The Value of HALP Score in Predicting Adverse In-Hospital Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThank you for the opportunity to review this manuscript. It focuses on whether HALP score can predict TAVR patients’ adverse outcomes while in hosp.
Great read and great work, important for physicians. I am recommending a major rev based on the following comments:
Abstract: modify the duration to include date and month.
Intro: add some evidence/data on post TAVR outcomes. I know you stated that these have improved, but quantifying for the reader might be great Good job setting the stage wrt risk stratification and gaps in it. I wanted to ask a clarifying question about this part: “Given the high inflammatory and nutritional burden among TAVR candidates” -given that HALP is calculated with HAL in the numerator and P in denominator, a low HALP score would indicate lower Hb and Albumin (as you note = hypoalbuminemia and anemia), i would just clarify lymphopenia in TAVR patients.
Methods: Add exact dates here if possible: April 2021 and October 2024, 140 patients I would add a definition for this “successful TAVR procedure” since an unsuccessful procedure could also be thought of as in-hospital mortality (altho I think you are indicating that procedural mortality is excluded and mortality after that would be counted as an outcome), add some clarity For IRB approval, was this an exemption? Since patients may not have provided consent at that stage? Or was it an approval with consent procedures. Were these the only comorbids identified? hypertension, diabetes mellitus, coronary artery disease, atrial fibrillation) Does that create a bias esp since some of the markers may have differences with other important comorbids (both cardiovascular and otherwise) What was the justification for bifurcating at the median vs using a validated cutoff for a similar condition, if any? See how determination of best cutoff val was made in a similar study on stemi PCI : https://pmc.ncbi.nlm.nih.gov/articles/PMC12043261/
Definitions of endpoints and statistical analyses are clear and detailed.
Results: Interesting to see that when comparing the two groups, in terms of ratios, Hb and Alb ratio between high HALP:low HALP are less than the same for lymp and PLT (reversed for PLT). i wonder if PLT lymp are contributing more to the difference in HALP scores between the two groups. Can you specify if all of the variables listed in table 3 were used in the MVR. i ask because earlier it was noted that cutoff was 10% and some variables from a clinical standpoint were also adjusted for. So wanted to confirm exactly which variables MVR adjusted for. Sorry if this was stated somewhere and i missed it. Would it help to have a figure/graph for ROC, might be a good addition given limited figures in this paper.
Discussion and conclusion look good. There is some redundancy between the last two lines of limitations and the last line of the conclusion.
Great work and good luck!
Author Response
Comments 1: Abstract: modify the duration to include date and month.
Response 1: Thank you for pointing this out. We agree with this comment, and the study period in the Abstract has been revised accordingly to include both the month and year (April 1, 2021 and October 31, 2024). The change can be found in the Abstract section (page 1, lines 13).
Comments 2: Intro: add some evidence/data on post TAVR outcomes. I know you stated that these have improved, but quantifying for the reader might be great Good job setting the stage wrt risk stratification and gaps in it. I wanted to ask a clarifying question about this part: “Given the high inflammatory and nutritional burden among TAVR candidates” -given that HALP is calculated with HAL in the numerator and P in denominator, a low HALP score would indicate lower Hb and Albumin (as you note = hypoalbuminemia and anemia), i would just clarify lymphopenia in TAVR patients.
Response 2: Thank you for this insightful comment. We agree that providing quantitative data on contemporary post-TAVR outcomes would strengthen the background and better contextualize the clinical relevance of early risk stratification. Accordingly, we revised the Introduction to include data from contemporary registries and studies reporting in-hospital or 30-day mortality rates generally below 3–5%, along with reductions in major procedural complications and shorter length of hospital stay compared with earlier TAVR eras.
In addition, we clarified the statement regarding the “high inflammatory and nutritional burden among TAVR candidates.” Specifically, we expanded this section to explicitly address lymphopenia, which is frequently observed in this population and reflects chronic systemic inflammation, immunosenescence, and immune dysregulation. We explained that lymphopenia, together with anemia and hypoalbuminemia, contributes biologically to a lower HALP score and supports its relevance as an integrated inflammatory–nutritional marker in patients undergoing TAVR.
These revisions were made to improve clarity and biological rationale. The corresponding changes can be found in the Introduction section (page 1 and 2, lines 39-44, 55-58, 66-71).
Comments 3: Methods: Add exact dates here if possible: April 2021 and October 2024, 140 patients I would add a definition for this “successful TAVR procedure” since an unsuccessful procedure could also be thought of as in-hospital mortality (altho I think you are indicating that procedural mortality is excluded and mortality after that would be counted as an outcome), add some clarity For IRB approval, was this an exemption? Since patients may not have provided consent at that stage? Or was it an approval with consent procedures. Were these the only comorbids identified? hypertension, diabetes mellitus, coronary artery disease, atrial fibrillation) Does that create a bias esp since some of the markers may have differences with other important comorbids (both cardiovascular and otherwise) What was the justification for bifurcating at the median vs using a validated cutoff for a similar condition, if any? See how determination of best cutoff val was made in a similar study on stemi PCI : https://pmc.ncbi.nlm.nih.gov/articles/PMC12043261/
Definitions of endpoints and statistical analyses are clear and detailed.
Response 3: Thank you for this detailed and constructive comment. We have addressed each point as follows.
First, the exact study period has been specified using day–month–year format. The Methods section now clearly states that patients were retrospectively enrolled between April 1, 2021, and October 31, 2024, with a total of 140 patients included.
Second, to avoid any ambiguity regarding patient inclusion and outcome definitions, we removed the term “successful TAVR procedure” from the Methods section. Inclusion criteria are now neutrally defined as all patients aged 18 years or older who underwent transcatheter aortic valve replacement during the study period. In-hospital mortality is explicitly defined in the Endpoints section as all-cause death occurring during the procedure or at any time before hospital discharge, ensuring comprehensive capture of both procedural and post-procedural mortality.
Regarding ethical approval, the study protocol was approved by the local ethics committee, and the requirement for informed consent was waived due to the retrospective design of the study. The ethics committee approval document was submitted to the journal during the manuscript submission process.
With respect to comorbidities, the listed conditions represent the most prevalent cardiovascular comorbidities routinely and systematically recorded in our institutional database. Other potentially relevant cardiovascular and non-cardiovascular comorbidities were not uniformly available and therefore could not be included in the analysis. This limitation and the possibility of residual confounding have now been explicitly acknowledged in the Limitations section.
Finally, because no validated HALP cut-off value has been established for patients undergoing TAVR, patients were stratified according to the median HALP value, a commonly used approach in exploratory prognostic studies. In addition, outcome-specific optimal cut-off values were determined using receiver operating characteristic (ROC) curve analysis and the Youden index, as described in the Statistical Analysis section.
The corresponding revisions can be found in the Methods and Limitations sections (page 2,3 and 10, lines 86-91 and 305-309).
Comments 4: Results: Interesting to see that when comparing the two groups, in terms of ratios, Hb and Alb ratio between high HALP:low HALP are less than the same for lymp and PLT (reversed for PLT). i wonder if PLT lymp are contributing more to the difference in HALP scores between the two groups. Can you specify if all of the variables listed in table 3 were used in the MVR. i ask because earlier it was noted that cutoff was 10% and some variables from a clinical standpoint were also adjusted for. So wanted to confirm exactly which variables MVR adjusted for. Sorry if this was stated somewhere and i missed it. Would it help to have a figure/graph for ROC, might be a good addition given limited figures in this paper.
Response 4: We thank the reviewer for this thoughtful observation. As correctly noted, although hemoglobin and albumin are major components of the HALP score, the relative differences between groups were more pronounced for lymphocyte and platelet counts. This pattern may suggest that inflammatory and thromboinflammatory pathways contribute substantially to the separation of HALP scores in our cohort. We have clarified this point in the Discussion section to reflect that this is a hypothesis-generating, data-driven interpretation rather than a definitive mechanistic conclusion (Discussion, page 9, lines 260–264).
Regarding the multivariable regression analyses, we have clarified the variable selection strategy in the Methods section. Variables included in the multivariable models were selected a priori based on clinical relevance, and all covariates listed in Table 3 were entered simultaneously into the multivariable models. (Methods, Statistical Analysis, page 4, lines 143–149).
In addition, in line with the reviewer’s suggestion, we have added a new figure presenting the receiver operating characteristic (ROC) curves of the HALP score for the major in-hospital adverse outcomes (Figure 2). This figure visually complements the AUC values and optimal cut-off points reported in Table 4 and facilitates interpretation of the discriminatory performance of the HALP score (Results, page 7, lines 199–200).
Comments 5: Discussion and conclusion look good. There is some redundancy between the last two lines of limitations and the last line of the conclusion.
Response 5: We thank the reviewer for this helpful comment. We agree that there was some redundancy between the Limitations and Conclusions sections. To address this, we revised the Conclusions by removing repetitive statements regarding study limitations and future research, while retaining a concise and clinically focused closing statement (Conclusions, page 10, lines 306-310).
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsThe Editor, Diagnostics, Dec 31, 2025 The Value of HALP Score in Predicting Adverse In-Hospital Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement by Ömer Faruk Çiçek; Mustafa Çetin and Ali Palice 1.Abstract, background.Edit: The HALP (hemoglobin, albumin, lymphocyte, and platelet) score is an easily obtainable composite index that reflects nutritional status and systemic inflammation. 2. Introduction. Write background, recent advances, relevance and novelty of your study, gaps in the knowledge, your hypothesis and finally objective. 3.Subjects and Methods is better than methods alone. Recruitment of patients Sample size Inclusion criteria Exclusion criteria, write number of subjects in bracket for each category (n= ?) Clinical characteristics of patients Criteria of diagnosis Collection of data Co-Morbidities Mortality Statistical analysis 4.Results. Write how many total patients excluded. Out of how many total considered for evaluation. Do not use abbreviations as far as possible in the tables. Give a figure for most important findings 5.Discussion Write the most important finding first followed by discussion of other similar studies. Did any body get GDMT based on Four Pillars of HF after valve replacement. SGLT2 inhibitors, such as dapagliflozin, improve outcomes after Transcatheter Aortic Valve Replacement (TAVR/TAVI) by reducing all-cause mortality and heart failure hospitalizations. These agents are associated with lower risks of bioprosthetic valve failure, improved cardiac remodeling, and, potentially, mitigation of kidney injury in high-risk,, often diabetic, patient populations. Trimaille A, Marchandot B, Morel O. SGLT2 Inhibition After Aortic Valve Replacement: The Role of the Native Valve. JACC Adv. 2025 Oct;4(10 Pt 2):102136. doi: 10.1016/j.jacadv.2025.102136. Epub 2025 Sep 18. PMID: 40972359; 6.References Give a 1-2 references from 2025, 2026
Comments on the Quality of English Languageneed improvement
Author Response
Comments 1: Abstract, background. Edit: The HALP (hemoglobin, albumin, lymphocyte, and platelet) score is an easily obtainable composite index that reflects nutritional status and systemic inflammation.
Response 1: Thank you for pointing this out. We agree with this comment, and the definition of the HALP score in the Abstract has been revised accordingly. The sentence defining the HALP score as a composite index reflecting nutritional status and systemic inflammation has been added to the Background of the Abstract. The change can be found in the Abstract section (page 1, lines 10-11).
Comments 2: Introduction. Write background, recent advances, relevance and novelty of your study, gaps in the knowledge, your hypothesis and finally objective.
Response 2: Thank you for this valuable comment. We agree and have revised the Introduction to clearly present the background, recent advances, knowledge gap, study relevance and novelty, hypothesis, and objective. The final paragraph of the Introduction has been reorganized accordingly, and relevant references have been incorporated to support recent advances in nutritional and inflammatory risk stratification in TAVR. The change can be found in the Introduction section (page 2, lines 73–83).
Comments 3: Subjects and Methods is better than methods alone. Recruitment of patients Sample size Inclusion criteria Exclusion criteria, write number of subjects in bracket for each category (n= ?) Clinical characteristics of patients Criteria of diagnosis Collection of data Co-Morbidities Mortality Statistical analysis
Response 3: Thank you for this helpful comment. We agree and have revised the Materials and Methods section to more clearly emphasize patient recruitment and sample size. The recruitment process and the final number of included patients (n = 140) are now explicitly stated, while the previously described clinical characteristics, diagnostic criteria, data collection procedures, comorbidities, definitions of mortality and in-hospital outcomes, and statistical analysis remain unchanged. The change can be found in the Materials and Methods section (page 2 and 3, lines 84–90).
Comments 4: Results. Write how many total patients excluded. Out of how many total considered for evaluation. Do not use abbreviations as far as possible in the tables. Give a figure for most important findings
Response 4: Thank you for this helpful comment. We agree and have revised the Results section and tables accordingly. The total number of patients assessed for eligibility, excluded, and included in the final analysis is now clearly reported and illustrated with a flow diagram (Figure 1). In addition, Tables 1–4 have been revised to improve clarity and readability by minimizing the use of abbreviations and replacing them with full terms wherever possible. All table footnotes were updated accordingly to ensure consistency. These changes can be found in the Results section, Figure 1, and Tables 1–4 (page 4, lines 157–159).
Comments 5: Discussion Write the most important finding first followed by discussion of other similar studies. Did any body get GDMT based on Four Pillars of HF after valve replacement. SGLT2 inhibitors, such as dapagliflozin, improve outcomes after Transcatheter Aortic Valve Replacement (TAVR/TAVI) by reducing all-cause mortality and heart failure hospitalizations. These agents are associated with lower risks of bioprosthetic valve failure, improved cardiac remodeling, and, potentially, mitigation of kidney injury in high-risk,, often diabetic, patient populations. Trimaille A, Marchandot B, Morel O. SGLT2 Inhibition After Aortic Valve Replacement: The Role of the Native Valve. JACC Adv. 2025 Oct;4(10 Pt 2):102136. doi: 10.1016/j.jacadv.2025.102136. Epub 2025 Sep 18. PMID: 40972359; 6.References Give a 1-2 references from 2025, 2026
Response 5: Thank you for this valuable and insightful comment. We revised the Discussion section to begin with a clear statement of the principal finding of the study, followed by a structured discussion comparing our results with previous studies. We further expanded the Discussion to address recent advances in post–aortic valve replacement management, including guideline-directed medical therapy for heart failure and the emerging role of sodium–glucose cotransporter 2 (SGLT2) inhibitors. We explicitly stated that post-TAVR pharmacological therapies were not evaluated in the present study and discussed their potential implications in the appropriate clinical context. In addition, a recent reference from 2025 was added to reflect contemporary evidence. These revisions can be found in the Discussion section (page 8,10 and 11, lines 217–223 and 278-289) and the updated References list [28].
The manuscript has been thoroughly edited to enhance clarity and improve the overall quality and precision of the English language.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsAre you able to update the ROC graphs to a better quality image - the visual/pixel quality is very blurry. Thank you for adding it. I wanted to have a detailed look at it before sharing a final recommendation/decision. Thank you.
Author Response
Comments 1: Are you able to update the ROC graphs to a better quality image - the visual/pixel quality is very blurry. Thank you for adding it. I wanted to have a detailed look at it before sharing a final recommendation/decision. Thank you.
Response 1: Thank you for this helpful comment. The ROC figure has been fully revised using the journal’s professional English and figure editing service and replaced with a high-resolution, multi-panel version. The updated figure provides improved visual clarity, consistent formatting, and clear delineation of all outcome-specific ROC curves, thereby allowing detailed inspection as requested. We believe that this revision adequately addresses the reviewer’s concern.
Reviewer 2 Report
Comments and Suggestions for AuthorsTry to give these data in the Methods; Patients with acute infections (n= ), hematologic diseases(n= ), end-stage hepatic failure(n= ), or active malignancy(n= ) were excluded from the study
Comments on the Quality of English Languageneed improvement
Author Response
Comments 1: Try to give these data in the Methods; Patients with acute infections (n= ), hematologic diseases(n= ), end-stage hepatic failure(n= ), or active malignancy(n= ) were excluded from the study
Response 1: We thank the reviewer for this suggestion. We have revised the Methods section by adding the number of excluded patients for each predefined exclusion criterion directly to the existing sentence. The updated exclusion counts (acute infection n = 4, hematologic diseases n = 5, end-stage hepatic failure n = 3, active malignancy n = 2) are now clearly reported and are consistent with the study flow diagram.
We appreciate the reviewer’s comment on the quality of the English language. Accordingly, the manuscript has been professionally edited by MDPI’s English language editing service, and the language has been revised by native English-speaking experts to meet the standards of an international scientific journal. The corresponding editing certificate is provided. We trust that the current version adequately addresses this concern.
Round 3
Reviewer 1 Report
Comments and Suggestions for AuthorsNo additional comments. Good luck!
