Efficacy of theophylline in patients affected by low-adenosine syncope

Michele Brignole (1) , Diana Solari (1) , Matteo Iori (2) , Nicola Bottoni (2) , Régis Guieu (3) , J. C. Deharo (3)

1 Department of Cardiology [Ospedali del Tigullio]
2 Arcispedale S Maria Nuova
3 DS-ACI / UMR MD2 - Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques

Background: Adenosine, an ATP derivative, may be implicated in some kinds of unexplained syncope. In patients with normal heart, normal ECG and recurrent sudden-onset syncope without prodromes have been shown to present with lowplasmatic adenosine levels and a high susceptibility to exogenous adenosine.The term “low-adenosine syncope” has been launched to describe this distinct clinical entity. Objectives: We decided to investigate whether chronic treatment of these patients with theophylline, a non-selective adenosine receptor antagonist, results in clinical benefit. Methods. We report on the prolonged clinical observation of 6 “low-adenosine” syncope patients (mean age 50±20 years, 4 females) treated with oral theophylline within the therapeutic range of 12-18 μg/ml. We were able to make an intrapatient comparison between a period with and a period without theophylline therapy. Results: In five patients, symptoms disappeared and the number of prolonged asystolic pauses detected by implantable loop recorder (ILR) fell impressively from a median of 1.11 per month (interquartile range 0.4 -1.8)during 13 months of no-treatment (range 2-36) to 0 per month(0-0.7) during 20 months of theophylline treatment (range 6-120). The 6th patient, was unresponsive to theophylline therapy, and a different mechanism of syncope was hypothesized. Conclusion: In this small series of highlyselected patients affected by syncope with low circulating adenosine levels, theophylline proved to be an effective therapy in most patients. The logical inference is that the adenosine pathway has a causal role in the mechanism of syncope in such patients.

Mots clés: Syncope; Theophylline; Adenosine; Xanthine; Implantable loop recorder; Atrioventricular block; Sinus arrest

Domaines: Cardiologie et système cardiovasculaire; Médicaments

Michele Brignole, Diana Solari, Matteo Iori, Nicola Bottoni, Régis Guieu, et al.. Efficacy of theophylline in patients affected by low-adenosine syncope. Heart Rhythm, 2016, 13 (5), pp.1151-1154. ⟨10.1016/j.hrthm.2015.12.016⟩. ⟨hal-01317462⟩