Research Article: Angiopoietin-2 in Adults with Congenital Heart Disease and Heart Failure

Date Published: June 24, 2013

Publisher: Public Library of Science

Author(s): Alexander Lukasz, Gernot Beutel, Philipp Kümpers, Agnieszka Denecke, Mechthild Westhoff-Bleck, Bernhard Schieffer, Johann Bauersachs, Jan T. Kielstein, Oktay Tutarel, Rajesh Gopalrao Katare.


Chronic heart failure is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD). While NT-proBNP is an established biomarker for heart failure of non-congenital origin, its application in ACHD has limitations. The angiogenic factors Angiopoietin-1 and -2 (Ang-1, Ang-2), vascular endothelial growth factor (VEGF), and soluble receptor tyrosine kinase of the Tie family (sTie2) correlate with disease severity in heart failure of non-congenital origin. Their role in ACHD has not been studied.

In 91 patients Ang-2 and NT-proBNP were measured and related to New York Heart Association class, systemic ventricular function and parameters of cardiopulmonary exercise testing. Ang-1, VEGF, and sTie2 were also measured.

Ang-2 correlates with NYHA class and ventricular dysfunction comparable to NT-proBNP. Further, Ang-2 showed a good correlation with parameters of cardiopulmonary exercise testing. Both, Ang-2 and NT-proBNP identified patients with severely limited cardiopulmonary exercise capacity. Additionally, Ang-2 is elevated in patients with a single ventricle physiology in contrast to NT-proBNP. VEGF, Ang-1, and sTie2 were not correlated with any clinical parameter.

The performance of Ang-2 as a biomarker for heart failure in ACHD is comparable to NT-proBNP. Its significant elevation in patients with single ventricle physiology indicates potential in this patient group and warrants further studies.

Partial Text

Chronic heart failure (CHF) is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD) [1]. Heart failure symptoms may not always correlate with objective measures like systemic ventricular function or parameters of cardiopulmonary exercise testing [2], [3]. The rarity of individual malformations and the complex anatomy and physiology make assessing the cardiac function difficult [4]. Therefore, the prevalence of heart failure in these patients is underappreciated [5], [6]. A simple investigation like a blood test to detect early stages of heart failure and predict those at risk of deterioration would be valuable [4]. B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are established biomarkers for diagnosis and management of heart failure due to acquired heart disease [7]. Unfortunately, the clinical use of those markers in adults with congenital heart disease is limited [8], [9]. Therefore diagnosis and treatment monitoring is frequently based on cardiopulmonary exercise testing [4], [6], [10], [11], which is time consuming and not feasible in special patient groups.

Ninety-one patients were included in this cross-sectional study. Ang-1, VEGF and Tie2 could only be analyzed in 80 patients. Table 1 and Table 2 show the clinical characteristics of the study population. Cardiopulmonary exercise testing was performed in 70 patients. Five of these performed a submaximal exercise test (respiratory exchange ratio <1.05) and were excluded from analysis. Nine patients were cyanotic. Out of these three had an exercise test. The values for EQCO2 were not used in these patients since EQCO2 is not a marker of prognosis in cyanotic patients. This is the first study to evaluate the role of circulating endothelial factors in adults with congenital heart disease. Ang-2 correlated with parameters of heart failure like NYHA classes and ventricular function. Furthermore, there was a good correlation between Ang-2 and parameters of cardiopulmonary exercise testing. Interestingly, elevated Ang-2 levels were found in patients with a single ventricle physiology. Source: