Minimally Invasive Aortic Valve Surgery: State-of-the-Art Review of Transaxillary, Thoracotomy, and Ministernotomy Approaches

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review this manuscript entitled "Minimally Invasive Aortic Valve Surgery: State-of-the-Art Review of Transaxillary, Thoracotomy, and Ministernotomy Approaches". This article aims to evaluate and compare the role of minimally invasive aortic valve replacement (MIAVR) via transaxillary access, right anterior thoracotomy (RAT), and ministernotomy within modern valve care pathways. The authors concluded that all three approaches achieved remarkable perioperative safety and durable long-term survival comparable to full sternotomy, while consistently delivering superior recovery profiles—reduced blood loss, shorter ventilation times, accelerated hospital discharge, and enhanced patient satisfaction. The manuscript is well written, and the topic is interesting. It can be accepted for publication pending some minor corrections:

1) I would suggest adding information regarding the type of this manuscript. The manuscript's title could be "Minimally Invasive Aortic Valve Surgery: Systematic Review of Transaxillary, Thoracotomy, and Ministernotomy Approaches".

2) I would suggest having a structured abstract including all sections, such as introduction, aims, methodology, results, and conclusions.

3) The introduction section should include up-to-date information on the epidemiology of aortic valve disease and its treatment. There are many references in this section from non recently published articles. I would suggest replacing them with published articles from the last decade.

4) I would suggest adding figures that describe each technique

5) I would suggest a brief discussion on the modified pericostal suture technique to reduce postoperative pain and provide optimum anatomic restoration after conversion of minimally invasive thoracic surgery to thoracotomy

6) Make a further discussion on the role of extensive chest wall stabilization after cardiopulmonary resuscitation and urgent cardiac surgery

7) Finally, I would suggest a brief discussion on the history of the development of the isolated heart perfusion experimental model and its pioneering role in understanding heart physiology

8) What is the role of artificial intelligence in Minimally Invasive Aortic Valve Surgery?  

Author Response

Comment 1: I would suggest adding information regarding the type of this manuscript. The manuscript's title could be "Minimally Invasive Aortic Valve Surgery: Systematic Review of Transaxillary, Thoracotomy, and Ministernotomy Approaches."

Response: We appreciate this suggestion. However, we respectfully maintain the current designation as "State-of-the-Art Review" rather than "Systematic Review" for the following methodological and conceptual reasons:

(1) According to established methodological literature (Grant & Booth, 2009; Sutton et al., 2019), a "state-of-the-art review" constitutes a distinct review type that not only synthesizes current evidence but also critically analyzes historical evolution, identifies pivotal developments, addresses contemporary controversies, and proposes future research directions, extending beyond the descriptive scope of traditional systematic reviews.

(2) Our manuscript transcends conventional systematic review methodology by incorporating:

• Historical evolution and maturation of the three MIAVR approaches from experimental techniques to guideline-endorsed standards
• Development of the novel Three-Pillar Decision Model integrating anatomical phenotype, institutional maturity, and patient priorities a conceptual framework absent from existing literature
• Critical analysis of unresolved controversies (transaxillary stroke risk, learning curve ethics, MIAVR versus TAVI in younger populations)
• Comprehensive discussion of future research priorities and technological innovations

(3) While we employed rigorous systematic review methodology (PRISMA 2020 guidelines, PROSPERO registration, quality assessment via Newcastle-Ottawa Scale), we additionally provide expert synthesis, critical appraisal, and novel conceptual frameworks characteristic of state-of-the-art reviews.

(4) Leading cardiovascular journals (European Journal of Cardio-Thoracic Surgery, Annals of Cardiothoracic Surgery, Journal of Thoracic and Cardiovascular Surgery) routinely publish such comprehensive expert syntheses as "state-of-the-art reviews," confirming the appropriateness of this classification.

Therefore, we respectfully request maintaining the current title: "Minimally Invasive Aortic Valve Surgery: State-of-the-Art Review of Transaxillary, Thoracotomy, and Ministernotomy Approaches."

Comment 2: I would suggest having a structured abstract including all sections, such as introduction, aims, methodology, results, and conclusions.

Response: We agree with this recommendation and have restructured the abstract to include clearly delineated sections:

• Background
• Objectives
• Methods
• Results
• Conclusions

Changes are highlighted in yellow in the revised manuscript (lines 23-44).

Comment 3: The introduction section should include up-to-date information on the epidemiology of aortic valve disease and its treatment. There are many references in this section from non-recently published articles. I would suggest replacing them with published articles from the last decade.

Response: We agree and have comprehensively updated the Introduction section with contemporary epidemiological data and recent references (2020-2026):

• Added Global Burden of Disease Study 2021 data demonstrating that calcific aortic valve disease (CAVD) affects approximately 13.3 million individuals globally (95% UI 11.4-15.2 million), with age-standardized prevalence of 158.35 per 100,000 population
• Incorporated recent trends in TAVR/TAVI adoption (2020-2026), including market growth projections and evolving age indications from the 2025 ESC/EACTS Guidelines
• Replaced older citations with contemporary publications from high-impact journals (European Heart Journal 2024-2025, JACC 2024, JTCVS 2023-2024)

All additions are highlighted in yellow in the revised manuscript (lines 54-57, ).

Comment 4: I would suggest adding figures that describe each technique.

Response: We agree with this valuable suggestion. We have generated three professional medical illustrations depicting each surgical approach:

 

• Figure 3: Transaxillary access approach, illustrating incision location in the anterior axillary fold, cannulation strategy via axillary artery side-graft, and surgical access to the aortic valve
• Figure 4: Right anterior thoracotomy (RAT) approach, demonstrating intercostal space incision (2nd-3rd ICS), complete sternal preservation, and lateral access to the ascending aorta
• Figure 5: Ministernotomy technique, showing partial upper sternal division (inverted J) and surgical field exposure

Comment 5: I would suggest a brief discussion on the modified pericostal suture technique to reduce postoperative pain and provide optimum anatomic restoration after conversion of minimally invasive thoracic surgery to thoracotomy.

Response: We appreciate this suggestion regarding the modified pericostal suture technique. However, we respectfully propose not incorporating this topic in the current manuscript for the following reasons:

The modified pericostal suture technique primarily addresses management following conversion or complications, whereas our state-of-the-art review focuses on optimal procedural execution to avoid such scenarios. Our manuscript emphasizes preoperative planning, patient selection, and technical excellence to minimize conversion risk—rather than managing conversion consequences.

Including discussion of complication management techniques would shift focus from our core message: how to establish and execute successful MIAVR programs that achieve optimal outcomes through appropriate patient selection and technical proficiency.

We acknowledge that the modified pericostal suture technique represents an important clinical consideration deserving dedicated analysis, but believe it would be more appropriately addressed in a focused manuscript on pain management and complication mitigation strategies in minimally invasive cardiac surgery. We would be pleased to explore this topic in future work.

Comment 6: Make a further discussion on the role of extensive chest wall stabilization after cardiopulmonary resuscitation and urgent cardiac surgery.

Response: We appreciate this interesting suggestion. However, we respectfully believe that chest wall stabilization following cardiopulmonary resuscitation and urgent cardiac surgery falls outside the scope of our state-of-the-art review.

Our manuscript focuses exclusively on elective MIAVR procedures in carefully selected patients, where minimally invasive strategies are planned preoperatively based on CT anatomical assessment and multidisciplinary Heart Team evaluation. Scenarios requiring cardiopulmonary resuscitation and urgent cardiac surgery represent fundamentally different clinical contexts with distinct priorities, constraints, and therapeutic goals.

Incorporating discussion of chest wall stabilization in emergency settings could introduce confusion regarding MIAVR indications and divert attention from our primary focus: elective, planned minimally invasive aortic valve replacement.

We agree this represents an important clinical topic that we would be pleased to address in a separate manuscript focused on emergency cardiac surgery. However, in the current work, we prefer to maintain focus on elective minimally invasive procedures.

Comment 7: Finally, I would suggest a brief discussion on the history of the development of the isolated heart perfusion experimental model and its pioneering role in understanding heart physiology.

Response: We appreciate this suggestion regarding the historical development of isolated heart perfusion models and their role in cardiac physiology. However, we respectfully believe this topic, while undoubtedly fascinating from a historical perspective, is not aligned with the clinical focus of our state-of-the-art review.

Our manuscript is directed toward contemporary clinical application of three MIAVR approaches in patients, concentrating on:

• Patient selection criteria and anatomical considerations
• Perioperative and long-term clinical outcomes
• Learning curves and program implementation strategies
• Practical decision-making algorithms for multidisciplinary Heart Teams

The history of experimental isolated heart perfusion models, while important for understanding the foundations of cardiac physiology and cardioplegia development, extends beyond the direct clinical scope of this work.

We would be pleased to explore this topic in a separate historical-educational manuscript addressing the evolution of cardiac surgery. For the current state-of-the-art review, we prefer to maintain focus on practical aspects of contemporary minimally invasive aortic valve surgery.

Comment 8: What is the role of artificial intelligence in Minimally Invasive Aortic Valve Surgery?

Response: Thank you for this important question. The role of artificial intelligence (AI) in MIAVR is addressed in our manuscript in   Artificial Intelligence for Patient Selection      (lines 505-513)

In this section, we detail potential AI applications including:

• Machine learning algorithms for analyzing preoperative CT imaging to predict optimal MIAVR approach
• Development of deep learning models trained on datasets of >1,000 patients with annotated CT images
• Generation of approach recommendations (ministernotomy/RAT/transaxillary) with confidence scores and anatomical justification
• Prospective validation assessing prediction accuracy, surgeon acceptance, and impact on conversion rates
• Potential benefits including standardized approach selection, reduced conversion rates, improved surgical planning, and democratization of MIAVR expertise for developing programs

We have expanded this section in the revised manuscript to more prominently emphasize AI as a critical future research direction. These additions are highlighted in yellow.

In summary, we greatly appreciate the constructive review that has strengthened our work.

Respectfully submitted, 

Adam Kowalówka 

Reviewer 2 Report

Comments and Suggestions for Authors

The title and abstract cover the topic in an adequate degree. The highlights are instructive. 

The introduction frames the problem and ends with clerly identifiable aims. 

The section methods includes a clear search strategy with seemingly valid search terms and inclusion and exclusion criteria. The intended use of the Newcastle-Ottawa Scale adds to the value of the paper. The flow chart is instructive.

In the section results, table 1 describes the results of the propensity score matching. Why and how this method is used is not described in the method section (I assume that what is described on lines 87-88 refers to individual studies). Moreover, the number of patients is lowered by the PSM technique while the relative numbers (% between brackets) and means+/-SD are affected only in a minor degree. This puts the need for a PSM in question.

A classic meta-analysis with odds ratio, 95% confidence interval and P values seems appropriate. The results of the Newcastle-OĴawa Scale should be shown separately and clearly identifiable. 

Table 2 shows a low rate of sternal complications after RAT. On would expect zero. This should be explained (because of conversion to sternotomy?)

Table 2 shows in the right column the p-values with respect to sternotomy. The authors should add the values for this surgicalapproach and explain the source of this information. 

The discussion addressed important points such as the learning curve and stroke rates in patients undergoing RAT and transaxillary approaches. The discussion with TAVI is relevant.

The Three-Pillar Decision Model for MIAVR approach seems relevant with relation to the anatomy of the patient and adds to the value of the paper. The flow chart is intsructive. 

The limitations are clearly described. The conclusions should be shortened to the most important take-home messages. 

Author Response

Comment 1: The title and abstract cover the topic in an adequate degree. The highlights are instructive.

Response: We sincerely appreciate this positive feedback regarding the title, abstract, and highlights. We are pleased that these elements effectively convey the scope and significance of our work.

Comment 2: The introduction frames the problem and ends with clearly identifiable aims.

Response: Thank you for this positive assessment of the Introduction section. We aimed to clearly articulate the clinical problem and research objectives, and we appreciate confirmation that this goal was achieved.

Comment 3: The section methods includes a clear search strategy with seemingly valid search terms and inclusion and exclusion criteria. The intended use of the Newcastle-Ottawa Scale adds to the value of the paper. The flow chart is instructive.

Response: We appreciate your recognition of the methodological rigor in our systematic review approach. We are pleased that the search strategy, inclusion/exclusion criteria, Newcastle-Ottawa Scale quality assessment, and PRISMA 2020 flowchart effectively communicate our systematic methodology.

Comment 4: In the section results, table 1 describes the results of the propensity score matching. Why and how this method is used is not described in the method section. I assume that what is described on lines 87-88 refers to individual studies. Moreover, the number of patients is lowered by the PSM technique while the relative numbers between brackets and means±SD are affected only in a minor degree. This puts the need for a PSM in question.

Response: We appreciate this important methodological observation and have made the following revisions:

(1) Added detailed PSM methodology to Methods section: highlighted in yellow, lines 117-135) that explains:

• PSM was applied in the individual studies included in our review (not by our review team)
• The technique employed 1:1 nearest-neighbor matching with caliper 0.1 SD of the logit propensity score
• The purpose was to minimize selection bias when comparing different MIAVR approaches or MIAVR versus full sternotomy
• Lines 87-88 refer to PSM performed in the original primary studies

 

(2) Clarified the value of PSM despite minimal changes in proportions/means: The reviewer correctly observes that proportions and means change only minimally post-matching. We have added explanation that:

• The primary goal of PSM is achieving better balance of confounding variables between groups (measured by standardized mean differences SMD), not necessarily changing proportions
• Table 1 demonstrates that post-matching, 89-91% of variables achieved excellent balance (SMD <0.1), whereas pre-matching, systematic differences existed
• Even when relative proportions remain similar, elimination of systematic differences (SMD reduction) is crucial for valid comparisons
• PSM removes patients without appropriate matches, improving cohort comparability even when overall characteristics appear similar

 

Comment 5: A classic meta-analysis with odds ratio, 95% confidence interval and P values seems appropriate. The results of the Newcastle-Ottawa Scale should be shown separately and clearly identifiable.

Response: We appreciate both components of this suggestion:

(1) Regarding classic meta-analysis: We carefully considered conducting formal meta-analysis with odds ratios, 95% confidence intervals, and P-values. However, given substantial heterogeneity in:

• Patient populations (varying anatomical criteria, different centers)
• Surgical techniques (different ministernotomy subtypes, RAT via different intercostal spaces)
• Outcome definitions (variable complication criteria)
• Valve prosthesis types

We determined that narrative synthesis was more appropriate, consistent with Cochrane guidelines for reviews with high clinical and methodological heterogeneity. This approach is explicitly stated in Methods Section  (lines 137-142)

(2) Regarding Newcastle-Ottawa Scale results: We agree with the recommendation for clearer NOS presentation. In the revised manuscript:

• We have added Supplementary Table 1 presenting detailed Newcastle-Ottawa Scale scores for all 42 included studies
• The table includes scores for each of the three domains (Selection, Comparability, Outcome) plus overall score
• In the main text Results section (lines 153-162, highlighted in yellow)

Comment 6: Table 2 shows a low rate of sternal complications after RAT. One would expect zero. This should be explained.

Response: We agree this requires explanation, as it represents an important clinical observation. In the revised manuscript, we have added detailed explanation in the Results section (lines 213-222)

Comment 7: Table 2 shows in the right column the p-values with respect to sternotomy. The authors should add the values for this surgical approach and explain the source of this information.

Response: We agree with this recommendation. 

(1) Source explanation: In the Table 2 footnote (highlighted in yellow), we explain:

   "Data for full sternotomy are derived from propensity-matched control groups reported in 28 of the 42 included studies. P-values in the comparison column represent statistical comparisons between each MIAVR approach versus full sternotomy from original study analyses. (Line 245-247)

(2) Methods clarification: In the Methods section (lines 104-106, highlighted in yellow), we added:

   "When available, comparative data versus full sternotomy from propensity-matched or adjusted analyses were extracted to assess relative benefits of MIAVR approaches." (line 134-136)

Comment 8: The discussion addressed important points such as the learning curve and stroke rates in patients undergoing RAT and transaxillary approaches. The discussion with TAVI is relevant.

Response: We sincerely appreciate this positive feedback regarding the Discussion section. We are pleased that our analysis of learning curves, stroke rates, and comparison with TAVI is considered valuable and clinically relevant.

Comment 9: The Three-Pillar Decision Model for MIAVR approach seems relevant with relation to the anatomy of the patient and adds to the value of the paper. The flow chart is instructive.

Response: Thank you very much for recognizing the value of our Three-Pillar Decision Model. This represents a novel contribution of our manuscript, integrating patient anatomy, institutional maturity, and patient priorities into a practical clinical decision-making algorithm. We appreciate confirmation that the flowchart effectively communicates this framework.

Comment 10: The limitations are clearly described. The conclusions should be shortened to the most important take-home messages.

Response: We agree with this recommendation and have substantially shortened the Conclusions section to focus exclusively on key take-home messages. (line 572-587)

In summary, we have implemented almost all suggested revisions and we are deeply grateful for this thorough and insightful review.

Respectfully submitted,

Adam Kowalówka

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The modifications within the manuscript are sufficient.