Thrombotic risk stratification using computational modeling in patients with coronary artery aneurysms following Kawasaki disease

Abstract

Kawasaki disease (KD) is the leading cause of acquired heart disease in children and can result in life-threatening coronary artery aneurysms in up to 25 % of patients. These aneurysms put patients at risk of thrombus formation, myocardial infarction, and sudden death. Clinicians must therefore decide which patients should be treated with anticoagulant medication, and/or surgical or percutaneous intervention. Current recommendations regarding initiation of anticoagulant therapy are based on anatomy alone with historical data suggesting that patients with aneurysms ≥8 mm are at greatest risk of thrombosis. Given the multitude of variables that influence thrombus formation, we postulated that hemodynamic data derived from patient-specific simulations would more accurately predict risk of thrombosis than maximum diameter alone. Patient-specific blood flow simulations were performed on five KD patients with aneurysms and one KD patient with normal coronary arteries. Key hemodynamic and geometric parameters, including wall shear stress, particle residence time, and shape indices, were extracted from the models and simulations and compared with clinical outcomes. Preliminary fluid structure interaction simulations with radial expansion were performed, revealing modest differences in wall shear stress compared to the rigid wall case. Simulations provide compelling evidence that hemodynamic parameters may be a more accurate predictor of thrombotic risk than aneurysm diameter alone and motivate the need for follow-up studies with a larger cohort. These results suggest that a clinical index incorporating hemodynamic information be used in the future to select patients for anticoagulant therapy.

Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

“…The chronic risk of thrombosis is greatest in those with giant aneurysms and is attributable to reduced shear stress and flow disturbances (stagnation) as noted in rheological studies 361,362 and flow simulations. 363,364 Other patient and aneurysm characteristics can also increase thrombosis risk ( Table 9). The degree to which both local and systemic endothelial dysfunction and inflammation contribute to thrombosis risk is not completely known.…”

A haemodynamic predictor of intraluminal thrombus formation in abdominal aortic aneurysms

“…as in aneurysms), particles that have previously accumulated a high shear history could potentially be advected to the wall even by a lower shear flow that would result in low WSSs on the endothelium. In this case, the computed TFP may provide much more information than simply a WSS-based parameter like ECAP, a measure such as (near wall) residence time, or a single measure of platelet shear history [31,37,40,41]. That is, the present findings motivate further consideration of the TFP, or a similarly combined index, that accounts for the potential of activated platelets being presented to a quiescent (non-thrombogenic) versus a susceptible (thrombogenic) endothelium.…”

Assessment of Coronary Artery Aneurysms Caused by Kawasaki Disease Using Transluminal Attenuation Gradient Analysis of Computerized Tomography Angiograms

“…11,14 The present study is the first to evaluate CAA caused by KD using TAG analysis. We found significantly lower TAG values for aneurysmal compared with nonaneurysmal arteries.…”

“…Invasive methods such us Doppler flow wire measurements 10–12 and patient-specific blood flow simulations in KD patients 13,14 reported abnormal hemodynamics in CAA and showed that hemodynamic parameters may be a promising approach for CAA assessment, in particular for identifying aneurysmal regions at higher risk of thrombosis. 11,14 The present study is the first to evaluate CAA caused by KD using TAG analysis.…”