Abstract

Objective: One of the main features in human Tetralogy of Fallot (TF) is right ventricular hypertrophy (RVH) due to pressure overload caused by (sub) pulmonary stenosis and/or volume overload due to ventricular septal defect. Currently, primary correction at young age is the treatment of choice. However, it is not yet known to what extent RVH in TF patients after corrective surgery regresses.

Methods: We examined endomyocardial biopsies for the expression of the extracellular matrix proteins collagen and fibronectin, in TF patients with RVH (TF1: primary corrective surgery, n = 11, mean age 0.7 ± 0.2 yr and TF2: secondary surgery, n = 6 mean age 36.9 ± 4.6 yr) and in age matched pulmonary autograft control patients with normal right ventricle (C1: group, n = 6, mean age 1.52 ± 0.2 yr and C2: n = 12, mean age 31.7 ± 4.2 yr).

Results: Picrosirius red staining quantified by video imaging showed significantly increased interstitial staining for collagens in TF1 (1.4 ± 0.2 fold) and TF2 (1.6 ± 0.2 fold) groups as compared to their controls. Immunohistochemical localization of fibronectin showed the expression in extracellular spaces, perivascular as well as in some cardiomyocytes. A semiquantitative analysis employing an inter-observer visualization method using a staining score ranging from 0 (no staining) to 4 (very strong staining) revealed increased expression of fibronectin in TF1 group only as compared to respective control. There were no differences in fibronectin expression in patients from TF2 group when compared with age-matched controls.

Conclusion: Our results indicate an increased amount of myocardial extracellular matrix deposition resulting in tissue fibrosis in TF patients with right ventricular hypertrophy. This leaves ample room for improvement of contemporary clinical treatment of TF.