Abstract
BACKGROUND: The purpose of this study was to investigate whether circulating pyruvate kinase M2 (PK-M2) levels are elevated in the peripheral blood and to assess their association with diagnosis and prognosis in patients with heart failure (HF). METHODS AND RESULTS: We conducted a prospective investigation involving 222 patients with HF and 103 control subjects, measuring PK-M2 concentrations using ELISA. The primary outcome, assessed over a median follow-up of 2 years (interquartile range: 776 to 926 days), was the time to the first occurrence of either rehospitalization for worsening HF or cardiovascular death. Patients with HF had higher PK-M2 levels than controls (17.4±4.1 versus 7.8±2.3 U/mL, P <0.001), and these levels correlated with HF severity (New York Heart Association cardiac function class). Patients with reduced left ventricular ejection fraction had higher PK-M2 concentrations than those with preserved ejection fraction (18.3±4.5 versus 16.7±3.6 U/mL, P <0.01). In a subset of patients with HF (n=52), PK-M2 levels significantly decreased following standardized HF treatment (mean difference, -4.3±0.5 U/mL, P <0.001). A high PK-M2 level had a 1.913-fold higher risk of the primary outcome (P=0.033) after adjusting for multiple cardiovascular risk factors, but not with cardiovascular death. Additionally, PK-M2 added incremental prognostic value beyond clinical predictors and N-terminal pro-brain natriuretic peptide (P <0.05). CONCLUSIONS: Elevated PK-M2 levels are associated with primary outcomes and rehospitalization for worsening heart failure in patients with HF. These findings suggest that PK-M2 is a potential biomarker for HF diagnosis and prognosis, warranting consideration for serial patient assessment.