Heart
failure (HF), a complex clinical syndrome, has become a global
burden on health and economics around the world. Phlegm-blood stasis
syndrome, one of the Traditional Chinese Medicine (TCM) syndrome differentiation,
is the core pathogenesis dynamically throughout the occurrence, development,
and prognosis of HF. Biomarkers having high sensitivity and specificity
are highly demanded to facilitate the accurate differentiation of
HF patients with phlegm-blood stasis syndrome. In the present study,
serum samples were collected from 20 healthy controls and 40 HF patients
(20 with and 20 without phlegm-blood stasis syndrome). We implemented
data-independent acquisition mass spectrometry (DIA-MS) for discovery
and parallel reaction monitoring (PRM) for validation of biomarkers
for heart failure with phlegm-blood stasis syndrome. A total of 84
different proteins were found in the HF with phlegm-blood stasis syndrome
(HF-TY) group compared with healthy controls. 37 candidate proteins
were selected for the PRM assay, and five validated proteins with
high sensitivity and specificity, including insulin-like growth factor-binding
protein 4 (IGFBP4), β-2-microglobulin (B2M), dystroglycan (DAG1),
immunoglobulin J chain (JCHAIN), and kallikrein B1 (KLKB1), were considered
potential biomarkers for heart failure patients with phlegm-blood
stasis syndrome. Newly identified biomarkers might provide insights
into the diagnosis and treatment of HF with TCM syndrome differentiation.