Increased Plasma Pyruvate Kinase M2 (PK‐M2) in Heart Failure: A Novel Biomarker Related to Cardiac Function and its Clinical Implications

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.