Wolff–Parkinson–White syndrome and antidromic atrioventricular reentrant tachycardia

This editorial refers to ‘Incidence and prognostic significance of spontaneous and inducible antidromic tachycardia’ by B. Brembilla-Perrot et al., on page 871.

The prevalence of regular paroxysmal supraventricular tachycardia (SVT) is 2.25/1000 persons and the incidence is 35/100 000 person-years, according to data from the Marshfield Epidemiologic Study Area. Thus, there are ∼570 000 patients, and 89 000 new cases/year with SVT in the US alone. In most parts of the world, atrioventricular reentrant tachycardia (AVRT), due to Wolff–Parkinson–White (WPW) syndrome or a concealed accessory pathway, is the second most common cause of SVT (after AV nodal reentrant tachycardia), and accounts for up to one-third of all SVT. In China, WPW syndrome is the most common cause of SVT, being responsible for more than 70% of cases.¹ In Western countries, the prevalence of WPW syndrome is 0.1–0.3%.¹ Thus, despite the fact that accessory pathways have been continually eliminated in electrophysiology laboratories during the last two decades, WPW syndrome is not likely to become extinct.

Clear indications for catheter ablation in patients with WPW syndrome are not established. In patients with asymptomatic pre-excitation, the risk of sudden cardiac death is low, ∼1.25/1000 person-years.² Symptomatic patients have a 7% risk of developing fast atrial fibrillation (AF) with a shortest pre-excited RR interval (SPERRI) ≤250 ms, and a 1.4% risk of haemodynamic collapse or cardiac arrest resulting from ventricular fibrillation, within the next 3–4 years.³ Main methods of risk stratification are exercise testing to reveal potential disappearance of pre-excitation, and recording of the SPERRI during AF (SPERRI < 250 ms indicates high risk). Those two criteria have been adopted by the 2012 Expert Consensus Statement of Pediatric and Congenital Electrophysiology Society and the Heart Rhythm Society. Additional risk factors are the estimation of the antegrade effective refractory period (ERP) of the pathway at electrophysiology study (ERP < 250 ms indicates high risk), male gender, young age, multiple accessory pathways, and inducibility of AVRT triggering AF. The clinical significance of antidromic, i.e. pre-excited, AVRT in this respect remains controversial.

Antidromic AVRT occurs when an accessory AV connection is used as the antegrade limb and the AV node or a second pathway serves as the retrograde limb of the circuit. It has been clinically documented in <5% of patients with WPW syndrome, and may be induced in <10% in the electrophysiology laboratory. In adults, this usually happens in patients with multiple pathways or with free wall pathways located at least >4 cm from the AV node, but in children it may be also seen with septal pathways.⁴

In this issue of the journal, Brembilla-Perrot et al.⁵ report their experience in an extensive series of 807 patients with WPW, 63 (8%) of which had antidromic AVRT inducible at electrophysiology study. Both paediatric and adult cases were considered with ages ranging from 8 to 74 years (33 ± 18 years). Although patients with inducible antidromic tachycardia had accessory pathways with shorter ERPs and there was an increased incidence of induced AF, the occurrence of adverse events such as death or fast pre-excited AF within a mean follow-up of 6 years did not differ from patients without inducible antidromic tachycardia.

Previous reports on the prognostic significance of inducible antidromic AVRT in adults have been rather controversial,^6,7 but it seems that, at least in children, it may represent an adverse prognostic sign.⁴ The data provided in this study also support such a notion in patients <19-year old, by observing a higher proportion of inducible, fast, pre-excited AF.⁵ This difference between children and adults might be related to the fact that the incidence of AVRT increases with age, but also does the tachycardia cycle length and antegrade refractory period of the pathway, and one-third of patients may lose the WPW pattern at ages 30–70 years. Thus, induction of pre-excited tachycardia appears to be a surrogate marker of a more ‘aggressive’ accessory pathway, but inducibility or clinical detection of antidromic AVRT may suggest an increased risk only in children. In the adult population, the prognostic significance of pre-excited tachycardia is not established.

Perhaps, advents in genetics might be able in the future to provide some additional information. There is a four-fold increase of pre-excitation in family members of WPW patients. A missense mutation in the gene PRKAG2 that encodes the regulatory γ-subunit of AMP-activated protein kinase has been associated with ventricular pre-excitation and conduction disease.¹ Patients have a variable combination of glycogen storage cardiomyopathy, progressive conduction system disease, ventricular pre-excitation, arrhythmias, and sudden death. The annulus fibrosus, which normally insulates the ventricles from inappropriate excitation by the atria, is thinned and disrupted by glycogen-filled myocytes, and these anomalous microscopic AV connections, rather than morphologically distinct bypass tracts, appear to provide the anatomic substrate for ventricular pre-excitation. Pre-excitation due to the R302Q mutation in PRKAG2 has been associated with Mahaim, i.e. nodoventricular fibres, that usually cause antidromic AVRT.⁸ A novel form of WPW syndrome is associated with microdeletion in the region of gene BMP2, that encodes the bone morphogenetic protein-2, a member of the transforming growth factor beta gene superfamily, and affects the development of annulus fibrosus. It is characterized by variable cognitive deficits, dysmorphic features, and prolonged AV conduction on atrial pacing.⁹

The relevance of these observations to the majority of patients presenting with pre-excitation on their electrocardiograms is not known; however, they might represent the beginning of a new era for a more precise characterization of WPW patients based on their genetic background. It is perhaps ironic, that 82 years after the initial description of the syndrome by Louis Wolff and Paul Dudley White in Boston and John Parkinson in London, the issues of risk stratification and evidence-based indications for catheter ablation of accessory pathways still remain controversial.

Conflict of interest: none declared.

References

Author notes