Introduction: In heart attacks, blood flow to the muscle is blocked and the muscle is damaged or dies and begins to dilate and form scar, ultimately resulting in incompetence of the mitral valve known as ischemic mitral regurgitation (IMR)[1]. The development of ischemic mitral regurgitation is associated with significant morbidity and mortality after a heart attack. Even moderate IMR is currently recommended for surgical intervention, which is usually initially effective. However, the late survivability of these patients is low[2], the surgery is invasive, and the intervention does not address the underlying issue. Biological and synthetic hydrogels for implantation have been considered[3], with varying success and in the past we discussed an injectable strategy[4]. Here we describe development of a strategy that is intended to be delivered thorascopically and applied to the outside of the heart wall. We describe the construction of the device, supporting mechanical data and summarize early in vivo data obtained from an ovine study.
Materials and Methods: The patch design is shown in Figure 1. The patch is designed to conform to the shape of the heart and cover the infarcted tissue resulting from a left ventricular MI. The device is composed of polyacrylamide (Hydrosource, LLC) enclosed in gelatin capsules (Size “00”; Now Natural Foods), confined between two layers of polyester mesh (140 μm thick, 150 μm opening size) (McMaster Carr) sewn into an empirically determined shape. This design delays hydration while the patch is positioned over the infarcted tissue. A finer polyester serves as a surgical attachment site. The device was electron beam sterilized at 32.5 kGy ± 2.5 kGy.
Results and Discussion: Tests confirm cyto- and endo- toxicity below the limits required for implantable materials. Swell ratio determined swelling of up to ~31x of the polymer, with rapid swelling reaching passing 50% swell in ~ 2 minutes). High swell ratio and rapid swelling time allows the device to rapidly reach its in-use conformation to allow the surgeon to verify placement and displacement of the underlying tissue. It also allows the device to be delivered in a 0.95 ml capsule and yet displace between 1 and 2 centimeters when swollen. The swelling pressure was 41 kPa across the device surface, which is approximately 3-4 times normal blood pressures. A brief summary of data will also be presented from chronic ovine studies.
Conclusions: The proposed design in this paper addresses weakness in the existing state of the art devices, and in our early attempts to develop an injectable hydrogel solution to this problem. The collected data indicate that the device is viable as proposed, although for further development, medical grade components would be required. The simple concept, and relative ease of delivery, makes this a promising approach, and the animal data supplied in brief at the end of the paper demonstrates that this concept has a high chance of success in the surgical environment.
References:
[1] Gorman, R. C., J. H. Gorman III, and L. H. Edmunds Jr., 2003, in Cardiac Surgery in the Adult, edited by L. H. Cohn and L. H. J. Edmunds (McGraw-Hill, New York), p. 751.
[2] "ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease" Circulation 114, 450-527, (2012).
[3] Nelson, D. M., Z. Ma, K. Fujimoto, R. Hashizume, and W. R. Wagner, "Intramyocardial Biomaterial Injection Therapy in the Treatment of Heart Failure: Materials, Outcomes and Challenges" Acta Biomaterials 7, 1-15, (2011).
[4] Hung, J. et al., "A Novel Approach for Reducing Ischemic Mitral Regurgitation by Injection of a Polymer to Reverse Remodel and Reposition Displaced Papillary Muscles" Circulation 118, S263-S269, (2008)