Novel valve replacement with an extracellular matrix scaffold in an infant with single ventricle physiology

Novel valve replacement with an extracellular matrix scaffold in an infant with single ventricle physiology

Cardiovascular Pathology 25 (2016) 165–168 Contents lists available at ScienceDirect Cardiovascular Pathology Clinical Case Report Novel valve rep...

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Cardiovascular Pathology 25 (2016) 165–168

Contents lists available at ScienceDirect

Cardiovascular Pathology

Clinical Case Report

Novel valve replacement with an extracellular matrix scaffold in an infant with single ventricle physiology Alvise Guariento a, Redmond Burke b, Marny Fedrigo c, Annalisa Angelini c, Nicola Maschietto d, Vladimiro Vida a, Gaetano Thiene c, Giovanni Stellin a, Massimo Padalino a,⁎ a

Pediatric and Congenital Cardiac Surgery Unit, Dept of Cardiac, Thoracic and Vascular Sciences, University of Padua Via Giustiniani 2, 35100 Padua, Italy Pediatric Cardiovascular Surgery Unit, Miami Children's Hospital 3100 SW 62nd Ave, Miami, FL 33155, USA) Cardiovascular Pathology Unit, Dept. of Cardiac, Thoracic and Vascular Sciences, University of Padua Via Giustiniani 2, 35100 Padua, Italy d Pediatric Cardiology Unit, Departments of Women's and Children's Health, University of Padua Via Giustiniani 2, 35100 Padua, Italy b c

a r t i c l e

i n f o

Article history: Received 25 July 2015 Received in revised form 10 September 2015 Accepted 12 September 2015

a b s t r a c t Valve replacement in children with functionally univentricular hearts remains challenging. The absence of small prostheses, the lack of growth, and the need for anticoagulation limit these procedures. We describe a 1-year follow-up of an extracellular matrix scaffold tube used as systemic atrio-ventricular valve in an infant. © 2015 Elsevier Inc. All rights reserved.

Keywords: Congenital heart disease Univerticular heart Valve replacement Bioengineered tissue

1. Introduction Surgery for systemic atrio-ventricular valve (AVV) regurgitation in children with functionally univentricular heart (fUVH) is challenging [1]. The use of porcine small intestine submucosa extracellular matrix (CorMatrix™ Cardiovascular Atlanta, GA, USA) scaffold has been reported in surgery for congenital heart disease [2,3] as it provides an interim collagen framework that allows host own cells to repopulate and regenerate tissue. Recently, effective use of a handmade CorMatrix™ AVV has been reported, but its durability is not known [4–6]. We report a 1-year follow-up with a CorMatrix tube implanted as systemic AVV in an infant with fUVH.

2. Case report 2.1. Clinical history A neonate with prenatal diagnosis of fUVH underwent bidimensional echocardiography and cardiac catheterization at birth which demonstrated an unbalanced atrioventricular septal

Disclosures: Conflicts of interest: none. ⁎ Corresponding author at: UOC Cardiochirurgia Pediatrica e Cardiopatie Congenite, Via Giustiniani 2, 35120 Padova, Italy. Tel.: +39-049-8212427; fax: +39-049-2409. E-mail address: [email protected] (M. Padalino). http://dx.doi.org/10.1016/j.carpath.2015.09.003 1054-8807/© 2015 Elsevier Inc. All rights reserved.

defect with an hypoplastic right ventricle (RV), D-Transposition of the Great Arteries, subpulmonary stenosis, and a severe AVV regurgitation (Fig. 1A–B). Following pulmonary artery banding and systemic AVV plasty at the age of 86 days, he developed a residual AVV regurgitation (Fig. 1C), causing congestive heart failure and mechanical ventilation dependency. At the age of 128 days, he underwent AVV replacement with a handmade CorMatrix tube (Fig. 2A). After uneventful redo-sternotomy, through a right atriotomy, the native anterior AVV leaflet was resected, together with accessory chordae tendineae and subpulmonary muscle bundles, to avoid SIS ECM valve impingement in native subvalvar apparatus. On the back table, a four-ply CorMatrix patch was open and hydrated and rolled, and its free edge portion was sutured with 5–0 polypropylene, to create a simple cylindrical tube, whose length was calculated leaving a ratio of annular diameter (measured at preoperative 2D echocardiography) to length of 1:1.2 (Fig. 2B). This tube was inserted in the AVV annulus and anchored distally to RV papillary muscles with interrupted pledgetted stitches, proximally to AVV annulus with a 5.0 polypropylene continuous suture. Saline float revealed competence of the new valve. Postoperative Trans-Esophageal Echocardiography (TEE) demonstrated new leaflets-wide opening, with no regurgitation and no ventricular outflow tract obstruction (Fig. 2C). Postoperative course was characterized by multiple failed extubations, and a tracheostomy was required 3 months later. Prolonged antibiotic intravenous therapy was necessary because of positive blood cultures for multidrug-resistant Pseudomonas Aeruginosa, Candida Albicans, and Enterobacter Cloacae.

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Fig. 1.

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○. Bidimensional echocardiography, short axis view. Superior (*) and inferior (**) bridging leaflet of AVV (A); ○. Computed tomography scan, transverse view. The common native AVV of the unbalanced atrio-ventricular septal defect (B); ○. Parasternal 4 chamber view. After palliative plasty, a significant residual AVV regurgitation is detectable at bidimensional and Doppler echocardiography (C). Left atrium; left ventricle.

Three dimensional echocardiography performed 4 months later demonstrated excellent CorMatrix tube valve function (Fig. 2D). He was discharged on home mechanical ventilation and vasodilator and diuretic therapy, 8 months after AVV replacement. Three months later (at the age of 16 months), during elective clinical and hemodynamic evaluation, an echocardiography exam demonstrated a severe right atrium dilatation, no AVV regurgitation, but a thickened CorMatrix tissue, with AVV stenosis (gradient 18/9 mmHg). Due to infection and progressing hemodynamic impairment, inotropic support and antibiotic therapy was started. He subsequently underwent uneventful surgery consisting in bidirectional cavo-pulmonary shunt and intraoperative dilation with Hegar dilator of the CorMatrix tube that was mildly stenotic, soft, with no calcification. Postoperatively, after successful weaning

Fig. 2.

off inotropic support and inhaled nitric oxide, he was transferred to intermediate care before discharge, but due to sepsis unresponsive to antibiotic therapy, he died on postoperative day 28.

2.2. Autopsy findings and histopathology examination Autopsy showed an intact CorMatrix valve, with moderate stenosis, a fibrous cloth, and no calcifications and/or vegetations on both sides. Histology of the CorMatrix valve showed the extracellular matrix (ECM) scaffold sleeve encircled by fibroblast hyperplasia on the atrial and ventricular side associated with fibrosis, an intense chronic inflammatory infiltrate, no signs of acute damage, and no calcifications (Fig. 3).

○. Diagram showing CorMatrix valve replacement. The tube is inserted in the AVV annulus and anchored distally to the right ventricular papillary muscles. The proximal part of the sleeve is anchored to the AVV annulus (A); ○. Back table construction. CorMatrix scaffold is rolled and sutured to create a cylindrical tube (B); ○. Postoperative trans-esophageal bidimensional (C) and 3D transthoracic echocardiography (D). It is showed an excellent tube systolic and diastolic function.

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Fig. 3. The right atrial side showed the bileaflet shape of the CorMatrix tube with moderate stenosis (A). The annulus had a thickened fibrous cloth without calcifications. The right ventricular side showed the AVV bileaflet shape without chordae tendinae but with a fibrous thickening of the sleeve (B). Histologically the ECM scaffold sleeve of systemic AVV showed the fibroblast hyperplasia on the atrial side associated with fibrosis encircling the scaffold (asterisk showed the scaffold and black arrow the thickening fibrosis). The calcifications are localized at the surgical stiches (C, Van Gieson elastic fiber staining). The scaffold (asterisk) has no calcifications and developed intensive fibroblastic reaction with fibrosis and lymphocytic inflammatory infiltrate in keeping with chronic inflammation (D, 10×). The immunophenotype of inflammatory infiltrate showed T lymphocytes (E, CD3 stain 20×), noncytotoxic (CD8-) (F, CD8 stain 20×). Some cells plug into the scaffold (G, H&E 20×), and most of them are positive for smooth muscle cells actin (H, smooth muscle cell stain 20×) and macrophages (I, CD68 stain 20×).

3. Discussion This is the longest follow-up ever reported of a CorMatrix tube AVV replacement in an infant with fUVH. Regurgitation of a common AVV in fUVH is an important risk factor for mortality and Fontan completion [1], since it reduces systemic ventricular volume preload and causes systemic venous congestion. Due to AVV anatomical abnormality, surgical repair of a common AVV in fUVH is a difficult task, and traditional reparative techniques can be unsatisfactory. Replacement of systemic AVV in infants has limited options (mechanical or bioprosthetic valves), with high surgical risk and inevitable reoperations with growth. Recently, successful surgical implant of Melody valve for mitral valve replacement in infants has been reported: this valve has small diameters (10–22 mm) and can be dilated percutaneously, allowing annular growth [7]. However, maximal Melody diameter may be inadequate in patients like ours, whose systemic AVV annulus was 24 mm. According to our experience, form follows function [8], and a collapsible tube inserted into the native valve site and subjected to the same constraints can take its function and form. Thus, we propose the use of a CorMatrix tube as an option to traditional valve prostheses in infants with fUVH. It was easy to implant, providing the patient with a competent AVV without the need of anticoagulation and valve-related adverse events (i.e., atrioventricular block). As reported elsewhere [4–6], it resulted quite durable in the early period, despite a progressing stenosis. However, our findings demonstrate that AVV stenosis was caused by increased thickness of the ECM tissue, and the absence of calcification made surgical dilation possible. Thus, in case of recurrent stenosis, percutaneous balloon dilatations may be effective. It is to note that histological findings did not show any sign of regeneration but only an integrity of the scaffold and the absence of

calcifications, a chronic inflammatory infiltrate as already demonstrated by other authors [9,10], and finally revealed fibrous pannus formation or neointimal response. Furthermore, microscopic examination showed partial substitution of the scaffold in absence of cytotoxic cells in keeping with modulating immunologic response. Despite this, technology in this format may not be the final solution for a living, durable, and hemodynamically optimal systemic AVV, a prosthetic tube may act as a systemic temporary valve for patients with fUVH physiology, in order to avoid the drawbacks of traditional prostheses. Further studies and longer follow-ups may confirm this experience.

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