Eosinophil-Linked Hyperdynamic Circulation in EGPA Improves under Anti-IL-5 Therapy: A Longitudinal Study

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Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by eosinophilic inflammation and potential cardiovascular involvement. While pulmonary hypertension (PH) is uncommon, the relationship between eosinophil burden and subclinical pulmonary vascular dysfunction remains unclear. Methods: We conducted a single-centre longitudinal study of 27 EGPA patients to evaluate the association between peripheral eosinophil counts (PEC) at diagnosis and echocardiographic markers of hyperdynamic circulation and early right ventricular-pulmonary artery (RV-PA) uncoupling. Patients starting anti-IL-5 therapy (mepolizumab/benralizumab) underwent echocardiographic assessments, including pulmonary artery systolic pressure (PAPs), tricuspid annular plane systolic excursion (TAPSE), TAPSE/PAPs ratio, and tricuspid regurgitation velocity (TRV) at three timepoints: baseline (at diagnosis), at therapy initiation (T0), and 24 months after (T24). Patients were stratified by median PEC at diagnosis. Multivariable regression and ROC analysis were used to explore associations and predictive thresholds. Results: At T0, 33% of patients exhibited elevated PAPs (>25 mmHg), without clinical PH. Higher PEC were significantly associated with elevated PAPs levels (p = 0.044) and decreased TAPSE/PAPs ratio (p = 0.037). Longitudinal analysis at baseline and T0 showed significant worsening in PAPs and TRV values, with improvement at T24 after anti-IL-5 therapy (PAPs Δ = −7.1 mmHg, p = 0.001; TRV Δ = −0.35 m/s, p = 0.005; TAPSE/PAPs Δ = +0.41 ± 0.55; p = 0.005). ROC analysis identified an eosinophil threshold of 3,465 cells/μL (AUC = 0.696; sensitivity = 91.7%) as potential predictor of elevated PAPs. Conclusions: Elevated PEC may signal early pulmonary vascular dysfunction and RV–PA uncoupling EGPA, which may be partially reverted with the anti-IL-5 therapy. These findings support the importance of early cardiovascular surveillance in eosinophil-rich EGPA phenotypes.

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