Beyond the Calcium Score: What Additional Information from a CT Scan Can Assist in Cardiovascular Risk Assessment?

Round 1

Reviewer 1 Report

The review is very interesting and important. It was written in a very professional way.  

Author Response

Response to Reviewer 1 Comments

We would like to thank the Editor and Reviewers for the careful and thorough reading of our manuscript and for the thoughtful comments and constructive suggestions, which help to improve the quality of this manuscript. Whereas some sections had significant overlap with previously published articles we made a significant rephrasing.

Point 1: the review is very interesting and important. It was written in a very professional way.

Response 1: We appreciate the positive feedback from the Reviewer.

Author Response File: Author Response.docx

Reviewer 2 Report

Proposed methodology is missing with more parameters..

Title of the paper needs significant improvement to make it a research-based topic.

The introduction can be enhanced with clarity.

Citations are not proper. The background is not proper. Figure 2 is not visible.

Recent references have not been included in this paper.

Author should cite some of recent work on his area.

One time a thorough revision is also required to rectify the types.

Novelty and significance of work must be consider.

Author Response

Response to Reviewer 2 Comments

We would like to thank the Editor and Reviewers for the careful and thorough reading of our manuscript and for the thoughtful comments and constructive suggestions, which help to improve the quality of this manuscript. Whereas some sections had significant overlap with previuosly published articles we made a significant rephrasing.

Point 1: Proposed methodology is missing with more parameters.

Response 1: We thank the reviewer for the comment. In the new version of the manuscript, we added a paragraph in the introduction where the methodology applied for the review writing is clearly explained (page 2, lines 56-61).

Point 2: Title of the paper needs significant improvement to make it a research-based topic

Response 2: Thanks for the comment. In the current title of our manuscript, we believe to have highlighted the main purpose of our work, thus on one hand, confirming the prognostic role of the calcium score, and, on the other side, suggesting potential new CT parameters that could be added for a more thorough assessment of CV risk. We tried to do this with an attractive title for the reader.

Point 3: The introduction can be enhanced with clarity.

Response 3: Thanks for the comment. We supplemented the introduction by explaining the methodology applied for the review writing. Moreover, we have modified many paragraphs of the manuscript trying to make them more fluid and clear.

Point 4: Citations are not proper. The background is not proper. Figure 2 is not visible

Response 4: We thank the reviewer for the comment. We edited and reinserted Figure 2 to make it more visible in the new version of the manuscript. Furthermore, we have updated citations adding new and more recent ones.

Point 5: Recent references have not been included in this paper.

Response 5: We agree with the reviewer. We have updated the manuscript with more recent citations in sections 1.4 (Plaque morphology), 2.2 (Pathophysiological mechanisms of calcium deposition) and 2.4 (Emerging technologies).

Point 6: Author should cite some of recent work on his area.

Response 6: We agree with the reviewer. We have updated the manuscript with more recent work and consequent citations in the new version. In particular we added informations about de-blooming algorithms, 3D reconstruction models and CT-derived hemodynamic parameters (page 5, lines 268-273 and page 11, lines 719-729).

Point 7: One time a thorough revision is also required to rectify the types.

Response 7: We thank the Reviewer for his/her comment. In light of the comment, in this revised version of the manuscript, we made a thorough revision to make the writing smoother. The manuscript has also been evaluated by a native English speaker.

Point 8: Novelty and significance of work must be consider.

Response 8: Thanks for the comment. We think that cardiac computed tomography angiography has shown in recent years remarkable progress with a significant increase in measurable parameters leading to better cardiovascular risk estimation, particularly regarding the progression of coronary atherosclerosis. With this review we aim to stimulate interest and debate on this topic potentially encouraging future research, in particular about early detection of patients at risk of developing severe atherosclerosis and adverse clinical events and potentially target for early preventive strategies.

Author Response File: Author Response.docx

Reviewer 3 Report

In this review paper, the authors comprehensively summarized the pathophysiological parameters of cardiovascular risks that can be derived from cardiac CT scan. The topic is clinically significant. Overall, the paper is well structured. However, some improvements are essential to achieve publishable standards:

1. There is a lack of in-depth discussion on artefacts. The blooming artefact (Refer: 10.3389/fcvm.2021.597568) and motion artefact (Refer: 10.1148/rg.2016160079) are two common artefacts that affect the quality of CT imaging. Especially, the blooming artefact can significantly influence the evaluation of calcification and plaque component analysis (Refer: 10.3389/fphys.2021.715265). Please add the abovementioned information and discuss the effect of artefact and the role of de-blooming algorithms in improving the accuracy of calcification evaluation.

2. The significance of CT-derived parameters need to be highlighted from a clinical perspective. Currently, besides clinical imaging and biochemical observations, the in-depth exploration of Pathophysiological mechanisms of cardiac and cardiovascular diseases that lead to hemodynamic abnormalities, e.g., myocardial ischemia, mainly depends on simplified electromechanical models (Refer: https://ieeexplore.ieee.org/abstract/document/6164503, 10.1007/978-3-642-15615-1_50, 10.1155/2012/948781), electrocardiogram (ECG)-based signal processing and feature extraction (Refer: 10.3389/fphys.2022.854191, 10.1161/STROKEAHA.117.017293, 10.11909/j.issn.1671-5411.2017.12.009), and computational fluid dynamics simulation (Refer: 10.1016/j.compbiomed.2022.105583). On the one hand, the CT-derived hemodynamic parameters could improve the reliability of the mathematical models towards patient-specific evaluation. On the other hand, the CT-derived parameters provide the possibility of developing coupled complex models based on multimodal data analysis and multidimensional modelling.

3. The interaction between CAD and CMD. i.e., coronary microvascular dysfunction, plays a key role in evaluation the cardiovascular function. The fractional flow reserve (FFR) derived from CT imaging and computational fluid dynamic simulation has been widely used in clinical practice to evaluate the hemodynamic severity of coronary stenosis (Refer: 10.2174/1573403X1504190819123137). However, CMD could decrease the trans-stenotic pressure gradient, leading to a higher FFR value (Refer: 10.1631/jzus.B2100425) which may affect the diagnosis. Therefore, in further studies, CT-derived hemodynamic and anatomic parameters can be combined with those from other imaging results (e.g., cardiovascular ultrasound) and physiological parameters (e.g., ECG features) the diagnostic accuracy.

4. There are some minor errors in language and format. I advise the authors to find a native English speaker for proofreading.

Author Response

Response to Reviewer 3 Comments

We would like to thank the Editor and Reviewers for the careful and thorough reading of our manuscript and for the thoughtful comments and constructive suggestions, which help to improve the quality of this manuscript. Whereas some sections had significant overlap with previously published articles we made a significant rephrasing

Point 1: there is a lack of in-depth discussion on artifacts. The blooming artifact (Refer: 10.3389/fcvm.2021.597568) and motion artifact (Refer: 10.1148/rg.2016160079) are two common artifacts that affect the quality of CT imaging. Especially, the blooming artifact can significantly influence the evaluation of calcification and plaque component analysis (Refer: 10.3389/fphys.2021.715265). Please add the abovementioned information and discuss the effect of artifact and the role of de-blooming algorithms in improving the accuracy of calcification evaluation

Response 1: We agree with the Reviewer, and we thank him/her for the comment. The image quality of CCT may be affected by artifacts (frequently motion and blooming artifacts), with consequent overestimation of calcific plaques. This limit can be exceeded using de-blooming algorithms and 3D reconstruction models. We discussed this point in the new version of the manuscript (page 5, lines 268-273).

Point 2: the significance of CT-derived parameters needs to be highlighted from a clinical perspective. Currently, besides clinical imaging and biochemical observations, the in-depth exploration of Pathophysiological mechanisms of cardiac and cardiovascular diseases that lead to hemodynamic abnormalities, e.g., myocardial ischemia, mainly depends on simplified electromechanical models (Refer: https://ieeexplore.ieee.org/abstract/document/6164503, 10.1007/978-3-642-15615-1_50, 10.1155/2012/948781), electrocardiogram (ECG)-based signal processing and feature extraction (Refer: 10.3389/fphys.2022.854191, 10.1161/STROKEAHA.117.017293, 10.11909/j.issn.1671-5411.2017.12.009), and computational fluid dynamics simulation (Refer: 10.1016/j.compbiomed.2022.105583). On the one hand, the CT-derived hemodynamic parameters could improve the reliability of the mathematical models toward patient-specific evaluation. On the other hand, the CT-derived parameters provide the possibility of developing coupled complex models based on multimodal data analysis and multidimensional modeling

Response 2: thanks for the comment. The CT-derived hemodynamic parameters have been proven to improve the accuracy of CCTA, in particular in the context of intermediate stenoses. Integrating them with plaque morphological features and with ECG-derived electromechanical parameters, we could get complex models based on multimodal data analysis with consequent patient-specific risk assessment and better selection of patients to refer to coronary angiography. We discussed this point in the new version of the manuscript (page 11, lines 719-729).

Point 3: the interaction between CAD and CMD. i.e., coronary microvascular dysfunction plays a key role in evaluation the cardiovascular function. The fractional flow reserve (FFR) derived from CT imaging and computational fluid dynamic simulation has been widely used in clinical practice to evaluate the hemodynamic severity of coronary stenosis (Refer: 10.2174/1573403X1504190819123137). However, CMD could decrease the trans-stenotic pressure gradient, leading to a higher FFR value (Refer: 10.1631/jzus.B2100425) which may affect the diagnosis. Therefore, in further studies, CT-derived hemodynamic and anatomic parameters can be combined with those from other imaging results (e.g., cardiovascular ultrasound) and physiological parameters (e.g., ECG features) the diagnostic accuracy.

Response 3: we thank the reviewer for the useful comment. The presence of concomitant microvascular dysfunction, decreasing trans-stenotic gradient, could cause CT-derived FFR overestimation and consequent underdiagnosis. The combination with electromechanical models could allow to overcome this limit and improve diagnostic accuracy. We discussed this point in the new version of the manuscript (page 11, lines 731-733).

Point 4: there are some minor errors in language and format. I advise the authors to find a native English speaker for proofreading.

Response 4: thanks for the comment. In the new version of the manuscript, we have made changes to correct linguistic errors and make reading more fluid. The revision was also performed by a native English speaker.

 

Author Response File: Author Response.docx

Round 2

Reviewer 3 Report

Thanks for the update. The majority of earlier comments have been well addressed. I recommend the publication of the current version. Please double check the spelling, grammar, and format in proofreading.