Junedh Amrute, Pulse Editor and Writer | November 14, 2017
The profound world-wide impact of coronary artery disease (CAD) is a major contributor to death in developed countries and accounts for almost one third of all deaths in individuals over 35 years [1]. CAD is characterized by the development of atherosclerosis and occlusive plaque burden in the coronary artery [2,3]. This stenosis severely impairs blood flow and results in fatal heart attacks.
Previously, open-heart bypass surgeries were the primary means of re-directing blood flow to address the stenoses, however, given the risks and long-term complications associated with open-heart surgeries there is a need for a non-invasive solution. Drug-eluting metallic stents enable non-invasive management of CAD, as they are inserted via a catheter through one of the major arteries like the femoral artery and usually, balloon-expanded to hold open a stenosed region enabling previously-constricted blood to pass freely [4]. While immensely capable, metallic stents induce damage to the arterial wall and permanently remodel the surrounding tissue. Furthermore, patients with metallic stents must comply with strict medication for their entire life otherwise the stenoses can come back to life. These medications often have long-term side-effects and detrimentally affect other organ systems.
Meanwhile, erodible polymeric implants hold the promise of restoring normal arterial function, can free patients from the web of lifelong medications, and obviate the long-term complications of metallic stents. Numerous companies have developed such implants and even inserted them into patients. While promising at first, these devices increase the propensity for the once disappeared plaque to reform and adversely affect patient health. This begs the question – why did this happen and more importantly, why did patients have to suffer for us to find out?
Polymeric implants are more fragile than metallic stents and to maintain the same level of mechanical integrity, they need to be larger. Given the small size of the coronary artery, a large device will severely disturb blood flow – as blood crashes against the device, it will recirculate – biologically, this stimulates a cellular pathway to create thrombus, an analogue of plaque. The newly synthesized thrombus will obscure arterial blood flow and we are back to square one, but this time have inserted a device, which is exaggerating the problem!
To foresee the shortcoming of such devices, it is critical to build patient-specific models, which allow us to understand the disease mechanism and devise appropriate treatment solutions. Given the relevant information, we can build patient-specific 3D models of coronary arteries with the device, pass a fluid through the geometry, and study blood velocity, recirculation zones, and other variables, which provide a more holistic insight into arterial function. Clinically, we only have access to 2D information such as cross-sectional images of the coronary artery and the challenge is to extract relevant information from these images to build the really powerful 3D models. We presented an algorithm, which automatically detects the lumen border and polymeric scaffold and can be used as an input to generate these necessary 3D models.
Developing a patient-specific 3D model will allow researchers to run structural and fluid computations within the stented coronary artery [5]. This crucial analysis will provide physicians with quantitative metrics to assess cardiovascular function post polymeric scaffold implantation and isolate contributing biomechanical factors. While the current generation of polymeric scaffolds have been withdrawn from the market, numerous companies are actively working to develop next generation polymeric implants. Such an algorithm will become even more important as it will enable us and others to study the biomechanical and hemodynamic effects of these devices. A holistic insight into cardiovascular function will allow us to move towards a continuum of more reliable and effective patient-specific treatment strategies.
References
1. F. Sanchis-Gomar et al., “Epidemiology of coronary heart disease and acute coronary syndrome.,” Ann. Transl. Med. 4(13), 256, AME Publications (2016) [doi:10.21037/atm.2016.06.33].
2. G. Sangiorgi et al., “Arterial Calcification and Not Lumen Stenosis Is Highly Correlated With Atherosclerotic Plaque Burden in Humans: A Histologic Study of 723 Coronary Artery Segments Using Nondecalcifying Methodology,” J. Am. Coll. Cardiol. 31(1) (1998).
3. J. L. Fleg et al., “Detection of High-Risk Atherosclerotic Plaque,” JACC Cardiovasc. Imaging 5(9) (2012).
4. M. P. Savage et al., “Stent Placement Compared with Balloon Angioplasty for Obstructed Coronary Bypass Grafts,” N. Engl. J. Med. 337(11), 740–747, Massachusetts Medical Society (1997) [doi:10.1056/NEJM199709113371103].
5. C. Chiastra et al., “Reconstruction of stented coronary arteries from optical coherence tomography images: Feasibility, validation, and repeatability of a segmentation method.,” PLoS One 12(6), e0177495, Public Library of Science (2017) [doi:10.1371/journal.pone.0177495].
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ABOUT THE AUTHOR Junedh Amrute is a Senior in the Bioengineering department at Caltech and is interested in using fundamentals from engineering and physics to study problems in cardiovascular medicine.