今日の臨床サポート

QT延長症候群

著者: 清水 渉 日本医科大学大学院医学研究科 循環器内科学分野

監修: 今井靖 自治医科大学 薬理学講座臨床薬理学部門・内科学講座循環器内科学部門

著者校正済:2021/10/27
現在監修レビュー中
参考ガイドライン:
  1. 日本循環器学会遺伝性不整脈の診療に関するガイドライン(2017年改訂版)青沼和隆
  1. 日本循環器学会/日本不整脈心電学会合:不整脈非薬物治療ガイドライン(2018年改訂版),野上昭彦、栗田隆志
  1. 日本循環器学会/日本不整脈心電学会合:2020年改訂版 不整脈薬物治療ガイドライン.小野克重、岩崎雄樹、清水 渉
患者向け説明資料
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。
※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、実際の保険適用の査定において保険適用及び保険適用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用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:
清水 渉 : 未申告[2021年]
監修:今井靖 : 講演料(第一三共株式会社)[2021年]

改訂のポイント:
  1. 先天性QT延長症候群では、新たなエビデンスの創出はないが、2020年3月に、2020年改訂版 不整脈薬物治療ガイドライン(日本循環器学会/日本不整脈心電学会合同ガイドライン)が公開となり、先天性QT延長症候群の薬物治療について、フローチャートを用いて解りやすく解説された。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. QT延長症候群(LQTS)とは、心電図上のQT時間の延長とTorsade de Pointes(TdP)と称される多形性心室頻拍を認め、失神や突然死の原因となる症候群である[1][2]
 
LQT2型先天性QT延長症候群の12誘導心電図とTorsade de Pointes (TdP)

QT時間の著明な延長(QT=560ms、QTc=580ms)を認め(a)、心室期外収縮の連発に引き続いて短-長-短の連結パターンでTdPが出現している(b)。

出典

img1:  著者提供
 
 
 
  1. QT延長はBazett式により心拍数補正した修正QT時間(QTc = QT/√RR)が440ms以上と定義する。
  1. 遺伝(家族)性を認め、安静時からQT時間が延長している先天性LQTSと、薬剤などの誘因が加わった場合にQT時間が著明に延長しTdPを発症する後天性(二次性)LQTSに分類される。
  1. 先天性LQTSでは遺伝子診断率が75%程度であり、遺伝子診断結果に基づいた患者指導および治療が行われている。
 
先天性QT延長症候群の原因遺伝子とイオンチャネル機能

 
  1. 頻度の多いLQT1、LQT2、LQT3型では、遺伝子型別に特徴的な心事故の誘因を認める。
 
遺伝子型別の心事故の誘因(発端者)

LQT1、LQT2、LQT3の発端者における遺伝子型別の心事故の誘因

出典

img1:  平成18-20年度厚生労働科学研究班~2008
 
 
 
エピネフリン負荷試験による遺伝子型(LQT1、LQT2、LQT3)の推定

エピネフリン負荷開始直後(ピーク時)の修正QT(QTc)延長が80ms未満であればLQT3または正常者と考えられる。一方、エピネフリン負荷開始直後(ピーク時)のQTc延長が80ms以上で、かつエピネフリン点滴中の定常状態でのQTc延長が35ms以上の場合にはLQT1、定常状態でのQTc延長が35ms未満の場合にはLQT2と考えられる。
参考文献:
  1. J Am Coll Cardiol. 2003 Feb 19;41(4):633-42. PMID:12598076
  1. Heart Rhythm. 2004 Sep;1(3):276-83. PMID:15851169
  1. 日本循環器学会他編: 循環器病の診断と治療に関するガイドライン(2011年度合同研究班報告)QT延長症候群(先天性・二次性)とBrugada症候群の診療に関するガイドライン 2012年度改訂版

出典

 
  1. 頻度は2,000人に1人(0.05%)で、明らかな性差はないとされている。
  1. 初回心イベント学童期から思春期に多く、初回心イベント発生率は、15歳を過ぎると女性に多くなる。
  1. 初発症状として致死性イベントを5%未満に認める。
国際多施設登録(米国、ヨーロッパ、日本)によるハイリスクLQT3患者(QTc>500ms)におけるβ遮断薬内服別および性別による累積初回心事故発生率

出典

img1:  Clinical Aspects of Type 3 Long-QT Syndrome: An International Multicenter Study.
 
 Circulation. 2016 Sep 20;134(12):872-82.・・・
問診・診察のポイント  
  1. 先天性LQTSの臨床診断は、2012年度改訂版のSchwartzの診断基準を用いて、心電図所見(QT時間、TdP、交代性T波、Notched T波、徐脈)、臨床症状(失神発作、先天性聾)、家族歴を点数化し、その合計点数が3.5点以上で診断確実、1.5~3点は疑い、1点以下は可能性が低いと判定する[3]
  1. 2012年改訂版 先天性QT延長症候群の診断基準:<図表>

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文献 

著者: Wataru Shimizu
雑誌名: Circ J. 2008 Dec;72(12):1926-36. Epub 2008 Nov 4.
Abstract/Text Over the past decade, molecular genetic studies have established a link between a number of inherited cardiac arrhythmias, including congenital long QT syndrome (LQTS) and Brugada syndrome (BrS), and mutations in genes encoding for ion channels or other membrane components. Twelve forms of LQTS have been identified in 50-70% of clinically affected patients. Genotype-phenotype correlations have been rigorously investigated in LQT1, LQT2 and LQT3 syndromes, which constitute more than 90% of genotyped LQTS patients, enabling stratification of risk and effective treatment of genotyped patients. Genotype-specific triggers for both the cardiac events and the clinical course have been reported, and genotype-specific therapy has been already introduced. More recently, mutation site-specific differences in the clinical phenotype have been reported in LQT1 and LQT2 patients, indicating the possibility of mutation site-specific management or treatment. In contrast, only one-third of BrS patients can be genotyped, and data on genotype-phenotype relationships in clinical studies are limited. A Haplotype B consisting of 6 individual DNA polymorphisms within the proximal promoter region of the SCN5A gene was recently identified only in Asians (frequency 22%). Individuals with Haplotype B show significantly longer duration of both PQ and QRS than those without Haplotype B, indicating that Haplotype B likely contributes to the higher incidence of BrS in Asian populations.

PMID 18981593  Circ J. 2008 Dec;72(12):1926-36. Epub 2008 Nov 4.
著者: Wataru Shimizu, Minoru Horie
雑誌名: Circ Res. 2011 Jun 24;109(1):97-109. doi: 10.1161/CIRCRESAHA.110.224600.
Abstract/Text Since 1995, when a potassium channel gene, hERG (human ether-à-go-go-related gene), now referred to as KCNH2, encoding the rapid component of cardiac delayed rectifier potassium channels was identified as being responsible for type 2 congenital long-QT syndrome, a number of potassium channel genes have been shown to cause different types of inherited cardiac arrhythmia syndromes. These include congenital long-QT syndrome, short-QT syndrome, Brugada syndrome, early repolarization syndrome, and familial atrial fibrillation. Genotype-phenotype correlations have been investigated in some inherited arrhythmia syndromes, and as a result, gene-specific risk stratification and gene-specific therapy and management have become available, particularly for patients with congenital long-QT syndrome. In this review article, the molecular structure and function of potassium channels, the clinical phenotype due to potassium channel gene mutations, including genotype-phenotype correlations, and the diverse mechanisms underlying the potassium channel gene-related diseases will be discussed.

PMID 21700951  Circ Res. 2011 Jun 24;109(1):97-109. doi: 10.1161/CIRCR・・・
著者: P J Schwartz, A J Moss, G M Vincent, R S Crampton
雑誌名: Circulation. 1993 Aug;88(2):782-4.
Abstract/Text
PMID 8339437  Circulation. 1993 Aug;88(2):782-4.
著者: Arthur A M Wilde, Arthur J Moss, Elizabeth S Kaufman, Wataru Shimizu, Derick R Peterson, Jesaia Benhorin, Coeli Lopes, Jeffrey A Towbin, Carla Spazzolini, Lia Crotti, Wojciech Zareba, Ilan Goldenberg, Jørgen K Kanters, Jennifer L Robinson, Ming Qi, Nynke Hofman, David J Tester, Connie R Bezzina, Marielle Alders, Takeshi Aiba, Shiro Kamakura, Yoshihiro Miyamoto, Mark L Andrews, Scott McNitt, Bronislava Polonsky, Peter J Schwartz, Michael J Ackerman
雑誌名: Circulation. 2016 Sep 20;134(12):872-82. doi: 10.1161/CIRCULATIONAHA.116.021823. Epub 2016 Aug 26.
Abstract/Text BACKGROUND: Risk stratification in patients with type 3 long-QT syndrome (LQT3) by clinical and genetic characteristics and effectiveness of β-blocker therapy has not been studied previously in a large LQT3 population.
METHODS: The study population included 406 LQT3 patients with 51 sodium channel mutations; 391 patients were known to be event free during the first year of life and were the focus of our study. Clinical, electrocardiographic, and genetic parameters were acquired for patients from 7 participating LQT3 registries. Cox regression analysis was used to evaluate the independent contribution of clinical, genetic, and therapeutic factors to the first occurrence of time-dependent cardiac events (CEs) from age 1 to 41 years.
RESULTS: Of the 391 patients, 118 (41 males, 77 females) patients (30%) experienced at least 1 CE (syncope, aborted cardiac arrest, or long-QT syndrome-related sudden death), and 24 (20%) suffered from LQT3-related aborted cardiac arrest/sudden death. The risk of a first CE was directly related to the degree of QTc prolongation. Cox regression analysis revealed that time-dependent β-blocker therapy was associated with an 83% reduction in CEs in females (P=0.015) but not in males (who had many fewer events), with a significant sex × β-blocker interaction (P=0.04). Each 10-ms increase in QTc duration up to 500 ms was associated with a 19% increase in CEs. Prior syncope doubled the risk for life-threatening events (P<0.02).
CONCLUSIONS: Prolonged QTc and syncope predispose patients with LQT3 to life-threatening CEs. However, β-blocker therapy reduces this risk in females; efficacy in males could not be determined conclusively because of the low number of events.

© 2016 American Heart Association, Inc.
PMID 27566755  Circulation. 2016 Sep 20;134(12):872-82. doi: 10.1161/C・・・
著者: Arthur J Moss, Wataru Shimizu, Arthur A M Wilde, Jeffrey A Towbin, Wojciech Zareba, Jennifer L Robinson, Ming Qi, G Michael Vincent, Michael J Ackerman, Elizabeth S Kaufman, Nynke Hofman, Rahul Seth, Shiro Kamakura, Yoshihiro Miyamoto, Ilan Goldenberg, Mark L Andrews, Scott McNitt
雑誌名: Circulation. 2007 May 15;115(19):2481-9. doi: 10.1161/CIRCULATIONAHA.106.665406. Epub 2007 Apr 30.
Abstract/Text BACKGROUND: Type-1 long-QT syndrome (LQTS) is caused by loss-of-function mutations in the KCNQ1-encoded I(Ks) cardiac potassium channel. We evaluated the effect of location, coding type, and biophysical function of KCNQ1 mutations on the clinical phenotype of this disorder.
METHODS AND RESULTS: We investigated the clinical course in 600 patients with 77 different KCNQ1 mutations in 101 proband-identified families derived from the US portion of the International LQTS Registry (n=425), the Netherlands' LQTS Registry (n=93), and the Japanese LQTS Registry (n=82). The Cox proportional hazards survivorship model was used to evaluate the independent contribution of clinical and genetic factors to the first occurrence of time-dependent cardiac events from birth through age 40 years. The clinical characteristics, distribution of mutations, and overall outcome event rates were similar in patients enrolled from the 3 geographic regions. Biophysical function of the mutations was categorized according to dominant-negative (> 50%) or haploinsufficiency (< or = 50%) reduction in cardiac repolarizing I(Ks) potassium channel current. Patients with transmembrane versus C-terminus mutations (hazard ratio, 2.06; P<0.001) and those with mutations having dominant-negative versus haploinsufficiency ion channel effects (hazard ratio, 2.26; P<0.001) were at increased risk for cardiac events, and these genetic risks were independent of traditional clinical risk factors.
CONCLUSIONS: This genotype-phenotype study indicates that in type-1 LQTS, mutations located in the transmembrane portion of the ion channel protein and the degree of ion channel dysfunction caused by the mutations are important independent risk factors influencing the clinical course of this disorder.

PMID 17470695  Circulation. 2007 May 15;115(19):2481-9. doi: 10.1161/C・・・
著者: Silvia G Priori, Carlo Napolitano, Peter J Schwartz, Massimiliano Grillo, Raffaella Bloise, Elena Ronchetti, Cinzia Moncalvo, Chiara Tulipani, Alessia Veia, Georgia Bottelli, Janni Nastoli
雑誌名: JAMA. 2004 Sep 15;292(11):1341-4. doi: 10.1001/jama.292.11.1341.
Abstract/Text CONTEXT: Data on the efficacy of beta-blockers in the 3 most common genetic long QT syndrome (LQTS) loci are limited.
OBJECTIVE: To describe and assess outcome in a large systematically genotyped population of beta-blocker-treated LQTS patients.
DESIGN, SETTING, AND PATIENTS: Consecutive LQTS-genotyped patients (n = 335) in Italy treated with beta-blockers for an average of 5 years.
MAIN OUTCOME MEASURES: Cardiac events (syncope, ventricular tachycardia/torsades de pointes, cardiac arrest, and sudden cardiac death) while patients received beta-blocker therapy according to genotype.
RESULTS: Cardiac events among patients receiving beta-blocker therapy occurred in 19 of 187 (10%) LQT1 patients, 27 of 120 (23%) LQT2 patients, and 9 of 28 (32%) LQT3 patients (P<.001). The risk of cardiac events was higher among LQT2 (adjusted relative risk, 2.81; 95% confidence interval [CI], 1.50-5.27; P =.001) and LQT3 (adjusted relative risk, 4.00; 95% CI, 2.45-8.03; P<.001) patients than among LQT1 patients, suggesting inadequate protection from beta-blocker therapy. Other important predictors of risk were a QT interval corrected for heart rate that was more than 500 ms in patients receiving therapy (adjusted relative risk, 2.01; 95% CI, 1.16-3.51; P =.01) and occurrence of a first cardiac event before the age of 7 years (adjusted RR, 4.34; 95% CI, 2.35-8.03; P<.001).
CONCLUSION: Among patients with genetic LQTS treated with beta-blockers, there is a high rate of cardiac events, particularly among patients with LQT2 and LQT3 genotypes.

PMID 15367556  JAMA. 2004 Sep 15;292(11):1341-4. doi: 10.1001/jama.292・・・
著者: G Michael Vincent, Peter J Schwartz, Isabelle Denjoy, Heikki Swan, Candice Bithell, Carla Spazzolini, Lia Crotti, Kirsi Piippo, Jean-Marc Lupoglazoff, Elizabeth Villain, Silvia G Priori, Carlo Napolitano, Li Zhang
雑誌名: Circulation. 2009 Jan 20;119(2):215-21. doi: 10.1161/CIRCULATIONAHA.108.772533. Epub 2008 Dec 31.
Abstract/Text BACKGROUND: Beta-blocker efficacy in long-QT syndrome type 1 is good but variably reported, and the causes of cardiac events despite beta-blocker therapy have not been ascertained.
METHODS AND RESULTS: This was a retrospective study of the details surrounding cardiac events in 216 genotyped long-QT syndrome type 1 patients treated with beta-blocker and followed up for a median time of 10 years. Before beta-blocker, cardiac events occurred in 157 patients (73%) at a median age of 9 years, with cardiac arrest (CA) in 26 (12%). QT-prolonging drugs were used by 17 patients; 9 of 17 (53%) had CA compared with 17 of 199 nonusers (8.5%; odds ratio, 12.0; 95% confidence interval, 4.1 to 35.3; P<0.001). After beta-blocker, 75% were asymptomatic, and cardiac events were significantly reduced (P<0.001), with a median event count (quartile 1 to 3) per person of 0 (0 to 1). Twelve patients (5.5%) suffered CA/sudden death, but 11 of 12 (92%) were noncompliant (n=8), were on a QT-prolonging drug (n=2), or both (n=1) at the time of the event. The risk for CA/sudden death in compliant patients not taking QT-prolonging drugs was dramatically less compared with noncompliant patients on QT-prolonging drugs (odds ratio, 0.03; 95% confidence interval, 0.003 to 0.22; P=0.001). None of the 26 patients with CA before beta-blocker had CA/sudden death on beta-blockers.
CONCLUSIONS: beta-Blockers are extremely effective in long-QT syndrome type 1 and should be administered at diagnosis and ideally before the preteen years. beta-Blocker noncompliance and use of QT-prolonging drug are responsible for almost all life-threatening "beta-blocker failures." beta-Blockers are appropriate therapy for asymptomatic patients and those who have never had a CA or beta-blocker therapy. Routine implantation of cardiac defibrillators in such patients does not appear justified.

PMID 19118258  Circulation. 2009 Jan 20;119(2):215-21. doi: 10.1161/CI・・・
著者: Wataru Shimizu, Arthur J Moss, Arthur A M Wilde, Jeffrey A Towbin, Michael J Ackerman, Craig T January, David J Tester, Wojciech Zareba, Jennifer L Robinson, Ming Qi, G Michael Vincent, Elizabeth S Kaufman, Nynke Hofman, Takashi Noda, Shiro Kamakura, Yoshihiro Miyamoto, Samit Shah, Vinit Amin, Ilan Goldenberg, Mark L Andrews, Scott McNitt
雑誌名: J Am Coll Cardiol. 2009 Nov 24;54(22):2052-62. doi: 10.1016/j.jacc.2009.08.028.
Abstract/Text OBJECTIVES: The purpose of this study was to investigate the effect of location, coding type, and topology of KCNH2(hERG) mutations on clinical phenotype in type 2 long QT syndrome (LQTS).
BACKGROUND: Previous studies were limited by population size in their ability to examine phenotypic effect of location, type, and topology.
METHODS: Study subjects included 858 type 2 LQTS patients with 162 different KCNH2 mutations in 213 proband-identified families. The Cox proportional-hazards survivorship model was used to evaluate independent contributions of clinical and genetic factors to the first cardiac events.
RESULTS: For patients with missense mutations, the transmembrane pore (S5-loop-S6) and N-terminus regions were a significantly greater risk than the C-terminus region (hazard ratio [HR]: 2.87 and 1.86, respectively), but the transmembrane nonpore (S1-S4) region was not (HR: 1.19). Additionally, the transmembrane pore region was significantly riskier than the N-terminus or transmembrane nonpore regions (HR: 1.54 and 2.42, respectively). However, for nonmissense mutations, these other regions were no longer riskier than the C-terminus (HR: 1.13, 0.77, and 0.46, respectively). Likewise, subjects with nonmissense mutations were at significantly higher risk than were subjects with missense mutations in the C-terminus region (HR: 2.00), but that was not the case in other regions. This mutation location-type interaction was significant (p = 0.008). A significantly higher risk was found in subjects with mutations located in alpha-helical domains than in subjects with mutations in beta-sheet domains or other locations (HR: 1.74 and 1.33, respectively). Time-dependent beta-blocker use was associated with a significant 63% reduction in the risk of first cardiac events (p < 0.001).
CONCLUSIONS: The KCNH2 missense mutations located in the transmembrane S5-loop-S6 region are associated with the greatest risk.

PMID 19926013  J Am Coll Cardiol. 2009 Nov 24;54(22):2052-62. doi: 10.・・・
著者: Dimitry Migdalovich, Arthur J Moss, Coeli M Lopes, Jason Costa, Gregory Ouellet, Alon Barsheshet, Scott McNitt, Slava Polonsky, Jennifer L Robinson, Wojciech Zareba, Michael J Ackerman, Jesaia Benhorin, Elizabeth S Kaufman, Pyotr G Platonov, Wataru Shimizu, Jeffrey A Towbin, G Michael Vincent, Arthur A M Wilde, Ilan Goldenberg
雑誌名: Heart Rhythm. 2011 Oct;8(10):1537-43. doi: 10.1016/j.hrthm.2011.03.049. Epub 2011 Mar 25.
Abstract/Text BACKGROUND: Men and women with type 2 long QT syndrome (LQT2) exhibit time-dependent differences in the risk for cardiac events. We hypothesized that data regarding the location of the disease-causing mutation in the KCNH2 channel may affect gender-specific risk in LQT2.
OBJECTIVE: This study sought to risk-stratify LQT2 patients for life-threatening cardiac events based on clinical and genetic information.
METHODS: The risk for life-threatening cardiac events from birth through age 40 years (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) was assessed among 1,166 LQT2 male (n = 490) and female (n = 676) patients by the location of the LQTS-causing mutation in the KCNH2 channel (prespecified in the primary analysis as pore-loop vs. non-pore-loop).
RESULTS: During follow-up, the cumulative probability of life-threatening cardiac events years was significantly higher among LQT2 women (26%) as compared with men (14%; P <.001). Multivariate analysis showed that the risk for life-threatening cardiac events was not significantly different between women with and without pore-loop mutations (hazard ratio 1.20; P =.33). In contrast, men with pore-loop mutations displayed a significant >2-fold higher risk of a first ACA or SCD as compared with those with non-pore-loop mutations (hazard ratio 2.18; P = .01). Consistently, women experienced a high rate of life-threatening events regardless of mutation location (pore-loop: 35%, non-pore-loop: 23%), whereas in men the rate of ACA or SCD was high among those with pore-loop mutations (28%) and relatively low among those with non-pore-loop mutations (8%).
CONCLUSION: Combined assessment of clinical and mutation-specific data can be used for improved risk stratification for life-threatening cardiac events in LQT2.

Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
PMID 21440677  Heart Rhythm. 2011 Oct;8(10):1537-43. doi: 10.1016/j.hr・・・
著者: Wataru Shimizu, Takashi Noda, Hiroshi Takaki, Takashi Kurita, Noritoshi Nagaya, Kazuhiro Satomi, Kazuhiro Suyama, Naohiko Aihara, Shiro Kamakura, Kenji Sunagawa, Shigeyuki Echigo, Kazufumi Nakamura, Tohru Ohe, Jeffrey A Towbin, Carlo Napolitano, Silvia G Priori
雑誌名: J Am Coll Cardiol. 2003 Feb 19;41(4):633-42.
Abstract/Text OBJECTIVES: This study was designed to test the hypothesis that epinephrine infusion may be a provocative test able to unmask nonpenetrant KCNQ1 mutation carriers.
BACKGROUND: The LQT1 form of congenital long QT syndrome is associated with high vulnerability to sympathetic stimulation and appears with incomplete penetrance.
METHODS: The 12-lead electrocardiographic parameters before and after epinephrine infusion were compared among 19 mutation carriers with a baseline corrected QT interval (QTc) of > or =460 ms (Group I), 15 mutation carriers with a QTc of <460 ms (Group II), 12 nonmutation carriers (Group III), and 15 controls (Group IV).
RESULTS: The mean corrected Q-Tend (QTce), Q-Tpeak (QTcp), and Tpeak-end (Tcp-e) intervals among 12-leads before epinephrine were significantly larger in Group I than in the other three groups. Epinephrine (0.1 microg/kg/min) increased significantly the mean QTce, QTcp, Tcp-e, and the dispersion of QTcp in Groups I and II, but not in Groups III and IV. The sensitivity and specificity of QTce measurements to identify mutation carriers were 59% (20/34) and 100% (27/27), respectively, before epinephrine, and the sensitivity was substantially improved to 91% (31/34) without the expense of specificity (100%, 27/27) after epinephrine. The mean QTce, QTcp, and Tcp-e before and after epinephrine were significantly larger in 15 symptomatic than in 19 asymptomatic mutation carriers in Groups I and II, and the prolongation of the mean QTce with epinephrine was significantly larger in symptomatic patients.
CONCLUSIONS: Epinephrine challenge is a powerful test to establish electrocardiographic diagnosis in silent LQT1 mutation carriers, thus allowing implementation of prophylactic measures aimed at reducing sudden cardiac death.

PMID 12598076  J Am Coll Cardiol. 2003 Feb 19;41(4):633-42.
著者: Wataru Shimizu, Takashi Noda, Hiroshi Takaki, Noritoshi Nagaya, Kazuhiro Satomi, Takashi Kurita, Kazuhiro Suyama, Naohiko Aihara, Kenji Sunagawa, Shigeyuki Echigo, Yoshihiro Miyamoto, Yasunao Yoshimasa, Kazufumi Nakamura, Tohru Ohe, Jeffrey A Towbin, Silvia G Priori, Shiro Kamakura
雑誌名: Heart Rhythm. 2004 Sep;1(3):276-83. doi: 10.1016/j.hrthm.2004.04.021.
Abstract/Text OBJECTIVES: The aim of this study was to test the hypothesis that epinephrine test may have diagnostic value for genotyping LQT1, LQT2, and LQT3 forms of congenital long QT syndrome (LQTS).
BACKGROUND: A differential response of dynamic QT interval to epinephrine infusion between LQT1, LQT2, and LQT3 syndromes has been reported, indicating the potential diagnostic value of the epinephrine test for genotyping the three forms.
METHODS: The responses of 12-lead ECG parameters to epinephrine were retrospectively examined in 15 LQT1, 10 LQT2, 8 LQT3, and 10 healthy volunteers to select the best ECG criteria for separating the four groups. The epinephrine test then was prospectively conducted in 42 probands clinically affected with LQTS, their 67 family members, and 10 new volunteers. The best criteria were applied in a blinded fashion to prospectively separate a different group of 31 LQT1, 23 LQT2, 6 LQT3, and 30 Control patients (10 genotype-negative LQT1, 10 genotype-negative LQT2 family members, and 10 volunteers).
RESULTS: The sensitivity (penetrance) by ECG diagnostic criteria was lower in LQT1 (68%) than in LQT2 (83%) or LQT3 (83%) before epinephrine and was improved with steady-state epinephrine in LQT1 (87%) and LQT2 (91%) but not in LQT3 (83%), without the expense of specificity (100%). The sensitivity and specificity to differentiate LQT1 from LQT2 were 97% and 96%, those from LQT3 were 97% and 100%, and those from Control were 97% and 100%, respectively, when Delta mean corrected Q-Tend >/=35 ms at steady state was used. The sensitivity and specificity to differentiate LQT2 from LQT3 or Control were 100% and 100%, respectively, when Delta mean corrected Q-Tend >/=80 ms at peak was used.
CONCLUSIONS: Epinephrine infusion is a powerful test to predict the genotype of LQT1, LQT2, and LQT3 syndromes as well as to improve the clinical diagnosis of genotype-positive patients, especially those with LQT1 syndrome.

PMID 15851169  Heart Rhythm. 2004 Sep;1(3):276-83. doi: 10.1016/j.hrth・・・

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