D1.506 - Mast cell activation and type 2 inflammation in heart failure with preserved ejection fraction: a pilot cross-sectional study

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a systemic inflammatory syndrome. We aimed to explore the association between markers of mast cell activation and type 2 inflammation and clinical and echocardiographic features of HFpEF.¹⁻⁴

In this single-centre, observational cross-sectional pilot study, 15 consecutive, clinically stable patients with HFpEF (left ventricular ejection fraction ≥50%) were enrolled. Allergic comorbidities were assessed using structured clinical history. Laboratory evaluation included baseline serum tryptase, total immunoglobulin E (IgE), peripheral eosinophil count, and N-terminal pro–B-type natriuretic peptide (NT-proBNP). Echocardiography assessed indices of diastolic dysfunction and filling pressures, including E/e′ ratio and left atrial volume index, as well as estimates of pulmonary pressures when available. Functional status was evaluated using New York Heart Association (NYHA) class and 6-minute walk distance (6MWD). Markers of mast cell activation and type 2 inflammation were detectable in the study population, with a relevant proportion of patients reporting allergic comorbidities.

Higher baseline serum tryptase levels were associated with worse diastolic function, reflected by higher E/e′ ratios, and reduced functional capacity, reflected by shorter 6MWD. Exploratory associations were also observed between eosinophil counts, IgE levels, and selected HFpEF severity markers. Given the pilot nature and limited sample size, all analyses were considered hypothesis-generating.⁵⁻⁸

In this pilot cohort, markers of mast cell activation and type 2 inflammation showed exploratory associations with diastolic dysfunction and functional impairment in HFpEF, supporting the hypothesis of an immuno-allergic HFpEF phenotype.¹,⁵,⁹