Efficacy of theophylline in patients affected by low adenosine syncope

Abstract

Total word count: 2583 (excluding front page)Statement. We declare no relationship with industry. The study was not funded. AbstractBackground.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 6 th 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.

Theophylline as an adjunct to control malignant ventricular arrhythmia associated with early repolarization

“…Owing to less I K,Ach expression in ventricular myocytes, adenosine has no relevant direct effect on the action potential duration in human ventricles but has been shown to indirectly attenuate the catecholamine‐stimulated inward I Ca,L current . Theophylline, a nonselective A1‐AR antagonist, increases the baseline heart rate and enhances the release of catecholamines from the sympathoadrenal system, being effective for treatment of patients with recurrent unexplained syncope potentially mediated by adenosine . We hereby report another potential indication for its use.…”

Syncope and paroxysmal atrioventricular block

“…Since patients with low plasma adenosine levels are highly susceptible to exogenous and endogenous adenosine, the effect of treatment with theophylline, a non‐selective adenosine receptor antagonist, in the prevention of syncopal recurrences has been investigated. In two recent small observational studies, oral theophylline appeared to be effective over a mean follow‐up of 16 and 17 months in patients with an established diagnosis of EI‐AVB and may be considered an alternative to permanent pacing in such patients [36,37].…”

Adenosine and the Cardiovascular System: The Good and the Bad

“…In this case, the APL is sufficient to activate high affinity A 1 R but not low affinity A 2A R, and thus, vasodilation is less important. In this subtype of syncope, the use of theophylline, a nonspecific adenosine receptor antagonist, is often effective in a preventive manner because theophylline binds to A 1 R and prevents adenosine binding [75,112]. Finally, if high APL plays a role in explaining VVS in patients, the cause of low APL in low adenosine syncope remains unknown.…”