Neural Control of Heart Rate Is an Arrhythmia Risk Modifier in Long QT Syndrome

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• 作者：Peter J. Schwartz ; Emilio Vanoli ; Lia Crotti ; Carla Spazzolini ; Chiara Ferr ; i ; Althea Goosen ; Paula Hedley ; Marshall Heradien ; Sara Bacchini ; Annalisa Turco ; Maria Teresa La Rovere ; Antonella Bartoli ; Alfred L. George Jr ; Paul A. Brink
• 刊名：Journal of the American College of Cardiology
• 出版年：2008
• 出版时间：4 March 2008
• 年：2008
• 卷：51
• 期：9
• 页码：920-929
• 全文大小：639 K

文摘

Objectives

The purpose of this study was to test the hypothesis that differences in autonomic responses might modify clinical severity in long QT syndrome type 1 (LQT1) patients, those with KCNQ1 mutations and reduced I_Ks, in whom the main arrhythmia trigger is sympathetic activation.

Background

Some long QT syndrome (LQTS) patients experience life-threatening cardiac arrhythmias, whereas others remain asymptomatic throughout life. This clinical heterogeneity is currently unexplained.

Methods

In a South African LQT1 founder population segregating KCNQ1-A341V, we correlated major cardiac events to resting heart rate (HR) and to baroreflex sensitivity (BRS) on and off beta-adrenergic blockers (BB).

Results

In 56 mutation carriers (MCs), mean HR was lower among asymptomatic patients (p < 0.05). Among MCs with a QT interval corrected for heart rate ≤500 ms, those in the lower HR tertile were less likely to have suffered prior cardiac events (odds ratio [OR] 0.19, 95 % confidence interval [CI] 0.04 to 0.79, p < 0.02). The BRS was lower among asymptomatic than symptomatic MCs (11.8 ± 3.5 ms/mm Hg vs. 20.1 ± 10.9 ms/mm Hg, p < 0.05). A BRS in the lower tertile was associated with a lower probability of being symptomatic (OR 0.13, 95 % CI 0.02 to 0.96, p < 0.05). A similar trend was observed during BB. The MCs in the lower tertile for both HR and BRS were less frequently symptomatic than MCs with different patterns (20 % vs. 76 % , p < 0.05). Subjects with either ADRA2C-Del322-325 or homozygous for ADRB1-R389, 2 polymorphisms predicting enhanced adrenergic response, were more likely to have BRS values above the upper tertile (45 % vs. 8 % , p < 0.05).

Conclusions

Lower resting HR and “relatively low” BRS are protective factors in KCNQ1-A341V carriers. A plausible underlying mechanism is that blunted autonomic responses prevent rapid HR changes, arrhythmogenic when I_Ks is reduced. These findings help understanding phenotypic heterogeneity in LQTS and identify a physiological risk modifier, which is probably genetically determined.