Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome characterized by heart failure symptoms despite preserved left ventricular ejection fraction. Its nonspecific presentation, overlapping comorbidities, variable natriuretic peptide levels, and lack of disease-defining biomarkers contribute to underdiagnosis and misclassification. Plasma extracellular vesicle proteomics may provide stable and disease-relevant molecular information for HFpEF-related phenotype classification.