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https://w.atwiki.jp/kasugabemani/pages/324.html
GENRE FORTUNE TAILBEAT（フォーチュン・テイルビート） TITLE GADARINA ARTIST D-crew? 作曲・編曲 D-crew 収録作品 pop n music13 カーニバル
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pop n music 13 カーニバル 「フォ」ーチュン「テ」イ「ル」ビート、縮めてホテル。
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ゲーム情報（登録されているタグ） ジャンル＞アーケード＆アクション ジャンル＞タイムマネージメント 製作会社＞Youda Games 製作会社＞未確認 言語＞英語 コメント欄へ移動 ゲーム配布ページ 英語 http //www.bigfishgames.com/download-games/5440/youda-marina/index.html 日本語 紹介文 Youda Marina brings together all the fun of landscape design with exciting Time Management action! Build the Marina of your dreams and get some sun and fun each time you play. Be creative with your exotic harbor and have fun managing its everyday problems. As the harbor master you will be responsible for keeping all your Marina visitors happy and spending money. Create the most beautiful marina in the world! Astonishing upgradesRelaxing tropical vibesDesign a marina! 画像 « » var ppvArray_0_d3eb02fc76de1d0ad43d3996bacdcb50 = new Array(); ppvArray_0_d3eb02fc76de1d0ad43d3996bacdcb50[0] = http //w.atwiki.jp/bfgmatome/?cmd=upload&act=open&page=Youda+Marina&file=en_youda-marina-screen1.jpg ; window.onload=function(){ ppvShow_0_d3eb02fc76de1d0ad43d3996bacdcb50(0); }; function ppvShow_0_d3eb02fc76de1d0ad43d3996bacdcb50(n){ if(!ppvArray_0_d3eb02fc76de1d0ad43d3996bacdcb50[n]){ alert( 画像がありません ); return; } ppv_0_d3eb02fc76de1d0ad43d3996bacdcb50$( ppv_img_0_d3eb02fc76de1d0ad43d3996bacdcb50 ).src=ppvArray_0_d3eb02fc76de1d0ad43d3996bacdcb50[n]; ppv_0_d3eb02fc76de1d0ad43d3996bacdcb50$( ppv_link_0_d3eb02fc76de1d0ad43d3996bacdcb50 ).href=ppvArray_0_d3eb02fc76de1d0ad43d3996bacdcb50[n]; ppv_0_d3eb02fc76de1d0ad43d3996bacdcb50$( ppv_prev_0_d3eb02fc76de1d0ad43d3996bacdcb50 ).href= javascript ppvShow_0_d3eb02fc76de1d0ad43d3996bacdcb50( +(n-1)+ ) ; ppv_0_d3eb02fc76de1d0ad43d3996bacdcb50$( ppv_next_0_d3eb02fc76de1d0ad43d3996bacdcb50 ).href= javascript ppvShow_0_d3eb02fc76de1d0ad43d3996bacdcb50( +(n+1)+ ) ; } function ppv_0_d3eb02fc76de1d0ad43d3996bacdcb50$(){ var elements = new Array(); for (var i = 0; i arguments.length; i++){ var element = arguments[i]; if (typeof element == string ) element = document.getElementById(element); if (arguments.length == 1) return element; elements.push(element); } return elements; } ボリューム レス一覧 875 名前： 名無しさんの野望 [sage] 投稿日： 2010/06/06(日) 17 38 32 ID UuOgQP0e youda系やってる人いる？ 自分は寿司、キャンプなどやって割と好みだったのだが 今回のサファリはびみょん。 （usaサイトのだけど言語選択で日本語でプレイできるお） 876 名前： 名無しさんの野望 [sage] 投稿日： 2010/06/06(日) 19 33 21 ID lcdtnyu8 . 875 やってる。マリーナとすしは面白い コメント 名前 コメント トップページに戻る
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Pandaring 入党時期 2011年9月初頭 バラック状況 2012年12月現在 #ref(http //www28.atwiki.jp/equites/?cmd=upload act=open page=Pandaring file=%E3%81%B1%E3%82%93%E3%81%A0%E3%81%B0%E3%82%89%E3%81%A3%E3%81%8F.jpg) 党首について 吸運怖いです（・ω・） 好きなNPC 魚子さん クルーズのおっさん ラルフさん ヴァレたん 好きなコス 魚子さんにやっとディグニット作りました（`･ω･´） 好きなエリア アルケルトモレッツァ トルシェー屋敷：クラシカルでｲｲﾈ!ｲｲﾈ!ｲｲﾈ! 好きなBGM 久保田修氏の曲はどれも素晴らしすぎる クエスト挑戦可否 聖魔水○ トルシェ地下○ ジャケン地下○ ひとこと 永遠の新入りぱんだです（・ω・）ノ 魚子さんの麗しさに釣られて某ネトゲから移住してきて一年経ちました。 今でも一番愛しているのは魚子さんです。ひれ伏します。 エモーション大好きっこなので、頻繁に土下座してます。 お仕事の都合で昼間うろうろしていることが多いです。 最近はWorldCrossPvPにハマっていて夜は反応ないこと多いです( A`) あまり操作も上手くないし無知な奴ですが、いろいろ誘ってください～。 LU 2012/12/08
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@wikiへようこそ ウィキはみんなで気軽にホームページ編集できるツールです。 このページは自由に編集することができます。 メールで送られてきたパスワードを用いてログインすることで、各種変更（サイト名、トップページ、メンバー管理、サイドページ、デザイン、ページ管理、等）することができます まずはこちらをご覧ください。 @wikiの基本操作 編集モード・構文一覧表 @wikiの設定・管理 分からないことは？ @wiki ご利用ガイド よくある質問 @wiki更新情報 @wikiへのお問合せフォーム 等をご活用ください アットウィキモードでの編集方法 文字入力 画像入力 表組み ワープロモードでの編集方法 文字入力 画像入力 表組み その他にもいろいろな機能満載！！ @wikiプラグイン一覧 @wikiかんたんプラグイン入力サポート バグ・不具合を見つけたら？ 要望がある場合は？ お手数ですが、お問合せフォームからご連絡ください。
https://w.atwiki.jp/wiihack/pages/53.html
Ocarina Ocarina Code Manager コードタイプ Ocarina Ocarinaはチートコードを使用するためのアプリケーションです 手順 1.Ocarina Code Managerを用いGCTファイルを作成し以下に配置 フォルダ構成 codes/*.gct 2.Ocarinaを実行しゲームディスクを挿入しWiiリモコンのAボタンを押す ゲームIDとGCTファイルのゲームIDが一致すればコードが適用されゲームが開始します Ocarina Code Manager Ocarina Code ManagerはOcarinaで使用するためのGCTファイルを作成するソフトです コードタイプ Standard memory fill codes GCT 8 bit 00XXXXXX ZZZZ00YY 16 bit 01XXXXXX ZZZZYYYY 32 bit 02XXXXXX YYYYYYYY Consecutive 03XXXXXX YYYYYYYY WiiRd 8 bit 00XXXXXX ZZZZ00YY or 10XXXXXX ZZZZ00YY 16 bit 02XXXXXX ZZZZYYYY or 12XXXXXX ZZZZYYYY 32 bit 04XXXXXX YYYYYYYY or 14XXXXXX YYYYYYYY Consecutive 06XXXXXX YYYYYYYY or 16XXXXXX YYYYYYYY You recognize WiiRd has two possibilities.They are not identical! The codes beginning with 0 mean they write to the address [base+XXXXXX] (XXXXXX may go up to 1FFFFFF) while the codes begining with 1 write to the address [pointer+XXXXXX] - this means that you can access regular memory using the “base address” even while you’re handling pointers in between. ZZZZ is handled the exact same way. Serial codes GCT 04XXXXXX YYYYYYYY TNNNZZZZ VVVVVVVV T being 0 for 8 bit, 1 for 16 bit, 2 for 32 bit WiiRd 08XXXXXX YYYYYYYY or 18XXXXXX YYYYYYYY TNNNZZZZ VVVVVVVV Same structure.. again 08 means use base address to apply offset, while 18 means pointer address! Conditional codes GCT 32 bit 1TXXXXXX YYYYYYYY (compare value YYYYYYYY) 16 bit 2TXXXXXX ZZZZYYYY (compare value ZZZZ YYYY) Endif 60000000 00000000 T see Gecko instructions too long to list WiiRd 32 bit 2TXXXXXX YYYYYYYY or 3TXXXXXX YYYYYYYY 16 bit 2UXXXXXX ZZZZYYYY or 3UXXXXXX ZZZZYYYY (compare value (not ZZZZ) YYYY) Endif E2000001 00000000 T 0 - equal (==) (equals GCT type C) T 2 - not equal (!=) (GCT D) T 4 - greater than ( ) (GCT E) T 6 - lower than ( ) (GCT F) U 8 - equal (==) (GCT C) U A - not equal (!=) (GCT D) U C - greater than ( ) (GCT E) U E - lower than ( ) (GCT F) As you see.. WiiRd only allows allows comparison until the next endif! However.. there is a trick - if you raise XXXXXX by 1 (so make 145544 to 145545) and your statement includes and endif - this is kinda neat if you have multiple statements in a row (like if player pressed D-Up - if he presses D-Down - the “if he presses D-Down” can include the endif for the selection before! Base address changing set Base address to XXXXXXXX GCT 30000000 XXXXXXXX WiiRd 42000000 XXXXXXXX for ba - 4A0000000 XXXXXXXX for po load Base address from XXXXXXXX GCT 31000000 XXXXXXXX WiiRd 40000000 XXXXXXXX for ba - 48000000 XXXXXXXX for po set Base address to data register N GCT 3200000N 00000000 WiiRd 4200100N 00000000 for ba - 4A00100N 00000000 for po store Base address to XXXXXXXX GCT 33000000 XXXXXXXX WiiRd 44000000 XXXXXXXX for ba - 4C000000 XXXXXXXX for po add XXXXXXXX to current base address GCT 34000000 XXXXXXXX WiiRd 42010000 XXXXXXXX for ba - 5A010000 XXXXXXXX for po You see… all codes can be used the exact same way! A very elegent way to make a full terminator in WiiRd to reset both the base address and the pointer ist WiiRd E0000000 80008000 //Sets ba and po to 80000000 Set Repeat Code Types GCT 40000000 000MNNNN //set block [block] 41000000 000M0000 //execute block WiiRd 6000NNNN 0000000M [block] 62000000 0000000M Load Store Code Types load XXXXXXXX into register specified by N GCT 5000000N XXXXXXXX WiiRd 8000000N XXXXXXXX load data at address XXXXXXXX into register N GCT 510U000N XXXXXXXX WiiRd 82U0000N XXXXXXXX U 0 8 bit; 1 16 bit; 2 32 bit Execute instructions from code list GCT 54000000 XXXXXXXX //execute XXXXXXXX operations WiiRd C0000000 NNNNNNNN //execute NNNNNNNN lines of operations Both GCT and WiiRd codes must end with blr! Perform the operation N=(XXXXXXXX ? N) where operation is specified by T/U GCT 5T00000N XXXXXXXX WiiRd 86U0000N XXXXXXXX Please note that the speicifications of T and U differ (see description documents)! Perform the operation n=(M ? N) where operation is specified by T/U GCT 5T0001MN 00000000 WiiRd 88TY000N 0000000M Please note that the speicifications of T and U differ (see description documents)! Hook Code Types Hook GCT C0XXXXXX YYYYYYYY WiiRd C6XXXXXX YYYYYYYY for ba or D6XXXXXX YYYYYYYY for po Insert Instruction Code Types Execute NNNNNNNN bytes/lines of code at instruction base+XXXXXX GCT C1XXXXXX NNNNNNNN (N=bytes) WiiRd C2XXXXXX NNNNNNNN (N=lines) for ba or D2XXXXXX NNNNNNNN (N=lines) for po Please make sure that in both cases one last value remains as 00000000 - this one will be overwritten to branch back to regular code. In case of WiiRd if your last code line would be 00000000 00000000 then, please use 60000000 00000000 instead! End If Code Types GCT 60000000 XXXXXXXX Set execution status to 0 (=execute) Set base address to XXXXXXXX if XXXXXXXX =! 0 WiiRd Regular endif E20000VV XXXXYYYYApplies VV endifs (you can close deep if trees that way).. set ba to XXXX0000 if XXXX!=0 and po to YYYY0000 if YYYY!=0 Full terminator E0000000 XXXXYYYYClears all if trees.. If XXXX!=0, ba = XXXX0000 - If YYYY!=0, po = YYYY0000
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@wikiへようこそ ウィキはみんなで気軽にホームページ編集できるツールです。 このページは自由に編集することができます。 メールで送られてきたパスワードを用いてログインすることで、各種変更（サイト名、トップページ、メンバー管理、サイドページ、デザイン、ページ管理、等）することができます まずはこちらをご覧ください。 @wikiの基本操作 用途別のオススメ機能紹介 @wikiの設定/管理 分からないことは？ @wiki ご利用ガイド よくある質問 無料で会員登録できるSNS内の@wiki助け合いコミュニティ @wiki更新情報 @wikiへのお問合せフォーム 等をご活用ください @wiki助け合いコミュニティの掲示板スレッド一覧 #atfb_bbs_list その他お勧めサービスについて 大容量１Ｇ、PHP/CGI、MySQL、FTPが使える無料ホームページは@PAGES 無料ブログ作成は@WORDをご利用ください 2ch型の無料掲示板は@chsをご利用ください フォーラム型の無料掲示板は@bbをご利用ください お絵かき掲示板は@paintをご利用ください その他の無料掲示板は@bbsをご利用ください 無料ソーシャルプロフィールサービス @flabo(アットフラボ) おすすめ機能 気になるニュースをチェック 関連するブログ一覧を表示 その他にもいろいろな機能満載！！ @wikiプラグイン @wiki便利ツール @wiki構文 @wikiプラグイン一覧 まとめサイト作成支援ツール バグ・不具合を見つけたら？ 要望がある場合は？ お手数ですが、お問合せフォームからご連絡ください。
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チートコードの使い方 あまりにも情報が古すぎるので、大幅に書き直しました。 by 匿名希望 2013/03/28 情報更新 チートコードの使い方 はじめに 前準備 The Homebrew Channel(通称 HBC)の導入 Gecko OSのダウンロード 解凍・配置 GCT(チートコード)ファイルの作成 0. コードマネージャーのダウンロード 1. ゲームIDの入力 2. ゲームタイトルの入力 3. ゲームIDとタイトルを保存 4. コードの作成 5. コードの入力 6. コード保存 7. チェックを付ける 8. TXT形式で保存 9. GCT形式で保存 最終的なSD 構成図 入力したコードをゲームに適用 おまけ 小ネタ. Gecko OSの背景を変更する 最終手段. Wii用コードフリーク コメント（質問や意見があればどうぞ） はじめに チートは個人で楽しむものです。 Wi-Fiで使うのは違法です。 チートをオンラインで使い、それにより他人へ迷惑をかけた場合、以下の法律に抵触する可能性があります。 ◆著作権法第20条 著作者人格権(同一性保持権)侵害 ～3年以下の懲役または300万円以下の罰金 ◆刑法第234条 威力業務妨害罪 ～3年以下の懲役又は50万円以下の罰金 ◆刑法第234条の2 電子計算機損壊等業務妨害罪 ～5年以下の懲役又は100万以下の罰金 前準備 The Homebrew Channel(通称 HBC)の導入 当然ですが、まず最初にWiiを改造し、最低でもHBCは導入しましょう。 また、これから行う説明を実行する PCは予め拡張子を表示する設定に変えておいて ください。 Gecko OSのダウンロード チートをゲームに適用するアプリを用意します。下記のどちらか1つをダウンロードしてください。 ダウンロード： Ocarina Gecko OS （ Gecko OS推奨 ） ※Ocarinaは同時に256行以上のチートコードを使えません。 ※Gecko OSはOcarinaの公式後継アプリです。Ocarinaと100%互換です。 ※OcarinaはSDHCカードから起動しようとすると｢SD card error｣と出て起動できません。Gecko OSを使いましょう。 以下、説明はGecko OSで行います。 Ocarinaを使う人は各自読み替えてください。 解凍・配置 ダウンロードしたGecko OSを解凍し、中をGecko1931 → Gecko1931 → HBC と進むとある「Gecko1931」フォルダを SDルートのappsフォルダ内にコピーしてください。 正しく配置すると、SDカードのフォルダ階層はこうなります。 SD ┗ apps ┗ Gecko1931 ┣ boot.elf ┣ meta.xml ┗ icon.png 以上でWiiへの導入は完了です。 GCT(チートコード)ファイルの作成 0. コードマネージャーのダウンロード チートコードを入力するPCアプリをダウンロードします。 Gecko OSの人は → Code Manager v1.0(Ocarinaの人は → Code Manager v1.1） (※「すべて展開」では解凍できない場合があります。エラーが出る場合、解凍ソフトを使ってください。) ＠スクリーンショット ※画像はv1.0 ○日本語 △英語 □ドイツ語 1. ゲームIDの入力 ○ゲームID △Game ID □Spiel-ID 発売して間もないゲームの場合、IDがリストに無い事があります。 そのゲームのコード掲載ページに書かれているか捜して見て、 ない場合はGecko OSで一度ゲームを起動してみてください。 表示項目の中に Game ID ****** とあるのでそれをメモってください。 2. ゲームタイトルの入力 ○ゲームタイトル △Game Name □Name これは説明するまでもないですね。チートしたいゲームの名前をわかりやすいよう適当に入力してください。 3. ゲームIDとタイトルを保存 ○IDとタイトルを保存 △Store ID/Name □ID/Name speichern このボタンを一度押して、記憶させます。※まだファイルとして保存したわけではありません。 4. コードの作成 ○コード/コメント/カテゴリーを追加 △Add code/category/comment □Code/Kategorie/Kommentar hinzufugen このボタンを押して、コード名を入力します。 5. コードの入力 ○コード(コメント/カテゴリーの場合は何も入力しないでください) △Code contents (leave empty for comment/category) □Code-Werte (leer lassen fur Kategorien/Kommentare) 上記の場所にコードを書き込むか、コピペで貼り付けてください。※コピーする時、空白の改行が入らないように注意してください。 6. コード保存 ○変更を保存 △Store modifications □Anderungen speichern ボタンを押して、コードを保存します。※ファイルに保存されるわけではありません。 コードを複数登録する場合、必要なだけ4から繰り返してください。 7. チェックを付ける 気が済むまでコードを入力し終えたら、実際に使いたいコードの横にあるチェックボックス□にチェックマーク☑を入れてください。 8. TXT形式で保存 一旦、後から自由に編集できるようTXT形式で保存します。 上部メニュー「ファイル」→「テキストファイルに保存」から保存してください。 「テキストファイルを開く」から保存したTXTを読み込むことで あとからコードを追加したりフリーズするコードを除去することができます。 9. GCT形式で保存 実際にGecko OSで使うコードファイルはGCT形式です。 ○GCT形式でエクスポート △Export to GCT □Als GCT-Datei exportieren というボタンを押し、SDカードがあるドライブを選択し保存してください。 最終的なSD 構成図 ここまでの手順がうまくいっていれば、SDカードはこんな感じになるはずです。 SD ┣ apps ┃ ┗ Gecko1931 ┃ ┣ boot.elf ┃ ┣ icon.png ┃ ┗ meta.xml ┗ codes ┗ BLNK01.gct (←[ゲームID].gct) 入力したコードをゲームに適用 では実際に、先ほど入力したコードをゲームで使ってみたいと思います。 先ほどのSDカードをWiiに接続し、チートを適用したいゲームのディスクをWiiに挿入してください。 それができたら、HBCからGecko OSを起動します。 Gecko起動後、何やらズラーっとメニューが出ます。気にせずそのままAボタンを押してください。 すると、ゲームIDとHook情報が表示されたあとチートが効いた状態でゲームが起動します。 ※起動後フリーズする場合、上述のコード入力作業、或いはそのコードそのものに問題があります。 ※OcarinaもGecko OSもWiiリモコンプラスに非対応です。(Ocarina・Geckoを起動した途端に操作が効かなくなる) ※旧型Wiiリモコンがない場合、ゲームキューブコントローラ(1P)の十字ボタンとABボタンで操作してください。(GCコンがなく、新型Wiiリモコンしかない場合、もう操作するのは不可能です) おまけ
https://w.atwiki.jp/nenya/pages/129.html
1941-3084 Copyright © 2009 American Heart Association. All rights reserved. Print ISSN 1941-3149. Online ISSN Greenville Avenue, Dallas, TX 72514 Circulation Arrhythmia and Electrophysiology is published by the American Heart Association. 7272 DOI 10.1161/CIRCEP.108.816892 Circ Arrhythm Electrophysiol 2009;2;495-503; originally published online August 2, 2009; Hideo Okamura and Hitonobu Tomoike Wataru Shimizu, Takashi Kurita, Kazuhiro Suyama, Takashi Noda, Kazuhiro Satomi, Naomasa Makita, Nobuhisa Hagiwara, Hiroshi Inoue, Hirotsugu Atarashi, Naohiko Aihara, Minoru Horie, Satoshi Ogawa, Ken Okumura, Kazufumi Tsuchihashi, Kaoru Sugi, Shiro Kamakura, Tohru Ohe, Kiyoshi Nakazawa, Yoshifusa Aizawa, Akihiko Shimizu, V3CLINICAL PERSPECTIVE Long-Term Prognosis of Probands With Brugada-Pattern ST-Elevation in Leads V1- http //circep.ahajournals.org/content/2/5/495.full on the World Wide Web at The online version of this article, along with updated information and services, is located http //www.lww.com/reprints Reprints Information about reprints can be found online at journalpermissions@lww.com 410-528-8550. E-mail Health, 351 West Camden Street, Baltimore, MD 21201-2436. Phone 410-528-4050. Fax Permissions Permissions Rights Desk, Lippincott Williams Wilkins, a division of Wolters Kluwer http //circep.ahajournals.org/site/subscriptions/ at Subscriptions Information about subscribing to Circulation Arrhythmia and Electrophysiology is online Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 Long-Term Prognosis of Probands With Brugada-Pattern ST-Elevation in Leads V1–V3 Shiro Kamakura, MD, PhD; Tohru Ohe, MD, PhD; Kiyoshi Nakazawa, MD, PhD; Yoshifusa Aizawa, MD, PhD; Akihiko Shimizu, MD, PhD; Minoru Horie, MD, PhD; Satoshi Ogawa, MD, PhD; Ken Okumura, MD, PhD; Kazufumi Tsuchihashi, MD, PhD; Kaoru Sugi, MD, PhD; Naomasa Makita, MD, PhD; Nobuhisa Hagiwara, MD, PhD; Hiroshi Inoue, MD, PhD; Hirotsugu Atarashi, MD, PhD; Naohiko Aihara, MD; Wataru Shimizu, MD, PhD; Takashi Kurita, MD, PhD; Kazuhiro Suyama, MD, PhD; Takashi Noda, MD, PhD; Kazuhiro Satomi, MD, PhD; Hideo Okamura, MD; Hitonobu Tomoike, MD, PhD; for the Brugada Syndrome Investigators in Japan Background—The prognosis of patients with saddleback or noncoved type (non–type 1) ST-elevation in Brugada syndrome is unknown. The purpose of this study was to clarify the long-term prognosis of probands with non–type 1 ECG and those with coved (type 1) Brugada-pattern ECG. Methods and Results—A total of 330 (123 symptomatic, 207 asymptomatic) probands with a coved or saddleback ST-elevation 1 mm in leads V1–V3 were divided into 2 ECG groups—type 1 (245 probands) and non–type 1 (85 probands)—and were prospectively followed for 48.715.0 months. The absence of type 1 ECG was confirmed by drug provocation test and multiple recordings. The ratio of individuals with a family history of sudden cardiac death (14%) was lower than previous studies. Clinical profiles and outcomes were not notably different between the 2 groups (annual arrhythmic event rate of probands with ventricular fibrillation; type 1 10.2%, non–type 1 10.6%, probands with syncope; type 1 0.6%, non–type 1 1.2%, and asymptomatic probands; type 1 0.5%, non–type 1 0%). Family history of sudden cardiac death at age45 years and coexistence of inferolateral early repolarization with Brugada-pattern ECG were independent predictors of fatal arrhythmic events (hazard ratio, 3.28; 95% confidence interval, 1.42 to 7.60; P0.005; hazard ratio, 2.66; 95% confidence interval, 1.06 to 6.71; P0.03, respectively, by multivariate analysis), although spontaneous type 1 ECG and ventricular fibrillation inducibility by electrophysiological study were not reliable parameters. Conclusions—The long-term prognosis of probands in non–type 1 group was similar to that of type 1 group. Family history of sudden cardiac death and the presence of early repolarization were predictors of poor outcome in this study, which included only probands with Brugada-pattern ST-elevation. (Circ Arrhythmia Electrophysiol. 2009;2 495-503.) Key Words death, sudden prognosis follow-up studies electrocardiography Brugada syndrome Brugada syndrome is a hereditary arrhythmogenic disease characterized by ST-elevation in the right precordial lead of standard ECGs and an increased risk of sudden cardiac death (SCD).1 The prognosis for this condition and the management approaches have been reported in several multicenter studies of patients with the coved type 1 ECG. However, no prospective data have been reported in patients with saddleback type or noncoved Brugada-pattern STelevation before, because they were excluded from previous Clinical Perspective on p 503 studies as atypical Brugada patients showing a benign clinical course. Besides, the data from previous studies are all conflicting with regard to the prognosis of the typical Bru- Received August 22, 2008; accepted July 14, 2009. From the Division of Cardiology (S.K., N.A., W.S., T.K., K.S., T.N., K.S., H.O., H.T.), National Cardiovascular Center, Suita, Japan; the Department of Cardiovascular Medicine (T.O.), Okayama University Graduate School of Medicine, Okayama, Japan; the Department of Cardiology (K.N.), St Marianna University, Kawasaki, Japan; the Division of Cardiology (Y.A.), Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; the Division of Cardiology (A.S.), Yamaguchi University Graduate School of Medicine, Ube, Japan; the Department of Cardiovascular Medicine (M.H.), Shiga University of Medical Science, Otsu, Japan; the Department of Cardiopulmonary Medicine (S.O.), Keio University, Tokyo, Japan; the Second Department of Internal Medicine (K.O.), Hirosaki University School of Medicine, Hirosaki, Japan; the Second Department of Internal Medicine (K.T.), Sapporo Medical University School of Medicine, Sapporo, Japan; the Division of Cardiovascular Medicine (K.S.), Toho University Medical Center Ohashi Hospital, Tokyo, Japan; the Department of Cardiovascular Medicine (N.M.), Hokkaido University Graduate School of Medicine, Sapporo, Japan; the Department of Cardiology (N.H.), Tokyo Women’s Medical University; the Second Department of Internal Medicine (H.I.), Toyama University, Toyama, Japan; and the Department of Internal Medicine, Nippon Medical School, Tama-Nagayama Hospital, Tokyo, Japan. Correspondence to Shiro Kamakura, MD, PhD, Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan. E-mail kamakura@hsp.ncvc.go.jp © 2009 American Heart Association, Inc. Circ Arrhythmia Electrophysiol is available at http //circep.ahajournals.org DOI 10.1161/CIRCEP.108.816892 Downloaded from circep.ahajournals.org at 4F9u5kuoka Red Cross Hospital on June 11, 2013 gada syndrome.2–5 This may be caused by cohort studies that included a significant number of family members other than probands, in which the prognosis of pedigree members can be affected by the disease severity of probands. Furthermore, a selection bias can be present if the data are analyzed retrospectively. Therefore, we aimed to investigate the long-term prognosis of probands with noncoved type ST-elevation in leads V1–V3, prospectively, and compared it with that of probands with the type 1 ST-elevation. Methods Patient Population A total of 330 individuals with spontaneous ST-elevation were registered consecutively in this study, namely, “a multicenter study for risk stratification and management in patients with Brugada syndrome.” The study was conducted at 26 institutions across Japan beginning in July 2001. These individuals were prospectively followed up for more than 12 months to the end of March 2007. Subjects were enrolled in this study if they met the following inclusion criteria (1) proband, (2) J-point (QRS-ST junction) amplitude of 0.1 mV (1 mm) with either coved or saddle back type ST-segment elevation in at least 2 of the 3 precordial leads (V1–V3) on resting standard 12-lead ECG, (3) normal findings on physical examination, and (4) no abnormality in either right or left ventricular morphology and/or function demonstrated by chest radiography and echocardiography. Patients with vasospastic angina and those with vasovagal syncope were excluded from this study. Patients were not administered antiarrhythmic drugs and did not have electrolyte abnormalities at the time of baseline ECG recording and other examinations. Classification of Groups We divided the 330 patients with Brugada-pattern ECG into 3 groups according to their symptoms The ventricular fibrillation (VF) group consisted of 56 probands with aborted sudden death and/or documented VF, the syncope group consisted of 67 probands with syncope without documented arrhythmias that was not typical for vasovagal syncope, and the asymptomatic group consisted of 207 asymptomatic individuals whose ECGs were mainly detected by individual annual medical checkup or health screening in their place of employment. We also divided these patients into 2 groups according to ECG morphology The type 1 group consisted of 245 probands with a spontaneous type 1 ECG or those who developed type 1 ECG with a drug provocation test. The non–type 1 group consisted of the remaining 85 probands who never showed type 1 ST-elevation even with the drug provocation test (Figure 1) and during the follow-up on standard 12-lead ECGs. Clinical Data, ECG, and Electrophysiological Testing Clinical data including age at the enrollment, sex, family history of SCD, and the presence of atrial fibrillation were collected for all patients. The standard ECGs were recorded more than 5 times during the follow-up period in all patients. ECG recording on higher intercostals spaces (third and/or second) in leads V1–V3 6 was encouraged in patients who had cardiac events during the follow-up period. A type 1 ECG was defined as a prominent coved ST-segment elevation displaying J-point wave amplitude or ST-segment elevation 2 mm or 0.2 mV.7,8 ECG patterns with a prominent coved ST-elevation 2 mm followed by a positive or flat T wave were also included in type 1 group (Figure 2A through C). A non–type 1 ECG was defined as one of the following type 2 ECG,7 type 3 ECG,7 and ECG displaying coved or saddleback ST-elevation with J-wave amplitude 1 mm and 2 mm (Figures 1 and 2D through 2G). The presence of early repolarization in the inferolateral leads9 was evaluated by baseline 12-lead ECGs at the time of enrollment to elucidate ECG findings associated with Brugada syndrome. Early repolarization was defined as an elevation of the J point in at least 2 leads. The amplitude of the J wave or J-point elevation had to be at least 1 mm above the baseline level, either as QRS slurring or notching in the inferior lead (II, III, and aVF), lateral (I, aVL, and V4–V6) lead, or both.9 ECGs were evaluated by 3 independent investigators (S.K., N.A., and W.S.) who were unaware of the patients’ other clinical information. The ECG type or morphology was established by the evaluation in which at least 2 of the 3 observers were in agreement. Sodium channel blocker pilsicainide (1 mg/kg body weight at a rate of 5 to 10 mg/min), disopyramide (1.5 mg/kg, 10 mg/min), flecainide (2 mg/kg, 10 mg/min), or procainamide (10 mg/kg, 100 mg/min) was administered intravenously in 270 (82%) patients (233, 15, 14, and 8, respectively) to test the conversion to typical coved ST-elevation.8,10,11 Baseline electrophysiological studies (EPS) were performed in 232 (70%) patients. A maximum of 3 ventricular extrastimuli were delivered from 2 right ventricular (RV) sites (RV apex and RV outflow tract) unless VF or polymorphic ventricular tachycardia (VT) (lasting 10 beats) that terminated spontaneously within 30 seconds, causing syncope, or requiring intervention to be terminated was elicited at a previous step. Premature beats were started in late diastole; coupling intervals were then reduced in 10-ms decrements until refractoriness was reached. Stimulation was performed at twice the diastolic threshold. Patients with inducible ventricular arrhythmias lasting less than 10 beats were classified as noninducible. The indices including age, sex distribution, a family history of SCD at Figure 1. Presentation of 12-lead ECGs of a patient with non–type 1 ST-elevation. A, Baseline 12-lead ECG; B, 12-lead ECG after provocation by intravenous administration of 50 mg pilsicainide in the same patient. Saddlebacktype ST-elevation in leads V1 and V2 was enhanced after pilsicainide but was not changed to type 1 ST-elevation. This 46-yearold male patient with a history of syncope but with no family history of SCD had inducible VF by electrophysiological study. He had spontaneous VF 11 months after enrollment. 496 Circ Arrhythmia Electrophysiol October 2009 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 less than 45 years of age, and VF/polymorphic VT inducibility were compared with those reported in previously published studies2,3,5 (Table 1). In addition to these parameters, the presence of atrial fibrillation, cardiac events at night, and inferolateral early repolarization were compared between type 1 and non–type 1 groups. Patient treatment was based on clinical judgment of the participating hospital. Twenty-eight (8%) probands received antiarrhythmic drugs (quinidine sulfate 400 mg, bepridil 200 mg, disopyramide 300 mg, aprindine 30 mg, and amiodarone 200 mg/d) for prevention of atrial fibrillation or VF. Calcium antagonists were administered in 18 (5%) probands for hypertension. Quinidine and bepridil were administered only after a documentation of VF during follow-up. Among the 330 patients, 125 (38%) received an implantable cardioverter-defibrillator (ICD). During follow-up, patients were considered to have an arrhythmic event if sudden death occurred or VF was documented. Statistical Analysis Data are presented as meanstandard deviation. The Fisher exact test or the 2 test was used for categorical variables. One-way ANOVA was used for comparisons of continuous variables among the different groups. Survival curves were plotted by the Kaplan- Meier method and analyzed by the log-rank test. Cox proportional hazards models were used to analyze factors associated with the time to the first arrhythmic event during follow-up in all probands as well as in type 1, non–type 1, VF, and non-VF (syncope and asymptomatic) groups. Variables were included in the multivariate analysis with the use of a forward stepwise procedure with a criteria of P0.05 for inclusion and P0.15 for removal from the model. A probability value of P0.05 was considered statistically significant. This study was performed under the ethical code approved by the Health, Labor, and Welfare Ministry of Japan. Written informed consent was obtained from all individuals. Results Clinical Profiles of All Probands The mean age of the 330 probands was 51.414.8 years (median, 53 years; range, 4 to 86 years). The majority (315; 95%) of probands were male. A low percentage (14%) of patients had a family history of SCD occurring before the age of 45 years. The induction rate of VF/polymorphic VT by EPS was higher (77/109 72%, P0.005) in symptomatic than asymptomatic probands (61/123 50%) (Table 1). Comparison of Clinical Characteristics Between Type 1 and Non–Type 1 Groups Type 1 ECG was found in 245 probands (VF group 45, 18%; syncope group 46, 19%; and asymptomatic group 154, 63%). Of these 245 probands, 173 (71%) showed type 1 ECG spontaneously and the remaining 72 (29%) showed characteristic type 1 morphology after class Ic or Ia antiarrhythmic drug administration. In 85 probands of the non–type 1 group (VF group 11, 13%; syncope group 21, 25%; and asymptomatic group 53, 62%), non–type 1 ECG remained during the drug provocation test (type 2 61, Figure 2. Presentation of type 1 and non–type 1 ECG. Coved-type ST-elevation with a J-wave amplitude 2 mm followed by a negative T wave (A) or a positive/flat T wave (B), and a coved ST-elevation followed by a smaller J wave than T wave (C) were defined as type 1 ECG. Coved (D) or saddleback-type ST-elevation (E) with a J-wave amplitude 2 mm, a saddleback ST-elevation with a J-wave amplitude 2 mm (F), and a saddleback ST-elevation displaying bigger J wave than T wave (G) were defined as non–type 1 ECG. Table 1. Comparison of Patient Characteristics Among 3 Large Registries Brugada et al2 Eckardt et al5 Kamakura et al Sympt Asympt Sympt Asympt Sympt (VF, S) Asympt No. 144 190 89 123 123 (56, 67) 207 Age, y 4116* 4016 4614 4414 50.416.6 51.913.6 Men, % 83 71 76 68 96 95 FH of SCD, % 34 72 21 33 19 (25, 13) 11 VF/VT inducibility, % 73 33 63 39 71 (65, 75) 50 Values in parentheses are for the patients with aborted sudden death and an episode of syncope. Sympt indicates symptomatic; Asympt, asymptomatic; S, syncope; FH of SCD, prevalence of patients with a family history of sudden cardiac death at 45 years old; and VF/VT inducibility, induction rate of VF or polymorphic ventricular tachycardia by EPS. *Age of patients with VF. Kamakura et al Prognosis of Probands With Brugada ECG 497 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 72%; coved with J-point amplitude 2 mm 24, 28%) and the follow-up period. Most of the clinical parameters except for VF/VT inducibility, namely, age, sex distribution, the prevalence of atrial fibrillation, the presence of a family history of SCD, cardiac events at night (8 PM to 8 AM), and early repolarization, were of similar occurrence between type 1 and non–type 1 groups (Table 2). Only 8% (7/85) of probands in the non–type 1 group and 11% (26/245) of those in the type 1 group were associated with early repolarization in the inferolateral leads. Follow-Up and Predictors of Outcome The mean follow-up period for the entire study population was 48.714.9 months. Follow-up time was similar among VF (51.915.0 months), syncope (48.514.0 months), and asymptomatic (47.715.0 months) groups and between type 1 (48.615.2 months) and non–type 1 (48.914.2 months) groups. Twenty-four patients had fatal arrhythmic events during follow-up. The frequency of events in the type 1 group—15 of 45 (33%) in patients with VF, 1 of 46 (2%) in syncope patients, and 3 of 154 (2%) in asymptomatic patients— was similar to that in the non– type 1 group (4/11 36%, 1/21 5%, and 0/53 0%, respectively, P0.22; Figure 3). In 5 patients who had events in the non–type 1 group, 2 had shown a type 1 ST-elevation only in the higher (second or third) intercostal spaces—1 in a follow-up ECG and 1 after drug provocation test. The observed frequency of arrhythmic events was significantly highly in patients with early repolarization in the inferolateral leads (7/33; 21% versus 17/297; 6%, P0.005), although there was no difference in risk between the 2 groups (type 1 6/26; 23%, non–type 1 1/7; 14%, P0.67). One asymptomatic patient with type 1 ECG died suddenly 3 months after enrollment. Six patients died of nonarrhythmic causes; 3 died of cancer, 1 because of rupture of abdominal aortic aneurysm, 1 because of pneumonia, and cause of death for 1 patient was unknown. Seven percent of all patients who entered the study dropped out, the most frequent reason for drop-out was inability of follow-up due to patient’s change of address. Figure 4 shows the Kaplan–Meier analysis of arrhythmic events in probands with type 1 and non–type 1 ECG. Probands in the VF group had significantly worse prognosis than those in the syncope and asymptomatic groups. The Table 2. Comparison of Clinical Profiles Between Probands With Type 1 ECG and Those With Non–Type 1 ECG Type 1 (n245) Non-Type 1 (n85) VF Syncope Asympt VF Syncope Asympt P Value No. 45 46 154 11 21 53 0.33 Age, y 48.217.8 52.515.6 52.313.1 48.018.1 51.915.8 50.715.2 0.99 Men, n (%) 44 (98) 44 (96) 146 (95) 11 (100) 19 (90) 51 (96) 0.90 FH of SCD, n (%) 11 (24) 8 (17) 17 (11) 3 (27) 1 (5) 5 (9) 0.06 Event at night, n (%) 37/45 (82) 15/45 (33) 5/9 (56) 7/18 (39) 0.06 Inferolateral ER, n (%) 8 (18) 3 (7) 15 (10) 2 (18) 1 (5) 4 (8) 0.85 Prevalence of AF, n (%) 19 (42) 7 (15) 21 (14) 4 (36) 3 (14) 8 (15) 0.87 VF/VT inducibility, n (%) 27/41 (66) 31/40 (78) 52/91 (57) 7/11 (64) 12/17 (71) 9/32 (28) 0.04 n (%) indicates the number and the ratio of patients with each parameter; event at night, event developed at night (8 PM to 8 AM); inferolateral ER, inferolateral early repolarization; AF, atrial fibrillation; VF/VT inducibility, induction rate of VF or polymorphic ventricular tachycardia by EPS. Figure 3. Flow chart of proband groups categorized according to symptom, ECG morphology, and VF/VT inducibility by electrophysiological study. Sp. Type 1 indicates spontaneous type 1 group; Dr. Type 1, drug-induced type 1 group; VF, a group with inducible VF/VT; Non, a group with noninducible VF/VT; EP, a group in which electrophysiological study was not performed; AE, fatal arrhythmic event during follow-up. The number indicates the number of probands in each category. 498 Circ Arrhythmia Electrophysiol October 2009 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 annual rate of arrhythmic events in probands with type 1 ECG was 10.2% in the VF group, 0.6% in the syncope group, and 0.5% in the asymptomatic group (Figure 4A). The cumulative rate of arrhythmic events in probands with non–type 1 ECG was similar to those with type 1 ECG. The annual arrhythmic event rate was 10.6%, 1.2%, and 0%, respectively (Figure 4B). By univariate analysis, a family history of SCD was a predictor for arrhythmic events in the type 1 group (hazard ratio [HR], 5.1; 95% CI, 2.0 to 12.8; P0.0004) and the non–type 1 group (HR, 12.3; 95% CI, 2.0 to 74.8; P0.006). Coexistence of posterolateral early repolarization with precordial Brugada-pattern ECG was another predictor in the type 1 group (HR, 4.2; 95% CI, 1.6 to 11.2; P0.003); however, other parameters were not reliable. Figure 5 shows the Kaplan–Meier curves of arrhythmic events in the type 1 group during follow-up, depending on the presence of a family history of SCD (Figure 5A), inferolateral early repolarization (Figure 5B), a spontaneous type 1 ST-elevation (Figure 5C), and inducibility of ventricular arrhythmias by EPS (Figure 5D). Multivariate analysis in all probands identified that the former 2 parameters were independent risk factors for arrhythmic events (a family history of SCD HR, 3.28; 95% CI, 1.42 to 7.60; P0.005; early repolarization HR, 2.66; 95% CI, 1.06 to 6.71; P0.03, Table 3) as well as a family history of SCD in analysis of probands without VF (syncope and asymptomatic groups) (HR, 12.5; 95% CI, 2.0 to 75.0; P0.005). Discussion Main Findings We present one of the largest series of consecutive patients with Brugada-pattern ECG. Importantly, in the present study only probands were included. Also, this study has the longest follow-up ever reported. The main finding is that probands who have a non–type 1 ECG, even after challenged with a sodium channel blocker, do not necessarily have a better prognosis than patients with spontaneous or drug-induced type 1 ECG. Patients presenting with aborted cardiac arrest had a grim prognosis and those presenting with syncope or no symptoms had an excellent prognosis irrespective of their ECG pattern (that is, type 1 versus non–type 1). Also, a family history of sudden death at age 45 years and coexistence of early repolarization in the inferolateral leads were predictors of poor outcome. In contrast, VF/VT inducibility during EPS was not a predictor of outcome. Comparison With Previous Studies In this study, the follow-up time was uniform among the 3 groups. The mean follow-up time for the asymptomatic individuals was the longest (47.715.0 months) compared with the studies by Brugada et al2 (2729 months), Priori et al3 (3444 months), and Eckardt et al5 (33.752.2 months). The percentage of female patients (5%) and patients with a family history of SCD (14%) was significantly smaller than 2 of these previous reports (5% versus 24% to 28%2,3,5; P0.001, and 14% versus 28% to 54%2,3,5; P0.001), although the percentage (14%) of a family history of SCD was similar to that of probands (20%) that Priori et al3 had reported. The values observed in the present study may reflect the true profile of the probands of Brugada syndrome in contrast to previous studies in which a significant number of family members were also enrolled. Prognosis of Probands Presenting With Syncope and Without Symptoms The prognosis of probands in the syncope and asymptomatic groups was very good, and the annual rate of arrhythmic events was 1.2%. In the syncope group, this rate is far less than reported in previous studies,2–5 although the 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months A Asymptomatic group B Syncope group VF group Asymptomatic group Syncope group VF group Type 1 group Non-Type 1 group Asymptomatic 154 152 142 123 113 90 48 Syncope 46 45 42 35 33 26 10 VF 45 40 31 27 25 23 13 N. of patients Asymptomatic 53 53 52 43 40 29 16 Syncope 21 21 20 19 16 13 7 VF 11 11 11 7 6 3 2 N. of patients P 0.0001 P=0.009 Figure 4. Kaplan–Meier analysis of arrhythmic events (SCD or documented VF) during follow-up depending on the clinical presentation (VF/aborted sudden death, syncope, or asymptomatic) in probands with type 1 ECG (A) and those with non–type 1 ECG (B). P0.0001 represents overall comparison, and P0.009 is for comparison between the VF group and the syncope group. There was no statistically significant difference (P0.95) in the events-free survival of VF probands comparing type 1 and non–type 1 groups. Kamakura et al Prognosis of Probands With Brugada ECG 499 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 rate in the asymptomatic group is similar to that in the Eckardt registry5 and the rate of around 10% for the VF group is comparable to the rate reported in the Brugada registries.2,8 The reason that the patients in the syncope group showed excellent prognosis is not entirely clear but may be related to the method of registry. Poor prognosis in prior studies is possibly related to the retrospective design of the studies consisting of probands and family members, 2,3,5 in which only severe syncope directly linked to VF tends to be categorized later as a syncope, despite difficulty to determine the cause of syncope at the onset. Even so, we cannot exclude the possibility that some patients with vasovagal syncope were inevitably included in the syncope group because not a few patients have undefined syncope and 30% of Brugada patients are reported to have both vasovagal syncope and the syncope due to ventricular arrhythmia.12 Another reason for the good prognosis is the difference of genetic background. Brugada syndrome is known to be common in Asian people, which possibly relates to the higher prevalence of polymorphism of haplotype B, associated with the cardiac sodium channel.13,14 The average prognosis of Asian patients with Brugada syndrome may be better than that of the white population, because individuals without a critical genetic defect are easily detected as a Brugada patient in a routine medical checkup. Further genetic studies are required to clarify the racial difference of outcome. Nevertheless, the patients in this study with an aborted sudden death showed worse prognosis than European people in the study by Eckardt et al5 and had a similar outcome to those who underwent ICD implantation.15 Prognosis of Probands With Non–Type 1 ECG The outcome of probands with non–type 1 ECG was similar to those with type 1 ECG and the rate of arrhythmic events in the VF group was considerably higher. Some of these patients had shown a coved (type 1) ST-elevation only in the higher (second or third) intercostal spaces during the drug provocation test or follow-up. Miyamoto et al16 reported that men with a spontaneous type 1 ECG A FH of SCD - 209 207 191 167 154 124 63 FH of SCD + 36 30 24 18 18 15 9 N. of pts. with FH FH of SCD - FH of SCD + p 0.0001 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months Early Rep - 219 214 197 166 155 127 63 Early Rep + 26 23 19 19 17 12 9 N. of pts. with early repolarization P=0.0013 Early Repolarization - Early Repolarization + B 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months 0 . 2 . 4 . 6 . 8 1 Free of SCD or VF 0 10 20 30 40 50 60 70 Months Drug induced 72 71 65 57 54 46 22 Spontaneous 173 165 149 128 118 93 49 N. of pts. with Type 1 ECG Noninducible 62 60 54 47 46 38 25 Inducible 110 105 97 85 77 63 26 N. of pts. with EPS P=0.16 Drug induced Type 1 Spontaneous Type 1 P=0.54 Noninducible VF Inducible VF C D Figure 5. Kaplan–Meier analysis of fatal arrhythmic events during follow-up depending on a family history (FH) of SCD (FH of SCD versus FH of SCD ) (A), inferolateral early repolarization (early repolarization versus early repolarization) (B), a spontaneous type 1 ST-elevation (drug-induced type 1 versus spontaneous type 1) (C), and inducibility of ventricular arrhythmias by EPS (noninducible VF versus inducible VF) (D). 500 Circ Arrhythmia Electrophysiol October 2009 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 recorded only at the higher leads V1 and V2 showed a prognosis similar to that of men with a type 1 ECG when using standard leads. In the past, patients with non–type 1 ST-elevation in standard ECG had been excluded from studies as a benign entity of Brugada syndrome. However, if patients had a history of aborted sudden death or agonizing nocturnal dyspnea, non–type 1 Brugada-pattern ECG should not be disregarded. Careful follow-up including ECG recording at the higher intercostals spaces and the implantation of ICD is probably required in such a patient to prevent SCD. Clinical Features of Probands With Non–Type 1 ECG The clinical profiles of probands were very similar between the non–type 1 group and the type 1 group (Table 2). Inferolateral early repolarization occurred equally in small percentage of patients in both groups (8% and 11%, respectively), which is comparable to the prevalence (12%) of early repolarization that Letsas et al17 reported in patients with Brugada syndrome. This means that the patient characteristics of the non–type 1 group are much closer to Brugada syndrome than early repolarization syndrome reported by Haı¨ssaguerre et al,9 in which the VF occurrence rate during sleeping was low (19%) and VF inducibility by EPS was only 34%. Moreover, they reported that several aspects including the relapsing VF and the efficacy of isoproterenol and quinidine,9,18 which were observed in some patients with early repolarization, were exactly like those of typical Brugada syndrome. Haı¨ssaguerre et al9 excluded patients with Brugada syndrome, defined as right bundle-branch block and ST-segment elevation 0.2mV in leads V1–V3, at the enrollment. However, considering that they possibly included patients with non–type 1 ECG as non-Brugada pattern in their study, some patients with prior VF and early repolarization might have represented non–type 1 Brugada patients of high risk. Predictors of Outcome It was reported that male sex, a previous episode of syncope, a spontaneous type 1 ECG, and inducibility of ventricular arrhythmias by EPS are predictors for poor outcome.2– 4 Brugada et al demonstrated that inducibility of ventricular arrhythmias was a reliable marker in patients with and without VF/SCD,2,4 although Priori et al3 did not find any significant difference in the analysis of all patients. A spontaneous type 1 ECG was also indicated as a reliable marker of poor prognosis by Brugada et al4 in the analysis of patients without VF/SCD and by Eckardt et al5 in all patients.5 However, we could not find any reliability in these markers (Figures 3 and 5). Inducibility of ventricular arrhythmias was not a significant predictor even if it was evaluated by programmed pacing only from the RV apex (type 1 group HR, 1.9 [95% CI, 0.7 to 5.2], P0.18; all probands HR, 1.5 [95% CI, 0.6 to 4.1], P0.34, by univariate analysis). In contrast, a family history of SCD occurring at age of 45 years is an independent risk factor of a poor prognosis in probands of any groups irrespective of their ECG type (type 1 or non–type 1) or symptoms (with VF or without VF). This was probably caused by a smaller proportion of probands with a family history of SCD as compared with previous studies2–5 A family history was not found to be a marker in studies that enrolled many patients with SCD or a family history of Brugada syndrome. These results indicate that we should evaluate risks for arrhythmic events cautiously in studies with a significant number of family members. Early repolarization pattern in the inferolateral leads was another indicator of poor prognosis, although Letsas et al17 did not find any association with arrhythmic events in the data collected from 3 European centers, which also included 30% of patients with a family history of SCD. The reason for the poor outcome in probands with early repolarization in this study is not clear. However, it is conceivable that the combination of precordial Brugada-pattern ST-elevation with inferolateral early repolarization may represent electric heterogeneity in extensive regions of ventricles, which can result in lethal ventricular arrhythmias. Study Limitations In this study, premature ventricular electric stimulation was given until refractoriness was reached. The minimal Table 3. Probability of Sudden Death or VF During Follow-Up Depending on Clinical and Electrophysiological Variables in All Probands (Type 1 and Non–Type 1 Groups) Univariate Analysis Multivariate Analysis HR 95% CI P Value HR 95% CI P Value Prior VF 21.46 8.00 –57.53 0.0001 17.48 6.22– 49.11 0.0001 FH of SCD 6.35 2.84–14.19 0.0001 3.28 1.42–7.60 0.005 Inferolateral ER 4.14 1.71–10.00 0.001 2.66 1.06–6.71 0.03 AF 2.15 0.92–5.03 0.07 0.87 0.36–2.09 0.75 Syncope 0.35 0.08–1.09 0.15 Sp. type1 2.31 0.67–7.94 0.18 VF induc. (apex/OT) 1.81 0.72–4.70 0.20 VF induc. (apex) 1.58 0.60–4.11 0.34 Male NA FH indicates family history; inferolateral ER, inferolateral early repolarization; AF, atrial fibrillation; Sp. type 1, spontaneous type 1 ST-elevation on 12-lead ECG at baseline; VF induc. (apex/OT), VF induction by programmed pacing at the RV apex or RV outflow tract; and VF induc. (apex), VF induction by programmed pacing at the RV apex. Kamakura et al Prognosis of Probands With Brugada ECG 501 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 coupling interval of extrastimuli was not constant between participating hospitals and was sometimes shortened to 200 ms to induce ventricular arrhythmias. We did not show the results of genetic analysis in this report, although more than half of the patients underwent genetic screening. Detailed results will be presented in a future report. So far, no positive relationship between genetic findings and patient outcomes has been found.3,19 We did not record ECGs at the higher intercostals spaces systematically except for probands with cardiac events, because the importance of “high-recording” became apparent in the course of this study.6 Therefore, some patients of the non–type 1 group may have shown type 1 ST-elevation at the higher precordial positions. Conclusions This study described the long-term prognosis of probands with noncoved (non–type 1) Brugada-pattern ECG compared with type 1 ECG. The annual incidence of fatal arrhythmic events was similar between the 2 groups, which reached 10.6% in probands with non–type 1 ECG and a prior episode of VF. A family history of SCD occurring at age of 45 years and the presence of early repolarization were indicators of poor outcome although VF inducibility and a spontaneous type 1 ST-elevation were not reliable indicators in this prospective study including only probands. Appendix The following investigators and institutions participated in this study A. Hukui, Yamagata University, Yamagata; M. Hiraoka, Tokyo Dental and Medical University, Tokyo; S. Takata, Kanazawa University, Kanazawa; H. Sakurada, Hiroo Metropolitan Hospital, Tokyo; Y. Eki, Ibaragi-higashi National Hospital, Tokai; Y. Sasaki, Nagano National Hospital, Ueda; Y. Tomita, Nagoya Medical Center, Nagoya; U. Shintani, Mie-chuo Medical Center, Tsu; T. Hashizume, Minami-Wakayama Medical Center, Tanabe; Y. Fujimoto, Okayama Medical Center, Okayama; W. Matsuura, Higashihiroshima Medical Center, Higashihiroshima; K. Sakabe, Zentuuji National Hospital, Zentuuji; and I. Matsuoka, Kagoshima Medical Center, Kagoshima, Japan. Sources of Funding This work was supported by a research grant for cardiovascular diseases (13A-1, 16C-3) from the Ministry of Health, Labor, and Welfare of Japan. Disclosures None. References 1. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death a distinct clinical and electrocardiographic syndrome a multicenter report. J Am Coll Cardiol. 1992;20 1391–1396. 2. Brugada J, Brugada R, Antzelevitch C, Towbin J, Nademanee K, Brugada P. Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3. Circulation. 2002;105 73–78. 3. Priori SG, Napolitano C, Gasparini M, Pappone C, Della Bella P, Giordano U, Bloise R, Giustetto C, De Nardis R, Grillo M, Ronchetti E, Faggiano G, Nastoli J. Natural history of Brugada syndrome insights for risk stratification and management. Circulation. 2002;105 1342–1347. 4. Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation. 2003;108 3092–3096. 5. Eckardt L, Probst V, Smits JP, Bahr ES, Wolpert C, Schimpf R, Wichter T, Boisseau P, Heinecke A, Breithardt G, Borggrefe M, LeMarec H, Bocker D, Wilde AA. Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome. Circulation. 2005; 111 257–263. 6. Shimizu W, Matsuo K, Takagi M, Tanabe Y, Aiba T, Taguchi A, Suyama K, Kurita T, Aihara N, Kamakura S. Body surface distribution and response to drugs of ST segment elevation in Brugada syndrome clinical implication of eighty-seven-lead body surface potential mapping and its application to twelve-lead electrocardiograms. J Cardiovasc Electrophysiol. 2000;11 396–404. 7. Wilde AA, Antzelevitch C, Borggrefe M, Brugada J, Brugada R, Brugada P, Corrado D, Hauer RN, Kass RS, Nademanee K, Priori SG, Towbin JA; Study Group on the Molecular Basis of Arrhythmias of the European Society of Cardiology. Proposed diagnostic criteria for the Brugada syndrome consensus report. Circulation. 2002;106 2514 –2519. 8. Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, Gussak I, LeMarec H, Nademanee K, Perez Riera AR, Shimizu W, Schulze-Bahr E, Tan H, Wilde AA. Brugada syndrome report of the second consensus conference; endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation. 2005;111 659–670. 9. Haı¨ssaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L, Pasquie´ JL, Nogami A, Babuty D, Yli-Mayry S, De Chillou C, Scanu P, Mabo P, Matsuo S, Probst V, Le Scouarnec S, Defaye P, Schlaepfer J, Rostock T, Lacroix D, Lamaison D, Lavergne T, Aizawa Y, Englund A, Anselme F, O’Neill M, Hocini M, Lim KT, Knecht S, Veenhuyzen GD, Bordachar P, Chauvin M, Jais P, Coureau G, Chene G, Klein GJ, Cle´menty J. Sudden cardiac arrest associated with early repolarization. N Engl J Med. 2008;358 2016–2023. 10. Hattori Y, Inomata N. Modes of the Na channel blocking action of pilsicainide, a new antiarrhythmic agent, in cardiac cell. Japan J Pharmacol. 1992;58 365–373. 11. Morita H, Morita ST, Nagase S, Banba K, Nishii N, Tani Y, Watanabe A, Nakamura K, Kusano KF, Emori T, Matsubara H, Hina K, Kita T, Ohe T. Ventricular arrhythmia induced by sodium channel blocker in patients with Brugada syndrome. J Am Coll Cardiol. 2003;42 1624 –1631. 12. Letsas KP, Efremidis M, Gavielatos G, Filippatos GS, Sideris A, Kardaras F. Neurally mediated susceptibility in individuals with Brugada-type ECG pattern. Pacing Clin Electrophysiol. 2008;31 418–421. 13. Nademanee K, Veerakul G, Nimmannit S, Nimmannit S, Chaowakul V, Bhuripanyo K, Likittanasombat K, Tunsanga K, Kuasirikul S, Malasit P, Tansupasawadikul S, Tatsanavivat P. Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation. 1997;96 2595–2600. 14. Bezzina CR, Shimizu W, Yang P, Koopmann TT, Tanck MWT, Miyamoto Y, Kamakura S, Roden DM. Wilde AA. Common sodium channel promoter haplotype in Asian subjects underlies variability in cardiac conduction. Circulation. 2006;113 338 –344. 15. Sacher F, Probst V, Iesaka Y, Jacon P, Laborderie J, Mizon-Ge´rard F, Mabo P, Reuter S, Lamaison D, Takahashi Y, O’Neill MD, Garrigue S, Pierre B, Jaïs P, Pasquie´ JL, Hocini M, Salvador-Mazenq M, Nogami A, Amiel A, Defaye P, Bordachar P, Boveda S, Maury P, Klug D, Babuty D, Haı¨ssaguerre M, Mansourati J, Cle´menty J, Le Marec H. Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome a multicenter study. Circulation. 2006;114 2317–2324. 16. Miyamoto K, Yokokawa M, Tanaka K, Nagai T, Okamura H, Noda T, Satomi K, Suyama K, Kurita T, Aihara N, Kamakura S, Shimizu W. Diagnostic and prognostic value of a type 1 Brugada electrocardiogram at higher (third or second) V1 to V2 recording in men with Brugada syndrome. Am J Cardiol. 2007;99 53–57. 17. Letsas KP, Sacher F, Probst V, Weber R, Knecht S, Kalusche D, Haı¨ssaguerre M, Arentz T. Prevalence of early repolarization pattern in inferolateral leads in patients with Brugada syndrome. Heart Rhythm. 2008;5 1685–1689. 18. Haı¨ssaguerre M, Sacher F, Nogami A, Komiya N, Bernard A, Probst V, Yli-Mayry S, Defaye P, Aizawa Y, Frank R, Mantovan R, Cappato R, Wolpert C, Leenhardt A, de Roy L, Heidbuchel H, Deisenhofer I, Arentz T, Pasquie´ JL, Weerasooriya R, Hocini M, Jais P, Derval N, Bordachar P, 502 Circ Arrhythmia Electrophysiol October 2009 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013 Cle´menty J. Characteristics of recurrent ventricular fibrillation associated with inferolateral early repolarization role of drug therapy. J Am Coll Cardiol. 2009;53 612– 619. 19. Kusano KF, Taniyama M, Nakamura K, Miura D, Banba K, Nagase S, Morita H, Nishii N, Watanabe A, Tada T, Murakami M, Miyaji K, Hiramatsu S, Nakagawa K, Tanaka M, Miura A, Kimura H, Fuke S, Sumita W, Sakuragi S, Urakawa S, Iwasaki J, Ohe T. Atrial fibrillation in patients with Brugada syndrome relationships of gene mutation, electrophysiology, and clinical backgrounds. J Am Coll Cardiol. 2008;51 1176 –1180. CLINICAL PERSPECTIVE The prognosis of patients with saddleback or noncoved type (non–type 1) ST-elevation in Brugada syndrome is unknown. We compared the long-term prognosis of 85 probands with non–type 1 ECG with 245 probands with coved (type 1) Brugada-pattern ECG prospectively. The absence of type 1 ECG was confirmed by drug provocation test and multiple recordings. Clinical profiles and outcomes did not differ between the non–type 1 and type 1 groups. The annual rate of fatal arrhythmic events was very low in asymptomatic probands and those with syncope but was higher in probands with ventricular fibrillation. A family history of sudden cardiac death at age 45 years and the presence of inferolateral early repolarization were indicators of poor prognosis, although ventricular fibrillation inducibility and a spontaneous type 1 ST-elevation were not reliable parameters in this prospective study including only probands. Kamakura et al Prognosis of Probands With Brugada ECG 503 Downloaded from circep.ahajournals.org at Fukuoka Red Cross Hospital on June 11, 2013
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【Tags Len Master Inari Rin Tokoro-P tI I】 Original Music title INARING☆マーチ English music title INARING☆March Romaji music title INARING☆Maachi Lyrics written by マスター・いなり (Master Inari) Music written by 所P (Tokoro-P) Music arranged by 所P (Tokoro-P) Singer(s) 鏡音リン (Kagamine Rin), 鏡音レン (Kagamine Len) Fanmade Promotional Video(s) Click here for the original Japanese Lyrics English Lyrics (translated by motokokusanagi2009)： This is my Mr. INARI Layee-odl-layee-odl-layee-o He is cute and yellowish Layee-odl-layee-odl-layee-o Even if sesame is in Mr. INARI Even if hijiki, a brown sea vegetable, is in Mr. INARI We love INARI (Blab Blab Blab) Now everybody! Let s make INARI Now everybody! Let s eat a lot of INARI THE☆ FIGHT☆ ER has love and hopes Go for it! Our I☆ NA☆ RI! (I m starving, I m starving ＃＄％＆☆♪) Is this golden INARI yours? Or is this metallic glittering silver INARI yours? Nope, mine is a very precious treasure and only two in the world exists! (Paooon！) INARI is our POW☆ ER INARI is our LIFE☆ THE☆TREASURE that protects our family Go for it! Our I☆ NA☆ RI! To those who are watching this INARI will help you earn more money Everybody s earth is in danger Layee-odl-layee-odl-layee-o We are the last INARI Layee-odl-layee-odl-layee-o The shining INARI and INARI ball Combine them into ☆INARING☆ Now everybody! Let s dance with I☆ NA☆ RI Now everybody! Let s enclose the world in I NA RI The bridge to the future! Go for it! Our I☆ NA☆ RI! Lalala… LOVE LOVE I☆ NA☆ RI Lalala… LOVE LOVE I☆ NA☆ RI THE☆VAL☆IANT goes to outer space! Go for it! Our I☆ NA☆ RI! Romaji lyrics (transliterated by motokokusanagi2009)： kore wa boku no oinari san desu yōro yōro yororeihi kitsune iro no kawaī yatsu sa yōro yōro yororeihi goma o mabushi temo hijiki o ire temo bokura wa inari ga daisuki sa (Blab Blab Blab) sā min na de inari o ni-gi-ro sā min na de inari o hō-ba-ro ai to kibō yadoru SE☆ N☆ SHI! sore yuke! bokura no I☆ NA☆ RI! (hara hetta hara hetta ＃＄％＆☆♪) anata ga otoshita nowa ki no inari desu ka? sore tomo metarikku ni kagayaku gin no inari desu ka? īe boku nowa sekai de futatsu no tottemo taisetsu na takaramono! (Paooon!) inari wa bokura no CHI☆ KA☆ RA inari wa bokura no I☆ NO☆ CHI kazoku o mamoru hō ☆ seki sore yuke! bokura no I☆ NA☆ RI! kore o goran ni natta mina san wa inari no gokago ni yori kinun ga agaru deshō min na no chikyū ga abunai yōro yōro yororeihi bokura ga saigo no inari da yōro yōro yororeihi kagayaku inari to manmaru inari o futatsu awase reba☆INARING☆ sā min na de inari to O☆ DO☆ RO sā inari de sekai o tsu-tsu-mō mirai o tsunagu kake hashi sore yuke! bokura no I☆ NA☆ RI! Lalala… LOVE LOVE I☆ NA☆ RI Lalala… LOVE LOVE I☆ NA☆ RI uchū e tobi dasu YU☆ U☆ SHA! sore yuke! bokura no I☆ NA☆ RI! [Master Inari, Tokoro-P, TokoroP]