Heparin Coated and Uncoated Polytetrafluoroethylene Shunts in Children With Congenital Heart Defects
World Journal for Pediatric and Congenital Heart Surgery 2014, Vol. 5(3) 391-392 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2150135114534996 pch.sagepub.com
James S. Tweddell, MD1 Keywords CHD, univentricular heart, shunts, systemic to pulmonary artery, congenital heart surgery, endothelium Submitted March 31, 2014; Accepted April 16, 2014.
In this issue of World Journal for Pediatric and Congenital Heart Surgery, Ho¨rer and colleagues from the German Heart Center in Munich report their evaluation of the development of neointima among patients who had undergone systemic to pulmonary artery shunt placement using either uncoated or heparin coated polytetrafluoroethylene (PTFE) shunts.1 The authors found similar degrees of neointimal proliferation in both the coated and uncoated shunts. A ‘‘real world’’ assessment of the heparin coated shunts is essential, and Ho¨rer and colleagues have performed careful histologic examination of the explanted shunts. At face value, there appears to be no benefit to the newer and more expensive grafts. There are, however, important limitations to this study that impact our understanding of how heparin coated shunts might benefit our patients. First, we don’t have the best understanding of the development of neointima in very small grafts with high-velocity flow. Neointima formation is the result of proliferating myofibroblasts within the lumen of a graft, particularly at the anastomotic sites. Both the coagulation and inflammatory processes contribute to its development. In systemic to pulmonary artery shunts, the neointima may result in critical reduction of shunt lumen, leading to worsening cyanosis. Heparin binds to the enzyme inhibitor antithrombin (AT) III, causing a conformational change that results in a 1,000-fold increase in AT activity. The activated AT then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa. Systemic to pulmonary artery shunts made of PTFE are thrombogenic, and coating the shunts with heparin might decrease the potential for acute shunt thrombosis. In addition, because thrombin generation results in platelet activation and adherence, one might postulate that heparin coating would inhibit the first steps in neointimal proliferation. In addition, heparin inhibits smooth muscle cell proliferation, but like many downstream effects of the amplifying and interconnected cascades of coagulation and inflammation, neointimal proliferation is a relentless process. Although heparin coating might decrease the potential for acute shunt thrombosis and has resulted in improved graft patency in other human studies, it seems less
likely that heparin coating alone will limit neointimal proliferation.2-6 Aspirin, which was used by the investigators, may be a better choice. Aspirin is a nonselective cyclooxygenase (COX) inhibitor, blocking both COX-1 and COX-2 pathways. The COX-1 inhibition results in decreased platelet adhesion and aggregation, whereas COX-2 inhibition decreases inflammation, limiting myofibroblast proliferation, therefore inhibiting two mechanistic pathways of neointimal development. In an observational study, aspirin limited neointimal formation and had a favorable impact on shunt patency and durability. But as in the current study, aspirin could not eliminate neointimal proliferation.7 Perhaps our expectation for heparin coated shunts should be limited to a decrease in acute shunt thrombosis. Indeed this benefit alone would be of value in our patient population. The second and perhaps greatest challenge in interpretation of the study by Ho¨rer and colleagues is the difference in shunt sizes between the heparin coated and control groups. In the control group, there were five shunts that were 3.5 mm in diameter and only one shunt that was 3.0 mm in diameter, whereas in the heparin coated group it was the reverse, with five shunts that were 3.0 mm and two shunts that were 3.5 mm larger. The authors compared the absolute sizes of the shunts and determined the difference was not significant, but because shunts come in discrete sizes perhaps shunt size should not be treated as a continuous variable. A chi-square comparison would suggest that the proportion of shunt sizes is different between the two groups. Smaller shunt sizes are associated with a higher degree of shunt-related complications.8 Furthermore, smaller shunt sizes are associated with higher blood velocity, and high
Division of Cardiothoracic Surgery, Children’s Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA. Corresponding Author: James S. Tweddell, Division of Cardiothoracic Surgery, Children’s Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA. Email: [email protected]
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World Journal for Pediatric and Congenital Heart Surgery 5(3)
velocity blood flow alone can result in platelet activation.9 Therefore, the difference in shunt size between the two groups is an important independent predictor of outcome that is not controlled for and limits our ability to interpret the data. The work by Ho¨rer and colleagues is an important contribution and while the results are inconclusive, they have identified that further work on the impact of heparin coated shunts and their role in congenital heart surgery is necessary.
small-caliber ePTFE grafts in a canine femoral artery bypass model. J Surg Res. 2004;118(1): 45-52. Lin PH, Chen C, Bush RL, Yao Q, Lumsden AB, Hanson SR. Small-caliber heparin-coated ePTFE grafts reduce platelet deposition and neointimal hyperplasia in a baboon model. J Vasc Surg. 2004;39(6): 1322-1328. Lindholt JS, Gottschalksen B, Johannesen N, et al. The Scandinavian Propaten((R)) trial—1-year patency of PTFE vascular prostheses with heparin-bonded luminal surfaces compared to ordinary pure PTFE vascular prostheses—a randomised clinical controlled multi-centre trial. Eur J Vasc Endovasc Surg. 2011; 41(5): 668-673. Pulli R, Dorigo W, Castelli P, et al. Midterm results from a multicenter registry on the treatment of infrainguinal critical limb ischemia using a heparin-bonded ePTFE graft. J Vasc Surg. 2010;51(5): 1167-1177.e1. Li JS, Yow E, Berezny KY, et al. Clinical outcomes of palliative surgery including a systemic-to-pulmonary artery shunt in infants with cyanotic congenital heart disease: does aspirin make a difference? Circulation. 2007;116(3): 293-297. Myers JW, Ghanayem NS, Cao Y, et al. Outcomes of systemic to pulmonary artery shunts in patients weighing less than 3 kg: analysis of shunt type, size, and surgical approach. J Thorac Cardiovasc Surg. 2014;147(2): 672-677. Waniewski J, Kurowska W, Mizerski JK, et al. The effects of graft geometry on the patency of a systemic-to-pulmonary shunt: a computational fluid dynamics study. Artif Organs. 2005;29(8): 642-650.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. 6.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. 7.
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