Diagnostic Value of Fractional Shortening and E-Point Septal Separation in Predicting Left Ventricular Longitudinal Strain in Dyspneic Emergency Patients

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The present study examines EPSS and fractional shortening obtained by point-of-care ultrasound in dyspneic emergency department patients and relates these measurements to biplane ejection fraction and global longitudinal strain. Although the statistical analyses are appropriate, several issues limit both the novelty of the study and the strength of the clinical conclusions.

First, the relationship between EPSS, fractional shortening, and reduced ejection fraction has been well described in prior emergency and POCUS studies. The role of EPSS in identifying overt systolic dysfunction, particularly HFrEF, is already established, and the present results largely confirm these earlier observations. Consequently, the incremental contribution beyond existing EF-based validation is limited and not clearly articulated.

Second, the use of GLS as a reference parameter in the acute emergency setting requires further justification. While GLS is an established marker of myocardial dysfunction in stable clinical contexts, its interpretation in acutely dyspneic patients is less certain. GLS is influenced by loading conditions, heart rate, and image quality, all of which may vary substantially in emergency department patients. The manuscript does not sufficiently address whether acute-phase GLS provides a stable or clinically meaningful benchmark for validating POCUS-derived indices.

Third, the study cohort is predominantly composed of patients with overt systolic dysfunction, with mean EF values in the reduced range and more than half of patients classified as having reduced EF. Under these conditions, the observed correlations between EPSS and GLS are likely driven by advanced global systolic impairment rather than subtle or isolated longitudinal dysfunction. Patients with preserved EF and reduced GLS are not adequately represented, limiting any inference regarding early myocardial dysfunction or HFpEF.

Fourth, EPSS is strongly dependent on left ventricular geometry and ejection fraction. Given this intrinsic dependence, the suggestion that EPSS may function as a surrogate for GLS risks overinterpretation. Without a meaningful subgroup of patients with preserved EF, it remains unclear whether EPSS provides information beyond conventional EF assessment or simply reflects global systolic failure.

Fifth, the clinical implications appear broader than warranted by the data. The findings support the use of EPSS for rapid identification of overt systolic dysfunction in the emergency department, a role that is already recognized in current practice. However, the study does not demonstrate that incorporating GLS adds actionable information for clinical decision-making, risk stratification, or triage in acute dyspneic patients.

Finally, the single-center design, small sample size, and absence of outcome-based analyses further limit generalizability. Without evidence of incremental diagnostic or prognostic value beyond established EF-based assessment, the broader clinical relevance remains uncertain.

In summary, the study confirms that EPSS is a practical bedside marker of reduced ejection fraction in the emergency setting, but the inclusion of GLS does not substantially extend existing knowledge. The conclusions should be revised to reflect that the findings primarily pertain to detection of overt systolic dysfunction (HFrEF), and implications for HFpEF or subclinical myocardial dysfunction should be avoided. A more focused interpretation aligned with the presented data would strengthen the manuscript.

Additionally, this manuscript would be strengthened by an assessment of incremental diagnostic value. As this is an original research article, it remains unclear whether EPSS or fractional shortening provide information beyond established measures rather than reproducing known associations.

Specifically, the authors may consider evaluating whether EPSS adds incremental value over conventional ejection fraction in predicting impaired GLS. This could be addressed using multivariable logistic regression or comparative ROC analyses (e.g., EF alone versus EF combined with EPSS). Even exploratory analyses would help clarify whether EPSS contributes independent diagnostic information or primarily reflects underlying EF.

If such analyses are not feasible due to sample size limitations, this should be explicitly acknowledged. In that case, the conclusions should be framed to emphasize EPSS as a practical and rapid surrogate for reduced EF in the emergency setting, rather than implying incremental diagnostic or pathophysiological insight.

 

 

 

Author Response

All changes made to the manuscript in response to the reviewers’ comments are highlighted in the revised version for ease of review.

Response to Reviewer #1

We sincerely thank the reviewer for the detailed, thoughtful, and constructive comments. We appreciate the opportunity to clarify the scope, novelty, and clinical interpretation of our study. We have carefully revised the manuscript in response to all comments, and our point-by-point responses are provided below.

Comment 1

The relationship between EPSS, fractional shortening, and reduced ejection fraction has already been described in prior emergency and POCUS studies, limiting the novelty of the present work.

Response:

We agree that the association between EPSS, fractional shortening, and reduced ejection fraction has been well established in the emergency and point-of-care ultrasound literature. The primary aim of our study was not to revalidate EPSS against ejection fraction alone, but rather to examine its relationship with global longitudinal strain (GLS), a more sensitive marker of myocardial systolic dysfunction that is not routinely available in emergency settings. To better clarify this incremental contribution, we revised the Introduction and Discussion to explicitly emphasize that the novelty of our study lies in contextualizing simple POCUS-derived indices relative to GLS, rather than extending EF-based validation alone.

Comment 2

The use of GLS as a reference parameter in acutely dyspneic emergency department patients requires further justification, given its dependence on loading conditions and image quality.

Response:

We appreciate this important physiological consideration. We agree that GLS may be influenced by loading conditions, heart rate, and image quality in acutely ill patients. In the revised manuscript, we have clarified that GLS was used as a reference marker of systolic myocardial performance rather than as a clinical decision-making or triage tool in the emergency setting. We have also added a specific discussion of these limitations to the Discussion and Limitations sections, emphasizing that GLS interpretation in acute dyspnea should be approached with caution.

Comment 3

The study cohort predominantly consists of patients with overt systolic dysfunction, limiting conclusions regarding HFpEF or subclinical myocardial dysfunction.

Response:

We agree with this observation. Our study population was largely composed of patients with reduced ejection fraction, and patients with preserved EF and isolated GLS impairment were underrepresented. Accordingly, we revised the Discussion and Conclusions to avoid implications related to HFpEF or early/subclinical myocardial dysfunction. The Conclusions now explicitly state that our findings primarily apply to the identification of overt systolic dysfunction (HFrEF) in dyspneic emergency department patients.

Comment 4

EPSS is strongly dependent on left ventricular geometry and ejection fraction, and suggesting it as a surrogate for GLS may represent an overinterpretation.

Response:

We fully agree. In response to this comment, we removed the term “surrogate” from key sections of the manuscript and replaced it with more appropriate terminology such as “correlate” or “associated parameter.” We also added a dedicated paragraph in the Discussion clarifying that EPSS reflects left ventricular geometry and global systolic impairment, whereas GLS measures myocardial deformation, and that the observed correlation likely reflects concordance in the setting of global systolic failure rather than a direct physiological equivalence.

Comment 5

The clinical implications appear broader than warranted by the data, particularly regarding triage, risk stratification, or clinical decision-making in the emergency setting.

Response:

We agree and have revised the manuscript accordingly. References to triage, risk stratification, or guiding acute management decisions have been removed or substantially softened. The Discussion and Conclusions now emphasize that EPSS serves as a rapid, practical bedside tool for identifying overt systolic dysfunction, which is directly supported by our diagnostic accuracy findings, rather than implying broader clinical or prognostic implications.

Comment 6

The single-center design, small sample size, lack of outcome-based analyses, and absence of incremental diagnostic value beyond ejection fraction limit the generalizability and clinical relevance of the findings.

Response:

We agree with these limitations. The revised manuscript now explicitly acknowledges the single-center design, relatively small sample size, and absence of outcome-based analyses in the Limitations section. With respect to incremental diagnostic value, we considered performing multivariable or comparative ROC analyses to assess whether EPSS provides information beyond conventional ejection fraction. However, given the modest sample size and the strong collinearity between EF, EPSS, and GLS, such analyses would be underpowered and potentially misleading. This limitation is now clearly stated in the manuscript. Accordingly, we have reframed the conclusions to emphasize EPSS as a practical and rapid bedside marker of overt systolic dysfunction rather than suggesting independent or incremental diagnostic insight beyond established EF-based assessment.

 

Finally, we believe that these revisions have resulted in a more focused, balanced, and appropriately framed manuscript, and we sincerely thank the reviewer for the constructive feedback, which has strengthened the overall quality of our work.

Reviewer 2 Report

Comments and Suggestions for Authors

This prospective observational study examines whether simple point-of-care echocardiographic measures (EPSS and fractional shortening) can reliably reflect left ventricular systolic function, using biplane EF and GLS as reference standards, in dyspneic patients presenting to the emergency department. The clinical question is relevant to everyday ED practice, particularly where rapid decision-making is required and advanced imaging may not be immediately available. Overall, the study is clearly presented and methodologically sound, but several aspects of the methodology, figure presentation, and interpretation would benefit from clarification to improve the robustness and clinical relevance of the conclusions.

Major Comments

• Clarification of GLS software and measurement methodology
  The manuscript states that GLS was derived using speckle-tracking echocardiography but does not clearly specify: the vendor-specific softwareused for GLS analysis (e.g., Philips QLAB or equivalent), whether endocardial border detection was automated or manually adjusted, whether inter- or intra-observer variability was assessed. Given that GLS is a central reference standard in this study, these details are essential for reproducibility and interpretation. This should be clarified in the Methods section (Echocardiographic Measurements).
• Exclusion criteria: COPD versus pneumonia
  Patients with clear exacerbation of obstructive lung disease were excluded; however, pneumonia accounted for 12.7% of final diagnoses. The rationale for excluding COPD but not pneumonia requires clarification. The authors should, justify the differential exclusion strategy.
• Interpretation of clinical applicability versus final diagnoses
  In the Discussion, the authors state that EPSS and FS may serve as practical alternatives to advanced imaging in the initial assessment of dyspneic patients. However, only 27% of patients were ultimately diagnosed with decompensated heart failure, while a substantial proportion had ACS, pneumonia, or non-cardiac etiologies. This discrepancy warrants a more nuanced interpretation. The authors should: clarify that EPSS and FS are screening or triage tools, not diagnostic replacements for advanced imaging, and acknowledge that abnormal parameters may reflect subclinical or comorbid LV dysfunction, rather than primary HF as the final diagnosis. Reframing this statement would prevent overgeneralization and better align the conclusions with the study population.

Minor Comments

• Figure 1 would benefit from explicit numeric distance annotations(e.g., measured EPSS in mm, LVIDd/LVIDs values) directly on the image.
• Figure 2 currently illustrates EF calculation but visually emphasizes only one apical view. Since biplane Simpson’s EF requires both apical four-chamber and two-chamber views, the figure should include both views
• The abstract would be strengthened by including: the number of patients included in the study, and mean age of the cohort.

 

Author Response

All changes made to the manuscript in response to the reviewers’ comments are highlighted in the revised version for ease of review.

Response to Reviewer #2

We sincerely thank the reviewer for the thoughtful and constructive comments, which have helped us improve the methodological clarity, figure presentation, and interpretation of the clinical implications of our study. We have carefully addressed each point raised, and our point-by-point responses are provided below.

Major Comment 1: Clarification of GLS software and measurement methodology

Comment:

The manuscript does not clearly specify the vendor-specific software used for GLS analysis, the method of endocardial border detection, or whether inter- or intra-observer variability was assessed.

Response:

We thank the reviewer for highlighting this important methodological issue. We agree that detailed description of GLS acquisition and analysis is essential for reproducibility and interpretation. Accordingly, we have revised the Echocardiographic Measurements section to explicitly state that GLS analysis was performed using vendor-specific speckle-tracking software (Philips QLAB, Philips Healthcare). Endocardial border detection was initially automated and manually adjusted by the operator when necessary to optimize myocardial tracking, and segments with inadequate tracking quality were excluded from analysis.

Inter- and intra-observer variability analyses were not performed in this study, which we now explicitly acknowledge as a limitation in the Limitations section. We believe that these clarifications substantially improve the transparency of our methodology.

Major Comment 2: Exclusion criteria – COPD versus pneumonia

Comment:

The rationale for excluding patients with COPD exacerbation but not those with pneumonia requires clarification.

Response:

We appreciate the opportunity to clarify this point. Patients presenting with a clear exacerbation of chronic obstructive pulmonary disease were excluded because hyperinflation, increased intrathoracic pressure, and poor acoustic windows in this population may significantly impair echocardiographic image quality and compromise the reliability of EPSS and FS measurements. In addition, in routine emergency practice, the diagnosis of COPD exacerbation is often established with high confidence based on clinical history and physical examination alone, reducing the need for sonographic cardiac evaluation.

In contrast, patients with pneumonia were included because lung infection frequently coexists with or mimics cardiac causes of dyspnea, and adequate echocardiographic windows can often still be obtained. Including these patients better reflects real-world emergency department presentations where diagnostic uncertainty is common. This rationale has been clarified in the Methods section.

Major Comment 3: Interpretation of clinical applicability versus final diagnoses

Comment:

Given that only a minority of patients were ultimately diagnosed with decompensated heart failure, the clinical applicability of EPSS and FS requires a more nuanced interpretation.

Response:

We fully agree with this important distinction. We recognize that identifying reduced left ventricular systolic function is not synonymous with establishing heart failure as the primary cause of dyspnea, particularly in a heterogeneous emergency department population where patients may present with pneumonia, acute coronary syndrome, or other non-cardiac conditions.

In response to this comment, we have revised the Discussion and Conclusion to clarify that EPSS and FS should be regarded as screening tools for identifying reduced left ventricular systolic function rather than diagnostic replacements for advanced echocardiographic imaging. We also explicitly acknowledge that abnormal EPSS or FS values may reflect underlying or comorbid left ventricular dysfunction in patients with non-cardiac final diagnoses, rather than indicating decompensated heart failure as the primary etiology of symptoms. This reframing prevents overgeneralization and aligns the interpretation more closely with the characteristics of our study population.

 

Minor Comment 1: Figure 1 annotations

Response:

We have revised Figure 1 to include explicit numeric annotations demonstrating EPSS measurements and left ventricular internal diameters (LVIDd and LVIDs) directly on the ultrasound images, improving visual clarity and interpretability.

Minor Comment 2: Figure 2 representation of biplane EF

Response:

We thank the reviewer for this important comment. We would like to clarify that left ventricular ejection fraction was calculated using the biplane Simpson’s method during transthoracic echocardiography. However, due to real-world emergency department workflow constraints, complete archiving of both apical four-chamber and two-chamber views was not available for all patients. This has now been explicitly clarified in the Methods section. Accordingly, Figure 2 presents representative apical imaging used for EF assessment rather than a complete archived biplane dataset.

Minor Comment 3: Abstract content

Response:

We have revised the Abstract to include the total number of patients enrolled (n = 63) and the mean age of the study population (61.7 ± 14.2 years), as suggested.

We believe that these revisions have improved the methodological transparency, interpretive balance, and overall clinical relevance of the manuscript. We sincerely thank the reviewer for the valuable feedback.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Authors have addressed all of my comments, except for fig 1. We need to see annotations with distances/arrows clearly showing EPSS, LVIDd and LVIDs. And it looks like the figure was taken as a picture from a phone. A screenshot with better resolution should be used instead.

Author Response

Comment:

Authors have addressed all of my comments, except for fig 1. We need to see annotations with distances/arrows clearly showing EPSS, LVIDd and LVIDs. And it looks like the figure was taken as a picture from a phone. A screenshot with better resolution should be used instead.

Response:

We thank the reviewer for this helpful comment. Figure 1 has been fully revised using high-resolution original screen captures obtained directly from the ultrasound system rather than a mobile phone photograph. Clear arrows and numeric annotations have been added to explicitly demonstrate EPSS, LVIDd, and LVIDs measurements on the images. We believe that these revisions significantly improve the clarity and quality of the figure.

Author Response File: Author Response.docx