Clinical consequences of atrial fibrillation in pulmonary arterial hypertension: insights from a large real-world cohort
M Ahmed, A Aglan, S Das, C Shah, S Elattar, A Fath, D Frenkel, G Lanier, S Iwai, J JacobsonAbstract
Background
Pulmonary arterial hypertension (PAH) is a progressive vasculopathy with high morbidity and mortality. Atrial fibrillation (AF) is common in PAH and associated with clinical deterioration, but its prognostic impact in PAH patients is not well defined.
Purpose
To describe the clinical course and long-term outcomes of patients with PAH who develop AF compared with those who remain in sinus rhythm.
Methods
We performed a retrospective cohort study using TriNetX, a large multi-centre electronic health record network. Adults with World Health Organization Group 1 PAH between 2015 and 2025 were included if they had a PAH diagnosis, right heart catheterisation, and at least one PAH-specific therapy. Patients were stratified by AF status: PAH with AF documented from 1 year before to 1 year after PAH therapy initiation (PAH–AF+) versus no AF recorded at any time (PAH–AF−). Time zero was 1 year after PAH therapy initiation, with follow-up to 5 years. Propensity-score matching (1:1) balanced demographics, comorbidities, PAH therapies, and laboratory values. The primary outcome was all-cause mortality. Secondary outcomes were all-cause hospitalisation, acute heart failure (HF), cardiogenic shock, intensive care unit (ICU) admission, ischaemic stroke, new dialysis, hepatic failure, and lung transplantation.
Results
We identified 20,420 patients with PAH, of whom 5,837 met criteria for PAH–AF+ and 12,291 for PAH–AF−. After matching, 3,904 patients were included in each group with well-balanced baseline characteristics. Over a mean follow-up of approximately 3 years, AF was associated with higher all-cause mortality (19.0% vs 16.9%; odds ratio [OR] 1.15, 95% confidence interval [CI] 1.03–1.30; p=0.02) and increased risks of hospitalisation (46.5% vs 37.0%; OR 1.48; p<0.001), acute HF (29.0% vs 16.1%; OR 2.14; p<0.001), cardiogenic shock (8.3% vs 4.5%; OR 1.91; p<0.001), ICU admission (21.9% vs 15.8%; OR 1.50; p<0.001), ischaemic stroke (7.1% vs 4.8%; OR 1.52; p<0.001), new dialysis (4.5% vs 2.5%; OR 1.88; p<0.001), and hepatic failure (1.7% vs 1.0%; OR 1.67; p=0.01). Lung transplantation did not differ significantly between groups.
Conclusions
In a large, rigorously defined PAH cohort, AF occurring around the time of PAH therapy initiation identified a high-risk subgroup with greater mortality, clinical decompensation, and multi-organ dysfunction despite similar baseline profiles after matching. AF in PAH appears to be both a marker of advanced disease and a potential driver of further deterioration, underscoring the need for early recognition, careful haemodynamic monitoring, and dedicated rhythm-management strategies in this vulnerable population.Clinical Outcomes