supportive care (BSC group). RESULTS: The median operative time was 92 min, blood loss did not exceed 30 g in any patient, and postoperative complications (Clavien-Dindo grade ≥2) were only seen in four patients (9.3 %). The median time to food intake was 3 days, and GOOSS scores were significantly improved in 41 patients (95.3 %). Chemotherapy was administered to 38 patients (88.4 %), of whom 11 later underwent radical resection, and 4 of 11 patients underwent conversion surgery following definitive chemotherapy. Median survival times were significantly superior in the NAC (n = 7; 46.8 months) and Conversion (n = 4; 35.9 months) groups than in the BSC group (n = 26; 12.2 months); however, the difference was not significant between the Conversion and NAC groups. CONCLUSIONS: LSPGJ is a feasible and safe minimally invasive induction surgery for patients with GOO from surgical and oncological perspectives.

Insight into specific pro-arrhythmic triggers in Brugada and early repolarization syndromes: results of long-term follow-up.

The pro-arrhythmic triggers in Brugada and early repolarization syndromes (BrS, ERS) have not been analyzed systematically except for case reports. We clinically investigated the circumstances which precede/predispose to arrhythmic events in these syndromes during long-term follow-up. A detailed history from the patients/witnesses was taken to investigate the antecedent events in the last few hours that preceded syncope/ventricular fibrillation (VF); medical records, ECG and blood test from the emergency room (ER) were reviewed. 19 patients that fulfilled the investigation criteria were followed up for 71 ± 49 months (34-190 months). Prior to the event (syncope/VF), the patients were partaking different activities in the following decreasing order; drinking alcoholic beverage, having meal, and getting up from sleep, exercise. 3 patients reported mental/physical stress prior to the event and 2 patients developed VF several days after starting oral steroid for treatment of bronchial asthma. In the ER, elevated J-wave amplitude (0.27 ± 0.15 mV) was found with 58 % of the patients having hypokalemia. After electrolyte correction and cessation of steroids, the following day plasma K+ (4.2 ± 0.3 mEq/L, P < 0.001) was significantly increased and J-wave amplitude (0.13 ± 0.1 mV, P < 0.001) was remarkably reduced. Three patients were kept on oral spironolactone/potassium supplements. During follow-up for 71 ± 49 (34-190) months, among 4 patients with VF recurrence, one patient developed VF after taking oral steroid. In ERS and BrS, hypokalemia and corticosteroid therapy add substantial pro-arrhythmic effects, but potentially treatable. Stopping steroid therapy and avoiding hypokalemia had excellent long-term outcome.

[Abnormalities of magnesium (Mg) metabolism and therapeutic significance of Mg administration in patients with metabolic syndrome, type 2 diabetes, heart failure and chronic hemodialysis].

Magnesium (Mg) , one of the fundamental minerals acting the co-factor of about 300 kinds of enzymes and natural Ca channel blocker, plays an important role of cardiovascular, neurological, and metabolic functions in physiological, and pathophysiological conditions. Common abnormal Mg metabolism is an absolute or relative deficiency of Mg due to an attenuated Mg intake and an enhanced urinary Mg excretion, particularly in the metabolic syndrome (MetS) , type 2 diabetes (DM) , chronic heart failure (CHF) and hemodialysis (HD) patients with diabetes. It has been reported the Mg deficiency relating to enhanced risk of MetS and type 2 DM, and to fatal cardiac events in CHF and an atherosclerotic, vascular calcification in HD patients. On the otherhand, severe and fatal hypermagnesemia is very rare, except for the condition associated with high dose administration of Mg, renal failure and an abnormally enhanced Mg absorption from damaged intestine in the mesenteric ischemia/infarction, severe constipation or ileus. In this paper, we conduct to review and discuss the pathophysiological and pathogenetical role of the abnormal Mg metabolism focused on Mg deficiency, and the protective and therapeutic significance of Mg administration in the MetS, type 2 DM, CHF and diabetic HD patients.

Recurrent ventricular fibrillation related to hypokalemia in early repolarization syndrome.

We describe a case of early repolarization syndrome in which augmented J waves were documented during an electrical storm associated with hypokalemia. The patient was referred to our hospital for therapy to treat recurrent ventricular fibrillation (VF). The 12-lead electrocardiogram showed giant J waves associated with hypokalemia during multiple episodes of VF. Although antiarrhythmic agents or deep sedation were not effective for the VF, an intravenous supplementation of potassium completely suppressed the VF with a reduction in the J-wave amplitude. Our report discusses the possible relationship between hypokalemia and VF in early repolarization syndrome.

Enhanced transmural dispersion of repolarization in patients with J wave syndromes.

INTRODUCTION: Recently, great attention has been paid to the risk stratification of asymptomatic patients with an electrocardiographic early repolarization (ER) pattern. We investigated several repolarization parameters including the Tpeak-Tend interval and Tpeak-Tend/QT ratio in healthy individuals and patients with J wave syndrome who were aborted from sudden cardiac death. METHODS AND RESULTS: Ninety-two subjects were enrolled: 12 patients with ventricular fibrillation associated with J waves, 40 healthy subjects with an uneventful ER pattern and 40 healthy control subjects (C) without any evident J waves. Using ambulatory electrocardiogram recordings, the average QT interval, corrected QT interval (QTc), Tpeak-Tend (Tp-e) interval, which is the interval from the peak to the end of the T wave, and Tp-e/QT ratio were calculated. Using ANOVA and post hoc analysis, there was no significant difference in the average QT and QTc in all 3 groups (QT; 396 ± 27 vs 405 ± 27 vs 403 ± 27 m, QTc; 420 ± 26 vs 421 ± 21 vs 403 ± 19 milliseconds in the C, ER pattern and J groups, respectively). The Tp-e interval and Tp-e/QT ratio were significantly more increased in the J wave group than the ER Pattern group (Tp-e: 86.7 ± 14 milliseconds vs 68 ± 13.2 milliseconds, P < 0.001, Tp-e/QT; 0.209 ± 0.04 vs 0.171 ± 0.03, P < 0.001), but they did not significantly differ between the C and ER pattern groups (Tp-e: 68.6 ± 7.5 vs 68 ± 13.2, P = 0.97, Tp-e/QT 0.174 ± 0.02 vs 0.171 ± 0.03, P = 0.4). CONCLUSION: As novel markers of heterogeneity of ventricular repolarization, Tpeak-Tend interval and Tp-Te/QT ratio are significantly increased in patients with J wave syndromes compared to age and sex-matched uneventful ER.

Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization.

BACKGROUND: Recently, we and others reported that early repolarization (J wave) is associated with idiopathic ventricular fibrillation. However, its clinical and genetic characteristics are unclear. METHODS AND RESULTS: This study included 50 patients (44 men; age, 45 ± 17 years) with idiopathic ventricular fibrillation associated with early repolarization, and 250 age- and sex-matched healthy controls. All of the patients had experienced arrhythmia events, and 8 (16%) had a family history of sudden death. Ventricular fibrillation was inducible by programmed electric stimulation in 15 of 29 patients (52%). The heart rate was slower and the PR interval and QRS duration were longer in patients with idiopathic ventricular fibrillation than in controls. We identified nonsynonymous variants in SCN5A (resulting in A226D, L846R, and R367H) in 3 unrelated patients. These variants occur at residues that are highly conserved across mammals. His-ventricular interval was prolonged in all of the patients carrying an SCN5A mutation. Sodium channel blocker challenge resulted in an augmentation of early repolarization or development of ventricular fibrillation in all of 3 patients, but none was diagnosed with Brugada syndrome. In heterologous expression studies, all of the mutant channels failed to generate any currents. Immunostaining revealed a trafficking defect in A226D channels and normal trafficking in R367H and L846R channels. CONCLUSIONS: We found reductions in heart rate and cardiac conduction and loss-of-function mutations in SCN5A in patients with idiopathic ventricular fibrillation associated with early repolarization. These findings support the hypothesis that decreased sodium current enhances ventricular fibrillation susceptibility.

Electrophysiological effects of carvedilol on rabbit heart pacemaker cells.

The electrophysiological effects of carvedilol, a beta-blocking agent with vasodilating actions, have been studied on rabbit pacemaker cells using the whole-cell patch clamp technique. Nystatin-perforated patch recordings from the sinoatrial (SA) and atrioventricular (AV) nodes demonstrated that 1-3 microM of carvedilol caused a decrease in the spontaneous firing frequency, depolarization of the maximal diastolic potential, and prolongation of the action potential duration in both species. Voltage clamp experiments were performed using SA and AV node myocytes to identify and define the carvedilol-induced changes in the Ca(2+) current, I(Ca), delayed rectifier K(+) current, I(K), and hyperpolarization-activated inward current, I(f). In the SA node cells, 1 microM of carvedilol blocked I(K), I(Ca), and I(f) by 72%, 47%, and 22%, respectively. In the AV node cells, the corresponding reductions were 64% (I(K)) and 46% (I(Ca)), respectively. In both the SA and AV nodes the decrease in I(K) appeared to be mainly due to the rapidly activating component of the delayed rectifier, I(Kr), since the high dose of carvedilol blocked I(K) in the SA and AV nodes to a submaximal degree. In conclusion, effective doses of carvedilol have classical class III antiarrhythmic actions and a negative chronotropic effect resulting from the inhibition of I(K) and I(Ca). Both actions may be efficacious for treating supraventricular tachyarrhythmias.

A case of a short-coupled variant of torsades de Pointes with electrical storm.

This case report describes a short-coupled variant of Torsades de Pointes with a characteristic ECG pattern consisting of a prominent J wave in leads V3-V6, in which an electrical storm was evoked with autonomic receptor stimulation and a blockade test. The patient's frequent VF attacks were triggered by short-coupled premature ventricular contractions with a right bundle branch block morphology and left-axis deviation, and were suppressed by deep sedation followed by a combination therapy using verapamil and mexiletine. Interestingly, with the use of those drugs, the prominent J wave diminished. The mechanism underlying this syndrome is discussed.