|Year : 2021 | Volume
| Issue : 1 | Page : 19-23
The role of fluoroscopically detected coronary calcium in predicting the presence of significant coronary lesions
Jostol Pinto, Sunitha K Viswanathan, George A Koshy, Prabha Nini Gupta, VV Radhakrishnan
Department of Cardiology, Government Medical College, Thiruvananthapuram, Kerala, India
|Date of Submission||20-Mar-2020|
|Date of Decision||18-Apr-2020|
|Date of Acceptance||12-Jul-2020|
|Date of Web Publication||18-Feb-2021|
Dr. Jostol Pinto
2-2-109/4, The Crystal House, Ladyhill Main Road, Urwa Chilimbi, Mangalore - 575 006, Karnataka
Source of Support: None, Conflict of Interest: None
Context: Coronary artery disease (CAD) accounts for over 16' of deaths worldwide. As part of its diagnosis and stratification of severity in a patient, a noninvasive modality would certainly be useful to triage CAD. Aims: To assess the diagnostic accuracy of fluoroscopically detected coronary artery calcification (CAC) as a tool to grade coronary stenosis. Settings and Design: Comparing severity of fluoroscopic CAC with a severity of CAD by coronary angiograms (CAGs) in a high-volume center. Subjects and Methods: Fluoroscopic presence of CAC was graded using the Yamanaka method and correlated with CAGs in 200 patients. Statistical Analysis Used: Sensitivity, specificity, predictive values, accuracy, Chi-squared tests for significance. Results: The overall prevalence of CAC was 43' varying with age, sex, and CAD severity. The most common location of CAC was the left anterior descending artery followed by right coronary artery. Fluoroscopic CAC had 94' specificity and 96.5' positive predictive value for significant stenosis, albeit lower sensitivity of 55.3'. While 63' of those patients with single-vessel CAC had multivessel CAD, 91' of those with multivessel CAC had multivessel CAD. CAC was detected as follows: 6' in minor CAD, 40' in single-vessel disease (VD), 64' in two- or three-VD, and 100' in those with four-VD (P = 0.001). CAC was seen in 69.6' of patients having chronic total occlusions (CTOs) while in only 32.6' without CTOs (P = 0.001). Conclusions: A strong relation is present between CAC and severity of CAD. CAC is not a good screening tool for CAD due to low sensitivity. Notably, multivessel CAC strongly predicts multivessel CAD.
Keywords: Coronary artery calcification, coronary artery disease, fluoroscopy, stratifying coronary artery disease
|How to cite this article:|
Pinto J, Viswanathan SK, Koshy GA, Gupta PN, Radhakrishnan V V. The role of fluoroscopically detected coronary calcium in predicting the presence of significant coronary lesions. J Indian coll cardiol 2021;11:19-23
|How to cite this URL:|
Pinto J, Viswanathan SK, Koshy GA, Gupta PN, Radhakrishnan V V. The role of fluoroscopically detected coronary calcium in predicting the presence of significant coronary lesions. J Indian coll cardiol [serial online] 2021 [cited 2021 Jun 13];11:19-23. Available from: https://www.joicc.org/text.asp?2021/11/1/19/309616
| Introduction|| |
Coronary artery disease (CAD) continues to remain as the most common cause of death globally, accounting for 15.9' of deaths. The World Health Organization estimates reveal that the global economic burden of CAD will rise from 47 million disability adjusted life years (DALYs) in 1990 to 82 million DALYs in 2020, most acutely felt in nations such as India, Egypt, and republics of the former Soviet Union. According to the American Heart Association, the projected direct (medical) and indirect (lost productivity) cost of all cardiovascular diseases is estimated to be over one trillion US dollars by 2030.
With such a harsh impact on mortality and morbidity, it is but imperative to discover practical and cost-effective methods in managing this burden. The coronary angiogram (CAG) has proven to be the gold standard in evaluating CAD in recent times, with other noninvasive tests such as coronary calcium scoring and computed tomographic CAG being auxiliary. Here, we have attempted another noninvasive method to stratify significant CAD based on fluoroscopy, which would assist in such triage. This could serve to stratify patients at higher risk of complications following coronary angioplasty, prepare with better devices to negotiate challenging lesions, provide better insight into the disease severity, and aid in patient selection for the use of adjunctive atheroablative devices.
| Subjects and Methods|| |
Our study is a diagnostic test evaluation done at the department of cardiology at our hospital which is a high-volume tertiary care center for? percutaneous coronary angioplasty (PCI). We studied 200 adults who underwent a CAG or an elective or primary PCI while excluding those patients who had earlier undergone coronary stenting or coronary artery bypass grafting. We also excluded patients not willing for participation in the study and those with hemodynamic or electrical instability.
After written informed consent, basic data of each patient enrolled were collected and documented. This included age, gender, indication for angiogram or PCI and pre-CAG diagnosis, risk factors including but not limited to diabetes mellitus, dyslipidemia, systemic hypertension, smoking, chronic kidney disease, presence of other medical comorbidities, and functional class of existing symptoms suggesting CAD. Patient's blood levels of urea and creatinine and electrocardiogram findings were also noted. Echocardiographic documentation of regional wall motion abnormality as well as left ventricular ejection fraction of each patient was recorded in detail using the GE Vivid E9 machine.
In the cardiac catheterization laboratory, CAGs and cine-fluoroscopic loops were acquired (using the “Siemens Artis Zee” Interventional Angiographic System) with default radiographic settings in the range of 100 mA, 70 kV, 6.8 ms to 467 mA, 81 kV, 3.2 ms with a standard frame rate of 15 Hz. These settings were not altered for the purpose of the study. As part of the conventional angiogram, three loops were recorded in low-intensity and cine-fluoroscopic imaging: the 40° left anterior oblique with 15° caudal tilt, the 20° right anterior oblique with 15° caudal tilt, and the anteroposterior with 15° cranial tilt. The total screening fluoroscopic time was the set of initial frames of each loop of the conventional angiogram, and hence patients had no additional radiation exposure. Patients continued with the rest of the CAG, which may or may not have been be followed by an angioplasty as per the predetermined plan. The findings of the study were not in any way used to alter the line of planned management.
The frames of low-intensity fluoroscopic and cine-fluoroscopic recordings prior to contrast administration were collated separately and analyzed for severity of coronary calcium, blinding the observer to the rest of the angiogram. The severity of calcium was graded semi-quantitatively by Yamanaka's method (Grades–04), as seen in [Figure 1], incorporating both density and extent.
|Figure 1: Semi-quantitative grading of coronary calcium in a vessel (Yamanaka method)|
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Grading of calcium was thus applied to any calcium noted in the territory of left anterior descending (LAD), left circumflex (LCX), right coronary artery (RCA), and/or left main coronary artery (LMCA). In our study, calcium score was calculated to estimate severity of coronary calcium using a simple additive formula:
Calcium score = LAD Grade + LCX grade + RCA grade + LMCA grade.
The recorded frames with contrast were separately collated and analyzed for severity of coronary luminal stenosis, after blinding (excluding) the initial fluoroscopic loops from this analysis. A more detailed amount of data was also collected pertaining to the angiogram such as types of lesions (whether discrete, tubular, diffuse, or near-total occlusions); the presence of chronic total occlusions (CTOs); presence of ectasias; whether the procedure was a primary PCI or an elective procedure; and whenever a vessel had multiple lesions (significant or not), the data included a description of each of the lesions.
The primary endpoint would be the presence of significant coronary stenosis (>50' of LMCA, or >70' of LAD, LCX, RCA, or their branches). Stenosis would include both those at the site of coronary calcium or in other branches. However, stenosis which were not significant (<50' for LMCA, <70' for other vessels) were also charted out while collecting data and have been used in analysis.
The cumulative recordings would then be used to correlate the fluoroscopic and angiographic observations and assess the diagnostic accuracy of fluoroscopy considering the angiographic result to be the gold standard for coronary luminal stenosis.
The data were elaborately organized into MS-Excel Spreadsheet and then analyzed using? Statistical Product and Service Solutions (SPSS, IBM Corporation, New York, USA) version 24. The results were expressed using tables, diagrams/graphs, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. Chi-square test was applied for test of significance wherever appropriate.
The study conformed to ethical principles of human research and was started only after institutional ethics committee clearance. Informed written consent was obtained from participants in their mother tongue. Confidentiality was maintained. Patients had to bear no additional expense and were not exposed to any additional radiation.
| Results|| |
A total of 200 patients were included in the final analysis. 75' of the patients were aged between 51 and 75 years. The youngest patient was aged 33 years, while the oldest was 80 years old. The prevalence of coronary calcium was 43' (86 out of 200): this varied with age as 18.2' in those under 50 years, 41.1' in those between 51 and 60 years, and 63.0' in those over 60 years of age. The prevalence in males was higher (44.8') than in females (39.4').
As depicted in [Figure 2], all 86 patients had involvement of the LAD. The second most common location of coronary calcium was the RCA (seen in 31.4' of patients, 27 out of 86). Only 4' were constituted by LMCA calcium (3 out of 86).
Our observations of the correlation of coronary artery calcification (CAC) and severity of CAD are represented partly in [Table 1],[Table 2],[Table 3],[Table 4].
|Table 1: Correlating number of significant stenotic lesions with severity of coronary calcium|
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|Table 2: Correlation of the mere presence of coronary calcium with significant coronary artery disease|
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|Table 3: Correlation of presence of any coronary calcium and number of coronaries with significant stenosis|
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|Table 4: Correlation of coronary calcium with presence of chronic total occlusions|
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Note: While analysing for severity of stenosis, in cases where a vessel had more than one significant stenosis, it was counted as one and not the total of all lesions. However, lesions in branches were also added. For example, if a patient had an 80' proximal LAD and a 90' mid-LAD lesion followed by a diffuse 90' stenosis of distal LAD and also an 80' lesion in the diagonal, it was counted as two significant lesions (one as significant LAD stenosis and another as diagonal stenosis). By this method, the “maximum number of significant lesions” in a given patient that could be counted would be 8 (LAD, diagonal, LCX, OM, RCA, right posterior descending artery (RPDA)/posterior lateral branch [PLB], Ramus, LMCA). This method was chosen to avoid wrongly assessing severity. For example, three significant tandem lesions in RCA should not be equated in severity to a patient with one significant lesion each in LAD, LCX, and RCA.
For the analysis of our data, minor CAD refers to those patients having maximal stenosis not exceeding 50' in LMCA or 70' in other vessels. Small-vessel disease (SVD) refers to significant stenosis in any of the following 5 combinations: LAD and/or diagonal, LCX and/or OM, RCA and/or RPDA/PLB, Ramus, or LMCA. Similarly, four-vessel disease (4VD) would mean 4 of the above 5 vessel combinations in the same patient.
In this study of 200 patients, 25' had normal coronaries/minor CAD. SVD, 2VD, and 3VD accounted for 25', 29', and 20', respectively, of the sample size. At the same time, the overall prevalence of coronary calcium was 43'. If we were to exclude those with normal coronaries/minor CAD, the prevalence of coronary calcium in this cohort of significant CAD (SVD, 2VD, 3VD, and 4VD) was 55.3'.
The presence of coronary calcium correlated very well with the increasing severity of significant coronary stenosis and this was statistically significant with P = 0.001. As the number of vessels involved in significant CAD increased, the relative proportion of the presence of coronary calcium also increased. It is critical to note that in this study of 200 patients, we found that the prevalence of coronary calcium was 40' in those with SVD, 63.8' in those with 2VD, 60' in those with 3VD, and 100' in those with 4VD. In stark contrast, only 6' of patients with normal coronaries/minor CAD had CAC.
In our study, 56 of 200 patients had CTOs. 69.6' of those with CTOs had coronary calcium (39 out of 56), while only 32.6' of those without CTOs had coronary calcium (47 out of 144). This difference was statistically significant (P = 0.001). Further, it should also be noted that the prevalence of coronary calcium in those with CTOs (69.6') was also higher than that of the overall sample size (43') or that of the cohort with significant CAD ± CTO (55.3').
| Discussion|| |
Other studies have documented that the prevalence of CAC is age and sex dependent, occurring in over 90' of men and 67' of women older than 70 years of age.,, In addition, CAC is most frequent in Caucasians. Our study was limited to the patients admitted to our center in South Kerala with no racial variation to be compared. Although no causal relationship with CAC could be established, the most common risk factors in our study were diabetes mellitus (44'), hypertension (44'), dyslipidemia, and smoking. However, 19' of the patients had no risk factors.
The most common two indications for undergoing a CAG in our study were acute coronary syndrome (ACS, 56') and chronic stable angina (CSA, 36'). In 2002, Yamanaka et al. described how CAC is most prevalent in those with CSA and significantly lesser in those presenting as ACS. Shemesh et al. in their paper (2013) have expressed that CAC more often presents as chronic CAD rather than ACS.
Among 86 patients positive for fluoroscopically detected CAC, all had involvement of the LAD; 54 patients (62.7') had CAC involving LAD alone. This agrees with previous studies.,, Among our 86 patients, 37.3' had multivessel CAC. We found a 94' specificity and 96.5' positive predictive value of fluoroscopic CAC in detecting significant stenosis, although overall sensitivity was only 55.3'. Previous studies have shown a good correlation between CAC and total atherosclerotic plaque burden.,,,
We found a statistically significant correlation with CAC and number of vessels involved with significant stenosis (P < 0.001), i.e., an increasing prevalence of CAC was noted as follows: minor CAD/normal coronaries (6') <<< SVD (40') <2VD (63.8') and 3VD (60') <4VD (100'). Notably 2VD and 3VD had a comparable prevalence of CAC.
As described in our results in detail, patients with CTOs had a very high prevalence of CAC (69.6'). The rather high representation of CTOs (28') in our sample probably reflects the cohort of patients that we cater to at our high-volume tertiary care center, i.e., highly symptomatic patients as well as post-ACS patients who form the majority of our sample: 56' of patients included had an ACS in the recent past (which may have exceeded 3 months), 36' had CSA, and nearly 17' had a positive exercise stress test. Further, as mentioned earlier inthe introduction to this study, a part of the delay in the ability tooffer CAG to the deserving many is due to the large populationthat our center caters to.
LAD calcium, the most common pattern, had an excellent negative predictive value (>90') for CAD involving LMCA, Ramus, diagonal, OM, RPDA/PLB, but not for the LAD, LCX, or RCA. Sensitivity was in general poor (33.3'–69.2'), theexception being 100' sensitivity for LMCA stenosis. WhileLCX and LMCA calcium were excellently specific (>90')for coronary stenoses in all vessels and their branches;RCA calcium was specific to CAD involving LAD, LCX,RCA (>90') more than other vessels (>85').
Of those 86 patients with CAC, 37' had “multivessel CAC.” Of those with single-vessel CAC, 63' had multivessel CAD, whereas 91' of those with multivessel CAC had multivessel CAD. Multivessel CAC is thus a very strong predictor of multivessel CAD.
Fluoroscopic CAC detection may thus be suggested as a completely noninvasive tool to stratify patients with more severe CAD, that is, among those patients deemed to have low-to-intermediate severity of CAD, the presence of CAC would strongly suggest that CAD is severe. Nevertheless, absence of CAC on fluoroscopy cannot exclude severe CAD. Hence, this should not be intended to be used as a screening tool for CAD. However, the ease at which it can be performed in seconds on an outpatient basis and the low-dose radiation associated (less than one-twentieth the dose of a CAG) suggests its utility in triage of patients with CAD. Considering its feasibility, it would be prudent to perform it as part of a CAG and not separately, because it would not provide adequate information as a standalone test but would certainly be corroborative in severe forms of CAD. Coronary calcium is an avenue of investigation being revisited now as evidenced by the upgraded recommendation in the 2019 European Society of Cardiology Guidelines for coronary computed tomography angiogram in symptomatic chronic coronary syndromes.
Limitations of our study
Our study was limited to patients visiting our tertiary care center and hence need not necessarily represent the population in general. Our sample comprised symptomatic individuals or those with known CAD; hence, the results of this study are better applied to such a cohort. While considering CAG to be the gold standard of diagnosis, fractional flow reserve or intravascular ultrasound (IVUS) was not employed. Intimal versus adventitial calcium was not differentiated; but in our defense, this can prove to be quite challenging in practice as well, especially in lesser grades of CAC and without confirmation with IVUS.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]