Investigation of the Role of Hemodynamics in Re-stenosis of CABG Patients

CFD simulations in this study provide detailed hemodynamics information, which cannot be obtained from cardiac images alone. The investigators hypothesize that our proposed simulations will provide strong correlation between hemodynamic parameters, such as WSSG and SPA, and clinically identified graft stenosis. These correlations will allow the investigators to identify the future patients at high risk of graft stenosis and lead to future researches on optimizing and refining surgical plans, such as finding optimal proximal and distal anastomoses locations, optimal graft length and diameter, which could lead to improved longevity of the graft. Once CFD coupled shape optimizer is validated, it could be part of the surgical simulator to help in training the next generation physicians. It could provide new viewpoints for assessing whether some modified surgical techniques are better or not. It could also aid in designing and evaluating the vascular medical devices, including stent, artificial graft, and etc., which would lead to better surgical outcome.

Since the introduction of saphenous vein grafting in the late 1960s, CABG, with or without arterial conduits, remains the gold standard for management of intractable angina due to coronary artery occlusive disease. According to the statistics of American Heart Association, 571,000 of bypass procedures were performed on 355,000 patients in 1999. In Singapore, 831 CABG surgeries were carried out in 2011. With the aging of society, the number of bypass operations is suspected to keep increasing over the years.

However, the CABG was not without complications. The saphenous vein, which is the most commonly used vessel for grafting, provides only palliation of the ongoing process. Approximately 15% to 20% saphenous vein grafts occlude in the first year. An additional 2% to 5% grafts occlude each year between 2 to 10 years postoperatively. At 10 to 14 years, 50% of the grafts are occluded. Similar data is reported in 2011 ACCF/AHA CABG guideline. Although thrombosis, intimal hyperplasia and atherosclerosis are found by pathological examinations, the exact mechanism of stenosis is still not fully understood. The investigators hypothesize that localized hemodynamic parameters is related to the sites of graft occlusion.

Hemodynamic parameters are propounded to be involved in localization of arterial stenosis in literatures. High wall shear stress was found to lead abnormal endothelia cells by Fry on the study of thoracic aorta in dogs. Intimal thicken and atherosclerosis was found to be developed in the low WSS region when studying stenosis on postmortem human carotid bifurcations, synthetic grafts on dog's carotid arteries and human coronary arteries. Both high and low WSS segments was found to interplay with plaque development on human coronary arteries. Bovine aortic endothelial cells density was found to increase in the high wall shear stress gradient regions by Depaola and colleagues. Significantly increased WSSG was found at the throat of the cervical carotid stenosis by Schirmer and colleagues for 8 patients. Stress phase angle was proposed to be a useful indicator in predicting sites prone to atherosclerosis by Torii et al. when investigating a patient's right coronary artery with stenosis. Low-density lipoprotein transportation was proposed to be a useful indicator in predicting sites prone to atherosclerosis on human left coronary artery by Olgac and colleagues.

All of these hemodynamic parameters are related to the forces acting on the endocellar cells, especially the wall shear stress. Signaling pathways have been proposed, which mediate the mechano- chemical transduction in endothelial cells in response to disturbed WSS. Among the WSS-related parameters, WSSG and SPA may be the most important, as WSSG measures the impact of changes in surface forces, while SPA refers to the phase angle between WSS and WCS. Therefore direct study on the human with CABG is necessary to provide strong correlation between graft stenosis and hemodynamic parameters, which would be helpful in identifying the patients at high risk of re-stenosis and optimizing the surgery from a mechanical standpoint. The current project aims to fill in this gap.

Eligibility Criteria:
Inclusion Criteria:

* Aged 21-80.
* Undergoing or underwent CABG with at least one saphenous vein graft. (Only for recruitment of CABG patients)
* No known history of coronary artery disease (only for recruitment of volunteers with Stable/unstable angina).

Exclusion Criteria:

* Individuals unable to provide informed consent.
* Non-cardiac illness with life expectancy \<2 years.
* Pregnant state.
* Allergy to iodinated contrast.
* Significant arrhythmia; heart rate ≥ 100 beats/min; systolic blood pressure ≤90 mmHg.
* Renal dysfunction(Glomerular filtration rate (GFR) \<30 mL/min/1.73m2).
* Contraindication to beta blockers or nitroglycerin.
* Canadian Cardiovascular Society class IV angina.