WPW syndrome is characterized by specific ECG changes that lead to ventricular pre-excitation, known as the “WPW pattern”, and is associated with recurrent tachyarrhythmias [1]. The baseline ECG typically exhibits a short PR interval (120 ms), a widened QRS complex, and a slurred upstroke (or downstroke) QRS, referred to as the “delta wave”. Ventricular pre-excitation occurs when an AP, a strand of myocardial cells with specific electrophysiological characteristics, activates both ventricles prematurely. The prevalence of WPW syndrome in the general population is estimated to be 1–3 in 1000 individuals [2]. WPW syndrome is associated with various SVTs, including AVRT and AF with rapid ventricular response, with AVRT being the most common arrhythmia linked to WPW, and AF occurring in up to 50% of patients with WPW [3, 4]. Several mechanisms may contribute to the development of AF in WPW syndrome. These include the spontaneous degeneration of AVRT into AF, the effects of the AP on atrial architecture, intrinsic atrial muscle vulnerability, and the role of autonomic tone. Pre-excited AF in WPW syndrome can potentially progress to VF, leading to syncope, cardiac arrest, and SCD. Factors such as syncope, a history of symptomatic tachycardia, younger age, multiple accessory pathways, accessory pathway effective refractory periods (APERP) 240 ms, and shortest pre-excited RR intervals (SPERRI) $\le$250 ms are associated with an increased risk of developing malignant arrhythmias [5]. In this case, the electrophysiological study, with the use of isoprenaline, identified an APERP of 250 msec and a SPERRI of 220 msec. Given these considerations, accurate ECG interpretation is crucial, as misdiagnosing pre-excited AF could result in administering incorrect treatments that may induce VF [6]. Recognizing ventricular pre-excitation is particularly important in the ED, especially when dealing with wide-complex tachycardias or patients admitted for syncope with a potential arrhythmogenic cause [7]. Various arrhythmias, such as polymorphic ventricular tachycardia and fast AF with aberrant conduction due to bundle branch block, can mimic pre-excited AF [8, 9]. Even in cases of particularly fast pre-excited AF, where the tachycardia cycle length is not notably irregular, AVNRT with aberrancy should be considered [10]. Despite the importance of recognizing signs of pre-excitation in WPW, pre-excited AF is often misdiagnosed, with ventricular tachycardia being the most likely incorrect diagnosis [11]. A study by Koźluk et al. [12] found that members of ED medical teams have limited skills in recognizing WPW syndrome with rapid AF, resulting in correct treatment in only 15% of cases.

In the acute setting, according to current guidelines [1], the pharmacological treatment of pre-excited AF in stable patients should avoid AV node blocking agents (particularly adenosine) since they may facilitate a potential induction of fast AF [13]. The preferred administration of intravenous drugs such as Ibutilide or Procainamide (Class IIa, level of evidence A), or class IC drugs like Flecainide or Propafenone (Class IIb, level of evidence B) is recommended in this scenario [1]. However, it is essential to note that IC drug agents are not entirely risk-free as they exert an effect on the AV node [14, 15]. Flecainide, a sodium channel-blocking drug, decreases the rise rate of phase 0 (resulting in depressed conduction velocity and prolonged conduction time), with little effect on the action potential duration, and it prolongs atrial and AP effective refractory period. Previous studies have documented that class I antiarrhythmic drugs could exhibit a proarrhythmic effect in various settings, mainly accelerating the ventricular response of supraventricular tachycardia [16]. Indeed, both the lack of a significant effect of IC drugs on the AV node and the effect on atrial and AP conduction could lead, at least in some cases, to an acceleration of ventricular rate response. In the chronic setting, amiodarone is no longer recommended (Class III) as it may often enhance AP conduction, with subsequent reports of ventricular fibrillation development [17, 18].

Synchronized direct current (DC) cardioversion is indicated (Class I) in hemodynamically unstable patients, as in our case where the patient presented with low blood pressure due to the long duration of a high ventricular rate tachycardia, or whenever drug therapy fails to convert or control the tachycardia. Patients with pre-excited AF may exhibit a poor response to antiarrhythmic drugs due to their weak action on AP conduction and no significant inhibition of AF recurrences. Furthermore, electrical cardioversion can only temporarily terminate the tachycardia with no real suppression of the recurrence of AF. In such cases, it is important to evaluate all possible concomitant factors that could play a role in perpetuating arrhythmogenesis, such as heart failure, infections, organic heart diseases, and hormonal imbalances, such as thyroid storms.

Thyroid storm is an endocrine emergency with a mortality rate of up to 10–30%, necessitating prompt recognition for timely initiation of treatment [19]. Individuals with hyperthyroidism face an increased risk of cardiac arrhythmias, particularly AF, with a prevalence of 5 to 15% [20]. While the association between new-onset AF and hyperthyroidism is uncommon in the absence of additional signs and symptoms of hyperthyroidism, as reported by Klein et al. [21], up to 13% of patients with unexplained AF may exhibit biochemical evidence of hyperthyroidism, highlighting the importance of measuring serum thyrotropin in patients with new-onset AF [21, 22]. The treatment of hyperthyroidism typically involves intravenous steroids and methimazole, as seen in our case, along with $\beta$-blockers. The excess of thyroid hormone can act as a trigger for the onset and perpetuation of tachyarrhythmias, necessitating the use of $\beta$-blockers. Managing pre-excited AF during a thyroid storm poses challenges due to the need to avoid $\beta$-blockers in this scenario. In a similar case described by Naqvi et al. [23], acute management involved amiodarone, metoprolol, steroids, and methimazole, with amiodarone chosen due to a national shortage of procainamide. While these authors considered amiodarone’s side effects on the thyroid gland negligible given the prompt effectiveness of methimazole and prednisone, caution is warranted. We do not recommend using amiodarone in this setting, not only due to potential additional risks on thyroid function but also because of enhanced accessory pathway conduction, potentially leading to ventricular fibrillation, as previously mentioned and reported in European Guidelines [1].

Treating hyperthyroidism has been reported to result in spontaneous cardioversion in nearly two-thirds of patients [20]. In this case, considering the waiting time between steroid and methimazole administration, we believe this was also the case. The mortality in patients with pre-excited AF due to thyroid storm is unknown. If catheter ablation remains the treatment of choice for symptomatic pre-excited AF (Class Ib) [1], an electrophysiology study should be deferred in this particular scenario until the complete resolution of thyroid storm. To maintain sinus rhythm, patients might be started on antiarrhythmic drugs (AAD) until catheter ablation. However, due to the pitfalls of amiodarone and potential risks associated with accelerating AF recurrences or converting it into atrial flutter with 1:1 conduction when administering flecainide, AADs were not initiated in this case. Moreover, these episodes were ascribed to the thyroid storm in a WPW syndrome with the accessory pathway likely being silent in the patient’s previous medical history. Nevertheless, the decision was made to monitor recurrences with an ILR for thorough monitoring, allowing consideration of eventual AAD therapy in case of arrhythmic recurrences, balancing the risk-benefit ratio. Proper hyperthyroidism management significantly helped the patient overcome AF recurrences, and they were safely managed until catheter ablation when they decided to undergo the procedure.

Catheter ablation of an AP has a high success rate (95%) and is associated with a low complication rate (3%), which mainly varies based on the AP location and the operators’ experience [3, 4]. Major complications include cardiac tamponade (0.13–1.1%) and complete AV block (0.17–2.7%), primarily observed in patients undergoing ablation of a septal/parahisian AP [24]. During the EP study, proper localization and subsequent catheter ablation of the AP are usually performed in sinus rhythm (for patients with an overt AP) or during ventricular pacing (for patients with a concealed AP). However, the procedure may be complicated by the occurrence of AF. Several studies have reported cases of AP catheter ablation performed during pre-excited AF, developed during the procedure [25], although not specifically during a thyroid storm. Kose et al. [26] were the first to report successful mapping and ablation of an AP in two patients during pre-excited AF, later confirming their findings in an eight-patient cohort. Previously, Hindricks et al. [27] reported successful localization and ablation of AP during AF in 18 of 19 patients with left-sided APs and in 2 patients with right-sided Aps [26, 27].

Based on these encouraging data and considering the need for an invasive strategy in patients presenting with unstable, refractory, and/or recurrent pre-excited AF, Chen et al. [28] reported the results of five patients with high-risk pre-excited AF who underwent emergency catheter ablation of the AP to effectively correct the hemodynamic instability induced by the unresponsive rapid conduction of AP in pre-excited AF. No complications were observed or reported in this study, but it’s important to note that no patients with thyroid storm, which poses a very high risk of recurrences, were included. Therefore, in patients presenting with recurrent pre-excited AF episodes refractory to acute electrical cardioversion and/or intravenous antiarrhythmic therapy, catheter ablation of the AP might be considered an emergency procedure to reduce the risk of life-threatening arrhythmias and sudden cardiac death, once it is established that the underlying cause must be treated as well.