Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in Patients with Neuroendocrine Tumors

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Introduction: Carcinoid heart disease (CHD) is a known complication of neuroendocrine tumors (NETs), particularly of those arising from the small intestine, appendix and proximal colon (previously known as mid-gut carcinoids). CHD is characterized by right heart fibrotic lesions and has traditionally been defined by the degree of valvular involvement, most commonly in the form of tricuspid regurgitation. Right ventricular (RV) dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2) is upregulated in many fibrotic disorders. Increased tumor expression of CCN2 has been shown in patients with small intestinal NETs associated with peritoneal fibrosis. At present, its role in carcinoid heart disease is unknown.

Aim(s): We hypothesized that CCN2 could be involved in the pathogenesis of CHD, and sought to investigate the relationship between plasma CCN2 and both valvular and mural involvement in CHD.

Materials and methods: Echocardiography was performed in 69 patients with small intestinal (n=67), appendiceal (n=1) or proximal colonic (n=1) neuroendocrine tumors. RV function was assessed using tissue Doppler analysis of myocardial systolic strain. Mean systolic strain from the three lateral segments of the RV was calculated. Plasma CCN2 was analyzed using an enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared and Fisher’s exact tests were used to compare groups where appropriate. Linear regression was used to evaluate correlation.

Conference: 7th Annual ENETSConcerence (2010)

Presenting Author:

Authors: Bergestuen D, Gravning J, Haugaa K, Sahakyan L, Aakhus S,

Keywords: carcinoid heart disease, neuroendocrine tumors, right ventricular function, connective tissue growth factor,