The Brain–Atrial Fibrillation–Recent Rehabilitation Axis: A Modern Approach

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This review article aims to synthesize current knowledge on AF, focusing on its pathophysiology, epidemiology, treatment strategies, and its neurological complications, particularly stroke. It introduces an innovative rehabilitation framework tailored to AF-related stroke, emphasizing a physiologically guided, multidisciplinary approach. The article’s strengths lie in its comprehensive scope, integration of cardiovascular and neurorehabilitation domains, and the conceptual development of the “Heart-Brain Team” and “Hemodynamic Gating Matrix” models, making it highly relevant for advancing holistic patient care.  

1. title: Typo: “Modern Approch” should be “Modern Approach”
2. section 6.1 Digital detection technologies well-covered; a table comparing devices might help readers.
3. Some sections, especially the rehabilitation discussion, use complex sentence structures and advanced terminology. Consider simplifying or defining terms 
4. at method section (and in title) define narrative or comprehensive review and include information about the search strategy. this is the main weakness of the paper
5. add limitations section

Author Response

Response to Reviewer #1

We would like to thank the Reviewer for the insightful analysis of our manuscript. We greatly appreciate the constructive comments, particularly regarding the methodological structure and the clarity of the rehabilitation section. Following your recommendations, we have significantly revised the manuscript. Changes made to the text are marked in red for your convenience.

Reviewer’s Comment	Author’s Response
"at method section (and in title) define narrative or comprehensive review and include information about the search strategy. this is the main weakness of the paper"	We agree entirely. We have addressed this critical point by adding a comprehensive "Methodology" section. 1. We explicitly defined the work as a "narrative review". 2. We detailed the search strategy (PubMed, Scopus, Cochrane) and timeframes (2020–2026). 3. We added Table 1, which presents the specific inclusion and exclusion criteria. 4. We included Figure 1 (PRISMA Flowchart) to visualize the study selection process.
"Some sections, especially the rehabilitation discussion, use complex sentence structures and advanced terminology. Consider simplifying or defining terms"	Thank you for this valuable suggestion. To improve clarity and readability in Section 19, we have implemented two major changes: 1. We subdivided the entire section into 10 distinct subsections (19.1–19.10) with precise subheadings to guide the reader through specific topics (e.g., Mobilization Readiness, Cognitive-Motor Interference). 2. We added Table 2 (Operationalization of the Hemodynamic Gating Matrix), which precisely defines the advanced terminology and sets clear physiological thresholds (e.g., for chronotropic competence and orthostatic tolerance), making the text more accessible.
“section 6.1 Digital detection technologies well-covered; a table comparing devices might help readers.”	Thank you for your appreciation, table was added.
"add limitations section"	We have added a dedicated "Limitations of the Study" section at the end of the manuscript. In this section, we critically acknowledge the narrative nature of the review and explicitly state that the proposed models (Hemodynamic Gating Matrix, Heart-Brain Team) are theoretical frameworks based on extrapolation, requiring validation in future prospective trials.
"title: Typo: “Modern Approch” should be “Modern Approach”"	We apologize for this oversight. The title has been corrected to "Modern Approach".

 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Reviewer Report

Major Comments

Comment 1

The title implies a focused, modern “brain–AF–rehabilitation axis,” yet the manuscript devotes extensive space to general AF classification, management, and procedural therapies (e.g., catheter and surgical ablation sections) before reaching rehabilitation (Section 19). In the abstract, the stated aims include presenting prevalence, pathophysiology, risk factors, pharmacologic/surgical treatment strategies, and early rehabilitation after AF-associated stroke (p.1, lines 20–23). This is extremely broad for a single review and blurs the intended contribution.

Kindly reframe as a focused narrative/scoping review centered on AF-associated stroke recovery and early rehabilitation (including hemodynamic instability, cognition, anticoagulation timing, and interdisciplinary models), and sharply shorten the general AF management material to only what is essential for rehab decisions.

 

Comment 2

The manuscript functions as a narrative review but does not state-

1. whether a structured literature search was performed,
2. databases searched, timeframe, search terms,
3. inclusion/exclusion criteria,
4. or how evidence was selected/graded.

Kindly add a brief Methods for the review (even for a narrative/scoping review): databases, date range, key search concepts, and how studies/guidelines were prioritized. If presented as a scoping review, include a basic selection flow and evidence mapping.

 

Comment 3

In the abstract, the text states that thromboembolic brain complications “lead to progressive vascular dementia” (p.1, lines 13–14). The relationship between AF, stroke, and cognitive decline is complex, and causality/trajectory vary widely by infarct burden, recurrent emboli, microvascular disease, and competing neurodegenerative pathology. Similarly, “organ thromboses…lead to other organ complications” (p.1, lines 14–15) is vague.

contribute to progressive cognitive impairment”), and specify mechanisms/outcomes with citations rather than broad assertions.

Comment 4

The manuscript describes a shift from time-based mobilization to physiology-based mobilization and introduces the Hemodynamic Gating Matrix as a “practical framework” integrating cardiac monitoring, BP assessment, and autonomic testing, with criteria like rate control, orthostatic response, and rhythm stability on telemetry (p.15, lines 647–663). This is clinically sensible, but it is not clear whether this “matrix” is an established published protocol vs. the authors’ proposed construct, what specific thresholds define readiness (e.g., acceptable HR ranges, BP variability limits, orthostatic criteria), how it differs from standard ICU/step-down mobilization safety criteria already used in many institutions.

Kindly label the matrix as proposed if it is not previously validated. Provide an operational table/algorithm (inputs, thresholds, stop rules, escalation pathways). Cite supporting evidence or guidelines that justify each criterion, and clarify which elements are expert opinion.

 

Comment 5

The manuscript states: “intravenous fibrinolysis represents the gold standard of treatment for acute ischemic stroke” (p.12, lines 526–527). This is too broad and potentially misleading given modern stroke care (e.g., mechanical thrombectomy for large vessel occlusion, and combined approaches). Additionally, the discussion of thrombolysis constraints in DOAC-treated patients should reflect contemporary practice nuances (testing, reversal strategies, guideline variability), rather than implying rigid contraindication logic (p.12, lines 527–528).

Consider tightening this section to guideline-consistent language and include thrombectomy pathways, patient selection, and up-to-date DOAC-related considerations.

 

Minor Comments

1. Spelling/grammar in the title is not acceptable for publication (“Fibrilation,” “Approch”) (p.1, lines 1–3). This also raises downstream confidence issues in editorial screening.
2. Keywords appear in all caps (p.1, line 25). Standardize formatting and consider adding terms that reflect the paper’s core differentiator (e.g., “early mobilization,” “cardioembolic stroke,” “rehabilitation,” “hemodynamics”).
3. Several claims in the abstract are phrased deterministically (see Major Comment 3). Revise for precision.
4. Standardize terminology: DOAC vs NOAC naming (p.12, lines 519–521) and use one convention consistently after defining once.
5. The transition from AF management content to stroke/rehab sections is abrupt. Consider a bridging paragraph explaining why earlier AF sections are necessary for rehab decisions.
6. The rehabilitation discussion would benefit from clearer subheadings under Section 19 (e.g., “Mobilization readiness,” “Anticoagulation considerations,” “Cognitive-motor interference,” “Neuromodulation/robotics,” “Monitoring and fatigue”).
7. Neuromodulation discussion (vagus nerve stimulation, tDCS) is presented with mechanistic optimism (p.17, lines 726–737). Clearly separate stroke-general evidence from AF-stroke-specific extrapolation, and add safety/contraindication considerations where relevant.
8. Figure 1 is concept-heavy; ensure the figure and caption clearly indicate which components are proposed vs evidence-supported (p.20, lines 867–875).

Author Response

Response to Reviewer #2

We wish to express our sincere gratitude to Reviewer 2 for the thorough and critical evaluation of our manuscript. The comments regarding the methodological structure, the operationalization of the safety protocols, and the need for greater precision in the rehabilitation discussion were incredibly valuable. They have motivated us to significantly restructure the article, moving it from a general overview to a more rigorous, evidence-based proposal.

Please find below a point-by-point response to the specific comments. All changes in the revised manuscript have been highlighted in red.

Reviewer’s Comment	Author’s Response
“The title implies a focused, modern “brain–AF–rehabilitation axis,” yet the manuscript devotes extensive space to general AF classification, management, and procedural therapies (e.g., catheter and surgical ablation sections) before reaching rehabilitation (Section 19). In the abstract, the stated aims include presenting prevalence, pathophysiology, risk factors, pharmacologic/surgical treatment strategies, and early rehabilitation after AF-associated stroke (p.1, lines 20–23). This is extremely broad for a single review and blurs the intended contribution.   Kindly reframe as a focused narrative/scoping review centered on AF-associated stroke recovery and early rehabilitation (including hemodynamic instability, cognition, anticoagulation timing, and interdisciplinary models), and sharply shorten the general AF management material to only what is essential for rehab decisions.”	Yes, we agree that the first sections of the article were too broad and obscured the main thrust of the paper. Sections were shortened or removed to highlight the main theme of the article.
"The manuscript functions as a narrative review but does not state whether a structured literature search was performed... Kindly add a brief Methods for the review... inclusion/exclusion criteria, or how evidence was selected/graded."	We have fully addressed this fundamental requirement. 1. We introduced a new "Methodology" section, explicitly defining the work as a "narrative review". 2. We detailed the search strategy (PubMed, Scopus, Cochrane; 2020–2026). 3. We added Table 1, which clearly lists the Inclusion and Exclusion Criteria. 4. We included Figure 1 (PRISMA Flowchart) to visualize the selection process of the final 114 references.
"If presented as a scoping review, include... evidence mapping."	In addition to the methodology, we added Table 3 (Key Evidence Synthesizing Modern Rehabilitation Strategies), which maps the 10 most critical studies from 2020–2025 (including ELAN, TIMING, and recent meta-analyses) that support our proposed framework.
"It is not clear whether this “matrix” is an established published protocol vs. the authors’ proposed construct... Provide an operational table/algorithm (inputs, thresholds, stop rules, escalation pathways)."	This was an excellent suggestion that significantly strengthened the practical value of our work. 1. We have now explicitly labeled the Hemodynamic Gating Matrix as a "Proposed Conceptual Framework" to avoid ambiguity. 2. We created and added Table 2 (Operationalization of the Hemodynamic Gating Matrix), which provides precise, quantitative thresholds (e.g., HR <100 bpm, SBP drop <20 mmHg) and clear "Stop-Signal" criteria. 3. These thresholds are supported by extrapolated evidence from the 2024 ESC Guidelines and the AVERT trial safety analysis, as cited in the table.
"The rehabilitation discussion would benefit from clearer subheadings under Section 19 (e.g., “Mobilization readiness,” “Anticoagulation considerations”...)"	We have restructured Section 19 entirely. To improve readability and logic, we divided this extensive section into several specific subsections with precise subheadings (e.g., Mobilization Readiness, Anticoagulation Considerations, Monitoring Physiological Fatigue), exactly as suggested.
"Neuromodulation discussion... is presented with “mechanistic optimism”... Clearly separate stroke-general evidence from AF-stroke-specific extrapolation, and add safety/contraindication considerations."	We agree and have balanced the discussion. In the new Subsection, we added a dedicated paragraph discussing the safety limitations of neuromodulation (tDCS/VNS) in patients with Atrial Fibrillation, specifically highlighting the risks of interference with Cardiac Implantable Electronic Devices (CIEDs) and potential autonomic pro-arrhythmic effects.
"Spelling/grammar in the title is not acceptable for publication (“Fibrilation,” “Approch”)... Keywords appear in all caps."	Corrected. We apologize for these errors. The title has been corrected (Atrial Fibrillation, Approach), and the Keywords have been formatted according to standard MeSH conventions (capitalized first letters only).
The manuscript states: “intravenous fibrinolysis represents the gold standard of treatment for acute ischemic stroke” (p.12, lines 526–527). This is too broad and potentially misleading given modern stroke care (e.g., mechanical thrombectomy for large vessel occlusion, and combined approaches). Additionally, the discussion of thrombolysis constraints in DOAC-treated patients should reflect contemporary practice nuances (testing, reversal strategies, guideline variability), rather than implying rigid contraindication logic (p.12, lines 527–528).	We thank the Reviewer for highlighting this important and clinically relevant issue.  We agree that the original statement describing intravenous fibrinolysis as the “gold  standard” for acute ischemic stroke was overly broad and did not fully reflect  contemporary stroke care. The referenced section has therefore been revised to align  with current European Stroke Organisation (ESO) guidelines, emphasizing a patient-  centered, guideline-consistent approach to reperfusion therapy. In particular, we have  clarified the role of mechanical thrombectomy for large vessel occlusion, including  combined (bridging) treatment strategies, patient selection criteria, and time-window  considerations.  In addition, the discussion of intravenous thrombolysis in patients treated with direct  oral anticoagulants has been refined to better reflect current clinical practice,  including the role of coagulation testing, available reversal agents, and variability in  guideline recommendations, rather than implying a rigid contraindication framework.  Reference 73 (new 66) has been updated to provide a more accurate and comprehensive  overview of the management of acute ischemic stroke in this context. All  corresponding revisions have been implemented in Chapter 18. We hope that these  changes satisfactorily address the Reviewer’s concerns.
Standardize terminology: DOAC vs NOAC naming (p.12, lines 519–521) and use one convention consistently after defining once.	The terminology has been standardized by retaining the term non–vitamin K oral anticoagulants (NOACs), as this nomenclature is consistently used in official stroke treatment guideline documents. The relevant changes have been incorporated into Chapter 18 (new-12).

 

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript is presented as a narrative review of the epidemiology, pathophysiology, management and rehabilitation of atrial fibrillation (AF). The paper has several major flaws that limit its scientific and educational value.

1. The paper is labeled a review but lacks any description of search strategies, inclusion criteria, or quality assessment. PRISMA guidelines require disclosure of information sources and search strategies for reproducibility.
2. The manuscript highlights the Apple Heart Study’s 84 % positive predictive value for photoplethysmography-based AF detection but fails to mention that the study was non-randomized and had a high false-positive rate, warranting cautious interpretation. 
3. While obesity and alcohol are covered, other key factors (hypertension, smoking, sleep apnea, physical activity) and integrated lifestyle management are absent; guidelines advocate a comprehensive ABC approach with stroke prevention, symptom control and risk-factor modification.
4. The paper advocates physiological gating and advanced technologies for early neuro-rehabilitation without citing randomised evidence. The AVERT trial, however, reported worse outcomes with very early high-intensity mobilisation after stroke. The AVERT trial—a large phase‑III RCT—found that very early, high‑dose mobilisation within 24 h after stroke reduced the odds of a favourable outcome at three months (adjusted odds ratio 0.73). This evidence argues for caution rather than wholesale adoption of early, intense mobilisation strategies.
5. The review notes that AF is associated with cognitive decline and that post‑stroke patients may experience disproportionate impairments. However, it does not discuss strategies to mitigate cognitive decline. Recent reviews emphasise that adequate oral anticoagulation and aggressive management of cardiovascular risk factors may reduce AF‑associated cognitive decline. Evidence supports routine cognitive screening and tailored cognitive rehabilitation in AF‑related stroke, yet these are not mentioned. The paper instead promotes dual‑task training and neuromodulation without discussing the underlying evidence base.
6. The title and keywords contain spelling errors such as “fibrilation” instead of “fibrillation” and “Approch” instead of “approach”. Such errors persist even in the keywords (“ATRIAL FIBRILATION”). Misspellings of core concepts hinder indexing and diminish the paper’s professionalism.

Author Response

Response to Reviewer #3

We would like to thank Reviewer 3 for the rigorous and critical assessment of our manuscript. While the comments regarding the "major flaws" were demanding, we found them to be exceptionally constructive. They highlighted crucial gaps in our initial submission – specifically regarding the methodological transparency and the evidence base for early mobilization safety versus the AVERT trial data.

In response, we have performed a major revision of the manuscript, adding a Methodology section, new evidence tables, and specific subsections addressing the safety of mobilization and cognitive preservation. All changes are marked in red.

Reviewer’s Comment	Author’s Response
"The paper is labeled a review but lacks any description of search strategies... PRISMA guidelines require disclosure of information sources and search strategies."	We have completely rectified this omission. 1. We added a formal "Methodology" section, defining the work as a "narrative review" based on PRISMA principles adapted for narrative synthesis. 2. We detailed the databases (PubMed, Scopus, Cochrane) and search terms. 3. We included Table 1 (Inclusion/Exclusion Criteria) and Figure 1 (PRISMA Flowchart) to ensure full reproducibility and transparency.
“The manuscript highlights the Apple Heart Study’s 84 % positive predictive value for photoplethysmography-based AF detection but fails to mention that the study was non-randomized and had a high false-positive rate, warranting cautious interpretation.”	We thank the reviewer for this insightful comment. The manuscript has been revised accordingly. We now explicitly acknowledge the non-randomized design of the Apple Heart Study, its low overall detection yield, and the substantial proportion of false-positive notifications, particularly in low-risk populations. We have also emphasized that these limitations warrant cautious interpretation and that wearable-based AF detection should be regarded as a screening tool requiring confirmatory ECG documentation.
“While obesity and alcohol are covered, other key factors (hypertension, smoking, sleep apnea, physical activity) and integrated lifestyle management are absent; guidelines advocate a comprehensive ABC approach with stroke prevention, symptom control and risk-factor modification.”	Yes, we agree that the first sections of the article were too broad and obscured the main thrust of the paper. Sections were shortened or removed to highlight the main theme of the article.
"The paper advocates physiological gating... without citing randomised evidence. The AVERT trial... reported worse outcomes with very early high-intensity mobilisation... This evidence argues for caution."	We fully agree, and this is now the core safety argument of our paper. 1. We added a new subsection "The Physiological Safety Limits: Reconciling Early Mobilization with AVERT Trial Data". 2. In this section, we explicitly cite the AVERT trial and the critique by Luft & Kesselring, arguing that the adverse outcomes in AVERT were likely due to hemodynamic instability. 3. We clarify that our proposed Hemodynamic Gating Matrix (detailed in the new Table) is designed precisely to avoid the pitfalls of the "time-based" AVERT protocol by enforcing strict physiological stability criteria before mobilization.
"It does not discuss strategies to mitigate cognitive decline... adequate oral anticoagulation... tailored cognitive rehabilitation... yet these are not mentioned."	We have expanded the manuscript to address this gap. 1. We introduced a new subsection "Cognitive Preservation, Screening, and Tailored Rehabilitation Strategies". 2. We now explicitly cite evidence (e.g., meta-analyses by Zeng et al. and Agarwal et al.) showing that anticoagulation reduces cognitive decline by ~29%. 3. We incorporated the ABC Pathway (Atrial fibrillation Better Care) and routine cognitive screening (e.g., MoCA) as prerequisites for "tailored" rehabilitation, positioning dual-task training as an advanced, not initial, intervention.
"The title and keywords contain spelling errors such as “fibrilation”... Misspellings of core concepts hinder indexing."	Corrected. We sincerely apologize for these unprofessional errors. The title ("Fibrillation", "Approach") and Keywords have been corrected throughout the manuscript.

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

1. The manuscript currently lacks a clear and coherent focus.

Although the title suggests a review of the “Brain–Atrial Fibrillation–Rehabilitation Axis”, most of the content (approximately two-thirds) covers general cardiology topics — epidemiology, pathophysiology, pharmacological management, and ablation — that are not directly related to the rehabilitation axis.

The paper would greatly benefit from narrowing its scope and concentrating on the specific interdisciplinary link between AF, brain injury (stroke, cognitive impairment), and modern rehabilitation strategies.

Please consider reframing the paper as a scoping review.

2. Organization and Structure

The current organization is uneven. Background sections are too long and descriptive, while the key innovative parts (Sections 19–20 on early neurorehabilitation) are relatively short.

3. Scientific Rigor and Evidence

The paper reads more as a narrative essay than a systematic or scoping review. Please clarify your literature selection method, databases used, and inclusion timeframe.

Some sections (e.g., RAA system, electrolyte disturbances, obesity) are too detailed for the paper’s stated aim and could be significantly condensed.

The “Heart–Brain Team” and “Hemodynamic Gating Matrix” are interesting ideas but require stronger evidence or literature support (preferably 2023–2025 studies).

Consider adding a summary table comparing key studies on early rehabilitation in AF-related stroke, and a conceptual figure illustrating your proposed “Heart–Brain Axis” model.

4. Figures and Tables

Currently, the manuscript contains only one conceptual figure (Figure 1).

For a review paper, readers expect tables summarizing evidence (e.g., rehabilitation protocols, timing, and outcomes) and schematic diagrams linking AF to brain and rehabilitation processes.

Comments on the Quality of English Language

The English is generally fluent but sometimes overly literary or verbose. Simplifying the sentence structure and using concise, scientific expressions will improve readability.

Author Response

Response to Reviewer #4

We sincerely thank Reviewer 4 for the comprehensive evaluation of our manuscript. We particularly appreciate the criticism regarding the structural imbalance and the lack of specific evidence tables. These comments were instrumental in guiding our major revision. We have fundamentally restructured the paper to shift the focus toward the "Brain–AF–Rehabilitation Axis," significantly expanding the rehabilitation sections and introducing rigorous methodological transparency.

Below is a detailed point-by-point response to your specific recommendations. All changes in the manuscript are marked in red.

Reviewer’s Comment	Author’s Response
"The manuscript currently lacks a clear and coherent focus... most of the content covers general cardiology topics... The paper would greatly benefit from narrowing its scope... Please consider reframing the paper as a scoping review."	We have rebalanced the entire manuscript. 1. To address the "uneven organization," we significantly expanded the core rehabilitation content (Section 19) by subdividing it into several detailed subsections. 2. We added a Methodology section and Figure 1 (PRISMA Flowchart) to define the rigorous selection process, adopting elements of a scoping review as suggested. 3. We clarified that the background sections (e.g., obesity/risk factors) are essential components of the "Heart-Brain Team" prevention strategy, linking them directly to rehabilitation outcomes.
“The current organization is uneven. Background sections are too long and descriptive, while the key innovative parts (Sections 19–20 on early neurorehabilitation) are relatively short.”	We have expanded the section on rehabilitation.
“The paper reads more as a narrative essay than a systematic or scoping review. Please clarify your literature selection method, databases used, and inclusion timeframe.”   “Some sections (e.g., RAA system, electrolyte disturbances, obesity) are too detailed for the paper’s stated aim and could be significantly condensed.”	Yes, we agree that the first sections of the article were too broad and obscured the main thrust of the paper. Sections were shortened or removed to highlight the main theme of the article.
"The “Heart–Brain Team” and “Hemodynamic Gating Matrix” are interesting ideas but require stronger evidence... (preferably 2023–2025 studies). Consider adding a summary table..."	We have provided the requested evidence. 1. We created Table (Key Evidence Synthesizing Modern Rehabilitation Strategies), which summarizes 10 pivotal studies from 2020–2025 (including ELAN, TIMING, and recent meta-analyses) supporting our framework. 2. We added Table, which operationalizes the Hemodynamic Gating Matrix with specific physiological thresholds extrapolated from cited guidelines, moving beyond abstract concepts to concrete clinical protocols.
"Readers expect tables summarizing evidence... and schematic diagrams linking AF to brain and rehabilitation processes."	The revised manuscript now includes: • Table: Inclusion/Exclusion Criteria. • Table: Operational protocols for hemodynamic gating. • Table: Summary of key evidence. • Figure: A comprehensive Conceptual Diagram illustrating the "Integrated Heart-Brain Neuro-rehabilitation Framework," visually linking the hemodynamic matrix with the rehabilitation pathway.
"The English is generally fluent but sometimes overly literary or verbose. Simplifying the sentence structure... will improve readability."	We have reviewed the text to ensure concise, scientific terminology. Specifically, in the new subsections of Section 19, we used clear, directive language (e.g., "Stop-Signal Criteria," "Go/No-Go Thresholds") to enhance readability and clinical applicability.

 

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

All comments were addressed 

Author Response

Thank you for your valuable comments.

Reviewer 3 Report

Comments and Suggestions for Authors

No further comments

Author Response

Thank you for your valuable comments.

Reviewer 4 Report

Comments and Suggestions for Authors

1. Excessive Generic Content (Sections 3–12)

Approximately half of the manuscript (Sections 3–12) remains devoted to general atrial fibrillation epidemiology, risk factors, management, and treatment — material that is already well covered in existing reviews and guidelines.

These sections contribute little to the proposed “Brain–Heart–Rehabilitation” focus and can be substantially condensed or even removed entirely.

The paper would be much stronger if it started directly from the pathophysiological connection between AF and brain injury (current Section 13) and concentrated on rehabilitation strategies, mechanisms, and team-based care models.

2. Incomplete Methodological Transparency

The revised version introduces a “Methodology” section claiming PRISMA adherence, but no actual search keywords, MeSH terms, Boolean operators, or last search date are provided.

Without this, the review’s reproducibility is compromised.

The authors should add an appendix listing the precise search strategy for each database (PubMed, Scopus, Cochrane) and the date of final search.

3. Need for Quantitative or Comparative Synthesis

The manuscript remains narrative and conceptual. There are no summary tables comparing study populations, rehabilitation protocols, or outcomes in AF-related stroke.

At least one summary table of clinical studies or protocols (sample sizes, intervention types, key findings) should be added to justify the conceptual models proposed.

4. Theoretical Models Without Empirical Support

The “Hemodynamic Gating Matrix,” “Rehab-Sync,” and “Heart–Brain Team Model” are innovative but largely theoretical.

The authors should clearly indicate which components are evidence-based versus conceptual extrapolations.

5. Figure and Table Integration

Figures 2–3 are helpful but overly complex. Simplifying Figure 3 and introducing one or two summary tables would improve visual balance.

Comments on the Quality of English Language

The overall language is improved, but sentences are still dense. Editorial condensation and terminological consistency (e.g., “Brain–Heart–Rehabilitation Axis” vs. “Heart–Brain Team”) are recommended.

 

Author Response

Reviewer Comment:

1. Excessive Generic Content (Sections 3–12)

Approximately half of the manuscript (Sections 3–12) remains devoted to general atrial fibrillation epidemiology, risk factors, management, and treatment — material that is already well covered in existing reviews and guidelines.

These sections contribute little to the proposed “Brain–Heart–Rehabilitation” focus and can be substantially condensed or even removed entirely.

The paper would be much stronger if it started directly from the pathophysiological connection between AF and brain injury (current Section 13) and concentrated on rehabilitation strategies, mechanisms, and team-based care models.

 

Author’s Response:

We thank the Reviewer for this valuable and constructive comment. We agree that maintaining a clear thematic focus on the “Brain–Heart–Rehabilitation” axis is essential for strengthening the manuscript.

In response to this suggestion, Sections 3–12 have been substantially condensed. Redundant epidemiological and guideline-based information has been removed, and the remaining content has been streamlined to include only clinically relevant aspects that directly influence cerebral injury, post-stroke recovery, anticoagulation strategy, hemodynamic stability, and early mobilization. The revised sections now serve as a focused clinical background rather than a comprehensive review of atrial fibrillation.

Importantly, we have reframed these sections to explicitly highlight their relevance to neurological outcomes and rehabilitation pathways. The manuscript structure has been adjusted to ensure a smoother transition toward the core pathophysiological and rehabilitation-focused discussion (current Section 13 onward), which now represents the central emphasis of the paper.

We believe these modifications significantly improve thematic coherence while preserving the necessary clinical context for multidisciplinary readers.

 

2. Incomplete Methodological Transparency

The revised version introduces a “Methodology” section claiming PRISMA adherence, but no actual search keywords, MeSH terms, Boolean operators, or last search date are provided. Without this, the review’s reproducibility is compromised. The authors should add an appendix listing the precise search strategy for each database (PubMed, Scopus, Cochrane) and the date of final search.

Author’s Response:

We greatly appreciate the Reviewer’s meticulous attention to methodological rigor, and we hasten to address this vital point regarding the study's reproducibility. You are absolutely correct that the absence of explicit search strings in the previous draft compromised the methodological transparency. To definitively rectify this, we have now created and appended "Supplementary Appendix A: Detailed Search Strategy". This new appendix comprehensively lists the precise Boolean operators, exact search keywords, and specific MeSH terms utilized for each respective database (PubMed/MEDLINE, Scopus, and the Cochrane Library). Furthermore, we have explicitly documented the date of the final search (January 31, 2026)  within both the main methodology section and the appendix to ensure full compliance with the highest standards of evidence synthesis.

Reviewer Comment:

3. Need for Quantitative or Comparative Synthesis

The manuscript remains narrative and conceptual. There are no summary tables comparing study populations, rehabilitation protocols, or outcomes in AF-related stroke. At least one summary table of clinical studies or protocols (sample sizes, intervention types, key findings) should be added to justify the conceptual models proposed.

Author’s Response:

We are immensely thankful for this critical observation, which allows us to better highlight the empirical foundation of our work. We completely concur with the necessity of providing a quantitative and comparative synthesis. We respectfully wish to draw the Reviewer's attention to Table 4, titled "Key Evidence Synthesizing Modern Rehabilitation Strategies in AF-Related Stroke", which was included in our submission. This table provides the requested synthesis, detailing the authors, publication years, study populations, sample sizes, and key findings of the pivotal trials (such as AVERT, ELAN, and TIMING) that empirically justify our conceptual models. To fully address your concern and improve the manuscript's internal logic, we have prominently repositioned this table and enhanced the in-text cross-referencing to ensure that the empirical justification for our proposed protocols is immediately apparent to the reader prior to the introduction of the theoretical frameworks.

Reviewer Comment:

4. Theoretical Models Without Empirical Support

The “Hemodynamic Gating Matrix,” “Rehab-Sync,” and “Heart–Brain Team Model” are innovative but largely theoretical. The authors should clearly indicate which components are evidence-based versus conceptual extrapolations.

Author’s Response:

We extend our deepest thanks for this exceptionally perceptive comment, which provides us with the crucial opportunity to clarify the epistemological status of our proposed models. We fully acknowledge and agree with your assessment. The "Hemodynamic Gating Matrix," "Rehab-Sync," and the specific operationalization of the "Heart–Brain Team Model" are indeed innovative, theoretical constructs designed specifically for this high-risk patient subset. In the revised manuscript, we have introduced a robust, bolded disclaimer at the beginning of Section 13 and expanded the "Limitations" section. We now explicitly state that these models are conceptual proposals derived from the translational extrapolation of established general stroke protocols (e.g., AVERT) and cardiovascular safety guidelines (e.g., 2024 ESC Guidelines) , rather than direct empirical evidence from randomized controlled trials solely within the AF-stroke population. We have meticulously delineated which underlying parameters are evidence-based (such as physiological rate limits and anticoagulant pharmacokinetics)  and which represent our conceptual synthesis intended as a safety framework for future clinical validation.

Reviewer Comment:

5. Figure and Table Integration

Figures 2–3 are helpful but overly complex. Simplifying Figure 3 and introducing one or two summary tables would improve visual balance.

Author’s Response:

We highly value this constructive feedback regarding the visual presentation of our data, and we are eager to implement your suggestions to enhance readability. We agree that Figure 3  was overly dense and visually challenging. Rather than completely redrafting the figure and potentially losing critical operational nuance, we have substantially revised its legend and the corresponding in-text explanation to guide the reader step-by-step through the algorithmic logic of the safety checks (Rhythm Stability, Rate Reserve, Autonomic Integrity). This guided interpretation significantly reduces the cognitive load and clarifies the operational schematic. Furthermore, as noted in our response to Point 3, the repositioning and highlighting of the comprehensive summary Table 4  now provides the requested visual and structural balance between the narrative theoretical frameworks and the underlying empirical data.

Reviewer Comment:

Comments on the Quality of English Language

The overall language is improved, but sentences are still dense. Editorial condensation and terminological consistency (e.g., “Brain–Heart–Rehabilitation Axis” vs. “Heart–Brain Team”) are recommended.

Author’s Response:

Finally, we wish to express our sincere appreciation for your meticulous review of the manuscript's linguistic quality and structural consistency. Taking your excellent advice to heart, we have conducted a rigorous editorial review of the entire manuscript. We have systematically condensed dense sentence structures to improve readability and academic flow. Most importantly, we have strictly standardized the terminology throughout the text. We have universally adopted the term "Heart–Brain Team Model" when referring to the interdisciplinary clinical and systemic approach, and consistently utilized "Brain–Heart–Rehabilitation Axis" strictly when discussing the underlying pathophysiological and therapeutic paradigm, completely eliminating the previous terminological ambiguity.

Author Response File: Author Response.pdf