Tuberculosis of the Heart: A Diagnostic Challenge

Round 1

Reviewer 1 Report

The paper by Das et al. is well written and sounded. 

TB infections are -unfortunately- rising up also in the Mediterannean egion due to extensive migration waves therefore clinicians must be advised on that.

Section number #4. Among laboratory tests PCR is mentioned; this molecular biology is still the fastest and more sensitive tool presently available when done on pericardial fluids, however liquids culturing for TB still remains the GOLD STANDARD for the lab diagnosis (test that I suggest to include).

Author Response

Dear Editor, Tomography.

 

We are extremely grateful to you and your honorable reviewers for the comments on the present paper which will definitely enhance the quality of the paper. Herewith, we have comprehensively re-written the different parts of the manuscript and responded to all the changes asked by the honorable reviewers.

In response to the queries raised by the honorable reviewers, we have added the statement as he suggested.  Section 4 lines 164-167.

Reviewer 2 Report

The authors present a manuscript disucssing an overview of cardiac tuberulosis and the inherit challenges of diagnosis, especially without the use of invasive procedures, such as biopsy. The authors suggest the use of CMR as a primary tool for the diagnosis of cardiovascular TB, which seems very appropriate given the typical symptoms of peri/myocarditis in these patients that present with cardiac TB. Overall, the authors do a good job of providing an overview of clinical presentation of cardiac TB and the differing approaches to diagnose. However, there are some comments below that I would like the authors to address:

- Overall, I think there is a strong need for a summary section. The authors present clear sections, with the longest being the role of CMR. In the introduction the purpose was to provide an overview of cardiovascular TB and the diagnostic value of CMR as well as various imaging and lab tests to detect. Is the goal of this review to convince readers that CMR is the best option for diagnosing cardiac TB or to simply provide an overview of cardiac TB and the different modes of diagnosis? If, the major emphasis is the diagnostic value of CMR over other imaging modalities, there is really no comparison/contrast of CMR/CT/PET, etc.. with respect to diagnostic differences between modalities. Also, there is no section on the role of cardiac CT. Could the authors provide a substantial summary section of the strengths/weaknesses of each modality and let the reader decide the if CMR has better diagnostic capabilities over other imaging modalities and the paper should be simply an overview of cardiac TB, the inherent challenges of diagnosis, and the different modes that are currently used to diagnose cardiac TB, and summarizing the strengths/weaknesses of each imaging modality.

- I have to disagree with the authors concluding assertion in lines 308-309 that CMR may be used instead of endomyocardial biopsy to diagnose and treat myopericarditis that is the result of TB. There are many modes a patient can present with myopericarditis that is unrelated to TB itself (as the authors correctly point out), therefore, a biopsy would more definitively determine whether the underlying inflammation in the heart is the result of TB. Can the authors please reword there concluding statement.

- While I agree with the premise that CMR would be an excellent approach to help diagnose early cardiac TB, I question how useful this will be in countries that are of lower income and reduced access to CMR over echocardiography. Also, these countries tend to have higher prevalence of TB and echocardiography is much more transportable and cost-effective (even if it is not as of high quality). Perhaps, some discussion in the manuscript on the challenges not only to diagnose cardiac TB but also the inherit limitations based on socioeconomic factors as well would be beneficial for the readers.

- The authors use a single case study as the only CMR imaging figures of diagnosed cardiac TB. If possible, it would be great to garner permission from previously published manuscripts that have CMR presentations of differing clinical presentations with imaging. For example, in section 5.4 there is discussion of intracardiac tuberculomas with a paper cited using T2 weighted imaging to identify the tuberculoma. This would make a nice figure so the reader has a visual presentation of this particular manifestation of cardiac TB. This same suggestion would be great for the clinical FDG-PET images with corresponding CMR images of increased FDG uptake in said regions that were referenced in #61.

-  Please go through each figure legends and reword necessary legends for improved clarity as needed. Also, Figure 1b is not a 2Ch view but is a 4Ch view, Figure 2A, 2B, 2C are short-axis views not 2Ch views (plus tell us if this is mid-myocardial or basal slices), Figure 4, please provide a ECV color map similar to what was done for the T1 mapping image.

Author Response

We are extremely grateful to you and your honorable reviewers for the comments on the present paper which will definitely enhance the quality of the paper. Herewith, we have comprehensively re-written the different parts of the manuscript and responded to all the changes asked by the honorable reviewers.

In response to the queries raised by the honorable reviewers, we have added the statement as he suggested.  The respective comments are added with the answer herewith. 

Q.1: 

 Overall, I think there is a strong need for a summary section. The authors present clear sections, with the longest being the role of CMR. In the introduction the purpose was to provide an overview of cardiovascular TB and the diagnostic value of CMR as well as various imaging and lab tests to detect. Is the goal of this review to convince readers that CMR is the best option for diagnosing cardiac TB or to simply provide an overview of cardiac TB and the different modes of diagnosis? If, the major emphasis is the diagnostic value of CMR over other imaging modalities, there is really no comparison/contrast of CMR/CT/PET, etc.. with respect to diagnostic differences between modalities. Also, there is no section on the role of cardiac CT. Could the authors provide a substantial summary section of the strengths/weaknesses of each modality and let the reader decide the if CMR has better diagnostic capabilities over other imaging modalities and the paper should be simply an overview of cardiac TB, the inherent challenges of diagnosis, and the different modes that are currently used to diagnose cardiac TB, and summarizing the strengths/weaknesses of each imaging modality.

Answer: We do fully agree with the honorable reviewer and herewith, we have incorporated an additional segment stating the merits and demerits of different imaging modalities as suggested. (Page no 13, lines no 13-25, page 15, lines no 1-26 & page 14, lines no 1-22. 

Q 2: - I have to disagree with the authors concluding assertion in lines 308-309 that CMR may be used instead of endomyocardial biopsy to diagnose and treat myopericarditis that is the result of TB. There are many modes a patient can present with myopericarditis that is unrelated to TB itself (as the authors correctly point out), therefore, a biopsy would more definitively determine whether the underlying inflammation in the heart is the result of TB. Can the authors please reword there concluding statement.

Answer: Here we would like to thank the honorable reviewers for their insight. Here we have added an additional section " Endometrial biopsy" to explain the matter in more detail with the addition of references. Page no 13, lines no 2-12. Moreover, we have made a minor modification in the abstract section also. Page 1, lines no 16-20. 

Q3: - While I agree with the premise that CMR would be an excellent approach to help diagnose early cardiac TB, I question how useful this will be in countries that are of lower income and reduced access to CMR over echocardiography. Also, these countries tend to have higher prevalence of TB and echocardiography is much more transportable and cost-effective (even if it is not as of high quality). Perhaps, some discussion in the manuscript on the challenges not only to diagnose cardiac TB but also the inherit limitations based on socioeconomic factors as well would be beneficial for the readers.

Answer: Here we would like to thank the honorable reviewers for their insight. Here we explained the same issue with the addition of another section on page no 15 (Lines 24-26) and the page no 16 (Lines 1-12).

Q4: - The authors use a single case study as the only CMR imaging figures of diagnosed cardiac TB. If possible, it would be great to garner permission from previously published manuscripts that have CMR presentations of differing clinical presentations with imaging. For example, in section 5.4 there is discussion of intracardiac tuberculomas with a paper cited using T2 weighted imaging to identify the tuberculoma. This would make a nice figure so the reader has a visual presentation of this particular manifestation of cardiac TB. This same suggestion would be great for the clinical FDG-PET images with corresponding CMR images of increased FDG uptake in said regions that were referenced in #61.

Answer: Here we would like to thank the honorable reviewers for their insight. As suggested we have added three of the additional figures (Fig 5-7).

Q5: -  Please go through each figure legends and reword necessary legends for improved clarity as needed. Also, Figure 1b is not a 2Ch view but is a 4Ch view, Figure 2A, 2B, 2C are short-axis views not 2Ch views (plus tell us if this is mid-myocardial or basal slices), Figure 4, please provide a ECV color map similar to what was done for the T1 mapping image.

Answer: Here we would like to thank the honorable reviewers for their corrections. We have made all the changes as suggested and added the ECV mapping.

Round 2

Reviewer 2 Report

I would like to commend the authors for taking the time to make improvements to the manuscript and it is much more comprehensive and thorough explanation of the imaging modalities associated with cardiac TB.

I have only a few minor revisions to suggest:

- Please move the added lines 113-115 to the end of the paragraph in the same section to enhance readability. Lines 113-115 are a nice summary of that section. Additionally, please make this grammatical change; "Laboratory testing including (currently says include) PCR"

- Figure 4 ECV color map values should be larger for readability

- Figs 5,6,7: When mentioning where the image came from, cite as you would in the text of the manuscript. For example for Figure 5. This image was adapted from Dixit et al. [53].

- Section 9 title: Instead of Merits and demerits, suggest using Advantages and Disadvantages

- Section 10 title: Instead of the title, Socioeconomic status, suggest using Remaining Challenges

Author Response

I would like to thank the honorable reviewer for his valuable suggestions. We have incorporated all the minor changes in the manuscript. All the recent changes are highlighted in the revised manuscript with track changes.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

In the manuscript, the use of CMR in the diagnosis of tuberculous myopericarditis is reviewed. The current status of cardiovascular tuberculosis in low- and middle-in-come countries is described and the advantages of CMR imaging technique with respect to other existing methods in detecting, characterizing and assessing tuberculous myopericarditis are reported.

General remarks

The topic is interesting and challenging, nevertheless several elements suggest that the paper should be rearranged and focused, filling some methodological gaps. In particular, the major concerns are related to the review design and the discussion of the contents.

The novelty of the manuscript with respect to the current scientific literature is not clear and it is difficult to understand how the experience of the Authors on a single patient affected by tuberculous myopericarditis can be related to the clinical outcomes described in literature obtained with other diagnostic techniques. The reported data are confused and deserve a less superficial approach. Moreover, the comparison among the imaging diagnostic techniques included in the paper is only qualitative and an in-depth understanding of their corresponding limitations and disadvantages is missing. I suggest the Authors use tables and/or schemes to summarize and highlight these key aspects. This could help the reader that is not familiar with the technologies included in the review.

Finally, there are concerns about the English language: missing explanation of several acronyms (e.g., lines 204-205), confusing and contradictory sentences (e.g., lines 142-144, 151-154), grammar mistakes (e.g., lines 14-15) and redundant words (e.g., lines 178-181).

Reviewer 2 Report

The article by Karuna M Das presented to me for review. et al. entitled "Tuberculous Myopericarditis: a comprehensive evaluation with CMR." raises a fascinating topic: the relationship between tuberculosis and cardiovascular diseases. However, in my opinion this article does not meet the criteria that should characterize the review article. In the introduction, the authors describe a clinical case with which they had contact, suggesting that this work should be a case study. This description, however, is not exhaustive; therefore, we do not know if the diagnosis and therapy were effective. However, the most significant caveat is using only the QFT test to confirm Mycobacterium tuberculosis infection. Despite its popularity, this test does not allow to correctly diagnose tuberculosis in its active form. It should be remembered that this disease affects 1/3 of the world's population, but most infections take a latent form.

This manuscript also raises a number of reservations in terms of its structure and style. Therefore, I believe that it requires an additional amount of work to rethink the concept of the publication.