Original Research

Association of Atrial Fibrillation and/or Flutter With Adverse Cardiac Outcomes and Mortality in Patients With Wolff-Parkinson-White Syndrome

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Background: Wolff-Parkinson-White (WPW) syndrome is characterized by the presence of accessory pathways and development of potentially malignant arrhythmias that can lead to sudden cardiac death. We aimed to determine the impact of atrial fibrillation and/or flutter (AF/AFL) on adverse cardiac outcomes and mortality in patients with WPW syndrome.

Methods: This study identified a cohort of Military Health System patients with WPW syndrome from January 1, 2014, to December 31, 2019. The cohort was divided into 2 subgroups by the presence or absence of AF/AFL. Cardiac composite outcome and mortality were assessed. Kaplan-Meier curves were constructed to assess the bivariate association between exposure and these 2 study outcomes. Cox proportional models were used to estimate the hazard ratios and 95% CIs associated with the cardiac composite outcome and mortality.

Results: Of 35,539 patients included in the study, 19,961 were female (56.2%), the mean (SD) age was 62.9 (18.0) years, and 5291 patients (14.9%) had AF/AFL. The cardiac composite outcome and mortality incidence rates per 100 person-years in the AF/AFL vs non-AF/AFL subgroups were 8.18 vs 4.90, and 4.09 vs 2.13, respectively (P < .001). There were 3130 (8.8%) deaths. After adjusting for confounding variables, the AF/AFL subgroup maintained a 12% and 16% higher association with the composite outcome and mortality, respectively.

Conclusions: Patients with WPW syndrome and AF/AFL have a higher association with adverse cardiac outcomes and death. Consideration for more aggressive electrophysiology screening and ablation strategies may be warranted in this population.


 

References

Wolff-Parkinson-White (WPW) syndrome is characterized by the presence of ≥ 1 accessory pathways and the development of both recurrent paroxysmal atrial fibrillation (AF) and supraventricular tachycardia that can lead to further malignant arrhythmias resulting in sudden cardiac death (SCD).1-7 Historically, incidental, ventricular pre-excitation on electrocardiogram has conferred a relatively low SCD risk in adults; however, newer WPW syndrome data suggest the endpoint may not be as benign as previously thought.7 The current literature has defined atrioventricular reentrant tachycardia triggering AF, rather than symptoms, as an independent risk factor for malignant arrhythmias. Still, long-term data detailing the association of AF with serious cardiac events and death in patients with WPW syndrome are still limited.1-7

While previous guidelines for the treatment of WPW syndrome only recommended routine electrophysiology testing (EPT) with liberal catheter ablation for symptomatic individuals, the 2015 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines now suggest its potential benefit for risk stratification in the asymptomatic population.8-12 Given the limited existing data, more long-term studies are needed to corroborate the latest EPT recommendations before routinely applying them in practice. Furthermore, since concomitant AF can lead to adverse cardiac outcomes in patients with WPW syndrome, additional data evaluating this association are also necessary. In this study, we aimed to determine the impact of atrial fibrillation and/or flutter (AF/AFL) on adverse cardiac outcomes and mortality in patients with WPW syndrome.

METHODS

This study used data from the Military Health System (MHS) Database Repository. The MHS is one of the largest health care systems in the country and includes information on about 10 million active duty and retired military service members and their families (51% male; 49% female).13,14 Data were fully anonymized and complied in accordance with federal and state laws, including the Health Insurance Portability and Accountability Act of 1996. The Naval Medical Center Portsmouth Institutional Review Board approved this study.

Study Design

This retrospective, observational cohort study identified MHS patients with WPW syndrome from January 1, 2014, to December 31, 2019. Patients were included if they had ≥ 2 International Classification of Diseases, Ninth Revision (ICD-9) or International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes for WPW syndrome (ICD-9, 426.7; ICD-10, I45.6) on separate dates; were aged ≥ 18 years at index date; and had ≥ 1 year of continuous eligibility prior to the index date (enrollment gaps ≤ 30 days were considered continuous). Patients were then divided into 2 subgroups by the presence or absence of AF/AFL using diagnostic codes. Patients were excluded if they had evidence of an implantable cardioverter-defibrillator, permanent pacemaker or were missing age or sex data. Patients were followed from index date until the first occurrence of the outcome of interest, MHS disenrollment, or the end of the study period.

Cardiac composite outcomes comprised of sudden cardiac arrest (SCA), ventricular fibrillation (VF), ventricular tachycardia and death, as well as death specifically, were the outcomes of interest and assessed after index date using ICD-9 and ICD-10 codes. Death was defined as all-cause mortality. Time to event was calculated based on the date of the initial component from the composite outcome and date of death specifically for mortality. Those not experiencing an outcome were followed until MHS disenrollment or the end of the study period.

Various patient characteristics were assessed at index including age, sex, military sponsor (the patient’s active or retired duty member through which their dependent receives TRICARE benefits) rank and branch, geographic region, type of US Department of Defense beneficiary, and index year. Clinical characteristics were assessed over a 1-year baseline period prior to index date and included the number of cardiologist and clinical visits for WPW syndrome, Charlson Comorbidity Index (CCI) scores calculated from diagnostic codes outlined in the Quan coding method, and preindex time.15 Comorbidities were assessed at baseline and defined as having ≥ 1 ICD-9 or ICD-10 code for a corresponding condition within 1 year prior to index.

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