Reverse Attenuation Gradient Sign
Explanation: The RAG sign helps in confirming the diagnosis of CTO (Fig. 1B) and in distinguishing it from subtotal occlusion (STO). In a normal coronary artery and in STO, the intravascular attenuation pattern has a steadily decreasing gradient from the proximal to the distal segments of the vessel (Fig. 1C and D). In the RAG sign, the gradient is reversed distal to an occlusive lesion, with attenuation increasing distally at a rate of 5.1±13.4 HU/10 mm.1,2 This represents development of retrograde collateral flow distal to CTO as an adaptive response to prolonged myocardial ischemia.3
Discussion: CTO is a total occlusion of a coronary artery with no antegrade flow, whereas STO is a high-grade stenosis (99%) with preserved antegrade flow. Distinguishing CTO from STO is clinically important, as CTO is associated with higher rates of unsuccessful recanalization and worse prognosis due to complications such as restenosis.4 Cardiac computed tomography (CT) is not always successful in differentiating these 2 entities, as both present with complete interruption of the contrast opacified lumen. Although there may be small channels within the atherosclerotic plaques that connect the proximal and distal lumen in STO, these channels are below the spatial resolution of CT.4
The RAG sign has been shown to have a positive predictive value of 100%1 and specificity of 93% to 100%1,2 in the diagnosis of CTO, indicating reverse distal flow from collaterals. However, this sign has a sensitivity of only 65%, indicating that this is not always present in CTO. This is likely due to bridging collaterals with antegrade filling of vessels distal to an occlusion or due to technical factors such as delayed acquisition, as a result of which all the segments distal to the occlusion are opacified without any gradient. These bridging collaterals are not reliably seen on CT, and hence an erroneous diagnosis of STO can be made.2,3 The sensitivity of CT to diagnose CTO can be increased by using a combination of parameters. Li et al2 reported a sensitivity of 90% by combining RAG, occlusion length >14.3 mm, and bridging collateral vessel, whereas Choi et al3,4 reported a sensitivity of 85% by combining RAG (>0.9 HU/10 mm), occlusion length >15 mm, blunt stump, collaterals, side branches, and cross-sectional calcification ≥50%. In STO, the lesion length is <14.3 to 15 mm, and there are no bridging collaterals.2,4
The RAG sign can be shown in good-quality coronary CT angiography exams, with either prospective ECG-gated or retrospective ECG-gated techniques. The RAG sign is more obvious in wide-array or volume scanners, in which the entire heart is imaged in 1 heartbeat and hence the acquisition time is the same for all coronary artery segments.2 It may not be readily apparent in earlier-generation multidetector scanners with smaller longitudinal coverage and also if scanning is performed late after intravenous contrast injection as all the coronary artery will be opacified (Table).