Atrial Arrhythmia and Anticoagulant Risks in Tetralogy of Fallot and Pulmonary Atresia with Intact Ventricular Septum

Background Adults with complex congenital heart disease (CHD), including tetralogy of Fallot (ToF) and pulmonary atresia with intact ventricular septum (PA-IVS), have a high prevalence of atrial fibrillation and flutter (AF). Objectives To evaluate thromboembolic and major bleeding risks in adults with ToF and PA-IVS and AF and compare bleeding outcomes between warfarin and direct oral anticoagulants (DOACs). Methods We conducted a retrospective cohort study of adults with Tetralogy of Fallot with pulmonary stenosis (TOF-PS), Tetralogy of Fallot with pulmonary atresia (TOF-PA), or PA-IVS treated for AF at Mayo Clinic sites from 1999 to 2023. Primary outcomes were thromboembolic events (stroke, transient ischemic attack, or systemic embolism) and major bleeding. Cox regression was used to identify clinical and echocardiographic predictors, controlling for age. Anticoagulant-associated bleeding was evaluated using multivariable Cox models. Results Among 300 patients (mean follow-up 7.9 years), 12 thromboembolic events occurred (5.23 per 1,000 person-years). CHA 2 DS 2 -VASc score predicted thromboembolism (c-statistic 0.78). Sixty-nine major bleeding events occurred (3.74 per 100 person-years). Bleeding risk was higher in ToF-PA than ToF-PS(HR 2.05; p=0.005) and in patients with prior Waterston shunts, RA pressure elevation, and RV dysfunction. DOAC use was associated with a higher bleeding risk compared with warfarin (adjusted HR 5.77; p<0.001). HAS-BLED demonstrated poor discrimination (c-statistic 0.59). Conclusions In adults with ToF and PA-IVS and AF, DOAC therapy was associated with substantially higher major bleeding risk than warfarin. CHA 2 DS 2 -VASc effectively predicted thromboembolism, whereas HAS-BLED performed poorly. Congenital- and right heart–specific factors should inform anticoagulation decisions in this high-risk population.