BackgroundUnlike most noninvasive imaging modalities, coronary computed tomography angiography can characterize subtypes of atherosclerotic plaque.ObjectivesThe purpose of this study was to investigate the prognostic implications of adverse coronary plaque characteristics in patients with suspected coronary artery disease.MethodsIn this SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) post hoc analysis, the presence of adverse plaque (positive remodeling or low attenuation plaque), obstructive disease, and coronary artery calcification within 15 coronary segments was assessed on coronary computed tomography angiography of 1,769 patients who were followed-up for 5 years.ResultsAmong study participants (mean age 58 ± 10 years; 56% male), 608 (34%) patients had 1 or more adverse plaque features. Coronary heart disease death or nonfatal myocardial infarction was 3 times more frequent in patients with adverse plaque (n = 25 of 608 [4.1%] vs. n = 16 of 1,161 [1.4%]; p < 0.001; hazard ratio [HR]: 3.01; 95% confidence interval (CI): 1.61 to 5.63; p = 0.001) and was twice as frequent in those with obstructive disease (n = 22 of 452 [4.9%] vs. n = 16 of 671 [2.4%]; p = 0.024; HR: 1.99; 95% CI: 1.05 to 3.79; p = 0.036). Patients with both obstructive disease and adverse plaque had the highest event rate, with a 10-fold increase in coronary heart disease death or nonfatal myocardial infarction compared with patients with normal coronary arteries (HR: 11.50; 95% CI: 3.39 to 39.04; p < 0.001). However, these associations were not independent of coronary artery calcium score, a surrogate measure of coronary plaque burden.ConclusionsAdverse coronary plaque characteristics and overall calcified plaque burden confer an increased risk of coronary heart disease death or nonfatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590)

Background: The future risk of myocardial infarction is commonly assessed using cardiovascular risk scores, coronary artery calcium score, or coronary artery stenosis severity. We assessed whether noncalcified low-attenuation plaque burden on coronary CT angiography (CCTA) might be a better predictor of the future risk of myocardial infarction. Methods: In a post hoc analysis of a multicenter randomized controlled trial of CCTA in patients with stable chest pain, we investigated the association between the future risk of fatal or nonfatal myocardial infarction and low-attenuation plaque burden (% plaque to vessel volume), cardiovascular risk score, coronary artery calcium score or obstructive coronary artery stenoses. Results: In 1769 patients (56% male; 58±10 years) followed up for a median 4.7 (interquartile interval, 4.0–5.7) years, low-attenuation plaque burden correlated weakly with cardiovascular risk score ( r =0.34; P <0.001), strongly with coronary artery calcium score ( r =0.62; P <0.001), and very strongly with the severity of luminal coronary stenosis (area stenosis, r =0.83; P <0.001). Low-attenuation plaque burden (7.5% [4.8–9.2] versus 4.1% [0–6.8]; P <0.001), coronary artery calcium score (336 [62–1064] versus 19 [0–217] Agatston units; P <0.001), and the presence of obstructive coronary artery disease (54% versus 25%; P <0.001) were all higher in the 41 patients who had fatal or nonfatal myocardial infarction. Low-attenuation plaque burden was the strongest predictor of myocardial infarction (adjusted hazard ratio, 1.60 (95% CI, 1.10–2.34) per doubling; P =0.014), irrespective of cardiovascular risk score, coronary artery calcium score, or coronary artery area stenosis. Patients with low-attenuation plaque burden greater than 4% were nearly 5 times more likely to have subsequent myocardial infarction (hazard ratio, 4.65; 95% CI, 2.06–10.5; P <0.001). Conclusions: In patients presenting with stable chest pain, low-attenuation plaque burden is the strongest predictor of fatal or nonfatal myocardial infarction. These findings challenge the current perception of the supremacy of current classical risk predictors for myocardial infarction, including stenosis severity. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01149590.

Purpose of ReviewCost-effective care pathways are integral to delivering sustainable healthcare programmes. Due to the overestimation of coronary artery disease using traditional risk tables, non-invasive testing has been utilised to improve risk stratification and initiate appropriate management to reduce the dependence on invasive investigations. In line with recent technological improvements, cardiac CT is a modality that offers a detailed anatomical assessment of coronary artery disease comparable to invasive coronary angiography.Recent FindingsThe recent publication of the National Institute for Health and Care Excellences (NICE) Clinical Guideline 95 update assesses the performance and cost utility of different non-invasive imaging strategies in patients presenting with suspected anginal chest pain. The low cost and high sensitivity of cardiac CT makes it the non-invasive test of choice in the evaluation of stable angina. This has now been ratified in national guidelines with NICE recommending cardiac CT as the first-line investigation for all patients presenting with chest pain due to suspected coronary artery disease. Additionally, randomised controlled trials have demonstrated that cardiac CT improves diagnostic certainty when incorporated into chest pain pathways.SummaryNICE recommend cardiac CT as the first-line test for the evaluation of stable coronary artery disease in chest pain pathways.

No abstract

Background: Microcalcifications in atherosclerotic plaques are destabilizing, predict adverse cardiovascular events, and are associated with increased morbidity and mortality. 18F-fluoride PET/CT imaging has demonstrated promise as a useful clinical diagnostic tool in identifying high risk plaques; however, there is confusion as to the underlying mechanism of signal amplification seen in PET-positive, CT-negative image regions. This study tested the hypothesis that 18F-fluoride PET/CT can identify early microcalcifications. Methods and Results: 18F-fluoride signal amplification derived from microcalcifications was validated against near infrared fluorescence (NIRF) molecular imaging and histology using an in vitro 3D hydrogel collagen platform, ex vivo human specimens, and a mouse model of atherosclerosis. Microcalcification size correlated inversely with collagen concentration. The 18F-fluoride ligand bound to microcalcifications formed by calcifying vascular smooth muscle cell-derived extracellular vesicles in the in vitro 3D collagen system and exhibited an increasing signal with an increase in collagen concentration (0.25mg/ml collagen - 33.8×102±12.4×102 CPM; 0.5 mg/ml collagen - 67.7×102±37.4×102 CPM, p=0.0014), suggesting amplification of the PET signal by smaller microcalcifications. We further incubated human atherosclerotic endarterectomy specimens with clinically-relevant concentrations of 18F-fluoride. The 18F-fluoride ligand labeled microcalcifications in PET-positive, CT-negative regions of explanted human specimens as evidenced by 18F-fluoride PET/CT imaging, NIRF and histological analysis. Additionally, the 18F-fluoride ligand identified micro- and macrocalcifications in atherosclerotic aortas obtained from LDLr-deficient mice. Conclusions: Our results suggest that 18F-fluoride PET signal in PET-positive, CT-negative regions of human atherosclerotic plaques is the result of developing microcalcifications, and high surface area in regions of small microcalcifications may amplify PET signal.

To improve the test-retest reproducibility of coronary plaque 18 F-sodium fluoride (18 F-NaF) positron emission tomography (PET) uptake measurements. Methods We recruited 20 patients with coronary artery disease who underwent repeated hybrid PET/CT angiography (CTA) imaging within 3 weeks. All patients had 30-min PET acquisition and CTA during a single imaging session. Five PET image-sets with progressive motion correction were reconstructed, (i) a static dataset using all the data (no-MC), (ii) end-diastolic PET (Standard), (iii) cardiac motion corrected (MC), (iv) combined cardiac and gross patient motion corrected (2xMC) and, (v) cardiorespiratory and gross patient motion corrected (3xMC). In addition to motion correction, all datasets were corrected for variations in the background activities which are introduced by variations in the injection-to-scan delays (background blood pool clearance correction, BC). Test-retest reproducibility of PET target-to-background ratio (TBR) was assessed by Bland-Altman analysis and coefficient of reproducibility. Results A total of 47 unique coronary lesions were identified on CTA. Motion correction in combination with BC improved the PET TBR test-retest reproducibility for all lesions (coefficient of reproducibility: Standard = 0.437, No-MC = 0.345 (27% improvement), Standard+BC = 0.365 (20% improvement), no-MC+BC = 0.341 (27% improvement), MC+BC = 0.288 (52% improvement), 2xMC+BC = 0.278 (57% improvement) and 3xMC+BC = 0.254 (72% improvement), all p<0.001). Importantly in a sub analysis of 18 F-NaF-avid lesions with gross patient motion >10mm following corrections reproducibility was improved by 133% (coefficient of reproducibility: standard= 0.745, 3xMC= 0.320). Conclusion Joint corrections for cardiac, respiratory and gross patient motion in combination with background blood pool corrections markedly improve test-retest reproducibility of coronary 18 F-NaF PET.

No abstract

Supplemental Digital Content is available in the text.