Clinical Predictors of ¹⁸F-Sodium Fluoride PET Coronary Uptake in Patients with Advanced Coronary Artery Disease

Objectives: ¹⁸F-sodium fluoride (¹⁸F-NaF) PET depicts developing microcalcifications in the vasculature, serving as a marker of disease activity in patients with established coronary artery disease (CAD), and providing independent prediction of myocardial infarction. To date the associations in ¹⁸F-NaF coronary activity and the risk of adverse events assessed using risk scores dedicated for prediction of recurrent cardiovascular events is not well characterized, hence the clinical rationale for performing coronary PET imaging is not yet established. In this study we investigated the relationship between ¹⁸F-NaF coronary uptake and clinical variables, as well as risk scores developed for estimating the risk of recurrent events in patients with established cardiovascular disease: REACH [Reduction of Atherothrombosis for Continued Health] and SMART [Secondary Manifestations of Arterial Disease].

Methods: Patients with known CAD underwent a 30 min single bed position ¹⁸F-NaF PET and CT angiography 1h after a 6.8 mCI injection of ¹⁸F-NaF on a hybrid PET/CT scanner. We assessed coronary ¹⁸F-NaF uptake using whole-vessel tubular and tortuous 3D volumes of interest (VOI) along the vessel centerlines, which were automatically extracted from CT angiography datasets. Within such VOIs the coronary microcalcification activity (CMA) was defined as the integrated activity in standard uptake value (SUV) units exceeding the background in the left atrium blood pool SUVmean+2 standard deviations (Figure 1). We used a previously established 1.56 CMA threshold to distinguish patients with low and high coronary ¹⁸F-NaF uptake.

Results: Among 293 study participants (65±9 years; 84% male) 237 (81%) had a history of revascularization, 191 (65%) had multi-vessel obstructive CAD and the median coronary calcium score was 334 [76-804]. Overall 109 (37.2%) patients presented with high ¹⁸F-NaF activity. There was no difference in the presence of comorbidities (diabetes, hypertension, hyperlipidemia), smoking or history of percutaneous coronary interventions between subjects with high and low ¹⁸F-NaF activity, all p>0.50. Similarly, there was no difference in the SMART and REACH scores according to ¹⁸F-NaF uptake: 20.2 ±10.0 vs 20.8±10.7, p=0.64 and 12.7±3.0 vs 13.3±2.7, p=0.24. On univariate regression analysis both the SMART and REACH scores emerged as predictors of ¹⁸F-NaF activity, yet the predictive capacity was very low r²=0.038, p=0.001 and r²=0.02, p=0.016 respectively.

Conclusions: In patients with established, advanced CAD there is no difference in comorbidities and clinical risk scores between patients with a high and low CMA as evidenced by ¹⁸F-NaF PET. While both ¹⁸F-NaF and risk scores have been shown to predict adverse events, the assessment of CMA appears to provide complementary information to the SMART and REACH models.

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