Intermittent ventricular preexcitation in children: not always a low-risk condition

Abstract

Introduction

Ventricular preexcitation (VP) may be intermittent in some patients. Historically, this has been thought to indicate a low-risk accessory pathway (AP) that conducts poorly in the anterograde direction.¹ However, rare cases of sudden cardiac death (SCD) in intermittent ventricular preexcitation (IVP) have been reported since the 1980s, and recently growing data have highlighted the potential risk of adverse events, even in patients with IVP.^2,3 Therefore, the most recent guidelines on asymptomatic VP in young patients suggest invasive risk stratification with electrophysiological testing (EPT) in these patients.^3,4

The aim of this study was to assess the electrophysiological characteristics of the AP in children with IVP and their relationship to clinical data.

Methods

This was a single-centre retrospective study on paediatric patients with symptomatic or asymptomatic IVP who underwent invasive risk stratification using EPT.

All patients underwent standard 12-lead ECG, 24-h ECG-Holter monitoring and exercise testing (ET). AP localization was assessed using common algorithms.⁵ The VP intermittency was defined either as beat-to-beat intermittency of delta wave on standard ECG or ECG-Holter monitoring or sudden loss of delta wave during ET.

Transoesophageal EPT protocol and definitions have been described elsewhere⁶ (a detailed description is provided in supplementary materials). High-risk IVP is defined as the shortest pre-excited RR interval (SPERRI) during atrial fibrillation (AF), shortest 1:1 AP conduction during incremental atrial pacing (in absence of AF inducibility), and/or AP effective refractory period (AP ERP) ≤ 250 ms at baseline or during exercise testing (ET) or isoproterenol infusion (ISO) [3].

Results

There were 67 patients (64.2% males) with a median age of 14 years (IQR 11.2–16.6). Twenty-three patients (34.3%) were symptomatic. All patients had a normal cardiac anatomy, except for one with an isolated bicuspid aortic valve. Only one patient had multiple APs (RL and LL). Risk assessment with EPT was performed both at baseline and after adrenergic stimulus in 61 patients (34 ISO and 27 ET).

Forty-six patients (68.7%) had high-risk EP parameters. In the other 21 (31.3%), the EP parameters suggested low risk. Comparing high- with low-risk patients, there was no significant difference among heart rates, in which patients lose preexcitation on their standard ECG (72 ± 24 vs. 75 ± 18 bpm), Holter (127 ± 36 vs. 131 ± 28 bpm), or exercise test (141 ± 16 vs. 145 ± 13 bpm). Orthodromic AVRT was inducible in 31 patients (46.3%), and there was no significant difference for AVNRT inducibility between patients at high risk and those at low risk, as well as for the other EP parameters (see Table 1).

Comparing symptomatic with asymptomatic patients, there was a significantly higher AVRT inducibility in those with symptoms. Additionally, there was a significantly shorter AP ERP in those who were asymptomatic. No other differences were found in these two groups (see Table 2).

Discussion

Management of patients affected by VP has profoundly evolved over the past 25 years.⁷ However, the historical consensus that IVP carries a negligible risk of life-threatening events because it represents an AP with poor anterograde conduction and long refractory periods (i.e. long AP ERP or SPERRI values)⁸ is still a matter of debate.^2,9 Indeed, patients with IVP may have a significant occurrence of SPERRI <200–250 ms, and non-invasive testing has poor specificity and sensitivity for predicting it.^2,10 Moreover, some authors reported no significant differences in high-risk AP prevalence between children with IVP and those with persistent VP (10–24% at baseline EPT).^1,2,8,9,11 In a recent multicentre study, IVP was documented in a significant proportion (up to 10%) of patients with resuscitated SCD or severe pre-excited AF.¹²

The main finding of our study is that 69% of the patients with IVP were at high risk, much higher than previously reported.³ This may be due to: (i) the use of current risk criteria (higher SPERRI and AP ERP cut-off values for EP risk both ≤250 ms apart from adrenergic stimulus);^2–4 (ii) the recruitment criteria, including asymptomatic young athletes who underwent EPT for sports eligibility, as recommended by current sports guidelines;^3,13 and (iii) evaluation of AP characteristics, even during adrenergic stress to test catecholamine sensitivity (which is known to affect nodal and AP refractory periods).¹⁴ Notably, in our study, we found that almost half of patients with IVP have inducible AVRT without a significant difference between patients at high risk and those at low risk. Nowadays, AVRT inducibility is also considered a marker of increased risk of SCD³ because AVRT degenerating to AF may be the triggering event of ventricular fibrillation.¹⁵ This finding suggests that invasive risk stratification should be considered, even in asymptomatic patients with IVP, to confirm the absence of inducible AVRT prior to defining the AP as ‘benign’.

Furthermore, asymptomatic patients showed a significantly shorter AP ERP. The reason cannot be known, but a shorter AP ERP may explain why spontaneous ectopic premature beats are less likely to penetrate the AV node to induce AVRT, making these patients asymptomatic. Interestingly, there was a significant difference in APERP and SPERRI/1:1 in the low-risk group (280 vs. 340 ms) compared to the high-risk group (230 vs. 230 ms). This finding may be due to a better adaptation of the conductive capabilities of the AP to heart rate.

Concerning AP location, historically, IVP was thought to be mostly due to the left-sided location of the APs together with its longer refractory period. However, in accordance with the recent literature, in this study, we did not find any significant difference between EP risk and AP location, even when considering left-sided APs separately.¹

The study has some limitations. As a retrospective single-centre study with a small number of patients, the results could be influenced by the population selection and characteristics. EP values indicating high-risk parameters were considered both at rest and during ET/ISO. However, in children, tissue refractoriness may be different and more sensitive to catecholamines compared to adults. Therefore, the use of identical cut-off values to define high-risk APs may be inaccurate.

Conclusions

This study suggests that non-invasive risk stratification can fail to identify symptomatic and asymptomatic children with IVP at risk of life-threatening events. Compared to previous data, in our study, the incidence of high-risk IVP has been underestimated and suggests that all children with VP should be evaluated with EPT.

Acknowledgements

The authors would like to thank Dr. Elisa Del Vecchio for her valuable collaboration in the editorial revision. Our centre is a health care provider of the European Reference Network (ERN) GUARD-Heart.

Funding

This work was supported by the Italian Ministry of Health with ‘Current Research funds’ (202203_FBG_DRAGO).

Data availability

All data are incorporated into the article and its online supplementary material.

References

Author notes