“In certain clinical circumstances, asymptomatic patients may require invasive risk stratification and possible catheter ablation, after thoughtful discussion of the risks and benefits of an invasive approach versus the natural history of Wolff–Parkinson–White.”
Successful catheter ablation of the accessory pathways eliminates the small risk of sudden death associated with the Wolff–Parkinson–White (WPW) ECG in asymptomatic patients. The low rate of serious complications and even death associated with catheter ablation arguably offsets the benefit associated with uniform catheter ablation in this population. The low positive predictive value of noninvasive and invasive variables along with the cost also argue against a uniform invasive approach in asymptomatic patients Citation[1]. Nonetheless, an invasive strategy in certain clinical circumstances and in patients who remain concerned about the small risk of life-threatening arrhythmia as a first presentation after a thoughtful discussion of the risks and benefits of an invasive approach is reasonable.
The controversy
The WPW ECG occurs in one to three per 1000 individuals. A substantial portion of this population is asymptomatic – approximately 65% of adolescents and 40% of individuals over 30 years of age Citation[2]. Atrial fibrillation (AF) conducted rapidly over the accessory pathways may result in ventricular fibrillation (VF) and may be the first devastating manifestation in these patients. The risk of AF is low, estimated at 0.9 (95% CI: 0.3–1.8) per 100 person-years of follow-up Citation[3]. The incidence of VF (including aborted) is lower, estimated at 0.2 (95% CI: 0.06–0.4) in children (<18 years), and even lower at 0.09 (95% CI: 0.03–0.2) in adults, per 100 patient-years of follow-up Citation[4]. It is notable that most patients presenting with VF were probably symptomatic prior to VF (thus lending itself to earlier diagnosis and therapy). Also when VF occurs most are aborted (~60%) Citation[2,4,5]. The low risk of death associated with asymptomatic WPW contrasts with the incidence of sudden death in population studies of 0.003–0.02 per 100 person-years in 0–49-year-olds Citation[4,5]. The lower background sudden death rate in the general population argue for attempts to identify at-risk asymptomatic WPW individuals. However, the very low incidence of sudden death in asymptomatic patients poses a great challenge to the specificity and positive predictive value of risk variables. Short preexcited RR interval (SPRRI) during AF is the pivotal variable without which VF is rare. However, the great majority of individuals with WPW, even with SPRRIs of <250 ms, will not experience sudden cardiac death Citation[2,6]. Therefore, identifying the at-risk patient remains a great challenge. Nevertheless, some variables are generally associated with a favorable long-term outcome. The abrupt loss of preexcitation during sympathetic stimulation deems the pathway incapable of robust antegrade conduction. Only abrupt and complete loss of preexcitation confirms fragile antegrade pathway conduction. Persistence of preexcitation should not be interpreted as an accurate predictor for SPRRIs (specificity 17%), with an even lower specificity for VF Citation[7]. Intermittent preexcitation generally also suggests that rapid antegrade conduction is weak Citation[8]. Intermittent preexcitation is estimated to occur in approximately 14% of asymptomatic patients with loss of preexcitation estimated at 2.5 (95% CI: 1.2–4.1) per 100 person-years of follow-up Citation[3]. This may be an underestimation with up to 31% of adults and 0–26% of children reportedly losing preexcitation over 5 years of follow-up Citation[2].
Thus, these facets argue against a population-wide uniform-invasive approach in asymptomatic patients. Inability to clearly demonstrate absolute and abrupt loss of manifest preexcitation (at rest or with exercise) warrants consideration on an individual basis for further testing to invasively evaluate the pathways. However, we need to acknowledge that such testing lacks specificity for predicting VF Citation[2,6].
Noninvasive risk assessment
Certain clinical variables are reportedly associated with a modest risk including male gender, age <30 years, history of AF, multiple pathways (suggested by multiple preexcited morphologies), prior syncope, structural heart disease and familial WPW Citation[2].
Serial ambulatory ECG monitoring should be considered to screen for paroxysmal AF, supraventricular tachycardia and loss of preexcitation, particularly in younger patients who may not be mindful or are incapable of articulating symptoms. Exercise testing should also be undertaken in asymptomatic individuals. Abrupt, complete and clear loss of preexcitation supports a low risk of sudden death. These patients can be reassured. Exercise testing may demonstrate subtle preexcitation that may be difficult to interpret. Apparent loss of preexcitation may occur due to a decrease in conduction time in the atrioventricular (AV) node relative to the pathway; and in particular, when the pathway is further away from the sinus node relative to the AV node and should not be equated to a long pathway refractory period.
When to undertake invasive testing & ablation
In asymptomatic patients where noninvasive testing has been unhelpful, an invasive approach and possible ablation may be offered to well-informed asymptomatic patients who prefer the one-off risk of serious complications or death from a procedure against the remote risk of VF. Furthermore, certain professional and recreational activities may mandate the need for invasive assessment in asymptomatic patients (e.g., pilots and professional athletes). Asymptomatic patients with cardiac comorbidities may also require invasive evaluation as they are less likely to tolerate tachycardia.
Death due to catheter ablation is reported to occur in 0.0–0.2% of cases, though this incidence may be variable in the community and may be under reported Citation[2,4,9]. Complication rates related to invasive electrophysiological testing and ablation range from 1.8 to 8.2% Citation[2,4]. Serious adverse events due to catheter ablation include AV block, cardiac perforation, coronary artery injury and thromboembolic events.
The goals of invasive testing are to characterize both the antegrade and retrograde conduction properties of the pathways, establish locations and assess the ease of inducing sustainable AF and supraventricular tachycardia. As previously mentioned, a SPRRI of <250 ms remains the ‘gold standard’ for assessing risk (despite low specificity). Isoproterenol, which is often used in an attempt to induce tachycardia and/or AF, will cause an even greater percentage of individuals to have SPRRIs of <250 ms. Isoproterenol, which has not been systematically evaluated for its ability to predict VF, has a greater effect on the AV node than on pathways Citation[10]. This differential effect may not uniformly influence the risk of VF, given that ventricular activation over the pathway may be more arrhythmogenic than over the specialized conduction system Citation[11].
Although the abrupt loss of preexcitation with isoproterenol identifies a low-risk pathway, the persistence of preexcitation does not identify a high-risk patient. Patients with decremental conduction also generally have feeble anterograde conduction and generally carry a lower risk. Patients lacking retrograde conduction similarly appear to be at lower risk Citation[2]. Thus, the presence or absence of multiple risk factors in combination would be expected to improve specificity but with the loss of sensitivity for identifying at-risk or low-risk individuals, respectively. The combination of a short pathway antegrade refractory period (<250 ms) and inducible tachycardia had a sensitivity of 94%, specificity of 68%, and positive and negative predictive values of 47 and 97%, respectively, for subsequent arrhythmia (which included supraventricular tachycardia) Citation[12]. A SPRRI <250 ms has been noted in up to a third of asymptomatic adults with WPW Citation[2]. It must be acknowledged that ablating all such patients will be targeting a substantial portion not destined to have life-threatening arrhythmias due to its low specificity.
Invasive testing should not be an impetus to automatically proceed with ablation. Careful deliberation is required to proceed with ablation, based on the location of the accessory pathways and its conduction properties. Acute pathway ablation success rates approach 95% Citation[2]. However, recurrence rates of 5–24% may temper the enthusiasm to ablate asymptomatic patients uniformly Citation[2,9,13]. Especially when pathway location is associated with the potential for higher rates of complications and/or graver consequences (e.g., para-hisian pathways and left-sided pathways) and when pathway/patient characteristics indicate low risk of VF. Cryoablation can be utilized in an attempt to enhance safety, particularly in those with septal pathways.
Special populations
Athletes
Guidelines suggest invasive risk stratification in athletes engaged in competitive sports Citation[2]. Ablation is advised in most asymptomatic athletes even though exercise does not significantly alter the properties of pathways Citation[14]. In those with a high-risk location and those averse to the potential risks, competitive sports can be continued when the pathway is judged to be low risk.
Children
Indications for invasive risk stratification and ablation are generally conservative in children. Supraventricular tachycardia can generally be managed medically. Complication rates may be higher in children with a low body weight. Complications appear to be related to radiofrequency energy dose, lesion number and total application time, indexed for body size. Ablation should be undertaken in experienced centers.
Congenital heart disease
Although the majority have normal anatomy, WPW also occurs in patients with congenital heart disease (commonly Ebstein anomaly) and cardiomyopathy. Supraventricular tachycardia can be hemodynamically compromising in these patients depending on the nature of the structural abnormality. It is reasonable to undertake invasive testing and ablation in these patients, following careful deliberation of any potential higher risks associated with unique anatomy. Ablation should be undertaken in experienced centers depending on the underlying anatomy.
Conclusion
The risk of sudden death as the first presentation in truly asymptomatic patients with WPW is exceedingly small. The risks associated with routine ablation in these patients are likely to offset the small benefit of ablation on a population basis. The very low event rate severely challenges diagnostic variables to accurately risk stratify asymptomatic patients. In certain clinical circumstances, asymptomatic patients may require invasive risk stratification and possible catheter ablation, after thoughtful discussion of the risks and benefits of an invasive approach versus the natural history of WPW.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
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