Prognostic value of N-terminal pro C-type natriuretic peptide in heart failure patients with preserved and reduced ejection fraction

Aims: A-type and B-type natriuretic peptides are established markers in chronic heart failure (HF). C-type natriuretic peptide (CNP) belongs to the same peptide family, but is predominantly localized in the endothelium. The prognostic role of CNP in heart failure has not been established. The aim of the study was to determine the prognostic power and clinical correlates of the N-terminal part of pro CNP (NT-proCNP) in patients with chronic HF. Methods and results: In 567 hospitalized heart failure patients, NT-proCNP levels were measured at hospital discharge. The primary endpoint was a combined endpoint of all-cause mortality and HF hospitalization after 18 months. Heart failure with a preserved ejection fraction (HFpEF) was pre-defined as an LVEF > 40%. Mean (±SD) age was 71 ± 11 years, 62% were male, mean LVEF was 32 ± 14%, and 23% had HFpEF. In multivariate linear regression, NT-proCNP levels showed a positive correlation with NT-proBNP levels and parameters of renal function, whereas a negative correlation with female sex and vascular endothelial growth factor was observed. After 18 months follow-up, 240 patients reached the combined endpoint. We observed interaction between NT-proCNP and LVEF for outcome (P = 0.046). Multivariate analyses revealed NT-proCNP to be strongly predictive for the primary endpoint [hazard ratio (HR) 1.78, 95% confidence interval (CI) 1.18–2.67, P = 0.006) in patients with HFpEF, but not in patients with a reduced ejection fraction (HFrEF) (HR 1.07, 95% CI 0.81–1.43, P = 0.616). Finally, reclassification showed significant additive value in patients with HFpEF (P  <  0.001), but not in those with HFrEF (P = 0.453). Conclusion: NT-proCNP is a strong independent marker for outcome in patients with HFpEF, but not in those with HFrEF.