Rapid and untypical calcification of the Sorin pericarbon stentless pericardial xenograft in a child

Abstract

Stentless valves are designed to reduce mechanical stress and it is hypothesized that degeneration is reduced. We report early calcification of a Sorin pericarbon stentless pericardial xenograft in aortic position leading to valve failure 2 years after valve replacement in an 11-year-old boy. Morphological evaluation of the explant revealed severe calcification of the leaflets in a uniformly distributed pattern. Positive staining for non-collagen bone matrix proteins was found in the organic matrix of calcific deposits and in infiltrated macrophages. The stentless design of the Sorin valve does not mitigate calcification and therefore cannot be recommended for children.

Stentless heart valve, Calcification, Children

1 Introduction

Stentless pericardial bioprosthesis are minimally obstructive and associated with low mean systolic gradients. The Sorin pericarbon stentless pericardial xenograft (SSPV) is convenient for implantation in children, due to the flexibility of the stentless design. The SSPV had already demonstrated excellent hemodynamics comparable to porcine stentless valves in an adult population [1]. Although encouraging midterm results with a low incidence of structural failure in a young population are reported, bioprosthetic valve replacement in children remains a controversial issue [2].

2 Case description

We report an 11-year-old boy with congenital valvular aortic stenosis who underwent a balloon valvuloplasty 2 months after birth and 7 months later an open valvulotomy. At the age of 6 years the boy became symptomatic with supraventricular tachycardia and showed aortic regurgitation grade II–III and a maximal systolic gradient of 50 mmHg. The Ross-operation was not feasible due to an asymmetric pulmonary valve, so we decided to implant an SSPV (21 mm). After 2 years echocardiographic controls revealed increasing aortic stenosis with mean gradient of 63 mmHg and the patient developed again clinical symptoms. Reoperation due to primary tissue failure became necessary. Because no homograft of appropriate size was available, the bioprosthesis was replaced with a Carbomedics Top Hat mechanical heart valve. The Carbomedics Top Hat valve was chosen because the supraannular implantation allowed the size of 21 without the need of annulus enlargement. The patient received standard anticoagulation with phenprocoumon with a target INR of 2.5.

Gross morphology, X-ray examination, histological analysis and immunohistochemistry was performed to evaluate the mode of bioprosthetic valve failure.

The explanted bioprosthesis showed stiffening of all cusps with severe mineralization verified by X-ray analysis (Fig. 1) . Calcific deposits were located at the central area and the free margins of the leaflets. Examination of valvular surface by scanning electron microscopy revealed clusters of endothelial-like cells at the outflow surface and rough collagen bundles of the bioprosthetic tissue at the inflow surface. Histological evaluation disclosed a neo-intimal layer on the outflow surface that extended over almost the entire surface. The layer was interspersed with numerous stellate connective tissue cells, rounded mononuclear cells and multinucleated giant cells. At the cuspal base capillaries were present in the outgrowing endocardium. In the center of the leaflet regular texture of collagen bundles was seen. Multiple spots of calcification, presented as basophilic irregularly outlined cellular deposits were rarely found in the center of bioprosthetic material, but frequently seen on the surface beneath the neo-intimal layer (Fig. 2B) .

Fig. 1

X-ray shows calcific deposits located at the central area and the free margins of the leaflets.

Fig. 2

(A) Immunostaining for bonesialoproteins (BSP) shows extracellular reactivity at the inflow surface (arrow) and neo-intimal cells, in particular multinucleated giant cells. ×150. (B) The inflow surface of the pericardial valvular leaflet (P) is covered by a loosely textured neo-intimal layer (NI). H&E ×100. (C) Immunostaining for osteopontin (OPN) shows extracellular reactivity in the loosened surface of the bioprosthesis while the matrix of the neo-intima remains unstained, neo-intimal cells are faintly reactive. ×150.

Immunohistochemical staining for non-collagen bone matrix proteins (ncBMPs: bone sialoprotein, osteonectin, osteopontin, antibodies supplied by Chemicon Intern Inc., Temecula, CA, USA; and osteocalcin, antibody supplied by Biogenesis, Poole, UK) revealed strong reactivity in multinucleated giant cells and in the interstitial space next to calcific deposits (Fig. 2A and C). Staining for von Willebrandt factor distinctly marked the endothelial lining of blood vessels in the neointima and endothelial cells at the outflow surface.

3 Discussion

Primary tissue failure of pericardial bioprosthesis caused by calcification is the limiting factor in long-term outcome. Correlation between areas of accentuated mechanical stress and calcification is described [3]. Development of stentless bioprostheses is suggested to be a promising approach in mitigating calcium deposition by reduction of mechanical stress. Besides the accelerating factor of mechanical stress, the preservation of the bioprosthetic tissue with glutaraldehyde is known to be causally related to bioprosthetic heart valve calcification [4]. Therefore, different postfixation treatments were developed in order to remove excess aldehyde from the tissue. The Sorin stentless bioprosthesis has no specific postfixation treatment. Severe stiffening of the leaflets was the main cause of valve failure. Recent studies described accentuated calcification at the commissural area and at the cuspal base, which are areas of increased mechanical flexion and tension [5]. In contrast, the SSPV showed a uniform distribution of calcific deposits independent of areas of accentuated mechanical stress. This indicates a high propensity for calcification of the pericardial tissue. These findings underline the importance of a specific postfixation treatment in order to remove excess aldehyde. Immunohistochemical analysis revealed positive staining for ncBMP in the organic matrix of calcific deposits, along the surface of these deposits and in infiltrated multinucleated giant cells. It has been proposed that the presence of ncBMPs could initiate dystrophic calcification [6,7]. Thus, dystrophic calcification is not simply a passive degeneration phenomenon, but represents an active process that is regulated by ncBMPs [6]. It can be suggested that infiltrated macrophages, which are gathered next to calcific deposits, play a crucial role in the mineralization process.

We conclude from our observation that the SSPV cannot be recommended for implantation in children. The stentless design of the SSPV failed to mitigate calcification in this young patient.