1Kerckhoff Klinik GmbH Abteilung für Kardiologie Bad Nauheim, Deutschland; 2Justus-Liebig-Universität Giessen Franz-Groedel-Institut (FGI) Bad Nauheim, Deutschland; 3Universitätsklinikum Gießen und Marburg GmbH Medizinische Klinik I - Kardiologie und Angiologie Gießen, Deutschland
Background: Hemodynamic measurements during exercise may unmask pathologies not recognizable at rest in patients with unexplained dyspnea. This may be helpful especially if echocardiography shows some degree of mitral regurgitation (MR). Right heart catheterization (RHC) may unmask significant MR by an abnormal rise of pulmonary artery wedge pressure (PAWP) during exercise. However, this is an invasive procedure and not widely available. Therefore, alternative tools for the diagnosis of left atrial stress pathophysiology are desirable. We hypothesized that the release of mid-regional proatrial natriuretic peptide (MR-proANP), a protein biomarker that reflects atrial stress levels, may be helpful as a surrogate for a significant increase of PAWP during exercise.
Methods: A total of 42 patients referred to our tertiary center for evaluation of MR using exercise RHC were included. The main inclusion criterion was the expected ability to perform bicycle exercise for more than 5 minutes during RHC. Blood samples for biomarker analysis were drawn immediately before starting exercise and immediately before the end of exercise, and hemodynamic measurements were performed in parallel. Resting and exercise measurements of MR-proANP were used to investigate associations between biomarker levels and the following outcome by logistic regression analysis: exercise PAWP > 25 mmHg.
Results: Patients had a mean age of 63 years (± 13), a median body mass index of 25 kg/m2 (IQR 23-28), 64% were male, 64% presented with symptoms according to NYHA class II or III, and median NT-proBNP serum level was 482 pg/ml (IQR 168-1064). Normal left ventricular ejection fraction was present in 71% of the patients, and 90% had moderate to severe or severe MR. Median RHC workload was 50 W (IQR 25-75), and median exercise duration was 11 min. (8.9-14). MR-proANP levels showed a significant rise during exercise. Furthermore, the association between MR-proANP levels and the outcome was significant both at rest and during exercise. Associations with the greatest AUC in ROC analysis were for the binary outcome exercise PAWP > 25 mmHg: MR-proANP at rest (OR 1.013, 95%CI 1.005-1.023; p=0.004; AUC 0.84, p=0.0002) and MR-proANP during exercise (OR 1.012, 95%CI 1.005-1.022; p=0.005; AUC 0.81, p=0.0006). Both associations were independent of baseline NT-proBNP levels and MR severity.
Conclusions: In our cohort of patients with MR undergoing exercise RHC, MR-proANP at rest and during exercise was significantly associated with a rise in exercise PAWP using a predefined threshold. MR-proANP measurements may be used to identify increased disease severity and to support therapeutic decisions in patients with MR. This approach merits further investigation to potentially reduce the need for invasive procedures.