Plasma adenosine and neurally mediated syncope: ready for clinical use

Abstract

Either central or peripheral baroreceptor reflex abnormalities and/or alterations in neurohumoral mechanisms play a pivotal role in the genesis of neurally mediated syncope. Thus, improving our knowledge of the biochemical mechanisms underlying specific forms of neurally mediated syncope (more properly termed ‘neurohumoral syncope’) might allow the development of new therapies that are effective in this specific subgroup. A low-adenosine phenotype of neurohumoral syncope has recently been identified. Patients who suffer syncope without prodromes and have a normal heart display a purinergic profile which is the opposite of that observed in vasovagal syncope patients and is characterized by very low-adenosine plasma level values, low expression of A2A receptors and the predominance of the TC variant in the single nucleotide c.1364 C>T polymorphism of the A2A receptor gene. The typical mechanism of syncope is an idiopathic paroxysmal atrioventricular block or sinus bradycardia, most often followed by sinus arrest. Since patients with low plasma adenosine levels are highly susceptible to endogenous adenosine, chronic treatment of these patients with theophylline, a non-selective adenosine receptor antagonist, is expected to prevent syncopal recurrences. This hypothesis is supported by results from series of cases and from observational controlled studies.

Heart rate variability and heart rate turbulence in patients with vasovagal syncope

“…With theophylline treatment, the average annual number of syncope episodes decreased from 2.6 to 0.4 [24]. In another report, Brignole et al suggested that adenosine plasma levels has a role in the different types of syncope [25]. These findings show that factors other than the ANS may have an important role in the pathogenesis of VVS.…”

The pathophysiology of vasovagal syncope: Novel insights

“…As the time of writing, it was not entirely clear whether this type of syncope should be classified as a type of reflex syncope. However, it may well overlap with VVS (Brignole et al, 2020). Adenosin causes bradycardia though A1 receptor stimulation and vasodilatation through A2 receptor stimulation, so its actions fit well with known mechanisms of reflex syncope (Brignole et al, 2020).…”

Adenosine—A drug with myriad utility in the diagnosis and treatment of arrhythmias

“…A low-adenosine phenotype of neurohumoral syncope has recently been identified and can be diagnosed by low serum adenosine levels. 8 These patients suffer syncope without prodromal symptoms with a normal baseline ECG and do not have any structural heart disease. The typical mechanism of syncope is an idiopathic paroxysmal atrioventricular block or sinus bradycardia, most often followed by sinus arrest.…”

“…7 Recently, an entity named neurohumoral syncope has been proposed to differentiate from classical vasovagal syncope because of the presence of low serum adenosine in the former. 8 In this review, we aim to provide an insight into the electrophysiological effect of adenosine, and in-depth analysis of the utility of adenosine in the field of cardiac electrophysiology in diverse clinical scenarios.…”

“…In the electrophysiology laboratory, adenosine plays a critical role in unmasking the accessory pathway conduction, 6 both before and after ablation and it also has a role in pulmonary vein isolation 7 . Recently, an entity named neurohumoral syncope has been proposed to differentiate from classical vasovagal syncope because of the presence of low serum adenosine in the former 8 …”