Non-contrast cardiac computed tomography in order to obtain the coronary artery calcium score has become an established diagnostic procedure in the clinical setting, and is commonly employed in clinical and population-based research. This state-of-the-art review paper highlights the potential gain in information that can be obtained from the non-contrast coronary calcium scans without any necessary modifications to the scan protocol. This includes markers of cardio-metabolic health, such as the amount of epicardial fat and liver fat, but also markers of general health including bone density and lung density. Finally, this paper addresses the importance of incidental findings and of radiation exposure accompanying imaging with non-contrast cardiac computed tomography. Despite the fact that coronary calcium scan protocols have been optimized for the visualization of coronary calcification in terms image quality and radiation exposure, it is important for radiologists, cardiologists and medical specialists in the field of preventive medicine to acknowledge that numerous additional markers of cardio-metabolic health and general health can be readily identified on a coronary calcium scan. Key Points � The coronary artery calcium score substantially increased the use of cardiac CT. � Cardio-metabolic and general health markers may be derived without changes to the scan protocol. � Those include epicardial fat, aortic valve calcifications, liver fat, bone density, and lung density. � Clinicians must be aware of this potential additional yield from non-contrast cardiac CT. . . . . Keywords Coronary artery calcium score Atherosclerosis X-ray computed tomography Biomarkers Preventive medicine Abbreviations Introduction ALARA As-low-as-reasonably-achievable CACS Coronary artery calcium score Over the past decade, non-contrast cardiac computed tomogra- CT Computed tomography phy (CT) has become an established diagnostic tool in clinical ECG Electrocardiography practice. The main purpose of these coronary calcium scans is to obtain the coronary artery calcium score (CACS) [1, 2], which is associated with a graded increased risk of future coronary events, * Daniel Bos heart failure and mortality [3–5], and even relates to dementia, email@example.com cancer and kidney disease [6, 7]. On the other hand, a negative or zero CACS denotes a mid- to long-term risk of coronary events Department of Radiology and Nuclear Medicine, Erasmus MC – that is close to zero [8, 9]. As such, the current ACC/AHA University Medical Centre Rotterdam, Rotterdam, The Netherlands guidelines on assessment of cardiovascular risk state that assess- Department of Epidemiology, Erasmus MC – University Medical ment of CACS may be considered based on a large number of Centre Rotterdam, P.O. Box 2040, 3000 observational studies: with a CACS of ≥ 300 Agatston units (or ≥ CA Rotterdam, The Netherlands 3 75th percentile for age, sex and ethnicity) supporting an upward Department of Epidemiology, Harvard T.H. Chan School of Public revision in risk assessment . A range of alternative ap- Health, Boston, MA, USA proaches to application of CACS for risk stratification in primary Department of Cardiology, Erasmus MC – University Medical Centre Rotterdam, Rotterdam, The Netherlands prevention has been proposed recently [11–13]. Eur Radiol (2018) 28:3082–3087 3083 Most clinical radiologists and cardiologists will be subsequent clinical events [17–19]. Importantly, these mea- aware of other cardiac imaging properties that can be sures of density and volume generally do not require addition- obtained from coronary calcium scans, such as large al processing or calculation, as these can be provided by most myocardial scars or dimensions of the heart and the commercially available CACS scoring software. Moreover, thoracic aorta . These can be assessed to detect the number and the regional distribution of calcifications can past-myocardial infarction, dilated cardiomyopathies, easily be visually assessed and provide additive predictive atrial enlargement, aneurysms and pericardial effusion. information regarding the future risk of major coronary events However, coronary calcium scans contain a wealth of . As a consequence, very recently a change in methodol- untapped information on other cardiovascular and non- ogy to assess coronary calcium scans was proposed in order to cardiovascular health parameters [15, 16]. It is important incorporate this additional information into a new CACS . for clinicians to be aware of the potential data on cardio-metabolic and general health that can be obtained Valvular calcification from such scans without making any modifications to the scan protocol (Table 1). Hence, the goal of this Using the same software as is used to obtain the CACS, one review is to provide an overview of some of the most can quantitatively assess the burden of aortic valve calcifica- apparent imaging markers related to cardio-metabolic tion (Fig. 1,blue) [22, 23] or mitral annular calcification in the and general health. Additionally, we discuss potential form of Agatston scores or volumes. The extent of aortic val- incidental findings and radiation exposure of coronary vular calcification is a direct representation of degenerative calcium scans. aortic valve stenosis  and is associated with adverse car- diovascular outcomes and mortality [25, 26]. More specifical- ly, recent evidence even highlighted that the load of aortic Markers of cardio-metabolic health valve calcification measured by CT provides incremental prognostic value to predict aortic valve stenosis progression With the increasing focus on preventive medicine and the and subsequent occurrence of clinical events . Similarly, accompanying demand for individual risk stratification, the mitral annular calcification, although less prevalent , was ability to calculate a patient’s risk of a clinical event relies found to be associated with CACS , and to increase the greatly on the accuracy and amount of the acquired informa- risk of atrial fibrillation . Additionally, progression of mi- tion. The coronary calcium scan can provide us with addition- tral annular calcification are an important predictor underlying al information regarding the patient’s cardiovascular health left atrial abnormalities that predispose to atrial fibrillation beyond the CACS. In the following paragraphs we address . several of these markers. Epicardial fat Coronary artery calcium volume and density Epicardial fat is defined as the layer of metabolically ac- The Agatston-based CACS is a summary measure based on tive adipose tissue that surrounds the myocardium and the the total volume and density of epicardial coronary calcifica- coronary arteries [32, 33]. Given this close anatomical tion into a single number ranging from 0 (i.e. the absence of connection, changes in the amount of epicardial fat may calcifications) to scores of several thousand indicating exten- directly influence these structures. Larger amounts of epi- sive coronary atherosclerosis. However, more recent evidence cardial fat are associated with more extensive coronary suggests that calcium volume and density each separately har- atherosclerosis [34–36], but also with direct arrhythmo- bour additional information with regard to the risk of genic effects on the myocardium in the form of an Table 1 Overview of imaging Cardio-metabolic health General health markers that can be derived from a coronary calcium scan Coronary artery calcium (Agatston score, volume and density) Vertebral bone density Aortic valve calcification (Agatston score, volume and density) Lung density Mitral annular calcification (Agatston score, volume and density) Dimensions of heart chambers and ascending aorta Epicardial fat volume Liver density Pulmonary artery diameter 3084 Eur Radiol (2018) 28:3082–3087 increased risk of new-onset atrial fibrillation and greater Pulmonary artery diameter burden of atrial fibrillation [37, 38]. Due to rapid im- provements in image-processing techniques it has become The diameter of the pulmonary artery (Fig. 1, orange) can be possible to quantify the amount of epicardial fat on non- measured on non-contrast scans using any CT-image viewer contrast CT scans [39, 40]. These quantification methods and may be considered as a marker of pulmonary arterial are robust and fully automatic, but have not yet reached pressure . When adjusted for body size by comparison the same level of usability as commercially available soft- to the aortic diameter in the same slice (i.e. the pulmonary- ware packages for calcium scoring. However, given the artery-to-aorta ratio), increased pulmonary artery diameters recent insights in the clinical importance of epicardial are related to risk of future adverse pulmonary events and fat, implementation of tools for epicardial fat quantifica- mortality, particularly in individuals with chronic obstructive tion in such software packages are expected. pulmonary disease [46, 47]. Liver density Beyond markers of cardio-metabolic health In most instances, a coronary calcium scan also includes In addition to aforementioned markers of cardio-metabolic visualization of the upper part of the liver. Despite this health, other structures that are imaged provide additional in- being only a limited part of the whole liver, measurement formation on for example fracture risk and the presence or risk of the mean attenuation value at two or three locations – of pulmonary events (Table 1). which can readily be done using any CT-image viewer – appears to reflect the total amount of fat in the liver [41, Bone density 42]. In turn, the amount of liver fat is regarded as an important precursor of the metabolic syndrome, and is With regard to measuring the bone density (Fig.1,pink),it related to both subclinical and clinical cardiovascular dis- should be acknowledged that apart from the heart, there may ease [43, 44]. Liver density may also reflect subclinical be considerable variation in the imaged area, depending on hepatic fluid congestion and liver fat is associated with patient size and position. Yet, the majority of scans will in- adverse cardiac remodelling, both of which may herald clude multiple thoracic vertebrae that can be assessed for bone future heart failure . mineral density – a key modifiable risk factor for osteoporotic Fig. 1 Imaging markers on non- contrast coronary calcium scans. Four slices of a coronary calcium scan of a single patient showing the heart at different levels with, in colour, the different tissues from which the potential imaging markers may be obtained Eur Radiol (2018) 28:3082–3087 3085 fractures [48, 49] – or the presence of vertebral osteoporotic doses have been decreasing over the last few years and are fractures . expected to decrease further with advances in technology . Specifically for prospective ECG-gated non-contrast coronary Lung density calcium scans, radiation exposure approximates 1.5 mSv (es- timated using ImpactDose version 2.3, 2016, CT Imaging Measuring lung density (Fig. 1, dark blue) as a direct marker GmbH, Erlangen, Germany) [58, 59]. For comparison, the of emphysema can be challenging, because in most clinical annual background radiation varies between 2 and 5 mSv. settings the field-of-view is narrowly set to visualize coronary Nonetheless, radiation exposure should always be weighed calcium only . Nonetheless, the overall lung density can against the information obtained from a coronary calcium generally be measured in the lower lobes of the lungs and in scan. Following the ALARA principle in minimizing radia- the areas surrounding the hila. However, it is important to tion exposure, it seems only reasonable to also force clinicians mention that apart from this dedicated, narrow field-of-view, and researchers to transpose this principle to data acquisition one may consider additionally reconstructing the coronary once a scan is made: acquire as much as reasonably achievable calcium scan with a wider field-of-view to also visualize all relevant information from every imaging study. the lung tissue that was originally in the scan field. Although the tops of the lungs will still be missing, one can obtain an accurate impression of the status of the remaining part of the Conclusion lungs with respect to the amount of emphysema [51, 52]. A downside of this wider field-of-view is the greater probability The clinical value of the CACS in terms of individual risk as- of detecting incidental findings. sessment of future cardiac events has led to an increased use of non-contrast cardiac CT in both clinical and research settings during the past decades. Many other markers of cardio- Incidental findings metabolic health and general health may readily be evaluated on these examinations. Clinical cardiologists, cardiovascular ra- When performing imaging, both in the clinical setting as well diologists and medical specialists in the field of preventive med- as in the research setting, incidental findings can be expected. icine should be aware of this potential diagnostic and prognostic However, the spectrum of potential incidental findings is rel- extra-coronary yield of the coronary calcium scan, and widen atively limited for coronary calcium scans . Apart from their professional field-of-view to look beyond the heart. cardiovascular abnormalities, incidental findings may espe- cially be detected in the liver and the lungs. Given that no Acknowledgements The authors thank Dr. Matthew J. Budoff, MD contrast is administered during a coronary calcium scan, po- FACC FAHA FSCCT (Division of Cardiology, Los Angeles tential findings in the liver are largely restricted to cystic le- Biomedical Research Institute, Harbor-UCLA Medical Center, sions. However, for the lungs a substantial number of pulmo- Torrance, CA, USA) for his comments on a draft version of the manuscript. nary nodules may be expected. Especially for older individ- uals and smokers, clear-cut criteria on the diagnostic work-up Funding The authors state that this work has not received any funding. of such pulmonary nodules have been established and refined in the past decade [54, 55]. Other less frequent incidental Compliance with ethical standards findings may include interstitial changes of the lung, pleural effusion, chest wall abnormalities, breast calcifications and Guarantor The scientific guarantor of this publication is Daniel Bos. mediastinal lymphadenopathy. Conflict of interest The authors of this manuscript declare no relation- ships with any companies whose products or services may be related to the subject matter of the article. Radiation Statistics and biometry No complex statistical methods were necessary A topic of concern accompanying the use of the coronary for this paper. calcium scan is the ionizing radiation exposure to the patient or, in the research setting, to the study participant . Two Informed consent Informed consent was not required because the cur- rent article is a review article. general key principles that should always be kept in mind when ordering a CT examination of any kind are justification Ethical approval Institutional Review Board approval was not required in ordering the examination and optimization of the scan pro- because the current article is a review article. tocol in the way that the radiation exposure is as-low-as- reasonably-achievable (ALARA). With the newer generation Methodology � Performed at one institution. CT scanners and improvements in scan protocols, radiation 3086 Eur Radiol (2018) 28:3082–3087 Open Access This article is distributed under the terms of the Creative 17. 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Published: Jan 30, 2018
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