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Cardiac imaging and non-invasive testing
Gender influence on the diagnostic accuracy of 64-slice multislice computed tomography coronary angiography for detection of obstructive coronary artery disease
  1. G Pundziute1,3,
  2. J D Schuijf1,
  3. J W Jukema1,4,
  4. J M van Werkhoven1,
  5. E Boersma5,
  6. A de Roos2,
  7. E E van der Wall1,4,
  8. J J Bax1
  1. 1
    Department of Cardiology, Leiden University Medical Centre, Leiden, The Netherlands
  2. 2
    Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands
  3. 3
    Department of Cardiology, Kaunas University of Medicine, Kaunas, Lithuania
  4. 4
    The Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
  5. 5
    Department of Epidemiology and Statistics, Erasmus University, Rotterdam, The Netherlands
  1. Dr J J Bax, Leiden University Medical Centre, Department of Cardiology, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; jbax{at}knoware.nl

Abstract

Objective: To compare the diagnostic accuracy of 64-slice multislice computed tomography (MSCT) coronary angiography between female and male patients using conventional coronary angiography as the reference standard.

Design: Diagnostic accuracy study.

Setting: University hospital.

Patients: 103 consecutive patients (51 men, 52 women, mean (SD) age 60 (10) years) with known and suspected coronary artery disease underwent 64-slice MSCT.

Main outcome measures: Diagnostic accuracy of 64-slice MSCT to detect obstructive (⩾50% luminal narrowing) stenoses in men and women.

Results: One male and two female patients were excluded from the analysis owing to non-diagnostic MSCT scans as a result of increased heart rate and breathing during the scan. Accordingly, on segmental level, 728/762 coronary segments were of sufficient quality in women (96% (95% CI 95% to 97%)) and 704/723 segments were interpretable in men (97% (95% CI 96% to 98%)). In the remaining 100 patients included in the further analyses, the sensitivity and specificity on a segmental level in women and men were 85% (95% CI 75% to 95%) vs 85% (95% CI 78% to 92%) and 99% (95% CI 98% to 100%) vs 99% (95% CI 98% to 100%), respectively. On a patient level, the sensitivity in women and men was 95% (95% CI 87% to 100%) vs 100%, specificity 93% (95% CI 83% to 100%) vs 89% (95% CI 74% to 100%), positive predictive value 91% (95% CI 79% to 100%) vs 94% (95% CI 86% to 100%), and negative predictive value 96% (95% CI 89% to 100%) vs 100%, respectively.

Conclusion: The findings confirm the high diagnostic accuracy of 64-slice MSCT coronary angiography in both male and female patients.

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Coronary artery disease (CAD) is the leading cause of mortality in the Western world. Although in men mortality due to CAD appears to be declining, an increase has recently been observed in women.13 Unfortunately, accurate diagnosis of CAD may be more challenging in women than in men. Limited exercise capacity is frequently encountered in women, resulting in inconclusive exercise electrocardiography results. In addition, higher false-positive rates may be seen.2 As a result, a considerable proportion of women are unnecessarily referred for conventional invasive coronary angiography, and obstructive CAD is absent in nearly half of women undergoing invasive coronary angiography.2

Multislice computed tomography (MSCT) coronary angiography allows direct non-invasive visualisation of coronary arteries and accurate detection of obstructive lesions as compared with invasive coronary angiography. Indeed, the reported mean sensitivity and specificity of 64-slice MSCT are 87% and 96%, respectively.4 In particular, the negative predictive value was extremely high (approaching 100%), allowing reliable exclusion of CAD. Nevertheless, to date, women have been substantially under-represented in MSCT diagnostic accuracy studies, with only about 20% of included patients being female.4 5

Accordingly, the purpose of this study was to compare the diagnostic accuracy of current 64-slice MSCT coronary angiography between men and women using conventional coronary angiography as the reference standard.

PATIENTS AND METHODS

Study group

A total of respectively 51 and 52 consecutive male and female patients presenting with known and suspected CAD (based on chest pain complaints and presence of risk factors for CAD) and scheduled for conventional invasive coronary angiography were included in the study. The aim of the study inclusion was to reach a 50% distribution of both genders in the total patient population. The median interval between conventional and MSCT coronary angiography was 4 (0–8) weeks. No intervening changes in the clinical condition of the patients occurred between the two examinations. Only patients with sinus rhythm and without contraindications to iodinated contrast medium were included in the study. All patients gave informed consent, which was approved by local ethics committee.

MSCT data acquisition

All MSCT coronary angiography examinations were performed with an Aquilion 64 system (Toshiba, Tokyo, Japan). If the heart rate was ⩾65 bpm oral β-blockers (metoprolol 50 or 100 mg, single dose, 1 hour before the examination) were provided, if tolerated. The following measures were used for 64-slice MSCT coronary angiography: collimation 64×0.5 mm, tube rotation time 400, 450 or 500 ms depending on the heart rate, tube current 300 or 350 mA, tube voltage 120 kV. Non-ionic contrast material was administered in the antecubital vein with an amount of 90–100 ml, depending on the total scan time, and a flow rate of 5 ml/s (Iomeron 400; Bracco Altana Pharma, Konstanz, Germany), followed by a saline solution flush of 50 ml. Automated bolus-tracking in the aortic root was used for timing of the scan. All images were acquired during a single inspiratory breath hold of about 10 seconds, with simultaneous registration of the patient’s electrocardiogram. With the aid of a segmental reconstruction algorithm, data of one, two or three consecutive heartbeats were used to generate a single image.

Images were reconstructed in the cardiac phase showing least motion artefacts. Typically this was an end-diastolic phase; however, additional reconstructions were made throughout the entire cardiac cycle, if needed. Reconstructed images were transferred to a remote workstation for post-processing.

MSCT data analysis

MSCT angiograms were evaluated in consensus by two experienced observers, who were unaware of the results of conventional coronary angiography. The presence of obstructive lesions (⩾50% luminal narrowing) was evaluated by scrolling through axial images, followed by visual assessment of curved multiplanar reconstructions in at least two orthogonal planes. Patients were excluded from the analysis of diagnostic accuracy of MSCT coronary angiography in cases of (a) an uninterpretable proximal or mid-segment or (b) more than two uninterpretable segments in the vessel. However, these patients were included in the analysis of interpretability. Coronary stents were included in the analysis and restenosis was defined as reduced or complete absence of contrast within the stent as well as reduced or absent contrast runoff distally.

Conventional invasive coronary angiography

Conventional invasive coronary angiography was performed according to the standard protocols. Coronary angiograms were visually assessed by one experienced observer who was unaware of the results of MSCT coronary angiography. Each coronary segment as defined by the American Heart Association/American College of Cardiology modified 17-segment model was evaluated in two orthogonal views for the presence of ⩾50% diameter stenosis.

Statistical analysis

Continuous variables are expressed as mean (standard deviation) and compared between the two groups by t test for independent samples. When not normally distributed, continuous data are expressed as median (interquartile range) and compared between the two groups by non-parametric Mann–Whitney test. Categorical variables are expressed as absolute numbers (percentages) and compared between the two groups by χ2 test or Fisher exact test for sparse data. The sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and diagnostic odds ratio were calculated based on the rates of true-positive, true-negative, false-positive and false-negative test results.6 The interpretability and diagnostic accuracy to detect stenoses of ⩾50 % were compared between the two groups using the 95% confidence intervals (95% CI). Conventional coronary angiography served as the reference standard. Diagnostic accuracy was evaluated on a segmental, vessel and patient basis. A vessel or patient was assigned as correctly positive if at least one obstructive lesion in the vessel or patient was detected correctly. Statistical analyses were performed using SPSS software (version 12.0; SPSS Inc, Chicago, IL, USA). p Values <0.05 were considered significant. The study conforms to the criteria as set in the STARD initiative.7

RESULTS

Patient characteristics

An increased heart rate and breathing during the scan rendered examinations of one male and two female patients non-diagnostic and as a consequence these patients were excluded from the MSCT diagnostic accuracy analysis. However, these patients were included in the evaluation of interpretability of the study results. Table 1 presents the clinical characteristics of the remaining 100 patients included in the study of diagnostic accuracy (50 men and 50 women, mean (SD) age 60 (10) years). In total, 36 (36%) patients presented with a previous history of CAD (myocardial infarction or percutaneous coronary intervention, or both), the remaining 64 (64%) patients presented with suspected CAD. Women showed a higher prevalence of family history of CAD and lower overall Agatston calcium score than men.

Table 1 Characteristics of the study group

MSCT coronary angiography

All patients

On the basis of conventional invasive coronary angiography, obstructive lesions were present in 54 (54%) patients (one-vessel disease was observed in 20 patients, two-vessel disease in 24 patients, three-vessel disease in 10 patients) (table 1).

Table 2 depicts the results of diagnostic accuracy to detect obstructive lesions with 64-slice MSCT. After exclusion of 13 segments owing to small vessel size and 40 segments owing to motion artefacts, 1432 coronary segments (38 segments with stents) were included in the analysis. Of 143 obstructive lesions detected on conventional invasive coronary angiography, 122 were correctly identified by MSCT, and disease was correctly ruled out in 1276 segments out of 1289, resulting in sensitivity of 85% (95% CI 80% to 91%), specificity of 99% (95% CI 98% to 100%), positive likelihood ratio of 84.59 (95% CI 49.04 to 145.91), negative likelihood ratio of 0.15 (95% CI 0.10 to 0.22), and diagnostic odds ratio of 570.23 (95% CI 279.91 to 1160.87). In total, 12 coronary vessels were excluded from the analysis. In the included vessels, the overall sensitivity was 90% (95% CI 84% to 96%) and the specificity was 97% (95% CI 95% to 99%). All but one patient with obstructive CAD on conventional invasive coronary angiography and included in the analysis were correctly identified by MSCT to have at least one obstructive lesion, resulting in sensitivity of 98% (95% CI 95% to 100%). Four patients were identified as false positive, resulting in specificity of 91% (95% CI 83% to 99%).

Table 2 Diagnostic accuracy of 64-slice multislice computed tomography (MSCT) in the entire study population

Women versus men

Figure 1 shows an example of obstructive CAD on 64-slice MSCT in a female patient. After exclusion of six segments owing to small vessel size and 28 segments owing to motion artefacts, 728 (96%) coronary segments (18 segments with stents) were included in the female population. In the male population, seven segments were excluded owing to small vessel size and 12 segments owing to motion artefacts, resulting in 704 (97%) segments included in the study (20 segments containing stents). Table 3 shows that no significant differences were seen between the number of interpretable segments in men and women. Moreover, similar diagnostic accuracy was found on a segmental, vessel and patient basis. On a segmental basis, the sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratio to detect obstructive stenoses in women were 85% (95% CI 75% to 95%), 99% (95% CI 98% to 100%), 82.98 (95% CI 39.34 to 174.99), 0.15 (95% CI 0.07 to 0.29), and 563.12 (95% CI 191.21 to 1659.22), respectively, and in men were 85% (95% CI 78% to 92%), 99% (95% CI 98% to 100%), 86.54 (95% CI 38.86 to 192.72), 0.15 (95% CI 0.09 to 0.24), and 581.46 (95% CI 220.59 to 1524.5), respectively—not significantly different between the two patient populations. No significant differences were seen between the number of interpretable vessels and patients in women and men. When shifting to vessel and patient level, both in men and women the sensitivity increased, while specificity decreased slightly. No significant influence of gender was seen (sensitivity, specificity, positive and negative likelihood ratios in women 95% (95% CI 87% to 100%), 93% (95% CI 83% to 100%), 13.36 (95% CI 3.50 to 50.97), and 0.05 (95% CI 0.01 to 0.33), respectively, and 100%, 89% (95% CI 74% to 100%), 9 (95% CI 2.44 to 33.24), and 0 (95% CI 0 to 0.09), respectively, in men).

Figure 1 A woman with obstructive coronary artery disease demonstrated with 64-slice multislice computed tomography (MSCT) coronary angiography. (A) Multiplanar reconstruction (MPR) of the left circumflex coronary artery (arrowheads) with minimal irregularities of the artery wall. (B) MPR of the right coronary artery showing occlusion in the middle part of the vessel (arrow). The distal part of the artery is filled through collaterals. (C, D) The findings were confirmed by conventional coronary angiography (arrowheads and arrow).
Table 3 Diagnostic accuracy of 64-slice MSCT in women versus men

DISCUSSION

The present study demonstrated a high diagnostic accuracy of 64-slice MSCT coronary angiography in both men and women with no significant differences in accuracy between women and men on a segmental, vessel and patient basis.

On a segmental level, the sensitivity in the whole study population was 85% with specificity as high as 99%, while only 4% of coronary segments were excluded from the analysis. These findings are in line with the previously published data of study populations composed of mainly male patients.4 814 Indeed, in previous studies of patients with similar CAD prevalence (>50%) as compared with the present study, the reported sensitivity on a segmental level ranged between 85% to 99% and the specificity varied from 94% to 98%.814 Moreover, in a recently published meta-analysis including nine studies and 544 patients, the mean sensitivity and specificity of 64-slice MSCT coronary angiography to detect obstructive lesions were 87% and 96%, respectively.4 When shifting to a patient level, however, the sensitivity increased to 98% with a slight decrease in specificity to 91%, while importantly the negative predictive value remained high (98%). In clinical practice, a patient-based analysis is even more relevant, since selection (or exclusion) of patients for further invasive diagnostic studies followed by therapeutic interventions is based on the negative predictive value.

No significant differences in the diagnostic accuracy of MSCT coronary angiography were demonstrated between women and men with similar age and clinical presentation. Importantly, non-invasive angiography by MSCT may be particularly beneficial in women, since previous studies have shown that absence of obstructive CAD on conventional coronary angiography is demonstrated in approximately half of symptomatic women as compared with only 17% in age-matched men.2 15 16 Similarly, the ability to predict CAD based on clinical symptoms appears to be limited in women of all age groups. Indeed, the observed disease prevalence with conventional coronary angiography in 55–65-year-old women has been shown to be half of that expected based on the likelihood of CAD determined by the Diamond and Forrester method.2 Moreover, traditional non-invasive tests may be suboptimal in women in the detection of CAD as compared with men. Indeed, for exercise electrocardiography a lower sensitivity and specificity of 60% and 70% have been shown in women as compared with men, in whom sensitivity and specificity are about 80%.2 Similarly, the sensitivity and specificity of stress myocardial perfusion imaging in women are 81% and 66%, respectively.2 17 Accordingly, non-invasive coronary angiography with MSCT, which allows direct visualisation and exclusion of coronary artery stenoses with high accuracy, may be a useful tool in the clinical management of women with suspected CAD. Importantly, when an MSCT scan is normal, the likelihood of obstructive stenoses in the epicardial coronary arteries is extremely low, since the negative predictive value of the technique exceeds 95%. Accordingly, the technique allows accurate ruling out of obstructive CAD in women.

Study limitations

Several limitations of the study should be acknowledged. Only patients scheduled for conventional coronary angiography were included in the study, resulting in high disease prevalence (44% in women and 64% in men). Therefore, the findings of the study need to be validated in a population with lower disease prevalence.

In addition, MSCT has several important limitations, in general. First, the radiation dose of 64-slice MSCT is 12–15 mSv with an estimated radiation dose even higher in women.18 Another important limitation of MSCT coronary angiography is that it does not provide information on functional significance of the detected stenoses, and functional testing remains necessary when stenoses are found.

CONCLUSION

The findings of this study confirm the high diagnostic accuracy of current non-invasive 64-slice MSCT coronary angiography in male and in female patients.

REFERENCES

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Footnotes

  • Funding: GP is financially supported by the training fellowship grant of the European Society of Cardiology, Huygens scholarship and Toshiba Medical Systems Europe. JWJ is an established investigator of the Netherlands Heart Foundation, grant number 2001T032. JJ Bax has received research grants from GE Healthcare and BMS Medical Imaging.

  • Competing interests: None declared.

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