Ventricular fibrillation in a patient with Wolff‐Parkinson‐White syndrome unrelated to pre‐excited atrial fibrillation

Abstract

A 52‐year‐old man was admitted due to out‐hospital cardiac arrest. Recurrent ventricular fibrillation (VF) occurred under therapeutic hypothermia thereafter. Previously inadverted full pre‐excitation was documented exclusively and immediately prior to 4 out of the 5 VF relapses. Coronary vasospasm and early repolarization were also documented. An electrophysiological study demonstrated poor anterograde conduction over a left‐sided accessory pathway. We theorize that maximum pre‐excitation favored in‐hospital VF by augmenting the repolarization vulnerability induced by therapeutic hypothermia, with coronary vasospasm accounting as the probable cause of out‐hospital VF. A plausible VF mechanism in WPW syndrome unrelated to pre‐excited atrial fibrillation is discussed.

1. INTRODUCTION

Pre‐excited atrial fibrillation (AF) with fast ventricular response leading to ventricular fibrillation (VF) is accepted as the arrhythmogenic mechanism of sudden cardiac death (SCD) in patients with Wolff‐Parkinson‐White (WPW) syndrome (Dreifus, Haiat, Watanabe, Arriaga, & Reitman, 1971). Ventricular pre‐excitation is associated with an increased dispersion of the ventricular depolarization/repolarization and with early repolarization, although it remains unclear whether the repolarization's dispersion is proportional or not to the degree of pre‐excitation (Balaji, Sokoloski, Case, & Gillette, 1998; Yagihara et al., 2012). A direct link between ventricular pre‐excitation and incident VF unrelated with AF, however, has yet to be reported.

2. CASE REPORT

A 52‐year‐old man without relevant prior medical history, except for occasional cocaine consumption and nondocumented palpitations lasting for up to 20 min, was admitted at our Institution due to resuscitated out‐of‐hospital cardiac arrest, with VF reported as the initial rhythm that was successfully defibrillated. The 12‐lead ECG after the resuscitation was regarded as normal. Urine cocaine levels were reported as positive. The patient was transferred to the Intensive Cardiac Care Unit under deep sedation after an emergent coronary angiography had revealed a nonobstructive lesion at the proximal level of the right coronary artery, with no other findings. A two dimensional echocardiography demonstrated normal regional and global left and right ventricular function. One hour after the index VF episode, a 12‐lead ECG showed intermittent/modest pre‐excitation suggestive of a left‐sided accessory pathway (AP, Figures 1 and 2). Therapeutic hypothermia aimed to neurologic protection was initiated.

Figure 1.

Dynamic 12‐lead ECG changes during initial hospitalization. The 12‐lead ECG at admission at the Intensive Cardiac Care Unit showed intermittent pre‐excitation (panels a and b), which evolved to maximum pre‐excitation once therapeutic hypothermia was initiated (c); minutes after the previous ECG, the degree of ventricular pre‐excitation diminished and early repolarization with “J” waves and fast‐downsloping ST‐segment elevation at the infero‐lateral ECG leads was registered (d), preceding the 5th and last VF episode

Figure 2.

ECG telemetry during the ventricular fibrillation episodes. Continuous ECG monitoring after the index VF episode showed intermittent pre‐excitation (solid and dashed arrows; panel a). Under therapeutic hypothermia, the QRS complexes prior to the following 4 VF episodes showed overt pre‐excitation, which was never documented during normothermia (panel b). Prior to the 5th and last VF episode, ventricular pre‐excitation was absent, the ECG showing early repolarization and manifest QTc prolongation leading to VF (panel c)

The first night after admission, the patient presented four episodes of recurrent VF that were terminated by an external defibrillator. The ECG telemetry immediately before each VF episode newly demonstrated a manifest QRS complex widening produced by full/maximum pre‐excitation, which had not been adverted prior to the arrhythmic storm. Few minutes later, a subsequent 12‐lead ECG showed a very apparent “J” wave preceding a downsloping ST‐segment elevation in the infero‐lateral ECG leads. One hour after, a fifth and last VF episode occurred. The ECG telemetry before this episode showed persistence of large “J” waves, a prolonged PR interval and absent ventricular pre‐excitation. Throughout all this period of electrical instability, a variable and increased QTc interval was observed in all 12‐lead ECGs performed. The dynamics of the biological markers of myocardial damage performed during the first 48 hr of hospital admission were not characteristic of persistent or intermittent myocardial ischemia.

After the last VF episode, therapeutic hypothermia was discontinued, intravenous magnesium sulfate was administered and treatment with nitrates and calcium antagonists was started. The subsequent 12‐lead ECG normalized back to a normal PR interval and an intermittent and less apparent ventricular pre‐excitation, along with QTc interval normalization. No further episodes of VF arrest occurred.

An electrophysiological study was performed the 4th day after the index VF episode, showing poor anterograde conduction through a left‐anterolateral AP (Mobitz II block during incremental atrial pacing at 480 ms, anterograde refractory period of 460 ms). Orthodromic supraventricular tachycardia with the AP acting as the retrograde limb was induced. Successful ablation of a left‐sided anterolateral AP was performed. Pharmacological adrenaline and flecainide challenges were performed after ablation, with no significant changes in the depolarization and repolarization ECG indexes.

Finally, the day 6th after the index VF episode a second coronary angiography including a vasospasm provocation test using intracoronary methylergometrine was performed. Severe spasm of the right coronary artery was induced, accompanied by typical angina‐type chest pain, thus confirming the diagnosis of vasospastic angina.

The patient was discharged under calcium antagonists and nitrates, and cocaine consumption was strongly discouraged. Implantable cardiac defibrillator was not indicated. After a 12‐month follow‐up period, the patient has remained free from syncope episodes, angina, or palpitations. The follow‐up 12‐lead ECG was normal, with no recurrence of ventricular pre‐excitation.

3. DISCUSSION

A number of electrophysiological phenomena that are individually linked to the occurrence of VF cluster together in this case, namely acute myocardial ischemia (as inferred by the induction of coronary vasospasm and favored by cocaine consumption), early repolarization (with the observation of large amplitude “J” waves during hypothermia), and manifest QRS and QTc interval prologation, the latter favored by concurrent maximum pre‐excitation. We consider it highly compelling that full pre‐excitation was not observed at any instance during the patient's hospital admission but immediately before and after four out of the five VF episodes. We believe the former mechanism (myocardial ischemia associated with coronary vasospasm, enhanced by cocaine consumption) accounts for the out‐hospital VF arrest. As for the in‐hospital VF episodes, we theorize that full pre‐excitation favored the occurrence of VF over a background of an increased vulnerability of the ventricular repolarization produced by “malignant” early repolarization induced by therapeutic hypothermia. Such assumption would set for the principle of a possible mechanism of VF in patients with Wolff‐Parkinson‐White (WPW) syndrome unrelated to pre‐excited atrial fibrillation (AF) with fast ventricular response.

We believe several aspects point against myocardial ischemia as the main determinant of the in‐hospital VF episodes, namely the lack of evolving ECG repolarization changes suggestive of ongoing myocardial ischemia, with an atypical fast‐downsloping ST‐segment elevation, along with a dynamic curve of the biological markers of myocardial damage not suggesting persistent coronary vasospasm. Additionally, we consider it somewhat suspicious that the induced coronary vasospasm during the methylergometrine test, which was performed after hypothermia was reverted and the AP eliminated, did not produce sustained or nonsustained ventricular arrhythmias. Should the ECG repolarization changes be considered secondary to myocardial ischemia, malignant early repolarization induced by hypothermia or a combination of them, a timely prolongation of the depolarization induced by maximum pre‐excitation (expressed as manifest QRS widening with a short PR interval) appears to have contributed to the arrhythmogenicity of such vulnerable ventricular myocardium.

To our knowledge, ventricular pre‐excitation leading to VF without concurrent AF has never been postulated as a potential cause of sudden cardiac death in the setting of WPW syndrome, and it therefore should be considered an, if any possible, extremely rare mechanism, maybe appearing only when other mechanisms concur. An etio‐pathogenic link between pre‐excitation and early repolarization, with the AP masking characteristic “J” waves in the inferior leads and also producing shortening of the ventricular effective refractory period, has been described elsewhere (Takada et al., 2002; Yagihara et al., 2012). Additional data suggest that WPW patients may have an altered local recovery and activation time within the pre‐excited area, thus leading to inhomogeneous regional ventricular repolarization (Balaji et al., 1998; Ghosh, Rhee, Avari, Wooddard, & Rudy, 2008; Mizumaki et al., 2011). Therapeutic hypothermia can help unmasking conduction through an AP and, in the other direction, early repolarization and its characteristic J waves can be masked by ventricular pre‐excitation (Miyoshi et al., 2019; Yagihara et al., 2012). A timely involvement of full pre‐excitation directly contributing to the VF relapses had never been suggested. In our case, it appears reasonable to assume that therapeutic hypothermia favored the occurrence of maximum pre‐excitation (due to concurring AV node block) and early repolarization, both enhancing a greater repolarization vulnerability and the occurrence of VF, independently to the occurrence of myocardial ischemia.

Admittedly, the last VF episode occurred without pre‐excitation being registered during the previous beats. Might this episode also be influenced by the ventricular pre‐excitation, this would only be plausible upon a theoretical pro‐arrhythmogenic effect of the cardiac memory, which produces a prolonged action potential duration at the site of the AP's ventricular insertion and consequent repolarization heterogeneity, as demonstrated with the use of vectocardiographic techniques (Ghosh et al., 2008; Wecke et al., 2013; Yagihara et al., 2012).

4. CONCLUSION

Our case report sets for the rationale of a theoretical impact of ventricular pre‐excitation on a higher degree of repolarization vulnerability leading to VF unrelated with AF. Provided the infrequent nature of the proposed arrhythmogenic mechanism, such phenomena would be restricted to patients with underlying vulnerable repolarization, such as that observed in the setting of myocardial ischemia and/or early repolarization.

CONFLICTS OF INTEREST

No conflicts of interest are to be declared among all authors.

Aranyo J, Bazan V, Rueda F, Sarrias A, Bisbal F, Villuendas R. Ventricular fibrillation in a patient with Wolff‐Parkinson‐White syndrome unrelated to pre‐excited atrial fibrillation. Ann Noninvasive Electrocardiol. 2019;24: e12662 10.1111/anec.12662