European Journal of Cardiovascular Medicine

Coronary artery disease (CAD) is India's biggest cause of death and the world's leading cause of mortality. Coronary artery disease is traditionally defined as a 50% or higher diameter constriction of a main coronary artery or branch. This constriction may result in a reduction of 75% of the lumen cross-sectional area.

In India, the prevalence of CAD is 21.4% for diabetics and 11% for nondiabetics. The frequency of CAD in rural areas is roughly half that of the urban population. Previously assumed to be largely a problem in rich nations, CAD is increasingly causing more mortality and disability in developing countries such as India, with rates rising disproportionately in comparison to developed countries. Obesity, type 2 diabetes, and metabolic syndrome, all of which are key risk factors for CAD, are on the rise, threatening to raise morbidity and mortality even further.

With urbanization in the developing world, the incidence of risk factors for CAD is quickly growing, to the point that these regions now bear the bulk of the worldwide burden of CAD. As a result, early identification is critical for identifying potentially modifiable risk factors and preventing or even promoting disease development.

Catheter angiography (CAG) is widely regarded as the gold standard for diagnosing coronary artery disease. The key advantage of CAG is that therapy may be delivered at the same session as the test process, hence it is advised for patients with an 80% pre-test likelihood of CAD. The advancement to more invasive catheter angiography enables for diagnosis and treatment in a single session without the additional radiation exposure of a prior CTA. However, about 50% of all CAG tests are not followed by later interventional or surgical therapy and are performed solely for diagnostic purposes and to confirm the existence and severity of CAD. So the question is whether it is appropriate to undergo an invasive operation for diagnostic reasons.

Non-invasive coronary CT angiography has been getting more attention as an alternate imaging method for stable individuals suspected of having CAD. The use of coronary CT angiography has been aided by technical improvements that have improved spatial and temporal resolution as well as better detection and awareness of the risk of ICA. Furthermore, coronary CT angiography is an intriguing choice because the majority of CAD patients are treated conservatively.¹

The difficulty in imaging coronary arteries non-invasively is connected to coronary structure and mobility. Because coronary arteries are often just millimeteres in width and vulnerable to motion artefact during the cardiac cycle, achieving acceptable spatial and temporal resolution in imaging can be difficult. These barriers have mostly been solved with the introduction and general availability of multi-slice multi-detector CT scanners and other technical improvements. However, image quality issues might persist. To attain the highest picture quality, noise, vascular enhancement, and coronary motion must all be optimized.² In this study, we highlight the role of coronary CT angiography with Conventional Angiography in patients with CAD.

Study design: This cross-sectional study was conducted in the Department of Radio diagnosis at PGIMER and Dr. Ram Manohar Lohia Hospital, Delhi. The patients included in the study were referred from the Department of Cardiology and Department of Medicine, PGIMER, and Dr. Ram Manohar Lohia Hospital, Delhi.

Sample size: A total of 30 patients of either sex were included in the study. Patients were evaluated on 40-slice Philips scanner and subsequently the patients were subjected to Conventional Angiography on a Philips system within 15 days.

Inclusion Criteria:

1. Patients with known or suspected coronary artery disease with evidence of ischemia based on one of the following
   1. TMT
   2. Dobutamine stress  echo
   3. ECG
2. Normal sinus rhythm
3. Patients more than 40 years of age
4. Able to hold breath for more than 15 sec

Exclusion Criteria:

1. Patients of acute MI/ unstable angina/ congestive heart failure
2. Heart rate > 65 beats per minute refractory to oral and i.v. β -blockers
3. Patients in which β-blockers are contraindicated.
4. Abnormal renal function (serum creatinine >1.5mg/dl).
5. Previous contrast allergy.
6. History of CABG and Stent
7. BMI ≥ 40kg/m2
8.  

Comparative Analysis: The accuracy of MDCT in detecting significant disease was compared with Conventional Coronary Angiography in a standard manner.

Procedure:

Invasive Coronary Angiography: Invasive Coronary Angiography was done by applying the Judkins approach using 4F catheter-acquired standardized projection. Quantitative coronary analysis was performed using the well-validated commercially available software package (Xcelera, Philips, Netherlands). Coronary stenosis was analysed using a well- validated commercially available software package. The angiograms were assessed by a cardiologist. The standard angiographic views were taken for the Left coronary artery (LAO cranial, LAO caudal, AP caudal, AP cranial, RAO cranial, RAO caudal) and Right coronary artery (LAO straight, LAO cranial, RAO straight). As well as some additional views were taken for clear visualization of individual arteries.

CT Coronary Angiography: Patients were evaluated for exclusion criteria and beta-blockers were administered to those with a heart rate above 65 b/min. A contrast injection was performed to check for reactions. Patients were well informed about examination procedures and symptoms. A CT scan was performed with ECG gating. The patient was injected with a non-ionic contrast agent and chaser bolus. The scan was triggered when the ascending aorta density exceeded 120HU above baseline attenuation. Data was post-processed using 'comp cardiac' software and compared with conventional angiography within 15 days

In our study, 30 patients aged ≥ 40 years were subjected to 40 slices of CCTA and then subsequently within 15 days were subjected to CAG. The study group consisted of 24 males (80%) and 6 females (20%). The mean ± SD time interval between the two procedures was 8.1 ± 4.1 days. All 30 patients received an oral ß-blocker (metoprolol) ranging from 25 – 100 mg before the scan to stabilize the heart rate. The mean (±SD) HR was 59.1 ± 3.4 bpm during the scan procedure. The average scan time was 14.1 ± 1.8 sec. The mean age of the study group was 52.3 years. The highest number of patients was in the age group of 50 – 59 (53.33%). 12 patients had diabetes mellitus, and 3 of them had both hypertension and diabetes mellitus. Hyperlipidemia was present in 9 patients. 6 patients (all males) were chain smokers. 12 patients had hypertension with 3 having a history of uncontrolled hypertension. Right-side dominance (90%) of coronary circulation was mostly seen. One of the cases showed co-dominant circulation. The breath hold time for CT coronary angiography was approximately 14 seconds on a 40-slice Philips Scanner. Most of the patients could hold their breath for the scan duration. The distal third of left anterior descending along with its 2^nd diagonal branch and the distal part of left circumflex along with its 2^nd obtuse marginal artery were non evaluable in one patient who could not hold his breath at the time of the scan.

Table 1: Calcium score – Agatston score (n=30) on coronary CT

Fig: 1: Correlation of calcium score with coronary artery disease status in patients with suspected coronary artery disease

The majority of the patients had normal calcium scores. Two patients had calcium scores of more than 400. Significant disease was defined as 50% or more diameter stenosis whereas non-significant disease was defined as diameter stenosis of less than 50%. Most of the patients who had normal angiograms had a calcium score of zero. On the contrary, almost 42% of patients having a calcium score of zero had significant disease. A calcium score of zero does not rule out the presence of significant coronary artery disease.

Table 2: Distribution of disease on per segment basis and per vessel basis on CCTA.

A total of 443 segments could be evaluated out of 462 segments. 19 segments were non evaluable 4 were in one patient who could not hold his breath at the time of scan. Most of the rest were due to the very small size of the vessel and slight motion blur.

Table 3: Distribution of disease on per segment basis and per vessel basis on CAG.

452 segments out of 462 segments could be evaluated on catheter angiography.10 segments that could not be evaluated on catheter angiography as RCA could not be catheterized in two patients by a cardiologist.

Table 4: Per-segment comparison of CCTA with CAG.

Proximal segments of individual arteries showed a very good correlation in comparison with catheter angiography. All the non-assessable segments were considered normal for statistical analysis. Difficulty in diagnosing the stenosis was particularly felt in branched vessels and most at ostial stenosis of branched vessels. In one case we missed the ostial stenosis of a diagonal branch of the left anterior descending artery.

Out of 452 catheter angiography segments, 63 were detected, with 39 significant. On coronary CT angiography, 68 were detected, with 41 significant. Two segments were present in one patient whose RCA couldn't be catheterized. Five significant lesions were missed on CT angiography, which were found to be significant on invasive catheter angiography and two segments were overestimated due to heavily calcified plaque.

Table 5: Per segment analysis of CCTA in comparison with CAG

Table 6: Per-vessel comparison of CCTA with CAG.

10 patients had significant stenosis in RCA on catheter angiography. None of the segments were missed on coronary CT angiography but one of the patients was over diagnosed on CCTA. Left anterior descending had significant stenosis in 11 patients, all of them were picked on CT. But in one patient CT over diagnosed the stenosis. Patients had significant stenosis on invasive angiography out of which only two were found significant on CCTA.

25 vessels were picked by catheter angiography as having >50 % diameter i.e. significant stenosis. CCTA correctly identified 24 of these vessels. CCTA over diagnosed the stenosis in 4 vessels, 2 of them were because of heavily calcified plaque at the sight of stenosis.

Table 7: Per vessel analysis of CCTA in comparison with CAG

Fig 2: Distribution of the cases on CCTA and CAG

Most patients with coronary artery disease had significant disease (60%), with 7 (23.33%) declared normal on CCTA, and 9 (30%) normal on conventional angiography.

Table 8: Comparison of left ventricular ejection fraction on CT and 2D Echo

Ejection fraction as calculated on MDCT and echocardiography had a good correlation. CT slightly over estimated the ejection fraction in most of the patients as CT slightly overestimates the end systolic volume due to lower temporal resolution in comparison with 2D echocardiography.

Fig 3: Histogram showing the difference of mean LVEF on CCTA and 2D Echo

Related images:

Fig 4: Proximal LAD stenosis 4(A): Automated calculation of percentage stenosis via ‘comp cardiac ‘software in a 52-year-old patient with proximal LAD stenosis

Figure 4(B) : CMPR (curved multiplanar reconstructed image) of 52 year old male having proximal significant stenosis.

Figure 4(C) : RAO  CRA  view of Left Circumflex and LAD, with LAD showing proximal stenosis.

Figure 5(A): LAO  CRA  view of RCA of a 45 year old female   on invasive angiography, illustrating distal stenosis

Figure 5(B): Corresponding MPR image Illustrating the same findings as seen in previous image.

Figure 5(C): Corresponding straight MPR illustrating significant stenosis inDistal RCA

The study involved 24 males and 6 females, with a mean age of 52.9 years. The majority of patients were aged 51-59 years. The study found a slightly more male predominance, possibly due to selection bias or small study size.

Our study found that out of 452 segments on catheter angiography, 63 were detected, with 39 being significant. On coronary CT angiography, 68 were detected, with 27 being non-significant and 41 being significant. Out of these segments, 39 were considered significant stenosis. Five lesions were missed on CT angiography, which were considered false negatives.

A total of 34 segments were true positives and the remaining 408 segments were true negatives. On per segment basis analysis, CT coronary angiography on 40 slice Philips scanner had an overall sensitivity of 87.2% (34 of 39), specificity of 98.8% (408 of 413), positive predictive value of 87.2% (34 of 39) and negative predictive value of 98.8% (408 of 413) with invasive catheter angiography as gold standard.

Our study also identified 25 vessels with significant stenosis on catheter angiography, with CCTA correctly identifying 24 of these vessels. The diagnostic accuracy, sensitivity, specificity, PPV, and NPV obtained in our study on vessel-based analysis were 98.4%, 94.7%, 85.7%, and 98.6%, respectively. The number of cases with significant stenosis involving RCA, LAD, LCX, and RIA was 10, 11, 3, 1, and 11, 12, 4, and 1, respectively. Discrete differences in sensitivity and specificity were observed for the RCA, LAD, LCX, and RIA arteries.

In previous studies using 16-slice MDCT, sensitivity has been reported to vary from 85-97% and specificity between 87-99%^3-6. Lim et al⁷ demonstrated the average sensitivity, specificity, PPV and NPV of 40-slice MDCT as 99, 98, 94, and 99%, respectively. The results of Grosse et al⁸ study are comparable to ours. Grosse et al studied 40 patients (28 men, 12 women) who underwent both 40-slice CT and CAG and emphasized the high diagnostic accuracy of 40-slice MDCT in the assessment of significant CAD per patient and per segment in a non-selected patient population with a high prevalence of CAD. Of a total of 545 segments, 43 segments (7.9%) could not be sufficiently evaluated by CT. Their analysis yielded an overall sensitivity, specificity, PPV, and NPV of 87%, 99%, 98%, and 95%, respectively. The Patient-based analysis also demonstrated a high NPV (91%) of CT for excluding significant CAD. Our results were in accordance to Lim et al⁷ and were better in comparison to Gross et al⁸.

Our study found a good correlation between coronary artery stenosis grading using CCTA and CAG, with better accuracy in main arteries compared to smaller branch vessels. Patients receiving sublingual nitroglycerine before CT angiography had better visualization of branched and smaller segments.^9-10

Raff et al¹¹ found specificity, sensitivity, and positive and negative predictive values for the presence of significant stenosis on 64 slice MDCT scanner were: by segment (n = 935), 86%, 95%, 66%, and 98%, respectively and by artery were (n = 279), 91%, 92%, 80%, and 97%, respectively.

The results of our study were found to be in accordance with those of 40 slice and 64 slice scanner and were better than those of 16 slice scanner. This shows that with controlled regular heart rate, good breath-holding capability, and sublingual nitroglycerine at the time of the scan, 40 slice MDCT scanner shows comparable results with 64 slice MDCT.

Two cases of complete occlusion of RCA have been seen in which the length of plaque and status of distal vessels were not assessable on catheter angiography. CT angiography helped in calculating the length of the block. Mollet et al¹² also reported that in patients with total occlusion, occlusion length and degree of calcification as assessed by CT are more accurate predictors of interventional success than are angiographic parameters.

Accurate detection of left ventricular volumes and EF is fundamental for the diagnosis, prognosis, and follow-up of many different forms of cardiovascular disease. Due to its particular advantages, echocardiography is the most widely used imaging technique for this purpose. It is an easily available bedside method that is also cheap, fast, and non-invasive. In our study, we found a good correlation between left ventricular volumes and EFs measured by 40-slice MDCT and 2D Echocardiography. LVEF was slightly overestimated with the difference in mean being 1.54.  Ko et al¹³ also found that LVEF was slightly over estimated by MDCT in comparison with 2D Echocardiography. Slight over estimation might be because all of the patients were given ß-blocker before CT but not before 2D Echocardiography. It may be also because the temporal resolution provided with MDCT was between 83 ms and 165 ms. A temporal resolution of 30–50 ms per image is necessary for the exact measurement of LVEF. Despite of few limitations as discussed our study suggests that assessment of LVEF and regional wall motion is feasible with the use of 40-slice MDCT and may be regarded as a useful clinical index that is reflective of 2D-TTE.

To conclude, 40-slice CCTA provides sufficiently high diagnostic accuracy in terms of sensitivity, specificity, PPV, and NPV to rule out significant stenosis in patients suspected of having CAD in a non-invasive manner. Non-invasive CCTA on 40 slice MDCT scanner is a potentially useful tool, in the diagnostic work-up of patients with typical angina pectoris, both to detect and to exclude significant CAD. However, further studies with larger cohorts of patients are needed to put these results into clinical perspective and to prove the diagnostic value of CCTA in the stepwise workup of patients with suspected CAD.

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