Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

I thanks the Authors for this comprehensive study. However, I have some questions.

1. 
   1. First, where was the Coronary Computed Tomography Angiography (CCTA) performed on patients presenting to the emergency room with chest pain? Was it performed in the emergency room or in the radiology department outside the emergency room? A patient presenting with chest pain can become unstable at any time.

2. Who interpreted the Coronary Computed Tomography Angiography (CCTA)? In a 24-hour facility like the emergency room, the patient is immediately admitted. Did the physician interpreting the CCTA work in the emergency room?

3. What was the average time for the CCTA for patients presenting to the emergency room with chest pain? We know that routine troponin results are available within an hour in most settings.

4. What was the number of slices used in the CCTA device? There are various brands of CCTA, ranging from 128-slice CT to 1152-slice CT. The probability of a correct diagnosis increases with the number of slices. As the device's slice count increases, the likelihood of heart rate interference decreases, resulting in better image quality. Please explain these points.

yours sincerely

Author Response

Comment 1:Where was the Coronary Computed Tomography Angiography (CCTA) performed on patients presenting to the emergency room with chest pain? Was it performed in the emergency room or in the radiology department outside the emergency room? A patient presenting with chest pain can become unstable at any time

Response 1:Thank you for pointing this out. We agree with this comment. Therefore, we have added clarification to indicate that in all included studies, CCTA was performed in radiology departments or dedicated cardiac imaging units, not within the emergency department itself. Only hemodynamically stable patients were selected for CCTA, and strict institutional protocols were in place for safe transport and monitoring during imaging. This addresses the safety concern regarding patients who may become unstable. This change has been made on Part 2.2 (Eligibility Criteria) of the revised manuscript.

[Updated text in the manuscript:]“In all included studies, CCTA was performed in radiology departments adjacent to or near the emergency department, rather than within the ED itself. Only patients who were clinically stable were considered eligible for CCTA. Safety protocols were followed to ensure appropriate monitoring and rapid access to care during and after imaging.”

Comment 2: Who interpreted the Coronary Computed Tomography Angiography (CCTA)? In a 24-hour facility like the emergency room, the patient is immediately admitted. Did the physician interpreting the CCTA work in the emergency room?

 

Response 2: Thank you for your thoughtful comment. We agree that timely and expert interpretation of CCTA is critical in emergency settings. Therefore, we have added clarification in the manuscript that in the included studies, CCTA was interpreted by board-certified cardiac radiologists or cardiovascular imaging specialists, not by emergency physicians. These specialists were typically part of hospital-based radiology or cardiology teams with on-call or in-house coverage models to ensure timely interpretation, especially at larger tertiary centers where many of the trials were conducted.

While interpreters were not physically based in the emergency department, most studies noted that CCTA results were available within a clinically actionable timeframe (typically <1 hour), allowing prompt triage decisions.

This clarification has been added to part 2.2, Eligibility criteria of the revised manuscript.

[Updated text in manuscript:] “In all included studies, CCTA was interpreted by board-certified cardiovascular radiologists or imaging cardiologists, not by emergency physicians.”

Comment 3:What was the average time for CCTA for patients presenting to the emergency room with chest pain? We know that routine troponin results are available within an hour in most settings.

Response 3:We agree that turnaround time is critical when comparing CCTA to high-sensitivity troponin testing in the emergency setting. Therefore, we have added clarifying text to the manuscript. In the majority of included trials, CCTA acquisition and interpretation were completed within 60 to 90 minutes from scan request to final report. Specifically, in the CT-STAT trial, the median time to diagnosis was 9.2 hours for CCTA versus 15.0 hours for myocardial perfusion imaging, demonstrating a significant improvement in workflow. In ROMICAT II, most CCTA results were returned within 1 hour of scan acquisition. Although not faster than initial troponin-only testing, CCTA offers the advantage of anatomic clarity, and can often enable definitive rule-out of CAD within a similar timeframe to full serial troponin protocols (which may take 3–6 hours).

This clarification has been added on Section 3.2 – Impact on ED Workflow and Discharge of the revised manuscript.

[Updated manuscript text:] “In most included studies, CCTA image acquisition and interpretation were completed within 60–90 minutes. For example, the CT-STAT trial reported a median time to diagnosis of 9.2 hours using CCTA compared to 15.0 hours with myocardial perfusion imaging. In ROMICAT II, CCTA interpretation occurred within approximately 1 hour of scan completion. These results support the feasibility of CCTA as a timely diagnostic tool, particularly when compared to traditional serial biomarker pathways.”

Comment 4: What was the number of slices used in the CCTA device? There are various brands of CCTA, ranging from 128-slice CT to 1152-slice CT. The probability of a correct diagnosis increases with the number of slices. As the device’s slice count increases, the likelihood of heart rate interference decreases, resulting in better image quality. Please explain these points.

Response 4: We agree that the number of detector slices used in CT scanners significantly influences image quality, acquisition time, and susceptibility to motion artifacts. Accordingly, we have added clarification in the manuscript. The included studies used a range of CT technologies, from 64-slice systems in earlier trials (e.g., ROMICAT II, ACRIN-PA) to 128- to 320-slice systems in more recent studies (e.g., CT-COMPARE, ICONIC, CRISP-CT).

While not all studies reported slice count explicitly, image quality was consistently reported as diagnostic in >95% of patients. Newer-generation CT scanners (256-, 320-, and 640-slice systems) allow for single-beat imaging, reduce heart rate sensitivity, and improve spatial/temporal resolution. These advances likely contributed to the improved diagnostic performance and lower radiation doses observed in newer studies.

This clarification has been added to Section:2.3: Data Extraction and Synthesis of the revised manuscript.

[Updated manuscript text:] The included studies utilized a range of scanner types, from earlier-generation 64-slice CT systems (e.g., ROMICAT II) to more advanced 128- and 320-slice scanners in recent trials. While slice count was not uniformly reported across studies, image quality was deemed diagnostic in over 95% of cases. Higher slice-count scanners offer improved spatial resolution, reduced motion artifact, and lower dependence on heart rate control, contributing to enhanced diagnostic accuracy and reduced need for beta-blockers or scan repetition.

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

General comments :

Well-written review which is very comprehensive; encompassing many -if not all- aspects (diagnostic, prognostic, economic, etc) of the incorporation of CCTA in the diagnostic strategy, and provide information on both acute and chronic coronary syndrome.

The paper is accompanied by good figures too, which make it even more pleasant to read.

 

Minor comments:

 

• I would maybe just remove the part on prolonged ED stays from serial biomarker testing in the intro first section, as I am not sure that waiting for a CCTA from ER is faster than repeat troponin.
• Do you have a reference for “Variability in practice arises due to differing interpretations of its diagnostic accuracy, impact on patient outcomes, and cost-effectiveness.”?
• Results section, when mentioning CATCH trial: “It demonstrated not only high diagnostic accuracy but also a trend toward improved long-term clinical outcomes”; I would just rephrase saying that a CCTA-guided treatment strategy improved clinical outcome, as it is the treatment strategy (that you further refer to) that changes the outcomes, not the fact of performing the CCTA.
• Figure 1: I would just add arrows to show what you are referring to
• Discussion: typo in “Importantly, newer studies such as PRECISE-CTCA and the COURSE trial address a persistent clinical challenge. patients“: should be colon before patients.

And further down in discussion, no need to repeat FAI abbreviation as already mentioned earlier in the body. And in the same line, you can use MACE abbreviation as also previously cited

• I would add maybe in the limitations section additional limitations from blooming (stents, heavy CAC), and say that can be mitigated by PCDCT (although out of scope and not use in an ER setting daily routine).

 

 

 

Author Response

Reviewer Comment1: 

I would maybe just remove the part on prolonged ED stays from serial biomarker testing in the intro first section, as I am not sure that waiting for a CCTA from ER is faster than repeat troponin.

Response: Thank you for this insightful comment. We agree that the comparison between CCTA and troponin timelines can vary depending on protocol and setting. We have revised the introduction to remove the statement that serial biomarker testing leads to prolonged ED stays. The updated sentence now reads:

“These limitations may contribute to delayed risk stratification and increased resource use, particularly in cases requiring prolonged observation or additional testing.”

This change was made in Section 1.1: Background and Clinical Importance.

Comment 2 Reviewer Comment:

Do you have a reference for “Variability in practice arises due to differing interpretations of its diagnostic accuracy, impact on patient outcomes, and cost-effectiveness”?

Response: We appreciate this comment and have added supporting references. Specifically, we cite Driessen et al. (PACIFIC trial, JACC 2020) and Weir-McCall et al. (JACC Cardiovasc Imaging, 2023), which address diagnostic variability and national imaging trends. This citation has been inserted in Section 1.3: Need for a Systematic Review.

Comment 3, Reviewer Comment:

Results section, when mentioning CATCH trial: “It demonstrated not only high diagnostic accuracy but also a trend toward improved long-term clinical outcomes”; I would just rephrase saying that a CCTA-guided treatment strategy improved clinical outcome…

Response: Thank you for pointing this out. We have revised the language to clarify that the improved outcomes were associated with the CCTA-guided treatment strategy, not the imaging alone.

The sentence now reads: “The CATCH trial demonstrated that a CCTA-guided treatment strategy was associated with improved long-term clinical outcomes, including a reduction in cardiovascular events.”

This update appears in Section 3.1: Diagnostic Accuracy of CCTA.

Comment 4 Reviewer Comment:

Figure 1: I would just add arrows to show what you are referring to.

Response:

We appreciate this helpful suggestion. Figure 1 has been updated to include arrows indicating the focal stenosis described in the legend. This should help clarify the anatomical findings shown in the image.

Comment 5, Reviewer Comment:

Discussion: typo in “Importantly, newer studies such as PRECISE-CTCA and the COURSE trial address a persistent clinical challenge. patients“should be colon before patients.

Response: Thank you for spotting this typographical error. The sentence has been corrected to: “Importantly, newer studies such as PRECISE-CTCA and the COURSE trial address a persistent clinical challenge: patients with inconclusive high-sensitivity troponin levels.”

This correction was made in the Discussion section.

Comment 6, Reviewer Comment:

Further down in the discussion, no need to repeat FAI abbreviation as already mentioned earlier in the body. And in the same line, you can use MACE abbreviation as also previously cited.

Response: We agree with the reviewer. We have removed the repeated definition of FAI and used the previously defined abbreviation MACE. This improves consistency and reduces redundancy in the manuscript.

The changes were made in the advanced imaging subsection of the Discussion.

Reviewer Comment 7:

I would add maybe in the limitations section additional limitations from blooming (stents, heavy CAC), and say that can be mitigated by PCDCT (although out of scope and not use in an ER setting daily routine).

 

Response: Thank you for this important technical suggestion. We have added the following to the Limitations section:

“Another notable limitation of CCTA is the reduced image interpretability in patients with dense coronary calcifications or intracoronary stents, due to blooming artifacts. These artifacts can obscure the vessel lumen and impair stenosis assessment. While newer technologies such as photon-counting CT (PCDCT) may mitigate these issues, they are not routinely used in emergency settings.”

Author Response File: Author Response.docx

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript is well written and provides an interesting overview of not only the diagnostic efficiency, but also the safety and cost-effectiveness of CT coronary angiography. Due to the heterogeneity in the design and outcomes of the analyzed papers, a formal meta-analysis was not performed, which is why some objective parameters (effect estimates and subgroup analyses) were omitted. The authors transparently state other limitations of the work. The only improvement I would suggest is to reformat the summary table in such a way as to reduce the font size and adjust the width of the columns.

Author Response

Comment :The only improvement I would suggest is to reformat the summary table in such a way as to reduce the font size and adjust the width of the columns. Response : We thank the reviewer for this formatting suggestion. We have reformatted the Summary Table of Included Studies by reducing the font size and adjusting column widths to improve readability and fit. These changes have been applied in the revised manuscript.