Unusual Native Valve Remnant in the Left Ventricular Outflow Tract After Valve-in-Ring Transcatheter Mitral Valve Replacement

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This case report by Masnaghetti et al. describes a rare and diagnostically challenging finding of a persistent native valve remnant in the LVOT following Valve-in-Ring (ViR) TMVR. The authors successfully utilized multimodality imaging to differentiate this remnant from more ominous pathologies like thrombus or vegetation. The case serves as an important reminder of the potential for unusual anatomical configurations in post-procedural patients and the value of advanced echocardiography.

1. Management and Anticoagulation: The authors state that conservative management was adopted given the absence of complications. However, in a patient with a prosthetic valve and a mobile structure in the LVOT, the risk of thrombus formation on the remnant tissue or the prosthesis is a valid concern. The manuscript does not clearly specify the anticoagulation or antiplatelet regimen used during the follow-up period. Please clarify if the patient was on therapeutic anticoagulation and discuss the rationale for the specific prophylactic strategy chosen to mitigate the risk of thrombus formation on this remnant tissue.

2. Discussion Section: The discussion currently focuses on the diagnostic challenge and on differentiating the mass. It would be beneficial to expand the discussion to address potential procedural precautions for future cases. Specifically, the authors should discuss whether this finding necessitates specific modifications during pre-procedural planning (e.g., more aggressive assessment of native leaflet anatomy) or whether intraoperative techniques (such as intentional anterior leaflet modification) should be considered to prevent entrapment or persistence of such remnants in the LVOT. Providing insights on how to prevent or anticipate this anatomical outcome would add significant value to the report.

Author Response

Comment 1. 

The authors state that conservative management was adopted given the absence of complications. However, in a patient with a prosthetic valve and a mobile structure in the LVOT, the risk of thrombus formation on the remnant tissue or the prosthesis is a valid concern. The manuscript does not clearly specify the anticoagulation or antiplatelet regimen used during the follow-up period. Please clarify if the patient was on therapeutic anticoagulation and discuss the rationale for the specific prophylactic strategy chosen to mitigate the risk of thrombus formation on this remnant tissue.

Response 1. 

We thank the Reviewer for this important observation. We have modified the text to improve clarity, as suggested:

• Lines 62-63: we added the sentence “The patient had permanent atrial fibrillation and was receiving chronic oral anticoagulation with warfarin.”
• Lines 71-72: we added the sentence “As such, the patient was under double antiplatelet therapy in addition to postoperative oral anticoagulation.”
• Lines 88-90 we changed the existing text in “Given the possibility of a thrombotic origin, the adequacy of oral anticoagulation with warfarin was carefully reassessed; however, as the patient was already within the therapeutic INR range, no changes in antithrombotic therapy were made.”
• Lines 120-126: we changed the existing text in “Patient was discharged at home with triple anticoagulation therapy (double antiplatelet therapy with acetylsalicylic acid and clopidogrel, and anticoagulation with warfarin). According to current postoperative recommendations for mitral valve surgery [6], and given the concomitant indication for anticoagulation due to atrial fibrillation [7], no additional anticoagulation was prescribed specifically to prevent thrombus formation on the suspected mitral valve remnant.” and added two references (number 6 and 7).

Comment 2. 

The discussion currently focuses on the diagnostic challenge and on differentiating the mass. It would be beneficial to expand the discussion to address potential procedural precautions for future cases. Specifically, the authors should discuss whether this finding necessitates specific modifications during pre-procedural planning (e.g., more aggressive assessment of native leaflet anatomy) or whether intraoperative techniques (such as intentional anterior leaflet modification) should be considered to prevent entrapment or persistence of such remnants in the LVOT. Providing insights on how to prevent or anticipate this anatomical outcome would add significant value to the report.

Response 2. 

We sincerely thank the Reviewer for this insightful and constructive observation. We agree that addressing potential procedural precautions enhances the clinical relevance of the manuscript.

Accordingly, we have expanded the Discussion to comment on both pre-procedural planning and procedural technique. We now clarify that, although detailed imaging assessment (including evaluation of anterior leaflet length) may theoretically identify patients at risk, even meticulous pre-implant planning cannot reliably predict the final position of the native leaflet after valve deployment, given the complex leaflet–prosthesis interactions involved.

While we acknowledge the Reviewer’s suggestion regarding more aggressive preventive strategies (such as intentional leaflet modification), we believe that current evidence does not support recommending systematic technical modifications for this rare and poorly characterized finding. For this reason, we have framed the discussion to reflect both the potential implications and the present limitations in prevention.

• Lines 154-166: we added the following text: “In this context, even accurate pre-procedural planning and comprehensive imaging assessment of leaflet anatomy cannot reliably predict the final spatial configuration of the native leaflet after valve deployment. Although an excessively long anterior mitral leaflet may theoretically predispose to displacement toward the LVOT, this event remains difficult to anticipate with certainty and, importantly, cannot be completely prevented. Pre-implant imaging allows accurate characterization of baseline anatomy but does not fully capture the complex leaflet-prosthesis interactions that occur during and after device expansion. In this patient, the transapical approach was selected, which provides a more direct trajectory to the mitral annulus compared with the transseptal route, where valve ad-vancement and positioning are technically more demanding. This approach facilitates limited leaflet manipulation during deployment, a key factor in minimizing the risk of anterior leaflet injury and subsequent post-procedural displacement.”

We hope this revision satisfactorily addresses the Reviewer’s comment.

Reviewer 2 Report

Comments and Suggestions for Authors

It is an interesting case report. Suggestions: 1) The intervention date (sometimes in May 2025) and the death date (somewhere in August 2025) must be clearly stated. 2) It should be explained why a post mortem was not done: an autopsy would solve the intriguing "per exclusionem" differential diagnosis. 3) Consequently, the limitations of this presentation must be properly discussed.

Author Response

Comments 1. 

The intervention date (sometimes in May 2025) and the death date (somewhere in August 2025) must be clearly stated.

Response 1. 

We agree with the Reviewer’s comment and have revised the manuscript accordingly:

• Line 65: the intervention date is now explicitly reported: “On May 19th, 2025.”
• Lines 127-128: the patient’s death exact date has been added: “on August 28, 2025”.

Comments 2. 

It should be explained why a post mortem was not done: an autopsy would solve the intriguing "per exclusionem" differential diagnosis.

Response 2. 

We appreciate the Reviewer’s comment and we have now clarified this aspect in the revised manuscript:

• Lines 130-131: we added a sentence to specify why autopsy was not done: “A postmortem examination was not performed because of explicit refusal by the patient’s family”.

Comments 3. 

Consequently, the limitations of this presentation must be properly discussed.

Response 3. 

We apologize for the lack of limitations in the previous version and thank the Reviewer for this important observation. As suggested, we have now clarified this aspect in the revised manuscript:

• Lines 168-174: we added limitations to the discussion paragraph, underlying the important issue that the final diagnosis, without postmortem examination, remains preumptive: “The main limitation of this report is the absence of a postmortem examination, which could have definitively clarified the nature of the mass. Nevertheless, infective endo-carditis appears highly unlikely, as the patient did not receive antimicrobial therapy after discharge and remained clinically free from signs of infection for almost three months. An autopsy would have allowed definitive differentiation between a native mitral valve remnant and thrombotic material. In the absence of histopathological confirmation, the final diagnosis remains presumptive.”