Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors The review is a well-illustrated synthesis of a very current topic: the role of MRI in the evaluation of myocarditis. The authors present in a logical manner the material, using many figures, relevant examples, and diagrams for a better understanding of the text. The review is of great practical value, being an up-to-date guide in the hands of practitioners. Maybe, at the end of the text, the data about cardiac amyloidosis and Fabry disease are not in line with the topic of the article.

Author Response

comment 1 : Maybe, at the end of the text, the data about cardiac amyloidosis and Fabry disease are not in line with the topic of the article

Response: thank you for the feedback. I removed these sections.

Reviewer 2 Report

Comments and Suggestions for Authors

I read the review ”The evolving role of cardiac magnetic resonance in the diagnosis and management of myocarditis” by Wissam Alam, Houssem Hamrouni, Ivelina Chovena, and Cyrus Moini, and I have several suggestions for the authors. 

1. Please rethink the article name, because when you read the title, you get the impression that you will read only good things about the CMR, but in reality yoy get more than that.

2. In the Introduction, please remove Table 1, as it provides a partial etiology, and I think that is not necessary in this review.

3. In the Materials and Methods: please add quotation marks to all the searching words that you used; clarify the type of the review; add a flow chart to understand the pathway that you used, mentioning all the articles that you initially discovered, the excluded articles, and the reason for the exclusion, if you used article for different languages please mention the translation source, or the name of the authors that readed those articles, mentioning also the number of the articles by languages. Mention the criteria that make an article ”relevant” for your work. Please define the inclusion and exclusion criteria clearly.

In the Stages of Myocarditis:

• In line 71, the authors suggest that myocarditis evolution depends solely on the patient; please correct this.
• In the acute myocarditis paragraph, please add data about myocardial enzymes and how they correlate with CMR findings. 
• In the subacute myocarditis paragraph, please add data on myocardial enzymes evolution and CMR findings.
• In the chronic myocarditis paragraph, please add data about the inflammation markers, myocardial enzymes, and how they are correlated with CMR findings.
• Please recreate the images clearly.

In The role of CMR in the diagnosis of myocarditis:

• Please add a short description of each phase of CMR evaluation to facilitate the reading of this review, as readers may not be experienced in CMR evaluation.
• Please transform lines 128-150 into a comparative table.
• Extend the idea from lines 153-154 a little to justify the decision.

In The role of CMR in determining the prognosis of myocarditis:

• Please start a discussion on the CMR vs. TTE LVEF evaluation.
• In the Late Gadolinium Enhancement paragraph, please add some data on the timing of the CMR reevaluation and its predictive role. The same remark for the Parametric Mapping paragraph.
• In the Myocardial Strain paragraph, please add a comparison with TTE.
• Please specify the level of restriction (total or percentage) on physical activity for athletes.
• Since you mentioned athletes as a special category, please also mention other special patient groups and how we should approach them.

In the CMR and false diagnosis of myocarditis:

• Add  ”positive”
• Before debating the differential diagnosis, please add data on the clinical presentation of a patient with myocarditis, and emphasize that the first clue is the clinical evaluation of a patient and the suspicion of myocarditis.
• Mention clearly that genetic testing is not an imperative evaluation after the first CMR.
• Maintain the same pattern in the discussion: TTE, ECG, CMR
• Please transform lines 254-265 into a comparative table (favorable on, against on)
• You discuss the ECG findings first in lines 266-268, but please mention that the findings on a myocarditic patient's ECG are not specific (you may even create a comparison table indicating the frequency of ECG findings for ACM and myocarditis.

For the Specific myocarditis pattern on CMR, please maintain the same pattern as in the previous part (ECG, TTE, CMR).

In the Future perspectives part:

• In lines 474-478, please explain how we can differentiate inflammation from myocarditis from other inflammations using this technique.
• How can we diminish the importance of the heart rate in the CMR evaluation? (most of the patients with myocarditis are tachycardic)

Author Response

Comment 1: Please rethink the article name, because when you read the title, you get the impression that you will read only good things about the CMR, but in reality yoy get more than that

Response: Thank you, we changed the title based on feedback  to better fit our article

Comment 2: In the Introduction, please remove Table 1, as it provides a partial etiology, and I think that is not necessary in this review

Response: Our intention was to keep the discussion of etiologies brief within the main text, as it is not the primary focus of this article. However, to ensure the reader has access to a comprehensive overview if desired, we have replaced Table 1 with a more exhaustive and detailed version

Comment 3: In the Materials and Methods: please add quotation marks to all the searching words that you used; clarify the type of the review; add a flow chart to understand the pathway that you used, mentioning all the articles that you initially discovered, the excluded articles, and the reason for the exclusion, if you used article for different languages please mention the translation source, or the name of the authors that readed those articles, mentioning also the number of the articles by languages. Mention the criteria that make an article ”relevant” for your work. Please define the inclusion and exclusion criteria clearly

Response: thank you for your comment. We reworked material and method to better illustrate the PRISMA workflow and added the chart

Comment 4:  In line 71, the authors suggest that myocarditis evolution depends solely on the patient; please correct this.

Response: We agree and  have revised the text to clarify that the clinical course is a result of the complex interaction between the specific etiology and the host's immune response and genetics

Comment 5: In the acute myocarditis paragraph, please add data about myocardial enzymes and how they correlate with CMR findings.

Response:  data added

Comment 6: In the subacute myocarditis paragraph, please add data on myocardial enzymes evolution and CMR findings

Response: data added

Comment 7: In the chronic myocarditis paragraph, please add data about the inflammation markers, myocardial enzymes, and how they are correlated with CMR findings.

Response: data added

Comment 8: Please recreate the images clearly.

Response: Thank you for the feedback . we recreated images clearly and corrected mistakes

Comment 9: Please add a short description of each phase of CMR evaluation to facilitate the reading of this review, as readers may not be experienced in CMR evaluation.

Response: description of the protocol for myocarditis added

Comment 10: Please transform lines 128-150 into a comparative table

Response: Added comparative table

Comment 11: Extend the idea from lines 153-154 a little to justify the decision.

Response: expended why EGE was removed from LLC criteria

Comment 12:  In The role of CMR in determining the prognosis of myocarditis: Please start a discussion on the CMR vs. TTE LVEF evaluation

Response: we added a paragraph for this as suggested

Comment 13: In the Late Gadolinium Enhancement paragraph, please add some data on the timing of the CMR reevaluation and its predictive role

Response: added data on the timing of the CMR reevaluation and its predictive role

Comment 14: The same remark for the Parametric Mapping paragraph.

Response: added data on the timing of the CMR reevaluation with parametric mapping and its predictive role 

Comment 15: In the Myocardial Strain paragraph, please add a comparison with TTE.

Response: we added a paragraph for this as suggested

Comment 16:  Please specify the level of restriction (total or percentage) on physical activity for athletes.

Response: added total restrictions of professional activity for athletes 

Comment 17: Since you mentioned athletes as a special category, please also mention other special patient groups and how we should approach them.

Response:  do you have special groups in mind ? we tried not to expand to other groups as the purpose of our article is the role of CMR in myocarditis . We chose to talk about athletes as we frequently encounter this population in our institution

Comment 18:  In the CMR and false diagnosis of myocarditis: Add  ”positive"

Response: added

Comment 19: Before debating the differential diagnosis, please add data on the clinical presentation of a patient with myocarditis, and emphasize that the first clue is the clinical evaluation of a patient and the suspicion of myocarditis.

Response: Thank you for your feedback. We briefly described the presentation of a patient with myocarditis in this paragraph : "These conditions can manifest with chest pain, troponin elevation, ECG changes, and ventricular dysfunction, mimicking acute myocarditis". We believe that it is outside the scope of this article to go into more details as we wish to mainly discuss the findings of MRI in these patients ,once the diagnosis of myocarditis is considered, inlcuding the shortfalls of this technique.

Comment 20: Mention clearly that genetic testing is not an imperative evaluation after the first CMR.

Response:  Added clarification on when to test for genetic cardiomyopathy with the necessary data

Comment 21: Maintain the same pattern in the discussion: TTE, ECG, CMR

Response: Dear colleague, thank you for your feedback. We tried to focus on CMR findings while avoiding to detail electric and echocardiographic findings as we do not wish to make  an extensive review about the diagnosis of myocarditis but more a focus on CMR

Comment 22:  Please transform lines 254-265 into a comparative table (favorable on, against on)

Response: Do you mean for ACM ? If so, the only criteria that favor ACM are predominantly right heart involvement and family history. we believe that there are not enough differentiating points to justify making a comparative table

Comment 23: You discuss the ECG findings first in lines 266-268, but please mention that the findings on a myocarditic patient's ECG are not specific 

Response: thank you , we changed the sentence to reflect that

Comment 24: For the Specific myocarditis pattern on CMR, please maintain the same pattern as in the previous part (ECG, TTE, CMR)

Response: thank you for your feedback. To keep in line with the above, we wish to focus on CMR findings without going to specifics about ECG and TEE

Comment 25: In lines 474-478, please explain how we can differentiate inflammation from myocarditis from other inflammations using this technique

Response: Slightly expanded explanation of this technique as suggested, while trying to keep with the suggestion of the other reviewers to shorten this part of the article that they find too long

Comment 26: How can we diminish the importance of the heart rate in the CMR evaluation? (most of the patients with myocarditis are tachycardic

Response: thank you for the idea. we added a paragraph at the end of the article to briefly address this while trying to stay concise

Reviewer 3 Report

Comments and Suggestions for Authors

General comments

This manuscript describes with exhaustivity the various stages and etiologies of myocarditis, with the help of multiparametric approach.

The evolution of LLC criteria is well documented, even if these criteria are only available for viral myocarditis.
There is an interesting chapter on CMR and false diagnoses of myocarditis with emphasis on the critical role of genetic testing in mimicking conditions.

The chapter upon “future perspectives” is somewhat too long and should be synthetized.

Abbreviations must be spelled at their first appearance all along the text.

 

Specific comments

Line 33. It should be mentioned that EMB is performed in the right cardiac chambers and results in numerous false negative studies.

Page 2, Table 1. Herpes virus HHV6 is not mentioned. Myocarditis due to Herpes virus often has specific clinical and MR features.

Page 3, Stages of myocarditis. In Figure 1, please make corrections for “acute myocaditis”, “persistent inflarmation”, “dilated cardiompapthy” and “dilated cardiompraphy”. Furthermore, why two LGE+ in the left column for acute myocarditis and persistent inflammation?

Page 7, Fig 3b legend. One should read “65-year-old”, “no hyperemia”

Page 8, line 209. “Not sustained ventricular tachycardia” should be spelled as is.
Page 8, line 221 and following. The sentence “LV systolic function has returned to normal range, normalization of myocardial serum biomarkers, Absence of frequent or complex arrythmias on the 24-hours ECG and exercise test” needs to be extensively reformulated for better comprehension.

Page 9, Fig 4. The authors should make corrections to “physical acitivty and competitive sports”

Page 11, line 278 “T1-weigheted” must be rewritten correctly

Page 12, line 328. One should read “The overlap between CMR phenotypes of myocarditis and genetic cardiomyopathies make it necessary…”

 

Author Response

Comment 1: The chapter upon “future perspectives” is somewhat too long and should be synthetized.

Response: The 'Future Perspectives' section has been streamlined to improve conciseness and eliminate redundancies

Comment 2: Abbreviations must be spelled at their first appearance all along the text

Response: we made the necessary corrections

Comment 3: Line 33. It should be mentioned that EMB is performed in the right cardiac chambers and results in numerous false negative studies

Response: added

Comment 4: Page 2, Table 1. Herpes virus HHV6 is not mentioned. Myocarditis due to Herpes virus often has specific clinical and MR features.

Response:  HHV6 added to the table. A specific section was added for HHV6 myocarditis to illustrate specific clinical and MRI characteristics.

Comment 5: Page 3, Stages of myocarditis. In Figure 1, please make corrections for “acute myocaditis”, “persistent inflarmation”, “dilated cardiompapthy” and “dilated cardiompraphy”. Furthermore, why two LGE+ in the left column for acute myocarditis and persistent inflammation

Response: Thank you very much for these corrections, we made the necessary changes

Comment 6: Page 7, Fig 3b legend. One should read “65-year-old”, “no hyperemia”

Response: Corrected

Comment 7: Page 8, line 209. “Not sustained ventricular tachycardia” should be spelled as is

Response: corrected

Comment 8: Page 8, line 221 and following. The sentence “LV systolic function has returned to normal range, normalization of myocardial serum biomarkers, Absence of frequent or complex arrythmias on the 24-hours ECG and exercise test” needs to be extensively reformulated for better comprehension.

Response: the sentence was reformulated for better comprehension 

Comment 9: Page 9, Fig 4. The authors should make corrections to “physical acitivty and competitive sports

Response: corrected

Comment 10: Page 11, line 278 “T1-weigheted” must be rewritten correctly

Response: corrected

Comment 11: Page 12, line 328. One should read “The overlap between CMR phenotypes of myocarditis and genetic cardiomyopathies make it necessary…

Response: reformulated as requested