Exercise midregional pro-atrial natriuretic peptide (MR-proANP) as a potential diagnostic tool to identify dynamic mitral regurgitation

Abstract Background Growing evidence suggests a clinical impact of dynamic mitral regurgitation (dynMR) which unmasks as severe only during exercise. Severe dynMR leads to an overload of the left atrium and an increase of pulmonary artery wedge pressure (PAWP) during exercise. Purpose We hypothesize that midregional pro-atrial natriuretic peptide (MR-proANP), a biomarker of atrial stress reflects dynamics of PAWP during exercise and might therefore identify dynMR. Methods Patients with suggested dynMR (≥ moderate MR at rest and exercise symptoms) underwent exercise right heart catheterization (eRHC). Healthy controls completed symptom-limited spiroergometry. MR-proANP serum levels were measured at rest and peak exercise, and were correlated to eRHC findings, especially PAWP changes. Subgroups included cohort 0 (controls), cohort 1 (moderate MR at rest, severe on exercise), cohort 2 (moderate at both), and cohort 3 (severe at rest). Results In total 25 MR patients underwent eRHC peak workload 50 (IQR 15 – 75) watt for 7.5 (IQR 6.5 – 9.0) min and 19 controls underwent spiroergometry peak workload 160 (IQR 125 – 195) watt for 12.5 (IQR 11.25 – 16.0) min. The results of MR-proANP measurement at rest and during exercise are illustrated in figure 1. Controls had low levels in the reference range at rest and during exercise. Overall, diseased patients (cohort 1-3) showed higher MR-proANP levels at rest than the control group (p = 0.001) and a higher relative increase during exercise 20 (8 – 42)% vs. 8 (5 – 17)%; p= 0.008). Patients with a significant MR at rest (cohort 3) or during exercise (cohort 1) showed higher MR-proANP levels compared to patients without a relevant MR (cohort 2), at rest (p = 0.015) and during exercise (p = 0.016). MR-proANP levels correlated with PAWP at rest (rs = 0.77; p 0.001) and at peak exercise (rs = 0.47; p = 0.017). Patients with no severe MR neither at rest nor during exercise, however showed a jump of the median PAWP at rest from 9 (7 -11) mmHg to 18 (16 – 24) mmHg during exercise and an excessive exercise dependent relative increase of the MR-proANP-level 42 (18 – 47) mmHg. Conclusion This study assessed exercise biomarker measurement as a new diagnostic approach in the context of exercise diagnostics. Exercise MR-proANP levels clearly discriminate healthy against diseased individuals. Patients with a significant MR seem to have elevated MR-proANP levels both at rest and at exercise. Excessive isolated exercise dependent dynamics of MR-proANP identify patients with isolated exercise dependent left atrial stress, likely due to various reasons.