Key result
Patients with reflex syncope show ~4.5-fold higher blood M2 receptor mRNA expression versus healthy controls.
Why the study?
Pathophysiology of reflex syncope is not fully understood, and this study aimed to examine blood M2 receptor and acetylcholinesterase expression in patients with reflex syncope.
Case-Control (n=136)
Single-blind
No
Effect estimate: Pr[patients>controls] = 0.99
Absolute Event Rate: 0.9% vs 0.2%
Blood mRNA overexpression of M2 receptors and acetylcholinesterase is present in adults and children with reflex syncope, identifying the first potential biological biomarkers for this condition.
May mark reflex syncope; hypothesis-generating and requires prospective validation before clinical use.
AIMS: Pathophysiology of reflex syncope is not fully understood but a vagal overactivity might be involved in this syncope. Previously, overexpression of muscarinic M2 receptors and acetylcholinesterase was found in particular in the heart and in lymphocytes of rabbits with vagal overactivity as well as in hearts of Sudden Infant Death Syndromes. The aim of this present study was to look at M2 receptor expression in blood of patients with reflex syncope. The second objective was to measure acetylcholinesterase expression in these patients. METHODS AND RESULTS: 136 subjects were enrolled. This monocenter study pooled 45 adults exhibiting recurrent reflex syncope compared with 32 healthy adult volunteers (18-50 years) and 38 children exhibiting reflex syncope requiring hospitalization compared with 21 controls (1-17 years). One blood sample was taken from each subject and blood mRNA expression of M2 receptors was assessed by qRT-PCR. Taking into account the non-symmetric distributions of values in both groups, statistical interferences were assessed using bayesian techniques. A M2 receptor overexpression was observed in adult and pediatric patients compared to controls. The medians [q1;q3] were 0.9 [0.3;1.9] in patients versus 0.2 [0.1;1.0] in controls; the probability that M2 receptor expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.99. Acetylcholinesterase expression was also increased 0.7 [0.4;1.6] in patients versus 0.4 [0.2;1.1] in controls; the probability that acetylcholinesterase expression was higher in patients than in controls (Pr[patients>controls]) was estimated at 0.97. Both in adults and children, the expression ratio of M2 receptors over acetylcholinesterase was greater in the patient group compared with the control group. CONCLUSION: M2 receptor overexpression has been detected in the blood of both, adults and children, exhibiting reflex syncope. As in our experimental model, i.e. rabbits with vagal overactivity, acetylcholinesterase overexpression was associated with M2 receptor overexpression. For the first time, biological abnormalities are identified in vagal syncope in which only clinical signs are, so far, taken into account for differential diagnosis and therapeutic management. Further work will be needed to validate potential biomarkers of risk or severity associated with the cholinergic system.
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Beutelstetter et al. (2019) conducted a case-control in Reflex syncope (n=136). Reflex syncope vs. Healthy controls was evaluated on Blood mRNA expression of M2 receptors (M2R) (Pr[patients>controls] = 0.99). Patients with reflex syncope exhibited significantly higher blood mRNA expression of muscarinic M2 receptors compared to healthy controls (median 0.9 vs 0.2, probability of superiority 0.99).
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