Screening Patients Using Digital Radiographs of the Aortic Arch to Reduce Unnecessary Computed Tomography for Coronary Artery Calcium Score

Transcription

1 Screening Patients Using Digital Radiographs of the Aortic Arch to Reduce Unnecessary Computed Tomography for Coronary Artery Calcium Score Chureerat Chantharat, M.D. Department of Radiology, Faculty of medicine. Prince of Songkla University, Hat Yai, Songkhla, Thailand.

2 Screening Patients Using Digital Radiographs of the Aortic Arch to Reduce Unnecessary Computed Tomography for Coronary Artery Calcium Score

3 1 Abstract Purpose: The main purpose is established appropriate screening method for all patients, who are sent to performed computed tomography for the coronary artery calcium score, for reducing number of procedures which result in waste time, unnecessary radiation and cost to the patients with reducing unnecessary cost and workload in the institution. Methods: There was restrospective study to record patients history including age, sex, date of request/performed images, aortic arch score by radiography and coronary artery calcium score by computed tomography between 1 January 2012 to 31 December Aortic arch calcific deposit score by chest radiography were using of assigning a score from 0-5 depending on the extent of calcification as following; score 0 indicative to no calcification, score 1 indicative to small spots of calcifications of the aortic arch, score 2 indicative to a single thick area of calcification of the aortic arch, score 3 indicative to two thick areas of calcifications of the aortic arch, score 4 indicative to equal or more than three thick areas of calcifications of the aortic arch and score 5 indicative to more than one quadrant thick areas of calcifications of the aortic arch by 2 radiologists, who have been well experience in interpretation of coronary artery disease for 3 and 6 years, respectively. They were blind the patient information and their reports for reducing bias. Then calculation to find out proper related cut-point of aortic arch score to coronary artery calcium score 400 were done.

4 2 Result: This study shows significant association between aortic arch calcific deposits and coronary calcium score (p-value < 0.05). The calculated cut-point of aortic arch score 4 is high specificity for prediction of coronary artery calcium score 400 between 83-91%. Conclusion: High aortic arch score 4 is valuable to management the patients with significant clinical presentations for coronary artery disease by shifting to coronary artery angiogram for prompt diagnosis and treatment.

5 3 Introduction Coronary artery disease remains one of the leading causes of morbidity and mortality worldwide. Coronary artery disease rates are affected by multiple risk factors, especially blood pressure, blood cholesterol, smoking, physical activity and diet. Death rates from coronary artery disease can be reduced by improving prevention programs, early diagnosis, and early treatment. Nowadays, there are many modalities for routine screening for coronary artery disease. Computed tomography to work up a coronary artery calcium score or check for stenosis is one choice. However this modality has limitations, especially if there is a high calcium score 400, because high calcium can cause artifacts which make assessment of coronary stenosis from a computed tomography angiogram difficult. This problem affects the patients and institutions. Many patients face a long wait for the computed tomography work up because a lot of patients are sent for this procedure. Unfortunately, in many cases, when they finally get the procedure it has been a waste of money and time because the results are too high calcium score, as noted above, and are thus not useful due to artifacts from high calcium levels, and other investigations may be required. Moreover, the patients have been exposed to unnecessary radiation and expense. The institutional effects are increased but unnecessary work load for the technicians and radiologists who perform the computed tomography for coronary artery calcium score, and the time they use to interpret the scans. This unnecessary work also costs money that could have been used elsewhere. So devising a screening method to help select appropriate patients for this procedure would be one way to reduce this problem.

6 4 Study design - Retrospective study Materials and Methods Study setting - Songklanagarind hospital Populations Inclusion criteria - Age over 15 years - Suspected coronary artery disease - Have chest radiograph within 3 months before check up coronary artery calcium score by computed tomography between 1 January 2012 to 31 December 2014 Exclusion criteria - On medical instruments such as coronary artery stent, aortic stent, pacemaker or staples - Have a history of coronary artery bypass graft - Incomplete information The output of the sample size calculation (16,17) For estimating the infinite population proportion Proportion (p) = 0.95, Error (d) = 0.03 Alpha (α) = 0.05, Z(0.025) = Sample size (n) = 203 (at least)

7 Recording information 1. Record patients history including age, date of request/performed images 2. Aortic arch calcific deposit score by chest radiography Record calcium deposit at the aortic arch by assigning a score from 0-5depending on the extent of calcification (figure 1) - Score 0 denotes no calcification. - Score 1 indicates small spots of calcifications of the aortic arch. - Score 2 indicates a single thick area of calcification of the aortic arch. - Score 3 indicates two thick areas of calcifications of the aortic arch. - Score 4 indicates equal or more than three thick areas of calcifications of the aortic arch. - Score 5 indicates equal or more than one thick quadrant thick areas of calcifications of the aortic arch. Recording information by 2 radiologists, who have been well experience in interpretation of coronary artery disease for 3 and 6 years, respectively. They were blind the patient information and their reports for reducing bias. 3. Coronary artery calcium score by computed tomography (PhilipMDCT) The coronary calcium score are calculated by computer program base no Agatston Score (13) (figure 2). 5

8 6 Plain chest radiography and computed tomography techniques 1. Plain chest radiograph using a Toshiba digital 100 kvp, 4 mas, with antiscatter grid (Bucky), patient distance from X-ray source about 180 cm. Exposure dose adjusted by AEC (Automatic Exposure Control) (14-15) 2. Computed tomography for coronary calcium score using a Philip 64-slices Brilliance TM MDCT with software V , 120 kvp, 55 mas for 5 cycles (14-15)

9 7 Statistical analysis - Calculations to find the relation of aortic arch arch score from digital radiographs to coronary artery calcium score. - Find out cut-point of aortic arch score from plain radiographs related to coronary artery calcium score 400(acceptable p- value < 0.05).

10 8 Result Study population The study was restrospective evaluation in 560 patients, who were performed computed tomography for coronary artery calcium score between 1 January 2012 to 31 December Only 236 patients were included into this study (male = 127, female = 109, between years; mean age 60 years).they were divided into 2 groups by coronary artery calcium score by using cut-point at 400 (figure 3). The population in groups of coronary artery calcium score < 400and 400 were 200 (84.7%) and 36(15.3%), respectively (table 1). The mean ages of patients in groups of coronary artery calcium score < 400 and 400were 58.8 and 68 years, respectively (table 1). There was variable duration to perform computed tomography for coronary artery calcium from 0 to 78 days in all patient and 4-60 days in patients with coronary artery calcium score 400 (table 1 and figure 4). Significant relationship between calcium deposits at the aortic arch (aortic arch score) and coronary artery calcium score was detected by both observers (table 1). However, the relationship of coronary artery calcium score and aortic arch score was slightly variable (figures5-7). At aortic arch score 3 is increased probability to detected patients, who had coronary artery calcium score 400 as compared with non-screening patients from 15% to be % (table 2) in observer 1. At aortic arch score 2 is increased probability to detected patients, who had coronary artery calcium score 400 as compared with non-screening patients from 15% to be % (table 3) in observer 2. From the result of two observers, those were nearly likelihood ratio of aortic arch score 0-1, 2-3 and 4-5 (table 2-3), so grouping data was

11 performed (table 4-5) before calculated cut-point of aortic arch score compared with coronary calcium score 400 and calculated interobserver agreement. When using cut-point of aortic arch score 3 in observer 1 and 2 in observer 2 are will increased probability to detected coronary artery calcium score 400 (table 2-3). However, for decreased false negative, because those patients will be waste of money and time with exposed to unnecessary radiation from performed computed tomography for coronary artery calcium score, the best cut-point is 4 (indicates equal, more than three areas or more than one quadrant of calcifications of the aortic arch) (table 4-5 and figures ). In this study was using cut-point of aortic arch score at 4to compare with <400 and 400 of coronary calcium score. The sensitivity and specificity in observer 1 were 36% and 83% (figure 8.2). The sensitivity and specificity in observer 2 were 16.7% on and 91% (figure 9.2). In this study, interobserver agreement is 70.76% and Kappa value is 0.52(moderate agreement). 9

12 10 Figure 1 Assigning aortic arch score Score 0 No calcification Score Small spots of calcifications of the aortic arch Score 2 A single thick area of calcification of the aortic arch

13 11 Score 3 Two thick areas of calcifications of the aortic arch Score 4 Equal or more than three thick areas of calcifications of the aortic arch Score 5 Equal or more than quadrant thick areas of calcifications of the aortic arch

14 Figure 2 Coronary artery calcium score by Agatston Method 12

15 13 Performed coronary artery calcium score (1 January 2012 to 31 December 2014) N = 560 Excluded patients N = 324 Included patient N = 236 (Male = 127, Female = 109) - On cardiac medical instruments - On coronary artery bypass graft - Incomplete information Calcium score < 400 N = 200 Calcium score 400 N = 36 Figure 3 The population in this study

16 14 Table 1 General information Calcium score < 400 Calcium score 400 Test stat. P value Total Age t-test (234 df) = 4.66 < mean(sd) 58.8 (11.2) 68 (9.1) Sex Chisq. (1 df) = male 105 (52.5%) 22 (61.1%) female 95 (47.5%) 14 (38.9%) duration Ranksum test 0.88 median(iqr) 23 (15,33.2) 21 (14.8,32.2) arch1 (observer 1) Fisher's exact (12.0%) 0 (0%) 1 81 (40.5%) 15 (41.7%) 2 35 (17.5%) 2 (5.6%) 3 25 (12.5%) 6 (16.7%) 4 18 (9.0%) 7 (19.4%) 5 17 (8.5%) 6 (16.7%) arch2 (observer 2) Fisher's exact (31.0%) 4 (11.1%) 1 45 (22.5%) 6 (16.7%) 2 49 (24.5%) 13 (36.1%) 3 26 (13.0%) 7 (19.4%) 4 10 (5.0%) 4 (11.1%) 5 8 (4.0%) 2 (5.6%)

17 15 Figure 4 Distribution of duration to perform computed tomography for coronary artery calcium score in groups of patients with coronary calcium score < 400 and 400

18 Table 2 Statistic analysis when divided arch score 0, 1, 2, 3, 4 and 5 to compare with calcium score < 400 and 400 of observer 1 16 Calcium score < 400 Calcium score 400 Probability Odds ratio LR+ Arch score Arch score Arch score Arch score Arch score Arch score Baseline Table 3 Statistic analysis when divided arch score 0, 1, 2, 3, 4 and 5 to compare with calcium score < 400 and 400 of observer 2 Calcium score < 400 Calcium score 400 Probability Odds ratio LR+ Arch score Arch score Arch score Arch score Arch score Arch score Baseline

19 Coronary artery calcium score Observer 1 Observer Aortic arch score Figure 5 Relationship between aortic arch score with coronary artery calcium score by observer 1 and % 53.5% 37.5% 30% 17.5% 9% Figure 6 Percentage of population in group of coronary artery calcium score < 400 by observer 1 and 2

20 % 41.7% 36.1% 27.8% 22.2% 16.7% Figure 7 Percentage of population in group of coronary artery calcium score 400 by observer 1 and 2 Table 4 Sensitivity and specificity when divided arch score 0-1, 2-3 and 4-5 to compare with calcium score < 400 and 400 of observer 1 Arch Score Calcium score < 400 Calcium score 400 Sensitivity Specificity (52.5) 15 (41.7) (30) 8 (22.2) (17.5) 13 (36.1)

21 Sensitivity Arch score 0-1 ; AUC = Arch score 2-3 ; AUC = Arch score 4-5 ; AUC = Specificity Figure 8.1 Sensitivity and specificity in different cut-point of aortic arch score of observer 1

22 Sensitivity Area under the curve = Specificity Figure 8.2 Sensitivity and specificity at aortic arch score 4 of observer 1

23 Sensitivity 21 Table 5 Sensitivity and specificity when divided arch score 0-1, 2-3 and 4-5 to compare with calcium score < 400 and 400 of observer 2 Arch Score Calcium score < 400 Calcium score 400 Sensitivity Specificity (53.5) 10 (27.8) (37.5) 20 (55.6) (9) 6 (16.7) Arch score 0-1 ; AUC = Arch score 2-3 ; AUC = Arch score 4-5 ; AUC = Specificity Figure 9.1 Sensitivity and specificity in different cut-point of aortic arch score of observer 2

24 Sensitivity Area under the curve = Specificity Figure 9.2 Sensitivity and specificity at aortic arch score 4 of observer 2 Clinical suspicious for CAD Aortic score < 4 Aortic arch score 4 CT scan Unnecessary CT Lifestyle modification Angiogram Figure 10 Model for practical guideline

25 23 Figure 11 Calcified costal cartilage mimic aortic calcification Figure 12 Calcified tracheal wall mimic aortic calcification

26 24 Figure 13 Overlying manubrium Figure 14 Perihilar infiltration mimic aortic calcification

27 Discussion 25 The results from this study shows significant association between age and coronary artery calcium score (p-value < 0.05) with slightly older age in the patient group of coronary artery calcium score 400. Significant association between aortic arch score and coronary artery calcium score 400 (p-value < 0.05) is also concordant the previous report by Bannas P et al (7). So high coronary calcium score should be consider, when high aortic arch score is detected. Using aortic arch score 4 is high specificity for prediction of coronary artery calcium score 400 score during 83-91%. The wasting time to perform computed tomography in this patient group was variable between 4 to 60 days. In the finally those patients should be definite diagnosis by coronary artery angiogram. The patients presented with highly suspicious coronary artery disease with aortic arch score 4 are should be shifting investigation to coronary artery angiogram because this patient group is highly limited to evaluated patency of coronary artery by computed tomography due to streak artifact from high coronary artery calcification. Moreover, the patients have been exposed to unnecessary radiation and expense. The benefits from shifting investigation to coronary artery are prompt diagnosis and treatment (figure 10). However, this study still has several limitations as described following; First, this study did not record information of coronary risk factors and get final definite diagnosis because there is incomplete information in hospital data base due to variable record from and management of clinicians.

28 Second, artifacts from chest radiography such as calcified costal cartilages, calcified tracheal wall, overlying manubrium and perihilar infiltration are mimicaortic arch calcific deposits causing over estimate aortic arch score (false positive) (figure 11-14). Third, aortic arch score is newly applied to use in this study. The score should be clarify to clinician and radiologist for understandabilityin the same direction before using in clinical practice. Fourth, there is slightly small group of the patient with coronary artery calcium score 400. Fifth, although the results from this study is slightly high specificity when using cut-point of aortic arch score at 4 but false positive and false negative patient groups cannot be excluded. So some patient with aortic arch score 4may be unnecessary invasive investigation by coronary artery angiogram. Using clinical correlation to screening patient is benefit to select proper investigation for the patient to decrease unnecessary computed tomography. 26

29 Conclusion 27 In conclusion, high calcium deposits at the aortic arch (aortic arch score 4) is valuable to management the patients with significant clinical presentations for coronary artery disease by shifting to coronary artery angiogram for prompt diagnosis and treatment.

30 References Holman RL, Mc GH, Jr., Strong JP, Geer JC. The natural history of atherosclerosis: the early aortic lesions as seen in New Orleans in the middle of the of the 20th century. The American journal of pathology. 1958;34(2): Demer LL, Tintut Y. Vascular calcification: pathobiology of a multifaceted disease. Circulation. 2008;117(22): Pakkal M, Raj V, McCann GP. Non-invasive imaging in coronary artery disease including anatomical and functional evaluation of ischaemia and viability assessment. The British journal of radiology. 2011;84 Spec No 3:S Budoff MJ. Interpreting the coronary-artery calcium score. The New England journal of medicine. 2012;366(16): Boaz DR, Veronica F, Robyn LM, et al. Relationship between baseline coronary calcium score and demonstration of coronary artery stenoses during follow up in the Multi-Ethnic Study of Atherosclerosis (MESA). JACC Cardiovasc Imaging. 2009;2(10): Alireza A, Hamidreza P, Ahmad S.The value of coronary artery calcium score assessed by dual-source computed tomography coronary angiography for predicting presence and severity of coronary artery disease. Pol J Radiol. 2014;79: Bannas P, Jung C, Blanke P, Treszl A, Derlin T, Adam G, et al. Severe aortic arch calcification depicted on chest radiography strongly suggests coronary artery calcification. European radiology. 2013;23(10): Iribarren C, Sidney S, Sternfeld B, Browner WS. Calcification of the aortic arch: risk factors and association with coronary heart disease, stroke, and peripheral vascular disease. Jama. 2000;283(21):

31 9. Iijima K, Hashimoto H, Hashimoto M, Son BK, Ota H, Ogawa S, et al. Aortic arch calcification detectable on chest X-ray is a strong independent predictor of cardiovascular events beyond traditional risk factors. Atherosclerosis. 2010;210(1): Wilson PW, Kauppila LI, O'Donnell CJ, Kiel DP, Hannan M, Polak JM, et al. Abdominal aortic calcific deposits are an important predictor of vascular morbidity and mortality. Circulation. 2001;103(11): Levitzky YS, Cupples LA, Murabito JM, Kannel WB, Kiel DP, Wilson PW, et al. Prediction of intermittent claudication, ischemic stroke, and other cardiovascular disease by detection of abdominal aortic calcific deposits by plain lumbar radiographs. The American journal of cardiology. 2008;101(3): Parr A, Buttner P, Shahzad A, Golledge J. Relation of infra-renal abdominal aortic calcific deposits and cardiovascular events in patients with peripheral artery disease. The American journal of cardiology. 2010;105(6): Pelberg R, Mazur W. Introduction to Calcium Scoring, Cardiac CT Angiography Manual [accessed 2013 Dec 30]: Available from: Gerber TC, Carr JJ, Arai AE, Dixon RL, Ferrari VA, Gomes AS, et al. Ionizing radiation in cardiac imaging: a science advisory from the American Heart Association Committee on Cardiac Imaging of the Council on Clinical Cardiology and Committee on Cardiovascular Imaging and Intervention of the Council on Cardiovascular Radiology and Intervention. Circulation. 2009;119(7): Fuller MJ. General Radiography [Internet]. wikiradiography[updated 2013 Aug 29; accessed 2013 Dec 30]. Available from: 29

32 16. Wayne WD. (1995). Biostatistics: A foundation of analysis in the health sciences (6 th ed.). John Wiley&Sons, Inc., Ngamjarus C., Chongsuvivatwong V. (2014). n4studies: Sample size and power calculations for ios. The Royal Golden Jubilee Ph.D. Program - The Thailand Research Fund&Prince of Songkla University. 30