Beta-adrenergic reactivity of erythrocyte membranes as a biomarker of the clinical phenotype of supraventricular reentrant tachycardias in children

Introduction. Paroxysmal supraventricular reentrant tachycardias (PSRTs) are the most common class of tachyarrhythmias in childhood. Their clinical course is characterized by marked heterogeneity. The severity of clinical manifestations depends not only on the electrophysiological properties of the arrhythmia substrate but also on the individual reactivity of the sympathetic nervous system (SNS). Despite understanding the general role of the SNS, assessing its individual contribution in a particular patient remains challenging. Beta-adrenergic reactivity of erythrocyte membranes (β-ARM) is an integral marker of β-adrenergic receptor function and assesses their functional state in vitro based on the degree of membrane stabilization under the influence of a β-blocker. An increase in β-ARM (> 20 arbitrary units) is interpreted as a sign of receptor desensitization–an adaptive response to chronic hyperstimulation, which serves as an indirect marker of prolonged sympathetic hyperactivation.

Aim: To assess β-ARM levels in children with various forms of WPW and determine their relationship with the presence, frequency, and severity of clinical paroxysms.

Material and Methods. A single-center retrospective study included 38 children aged 7 to 17 years, including 15 (Group 1) with asymptomatic WPW syndrome and 23 (Group 2) with symptomatic WPW syndrome (WPW syndrome and AVNRT). β-ARM levels were determined photometrically by in vitro inhibition of hypotonic hemolysis with a nonselective β-blocker. Clinical severity was assessed using an original scoring system. Statistical analysis included the Mann – Whitney U test, Spearman correlation, and logistic regression.

Results. The level of β-adrenergic activity of erythrocyte membranes (β-ARM) was significantly higher in children with symptomatic supraventricular reentrant tachycardias compared to asymptomatic WPW phenomenon (21.5 ± 8.9 arbitrary units vs 14.2 ± 3.5 arbitrary units; p = 0.01). Each 1% increase in β-ARM increased the odds of a symptomatic course by 2.05 times (OR = 2.05; 95% CI: 1.28–3.28; p = 0.003). Higher values of β-ARM were found in patients with paroxysms at rest (22.5 [20.8; 24.2] arbitrary units) compared to those with exercise (18.9 [16.1; 21.7] arbitrary units; p = 0.032), as well as in patients requiring drug relief (20.51 [17.70; 37.47] arbitrary units) compared to those spontaneously relieved (16.20 [10.44; 20.00] arbitrary units; p = 0.041). The most severe course, characterized by frequent, treatment-resistant, prolonged paroxysms with a high heart rate, is associated with the highest β-ARM level (32.6 [24.12; 38.62] arbitrary units; p = 0.009).

Conclusion. Elevated β-ARM levels, reflecting β-adrenergic receptor desensitization, are a statistically significant predictor of symptomatic PSRT course in children and are associated with a more severe clinical phenotype. Determination of β-ARM can serve as an additional non-invasive tool for risk stratification in children with asymptomatic WPW.

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