Serial measurements of midregion proANP and copeptin in ambulatory patients with heart failure: Incremental prognostic value of novel biomarkers in heart failure

Background: Disease progression in heart failure (HF) reflects derangements in neurohormonal systems, and biomarkers of these systems can help to establish the diagnosis and assess the prognosis. Serial measurements of the precursor peptides of the natriuretic and vasopressin systems (midregional proatrial natriuretic peptide (MR-proANP) and C-terminal provasopressin (copeptin), respectively) should add incremental value to risk stratification in ambulatory patients with HF. Methods and results: A cohort of 187 patients with class III-IV HF was prospectively enrolled, with biomarkers collected every 3 months over 2 years and analysed in relation to death/transplantation. Time-dependent analyses (dichotomous and continuous variables) showed that increases in MR-proANP (HR 7.6, 95% CI 1.85 to 31.15, p<0.01) and copeptin (HR 2.7, 95% CI 1.27 to 5.61, p=0.01) were associated with increased risk, but, in multivariate analysis adjusted for troponin T (cTnT) ≥0.01 ng/ml, only raised MR-proANP remained an independent predictor (HR 5.49, 95% CI 1.31 to 23.01, p=0.02). Combined increases in MR-proANP and copeptin (HR 9.01, 95% CI 1.24 to 65.26, p=0.03) with cTnT (HR 11.1, 95% CI 1.52 to 80.85, p=0.02), and increases ≥30% above already raised values identified the patients at greatest risk (MR-proANP: HR 10.1, 95% CI 2.34 to 43.38, p=0.002; copeptin: HR 11.5, 95% CI 2.74 to 48.08, p<0.001). Conclusions: A strategy of serial monitoring of MR-proANP and, of lesser impact, copeptin, combined with cTnT, may be advantageous in detecting and managing the highest-risk outpatients with HF.