Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome

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 Towbin, Carlo Napolitano, Silvia G. Priori

Research output: Contribution to journalArticle

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Abstract

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 ≥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 μg/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.

Original languageEnglish (US)
Pages (from-to)633-642
Number of pages10
JournalJournal of the American College of Cardiology
Volume41
Issue number4
DOIs
StatePublished - Feb 19 2003
Externally publishedYes

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Long QT Syndrome
Epinephrine
Mutation
Penetrance
Sudden Cardiac Death
Sensitivity and Specificity
Control Groups

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome. / Shimizu, Wataru; Noda, Takashi; Takaki, Hiroshi; Kurita, Takashi; Nagaya, Noritoshi; Satomi, Kazuhiro; Suyama, Kazuhiro; Aihara, Naohiko; Kamakura, Shiro; Sunagawa, Kenji; Echigo, Shigeyuki; Nakamura, Kazufumi; Ohe, Tohru; Towbin, Jeffrey; Napolitano, Carlo; Priori, Silvia G.

In: Journal of the American College of Cardiology, Vol. 41, No. 4, 19.02.2003, p. 633-642.

Research output: Contribution to journalArticle

Shimizu, W, Noda, T, Takaki, H, Kurita, T, Nagaya, N, Satomi, K, Suyama, K, Aihara, N, Kamakura, S, Sunagawa, K, Echigo, S, Nakamura, K, Ohe, T, Towbin, J, Napolitano, C & Priori, SG 2003, 'Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome', Journal of the American College of Cardiology, vol. 41, no. 4, pp. 633-642. https://doi.org/10.1016/S0735-1097(02)02850-4
Shimizu, Wataru ; Noda, Takashi ; Takaki, Hiroshi ; Kurita, Takashi ; Nagaya, Noritoshi ; Satomi, Kazuhiro ; Suyama, Kazuhiro ; Aihara, Naohiko ; Kamakura, Shiro ; Sunagawa, Kenji ; Echigo, Shigeyuki ; Nakamura, Kazufumi ; Ohe, Tohru ; Towbin, Jeffrey ; Napolitano, Carlo ; Priori, Silvia G. / Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome. In: Journal of the American College of Cardiology. 2003 ; Vol. 41, No. 4. pp. 633-642.
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abstract = "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 ≥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 μg/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.",
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T1 - Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome

AU - Shimizu, Wataru

AU - Noda, Takashi

AU - Takaki, Hiroshi

AU - Kurita, Takashi

AU - Nagaya, Noritoshi

AU - Satomi, Kazuhiro

AU - Suyama, Kazuhiro

AU - Aihara, Naohiko

AU - Kamakura, Shiro

AU - Sunagawa, Kenji

AU - Echigo, Shigeyuki

AU - Nakamura, Kazufumi

AU - Ohe, Tohru

AU - Towbin, Jeffrey

AU - Napolitano, Carlo

AU - Priori, Silvia G.

PY - 2003/2/19

Y1 - 2003/2/19

N2 - 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 ≥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 μg/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.

AB - 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 ≥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 μg/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.

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