Mid-regional pro-atrial natriuretic peptide and copeptin as indicators of disease severity and therapy response in CTEPH

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) leads to right heart failure. Pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) restore pulmonary haemodynamics and allow cardiac recovery. This study examined the relationship of copeptin and mid-regional pro-atrial natriuretic peptide (MR-proANP) levels to disease severity and therapy response. METHODS: This observational cohort study included 125 patients (55 PEA/70 BPA) who underwent treatment and completed a 6-/12-month follow-up. Biomarkers, measured at baseline, prior to every BPA and at follow-up, were compared to 1) severe disease at baseline (right atrial pressure (RAP) ≥8 mmHg and cardiac index ≤2.4 L·min(−1)·m(−2)) and 2) optimal therapy response (no persistent pulmonary hypertension combined with a normalised RAP (mean PAP ≤25 mmHg, pulmonary vascular resistance (PVR) ≤3 WU and RAP ≤6 mmHg) or a reduction in mean PAP ≥25%, PVR ≥35% and RAP ≥25%). RESULTS: Severely diseased patients had higher levels of MR-proANP (320 (246–527) pmol·L(−1) versus 133 (82–215) pmol·L(−1); p=0.001) and copeptin (12.7 (7.3–20.6) pmol·L(−1) versus 6.8 (4.4–12.8) pmol·L(−1); p=0.015) at baseline than the rest of the cohort. At baseline, MR-proANP (area under the curve (AUC) 0.91; cut-off value 227 pmol·L(−1); OR 56, 95% CI 6.9–454.3) and copeptin (AUC 0.70; cut-off value 10.9 pmol·L(−1); OR 1.5, 95% CI 1.2–1.9) identified severely diseased patients. After PEA/BPA, levels of MR-proANP (99 (58–145) pmol·L(−1); p<0.001) and copeptin (6.3 (3.7–12.6) pmol·L(−1); p=0.009) decreased and indicated optimal therapy response (MR-proANP <123 pmol·L(−1) (AUC 0.70) and copeptin <10.1 pmol·L(−1) (AUC 0.58)). CONCLUSION: MR-proANP and copeptin levels are affected in CTEPH and decrease after therapy. MR-proANP identifies a severe disease status and optimal therapy response.