Combination Treatment of Balloon Pulmonary Angioplasty and Direct Oral Anticoagulant in a Patient with Chronic Thromboembolic Pulmonary Hypertension Complicated by Protein S Deficiency

Round 1

Reviewer 1 Report

This is an interesting case-report article with sufficient additional information about management of patient suffering from two rare diseases. Indeed even in the newest ESC PH guidelines there is no information how to manage this type of patients, so every case-report is helpful. 

I would only add a simple statement about pharmacological treatment with riociguat. As patient has now mPAP 21mmHg (above new threshold (20))do you consider to add this drug beside of OAC?

Congratulations! 

Author Response

Reviewer 1

General comment.

This is an interesting case-report article with sufficient additional information about management of patient suffering from two rare diseases. Indeed even in the newest ESC PH guidelines there is no information how to manage this type of patients, so every case-report is helpful.

Response.

We express our great appreciation for the reviewer’s critical suggestions and comments. We attempted our best to answer all the comments and revise our draft. We also corrected typographs and grammatical errors. We believe that the revised draft would be suitable for the publication.

Comment 1.

I would only add a simple statement about pharmacological treatment with riociguat. As patient has now mPAP 21mmHg (above new threshold (20))do you consider to add this drug beside of OAC?

Answer 1.

We appreciate your comment. Although it is unclear whether riociguat improves long-term prognosis in cases such as ours, it has the potential to improve exercise tolerance and might be considered as a treatment option depending on the clinical course, including subjective symptoms.

Before 1.

DISCUSSION

Angioplasty to improve exercise tolerance

None.

After 1.

DISCUSSION

Angioplasty to improve exercise tolerance

In addition to angioplasty, medical therapy, including riociguat, may improve exercise tolerance and combination therapy is expected.

Author Response File: Author Response.docx

Reviewer 2 Report

 Izumida et al studied Combination Treatment of Balloon Pulmonary Angioplasty...

This study is not so novel, but it has significant content and it is valuable in its field.

I have some main comments:

The abstract is not complete. Please improve it as it includes all sections of an abstract.

The introduction is so short.  It does not provide sufficient background and does not include all relevant references. More related and recent references are needed. Also, the aim of the study is not clear in the introduction section. The justifications are not potent.

Methods: the study process should include more details and relevant references should be added.

Discussion: The discussion section is short and it needs more companionship with other studies.

The manuscript needs a conclusion section.

The figures are good. Thanks.

The references need to improve as I said in the introduction comments. 

Generally, the manuscript can improve.  

Author Response

Reviewer 2

General comment.

Izumida et al studied Combination Treatment of Balloon Pulmonary Angioplasty… This study is not so novel, but it has significant content and it is valuable in its field.

Response.

We express our great appreciation for the reviewer’s critical suggestions and comments. We attempted our best to answer all the comments and revise our draft. We also corrected typographs and grammatical errors. We believe that the revised draft would be suitable for the publication.

Comment 1.

The abstract is not complete. Please improve it as it includes all sections of an abstract.

Answer 1.

We appreciate your comment. As you pointed out, we modified the abstract according to the information for authors.

Before 1.

None.

After 1.

Please see our abstract.

Comment 2.

The introduction is so short. It does not provide sufficient background and does not include all relevant references. More related and recent references are needed. Also, the aim of the study is not clear in the introduction section. The justifications are not potent.

Answer 2.

Thank you for your comment. We have reconstructed the introduction to be more theoretical and added the below sentence and related references.

Before 2.

INTRODUCTION

None.

After 2.

INTRODUCTION

We presented here a patient with CTEPH complicated by protein S deficiency successfully treated with balloon pulmonary angioplasty, and discussed the therapeutic strategy in a patient with CTEPH and protein S deficiency.

Comment 3.

Methods: the study process should include more details and relevant references should be added.　

Answer 3.

Because this manuscript is a case report, we are not allowed to include methods section. Instead, we attempted our best to state more detail about the case presentation.

Before 3.

See previous case presentation section.

After 3.

See updated case presentation section.

Comment 4.

Discussion: The discussion section is short and it needs more companionship with other studies.

Answer 4.

Thank you for your comment. Because of its rarity, there have been few reports of complications. References have been added regarding the evidence for CTEPH treatment content.

Before 4.

None.

After 4.

Please see our revised manuscript.

Comment 5.

The manuscript needs a conclusion section.

Answer 5.

Thank you for your comment. We added a conculsion section.

Before 5.

None

After 5.

CONCLUSION

Current established standard therapeutic strategy for CTEPH including pulmonary angioplasty might be safe and effective even in patients with concomitant inherent coagulation abnormalities.

Comment 6.

The references need to improve as I said in the introduction comments.

Answer 6.

Thank you for your comment. References have been added, regarding the evidence for CTEPH treatment content.

Before 6.

None.

After 6.

Please see our manuscript.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

It can be accepted.