Neuroendocrine activation and diagnostics in pulmonary embolism: Translational studies.

Acute pulmonary embolism (PE) is a severe and potentially fatal disease which acutely augments the right ventricle (RV) strain. Development of RV dysfunction (RVD) in the disease process is synonymous with an overall poor prognosis. The diagnosis of PE is usually established by a combination of clinical assessment, D-dimer test and medical imaging with either lung scintigraphy or pulmonary multidetector computer tomography (MDCT) angiography. Which of the two methods to use in PE diagnostic has not been determined and very limited data comparing these modalities are available. Assessment of RV function is cumbersome due to complex geometry. RVD is usually established by echocardiography which is observer dependent, has low reproducibility, and requires expertise. Therefore, a simple and reproducible biochemical method to assess RVD in patients with PE would be desirable. Brain natriuretic peptide (BNP), pro-atrial natriuretic peptide (pro-ANP), cardiac troponin I (TnI), and endothelin-1 (ET-1) have been the most studied plasma biomarkers in the context of risk stratification in PE. BNP is mainly produced in the ventricles of the heart. It is released from the left ventricle in response to increased filling pressure and is increased in chronic left heart failure. Pro-ANP is primarily produced in the atria, is released by atrial distention and is elevated in chronic pulmonary hypertension and could be an early marker for RVD. Plasma level of ET-1 has been shown to correlate with pulmonary pressure and is released from endothelial cells in the pulmonary vessels. Additionally, increases in circulating levels of ET-1 have been reported in an experimental animal model of PE. TnI is part of a complex of regulatory proteins in the cardiac myofilaments and is released upon myocyte injury. It is related to short term clinical outcome, prolonged hypotension, and cardiogenic shock after myocardial infarction and is a predictor of 30-day mortality and RVD using echocardiography in patients with PE. Our hypothesis was therefore that the neuroendocrine activation of BNP, pro-ANP, ET-1, and TnI alone or in combination could serve as markers of RVD in patients with PE. The use of plasma biomarkers would be much simpler than reproducible medical imaging methods such as magnetic resonance imaging (MRI), radionuclide based methods etc.