Coronary Heart Disease (CHD) is the leading cause of death and morbidity worldwide, with a high socioeconomic burden and one million deaths in the U.S. About 50 per cent of acute myocardial infarctions occur in previously asymptomatic patients, pinpointing at the major weakness of current strategies for screening of CHD.
Conventional assessment based on cardiovascular risk factors (EuroSCORE or ASCVD) allows for a 10-year cardiac event prediction, but fails to accurately diagnose CHD at early stages, in which fatal outcomes would be still preventable by initiating medical therapy and risk factor intervention.
Coronary computed tomography angiography (CTA) is a novel non-invasive imaging technique, enabling a direct visualisation of the coronary arteries at high resolution in submillimetre range (<0.3mm), hence CTA creates new horizons for screening of CHD.
Early stages of atherosclerosis, such as non-calcified fibroatheroma can be detected with high accuracy, even in the absence of coronary calcification. These non-calcified lesions can be further characterised by their specific x-ray absorption, the CT-attenuation (Hounsfield Units, HU) by value of less than <160 HU. Non-calcified plaque can be stratified by their specific tissue components into lipid-necrotic core (<30HU), and fibro-fatty lesions (30-160HU). Both have been liked with adverse outcomes, especially the necrotic core plaque (LAP<30HU) (5-9) but also fibro-fatty (LAP<60HU) and specific imaging features such as the hyperdense rim “Napkin Ring” sign (Fig 1b).
Comparative studies with OCT and pathohistology have identified four major criteria for plaque “vulnerability”: Beyond LAP and Napkin Ring Sing, spotty calcification of less than 3mm and positive remodelling (Remodelling Index>1.1) are regarded as markers for “high-risk” plaque. These criteria define a precursor (culprit) lesions for later acute coronary syndromes.
During the natural course of atherosclerosis over decades, noncalcified fibroatheroma transforms into a dense- compact calcified lesions at later stages, which may narrow the vessels (Fig 1c) up to severe >70 per cent stenosis, and require treatment with percutaneous transarterial coronary angioplasty (PTCA) and STENT implantation (Fig 1d), in order to prevent adverse outcome.
Newest data from the ICONIC registry have shown that CTA enables monitoring of lesions, and revealed that the denser the plaque, the less likely the chance of ACS. In lesions with more than 350 HU compactness, the number of ACS decreased, and above 1000 HU (“1 K”, syn. marble plaque”) a significant decline was observed.
This effect can be obtained by medication such as statins, which act anti-inflammatory and reduce blood cholesterol (c-LDL) hence, the transformation of fibrous into stable calcified lesions. During statin therapy, the total plaque volume progression, and especially the necrotic core, fibrous and fibrofatty lesions growth was significantly lower – in large international multicentric study registry (PARADIGM) enrolling 1241 patients over a mean period of two years.
Of note, these lesions may be found even in patients without coronary calcification (calcium score zero), in about a quarter (25.9 per cent), while the rate of significant >50 per cent coronary stenosis was with 5.1 per cent low but not negligible.
The coronary CT calcium score is another imaging tool for quantification of coronary calcium and risk stratification based on total calcium volume and density (Agatston Score), however it misses the chance to detect early fibroatheroma.
Data from CONFIRM registry, a large international multicentric trial, have shown that coronary stenosis and plaque burden by CTA improve risk stratification as compared to calcium scoring.
Beyond, the strength of CTA lies in the excellent false negative rate (90-99 per cent NPV) for exclusion of CHD, ensuring a safe and reliable exclusion of CHD in individuals, in whom CHD is already suspected by regular clinical work-up exams. Such patients are those with atypical chest pain symptoms, and low-to-intermediate ASCVD risk.
Most recently, two prospective randomised multicentric trials in the U.S. and Europe (PROMISE and SCOT-HEART), have proven the safety and efficacy of coronary CTA for patients with stable chest pain. The SCOT HEART trial has even shown favourable outcomes in patients undergoing CTA, as compared to standard of care (SOC), in terms of a lower event rate in the CTA group (2.3 vs 2.9 per cent, p=0.004).
A new field is currently emerging in cardiovascular imaging: artificial intelligence (AI)/machine learning. AI based–deep learning tools provide three promising potentials. First, they improve risk prediction, when combining CTA imaging parameters with conventional risk factors. Second, “radiomics” based analysis allows for assignment of a voxel into texture and feature based parameters and hence a more detailed sub-analysis of images. And third, automated feature recognition allows for a more accurate segmentation of both calcium and of coronary vessels from CTA.
Therefore, they provide the potential to improve diagnostic accuracy and efficacy in clinical practice, for example, the quantification of global plaque burden, a predictor for adverse outcomes and ischemia or automated extraction and interpolation of calcium load from standardised chest CT. Machine learning tools also allow for complex analytics such as quantification of flow, as recently shown for computation of the fractional flow reserve (FFR) by CTA (20).
Importantly, early risk factor management, such as by reducing c-LDL by medication such as statins or eztemibe or PSK 9 inhibitors have shown reduction in plaque burden progression and initiate the transformation of vulnerable lesions into stable. Only as little as 39 mg/dl c-LDL reduction results in a 25 per cent lower ASCVD risk. Total plaque burden is one of the main drivers for ischemia and adverse outcomes, even in patients with non-obstructive lesions (ANOCA), especially “vulnerable” low attenuation plaques with positive remodelling.
Also, lifestyle modifications play a key role: regular exercise, weight control, smoking cessation and blood pressure control are crucial factors to prevent progression of atherosclerosis and adverse outcome.
Coronary CTA is a promising novel technique for accurate screening of coronary heart disease. CTA enables early detection and consecutively, the initiation of preventive actions with a great potential to reduce global burden of CHD, and most importantly, fatal outcome with personal tragedies affecting all age groups including even young or middle-aged individuals.
References available on request.