Exercise MR-proANP unmasks latent right heart failure in CTEPH

Abstract

Abstract Background Chronic right heart failure is the major determinant of outcome in chronic thromboembolic pulmonary hypertension (CTEPH). Thus, its early detection is crucial for optimal patient management. Hemodynamic assessment with invasive right heart catheterization and the measurement of natriuretic peptides at rest are established diagnostic tools in this context. An elevated right atrial pressure (RAP) is a sensitive parameter of right right heart failure. Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a natriuretic peptide that reflects right atrial stress levels. There is a growing recognition of exercise diagnostics in the assessment of right heart failure, particularly in patients with normal or borderline findings at rest. There are no data on the dynamics of MR-proANP in correlation to RAP during physical exercise. Purpose The present study was designed to investigate the dynamics of RAP and MR-proANP during physical exercise in patients with CTEPH and to determine whether these parameters might serve as a tool to measure exercise-dependent atrial stress as an indicator of right heart failure. Methods This observational cohort study included 100 CTEPH patients who underwent right heart catheterization during physical exercise (eRHC). Blood samples for MR-proANP measurement were taken prior, during, and after eRHC. MR-proANP levels were correlated to RAP levels at rest, at peak exercise (eRAP), and during recovery. RAP at rest ≤7 mmHg was defined as normal and eRAP >15 mmHg as suggestive of right heart failure. Results During eRHC mean RAP increased from 6±4 mmHg to 16±7 mmHg (p<0.001). MR-proANP levels and dynamics correlated with RAP at rest (rs=0.61; p<0.001; figure 1a) and at peak exercise (rs=0.66; p<0.001; Figure 1b). Furthermore, the relative percent increase in MR-proANP correlated with the relative percent increase in eRAP (rs=0.52; p<0.001; Figure 1c) Logistic regression analysis revealed the peak MR-proANP level (B=0.058; p=0.004) and the right atrial area (B=0.389; p<0.001) to be associated with eRAP dynamics. A peak MR-proANP level ≥139 pmol/L (AUC=0.81) and recovery level ≥159 pmol/L (AUC=0.82) predicted an eRAP >15 mmHg. Physical exercise unmasked RH failure in 39% of patients with normal RAP at rest; they were also characterized by a more distinct increase in MR-proANP levels (p=0.005) and higher peak (p<0.001) and recovery levels (p<0.001). Conclusions RAP and MR-proANP dynamics unmask manifest and latent right heart failure in CTEPH patients, which may be useful in estimating prognosis. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): SFB 1213 area CP-01 projectWilliam G. Kerckhoff-FoundationKerckhoff Heart Research Institute (KHFI)German Center for Cardiovascular Research (DZHK)