Differentiating Macrovascular and Microvascular Ischemia Using Fractal Analysis of Dynamic Myocardial Perfusion Stress-CT

OBJECTIVES: Fractal analysis of dynamic myocardial stress computed tomography perfusion imaging (4D-CTP) has shown potential to noninvasively differentiate obstructive coronary artery disease (CAD) and coronary microvascular disease (CMD). This study validates fractal analysis of 4D-CTP in a multicenter setting and assesses its diagnostic accuracy in subgroups with ischemia and nonobstructed coronary arteries (INOCA) and with mild to moderate stenosis. MATERIALS AND METHODS: From the AMPLIFiED multicenter trial, patients with suspected or known chronic myocardial ischemia and an indication for invasive coronary angiography were included. Patients underwent dual-source CT angiography, 4D-CTP, and CT delayed-enhancement imaging. Coronary artery disease, CMD, and normal perfusion were defined by a combined reference standard comprising invasive coronary angiography with fractional flow reserve, and absolute or relative CT-derived myocardial blood flow. Nonobstructed coronary arteries were defined as ≤25% stenosis and mild to moderate stenosis as 26%-80%. RESULTS: In 127 patients (27% female), fractal analysis accurately differentiated CAD (n = 61, 23% female), CMD (n = 23, 30% female), and normal perfusion (n = 34, 35% female) with a multiclass area under the receiver operating characteristic curve (AUC) of 0.92 and high agreement (multiclass κ = 0.89). In patients with ischemia (n = 84), fractal analysis detected CAD (n = 61) over CMD (n = 23) with sensitivity of 95%, specificity of 74%, accuracy of 89%, and AUC of 0.83. In patients with nonobstructed coronary arteries (n = 33), INOCA (n = 15) was detected with sensitivity of 100%, specificity of 78%, accuracy of 88%, and AUC of 0.94. In patients with mild to moderate stenosis (n = 27), fractal analysis detected CAD (n = 19) over CMD with sensitivity of 84%, specificity of 100%, accuracy of 89%, and AUC of 0.95. CONCLUSIONS: In this multicenter study, fractal analysis of 4D-CTP accurately differentiated CAD and CMD including subgroups with INOCA and with mild to moderate stenosis.