研究者詳細 - 高月　誠司

論文 - 高月　誠司

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High take-off left inferior pulmonary vein as an obstacle in creating a conduction block at the lateral mitral isthmus

Takatsuki Seiji, Extramiana Fabrice, Hayashi Meiso, Haggui Abdeddayem, Messali Anne, Milliez Paul, Leenhardt Antoine, Cauchemez Bruno

Europace 11 （ 7 ） 910 - 916 2009年07月

ISSN 1099-5129

AimsCreation of complete linear lesions in the lateral mitral isthmus (LMI) by catheter ablation for treating atrial fibrillation remains technically challenging. We aimed to clarify whether a high take-off left inferior pulmonary vein (LIPV) can hamper the creation of a complete block at the LMI.Methods and resultsWe included 81 consecutive patients who underwent linear ablation at the LMI and cardiac computed tomography (CT) before ablation. We defined a high take-off LIPV when the level of the lower edge of the LIPV ostium was higher than that of the top of mitral annulus on CT. The clinical backgrounds, parameters, and long-term follow-up were then compared between the success (successful creation of a complete LMI block) and failure groups. A complete LMI block was obtained in 60/81 (76) patients. In the failure group, a high take-off LIPV was noted more commonly and the LMI tended to be longer than the success group. Multivariate analysis revealed that a high take-off LIPV was an independent predictor of failure to achieve a complete LMI block. The sinus rhythm maintenance rate was not different between the success and failure groups.ConclusionA high take-off LIPV hampered the creation of complete linear lesions in the LMI.

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Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia

Hayashi Meiso, Denjoy Isabelle, Extramiana Fabrice, Maltret Alice, Buisson Nathalie Roux, Lupoglazoff Jean Marc, Klug Didier, Hayashi Miyuki, Takatsuki Seiji, Villain Elisabeth, Kamblock Joël, Messali Anne, Guicheney Pascale, Lunardi Joël, Leenhardt Antoine

Circulation 119 （ 18 ） 2426 - 2434 2009年05月

ISSN 0009-7322

Background - The pathophysiological background of catecholaminergic polymorphic ventricular tachycardia is well understood, but the clinical features of this stress-induced arrhythmic disorder, especially the incidence and risk factors of arrhythmic events, have not been fully ascertained. Methods and Results - The outcome in 101 catecholaminergic polymorphic ventricular tachycardia patients, including 50 probands, was analyzed. During a mean follow-up of 7.9 years, cardiac events defined as syncope, aborted cardiac arrest, including appropriate discharges from implantable defibrillators, or sudden cardiac death occurred in 27 patients, including 2 mutation carriers with normal exercise tests. The estimated 8-year event rate was 32% in the total population and 27% and 58% in the patients with and without β-blockers, respectively. Absence of β-blockers (hazard ratio [HR], 5.48; 95% CI, 1.80 to 16.68) and younger age at diagnosis (HR, 0.54 per decade; 95% CI, 0.33 to 0.89) were independent predictors. Fatal or near-fatal events defined as aborted cardiac arrest or sudden cardiac death occurred in 13 patients, resulting in an estimated 8-year event rate of 13%. Absence of β-blockers (HR, 5.54; 95% CI, 1.17 to 26.15) and history of aborted cardiac arrest (HR, 13.01; 95% CI, 2.48 to 68.21) were independent predictors. No difference was observed in cardiac and fatal or near-fatal event rates between probands and family members. Conclusions - Cardiac and fatal or near-fatal events were not rare in both catecholaminergic polymorphic ventricular tachycardia probands and affected family members during the long-term follow-up, even while taking β-blockers, which was associated with a lower event rate. Further studies evaluating concomitant therapies are necessary to improve outcome in these patients. © 2009 American Heart Association, Inc.

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Novel three-dimensional imaging of the anatomical relationship between the pulmonary vein and left atrium

Yamada Minoru, Jinzaki Masahiro, Sato Kozo, Tanami Yutaka, Fukumoto Kotaro, Tanimoto Kojiro, Takatsuki Seiji, Ogawa Satoshi, Kuribayashi Sachio

Circulation Journal 73 （ 3 ） 573 - 574 2009年03月

ISSN 1346-9843

Background: Visualization of the inner anatomical relationship of the pulmonary veins (PVs) and left atrium (LA) is important for achieving a better success rate and avoiding complications in circumferential LA ablation for atrial fbrillation (AF). Methods and Results: Twelve patients with AF underwent computed tomography and novel post-processing images that emphasized the boundaries of the PVs and LA were produced. Conclusions: The "Transparent View" images enabled visualization of the inner anatomical relationship of the PVs and LA in the same geometry as in pulmonary venography in all cases.

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The mechanism of PDT-induced electrical blockade

Ito A., Matsuo H., Suenari T., Miyoshi S., Takatsuki S., Ogawa S., Arai T.

2009年

We have proposed a new type of atrial fibrillation treatment with the early state photodynamic therapy (PDT), in which the interval time between the photosensitizer injection and irradiation is shorter than that in conventional way. We had demonstrated the acute electrical blockade by the PDT with talaporfin sodium and a red (670 nm) diodelaser in ex vivo and in vivo experiment using rat normal myocardial tissue. The previous study of intracellular Ca²⁺ concentration measurement in rat cardiac myocytes during the PDT indicated that Ca²⁺ influx induced by the plasma membrane damage might be the main cause of the acute reaction of myocardial tissue. We found that the cell damage of cardiac myocytes triggered by the PDT was mainly influenced by the site where the photosensitizer exists. In this study, we examined the relationship between the sites of talaporfin sodium existing and cell death phenotypes in response to the PDT, in order to clarify the mechanism of the acute electrical blockade induced by the PDT in myocardial tissue. The talaporfin sodium fluorescence was observed after the various incubation times to visualize the time-lapse intracellular photosensitizer localization. The distribution of the photosensitizer was dependent on the incubation time. The change in intracellular Ca²⁺ concentration during the PDT was examined with a fluorescent Ca²⁺ indicator by a high-speed Nipkow confocal laser microscope (CSU-X1, Yokogawa Electric Company). We obtained the Ca²⁺ dynamics during the PDT which can explain the PDT-induced cell death pathways. We concluded that the Ca²⁺ influx induced by plasma membrane damage is the possible mechanism of the electrical blockade by the early state PDT. © 2009 SPIE.

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Short-long-short sequence caused by ventricular safety pacing inducing ventricular tachycardia in a patient with a dual-chamber implantable cardioverter defibrillator

Hayashi Meiso, Takatsuki Seiji, Messali Anne, Milliez Paul, Extramiana Fabrice, Leenhardt Antoine

Europace 10 （ 10 ） 1238 - 1242 2008年10月

ISSN 1099-5129

Ventricular safety pacing (VSP) is an algorithm used to prevent crosstalk inhibition and ventricular capture during the vulnerable period. We report a 78-year-old man with implantable dual-chamber defibrillator, in whom clusters of ventricular tachycardias (VTs) were provoked by the VSP. During rapid DDDR pacing, the delivery of the VSP after every other atrial-paced beat resulted in short-long-short ventricular sequences and induced VTs. An atrial-based lower rate timing, long atrioventricular pacing interval, and automatic gain control also accounted for this arrhythmogenic ventricular sequence. The VSP and the subsequent VT were eliminated by decreasing the pacing rate. © The Author 2008.

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Ventricular Repolarization Restitution Properties in Patients Exhibiting Type 1 Brugada Electrocardiogram With and Without Inducible Ventricular Fibrillation

Hayashi Meiso, Takatsuki Seiji, Maison-Blanche Pierre, Messali Anne, Haggui Abdeddayem, Milliez Paul, Leenhardt Antoine, Extramiana Fabrice

Journal of the American College of Cardiology 51 （ 12 ） 1162 - 1168 2008年03月

ISSN 0735-1097

Objectives: This study aimed to elucidate the contribution of the repolarization restitution property to the sustained ventricular fibrillation (VF) in Brugada syndrome. Background: Although phase 2 re-entry develops as the trigger of VF, the other precipitating factors have remained unclear. Methods: Twenty-one patients with a type 1 Brugada electrocardiogram underwent programmed electrical stimulation. Before the VF induction, single extrastimuli were delivered at 3 basic drive cycle lengths (BCLs) (400 ms, 600 ms, and 750 ms) from the right ventricular apex (RVA) and outflow tract (RVOT), and the activation recovery interval (ARI) was measured at 5-mm vicinity of the pacing site. The maximum ARI restitution slope was determined using the overlapping least-squares linear segments. Results: We found that VF was inducible in 10 patients. A repeated-measure analysis of variance revealed that the slope in the RVA was steeper in patients with inducible VF than in those without but that in the RVOT was similar. The slope was steeper at longer BCLs and also steeper in the RVA than RVOT at BCLs of 600 and 750 ms. In patients with inducible VF, the percentage of patients exhibiting a slope >1 was 0%, 20%, and 75% in the RVA and 0%, 0%, and 14% in the RVOT at BCLs of 400 ms, 600 ms, and 750 ms, respectively. No patients without inducible VF had a slope >1. Conclusions: These results suggest the repolarization restitution property is a contributing factor to the propensity for VF in Brugada syndrome and, regarding this property, the RVA plays more important role than the RVOT. © 2008 American College of Cardiology Foundation.

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A case of vagally mediated idiopathic ventricular fibrillation

Kataoka Masaharu, Takatsuki Seiji, Tanimoto Kojiro, Akaishi Makoto, Ogawa Satoshi, Mitamura Hideo

Nature Clinical Practice Cardiovascular Medicine 5 （ 2 ） 111 - 115 2008年02月

ISSN 1743-4297

Background: A 25-year-old woman experienced three episodes of syncope over the course of 2 years. The attacks all occurred just after she had sat down, and two were accompanied by convulsions. She had no obvious prodromes and no personal or family history of cardiovascular disease. Investigations: Electrocardiography, chest radiography, echocardiography, cerebral and cardiac MRI, electroencephalography, 24 h Holter monitoring, electrophysiological study with drug provocation testing and heart-rate variability analysis. Diagnosis: Vagally mediated ventricular fibrillation initiated by premature ventricular complexes arising from the right ventricular outflow tract. Management: Catheter ablation was performed at the right ventricular outflow tract and an implantable cardioverter-defibrillator was fitted.

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Conduction through the lateral mitral isthmus

Takatsuki Seiji, Extramiana Fabrice, Hayashi Meiso, Leenhardt Antoine

Journal of Cardiovascular Electrophysiology 19 （ 1 ） 98 - 99 2008年01月

ISSN 1045-3873

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Functional bundle branch block and orthodromic reciprocating tachycardia cycle length

Extramiana Fabrice, Takatsuki Seiji, Hayashi Meiso, Leenhardt Antoine

Europace 9 （ 10 ） 920 - 922 2007年10月

ISSN 1099-5129

Aims: To show 2 examples in which the analysis of the effect of bundle branch block on orthodromic reciprocating tachycardia cycle length was misleading. Methods and results: We performed an electrophysiological study in two patients with orthodromic reciprocating tachycardia showing a transition from wide to narrow QRS during tachycardia. Our two cases of left bundle branch block during reciprocating tachycardia using infero-septal pathways show that ventricular to atrial conduction time prolongation may be larger than 30 ms and may be concealed by a shortening of atrial to ventricular conduction time. In the 2 cases, the atrial insertion of the accessory pathway could be successfully ablated from the right atria at the ostium of the coronary sinus. Conclusions: The observation of the association between left bundle branch block and cycle length prolongation during reciprocating tachycardia may be associated with a successful ablation at the ostium of the coronary sinus. © The European Society of Cardiology 2007. All rights reserved.

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T-wave morphology parameters based on principal component analysis reproducibility and dependence on T-offset position

Extramiana Fabrice, Haggui Abdeddayem, Maison-Blanche Pierre, Dubois Rémi, Takatsuki Seiji, Beaufils Philippe, Leenhardt Antoine

Annals of Noninvasive Electrocardiology 12 （ 4 ） 354 - 363 2007年10月

ISSN 1082-720X

Background: T-wave morphology parameters based on principal component analysis (PCA) are candidate to better understand the relation between QT prolongation and torsades de pointes. We aimed to assess the repeatability and to determine the influence of T-end position on PCA parameters. Methods: Digital ECGs recorded from 30 subjects were used to assess short term (5 minutes), circadian and long-term (28 days) repeatability of PCA parameters. The T-end cursor position was moved backward and forward (± 8 ms) from its optimal position. We calculated QRS-T angle, PCA ratio, and T-wave residuum (TWR). Results: At long-term evaluation, coefficients of variation were 11.3 ± 9.9%, 11.7 ± 7.1%, and 23.0 ± 22.0% for the QRS-T angle, PCA ratio, TWR, respectively. After moving the T-end cursor, repeatability was 0.42 ± 0.2%, 1.00 ± 1.04%, 4.0 ± 4.2% for the same PCA parameters. Conclusions: T-wave morphology parameters based on PCA are reproducible with the exception of TWR and QRS-T angle. In addition, PCA is robust, showing only little dependence on T-end cursor position. These data should be taken into account for safety pharmacology trials. © 2007, Copyright the Authors.

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Multiple gap phenomena associated with dual His bundle pathways having a lower common tract

Takatsuki Seiji, Extramiana Fabrice, Mitamura Hideo, Leenhardt Antoine

Journal of Electrocardiology 40 （ 5 ） 437 - 441 2007年09月

ISSN 0022-0736

We report a case showing 4 types of aberrant conduction and 2 types of gap phenomena produced by single atrial extrastimulus during sinus rhythm. One of the gap phenomena was associated with dual His bundle pathways, demonstrating a fast-to-slow jump-up phenomenon. Of note, a sharp potential considered as retrograde His bundle activations was recorded, which indicated that the activation wave front descended the slow His bundle pathway and turned up the fast His bundle pathway. © 2007 Elsevier Inc. All rights reserved.

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Transition to wide QRS tachycardia

Takatsuki Seiji, Mitamura Hideo, Tanimoto Kojiro, Leenhardt Antoine, Ogawa Satoshi

Journal of Cardiovascular Electrophysiology 18 （ 1 ） 111 - 113 2007年01月

ISSN 1045-3873

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Clinical implications of "pure" Hisian pacing in addition to para-Hisian pacing for the diagnosis of supraventricular tachycardia

Takatsuki Seiji, Mitamura Hideo, Tanimoto Kojiro, Fukuda Yukiko, Ieda Masaki, Miyoshi Shunichiro, Soejima Kyoko, Extramiana Fabrice, Leenhardt Antoine, Ogawa Satoshi

Heart Rhythm 3 （ 12 ） 1412 - 1418 2006年12月

ISSN 1547-5271

Background: Para-Hisian pacing is an effective method of differentiating between pathways for retrograde conduction over the accessory pathway (AP) and over the atrioventricular node (AVN). When performing para-Hisian pacing, the pacing spike sometimes captures only the His bundle, which we named "pure" Hisian pacing (Hc). Objective: We evaluated the significance of pure Hisian pacing for predicting the pathways of ventriculoatrial conduction. Methods: In 62 patients with supraventricular tachycardia, both para-Hisian and pure Hisian pacing were carried out during the sinus rhythm, resulting in three different types of electrocardiographic complexes with wide (local ventricular myocardial capture), slightly narrow (both local myocardial and His bundle capture), and very narrow QRS widths (Hc). A change of atrial activation sequence as demonstrated by these pacing modes indicated the presence of multiple retrograde pathways. The diagnosis of retrograde pathways by para-Hisian pacing with or without Hc was evaluated. Results: In 22 patients with AVN reentrant tachycardia, para-Hisian pacing alone was able to correctly predict ventriculo-atrial conduction exclusively through the AVN without requiring findings from Hc. In 40 AP patients, para-Hisian pacing showed a pattern of retrograde conduction through the AVN in six, through both the AVN and AP in 10, and through an AP in 24 patients. Four of these 24 patients were diagnosed as having multiple pathways (AP+AVN or dual APs) by the addition of Hc. Conclusion: Pure Hisian pacing can help disclose another pathway for retrograde conduction in AP patients, which is unpredicted by ordinary para-Hisian pacing. © 2006 Heart Rhythm Society.

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Dysplasie ventriculaire droite arythmogène

Leenhardt A., Milliez P., Haggui A., Takatsuki S., Hayashi M., Meddane M., Dejode P., Denjoy I., Extramiana F.

Archives des Maladies du Coeur et des Vaisseaux 99 （ SPEC. ISS. 5 ） 7 - 14 2006年12月

ISSN 0003-9683

Arrhythmogenic right ventricular dysplasia (ARVD) is a cardiomyopathy of the right ventricle due to adipose infiltration of the myocardium with surviving myocardial fibres surrounded by fibrosis. It gives rise to right ventricular dilatation, which starts locally before becoming diffuse, and, sometimes in the late stages, to symptoms of cardiac failure. It may also be associated with left ventricular involvement. The main complication is sudden death due to a ventricular arrhythmia. ARVD is responsible for 3 to 10% of all unexplained sudden deaths before 65 years of age. ARVD has a genetic origin, with some recessive but a majority of autosomal dominant forms. Nine different loci have been reported in the autosomal dominant forms and four genes have been identified. A number of these mutations is responsible for abnormalities of cellular junction, more specifically of the desmosomes. These studies have shown several different forms of ARVD and, consequently, the term arrhythmogenic right ventricular cardiomyopathy would be a more appropriate terminology for the pathology. This paper reviews the diagnostic, genetic and therapeutic aspects of the disease. In particular, the evaluation of the arrhythmic risk is underlined as it is an important and difficult problem which has not yet been satisfactorily resolved. It requires integration of clinical and electrocardiographic criteria with morphological and functional imaging methods. Molecular biology could play a role in the prognostic assessment in the future.

Quantitative assessment of ST segment elevation in Brugada patients

Extramiana Fabrice, Seitz Julien, Maison-Blanche Pierre, Badilini Fabio, Haggui Abdeddayem, Takatsuki Seiji, Milliez Paul, Denjoy Isabelle, Cauchemez Bruno, Beaufils Philippe, Leenhardt Antoine

Heart Rhythm 3 （ 10 ） 1175 - 1181 2006年10月

ISSN 1547-5271

Background: ST segment elevation in the right precordial leads constitutes the electrocardiogram (ECG) hallmark of Brugada syndrome (BS). This pattern is variable and can be concealed, but the magnitude and the cause of ST segment fluctuations have been poorly investigated. Objective: Our goal was to quantify ST changes and to assess rate and autonomic influences on ST level. Methods: A 12-lead ECG was continuously recorded during 24 hours in 20 patients with BS (ages 49 ± 12) and 10 healthy subjects (ages 32 ± 7). Using two-dimensional binning we obtained average QRS-T complexes every 30 minutes (time bins) and at different RR intervals (rate bins) for each subject. ST level was measured at five different points located 90, 100, 110, 120, and 140 ms after Q onset (Qo). In BS patients, the highest ST elevation was measured 110 ms after Qo (Qo+110). Results: ST level changes between time points were significantly greater in patients with BS compared with control subjects: on lead V2, the range of ST level at Qo+110 was 264 ± 85 μV in BS and 91 ± 22 μV in control subjects (P <.01). In BS, ST level decreased with heart rate acceleration: the difference in ST level at Qo+110 for RR = 900 and 600 ms was 55 ± 53 μV (P <.01). HFnu was positively, although weakly, correlated with ST level (R² = 0.02, P <.01). Conclusions: ECG changes observed in patients with BS are related in part to heart rate influences on ST segment level. These spontaneous fluctuations over a 24-hour time period suggest that Holter recordings may improve the ECG diagnosis sensitivity in BS. © 2006 Heart Rhythm Society.

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Amiodarone therapy in patients implanted with cardioverter-defibrillator for life-threatening ventricular arrhythmias

Satomi Kazuhiro, Kurita Takashi, Takatsuki Seiji, Yokoyama Yasuhiro, Chinushi Masaomi, Tsuboi Naoya, Nitta Takashi, Shoda Morio, Mitamura Hideo

Circulation Journal 70 （ 8 ） 977 - 984 2006年

ISSN 1346-9843

Background: Whether amiodarone can improve the patient's clinical outcome by reducing implantable cardioverter-defibrillator (ICD) therapy deliveries for ventricular tachycardia or fibrillation (VT/VF) has not been clearly evaluated. Methods and Results: A total of 507 patients with VT/VF due to organic heart disease who had ICDs implanted were enrolled in this study. The patients were divided into 3 groups: Amiodarone (n=247), Class I antiarrhythmic drug (n=103) and Control (n=157) groups, and the total cause mortality and arrhythmic event free survival rates were evaluated between the groups. The mean follow-up period was 38±27 months. The left ventricular ejection fraction was significantly decreased in the Amiodarone group (Amiodarone: 37±15%; Class I: 39±16%; Control: 44±17%). The mortality and arrhythmic events were significantly higher in the Class I group than the Amiodarone group (p<0.05), but there was no significant difference between the Amiodarone and Control groups (arrhythmic event free rate at 5 years: Amiodarone: 53%; Class I: 35%; Control: 48%; 5 year survival: 86%, 74% and 77%, respectively). Side effects from amiodarone were found in 12% of the patients, but no fatal events were observed. Conclusions: The present study could not demonstrate the benefit of amiodarone in ICD patients, probably due to a significant clinical bias exerted in selecting this drug.

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Link between SCN5A mutation and the Brugada syndrome ECG phenotype

Miyoshi Shunichiro, Mitamura Hideo, Fukuda Yukiko, Tanimoto Kojiro, Hagiwara Yoko, Kanki Hideaki, Takatsuki Seiji, Murata Mitsushige, Miyazaki Toshihisa, Ogawa Satoshi

Circulation Journal 69 （ 5 ） 567 - 575 2005年05月

ISSN 1346-9843

Background: The specific changes in the gating kinetics of the sodium current (INa) responsible for its phenotype have remained to be elucidated. In the present study the effect of changes in the gating kinetics of INa on early repolarization (ER) and initiation of phase 2 reentry (P2R) were evaluated in a theoretical epicardial ventricular fiber model. Methods and Results: Miyoshi-ICaL was incorporated into the modified Luo-Rudy dynamic (LRd) model. Dispersion at Ito-density was set within a theoretical fiber composed of serially arranged epicardial cells with gap junctions. The following changes in INa kinetics were made: (1) a -10mV shift in steady-state inactivation, (2) a +10mV shift in steady-state activation curve, (3) a small inactivation time constant (DEC); P2R and ER were observed. A conduction disturbance within the fiber was simulated and only when the INa-density was decreased did DEC, especially, show a marked increase in the likelihood of causing ER and P2R. Conduction disturbance significantly increased the likelihood causing ER or P2R. Conclusions: In this one-dimension model with Ito-density dispersion, DEC-INa precipitates INa-blocker inducible ER. This suggests that the characteristic ST-segment elevation in the Brugada syndrome with SCN5A mutation can be interpreted in part by DEC-INa. Concomitant conduction disturbance may be required to cause P2R at physiological Ito density.

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Temporal patterns of progression and regression of electrical and mechanical remodeling of the atrium

Kinebuchi Osamu, Mitamura Hideo, Shiroshita-Takeshita Akiko, Kurita Yasuo, Ohashi Narutaka, Tanimoto Kojiro, Fukuda Yukiko, Ieda Masaki, Sato Toshiaki, Hara Motoki, Takatsuki Seiji, Ogawa Satoshi

International Journal of Cardiology 98 （ 1 ） 91 - 98 2005年01月

ISSN 0167-5273

Objectives: We evaluated serial changes of electrical and mechanical parameters of atrial remodeling in dogs subjected to rapid atrial pacing. Background: Prolonged rapid atrial excitation causes electrical and mechanical remodeling, which contributes to persistence of atrial fibrillation and clot formation. However, the temporal relationship between these two types of atrial remodeling remains unknown. Methods: In 8 dogs, rapid pacing at 400 ppm was continued for 14 days. The electrophysiologic and transesophageal echocardiographic studies were performed on the day before and after 2, 7, and 14 days of rapid pacing, then 1 and 7 days after the cessation of pacing. These were compared with sham-operated dogs (instrumented but not paced, n=6). Results: With rapid pacing, there was an immediate shortening of the effective refractory period (ERP) and decreases in the transmitral atrial wave velocity (MAV) and the left atrial appendage emptying velocity (LAAV). In contrast, conduction velocity (CV) decreased and the left atrial appendage area (LAAA) increased progressively over 14 days. During the recovery, ERP, MAV, and LAAV returned to the baseline in 1 day, whereas CV and LAAA did in 7 days. ERP was highly positively correlated with LAAV (r=0.78, p<0.001) and MAV (r=0.73, p<0.001), while CV was negatively correlated only with LAAA (r=-0.58, p<0.001). Conclusions: Pacing-induced electrical and mechanical remodeling of the atrium exhibits divergent patterns of progression and regression such that changes of ERP and contractile function take place more rapidly than those of CV and atrial size. © 2004 Elsevier Ireland Ltd. All rights reserved.

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A comparison between calcium channel blocking drugs with different potencies for T- and L-type channels in preventing atrial electrical remodeling

Ohashi Narutaka, Mitamura Hideo, Tanimoto Kojiro, Fukuda Yukiko, Kinebuchi Osamu, Kurita Yasuo, Shiroshita-Takeshita Akiko, Miyoshi Shunichiro, Hara Motoki, Takatsuki Seiji, Ogawa Satoshi

Journal of Cardiovascular Pharmacology 44 （ 3 ） 386 - 392 2004年09月

ISSN 0160-2446

Calcium overload plays a key role in the development of atrial electrical remodeling. The effect of an L-type Ca channel blocker in preventing this remodeling has been reported to be short lasting, partly due to down-regulation of this channel and persisting Ca entry through the T-type Ca channel. To prove if efonidipine, a dual L- and T-type Ca channel blocker exerts a greater effect than an L-type Ca channel blocker verapamil, 21 dogs underwent rapid atrial pacing at 400 bpm for 14 days, pretreatment with efonidipine in 7 (E), verapamil in 7 (V), and none in 7 (C). We measured the atrial effective refractory period (ERP) serially during 14 days of rapid pacing. In response to rapid pacing, ERP decreased progressively in C. In contrast, in E and V, ERP remained greater than ERP in C (P < 0.01) on days 2 through 7. However, on the 14th day, ERP in V decreased to the level seen in C, whereas ERP in E remained significantly longer than ERPs in C or V (P < 0.01). The blockade L-type Ca channel alone is not sufficient, but the addition of a T-type Ca channel blockade shows a more sustained effect to prevent atrial electrical remodeling.

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Oral verapamil attenuates the progression of pacing-induced electrical and mechanical remodeling of the atrium

Kinebuchi Osamu, Mitamura Hideo, Shiroshita-Takeshita Akiko, Kurita Yasuo, Ieda Masaki, Ohashi Narutaka, Fukuda Yukiko, Sato Toshiaki, Miyoshi Shunichiro, Hara Motoki, Takatsuki Seiji, Nagumo Miyako, Ogawa Satoshi

Circulation Journal 68 （ 5 ） 494 - 500 2004年05月

ISSN 1346-9843

Background: Calcium overload plays a major role in the development of electrical and mechanical remodeling during atrial fibrillation, but the potential of verapamil, a Ca blocker, for preventing atrial electrical remodeling remains controversial. Methods and Results: Pacing and recording electrodes were sutured to the right atrium in 16 dogs. After a 5-day recovery period, rapid atrial pacing at 400 ppm was initiated in 8 dogs (control group). In the remaining 8 dogs, oral administration of verapamil (8 mg/kg per day) was started 1 week before the initiation of rapid pacing (verapamil group). On the day before and at 2, 7, 14 days after rapid pacing, electrophysiological (EP) and transesophageal echocardiographic (TEE) studies were performed under autonomic blockade. In response to rapid pacing, EP and TEE parameters changed progressively in the control group (p<0.05 vs day 0), whereas in the verapamil group, no significant changes in the various parameters were observed for the first 7 days. However, verapamil failed to prevent progression of both types of remodeling after 14 days of pacing. Conclusion: Verapamil can attenuate the progression of electrical and mechanical remodeling of the atrium for at least 7 days.

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