Comparative diagnostic performance of coronary CT angiography and invasive coronary angiography in patients with suspected coronary artery disease

Abstract

Background

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although invasive coronary angiography (ICA) is the reference standard for diagnosing CAD, coronary computed tomography angiography (CCTA) has emerged as a valuable non-invasive alternative. This study compared the diagnostic performance of CCTA with ICA in patients with suspected CAD.

Methods

In this descriptive cross-sectional study, 155 patients who underwent both CCTA and ICA were included. Coronary stenosis was classified as mild (1–49%), moderate (50–69%), or severe (≥ 70%). ICA served as the reference standard. Diagnostic performance was evaluated using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy.

Results

The mean age of the patients was 57.3 ± 9.15 years, and 67.7% were male. CCTA demonstrated a sensitivity of 96.0%, specificity of 33.3%, PPV of 85.7%, NPV of 66.7%, and an overall accuracy of 83.9%. The LAD showed the highest vessel-based sensitivity (87%), whereas the LCX had the lowest (60%). CCTA correctly identified all cases of moderate stenosis and detected 69% of severe stenoses.

Conclusion

CCTA demonstrated high sensitivity for detecting CAD but relatively limited specificity in this high-risk population. These findings support its role as a useful non-invasive diagnostic tool, while ICA remains the reference standard for confirming coronary artery stenosis.

Introduction

Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality worldwide. This disease represents a major public health challenge [1]. According to the World Health Organization (WHO) reports, ischemic heart disease accounted for approximately 9 million deaths globally in 2022, highlighting the critical need for early and accurate diagnosis to reduce disease-related complications and mortality [2]. CAD, as a major challenge of medical science, is primarily caused by atherosclerotic plaque formation within the coronary arteries, leading to luminal narrowing, impaired myocardial perfusion, and potentially life-threatening events such as myocardial infarction [3]. Invasive coronary angiography (ICA) is widely regarded as the reference standard for the detection and assessment of coronary artery stenosis. This technique provides high spatial resolution and allows precise evaluation of the location and severity of coronary lesions [4]. However, despite its diagnostic accuracy, ICA is an invasive procedure associated with several limitations, such as procedure-related complications, exposure to ionizing radiation and contrast agents, high costs, and the need for hospitalization. These disadvantages have led to increased interest in noninvasive imaging methods for evaluating suspected CAD [5]. Coronary computed tomography angiography (CCTA) has emerged as a promising non-invasive imaging technique that enables direct visualization of the coronary arteries with high spatial and temporal resolution [6]. Advances in CT technology have significantly improved image quality, allowing accurate detection of coronary artery stenosis and plaque characteristics [7]. CCTA is particularly valuable in patients with low to intermediate pretest probability of CAD and has demonstrated high negative predictive value for excluding clinically significant CAD [8]. Recent international clinical practice guidelines have further strengthened the role of CCTA in the evaluation of patients with suspected coronary artery disease. The 2024 European Society of Cardiology (ESC) Guidelines for the management of chronic coronary syndromes [9] and the 2021 American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Evaluation and Diagnosis of Chest Pain recommend CCTA as a first-line non-invasive imaging modality for the assessment of patients with stable chest pain or suspected chronic coronary syndromes, particularly in individuals without previously established obstructive CAD. These recommendations are based on the high diagnostic sensitivity of CCTA and its ability to exclude clinically significant coronary artery disease while also providing valuable information regarding coronary plaque burden and morphology [10]. In addition to the aforementioned advantages of CCTA, this method offers advantages such as shorter examination time, reduced patient discomfort, and avoidance of catheter-related risks [11]. Although numerous studies have evaluated the diagnostic performance of CCTA compared with ICA, differences in study populations, disease prevalence, imaging protocols, and referral patterns continue to influence the reported diagnostic accuracy across different clinical settings. Therefore, additional real-world evidence from diverse patient populations remains valuable for further validating its clinical utility. Therefore, the present study was conducted to compare the diagnostic accuracy of CCTA with that of conventional invasive coronary angiography in evaluating coronary artery disease and to assess the potential role of CCTA as a reliable non-invasive alternative in clinical practice.

Methods

Study design and ethical approval

This descriptive cross-sectional study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Ethical approval was obtained from the Research Ethics Committee of Ardabil University of Medical Sciences, Ardabil, Iran (Ethical code: IR.ARUMS.MEDICINE.REC.1402.056). All patient information was kept confidential, and the collected data were used solely for research purposes.

Study population and sample size

This retrospective cross-sectional study included 155 consecutive patients with CAD who underwent both CCTA and invasive coronary angiography (ICA) as part of their routine clinical evaluation during the study period. The study population consisted of 155 patients with CAD who underwent both coronary CCTA and ICA during the study period. The required sample size was calculated using standard formulas for diagnostic accuracy studies, considering previously reported sensitivity and specificity values, the confidence level, and statistical power from earlier studies [12]. Ultimately, data from 155 eligible patients were included in the final analysis.

Inclusion and exclusion criteria

Patients aged 30 years or older with suspected CAD who underwent both CCTA and ICA were eligible for inclusion. Patients with or without a history of coronary stent implantation and those with or without previous coronary artery bypass grafting (CABG) were included. Complete and diagnostically adequate CCTA and ICA images, together with finalized reports, were required for inclusion. Exclusion criteria included poor image quality resulting in non-diagnostic examinations, incomplete imaging or clinical records, severe renal insufficiency precluding iodinated contrast administration, severe heart failure or cardiogenic shock limiting the feasibility of CCTA, pregnancy, and contraindications to iodinated contrast media.

Imaging data collection and assessment

Clinical and imaging data were retrospectively collected from the patients’ electronic medical records and the institutional Picture Archiving and Communication System (PACS). Coronary CT angiography was performed using a 128-slice GE multidetector CT scanner. Image acquisition was performed using prospective electrocardiogram (ECG)-gating according to the institution’s standardized CCTA protocol. Intravenous metoprolol was administered when clinically indicated to achieve an appropriate heart rate before scanning, and sublingual nitroglycerin was routinely administered immediately before image acquisition to optimize coronary artery visualization. Scanning parameters, including tube voltage, tube current modulation, slice thickness, gantry rotation time, and pitch, were selected according to the institutional imaging protocol to obtain optimal image quality while minimizing radiation exposure. Images were reconstructed using the manufacturer’s standard iterative reconstruction algorithm. Coronary CT angiograms were independently interpreted by an experienced cardiovascular radiologist and an experienced cardiologist, both of whom were blinded to the invasive coronary angiography findings. In cases of discrepant interpretations, a consensus was reached through joint review. Invasive coronary angiography was performed via the femoral approach by experienced interventional cardiologists according to standard clinical practice. The interval between CCTA and ICA was less than one month for all included patients. ICA served as the reference standard for the assessment of coronary artery stenosis. The degree of coronary artery stenosis was evaluated in the left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA). Stenosis severity was classified according to the percentage of luminal narrowing as follows:

• Mild stenosis: 1–49%.

• Moderate stenosis: 50–69%.

• Severe stenosis: ≥70%.

For vessel-based analysis, each major coronary artery was evaluated independently. When multiple lesions were present within the same vessel, each lesion was assessed separately and matched with the corresponding findings on invasive coronary angiography. Vessel-level diagnostic outcomes were classified as true-positive (TP), false-positive (FP), true-negative (TN), or false-negative (FN) according to ICA findings.

Statistical analysis

Continuous variables were expressed as mean ± standard deviation (SD), whereas categorical variables were presented as frequency and percentage. The diagnostic performance of CCTA was evaluated using ICA as the reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy were calculated, together with their corresponding 95% confidence intervals (95% CIs). Diagnostic outcomes were classified as TP, FP, TN, and FN based on comparisons between CCTA and ICA findings. Diagnostic agreement between CCTA and ICA was assessed using Cohen’s kappa coefficient. McNemar’s test was performed to evaluate differences between paired diagnostic results. Receiver operating characteristic (ROC) curve analysis was conducted to further assess the diagnostic performance of CCTA. Interobserver agreement between the two image interpreters was also evaluated using Cohen’s kappa coefficient. Patient-based and vessel-based analyses were performed separately. Vessel-level analyses included the LMCA, LAD, LCX, and RCA. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY, USA). A two-sided P-value < 0.05 was considered statistically significant.

Results

Patient characteristics

A total of 155 patients were included in the study. The mean age was 57.3 ± 9.15 years (range, 37–72 years). Among them, 105 (67.7%) were male and 50 (32.3%) were female. Most patients were married (80.6%) and resided in urban areas (96.8%). Baseline demographic characteristics of the study population are summarized in Table 1.

Table 1.

Demographic characteristics of the study population (n = 155)

Variable	Value
Age (years), mean ± SD	57.3 ± 9.15
Male sex, n (%)	105 (67.7)
Female sex, n (%)	50 (32.3)
Married, n (%)	125 (80.6)
Urban residence, n (%)	150 (96.8)
No prior coronary intervention, n (%)	105 (67.7)

Representative CCTA and corresponding ICA images from one patient with coronary artery stenosis are presented in Fig. 1.

Fig. 1.

Original images from a patient who underwent both CCTA and ICA. (A) CCTA demonstrating coronary artery stenosis. (B) Corresponding ICA confirms the same lesion

Extent of coronary artery involvement

The extent of coronary artery involvement assessed by CCTA and ICA is summarized in Table 2. Based on ICA, 125 patients (80.6%) had significant CAD, whereas 30 patients (19.4%) had no significant coronary stenosis. Overall, CCTA demonstrated a distribution of vessel involvement comparable to that of ICA, with the LAD being the most frequently affected coronary artery in both imaging modalities. No isolated LMCA involvement was identified by either modality.

Table 2.

Comparison of coronary artery stenosis severity between CCTA and ICA

Number of Diseased Vessels	CCTA n (%)	ICA n (%)
No vessel disease	5 (3.2)	30 (19.4)
One-vessel disease	55 (35.5)	40 (25.8)
Two-vessel disease	55 (35.5)	55 (35.5)
Three-vessel disease	35 (22.6)	40 (25.8)
Four-vessel disease	5 (3.2)	15 (9.7)

Severity of coronary artery stenosis

The severity of coronary artery stenosis assessed by CCTA and ICA is presented in Table 3. Overall, the LAD showed the highest prevalence of coronary artery stenosis in both imaging modalities, whereas LMCA involvement was the least frequent.

Table 3.

Severity of coronary artery stenosis assessed by CCTA and ICA according to the degree of luminal narrowing

Vessel	Imaging Modality	Mild (< 50%)	Moderate (50–69%)	Severe (≥ 70%)
LMCA	CCTA	83.9%	3.2%	12.9%
	ICA	90.3%	6.5%	3.2%
LAD	CCTA	16.1%	35.5%	48.4%
	ICA	22.6%	25.8%	51.6%
LCX	CCTA	64.5%	12.9%	22.6%
	ICA	51.6%	6.5%	41.9%
RCA	CCTA	64.5%	16.1%	19.4%
	ICA	61.3%	6.5%	32.3%

Diagnostic performance of coronary CT angiography

Using ICA as the reference standard, CCTA demonstrated high sensitivity but relatively low specificity for the detection of significant CAD. At the patient level, CCTA correctly identified 120 of 125 patients with significant CAD, yielding a sensitivity of 96.0%. Among the 30 patients without significant CAD, CCTA correctly classified 10 patients, resulting in a specificity of 33.3%. The PPV and NPV were 85.7% and 66.7%, respectively, while the overall diagnostic accuracy was 83.9%. The diagnostic performance indices and their corresponding 95% confidence intervals are summarized in Table 4.

Table 4.

Diagnostic performance of coronary CT angiography

Diagnostic Index	Value (%)	95% CI
Sensitivity	96.0	91.0–98.3
Specificity	33.3	19.2–51.2
Positive Predictive Value (PPV)	85.7	78.9–90.5
Negative Predictive Value (NPV)	66.7	41.7–84.8
Accuracy	83.9	77.3–88.8

Confusion matrix analysis

The patient-based confusion matrix comparing CCTA with ICA is presented in Table 5. CCTA correctly identified 120 true-positive and 10 true-negative cases, whereas 20 false-positive and 5 false-negative findings were observed. These results are consistent with the high sensitivity and relatively low specificity of CCTA in the studied population.

Table 5.

Confusion matrix comparing CCTA with ICA

CCTA	ICA Positive	ICA Negative	Total
Positive	120 (TP)	20 (FP)	140
Negative	5 (FN)	10 (TN)	15
Total	125	30	155

Subgroup analyses

Additional analyses were performed to evaluate the diagnostic performance of CCTA according to coronary vessel, stenosis severity, and history of prior coronary intervention. Vessel-based analysis demonstrated variability among the major coronary arteries, with the highest sensitivity observed in the LAD (87%) and the lowest in the LCX (60%), while diagnostic performance for the RCA was intermediate. According to stenosis severity, CCTA correctly identified all cases of moderate stenosis (50–69%), whereas 69% of severe stenoses (≥ 70%) were detected. Among patients with previous coronary intervention, 92 patients had prior coronary stent implantation, and 63 had previous CABG. In this subgroup, CCTA detected all abnormal cases, yielding a sensitivity of 100% and a PPV of 80%.

Discussion

Coronary artery disease (CAD) remains one of the leading causes of morbidity and mortality worldwide, making accurate and timely diagnosis essential for appropriate risk stratification and clinical decision-making [13]. Owing to its non-invasive nature and excellent visualization of the coronary arteries, coronary computed tomography angiography (CCTA) has become an important imaging modality for the evaluation of patients with suspected CAD [14]. In the present study, CCTA demonstrated high sensitivity (96.0%) and an overall diagnostic accuracy of 83.9% for detecting significant CAD. However, specificity (33.3%) and the negative predictive value (66.7%) were relatively lower, indicating that although CCTA was highly effective in identifying patients with significant coronary stenosis, its ability to exclude disease was more limited in our study population. The diagnostic performance observed in this study is generally consistent with previous reports demonstrating high sensitivity but variable specificity for CCTA. Several studies have shown that CCTA is particularly useful for detecting anatomically significant coronary stenosis, whereas its specificity may decrease in patients with extensive coronary calcification or previous coronary interventions. Advances in CT technology, including ultra-high-resolution CT (UHR-CT), have improved diagnostic performance, with reported sensitivities and specificities approaching 86% and 88%, respectively [15]. Furthermore, recent studies incorporating artificial intelligence–based image analysis have reported substantial improvements in diagnostic accuracy, particularly in reducing false-positive findings and improving image interpretation [16]. One important finding of the present study was the relatively low specificity and moderate negative predictive value of CCTA. These findings should be interpreted in the context of the study population. Only patients who underwent both CCTA and invasive coronary angiography (ICA) were included, resulting in a referral-based study population with a high prevalence of CAD (80.6%). Such patient selection is likely to have introduced referral (selection) bias and increased the pretest probability of disease. Because predictive values are strongly influenced by disease prevalence, the high prevalence of CAD in our cohort likely contributed to the relatively high PPV and comparatively lower NPV observed in this study. Therefore, these findings should not be generalized to lower-risk populations undergoing CCTA for the initial evaluation of suspected CAD. Several technical and clinical factors may also explain the relatively low specificity observed in the present study. Severe coronary calcification may produce blooming artifacts that overestimate the degree of luminal narrowing on CCTA images, leading to false-positive findings. Motion artifacts caused by elevated or irregular heart rates, partial-volume effects, and image reconstruction limitations may further reduce diagnostic accuracy. In addition, interpretation bias and the inclusion of patients with previous coronary interventions, particularly coronary stent implantation, may have contributed to the observed reduction in specificity. Similar challenges have been reported in previous studies evaluating the diagnostic performance of CCTA in high-risk patient populations [17, 18]. Vessel-based analysis demonstrated that the diagnostic performance of CCTA varied among the major coronary arteries. The highest sensitivity was observed in the LAD (87%), whereas the LCX showed the lowest sensitivity (60%), with intermediate performance for the RCA. Similar findings have been reported in previous studies, suggesting that anatomical characteristics, vessel orientation, cardiac motion, and the burden of coronary calcification can all influence the diagnostic accuracy of CCTA in different coronary vessels [19, 20].

The superior performance observed in the LAD may be related to its larger caliber and relatively favorable anatomical course, whereas the lower sensitivity in the LCX may reflect its smaller size, greater anatomical variability, and susceptibility to motion-related image degradation. When diagnostic performance was evaluated according to stenosis severity, CCTA correctly identified all cases of moderate stenosis (50–69%) and detected 69% of severe stenoses (≥ 70%). These findings suggest that the diagnostic performance of CCTA varies according to lesion severity and anatomical characteristics. Unlike the initial interpretation, the relatively lower negative predictive value observed in this study should not be interpreted as evidence that moderate stenoses were underestimated, since all moderate lesions were correctly identified in our cohort. Rather, the reduced NPV most likely reflects the high prevalence of CAD and the selected high-risk study population. Previous investigations have similarly shown that although CCTA is highly effective for identifying anatomically significant coronary stenosis, assessment of lesion severity may still be influenced by plaque characteristics, coronary calcification, and image quality [21, 22]. Among patients with previous coronary interventions, including CABG, CCTA demonstrated excellent sensitivity for detecting abnormal findings. However, interpretation of CCTA in these patients remains technically challenging because metallic stents, heavy calcification, surgical grafts, and motion artifacts may reduce image quality and increase diagnostic uncertainty. Nevertheless, the present findings support the potential role of CCTA as a valuable non-invasive imaging modality for the follow-up assessment of selected patients after coronary revascularization, while acknowledging that invasive coronary angiography remains necessary whenever CCTA findings are inconclusive or inconsistent with the clinical presentation. Previous studies have similarly demonstrated that the diagnostic performance of CCTA in patients with prior coronary interventions is influenced by several technical factors, including stent diameter, stent material, coronary calcification, and cardiac motion. In addition, studies involving complex patient populations, such as those undergoing transcatheter aortic valve implantation (TAVI), have reported high sensitivity but relatively limited specificity, highlighting the technical challenges associated with CCTA interpretation in these settings [23, 24]. Despite these limitations, CCTA remains valuable for the non-invasive assessment of coronary stents and bypass grafts, with previous reports demonstrating excellent negative predictive values under appropriate imaging conditions [25, 26]. Nevertheless, severe coronary calcification continues to represent one of the major factors limiting diagnostic accuracy, consistent with the findings of the present study [26]. This study has several limitations. First, it was conducted at a single center with a relatively small sample size, which may limit the generalizability of the findings. Second, inclusion of only patients who underwent both CCTA and ICA resulted in a referral-based, high-risk population with a high prevalence of CAD, potentially introducing selection bias and influencing the observed diagnostic performance. Finally, coronary calcification, motion artifacts, and previous coronary interventions may have affected CCTA image quality and diagnostic accuracy. Despite these limitations, this study provides additional real-world evidence supporting the high sensitivity of CCTA for detecting significant CAD in a high-risk population. Future multicenter studies with larger cohorts and standardized imaging protocols are needed to further validate these findings and improve the diagnostic performance of CCTA.

Clinical implications

Despite these limitations, the results of this study support the role of CCTA as a reliable non-invasive diagnostic modality for the detection of significant coronary artery disease, particularly in identifying abnormal findings and severe stenosis. CCTA may be especially valuable for initial evaluation and follow-up in selected patient populations, while invasive coronary angiography remains essential for definitive diagnosis and therapeutic planning.

Author contributions

AFZ contributed to the conception and design of the study, performed the main analyses, interpreted the data, and drafted the manuscript. MJS contributed to the study design, data analysis, and critical revision of the manuscript. MM assisted with data collection, experimental work, and manuscript editing. SR supervised the research project, provided scientific guidance, reviewed the manuscript, and approved the final version for submission. All authors read and approved the final manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethical approval

This study was approved by the Research Ethics Committee of Ardabil University of Medical Sciences, Ardabil, Iran (Ethical code: IR.ARUMS.MEDICINE.REC.1402.056), and all procedures were conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants before inclusion in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.