Usefulness of epicardial impedance evaluation for epicardial mapping and determination of epicardial ablation site for ventricular tachycardia: A pilot study.

BACKGROUND: During epicardial mapping, determination of appropriate ablation sites in low voltage areas (LVA) is challenging because of large epicardial areas covered by adipose tissue. OBJECTIVE: To evaluate the impedance difference between epicardial fat and the epicardial LVA using multiple detector computed tomography (MDCT). METHODS: We enrolled patients who underwent ventricular tachycardia (VT) ablation via the epicardial approach after endocardial ablation failure. After the procedure, MDCT-derived images of epicardial fat were loaded to the mapping system. Then, all points acquired during sinus rhythm were retrospectively superimposed and analyzed. RESULTS: This study included data from 7 patients (62.5 ± 3.9 years old) who underwent eight epicardial VT ablation procedures. After the procedure, MDCT-derived images of epicardial fat were registered in eight procedures. Retrospective analysis of 1,595 mapping and 236 ablation points was performed. Of the 1,595 mapping points on the merged electroanatomical and epicardial fat maps, normal voltage area (NVA) and low voltage area (LVA) without fat had lower impedance than those with fat (NVA without fat 182 ± 46 Ω vs. NVA with fat 321 ± 164.0 Ω, P  =  0.001, LVA without fat 164 ± 69 Ω vs. LVA with fat 248 ± 89 Ω, P  =  0.002). Of the 236 ablation points, initial impedance before ablation was higher on epicardial fat than on epicardial LVA without fat (134 ± 16 Ω vs. 156 ± 28 Ω, P  =  0.01). CONCLUSIONS: Real time epicardial impedance evaluation may be useful to determine effective epicardial ablation sites and avoid adipose tissue. However, the number of patients in the present study is limited. Further investigation with a large number of patients is needed to confirm our result.

Clinical Characteristics and Long-Term Prognosis of Senior Patients With Brugada Syndrome.

OBJECTIVES: This study investigated clinical characteristics and prognosis of Brugada syndrome (BrS) in patients older than 60 years of age during a long-term follow-up period. BACKGROUND: Clinical characteristics and prognosis of senior patients with BrS have not been clearly elucidated. METHODS: A total of 181 patients with BrS were divided into 2 groups by age at the time of diagnosis: the younger group was <60 years of age (n = 123), and the senior group was ≥60 years of age (n = 58). RESULTS: Mean ages were 42.7 ± 11 years and 68.6 ± 7.1 years, respectively. Prevalence of spontaneous type 1 electrocardiogram (ECG) was lower in the senior group (22 of 58; 37.9%) than in the younger group (64 of 123; 51.9%) (p = 0.027). Among various ECG parameters, the senior group had a lower incidence of prolonged r-J intervals in V2 ≥90 ms than the younger group (34 of 58; 58.6% vs. 90 of 123; 73.1%, p = 0.049) and day-to-day variation of Brugada ECG patterns (3 of 58; 5.2% vs. 23 of 123; 18.7%, p = 0.032). During a mean follow-up period of 7.6 ± 5.8 years, no senior patients experienced documented fatal ventricular arrhythmias, but 11 younger patients did. Kaplan-Meier analysis revealed a better prognosis in the senior group than in the younger group (log-rank, p = 0.011). CONCLUSIONS: Senior BrS patients, ≥60 years of age, had a better prognosis than those <60 years of age. Implantable cardioverter-defibrillator insertion for senior patients with BrS needs careful consideration.

Aliskiren suppresses atrial electrical and structural remodeling in a canine model of atrial fibrillation.

Aliskiren, a direct renin inhibitor is expected to achieve sufficient suppression of renin-angiotensin system. We evaluated the effect of aliskiren on the electrical and structural remodeling in a canine atrial fibrillation (AF) model. Twenty-eight dogs were divided into three groups: (1) pacing control group (n = 12), with continuous atrial rapid pacing for 3 or 6 weeks, (2) pacing + aliskiren group (n = 12), with oral aliskiren (30 mg/kg/day), and (3) sham group (n = 4), no pacing nor drug administration. Electrophysiological properties and AF inducibility were evaluated every week. After the protocol, the left atrial tissue was sampled for the further histological and mRNA analysis. The electrical remodeling, AF inducibility, the left atrial enlargement and interstitial fibrosis were observed in pacing control group and were more prominent in the 6-week protocol (vs. 3 week, p < 0.05). The mRNA expressions of matricellular proteins exhibited upregulation in 3-week pacing control, but these upregulations became insignificant in 6 weeks. In contrast, collagen type 3 exhibited significant upregulation in 6 week but not in 3-week protocol. These changes were suppressed in the pacing + aliskiren group. Aliskiren suppressed the atrial remodeling in a canine AF model. This effect was accompanied by the suppression of tissue fibrosis.

Sodium Bicarbonate-Ascorbic Acid Combination for Prevention of Contrast-Induced Nephropathy in Chronic Kidney Disease Patients Undergoing Catheterization.

BACKGROUND: Sodium bicarbonate and ascorbic acid have been proposed to prevent contrast-induced nephropathy (CIN). The present study evaluated the effect of their combined use on CIN incidence.Methods and Results:We prospectively enrolled 429 patients with chronic kidney disease (CKD: baseline estimated glomerular filtration rate <60 mL/min/1.73 m2) prior to elective coronary catheterization. CIN was defined as absolute (≥0.5 mg/dL) or relative (≥25%) increase in serum creatinine within 72 h. In the saline hydration (n=218) and combined sodium bicarbonate+ascorbic acid (n=211) groups, a total of 1,500-2,500 mL 0.9% saline was given before and after the procedure. In addition, the combination group received 20 mEq sodium bicarbonate and 3 g ascorbic acid i.v. before the procedure, followed by 2 g ascorbic acid after the procedure and a further 2 g after 12 h. There were no significant differences between the basic characteristics and contrast volume in the 2 groups. CIN occurred in 19 patients (8.7%) in the saline group, and in 6 patients (2.8%) in the combined treatment group (P=0.008). CONCLUSIONS: Combined sodium bicarbonate and ascorbic acid could prevent CIN following catheterization in CKD patients.

Long-term efficacy of catheter ablation for paroxysmal atrial fibrillation in patients with Brugada syndrome and an implantable cardioverter-defibrillator to prevent inappropriate shock therapy.

BACKGROUND: In patients with an implantable cardioverter-defibrillator (ICD) and Brugada syndrome (BrS), the long-term efficacy of catheter ablation for preventing inappropriate shock therapy due to paroxysmal atrial fibrillation (PAF) has not been elucidated. OBJECTIVE: To evaluate the efficacy of atrial fibrillation (AF) ablation for PAF for prevention of inappropriate ICD therapy over a longer follow-up period. METHODS: We enrolled 76 men with BrS and an ICD, with a mean age of 46.2 ± 16.5 years. Twenty-one patients had AF (19 had PAF, 1 had persistent AF, and 1 had longstanding persistent AF). Fourteen patients with PAF underwent pulmonary vein isolation (PVI) and received follow-up electrophysiological study (EPS) 6 months after the first PVI. If necessary, ablation was performed. RESULTS: Over a mean follow-up period of 3.3 ± 1.4 years after the repeat session, 13 of the 14 patients (92.9%) had no recurrence of AF. Six patients with PAF without inappropriate ICD therapy before PVI had no recurrence of AF and no inappropriate therapy during follow-up. Among the 8 patients who had inappropriate therapy because of PAF before PVI, 1 patient who had recurrent AF underwent another ablation session. After this final session, there were no recurrences of AF and no inappropriate therapy (mean follow-up period 3.1± 1.2 years). CONCLUSION: Catheter ablation is effective in patients with BrS and an ICD, and prevents inappropriate ICD therapy owing to PAF; thus, catheter ablation is an appropriate first-line therapy for PAF among such patients.

Early repolarization pattern and its day-to-day dynamic change as markers for ventricular fibrillation in patients with vasospastic angina.

AIMS: An early repolarization (ER) pattern is a risk factor for ventricular fibrillation (VF) in certain diseases. However, it is unclear whether this association holds for patients with vasospastic angina (VSA). Moreover, the reported long-term follow-up of implantable cardioverter defibrillator (ICD) therapy for VSA patients is limited to 3 years. This study aimed to clarify the relation between ER and VF in patients with VSA and to investigate the long-term outcomes of ICD therapy. METHODS AND RESULTS: This retrospective, observational survey evaluated 265 consecutive VSA patients, including 21 with VF. Their electrocardiogram findings and clinical course were analysed over a mean follow-up of 5.5 ± 3.3 years. Early repolarization was observed in 64 patients (24.2%) and was more frequent in patients with VF history than those without (P = 0.001). Early repolarization was independently associated with VF history. During follow-up, four patients had VF recurrences. Ventricular fibrillation recurrence was higher in patients with ER (log-rank, P = 0.018) or VF history (log-rank, P < 0.001) than those without. Among patients with ER, day-to-day variations in ER (P = 0.003) and notching of ER pattern (P = 0.03) were associated with VF history. Cases with day-to-day variation showed a higher incidence of VF recurrence during follow-up (log-rank, P = 0.007). During long-term follow-up, 23.5% of patients with an ICD received appropriate shock therapy. CONCLUSION: The presence of ER, especially with day-to-day variation, can help predict VF recurrence in VSA patients. Implantable cardioverter defibrillator implantation is a reasonable approach for the secondary prevention of VF in high-risk VSA patients.

Transient sinus node dysfunction following sinus node artery occlusion due to radiofrequency catheter ablation of the septal superior vena cava-right atrium junction.

We performed catheter ablation to septal superior vena cava (SVC)-right atrium (RA) junction rapid firing in a 57-year-old man with paroxysmal atrial fibrillation. He later experienced transient sinus node dysfunction resulting from injury to the sinus node artery (SNA), which branched only from the proximal region of the left circumflex artery. The direction of the SNA should be considered during catheter ablation at the septal SVC-RA junction, especially if the sinus node is supplied by only one SNA from the right coronary artery or the left circumflex artery.

Peri-Mitral Atrial Tachycardia Using the Marshall Bundle Epicardial Connections.

OBJECTIVES: The aim of this study was to determine whether re-entrant circuits were associated with the ligament of Marshall (LOM). BACKGROUND: Peri-mitral atrial tachycardias (PMATs) following pulmonary vein isolation (PVI) or mitral valve surgery are common. METHODS: Six PMATs involving epicardial circuits were identified from 38 patients. Of these, 4 PMATs involved the LOM (PMAT-LOM, mean cycle length 308 ± 53 ms), as confirmed by the insertion of a 2-F electrode in the vein of Marshall (VOM). All patients underwent PVI and mitral isthmus ablation. The PMAT-LOMs were diagnosed based on left atrium (LA) activation maps that covered <90% of tachycardia cycle length (TCL), and a difference between the post-pacing interval and TCL that was: 1) ≤20 ms at the VOM, the ridge between the left pulmonary vein and appendage, the anterior wall of the LA, and along the 6 to 11 o'clock direction of the mitral annulus; and 2) >20 ms at the distal coronary sinus (CS), the posterior wall of the LA, and the mitral isthmus ablation line (or noncapture). Catheter ablation was performed at the ridge for all PMAT-LOMs. RESULTS: Three tachycardias were successfully terminated at the ridge, which showed continuous fractionated potential lasting >100 ms, confirming the bidirectional block of Marshall bundle (MB)-LA connections. The remaining tachycardia required ablation for the CS-MB connections, confirming bidirectional block of CS-MB connections. CONCLUSIONS: PMAT-LOMs following PVI or valve surgery accounted for up to 11% of PMATs. The bidirectional block of either MB-LA or CS-MB connections is required to eliminate PMAT-LOMs.

Effect of carvedilol on atrial remodeling in canine model of atrial fibrillation.

AIMS: We evaluated the effect of carvedilol, a beta-blocker with anti-oxidative action, against the atrial fibrillation (AF) inducibility, the development of atrial remodeling and the oxidative stress markers in a canine AF model. METHODS AND RESULTS: AF model was produced by performing 6-week rapid atrial stimulation in 15 dogs. The animals were divided into the following three groups: (I) pacing + carvedilol group (n=5); (II) pacing control group (n=5); and (III) non-pacing group (n=5). AF inducibility was gradually increased along the time course in the pacing control group. In the pacing + carvedilol group, the AF inducibility was suppressed especially in the latter phase of protocol in comparison with the pacing control group. Although carvedilol has beta-blocking effect, pacing control and pacing + carvedilol groups did not exhibit difference in the heart rate (177±13 vs. 155±13 bpm, P=0.08). On 8-hydroxy-2'-deoxyguanosine (8-OHdG), dihydroethidium and dichlorodihydrofluorescein diacetate staining, enhanced oxidative stress was observed in the atrial tissue in the pacing control, but not in the pacing + carvedilol group. CONCLUSIONS: Carvedilol suppressed AF inducibility and oxidative stress in the canine AF model.

Regiocomplementary cycloaddition reactions of boryl- and silylbenzynes with 1,3-dipoles: selective synthesis of benzo-fused azole derivatives.

Benzo-fused nitrogen-containing heterocycles are abundant in biologically active compounds. One of the most important methods for preparing such heterocycles is the (3 + 2) cycloaddition reaction of benzynes with 1,3-dipolar compounds. However, the reactions of unsymmetrically substituted benzynes generally show low selectivity and hence yield mixtures of two regioisomers. In this paper, we describe the synthesis of both regioisomers of multisubstituted benzo-fused azole derivatives such as benzotriazoles, 1H-indazoles, and benzo[d]isoxazoles through the regiocomplementary (3 + 2) cycloaddition reactions of 3-boryl- and 3-silylbenzynes with 1,3-dipoles. The improved generation of 3-borylbenzynes from new precursors was one of the most important results of this work, which produced the successful (3 + 2) cycloaddition reactions with exclusive and proximal selectivities. On the other hand, similar reactions of 3-silylbenzynes selectively afforded distal cycloadducts. Analysis of the reaction pathways of these amazing regioselectivities by density functional theory calculations revealed that the (3 + 2) cycloadditions of borylbenzynes are controlled by the electrostatic effect of the boryl group, while those of silylbenzynes are controlled mainly by the steric effect of the bulky silyl groups that produced electrostatically unfavorable adducts via anomalous transition states.

Prediction of inappropriate implantable cardioverter-defibrillator therapies through parameters obtained in a simple exercise stress test.

Although the clinical benefits of implantable cardioverter-defibrillators (ICDs) have been demonstrated, inappropriate therapies (IATs) cannot be completely avoided even with the most advanced devices. Recently, IATs are considered to decrease the ventricular function and prognosis of a patient. The aim of this study was to investigate the predictors of IAT with parameters during cardiopulmonary exercise stress test (CPX). Sixty consecutive ICD patients underwent symptom-limited CPX, and were divided into IAT (+) and IAT (-) groups. During and after CPX, ECG and hemodynamic parameters of systemic blood pressure, heart rate, and maximal O2 consumption (max VO2) were evaluated every minute. In selected patients, sympathetic and parasympathetic activities were evaluated with analyses of heart rate variability (HRV). No significant differences were observed in clinical background parameters. In the CPX parameters, only the maximal heart rate exhibited a significant difference between the IAT (+) group and the IAT (-) group (154.8 ± 5.9 versus 137.9 ± 4.2 beats per minute, P = 0.032), and LF/HF was higher during the recovery phase 4 minutes after peak exercise in the former group (4.5 ± 1.0 versus 2.4 ± 0.9, P = 0.021). In ICD patients, IAT can be predicted using simple parameters of increased sympathetic activity such as increased maximal heart rate and increased LF/HF ratio during and after the exercise stress test.

Evaluation of the impact of atrial fibrillation on rehospitalization events in heart failure patients in recent years.

BACKGROUND: Although we have previously reported that the presence of paroxysmal atrial fibrillation (AF) is an independent risk factor for rehospitalization in patients with congestive heart failure (CHF) in a population from 1996 to 2002, the impact of AF configuration as a risk factor in a more recent population remains to be clarified. METHODS AND RESULTS: 319 patients with CHF admitted to our institute in 2006-2007 were retrospectively evaluated. The patients were divided into 3 groups in accordance with their basic cardiac rhythm, i.e. sinus rhythm (n=210), chronic AF (n=68), and paroxysmal AF (n=41). During the follow-up period of 19 ± 17 months, there was no significant difference in mortality or rehospitalization events among the 3 groups (p=0.542). In the multivariate analysis, no administration of ß-blockers was the only independent risk factor for rehospitalization due to CHF exacerbation. CONCLUSIONS: The clinical impact of AF configuration as a risk factor of rehospitalization due to CHF exacerbation was considered to be decreased in recent years.

Angiotensin II-mediated up-regulation of connective tissue growth factor promotes atrial tissue fibrosis in the canine atrial fibrillation model.

AIMS: Remodelling of the extracellular matrix (ECM) plays an important role in the production of arrhythmogenic substrate for atrial fibrillation (AF), and is considered to be promoted by the connective tissue growth factor (CTGF). Our objective was to assess the relationship between CTGF and ECM synthesis, and the effect of olmesartan on these processes. METHODS AND RESULTS: Fifteen canine AF models were produced by rapid atrial stimulation. They were divided into three groups: pacing control (n = 5): 6-week pacing, pacing + olmesartan (n = 5): pacing with olmesartan (2 mg/kg/day), and non-pacing group (n = 5). In the pacing control group, messenger ribonucleic acid expressions of CTGF and collagen types 1 and 3 were up-regulated in comparison with the non-pacing group (P < 0.05) while transforming growth factor-ß (TGF-ß) did not exhibit a significant difference. In the pacing + olmesartan group, these up-regulations were suppressed (P < 0.05). In fluorescent immunostaining, the expression of CTGF was localized in the cytoplasm. The protein level of collagen type 3 was increased in the pacing control and it was suppressed in the pacing + olmesartan group. CONCLUSIONS: CTGF and associated genes were up-regulated in the atria with the appearance of fibrosis. Because this up-regulation was independent of TGF-ß and suppressed by olmesartan, CTGF up-regulation was considered to be mediated by angiotensin II.

Repetitive evaluation of fibrillation cycle length predicts the efficacy of bepridil for interruption of long-lasting persistent atrial fibrillation.

Although bepridil is effective for conversion of long-lasting persistent atrial fibrillation (AF) to sinus rhythm, it sometimes takes a long time to interrupt AF and there is no feasible index to predict its efficacy.In 60 patients with long-lasting persistent AF, bepridil (100-200 mg/day) was administered and continued for 8 weeks while body surface ECG was recorded every 2 weeks. The fibrillation cycle length (FCL) was evaluated using the spectral analysis of the fibrillation waves in each ECG. AF was interrupted in 32 patients receiving bepridil. The conversion was observed at 2 weeks in 4, at 4 weeks in 7, at 6 weeks in 7, and at 8 weeks in 14 patients. When comparing these responders and nonresponders, clinical background characteristics other than the dosage of bepridil did not show any difference and neither did temporal changes in QT parameters and heart rate. In contrast, the FCL and ΔFCL (prolongation in FCL from baseline) became significantly larger in responders than in nonresponders at later observation points (FCL: 177 ± 17 versus 164 ± 19 ms, P = 0.018, and ΔFCL: 38 ± 16 versus 22 ± 12 ms, P < 0.001, at 4-week point; FCL: 188 ± 17 versus 169 ± 19 ms, P = 0.004, and ΔFCL: 49 ± 18 versus 27 ± 14 ms, P < 0.001, at 6-week point).Repetitive evaluation of FCL using spectral analysis of fibrillation waves can be a feasible index to predict the efficacy of bepridil therapy.

Progression of ventricular remodeling and arrhythmia in the primary hyperoxidative state of glutathione-depleted rats.

BACKGROUND: Although oxidative stress is considered to promote arrhythmogenic substrates in diseased model animals, it is difficult to evaluate its primary role. In this study, we evaluated the promotion of arrhythmogenic substrates in the primary hyperoxidative state. METHODS AND RESULTS: Sprague-Dawley rats were treated with L-buthionine-sulfoximine (BSO, 30 mmol · L(-1) · day(-1)) for 14 days. On day 7 or 14, the serum levels of derivatives of reactive oxygen metabolites (d-ROM) were measured, and immune staining of 8-hydroxy-2'-deoxyguanosine (8O HdG) was performed to assess oxidative stress. The ventricular effective refractory period (ERP), monophasic action potential duration (MAPD), and the inducibility of ventricular arrhythmia were also evaluated. BSO rats exhibited higher serum d-ROM and clearer 8OHdG staining than the controls. The inducibility of ventricular arrhythmia was higher in the BSO rats than in the controls. The ERP was shorter in the BSO rats than the control (day 14, 32 ± 1 vs. 36 ± 1 ms, P<0.05), whereas the MAPD(90) was longer in the BSO rats (day 14, 76 ± 5 vs. 55 ± 4 ms, P<0.05). The mRNA levels of Kv4.2, erg, and SERCA2a were downregulated in the BSO rats (P < 0.05), and Western blot analysis exhibited the downregulation of erg and SERCA2 expression in the BSO rats (P < 0.05). CONCLUSIONS: Systemic oxidative stress might be one of the primary factors promoting cardiac electrophysiological remodeling and increasing the inducibility of arrhythmia independently of major organ disorders.