Non-lipid-rich low attenuation plaque with intraplaque haemorrhage assessed by multimodality imaging: a case report

Background The lipid-rich necrotic core is a major pathological hallmark of acute coronary syndrome. Low attenuation plaque (LAP) on coronary computed tomography angiography (CCTA), defined as plaque CT attenuation of <30 Hounsfield units, is commonly believed to correspond to the lipid component. This report presents a non-lipid-rich LAP with intraplaque haemorrhage of the left main coronary artery (LM), as assessed by CCTA, near-infrared spectroscopy (NIRS), and non-contrast magnetic resonance imaging (MRI) using coronary atherosclerosis T1-weighted characterisation with integrated anatomical reference technique, recently developed by our group. Case Summary A 75-year-old woman presented with chest discomfort on exertion. CCTA revealed severe stenosis of the mid-left circumflex coronary artery and minimal stenosis with a large eccentric LM plaque. The LM lesion had an LAP, with a minimum plaque attenuation of 25 Hounsfield units. On non-contrast T1-weighted MRI, a high-intensity plaque with a plaque-to-myocardium signal intensity ratio of 3.02 was observed within the vessel wall, indicating intraplaque haemorrhage. NIRS categorised the lesion as non-lipid-rich, with a maximum lipid core burden index in 4 mm of 169. Discussion Intraplaque haemorrhage is a key feature of plaque instability, which is different from the lipid-rich necrotic core. Non-contrast T1-weighted MRI is ideal for detecting intraplaque haemorrhage with short T1 values. The imaging findings suggest that LAP on CCTA may represent not only lipid-rich plaques but also intraplaque haemorrhage. MRI provides a unique insight into plaque vulnerability from a different perspective than lipid assessment. Multimodality imaging, including MRI, facilitates the understanding complicated plaque morphologies.

Association of coronary artery calcium score groups with qualitative and quantitatively assessed adverse plaque

Introduction Coronary artery calcification is a marker of cardiovascular risk, but its association with qualitatively and quantitatively assessed plaque subtypes on coronary computed tomography (CT) angiography (CCTA) is unknown. Methods In this post-hoc analysis, CT images and clinical outcomes were assessed in SCOT-HEART trial participants. Agatston coronary artery calcium score (CACS) was measured on non-contrast CT and was stratified as zero (0 Agatston units, AU), minimal (1 to 9AU), low (10 to 99AU), moderate (100 to 399AU), high (400 to 999AU) and very high (≥1000AU). Adverse plaques were investigated with qualitative (visual categorisation of positive remodelling, low-attenuation plaque, spotty calcification, napkin ring sign) and quantitative (calcified, non-calcified, low-attenuation and total plaque burden) methods. Results Images of 1769 patients were assessed (mean age 58±9 years, 56% male, median Agatston score 21 [interquartile range 0 to 230] AU). Of these 36% had a zero, 9% minimal, 20% low, 17% moderate, 10% high and 8% very high CACS. Amongst patients with a zero CACS, 14% had nonobstructive disease, 2% had obstructive disease, 2% had visually assessed adverse plaques and 13% had quantitative low-attenuation plaque (LAP) burden >4% (Figure 1). Non-calcified and low-attenuation plaque burden increased between patients with zero, minimal and low CACS (p<0.001), but there was no difference between those with medium, high and very high CACS. Over a median follow-up of 4.8 [4.1 to 5.7] years, fatal or non-fatal myocardial infarction occurred in 41 patients, 10% of whom had zero CACS. CACS ≥1000AU (Hazard ratio (HR) 4.55 [1.20 to 17.3], p=0.026) and low-attenuation plaque burden (HR 1.74 [1.19 to 2.54], p=0.004) were the only predictors of myocardial infarction, independent of obstructive disease and cardiovascular risk score. Figure 2 shows example CCTA images in a patient with zero CACS, non-calcified plaque (red), low attenuation plaque (orange) burden >4% and obstructive disease in the left anterior descending coronary artery. Conclusions In patients with stable chest pain, a zero CACS is associated with a good prognosis, but 1 in 6 have coronary artery disease, including the presence of adverse plaques. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation, National Institute of Health/National Heart, Lung, and Blood Institute

Pericoronary adipose tissue attenuation, low-attenuation plaque burden and 5-year risk of myocardial infarction

Introduction Pericoronary adipose tissue (PCAT) attenuation has emerged as a surrogate marker of pericoronary inflammation. To date, no studies have compared the impact of pericoronary adipose tissue (PCAT) attenuation and quantitative plaque burden on cardiac outcomes. Purpose We aimed to establish the relative merits of these approaches to risk prediction and hypothesised that the combination of PCAT attenuation and quantitative plaque burden measures could provide additive and improved prediction of myocardial infarction in patients with stable chest pain. Methods In a post-hoc analysis of a randomized controlled trial, we investigated the association between the future risk of fatal or non-fatal myocardial infarction and PCAT attenuation measured from CT coronary angiography using multivariable Cox regression models including plaque burden, obstructive coronary disease and cardiac risk score (incorporating age, sex, diabetes, smoking, hypertension, hyperlipidaemia and family history of cardiovascular disease). Results In 1697 evaluable participants (mean age 58±10 years), there were 37 myocardial infarctions after a median follow-up of 4.7 [interquartile interval, 4.0–5.7] years. Median low-attenuation plaque burden was 4.20 [0–6.86] % and mean PCAT −76±8 Hounsfield units (HU). PCAT attenuation of the right coronary artery (RCA) was predictive of myocardial infarction (hazard ratio [HR] 1.55, 95% CI 1.08–2.22; p=0.017, per 1 standard deviation increment) with an optimum threshold of −70.5 HU [Hazards ratio (HR) 2.45, 95% CI 1.2–4.9; p=0.01]. Univariable analysis also identified the burden of non-calcified, low-attenuation and calcified plaque as well as Agatston coronary calcium score, presence of obstructive coronary artery disease and cardiovascular risk score were predictors of myocardial infarction (Figure 1). In multivariable analysis, only the low-attenuation plaque burden (HR 1.80, 95% CI 1.16 to 2.81, p=0.011, per doubling) and PCAT-RCA (HR 1.47 95%1.02 to 2.13, p=0.040, per standard deviation increment) remained predictors of myocardial infarction (Figure 1). In multivariable analysis, adding PCAT-RCA ≥-70.5 HU to low-attenuation plaque burden >4% (optimum threshold for future myocardial infarction; HR = 4.87, 95% CI 2.03–11.78; p<0.0001) led to improved prediction of future myocardial infarction (HR 11.7, 95% CI 3.3–40.9; p<0.0001); Figure 2. In ROC analysis, integration of PCAT-RCA attenuation and LAP burden, increased the prediction for myocardial infarction compared to LAP alone (ΔAUC=0.04; p=0.01). Conclusion CT coronary angiography defined PCAT attenuation and low-attenuation plaque have marked and additive predictive value for the risk of fatal or non-fatal myocardial infarction. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Chief Scientist Office of the Scottish Government Health and Social Care Directorates, British Heart Foundation, National Institute of Health/National Heart, Lung, and Blood Institute grant

Blood iron level and vulnerable coronary atherosclerotic plaques

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Science Centre, Poland BACKGROUND Vulnerable plaque rupture is one of the causes of acute coronary syndromes. Preliminary research indicate that iron might accelerate the oxidation of low density lipoproteins (LDL) which can then be taken up by the LDL receptor on macrophages leading to their development into foam cells. Foam cell infiltration and necrotic core expansion are key events in atherogenesis and vulnerable plaque formation. However, the potential pathophysiological roles of iron in plaque development remain uncertain. PURPOSE The aim of the study was to investigate the relationship between iron and the type and composition of atherosclerotic plaques in the coronary arteries. METHODS In 200 patients with ≥1 stenosis ≥50% in computed tomography coronary angiography (CTCA) made for clinical indications we assessed: free iron level, the presence of high-risk plaque features: low-attenuation plaque (LAP), napkin-ring sign (NRS), positive remodeling (PR) and spotty calcium (SC) (CT Coronary, Syngo, Siemens), type of plaque (calcified, mixed, non-calcified) and their composition (calcified, fibrous, fibro-fatty, necrotic core) (QAngioCT, Medis). Fibro-fatty and necrotic core were analyzed together as vulnerable plaque component. The study was financed by the National Science Centre (2016/21/N/NZ5/01450). RESULTS Of 200 patients (125 men, 66 ± 10 years), the mean iron level (µg/dl) was 91 ±30 for women and 103 ±33 for men (p = 0.5). 3 patients had iron deficiency and 2 patients had iron overload. In CTCA analysis there were 815 calcified, 344 non-calcified and 438 mixed plaques. There was a trend in correlation between iron level and non-calcified plaque presence (p = 0.06). LAP was detected in 56 patients, NRS in 83, PR in 132, and SC in 125. Patients with LAP had higher iron levels (113 vs 93 µg/dl; p < 0.001). There was no association between iron and NRS, PR or SC (p > 0.05). In univariate regression analysis, the predictors of LAP were iron (p < 0.001) and male gender (p = 0.01). In multivariate regression analysis, iron was an independent predictor of LAP (p < 0.001; OR 1.02; 95%CI 1.01-1.03). Higher iron levels correlated with more fibro-fatty (p = 0.009) and necrotic core (p = 0.02); less calcified (p = 0.04); and with no relation to fibrous (p = 0.9), thus higher iron levels were associated with greater vulnerable plaque component (p = 0.003). CONCLUSIONS Higher iron levels are more likely to be associated with low-attenuation plaque and a greater vulnerable component of atherosclerotic plaques.

Clinical Relevance of Coronary Computed Tomography Angiography Beyond Coronary Artery Stenosis

Background The capabilities of coronary computed tomography angiography (CCTA) have advanced significantly in the past decade. Its capacity to detect stenotic coronary arteries safely and consistently has led to a marked decline in invasive diagnostic angiography. However, CCTA can do much more than identify coronary artery stenoses. Method This review discusses applications of CCTA beyond coronary stenosis assessment, focusing in particular on the visual and quantitative analysis of atherosclerotic plaque. Results Established signs of visually assessed high-risk plaque on CT include positive remodeling, low-attenuation plaque, spotty calcification, and the napkin-ring sign, which correlate with the histological thin-cap fibroatheroma. Recently, quantification of plaque subtypes has further improved the assessment of coronary plaque on CT. Quantitatively assessed low-attenuation plaque, which correlates with the necrotic core of the thin-cap fibroatheroma, has demonstrated superiority over stenosis severity and coronary calcium score in predicting subsequent myocardial infarction. Current research aims to use radiomic and machine learning methods to further improve our understanding of high-risk atherosclerotic plaque subtypes identified on CCTA. Conclusion Despite rapid technological advances in the field of coronary computed tomography angiography, there remains a significant lag in routine clinical practice where use is often limited to lumenography. We summarize some of the most promising techniques that significantly improve the diagnostic and prognostic potential of CCTA. Key Points: Citation Format