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CLINICAL STUDY

Differential effects of beta-blockade on dispersion of repolarization in the absence and presence of sympathetic stimulation between the lqt1 and lqt2 forms of congenital long qt syndrome

Wataru Shimizu, MD, PhD^*,*, Yasuko Tanabe, MD^*, Takeshi Aiba, MD, PhD^*, Masashi Inagaki, MD, PhD, Takashi Kurita, MD, PhD^*, Kazuhiro Suyama, MD, PhD^*, Noritoshi Nagaya, MD, PhD^*, Atsushi Taguchi, MD^*, Naohiko Aihara, MD^*, Kenji Sunagawa, MD, PhD, Kazufumi Nakamura, MD, PhD, Tohru Ohe, MD, PhD, FACC, Jeffrey A. Towbin, MD, Silvia G. Priori, MD, PhD^|| and Shiro Kamakura, MD, PhD^*

^* Division of Cardiology, Department of Internal MedicineSuita, Osaka, Japan
Department of Cardiovascular Dynamics, National Cardiovascular Center, Suita, Japan
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan
Department of Pediatrics (Cardiology), Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
^|| Molecular Cardiology, Salvatore Maugeri Foundation, Pavia, Italy

Manuscript received December 6, 2001; revised manuscript received March 7, 2002, accepted March 27, 2002.

^* Reprint requests and correspondence: Dr. Wataru Shimizu, Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565 Japan.
wshimizu{at}hsp.ncvc.go.jp

OBJECTIVES: This study compared the effects of beta-blockade on transmural and spatial dispersion of repolarization (TDR and SDR, respectively) between the LQT1 and LQT2 forms of congenital long QT syndrome (LQTS).

BACKGROUND: The LQT1 form is more sensitive to sympathetic stimulation and more responsive to beta-blockers than either the LQT2 or LQT3 forms.

METHODS: Eighty-seven-lead, body-surface electrocardiograms (ECGs) were recorded before and after epinephrine infusion (0.1 µg/kg body weight per min) in the absence and presence of oral propranolol (0.5–2.0 mg/kg per day) in 11 LQT1 patients and 11 LQT2 patients. The Q-T_end interval, the Q-T_peak interval and the interval between T_peak and T_end (T_p-e), representing TDR, were measured and averaged from 87-lead ECGs and corrected by Bazett’s method (corrected Q-T_end interval [cQT_e], corrected Q-T_peak interval [cQT_p] and corrected interval between T_peak and T_end [cT_p-e]). The dispersion of cQT_e (cQT_e-D) was obtained among 87 leads and was defined as the interval between the maximum and minimum values of cQT_e.

RESULTS: Propranolol in the absence of epinephrine significantly prolonged the mean cQT_p value but not the mean cQT_e value, thus decreasing the mean cT_p-e value in both LQT1 and LQT2 patients; the differences with propranolol were significantly larger in LQT1 than in LQT2 (p < 0.05). The maximum cQT_e, minimum cQT_e and cQT_e-D were not changed with propranolol. Propranolol completely suppressed the influence of epinephrine in prolonging the mean cQT_e, maximum cQT_e and minimum cQT_e values, as well as increasing the mean cT_p-e and cQT_e-D values in both groups.

CONCLUSIONS: Beta-blockade under normal sympathetic tone produces a greater decrease in TDR in the LQT1 form than in the LQT2 form, explaining the superior effectiveness of beta-blockers in LQT1 versus LQT2. Beta-blockers also suppress the influence of sympathetic stimulation in increasing TDR and SDR equally in LQT1 and LQT2 syndrome.

Abbreviations and Acronyms   APD   action potential duration   ECG   electrocardiogram   LQTS   long QT syndrome   cQTe   (corrected) Q-Tend interval   cQTp   (corrected) Q-Tpeak interval   cQTe-D   (corrected) dispersion of QTe   SDR   spatial dispersion of repolarization   cTp-e   (corrected) interval between Tpeak and Tend   TDR   transmural dispersion of repolarization

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