Incident atrial fibrillation and pyoderma gangrenosum: long-term thromboembolic, heart failure, and mortality risk

BACKGROUND: Systemic inflammation is increasingly linked to atrial arrhythmogenesis, yet arrhythmic risk and downstream cardiovascular complications remain poorly quantified for inflammatory diseases managed outside cardiology, including neutrophilic dermatoses such as pyoderma gangrenosum (PG). METHODS: We performed a global, large retrospective cohort study, including 147 healthcare organizations. Adults were included in three separate 1:1 propensity score-matched cohorts: (1) PG vs non-PG to assess incident AF and relevant arrhythmogenic heart disease; (2) PG with vs without AF to examine AF-related outcomes within PG; and (3) AF with vs without PG to examine the impact of PG within AF. Patients were followed for up to 5 years. Cox proportional hazards models, 90-day sensitivity analyses, and negative control outcomes enhance robustness. RESULTS: Among 11,351 adults with PG and 2,132,938 without PG, matching yielded 11,216 well-balanced in each cohort. PG was associated with higher 5-year AF incidence (HR 1.61, p < 0.001). Among 1286 PG patients with AF and 10,834 without AF, 1133 pairs were matched. In the PG population, AF was associated with higher risks of systemic thromboembolism (HR 2.26, p < 0.001), heart failure (HR 4.19, p < 0.001), and all-cause mortality (HR 1.59, p < 0.001). In the AF population (1286 AF patients with PG; 2,400,413 without PG), PSM yielded 1265 pairs. PG was associated with increased systemic embolism (HR 2.03, p < 0.001), heart failure (HR 2.17, p < 0.001), and mortality (HR 1.53, p < 0.001). Negative control outcomes were consistently null; Cox proportional hazards models and sensitivity analyses showed similar patterns. CONCLUSIONS: PG was associated with increased incident AF and, among patients with AF, identified a high-risk phenotype with substantially higher thromboembolic events, heart failure, and mortality.