Author + information
- R. Scott Baker, BS,
- Farhan Zafar, MD,
- Ryan A. Moore, MD,
- Michael D. Taylor, MD, PhD and
- David Luís Simón Morales, MD∗ ()
- ↵∗Pediatric Cardiothoracic Surgery, Cincinnati Children’s Hospital Medical Center, The University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 2004, Cincinnati, Ohio 45229
Prosthetic valve replacement options in children lack the ability to grow with the patient and often require multiple reoperations. Adverse events are also magnified in the pediatric population, in whom the need for a functional valve is decades longer and the issue of growth leading to body–size-to-valve mismatch is significant. Small intestinal submucosa–derived extracellular matrix (SIS-ECM) has been used successfully to repair a variety of tissues including vessels, myocardium, and valves (1,2). The objective of this study, a follow-up to previously published work in the Journal (2), was to assess the long-term remodeling potential of a tubular tricuspid valve (TV) bioprosthesis made of CorMatrix SIS-ECM (CorMatrix Cardiovascular, Inc., Roswell, Georgia) by seeing if the previously reported growth, structure, function, and freedom from calcification in a growing ovine model continued past 8 months.
We studied 4 3-month-old lambs for 18 months following SIS-ECM TV replacement via right thoracotomy using absorbable suture and SIS-ECM pledgets for papillary attachments. All lambs underwent serial echocardiography (4-month intervals) and magnetic resonance imaging (6-month intervals) to measure annulus diameter, valve, and right ventricular function. All sheep received humane care in compliance with The Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (3). All protocols used in this study were approved by the Cincinnati Children’s Research Foundation Institutional Animal Care and Use Committee.
All animals grew normally over the 18-month study period (27 ± 2 kg to 104 ± 8 kg) without surgical complications and weighed 39 kg more on average than those in the 8-month study (2). There was stable trivial-to-mild regurgitation of the SIS-ECM valve and normal right ventricular diastolic and systolic function on cardiac magnetic resonance imaging, which was confirmed by echocardiography. The annular diameter on average increased from 17 ± 1 mm to 32 ± 2 mm over the study period (individual annular increases were 18, 14, 16, and 15 mm). The average annular diameter increased by 10 mm in the 8-month study (2). One sheep had episodic atrial fibrillation and a consistently enlarged right atrium; however, it completed the study period without any sequalae.
Explanted SIS-ECM valves resembled native tissue in gross appearance with further development of chordae, which was not noted at 8 months (Figure 1A). Histopathology demonstrated migration of resident mesenchymal cells (α-smooth muscle actin positive) into the scaffold, and tri-laminar ECM organization similar to a native valve and chordae without indications of inflammation or calcification at 18 months (Figure 1B), as seen in the previous study.
Long-term follow-up of a growing ovine model with tubular SIS-ECM TV bioprostheses demonstrated valve “growth” and chordae formation and a cell-matrix structure similar to mature native valve tissues without indication of calcification, while maintaining normal valve function throughout the 18-month study period. Calcific degeneration is commonly seen by 3 months in the juvenile sheep model with currently available bioprosthetic valves (4). However, the small sample size (n = 4) is a clear limitation of this investigation.
The SIS-ECM valve may provide a novel, durable solution for tricuspid valve replacement in children and adults. Currently, surgery is the primary, effective management for valve disease, but it remains suboptimal as native valve disease is often “replaced” by prosthetic valve disease (5). Worldwide, >200 of these valves have been implanted in adults and in much smaller numbers in children. Ovine studies examining SIS-ECM valvular implants in the mitral position are also underway.
Please note: This project was funded by the authors’ institution; no other entity had any role in this study. The SIS-ECM tricuspid valve is a product of CorMatrix Inc. Dr. Morales has served as a consultant for and on the medical advisory board of CorMatrix, Berlin Heart, Syncardia, HeartWare, and Oregon Heart; and has received personal compensation for his role in the form of company options, has received compensation for travel and accommodations, and has received research funding (for a separate, prior research study) from CorMatrix Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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- National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals
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