Thromb Haemost 2012; 108(02): 367-372
DOI: 10.1160/TH11-12-0901
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

NT-pro-BNP levels in patients with acute pulmonary embolism are correlated to right but not left ventricular volume and function

Sharif M. Pasha
1   Department of Thrombosis and Haemostasis, Leiden University Medical Centre, Leiden, The Netherlands
,
Frederikus A. Klok
1   Department of Thrombosis and Haemostasis, Leiden University Medical Centre, Leiden, The Netherlands
,
Noortje van der Bijl
2   Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands
,
Albert de Roos
2   Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands
,
Lucia J. M. Kroft
2   Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands
,
Menno V. Huisman
1   Department of Thrombosis and Haemostasis, Leiden University Medical Centre, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 29 December 2011

Accepted after major revision: 09 May 2012

Publication Date:
25 November 2017 (online)

Summary

N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) is primarily secreted by left ventricular (LV) stretch and wall tension. Notably, NT-pro-BNP is a prognostic marker in acute pulmonary embolism (PE), which primarily stresses the right ventricle (RV). We sought to evaluate the relative contribution of the RV to NT-pro-BNP levels during PE. A posthoc analysis of an observational prospective outcome study in 113 consecutive patients with computed tomography (CT)-proven PE and 226 patients in whom PE was clinically suspected but ruled out by CT. In all patients RV and LV function was established by assessing ECG-triggered-CT measured ventricular end-diastolic-volumes and ejection fraction (EF). NT-pro-BNP was assessed in all patients. The correlation between RV and LV end-diastolic-volumes and systolic function was evaluated by multiple linear regression corrected for known con-founders. In the PE cohort increased RVEF (β-coefficient (95% confidence interval [CI]) –0.044 (± –0.011); p<0.001) and higher RV enddiastolic-volume (β-coefficient 0.005 (± 0.001); p<0.001) were significantly correlated to NT-pro-BNP, while no correlation was found with LVEF ( β-coefficient 0.005 (± 0.010); p=0.587) and LV end-diastolic-volume (β-coefficient –0.003 (± 0.002); p=0.074). In control patients without PE we found a strong correlation between NT-pro-BNP levels and LVEF ( β-coefficient –0.027 (± –0.006); p<0.001) although not LV enddiastolic-volume (β-coefficient 0.001 (± 0.001); p=0.418). RVEF (β-co-efficient –0.002 (± –0.006); p=0.802) and RV end-diastolic-volume (β-coefficient <0.001 (± 0.001); p=0.730) were not correlated in patients without PE. In PE patients, lower RVEF and higher RV end-diastolic-volume were significantly correlated to NT-pro-BNP levels as compared to control patients without PE. These observations provide patho-physiological ground for the well-known prognostic value of NT-pro-BNP in acute PE.

 
  • References

  • 1 Aujesky D, Obrosky DS, Stone RA. et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005; 172: 1041-1046.
  • 2 van der Meer RW, Pattynama PM, van Strijen MJ. et al. Right ventricular dysfunction and pulmonary obstruction index at helical CT: prediction of clinical outcome during 3-month follow-up in patients with acute pulmonary embolism. Radiology 2005; 235: 798-803.
  • 3 Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 2007; 116: 427-433.
  • 4 Klok FA, Djurabi RK, Nijkeuter M. et al. High D-dimer level is associated with increased 15-d and 3 months mortality through a more central localization of pulmonary emboli and serious comorbidity. Br J Haematol 2008; 140: 218-222.
  • 5 Klok FA, Mos IC, Huisman MV. Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis. Am J Respir Crit Care Med 2008; 178: 425-430.
  • 6 Levin ER, Gardner DG, Samson WK. Natriuretic peptides. N Engl J Med 1998; 339: 321-328.
  • 7 Sagnella GA. Practical implications of current natriuretic peptide research. J Renin Angiotensin Aldosterone Syst 2000; 01: 304-315.
  • 8 Dickstein K, Cohen-Solal A, Filippatos G. et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008; 29: 2388-2442.
  • 9 Tulevski II, Hirsch A, Sanson BJ. et al. Increased brain natriuretic peptide as a marker for right ventricular dysfunction in acute pulmonary embolism. Thromb Haemost 2001; 86: 1193-1196.
  • 10 Kucher N, Printzen G, Doernhoefer T. et al. Low pro-brain natriuretic peptide levels predict benign clinical outcome in acute pulmonary embolism. Circulation 2003; 107: 1576-1578.
  • 11 tenWolde M, Tulevski II, Mulder JW. et al. Brain natriuretic peptide as a predictor of adverse outcome in patients with pulmonary embolism. Circulation 2003; 107: 2082-2084.
  • 12 Vuilleumier N, Righini M, Perrier A. et al. Correlation between cardiac biomarkers and right ventricular enlargement on chest CT in non massive pulmonary embolism. Thromb Res 2008; 121: 617-624.
  • 13 Henzler T, Roeger S, Meyer M. et al. Pulmonary embolism: ct signs and cardiac biomarkers for predicting right ventricular dysfunction. Eur Respir J 2012; 39: 919-926.
  • 14 Klok FA, Van Der Bijl N, Eikenboom HC. et al. Comparison of CT assessed right ventricular size and cardiac biomarkers for predicting short-term clinical outcome in normotensive patients suspected of having acute pulmonary embolism. J Thromb Haemost 2010; 08: 853-856.
  • 15 Van Der Bijl N, Klok FA, Huisman MV. et al. Measurement of right- and left ventricular function by ECG-synchronized CT in patients with acute pulmonary embolism: usefulness for predicting short-term outcome. Chest 2011; 140: 1008-1015.
  • 16 Pasha SM, Klok FA, Snoep JD. et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a metaanalysis. Thromb Res 2010; 125: e123-e127.
  • 17 Chartrand-Lefebvre C, Howarth N, Lucidarme O. et al. Contrast-enhanced helical CT for pulmonary embolism detection: inter- and intraobserver agreement among radiologists with variable experience. AJR Am J Roentgenol 1999; 172: 107-112.
  • 18 Dogan H, Kroft LJ, Huisman MV. et al. Right ventricular function in patients with acute pulmonary embolism: analysis with electrocardiography-synchronized multi-detector row CT. Radiology 2007; 242: 78-84.
  • 19 Maffei E, Messalli G, Martini C. et al. Left and right ventricle assessment with Cardiac CT: validation study vs. Cardiac MR. Eur Radiol 2012; 22: 1041-1049.
  • 20 Lorenz CH, Walker ES, Morgan VL. et al. Normal human right and left ventricular mass, systolic function, and gender differences by cine magnetic resonance imaging. J Cardiovasc Magn Reson 1999; 01: 7-21.
  • 21 Souza R, Bogossian HB, Humbert M. et al. N-terminal-pro-brain natriuretic peptide as a haemodynamic marker in idiopathic pulmonary arterial hypertension. Eur Respir J 2005; 25: 509-513.
  • 22 Fijalkowska A, Kurzyna M, Torbicki A. et al. Serum N-terminal brain natriuretic peptide as a prognostic parameter in patients with pulmonary hypertension. Chest 2006; 129: 1313-1321.
  • 23 Nagaya N, Nishikimi T, Uematsu M. et al. Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. Circulation 2000; 102: 865-870.
  • 24 Leuchte HH, Holzapfel M, Baumgartner RA. et al. Characterization of brain natriuretic peptide in long-term follow-up of pulmonary arterial hypertension. Chest 2005; 128: 2368-2374.
  • 25 Agterof MJ, Schutgens RE, Snijder RJ. et al. Out of hospital treatment of acute pulmonary embolism in patients with a low NT-proBNP level. J Thromb Haemost 2010; 08: 1235-1241.
  • 26 Aujesky D, Perrier A, Roy PM. et al. Validation of a clinical prognostic model to identify low-risk patients with pulmonary embolism. J Intern Med 2007; 261: 597-604.
  • 27 Vuilleumier N, Le Gal G, Cornily JC. et al. Is N-terminal pro-brain natriuretic peptide superior to clinical scores for risk stratification in non-massive pulmonary embolism?. J Thromb Haemost 2010; 08: 1433-1435.
  • 28 Dewey M, Muller M, Eddicks S. et al. Evaluation of global and regional left ventricular function with 16-slice computed tomography, biplane cineventriculography, and two-dimensional transthoracic echocardiography: comparison with magnetic resonance imaging. J Am Coll Cardiol 2006; 48: 2034-2044.
  • 29 Guo YK, Gao HL, Zhang XC. et al. Accuracy and reproducibility of assessing right ventricular function with 64-section multi-detector row CT: comparison with magnetic resonance imaging. Int J Cardiol 2010; 139: 254-262.
  • 30 Puls M, Dellas C, Lankeit M. et al. Heart-type fatty acid-binding protein permits early risk stratification of pulmonary embolism. Eur Heart J 2007; 28: 224-229.
  • 31 Vuilleumier N, Le Gal G, Verschuren F. et al. Cardiac biomarkers for risk stratification in non-massive pulmonary embolism: a multicenter prospective study. J Thromb Haemost 2009; 07: 391-398.
  • 32 Kostrubiec M, Pruszczyk P, Bochowicz A. et al. Biomarker-based risk assessment model in acute pulmonary embolism. Eur Heart J 2005; 26: 2166-2172.