Vectorcardiography analysis of the repolarization response to pharmacologically induced autonomic nervous system modulation in healthy subjects

Abstract

Autonomic nervous system activity is essential for regulation of ventricular repolarization (VR) and plays an important role in several arrhythmogenic conditions. This study in 31 healthy adult subjects (16 men, 15 women) evaluated the VR response to pharmacologically modulated autonomic nervous system activity applying vectorcardiography (VCG) analysis. During continuous VCG recording, 0.01-0.1 μg·kg(-1)·min(-1) isoprenaline (Iso) was infused at an increasing flow rate until three targeted heart rates (HR) were reached. After Iso washout, one intravenous bolus of 0.04 mg/kg atropine was given followed by an intravenous bolus of 0.2 mg/kg propranolol. A 5-min steady-state VCG recording was analyzed for each of the seven phases (including baseline 1 and 2). Furthermore, during the first 4 min following atropine, six periods of 10-s VCG were selected for subanalysis to evaluate the time course of change. The analysis included QRS, QT, and T-peak to T-end intervals, measures of the QRS and T vectors and their relation, as well as T-loop morphology parameters. By increasing HR, Iso infusion decreased HR dependent parameters reflecting total heterogeneity of VR (T area) and action potential morphology (ventricular gradient). In contrast, Iso prolonged QT HR corrected according to Bazett and increased the T-peak to T-end-to-QT ratio to levels observed in arrhythmogenic conditions. HR acceleration after atropine was accompanied by a transient paradoxical QT prolongation and delayed HR adaptation of T area and ventricular gradient. In addition to the expected HR adaptation, the VR response to β-adrenoceptor stimulation with Iso and to muscarinic receptor blockade with atropine thus included alterations previously observed in congenital and acquired long QT syndromes, demonstrating substantial overlap between physiological and pathophysiological electrophysiology.

Electrophysiological phenotype in the LQTS mutations Y111C and R518X in the KCNQ1 gene

“…Additionally, phys-ical exercise and emotional stress were the most common triggers for syncopal episodes in Y111C mutation carriers (34). In fact, even in healthy individuals, a transient paradoxical QT prolongation and delayed HR adaptation of T area and VG results from ␤-adrenergic stimulation after muscarinic blockade with atropine (28). Whether such responses are more prominent in LQTS mutation carriers and can be used to identify patients at risk for malignant arrhythmias warrants further study.…”

Global electrical heterogeneity: A review of the spatial ventricular gradient

“…It should be noted, however, that there is significant variability in the magnitude and orientation of the SVG even among healthy people, and this variation is likely due to variations in orientation of the heart within the chest, heart rate, [25,28,29], postural changes [30], and autonomic influences independent of heart rate [31]. …”

Repolarisation Descriptors and Heart Rate Variability in Hemodialysed Patients

“…Previous studies have investigated the relationship between descriptors of repolarisation aberration and autonomic nervous system in subjects with structurally normal hearts. TCRT and the ventricular gradient have been shown to decrease in response to autonomic provocations induced by postural changes (sitting, standing) (Batchvarov et al 2002) and ventricular gradient decreased following pharmacological autonomic provocation with isoprenaline infusion (Vahedi et al 2012) beyond the expected HR effects. Our results extend these observations suggesting a potential impact of autonomic system independent of heart rate and are in line with a study in patients with diabetes mellitus showing increased QRS-T angle in patients with depressed HRV (Voulgari et al 2010).…”