Modulation of QT Interval During Autonomic Nervous System Blockade in Humans

Diedrich, André; Jordan, Jens; Shannon, J. R.; Robertson, David L.; Biaggioni, Italo

doi:10.1161/01.cir.0000035241.76918.6c

Cited by 65 publications

(77 citation statements)

References 34 publications

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“…*P Ͻ 0.05. It is well established that the average QT interval of the body surface ECG is modulated by the autonomic nervous system (11,37), and our data suggest that this autonomic influence extends to beat-to-beat fluctuations of the QT interval. Although the underlying mechanisms are currently unknown, the lack of homogeneity of ␤-adrenoceptors and variable arborization of the sympathetic nerves (25, 37) may contribute to spatial dispersion in the action potential duration in the ventricular myocardium and thereby increase QT interval variability during periods of higher sympathetic activity.…”

Section: Discussionsupporting

confidence: 67%

Relation between QT interval variability and cardiac sympathetic activity in hypertension

Baumert

Schlaich

Nalivaiko

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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vated QT interval variability is a predictor of malignant ventricular arrhythmia, but the underlying mechanisms are incompletely understood. A recent study in dogs with pacing-induced heart failure suggests that QT variability is linked to cardiac sympathetic nerve activity. The aim of this study was to determine whether increased cardiac sympathetic activity is associated with increased beat-to-beat QT interval variability in patients with essential hypertension. We recorded resting norepinephrine (NE) spillover into the coronary sinus and single-lead, short-term, high-resolution, body-surface ECG in 23 patients with essential hypertension and 9 normotensive control subjects. To assess beat-to-beat QT interval variability, we calculated the overall QT variability (QTVN) as well as the QT variability index (QTVi). Cardiac NE spillover (12.2 Ϯ 6.5 vs. 20.7 Ϯ 14.7, P ϭ 0.03) and QTVi (Ϫ1.75 Ϯ 0.36 vs. Ϫ1.42 Ϯ 0.50, P ϭ 0.05) were significantly increased in hypertensive patients compared with normotensive subjects. QTVN was significantly correlated with cardiac NE spillover (r 2 ϭ 0.31, P ϭ 0.001), with RR variability (r 2 ϭ 0.20, P ϭ 0.008), and with systolic blood pressure (r 2 ϭ 0.16, P ϭ 0.02). Linear regression analysis identified the former two as independent predictors of QTVN. In conclusion, elevated repolarization lability is directly associated with sympathetic cardiac activation in patients with essential hypertension. norepinephrine spillover THE QT INTERVAL OF THE BODY surface ECG reflects global depolarization and repolarization in the ventricular myocardium and undergoes subtle beat-to-beat fluctuations (9). Elevated beat-to-beat QT interval variability has been demonstrated in various cardiac (6, 26) but also noncardiac conditions (4, 36). Importantly, QT variability has been shown to be elevated in dogs before pharmacologically induced Torsades de Pointes (32, 34) and in patients with structural heart disease before ventricular tachycardia/ventricular fibrillation events (33). Furthermore, QT variability was associated with an increased risk of ventricular tachycardia/ventricular fibrillation in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II (17) and was predictive of sudden cardiac death in patients with asymptomatic chronic heart failure with mild to moderate left ventricular (LV) diastolic dysfunction (27). However, the mechanisms contributing to beat-to-beat QT interval variability are incompletely understood. Besides electrical restitution, which reflects the intrinsic adaptation of the action potential duration to changes in cycle length (14), the autonomic nervous system is thought to play a key role in the genesis of beat-to-beat QT interval variability. Previous studies addressing this issue have provided conflicting results. A recent study in dogs showed that QT variability was related to left stellate-ganglion activity, but only after the dogs had developed heart failure (28). In healthy humans, pharmacological activation or blockade of ␤-adren...

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Section: Discussionsupporting

confidence: 67%

Relation between QT interval variability and cardiac sympathetic activity in hypertension

Baumert

Schlaich

Nalivaiko

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…7,[32][33][34] Prolongation of the QTc occurs in various forms of autonomic failure including diabetic autonomic neuropathy, 35 familial dysautonomia, 36 and primary autonomic failure, 37 and, similarly, nonselective pharmacological autonomic blockade causes dose-dependent QTc prolongation. 38 Failure to adapt the QT interval in response to changes in sympathetic innervation explains the occurrence of malignant arrhythmias in congenital LQTS. Provocation tests using epinephrine 39 or exercise 13 can be used to unmask QT prolongation in LQTS mutation carriers.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa

et al. 2016

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Background-Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia. Methods and Results-Sixty-one adolescent female patients with anorexia nervosa and 45 age-and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; P<0.001) and lower peak heart rates (159±20 versus 184±9 beats/min; P<0.001). The mean QTc intervals were longer at peak exercise in patients (442±29 versus 422±19 ms; P<0.001). During submaximal exertion at comparable heart rates (114±6 versus 115±11 beats/min; P=0.54), the QTc interval had prolonged significantly more in patients than controls (37±28 versus 24±25 ms; P<0.016). The RR/QT slope, best described by a curvilinear relationship, was more gradual in patients than in controls (13.4; 95% confidence interval,12.8-13.9 versus 15.8; 95% confidence interval, 15.3-16.4 ms QT change per 10% change in RR interval; P<0.001) and steepest in patients within the highest body mass index tertile versus the lowest (13.9; 95% confidence interval, 12.9-14.9 versus 12.3; 95% confidence interval, 11.3-13.3; P=0.026). Conclusions-Despite

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“…The circadian pattern of autonomic tone has been reported to be correlated with the diurnal variation of corrected QT (QTc) intervals in humans (5,6). A continuous infusion of trimethaphan, an antagonist of nicotinic receptors in autonomic ganglia, was also shown to dose-dependently prolong QTc intervals in healthy humans (7). Moreover, in a dog telemetry model, the QT interval at high parasympathetic or low sympathetic tone was significantly longer than that at the low parasympathetic or high sympathetic tone when the RR interval was constant (8).…”

Section: Introductionmentioning

confidence: 95%

Involvement of the Autonomic Nervous System in Diurnal Variation of Corrected QT Intervals in Common Marmosets

Honda

Komatsu²,

Isobe³

et al. 2013

J Pharmacol Sci

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Abstract. Our previous study has shown that the corrected QT (QTc) interval of the electrocardiogram is longer during the dark period than during the light period in telemetered common marmosets. In the present study, we investigated the involvement of sympathetic and parasympathetic nervous activities in the changes of QTc interval associated with the light-dark cycle. Telemetry transmitters were implanted in six common marmosets to continuously record the electrocardiogram. The QT intervals obtained were corrected for the RR interval by applying individual probabilistic QT-rate correction formulae. Power spectral analysis of heart rate variability was performed to quantify each autonomic nervous function. Changes in QTc intervals and autonomic nervous tones were associated with the light-dark cycle. Parasympathetic nervous activity and QTc intervals significantly increased by approximately 10 ms during the dark period. Atropine, a muscarinic receptor antagonist, suppressed the increased parasympathetic tone and QTc prolongation during the dark period. In contrast, propranolol, a β-adrenoceptor antagonist, decreased the sympathetic activity and increased QTc intervals during the light period. These results suggest that the parasympathetic nerve functions prolong QTc intervals during the dark period, while the sympathetic nerve functions shorten them during the light period in common marmosets.

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Modulation of QT Interval During Autonomic Nervous System Blockade in Humans

Cited by 65 publications

References 34 publications

Relation between QT interval variability and cardiac sympathetic activity in hypertension

Relation between QT interval variability and cardiac sympathetic activity in hypertension

Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa

Involvement of the Autonomic Nervous System in Diurnal Variation of Corrected QT Intervals in Common Marmosets

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