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発作性心房細動

薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
蜂谷仁 : 特に申告事項無し[2022年]
監修:今井靖 : 講演料(第一三共株式会社)[2022年]

改訂のポイント:
  1. 2021年 JCS/ J HRS ガイドライン フォーカスアップデート版 不整脈非薬物治療より、「心不全を伴うAFに対するカテーテルアブレーションの推奨とエビデンスレベル」について追記した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 心房細動とは、心房に変動する複数のリエントリーが成立し心房が統率のないまま局所的には350~600回/分またはそれ以上の頻度で興奮している状態である。R-R間隔は不整で、絶対性不整脈と呼ばれる。
 
心電図による鑑別

いずれも心拍、脈拍とも不規則に自覚される。心房細動では心電図上P波は認められず細動波となっている。一方上室期外収縮の呈示心電図では洞調律時P波と平坦な基線、T波上にP波(上室期外収縮)が認められる(↓)。心室期外収縮ではQRS幅は広くなる。もちろんその他の不整脈;心房粗動などでも不規則な心拍、脈拍が自覚され得る。
*心房粗動では、房室伝導比が一定であれば規則的心拍、伝導比が不定で変化する場合は不規則となる。

 
  1. わが国では、心房細動患者は約100万人と推定されている。うち、70歳を超えると女性で1~2%、男性で3~4%と罹患率が高い。日本の全人口にあてはめると、心房細動有病率は0.56%と推定されている。
  1. 発症7日以内で自然に洞調律へ復する発作性心房細動、7日以上持続する持続性心房細動、1年以上持続する長期持続性心房細動に分類される。
  1. 血栓塞栓症発症が、心房細動患者におけるリスクとなる。合併疾患により、その発症率は大きく異なる。
  1. 基礎疾患としては弁膜症(主に僧帽弁狭窄症)が多かったが、最近では非弁膜症性心房細動の頻度が高い。虚血性心疾患、高血圧、甲状腺機能亢進症などが挙げられる。
問診、診察のポイント  
  1. 動悸が主訴であることが多い。心拍が規則的か不規則か確認する。

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文献 

B F Gage, A D Waterman, W Shannon, M Boechler, M W Rich, M J Radford
Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation.
JAMA. 2001 Jun 13;285(22):2864-70.
Abstract/Text CONTEXT: Patients who have atrial fibrillation (AF) have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions.
OBJECTIVE: To assess the predictive value of classification schemes that estimate stroke risk in patients with AF.
DESIGN, SETTING, AND PATIENTS: Two existing classification schemes were combined into a new stroke-risk scheme, the CHADS( 2) index, and all 3 classification schemes were validated. The CHADS( 2) was formed by assigning 1 point each for the presence of congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and by assigning 2 points for history of stroke or transient ischemic attack. Data from peer review organizations representing 7 states were used to assemble a National Registry of AF (NRAF) consisting of 1733 Medicare beneficiaries aged 65 to 95 years who had nonrheumatic AF and were not prescribed warfarin at hospital discharge.
MAIN OUTCOME MEASURE: Hospitalization for ischemic stroke, determined by Medicare claims data.
RESULTS: During 2121 patient-years of follow-up, 94 patients were readmitted to the hospital for ischemic stroke (stroke rate, 4.4 per 100 patient-years). As indicated by a c statistic greater than 0.5, the 2 existing classification schemes predicted stroke better than chance: c of 0.68 (95% confidence interval [CI], 0.65-0.71) for the scheme developed by the Atrial Fibrillation Investigators (AFI) and c of 0.74 (95% CI, 0.71-0.76) for the Stroke Prevention in Atrial Fibrillation (SPAF) III scheme. However, with a c statistic of 0.82 (95% CI, 0.80-0.84), the CHADS( 2) index was the most accurate predictor of stroke. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3-1.7) for each 1-point increase in the CHADS( 2) score: 1.9 (95% CI, 1.2-3.0) for a score of 0; 2.8 (95% CI, 2.0-3.8) for 1; 4.0 (95% CI, 3.1-5.1) for 2; 5.9 (95% CI, 4.6-7.3) for 3; 8.5 (95% CI, 6.3-11.1) for 4; 12.5 (95% CI, 8.2-17.5) for 5; and 18.2 (95% CI, 10.5-27.4) for 6.
CONCLUSION: The 2 existing classification schemes and especially a new stroke risk index, CHADS( 2), can quantify risk of stroke for patients who have AF and may aid in selection of antithrombotic therapy.

PMID 11401607
Takanori Ikeda
Which score should be used for risk stratification of ischemic stroke in patients with atrial fibrillation.
Circ J. 2014;78(6):1331-2. doi: 10.1253/circj.cj-14-0409. Epub 2014 May 7.
Abstract/Text
PMID 24805355
Shinya Suzuki, Takeshi Yamashita, Ken Okumura, Hirotsugu Atarashi, Masaharu Akao, Hisashi Ogawa, Hiroshi Inoue
Incidence of ischemic stroke in Japanese patients with atrial fibrillation not receiving anticoagulation therapy--pooled analysis of the Shinken Database, J-RHYTHM Registry, and Fushimi AF Registry.
Circ J. 2015;79(2):432-8. doi: 10.1253/circj.CJ-14-1131. Epub 2014 Dec 11.
Abstract/Text BACKGROUND: The incidence rate of ischemic stroke in Japanese non-valvular atrial fibrillation (NVAF) patients without anticoagulation therapy remains unclear.
METHODS AND RESULTS: We performed a pooled analysis of 3,588 patients from the Shinken Database (n=1,099), J-RHYTHM Registry (n=1,002), and Fushimi AF Registry (n=1,487) to determine the incidence rate of ischemic stroke in Japanese NVAF patients without anticoagulation therapy. Average patient age was 68.1 years. During the follow-up period (total, 5,188 person-years; average, 1.4 years), 69 patients suffered from ischemic stroke (13.3 per 1,000 person-years; 95% confidence intervals [CI]: 10.5-16.8). The incidence rates of ischemic stroke were 5.4, 9.3, and 24.7 per 1,000 person-years and 5.3, 5.5, and 18.4 per 1,000 person-years in patients with low (0), intermediate (1), and high (≥ 2) CHADS2 and CHA2DS2-VASc scores, respectively. History of ischemic stroke or transient ischemic attack (hazard ratio [HR], 3.25; 95% CI: 1.86-5.67), age ≥ 75 years (HR, 2.31; 95% CI: 1.18-4.52), and hypertension (HR, 1.69; 95% CI: 1.01-2.86) were independent risk factors for ischemic stroke.
CONCLUSIONS: A low incidence rate of ischemic stroke was observed in Japanese NVAF patients except for those with CHADS2 score ≥ 2. In this pooled analysis, history of ischemic stroke or transient ischemic attack, advanced age, and hypertension were identified as independent risk factors for ischemic stroke.

PMID 25501800
K H Humphries, C R Kerr, S J Connolly, G Klein, J A Boone, M Green, R Sheldon, M Talajic, P Dorian, D Newman
New-onset atrial fibrillation: sex differences in presentation, treatment, and outcome.
Circulation. 2001 May 15;103(19):2365-70.
Abstract/Text BACKGROUND: Although sex differences in coronary artery disease have received considerable attention, few studies have dealt with sex differences in the most common sustained cardiac arrhythmia, atrial fibrillation (AF). Differences in presentation and clinical course may dictate different approaches to detection and management. We sought to examine sex-related differences in presentation, treatment, and outcome in patients presenting with new-onset AF.
METHODS AND RESULTS: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled subjects at the time of first ECG-confirmed diagnosis of AF. Participants were followed at 3 months, at 1 year, and annually thereafter. Treatment was at the discretion of the patients' physicians and was not directed by CARAF investigators. Baseline and follow-up data collection included a detailed medical history, clinical, ECG, and echocardiographic measures, medication history, and therapeutic interventions. Three hundred thirty-nine women and 560 men were followed for 4.14+/-1.39 years. Compared with men, women were older at the time of presentation, more likely to seek medical advice because of symptoms, and experienced significantly higher heart rates during AF. Compared with older men, older women were half as likely to receive warfarin and twice as likely to receive acetylsalicylic acid. Compared with men on warfarin, women on warfarin were 3.35 times more likely to experience a major bleed.
CONCLUSIONS: Anticoagulants are underused in older women with AF relative to older men with AF, despite comparable risk profiles. Women receiving warfarin have a significantly higher risk of major bleeding, suggesting the need for careful monitoring of anticoagulant intensity in women.

PMID 11352885
I C Van Gelder, H J Crijns, R G Tieleman, J Brügemann, P J De Kam, A T Gosselink, F W Verheugt, K I Lie
Chronic atrial fibrillation. Success of serial cardioversion therapy and safety of oral anticoagulation.
Arch Intern Med. 1996 Dec 9-23;156(22):2585-92.
Abstract/Text BACKGROUND: Serial electrical cardioversion is often used for treatment of atrial fibrillation, but its long-term efficacy has not been determined prospectively.
OBJECTIVES: To determine the long-term success rate of the serial electrical cardioversion approach in patients with chronic atrial fibrillation, to identify factors that predict its success, and to assess the efficacy and safety of oral anticoagulation in these patients.
METHODS: Patients with chronic (> 24 hours) atrial fibrillation received anticoagulant therapy for at least 4 weeks prior to electrical cardioversion. No prophylactic antiarrhythmic agent was given after the first shock. Relapses were managed by using repeated cardioversions, after which serial antiarrhythmic drug therapy was started. Treatment with anticoagulants was withdrawn after 4 weeks of sinus rhythm.
RESULTS: Two hundred thirty-six patients were followed up for a mean +/- SD of 3.7 +/- 1.6 years. The actuarial cumulative percentages of patients who maintained sinus rhythm after serial cardioversion treatment was 42% and 27% after 1 and 4 years, respectively. Multivariate analysis showed that factors that were associated with failure of this approach included duration of atrial fibrillation that exceeded 36 months (risk ratio, 5.0; P < .001), poor exercise tolerance (functional class III; risk ratio, 1.8; P = .001), and age older than 56 years (risk ratio, 1.5; P = .04). The anticoagulation level (international normalized ratio, 2.4-4.8) was associated with an incidence of thromboembolic events and bleeding complications of 0.2% and 1.5%, respectively.
CONCLUSIONS: Many patients with chronic atrial fibrillation failed to respond to the serial electrical cardioversion strategy. However, in younger patients with a fair exercise tolerance and a duration of atrial fibrillation shorter than 36 months, this approach may be worthwhile. In addition, thromboembolic events were infrequent in the patients who were subjected to this regimen.

PMID 8951302
Satoshi Ogawa, Takeshi Yamashita, Tsutomu Yamazaki, Yoshifusa Aizawa, Hirotsugu Atarashi, Hiroshi Inoue, Tohru Ohe, Hiroshi Ohtsu, Ken Okumura, Takao Katoh, Shiro Kamakura, Koichiro Kumagai, Yoshihisa Kurachi, Itsuo Kodama, Yukihiro Koretsune, Tetsunori Saikawa, Masayuki Sakurai, Kaoru Sugi, Toshifumi Tabuchi, Haruaki Nakaya, Toshio Nakayama, Makoto Hirai, Masahiko Fukatani, Hideo Mitamura, J-RHYTHM Investigators
Optimal treatment strategy for patients with paroxysmal atrial fibrillation: J-RHYTHM Study.
Circ J. 2009 Feb;73(2):242-8. Epub 2008 Dec 8.
Abstract/Text Background Although previous clinical trials demonstrated the non-inferiority of a rate control to rhythm control strategy for management of atrial fibrillation (AF), the optimal treatment strategy for paroxysmal AF (PAF) remains unclear. Methods and Results A randomized, multicenter comparison of rate control vs rhythm control in Japanese patients with PAF (the Japanese Rhythm Management Trial for Atrial Fibrillation (J-RHYTHM) study) was conducted. The primary endpoint was a composite of total mortality, symptomatic cerebral infarction, systemic embolism, major bleeding, hospitalization for heart failure, or physical/psychological disability requiring alteration of treatment strategy. In the study, 823 patients with PAF were followed for a mean period of 578 days. The primary endpoint occurred in 64 patients (15.3%) assigned to rhythm control and in 89 patients (22.0%) to rate control (P=0.0128). No significant differences between the treatment strategies were observed in the incidences of death, stroke, bleeding and heart failure. Meanwhile, significantly fewer patients requested changes of assigned treatment strategy in the rhythm control vs the rate control group, which was accompanied by improvement in AF-specific quality of life scores. Conclusion The J-RHYTHM study showed that rhythm control was associated with fewer primary endpoints than rate control. However, mortality and cardiovascular morbidity were not affected by the treatment strategy (umin-CTR No. C000000106).

PMID 19060419
Abstract/Text Based on the results of the Cardiac Arrhythmia Suppression Trial (CAST), strategies for the treatment of tachyarrhythmias have changed rapidly. The Japanese Antiarrhythmics Long-Term (JALT) study was planned to investigate the present methods for choosing antiarrhythmic drugs, and the effects on long-term prognosis in patients with tachyarrhythmias in Japan. Following a 6-month preliminary study (JALT-1), there was a multicenter nonrandomized prospective study (JALT-2), with a 2-year follow-up, of patients with paroxysmal atrial fibrillation (PAF), sustained ventricular tachycardia (SVT) and nonsustained VT (NSVT). Four hundred fifty-five patients were registered, and 361 of them (79%) were analyzed. Cerebral infarction occurred in 10 of 193 patients (5.2%) with PAF. Transition to chronic AF was observed in 21 patients (10.9%), but in none of the patients receiving Ca antagonist therapy. Twenty-five patients died: 5 deaths were arrhythmic, 10 were because of pump failure, and 9 were noncardiac. The most significant difference in drug selection between JALT-1 and JALT-2 was the increase in the use of slow kinetic Na channel blockers for PAF and the decrease in the use of the same agents for VT in the JALT-2 study. A marked change of therapeutic strategy occurred in JALT-2 compared with JALT-1. Most patients with a poor prognosis had underlying heart diseases and heart failure, but the per annum rate of death by arrhythmia and pump failure in JALT-2 was less than that in JALT-1.

PMID 11316122
Paolo Alboni, Giovanni L Botto, Nicola Baldi, Mario Luzi, Vitantonio Russo, Lorella Gianfranchi, Paola Marchi, Massimo Calzolari, Alberto Solano, Raffaele Baroffio, Germano Gaggioli
Outpatient treatment of recent-onset atrial fibrillation with the "pill-in-the-pocket" approach.
N Engl J Med. 2004 Dec 2;351(23):2384-91. doi: 10.1056/NEJMoa041233.
Abstract/Text BACKGROUND: In-hospital administration of flecainide and propafenone in a single oral loading dose has been shown to be effective and superior to placebo in terminating atrial fibrillation. We evaluated the feasibility and the safety of self-administered oral loading of flecainide and propafenone in terminating atrial fibrillation of recent onset outside the hospital.
METHODS: We administered either flecainide or propafenone orally to restore sinus rhythm in 268 patients with mild heart disease or none who came to the emergency room with atrial fibrillation of recent onset that was hemodynamically well tolerated. Of these patients, 58 (22 percent) were excluded from the study because of treatment failure or side effects. Out-of-hospital self-administration of flecainide or propafenone--the "pill-in-the-pocket" approach--after the onset of heart palpitations was evaluated in the remaining 210 patients (mean age [+/-SD], 59+/-11 years).
RESULTS: During a mean follow-up of 15+/-5 months, 165 patients (79 percent) had a total of 618 episodes of arrhythmia; of those episodes, 569 (92 percent) were treated 36+/-93 minutes after the onset of symptoms. Treatment was successful in 534 episodes (94 percent); the time to resolution of symptoms was 113+/-84 minutes. Among the 165 patients with recurrences, the drug was effective during all the arrhythmic episodes in 139 patients (84 percent). Adverse effects were reported during one or more arrhythmic episodes by 12 patients (7 percent), including atrial flutter at a rapid ventricular rate in 1 patient and noncardiac side effects in 11 patients. The numbers of monthly visits to the emergency room and hospitalizations were significantly lower during follow-up than during the year before the target episode (P<0.001 for both comparisons).
CONCLUSIONS: In a selected, risk-stratified population of patients with recurrent atrial fibrillation, pill-in-the-pocket treatment is feasible and safe, with a high rate of compliance by patients, a low rate of adverse events, and a marked reduction in emergency room visits and hospital admissions.

Copyright 2004 Massachusetts Medical Society.
PMID 15575054
Abstract/Text The efficacy and safety of a single oral dose of 150-mg pilsicainide, a new class Ic antiarrhythmic drug, in converting recent-onset atrial fibrillation to sinus rhythm were evaluated in 75 patients (51 men, 24 women; age 23 to 74 years). Conversion to sinus rhythm was achieved within 90 minutes in 45% of patients given pilsicainide and in 8.6% of those on placebo (p < 0.01), with no major adverse effects.

PMID 8831412
P Alboni, C Tomasi, C Menozzi, N Bottoni, N Paparella, G Fucà, M Brignole, R Cappato
Efficacy and safety of out-of-hospital self-administered single-dose oral drug treatment in the management of infrequent, well-tolerated paroxysmal supraventricular tachycardia.
J Am Coll Cardiol. 2001 Feb;37(2):548-53.
Abstract/Text OBJECTIVES: We tested the efficacy of two drug treatments, flecainide (F) and the combination ofdiltiazem and propranolol (D/P), administered as a single oral dose for termination of the arrhythmic episodes.
BACKGROUND: Both prophylactic drug therapy and catheter ablation are questionable as first-line treatments in patients with infrequent and well-tolerated episodes of paroxysmal supraventricular tachycardia (SVT).
METHODS: Among 42 eligible patients (13% of all screened for SVT) with infrequent (< or =5/year), well-tolerated and long-lasting episodes, 37 were enrolled and 33 had SVT inducible during electrophysiological study. In the latter, three treatments (placebo, F, and D/P) were administered in a random order 5 min after SVT induction on three different days.
RESULTS: Conversion to sinus rhythm occurred within 2 h in 52%, 61%, and 94% of patients on placebo, F and D/P, respectively (p < 0.001). The conversion time was shorter after D/P (32 +/- 22 min) than after placebo (77 +/- 42 min, p < 0.001) or F (74 +/- 37 min, p < 0.001). Four patients (1 placebo, 1 D/P, and 2 F) had hypotension and four (3 D/P and 1 F) a sinus rate <50 beats/min following SVT interruption. Patients were discharged on a single oral dose of the most effective drug treatment (F or D/P) at time of acute testing. Twenty-six patients were discharged on D/P and five on F. During 17 +/- 12 months follow-up, the treatment was successful in 81% of D/P patients and in 80% of F patients, as all the arrhythmic episodes were interrupted out-of-hospital within 2 h. In the remaining patients, a failure occurred during one or more episodes because of drug ineffectiveness or drug unavailability. One patient had syncope after D/P ingestion. During follow-up, the percentage of patients calling for emergency room assistance was significantly reduced as compared to the year before enrollment (9% vs. 100%, p < 0.0001).
CONCLUSIONS: The episodic treatment with oral D/P and F, as assessed during acute testing, appears effective in the management of selected patients with SVT. This therapeutic strategy minimizes the need for emergency room admissions during tachycardia recurrences.

PMID 11216977
A Capucci, T Lenzi, G Boriani, G Trisolino, N Binetti, M Cavazza, G Fontana, B Magnani
Effectiveness of loading oral flecainide for converting recent-onset atrial fibrillation to sinus rhythm in patients without organic heart disease or with only systemic hypertension.
Am J Cardiol. 1992 Jul 1;70(1):69-72. doi: 10.1016/0002-9149(92)91392-h.
Abstract/Text Sixty-two patients with recent-onset (less than or equal to 1 week) atrial fibrillation (New York Heart Association functional class 1 and 2) were randomized in a single-blind study to 1 of the following treatment groups: (1) flecainide (300 mg) as a single oral loading dose; or (2) amiodarone (5 mg/kg) as an intravenous bolus, followed by 1.8 g/day; or (3) placebo for the first 8 hours. Twenty-four-hour Holter recording was performed, and conversion to sinus rhythm at 3, 8, 12 and 24 hours was considered as the criterion of efficacy. Conversion to sinus rhythm was achieved within 8 hours (placebo-controlled period) in 20 of 22 patients (91%) treated with flecainide, 7 of 19 (37%) treated with amiodarone (p less than 0.001 vs flecainide), and 10 of 21 (48%) treated with placebo (p less than 0.01 vs flecainide). Resumption of sinus rhythm within 24 hours occurred in 21 of 22 patients (95%) with flecainide and in 17 of 19 (89%) with amiodarone (p = not significant). Mean conversion times were shorter for flecainide (190 +/- 147 minutes) than for amiodarone (705 +/- 418; p less than 0.001). No major side effects occurred. At Holter monitoring, a pause of 9.3 seconds was observed in 1 asymptomatic patient treated with flecainide. Phases of atrial flutter with a ventricular rate less than or equal to 150 beats/min were detected before sinus conversion in 1 patient receiving placebo and in 2 receiving flecainide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 1615873
A Capucci, G Boriani, G L Botto, T Lenzi, I Rubino, C Falcone, G Trisolino, S Della Casa, N Binetti, M Cavazza
Conversion of recent-onset atrial fibrillation by a single oral loading dose of propafenone or flecainide.
Am J Cardiol. 1994 Sep 1;74(5):503-5. doi: 10.1016/0002-9149(94)90915-6.
Abstract/Text
PMID 8059737
M Haïssaguerre, P Jaïs, D C Shah, A Takahashi, M Hocini, G Quiniou, S Garrigue, A Le Mouroux, P Le Métayer, J Clémenty
Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins.
N Engl J Med. 1998 Sep 3;339(10):659-66. doi: 10.1056/NEJM199809033391003.
Abstract/Text BACKGROUND: Atrial fibrillation, the most common sustained cardiac arrhythmia and a major cause of stroke, results from simultaneous reentrant wavelets. Its spontaneous initiation has not been studied.
METHODS: We studied 45 patients with frequent episodes of atrial fibrillation (mean [+/-SD] duration, 344+/-326 minutes per 24 hours) refractory to drug therapy. The spontaneous initiation of atrial fibrillation was mapped with the use of multielectrode catheters designed to record the earliest electrical activity preceding the onset of atrial fibrillation and associated atrial ectopic beats. The accuracy of the mapping was confirmed by the abrupt disappearance of triggering atrial ectopic beats after ablation with local radio-frequency energy.
RESULTS: A single point of origin of atrial ectopic beats was identified in 29 patients, two points of origin were identified in 9 patients, and three or four points of origin were identified in 7 patients, for a total of 69 ectopic foci. Three foci were in the right atrium, 1 in the posterior left atrium, and 65 (94 percent) in the pulmonary veins (31 in the left superior, 17 in the right superior, 11 in the left inferior, and 6 in the right inferior pulmonary vein). The earliest activation was found to have occurred 2 to 4 cm inside the veins, marked by a local depolarization preceding the atrial ectopic beats on the surface electrocardiogram by 106+/-24 msec. Atrial fibrillation was initiated by a sudden burst of rapid depolarizations (340 per minute). A local depolarization could also be recognized during sinus rhythm and abolished by radiofrequency ablation. During a follow-up period of 8+/-6 months after ablation, 28 patients (62 percent) had no recurrence of atrial fibrillation.
CONCLUSIONS: The pulmonary veins are an important source of ectopic beats, initiating frequent paroxysms of atrial fibrillation. These foci respond to treatment with radio-frequency ablation.

PMID 9725923
Atsushi Takahashi, Yoshito Iesaka, Yoshihide Takahashi, Ryoko Takahashi, Kenzaburo Kobayashi, Katsumasa Takagi, Osamu Kuboyama, Takeo Nishimori, Hidenobu Takei, Hiroshi Amemiya, Hideomi Fujiwara, Masayasu Hiraoka
Electrical connections between pulmonary veins: implication for ostial ablation of pulmonary veins in patients with paroxysmal atrial fibrillation.
Circulation. 2002 Jun 25;105(25):2998-3003.
Abstract/Text BACKGROUND: Electrical disconnection of the myocardial extensions into arrhythmogenic pulmonary veins (PVs) is recognized as a curative technique for paroxysmal atrial fibrillation (AF). However, the presence of electrical connections between the PVs, which may make achievement of PV disconnection difficult, has not been systematically evaluated.
METHODS AND RESULTS: Forty-nine consecutive patients with drug-resistant AF underwent ostial radiofrequency (RF) catheter ablation of arrhythmogenic PVs with foci triggering AF. Pacing from inside the targeted PV was performed after each RF delivery to identify the left atrial exit site of the residual venoatrial conduction. Successful PV disconnection was defined as achieving elimination of the PV potentials during sinus rhythm or left atrial pacing, and the loss of left atrial conduction during intra-PV pacing. A total of 112 arrhythmogenic PVs were identified. PV disconnection was achieved with 10+/-6.1 minutes of RF delivery to the ostia of 101 targeted PVs. In 7 left superior (LS) PVs from 7 patients (14%), the earliest atrial activity was recorded from the left inferior (LI) PV ostium during intra-LSPV pacing after 11+/-4.7 minutes of RF delivery to the LSPV ostium. Disconnection of these LSPVs was achieved by LIPV disconnection. In the remaining 4 PVs from 4 patients, PV disconnection could not be achieved.
CONCLUSIONS: Fourteen percent of the patients had electrical connections between contiguous PVs. In these patients, ostial ablation of an untargeted PV was required for successful targeted PV disconnection.

PMID 12081994
Feifan Ouyang, Dietmar Bänsch, Sabine Ernst, Anselm Schaumann, Hitoshi Hachiya, Minglong Chen, Julian Chun, Peter Falk, Afsaneh Khanedani, Matthias Antz, Karl-Heinz Kuck
Complete isolation of left atrium surrounding the pulmonary veins: new insights from the double-Lasso technique in paroxysmal atrial fibrillation.
Circulation. 2004 Oct 12;110(15):2090-6. doi: 10.1161/01.CIR.0000144459.37455.EE. Epub 2004 Oct 4.
Abstract/Text BACKGROUND: Paroxysmal atrial fibrillation (PAF) can be eliminated with continuous circular lesions (CCLs) around the pulmonary veins (PVs), but it is unclear whether all PVs are completely isolated.
METHODS AND RESULTS: Forty-one patients with symptomatic PAF underwent 3D mapping, and all PV ostia were marked on the 3D map based on venography. Irrigated radiofrequency energy was applied at a distance from the PV ostia guided by 2 Lasso catheters placed within the ipsilateral superior and inferior PVs. The mean radiofrequency duration was 1550+/-511 seconds for left-sided PVs and 1512+/-506 seconds for right-sided PVs. After isolation, automatic activity was observed in the right-sided PVs in 87.8% and in the left-sided PVs in 80.5%. During the procedure, a spontaneous or induced PV tachycardia (PVT) with a cycle length of 189+/-29 ms was observed in 19 patients. During a mean follow-up of 6 months, atrial tachyarrhythmias recurred in 10 patients. Nine patients underwent a repeat procedure. Conduction gaps in the left CCL in 9 patients and in the right CCL in 2 patients were closed during the second procedure. A spontaneous PVT with a cycle length of 212+/-44 ms was demonstrated in 7 of 9 patients, even though no PVT had been observed in 6 of these 7 patients during the first procedure. No AF recurred in 39 patients after PV isolation during follow-up.
CONCLUSIONS: Automatic activity and fast tachycardia within the PVs could reflect an arrhythmogenic substrate in patients with PAF, which could be eliminated by isolating all PVs with CCLs guided by 3D mapping and the double-Lasso technique in the majority of patients.

PMID 15466640
Feifan Ouyang, Roland Tilz, Julian Chun, Boris Schmidt, Erik Wissner, Thomas Zerm, Kars Neven, Bulent Köktürk, Melanie Konstantinidou, Andreas Metzner, Alexander Fuernkranz, Karl-Heinz Kuck
Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons from a 5-year follow-up.
Circulation. 2010 Dec 7;122(23):2368-77. doi: 10.1161/CIRCULATIONAHA.110.946806. Epub 2010 Nov 22.
Abstract/Text BACKGROUND: Paroxysmal atrial fibrillation (AF) naturally progresses toward chronic AF at an estimated rate of 15% to 30% over a 1- to 3-year period. Pulmonary vein (PV) isolation is increasingly performed for the treatment of drug-refractory paroxysmal AF. The long-term data on clinical outcome after circumferential PV isolation are limited.
METHODS AND RESULTS: From 2003 to late 2004, 161 patients (121 men; age, 59.8±9.7 years) with symptomatic paroxysmal AF and normal left ventricular function underwent circumferential PV isolation guided by 3-dimensional mapping and double Lasso technique. Right-sided and left-sided continuous circular lesions encircling the ipsilateral PVs were placed with irrigated radiofrequency energy. The procedure end point was the absence of all PV spikes for at least 30 minutes after PV isolation verified by 2 Lasso catheters placed within the ipsilateral PVs. Sinus rhythm was present in 75 patients (46.6%) after the initial procedure during a median follow-up period of 4.8 years (0.33 to 5.5 years). A second procedure was performed in 66 and a third procedure in 12 patients. Recovered PV isolation conduction was observed in 62 of 66 patients (94.0%) during the second and in 8 of 12 patients (66.7%) during the third procedure. After a median of 1 (1 to 3) procedure, stable sinus rhythm was achieved in 128 of 161 patients (79.5%), whereas clinical improvement occurred in an additional 21 of 161 patients (13.0%) during a median follow-up of 4.6 years (0.33 to 5.5 years). Four patients in stable sinus rhythm died during follow-up. Progression toward chronic AF was observed in 4 patients (2.4%); however, only 2 patients reported symptoms.
CONCLUSION: In patients with paroxysmal AF and normal left ventricular function, circumferential PV isolation results in stable sinus rhythm in the majority of patients, and low incidence of chronic AF was observed after ablation during up to 5 years of follow-up.

PMID 21098450
Riccardo Cappato, Hugh Calkins, Shih-Ann Chen, Wyn Davies, Yoshito Iesaka, Jonathan Kalman, You-Ho Kim, George Klein, Douglas Packer, Allan Skanes
Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation.
Circulation. 2005 Mar 8;111(9):1100-5. doi: 10.1161/01.CIR.0000157153.30978.67. Epub 2005 Feb 21.
Abstract/Text BACKGROUND: The purpose of this study was to conduct a worldwide survey investigating the methods, efficacy, and safety of catheter ablation (CA) of atrial fibrillation (AF).
METHODS AND RESULTS: A detailed questionnaire was sent to 777 centers worldwide. Data relevant to the study purpose were collected from 181 centers, of which 100 had ongoing programs on CA of AF between 1995 and 2002. The number of patients undergoing this procedure increased from 18 in 1995 to 5050 in 2002. The median number of procedures per center was 37.5 (range, 1 to 600). Paroxysmal AF, persistent AF, and permanent AF were the indicated arrhythmias in 100.0%, 53.0%, and 20.0% of responding centers, respectively. The most commonly used techniques were right atrial compartmentalization between 1995 and 1997, ablation of the triggering focus in 1998 and 1999, and electrical disconnection of multiple pulmonary veins between 2000 and 2002. Of 8745 patients completing the CA protocol in 90 centers, of whom 2389 (27.3%) required >1 procedure, 4550 (52.0%; range among centers, 14.5% to 76.5%) became asymptomatic without drugs and another 2094 (23.9%; range among centers, 8.8% to 50.3%) became asymptomatic in the presence of formerly ineffective antiarrhythmic drugs over an 11.6+/-7.7-month follow-up period. At least 1 major complication was reported in 524 patients (6.0%).
CONCLUSIONS: The findings of this survey provide a picture of the variable and evolving methods, efficacy, and safety of CA for AF as practiced in a large number of centers worldwide and may serve as a guide to clinicians considering therapeutic options in patients suffering from this arrhythmia.

PMID 15723973
Riccardo Cappato, Hugh Calkins, Shih-Ann Chen, Wyn Davies, Yoshito Iesaka, Jonathan Kalman, You-Ho Kim, George Klein, Andrea Natale, Douglas Packer, Allan Skanes
Prevalence and causes of fatal outcome in catheter ablation of atrial fibrillation.
J Am Coll Cardiol. 2009 May 12;53(19):1798-803. doi: 10.1016/j.jacc.2009.02.022.
Abstract/Text OBJECTIVES: The purpose of this study was to provide a systematic multicenter survey on the incidence and causes of death occurring in the setting of or as a consequence of catheter ablation (CA) of atrial fibrillation (AF).
BACKGROUND: CA of AF is considered to be generally safe. However, serious complications, including death, have been reported.
METHODS: Using a retrospective case series, data relevant to the incidence and cause of intra- and post-procedural death occurring in patients undergoing CA of AF between 1995 and 2006 were collected from 162 of 546 identified centers worldwide.
RESULTS: Thirty-two deaths (0.98 per 1,000 patients) were reported during 45,115 procedures in 32,569 patients. Causes of deaths included tamponade in 8 patients (1 later than 30 days), stroke in 5 patients (2 later than 30 days), atrioesophageal fistula in 5 patients, and massive pneumonia in 2 patients. Myocardial infarction, intractable torsades de pointes, septicemia, sudden respiratory arrest, extrapericardial pulmonary vein (PV) perforation, occlusion of both lateral PVs, hemothorax, and anaphylaxis were reported to be responsible for 1 death each, while asphyxia from tracheal compression secondary to subclavian hematoma, intracranial bleeding, acute respiratory distress syndrome, and esophageal perforation from an intraoperative transesophageal echocardiographic probe were causes of 1 late death each.
CONCLUSIONS: Death is a complication of CA of AF, occurring in 1 of 1,000 patients. Knowledge of possible precipitating causes is key to operators and needs to be considered during decision making with patients.

PMID 19422987
Koji Higuchi, Yasuteru Yamauchi, Kenzo Hirao, Takeshi Sasaki, Hitoshi Hachiya, Yukio Sekiguchi, Junichi Nitta, Mitsuaki Isobe
Superior vena cava as initiator of atrial fibrillation: factors related to its arrhythmogenicity.
Heart Rhythm. 2010 Sep;7(9):1186-91. doi: 10.1016/j.hrthm.2010.05.017. Epub 2010 May 12.
Abstract/Text BACKGROUND: The superior vena cava (SVC) is an important focus of atrial fibrillation (AF) for which SVC isolation is effective. However, SVC isolation may cause serious complications, and indications for SVC isolation combined with pulmonary vein (PV) isolation are unclear.
OBJECTIVE: The purpose of this study was to identify structural and electrophysiologic differences that might exist between the SVC of patients with and those without SVC triggering of AF.
METHODS: This study included paroxysmal (n = 46) and persistent (n = 14) AF patients without structural heart disease who underwent circumferential antral PV isolation. Patients with AF of SVC origin were assigned to the SVC group (n = 12); the remaining patients were assigned to the control group (n = 48). The area where SVC potentials were recorded was defined as the SVC sleeve. The length of the SVC sleeve and the maximum amplitude of the SVC potential were measured.
RESULTS: SVC group patients had a longer SVC sleeve (34.7 +/- 4.4 mm vs 16.5 +/- 11.4 mm, P <.0001) than did control group patients. Maximum amplitude of the SVC potential was greater in SVC group patients than in control group patients (1.50 +/- 0.43 mV vs 0.98 +/- 0.60 mV, P = .03). SVC sleeve length >30 mm and maximum amplitude of SVC potential >1.0 mV strongly predicted an SVC focus of AF (100% sensitivity, 94% specificity). Fifty of 60 patients became AF-free without antiarrhythmic drugs after undergoing circumferential antral PV isolation and/or SVC isolation.
CONCLUSION: The results of this study suggest that in patients with long SVC sleeve (>30 mm) and large SVC potential (>1.0 mV), arrhythmogenic triggers of AF reside in the SVC.

Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
PMID 20470902
David J Wilber, Carlo Pappone, Petr Neuzil, Angelo De Paola, Frank Marchlinski, Andrea Natale, Laurent Macle, Emile G Daoud, Hugh Calkins, Burr Hall, Vivek Reddy, Giuseppe Augello, Matthew R Reynolds, Chandan Vinekar, Christine Y Liu, Scott M Berry, Donald A Berry, ThermoCool AF Trial Investigators
Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial.
JAMA. 2010 Jan 27;303(4):333-40. doi: 10.1001/jama.2009.2029.
Abstract/Text CONTEXT: Antiarrhythmic drugs are commonly used for prevention of recurrent atrial fibrillation (AF) despite inconsistent efficacy and frequent adverse effects. Catheter ablation has been proposed as an alternative treatment for paroxysmal AF.
OBJECTIVE: To determine the efficacy of catheter ablation compared with antiarrhythmic drug therapy (ADT) in treating symptomatic paroxysmal AF.
DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 19 hospitals of 167 patients who did not respond to at least 1 antiarrhythmic drug and who experienced at least 3 AF episodes within 6 months before randomization. Enrollment occurred between October 25, 2004, and October 11, 2007, with the last follow-up on January 19, 2009.
INTERVENTION: Catheter ablation (n = 106) or ADT (n = 61), with assessment for effectiveness in a comparable 9-month follow-up period.
MAIN OUTCOME MEASURES: Time to protocol-defined treatment failure. The proportion of patients who experienced major treatment-related adverse events within 30 days of catheter ablation or ADT was also reported.
RESULTS: At the end of the 9-month effectiveness evaluation period, 66% of patients in the catheter ablation group remained free from protocol-defined treatment failure compared with 16% of patients treated with ADT. The hazard ratio of catheter ablation to ADT was 0.30 (95% confidence interval, 0.19-0.47; P < .001). Major 30-day treatment-related adverse events occurred in 5 of 57 patients (8.8%) treated with ADT and 5 of 103 patients (4.9%) treated with catheter ablation. Mean quality of life scores improved significantly in patients treated by catheter ablation compared with ADT at 3 months; improvement was maintained during the course of the study.
CONCLUSION: Among patients with paroxysmal AF who had not responded to at least 1 antiarrhythmic drug, the use of catheter ablation compared with ADT resulted in a longer time to treatment failure during the 9-month follow-up period.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00116428.

PMID 20103757
Jean-François Roux, Erica Zado, David J Callans, Fermin Garcia, David Lin, Francis E Marchlinski, Rupa Bala, Sanjay Dixit, Michael Riley, Andrea M Russo, Mathew D Hutchinson, Joshua Cooper, Ralph Verdino, Vickas Patel, Parijat S Joy, Edward P Gerstenfeld
Antiarrhythmics After Ablation of Atrial Fibrillation (5A Study).
Circulation. 2009 Sep 22;120(12):1036-40. doi: 10.1161/CIRCULATIONAHA.108.839639. Epub 2009 Sep 8.
Abstract/Text BACKGROUND: Atrial arrhythmias are common early after atrial fibrillation (AF) ablation. We hypothesized that empirical antiarrhythmic drug (AAD) therapy for 6 weeks after AF ablation would reduce the occurrence of atrial arrhythmias.
METHODS AND RESULTS: We randomized consecutive patients with paroxysmal AF undergoing ablation to empirical antiarrhythmic therapy (AAD group) or no antiarrhythmic therapy (no-AAD group) for the first 6 weeks after ablation. In the no-AAD group, only atrioventricular nodal blocking agents were prescribed. All patients wore a transtelephonic monitor for 4 weeks after discharge and were reevaluated at 6 weeks. The primary end point of the study was a composite of (1) atrial arrhythmias lasting more than 24 hours; (2) atrial arrhythmias associated with severe symptoms requiring hospital admission, cardioversion, or initiation/change of antiarrhythmic drug therapy; and (3) intolerance to antiarrhythmic agent requiring drug cessation. Of 110 enrolled patients (age 55+/-9 years, 71% male), 53 were randomized to AAD and 57 to no-AAD. There was no difference in baseline characteristics between groups. During the 6 weeks after ablation, fewer patients reached the primary end point in the AAD compared with the no-AAD group (19% versus 42%; P=0.005). There remained fewer events in the AAD group (13% versus 28%; P=0.05) when only end points of AF >24 hours, arrhythmia-related hospitalization, or electrical cardioversion were compared.
CONCLUSIONS: AAD treatment during the first 6 weeks after AF ablation is well tolerated and reduces the incidence of clinically significant atrial arrhythmias and need for cardioversion/hospitalization for arrhythmia management.

PMID 19738139
Karl-Heinz Kuck, Josep Brugada, Alexander Fürnkranz, Andreas Metzner, Feifan Ouyang, K R Julian Chun, Arif Elvan, Thomas Arentz, Kurt Bestehorn, Stuart J Pocock, Jean-Paul Albenque, Claudio Tondo, FIRE AND ICE Investigators
Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation.
N Engl J Med. 2016 Jun 9;374(23):2235-45. doi: 10.1056/NEJMoa1602014. Epub 2016 Apr 4.
Abstract/Text BACKGROUND: Current guidelines recommend pulmonary-vein isolation by means of catheter ablation as treatment for drug-refractory paroxysmal atrial fibrillation. Radiofrequency ablation is the most common method, and cryoballoon ablation is the second most frequently used technology.
METHODS: We conducted a multicenter, randomized trial to determine whether cryoballoon ablation was noninferior to radiofrequency ablation in symptomatic patients with drug-refractory paroxysmal atrial fibrillation. The primary efficacy end point in a time-to-event analysis was the first documented clinical failure (recurrence of atrial fibrillation, occurrence of atrial flutter or atrial tachycardia, use of antiarrhythmic drugs, or repeat ablation) following a 90-day period after the index ablation. The noninferiority margin was prespecified as a hazard ratio of 1.43. The primary safety end point was a composite of death, cerebrovascular events, or serious treatment-related adverse events.
RESULTS: A total of 762 patients underwent randomization (378 assigned to cryoballoon ablation and 384 assigned to radiofrequency ablation). The mean duration of follow-up was 1.5 years. The primary efficacy end point occurred in 138 patients in the cryoballoon group and in 143 in the radiofrequency group (1-year Kaplan-Meier event rate estimates, 34.6% and 35.9%, respectively; hazard ratio, 0.96; 95% confidence interval [CI], 0.76 to 1.22; P<0.001 for noninferiority). The primary safety end point occurred in 40 patients in the cryoballoon group and in 51 patients in the radiofrequency group (1-year Kaplan-Meier event rate estimates, 10.2% and 12.8%, respectively; hazard ratio, 0.78; 95% CI, 0.52 to 1.18; P=0.24).
CONCLUSIONS: In this randomized trial, cryoballoon ablation was noninferior to radiofrequency ablation with respect to efficacy for the treatment of patients with drug-refractory paroxysmal atrial fibrillation, and there was no significant difference between the two methods with regard to overall safety. (Funded by Medtronic; FIRE AND ICE ClinicalTrials.gov number, NCT01490814.).

PMID 27042964
Florian Straube, Uwe Dorwarth, Sonia Ammar-Busch, Timo Peter, Georg Noelker, Thomas Massa, Malte Kuniss, Niels Christian Ewertsen, Kyoung Ryul Julian Chun, Juergen Tebbenjohanns, Roland Tilz, Karl Heinz Kuck, Taoufik Ouarrak, Jochen Senges, Ellen Hoffmann, FREEZE Cohort Investigators
First-line catheter ablation of paroxysmal atrial fibrillation: outcome of radiofrequency vs. cryoballoon pulmonary vein isolation.
Europace. 2016 Mar;18(3):368-75. doi: 10.1093/europace/euv271. Epub 2015 Oct 25.
Abstract/Text AIMS: First-line ablation prior to antiarrhythmic drug (AAD) therapy is an option for symptomatic paroxysmal atrial fibrillation (PAF); however, the optimal ablation technique, radiofrequency (RF), or cryoballoon (CB) has to be determined.
METHODS AND RESULTS: The FREEZE Cohort Study compares RF and CB ablation. Treatment-naïve patients were documented in the FREEZEplus Registry. Periprocedural data and outcome were analysed. From 2011 to 2014, a total of 373/4184 (8.9%) patients with PAF naïve to AAD were identified. Pulmonary vein isolation (PVI) was performed with RF (n = 180) or CB (n = 193). In the RF group, patients were older (65 vs. 61 years, P < 0.01) compared with the CB group. The procedure time was significantly shorter and radiation exposure higher in the CB group. Major adverse events occurred in 1.6% (CB) and 3.7% (RF) of patients (P = 0.22). AF/atrial tachycardia (AT) recurrence until discharge was 4.5% (RF) and 8.5% (CB, P = 0.2). Follow-up (FU) ≥12 months was available in 99 (RF) and 107 (CB) patients. After 1.4 years of FU, freedom from AF/atrial tachycardia (AT) was 61% (RF) and 71% (CB, P = 0.11). In the RF group, more patients underwent cardioversion, and a trend for more repeat ablations was observed. Persistent phrenic nerve palsy was observed in one patient treated by CB.
CONCLUSION: First-line ablation for PAF is safe and effective with either RF or CB. The procedure was faster with the CB, but the radiation exposure was higher. Although there was a trend for more recurrences and complications in the RF group, a more favourable risk profile in patients undergoing CB ablation might have biased the results.
CLINICALTRIALSGOV IDENTIFIER: NCT01360008.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
PMID 26504108
Takatsugu Kajiyama, Shinsuke Miyazaki, Junji Matsuda, Tomonori Watanabe, Takayuki Niida, Takamitsu Takagi, Hiroaki Nakamura, Hiroshi Taniguchi, Hitoshi Hachiya, Yoshito Iesaka
Anatomic Parameters Predicting Procedural Difficulty and Balloon Temperature Predicting Successful Applications in Individual Pulmonary Veins During 28-mm Second-Generation Cryoballoon Ablation.
JACC Clin Electrophysiol. 2017 Jun;3(6):580-588. doi: 10.1016/j.jacep.2017.01.004. Epub 2017 Mar 29.
Abstract/Text OBJECTIVES: This study sought to identify anatomic parameters predicting procedural difficulty in achieving pulmonary vein isolation (PVI) and in-procedural predictors of successful applications during second-generation cryoballoon (CB) ablation.
BACKGROUND: PV anatomies vary and influence the procedural difficulty during CB PVI.
METHODS: In total, 408 initial freezes among 110 patients undergoing PVI for paroxysmal atrial fibrillation using 28-mm second-generation CBs with single 3-min freeze techniques were included. The anatomic parameters were obtained from pre-procedural cardiac computed tomography. The nadir balloon temperature and temperature at the start of the plateau phase were recorded during each freeze.
RESULTS: Acute PVI was achieved by initial applications in 335 pulmonary veins (PVs) (82.1%) and touch-up was required in 13 (3.2%). A multivariate analysis revealed that a thinner left lateral ridge (<4.7 mm), higher ovality (>50.5%), and longer PV ostium-bifurcation distance (>26.1 mm) required multiple applications for a successful left superior PVI. Older age (>68 years), and shorter PV ostium-bifurcation distance (<10.4 mm) required multiple applications for a successful right superior and right inferior PVI, respectively. Shorter PVTLs were also associated with requiring touch-up of the RIPV. Balloon temperatures were lower for successful than failed PVI applications. Successful PVIs were predicted using the nadir balloon temperature at 33.0 ± 2.6 s, 33.0 ± 2.5 s, 33.6 ± 2.5 s, and 33.0 ± 2.5 s from the initiation of freezes with positive predictive values of 87.7%, 88.5%, 98.5%, and 81.6% using cutoff temperatures of -34°C, -33°C, -37°C, and -33°C in the left superior, left inferior, right superior, and right inferior PVs, respectively.
CONCLUSIONS: The anatomic information might predict procedural difficulty and the balloon temperature a successful PVI during the early CB ablation freezing phase.

Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 29759431
Tadafumi Nanbu, Akihiko Yotsukura, Fumihiko Sano, George Suzuki, Yuki Ishidoya, Izumi Yoshida, Masayuki Sakurai
A relation between ablation area and outcome of ablation using 28-mm cryoballon ablation: Importance of carina region.
J Cardiovasc Electrophysiol. 2018 Sep;29(9):1221-1229. doi: 10.1111/jce.13648. Epub 2018 Jun 12.
Abstract/Text INTRODUCTION: Pulmonary vein isolation (PVI) with wide antral ablation leads to better outcomes in atrial fibrillation ablation therapy, but the ablation area is relatively small during cryoballoon ablation (CBA). The present study tested the hypothesis that wide ablation can lead to better outcomes in CBA.
METHODS AND RESULTS: Ninety-six patients with atrial fibrillation were enrolled (paroxysmal 76%, 64.1 ± 11.7 years). All patients underwent preprocedural computed tomography and the PV diameter at left atrial PV junction was measured. PV isolation was performed using a 28-mm CB for 3 minutes with single freezing. Sinus rhythm bipolar voltage amplitude maps with the NavX mapping system were generated after ablation. According to the voltage map, patients were divided into 3 subgroups (68 in the extensive isolation group, 17 in the individual isolation group, and 10 in the incomplete isolation group). Atrial tachyarrhythmias recurred in 9 patients of the extensive isolation group and 6 in the individual isolation group. The rate of 12-month freedom from tachyarrhythmia after a single ablation procedure was 84% (95% confidence interval [C.I.], 72%-91%) in the extensive group and 57% (95% C.I., 28%-78%) in the individual group (P = 0.048). Multiple logistic regression analyses revealed that maximal PV diameter was the only predictor to achieve extensive PVI (odds ratio, 1.57; 95% C.I. 1.08-2.29 P = 0.018).
CONCLUSION: Extensive isolation is superior to individual isolation for achieving freedom from atrial arrhythmia in long term follow-up by CBA. Evaluating PV diameter at the left atrial PV junction is essential for applying CBA.

© 2018 Wiley Periodicals, Inc.
PMID 29846996
Ryohsuke Narui, Michifumi Tokuda, Masato Matsushima, Ryota Isogai, Kenichi Tokutake, Kenichi Yokoyama, Mika Hioki, Keiichi Ito, Shin-Ichi Tanigawa, Seigo Yamashita, Keiichi Inada, Kenri Shibayama, Seiichiro Matsuo, Satoru Miyanaga, Kenichi Sugimoto, Michihiro Yoshimura, Teiichi Yamane
Incidence and Factors Associated With the Occurrence of Pulmonary Vein Narrowing After Cryoballoon Ablation.
Circ Arrhythm Electrophysiol. 2017 Jun;10(6). doi: 10.1161/CIRCEP.116.004588.
Abstract/Text BACKGROUND: In contrast with traditional radiofrequency ablation, little is known about the influence of cryoballoon ablation on the morphology of pulmonary veins (PVs). We evaluated the influence of cryoballoon ablation on the PV dimension (PVD) and investigated the factors associated with a reduction of the PVD.
METHODS AND RESULTS: Seventy-four patients who underwent cryoballoon ablation for paroxysmal atrial fibrillation were included in the present study. All subjects underwent contrast-enhanced computed tomography both before and at 3 months after the procedure. The PVD (cross-sectional area) was measured using a 3-dimensional electroanatomical mapping system. Each PV was evaluated according to the PVD reduction rate (ΔPVD), which was calculated as follows: (1-post-PVD/pre-PVD)×100 (%). Ninety-two percent of the PVs (271/296) were successfully isolated only by cryoballoon ablation; the remaining 8% of the PVs required touch-up ablation and were excluded from the analysis. Mild (25%-50%), moderate (50%-75%), and severe (≥75%) ΔPVD values were observed in 87, 14, and 3 PVs, respectively, including 1 case with severe left superior PV stenosis (ΔPVD: 94%) in a patient who required PV angioplasty. In multivariable analysis, a larger PV ostium and lower minimum freezing temperature during cryoballoon ablation were independently associated with PV narrowing (odds ratio, 1.773; P=0.01; and odds ratio, 1.137; P<0.001, respectively).
CONCLUSIONS: A reduction of the PVD was often observed after cryoballoon ablation for atrial fibrillation. A larger PV ostium and lower minimum freezing temperature during cryoballoon ablation were associated with an increased risk of PVD reduction.

© 2017 American Heart Association, Inc.
PMID 28630168
Hiroshi Sohara, Tohru Ohe, Ken Okumura, Shigeto Naito, Kenzo Hirao, Morio Shoda, Youichi Kobayashi, Yasuteru Yamauchi, Yoshio Yamaguchi, Taishi Kuwahara, Haruo Hirayama, Chun YeongHwa, Kengo Kusano, Kazuaki Kaitani, Kimikazu Banba, Satoki Fujii, Koichiro Kumagai, Hisashi Yoshida, Masashi Matsushita, Shutaro Satake, Kazutaka Aonuma
HotBalloon Ablation of the Pulmonary Veins for Paroxysmal AF: A Multicenter Randomized Trial in Japan.
J Am Coll Cardiol. 2016 Dec 27;68(25):2747-2757. doi: 10.1016/j.jacc.2016.10.037.
Abstract/Text BACKGROUND: Point-by-point catheter ablation is an established treatment for drug-refractory paroxysmal atrial fibrillation (PAF). However, it is time consuming, requires excellent technique to achieve complete pulmonary vein (PV) isolation, and is associated with severe complications.
OBJECTIVES: The purpose of this study was to evaluate the safety and effectiveness of a HotBalloon ablation (HBA) compared with antiarrhythmic drug therapy (ADT) for the treatment of PAF.
METHODS: A prospective multicenter randomized controlled study was conducted in Japan. Patients with symptomatic PAF refractory to antiarrhythmic drugs (Class I to IV) were randomized to HBA or ADT at a 2:1 ratio and assessed for effectiveness in a comparable 9-month follow-up period.
RESULTS: A total of 100 patients in the HBA group and 43 patients in the ADT group received treatment at 17 sites. HBA procedure produced acute complete PV isolation in 98.0% (392 of 400) of the PVs and in 93.0% (93 of 100) of patients in the HBA group. The chronic success rates after the 9-month effective evaluation period were 59.0% in the HBA group (n = 100) and 4.7% in the ADT group (n = 43; p < 0.001). The incidence of major complications was 11.2% (15 of 134 patients). The incidences of PV stenosis (>70%) and transient phrenic nerve injury were 5.2% and 3.7%, respectively. The mean fluoroscopy time was 49.4 ± 26.6 min (n = 134), and the mean procedure duration was 113.9 ± 31.9 min (n = 133).
CONCLUSIONS: This study demonstrates the superiority of HBA compared with ADT for treatment of patients with PAF, and a favorable safety profile.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
PMID 28007137
Koichi Nagashima, Yasuo Okumura, Ichiro Watanabe, Shiro Nakahara, Yuichi Hori, Kazuki Iso, Ryuta Watanabe, Masaru Arai, Yuji Wakamatsu, Sayaka Kurokawa, Hiroaki Mano, Toshiko Nakai, Kimie Ohkubo, Atsushi Hirayama
Hot Balloon Versus Cryoballoon Ablation for Atrial Fibrillation: Lesion Characteristics and Middle-Term Outcomes.
Circ Arrhythm Electrophysiol. 2018 May;11(5):e005861. doi: 10.1161/CIRCEP.117.005861.
Abstract/Text BACKGROUND: Hot balloon ablation (HBA) and cryoballoon ablation (CBA) were developed to simplify ablation for atrial fibrillation. Because the lesion characteristics and efficacy of these balloon modalities have not been clarified, we compared lesion characteristics and outcomes of HBA and CBA.
METHODS: Of 165 consecutive patients who underwent initial catheter ablation for atrial fibrillation, 74 propensity scorematched (37 HBA and 37 CBA) patients were included in our study.
RESULTS: Patients' clinical characteristics, including age, sex, body mass index, atrial fibrillation subtype, CHA2DS2-VASc score, and left atrial dimension, were similar between the 2 groups. Touch-up radiofrequency ablation was required for residual/dormant pulmonary vein conduction in 52% of the patients with HBA versus 24% of the patients with CBA (P=0.02) and often in the anterior aspect of the left superior pulmonary vein after HBA (41%) versus the inferior aspect of the inferior pulmonary veins after CBA (22%). HBA lesions were smaller than CBA lesions (23.8±7.9 versus 33.5±14.5 cm2; P=0.0007). Similar results were observed when lesions in each pulmonary vein were compared between groups. Twentyfour hours after the procedure, serum levels of the cardiac biomarkers, including troponin-T, creatine kinase, and creatine kinase-MB, were higher in the HBA group than in the CBA group. Atrial fibrillation recurrence did not differ between the groups within 6 (3% versus 11%; P=0.36) or 12 months (16% versus 16%; P=1.00).
CONCLUSIONS: Although HBA lesions appear to be smaller than CBA lesions, middle-term outcomes are not statistically different between these balloon modalities.

© 2018 American Heart Association, Inc.
PMID 29700055
Masaki Ohsawa, Akira Okayama, Kiyomi Sakata, Karen Kato, Kazuyoshi Itai, Toshiyuki Onoda, Hirotsugu Ueshima
Rapid increase in estimated number of persons with atrial fibrillation in Japan: an analysis from national surveys on cardiovascular diseases in 1980, 1990 and 2000.
J Epidemiol. 2005 Sep;15(5):194-6.
Abstract/Text
PMID 16195640
ACTIVE Writing Group of the ACTIVE Investigators, S Connolly, J Pogue, R Hart, M Pfeffer, S Hohnloser, S Chrolavicius, M Pfeffer, S Hohnloser, S Yusuf
Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial.
Lancet. 2006 Jun 10;367(9526):1903-12. doi: 10.1016/S0140-6736(06)68845-4.
Abstract/Text BACKGROUND: Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation. However, long-term monitoring is necessary and many patients cannot achieve optimum anticoagulation. We assessed whether clopidogrel plus aspirin was non-inferior to oral anticoagulation therapy for prevention of vascular events.
METHODS: Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalised ratio of 2.0-3.0; n=3371) or clopidogrel (75 mg per day) plus aspirin (75-100 mg per day recommended; n=3335). Outcome events were adjudicated by a blinded committee. Primary outcome was first occurrence of stroke, non-CNS systemic embolus, myocardial infarction, or vascular death. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00243178.
RESULTS: The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy. There were 165 primary events in patients on oral anticoagulation therapy (annual risk 3.93%) and 234 in those on clopidogrel plus aspirin (annual risk 5.60%; relative risk 1.44 (1.18-1.76; p=0.0003). Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events (relative risk 1.50, 95% CI 1.19-1.89) and a significantly (p=0.03 for interaction) lower risk of major bleeding with oral anticoagulation therapy (1.30; 0.94-1.79) than patients not on this treatment at study entry (1.27, 0.85-1.89 and 0.59, 0.32-1.08, respectively).
CONCLUSION: Oral anticoagulation therapy is superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation at high risk of stroke, especially in those already taking oral anticoagulation therapy.

PMID 16765759
Hiroshi Sato, Kinji Ishikawa, Akira Kitabatake, Satoshi Ogawa, Yukio Maruyama, Yoshiyuki Yokota, Takaya Fukuyama, Yoshinori Doi, Seibu Mochizuki, Tohru Izumi, Noboru Takekoshi, Kiyoshi Yoshida, Katsuhiko Hiramori, Hideki Origasa, Shinichiro Uchiyama, Masayasu Matsumoto, Takenori Yamaguchi, Masatsugu Hori, Japan Atrial Fibrillation Stroke Trial Group
Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial.
Stroke. 2006 Feb;37(2):447-51. doi: 10.1161/01.STR.0000198839.61112.ee. Epub 2005 Dec 29.
Abstract/Text BACKGROUND AND PURPOSE: Although the efficacy of anticoagulant therapy for primary prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF) has been established, efficacy of antiplatelet therapy for low-risk patients is disputable in Japanese patients because of the frequent hemorrhagic complications. We examined the efficacy and safety of aspirin therapy in Japanese patients with NVAF in a prospective randomized multicenter trial.
METHODS: Patients with NVAF were randomized to an aspirin group (aspirin at 150 to 200 mg per day) or a control group without antiplatelet or anticoagulant therapy. Primary end points included cardiovascular death, symptomatic brain infarction, or transient ischemic attack.
RESULTS: A total of 426 patients were randomized to aspirin group and 445 to no treatment. The trial was stopped earlier because there were 27 primary end point events (3.1% per year; 95% CI, 2.1% to 4.6% per year) in the aspirin group versus 23 (2.4% per year; 95% CI, 1.5% to 3.5% per year) in the control group, suggesting a low possibility of superiority of the aspirin treatment for prevention of the primary end point. In addition, treatment with aspirin caused a marginally increased risk of major bleeding (7 patients; 1.6%) compared with the control group (2 patients; 0.4%; Fisher exact test P=0.101).
CONCLUSIONS: For prevention of stroke in patients with NVAF, aspirin at 150 to 200 mg per day does not seem to be either effective or safe. Further prospective studies are needed to determine the best preventive therapy for cerebrovascular events in Japanese patients with NVAF.

PMID 16385088

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