Comparative hemodynamics of ATTR and AL amyloidosis with exercise-induced pulmonary hypertension: A retrospective analysis

Arif Albulushi; Amna Al-Busaidi; Kumayl Al-Lawatia; Thuraiya Al-Rawahi; Matlooba Al-Zadjali

doi:10.12688/f1000research.148652.1

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Research Article

Comparative hemodynamics of ATTR and AL amyloidosis with exercise-induced pulmonary hypertension: A retrospective analysis

[version 1; peer review: 1 not approved]

Arif Albulushi ^1,2, Amna Al-Busaidi¹, Kumayl Al-Lawatia¹, Thuraiya Al-Rawahi³, Matlooba Al-Zadjali¹

Arif Albulushi ^1,2, Amna Al-Busaidi¹, [...] Kumayl Al-Lawatia¹, Thuraiya Al-Rawahi³, Matlooba Al-Zadjali¹

PUBLISHED 08 Jul 2024

Author details Author details

¹ Division of Adult Cardiology, National Heart Center, The Royal Hospital, Muscat, Oman
² Division of Cardiovascular Medicine, University of Nebraska Medical Center, Omaha, USA
³ College of Medicine, Royal College of Surgeons in Ireland, Muharraq, Bahrain

Arif Albulushi
Roles: Conceptualization

Amna Al-Busaidi
Roles: Supervision

Kumayl Al-Lawatia
Roles: Investigation, Supervision, Validation

Thuraiya Al-Rawahi
Roles: Methodology, Supervision

Matlooba Al-Zadjali
Roles: Resources, Validation

OPEN PEER REVIEW

REVIEWER STATUS

This article is included in the Health Services gateway.

Abstract

Background

Cardiac amyloidosis, characterized by the deposition of amyloid proteins in the heart tissue, presents in two main types: transthyretin (ATTR) and light-chain (AL) amyloidosis. The hemodynamic response to exercise and the relationship with pulmonary hypertension (PH) in these patients is not well understood.

Methods

This retrospective study analyzed 100 patients diagnosed with either ATTR or AL amyloidosis. We assessed the prevalence of PH at rest and its induction during exercise stress tests. Hemodynamic parameters were measured to identify differences in the cardiac response to exercise between the two subtypes.

Results

A higher prevalence of PH was noted in the ATTR group compared to the AL group. Exercise stress tests induced significant PH, particularly in the ATTR subgroup. Subtle yet clinically relevant hemodynamic differences were observed between the amyloidosis subtypes.

Conclusions

Our findings suggest that the amyloidosis subtype is an important factor in the management of PH. There is a need for tailored clinical approaches to address the distinct pathophysiological mechanisms in ATTR and AL amyloidosis. This study contributes to a better understanding of the hemodynamic changes during exercise in cardiac amyloidosis and underscores the importance of subtype-specific management strategies.

Keywords

Cardiac Amyloidosis, Chronic Heart Failure, Exercise-Induced PH, Hemodynamic Response

Corresponding author: Arif Albulushi

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2024 Albulushi A et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Albulushi A, Al-Busaidi A, Al-Lawatia K et al. Comparative hemodynamics of ATTR and AL amyloidosis with exercise-induced pulmonary hypertension: A retrospective analysis [version 1; peer review: 1 not approved]. F1000Research 2024, 13:769 (https://doi.org/10.12688/f1000research.148652.1) First published: 08 Jul 2024, 13:769 (https://doi.org/10.12688/f1000research.148652.1) Latest published: 08 Jul 2024, 13:769 (https://doi.org/10.12688/f1000research.148652.1)

Introduction

Cardiac amyloidosis, typified by ATTR (transthyretin) and AL (light-chain) amyloidosis, represents a spectrum of conditions characterized by extracellular deposition of misfolded proteins in the cardiac matrix, leading to diastolic dysfunction and restrictive cardiomyopathy.¹^,² The intricacies of cardiac amyloidosis, coupled with its clinical manifestations, present a diagnostic challenge, often leading to delayed or missed diagnoses.³

Recent research underscores the prevalence of pulmonary hypertension (PH) in patients with cardiac amyloidosis, revealing its potential impact on prognosis and management strategies.⁴ ATTR amyloidosis, a hereditary or wild-type form, and AL amyloidosis, associated with plasma cell dyscrasia, each have distinct pathophysiological profiles but share the common complication of PH, contributing to increased morbidity and mortality.⁵

The hemodynamic burden imposed by amyloid deposition in the myocardium is not fully understood, especially under conditions of stress or exercise.⁶ This study aims to elucidate the hemodynamic changes associated with ATTR and AL amyloidosis at rest and during exercise, examining the prevalence of PH and its induction through stress testing to better understand the physiological demands placed on the heart in the presence of amyloid fibril infiltration.

By exploring the interplay between ATTR and AL amyloidosis with exercise-induced PH, this study aims to provide deeper insights into the hemodynamic alterations and their clinical implications, thereby informing more targeted therapeutic approaches for this patient population.

Methods

This retrospective cohort study analyzes the hemodynamic data from ATTR and AL amyloidosis patients between January 2015 and December 2023. Our primary aim was to compare the prevalence and severity of pulmonary hypertension (PH) and exercise-induced hemodynamic changes between the two amyloidosis types.

Study population

100 patients diagnosed with cardiac amyloidosis, confirmed via biopsy, were included. Of these, 40 had ATTR amyloidosis and 60 had AL amyloidosis.

Hemodynamic assessment

All patients underwent right heart catheterization (RHC) at rest. A subset of 70 patients also participated in exercise tests to induce PH. Hemodynamic parameters including mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure (PCWP), and right atrial pressure (RAP) were recorded. The change in mPAP relative to cardiac output (ΔmPAP/ΔCO) was used to assess the exercise-induced PH. Exercise-induced pulmonary hypertension (PH) is characterized by an increase in mean pulmonary arterial pressure (mPAP) to >30 mmHg at a cardiac output (CO) of <10 L/min during exercise, or a total pulmonary vascular resistance (TPVR) >3 Wood units (WU). Additionally, a rise in mean pulmonary arterial pressure relative to the increase in cardiac output (ΔmPAP/ΔCO) exceeding 3 mmHg/L/min, and an elevation in pulmonary arterial wedge pressure (ΔPAWP/ΔCO) surpassing 2 mmHg/L/min from rest to exercise, indicate post-capillary exercise-induced PH.⁷

Statistical analysis

Differences in PH prevalence between ATTR and AL groups were compared using the chi-square test, and exercise-induced hemodynamic changes were analyzed with the Mann-Whitney U test. A p-value of less than 0.05 was considered statistically significant.

Ethical considerations

This study was approved by IRB at UNMC, Ethical Approval Committee: 0839-21-CB (12/2/2021). Due to the retrospective nature of the data analysis, the requirement for informed consent was waived. The study adhered to the ethical principles outlined in the Declaration of Helsinki for medical research involving human subjects.

Results

Our study's cohort featured 100 patients with cardiac amyloidosis, 40 with transthyretin amyloidosis (ATTR), and 60 with light-chain amyloidosis (AL) otherwise no difference in demographics Table 1. The incidence of pulmonary hypertension (PH) was higher in the ATTR group at 66% compared to 57% in the AL group, a difference that was on the cusp of statistical significance (p=0.051) Figure 1.

Table 1. Clinical Parameters of the Study Cohort.

Parameter	ATTR	AL (n=60)
Age (years)	65 ± 10	62 ± 11
Gender male {%)	60%	55%
Body mass index (kg/m²)	28 ± 4	27 ± 5
Systolic blood pressure (mmHg)	130 ± 15	125 ± 20
Diastolic blood pressure (mmHg)	80 ± 10	78 ± 12
NYHA functional class ≥3 {%)	40%	35%
N-terminal pro B-type natriuretic peptide (ng/L)	3000 ± 500	2800 ± 600
Troponin T (ng/L)	0.05 ± 0.01	0.04 ± 0.02
Creatinine (μmol/L)	110 ± 20	100 ± 25
Estimated glomerular filtration rate (ml/min/1.73 m²)	55 ± 10	60 ± 15
Hereditary ATTR-CM {%)	30%	-
Hypertension {%)	50%	55%
Diabetes mellitus {%)	20%	25%
Previous stroke or TIA {%)	10%	8%
Chronic obstructive pulmonary disease {%)	15%	10%
Atrial fibrillation {%)	25%	20%
Carpal tunnel syndrome {%)	35%	30%
Spinal stenosis {%)	5%	8%
Left ventricular ejection fraction {%)	50 ± 5	48 ± 6
lnterventricular septum diastolic diameter (mm)	12 ± 2	11 ± 3
Left atrial area (cm²)	20 ± 4	22 ± 5

Figure 1. Prevalence of Pulmonary Hypertension in ATTR vs. AL Amyloidosis.

Upon exercise stress testing, PH was elicited in the entirety of the ATTR subgroup and 90% of the AL subgroup, marking a significant differential response to physical exertion (p=0.04). Detailed hemodynamic profiling during exercise unveiled a nuanced interplay between ventricular response and vascular load. The median increase in mean pulmonary arterial pressure relative to cardiac output (ΔmPAP/ΔCO) was marginally higher for ATTR patients. Similarly, the median rise in pulmonary artery wedge pressure per unit cardiac output (ΔPAWP/ΔCO) also favored ATTR amyloidosis, though this did not reach a level of statistical significance Figure 2.

Figure 2. Hemodynamic Changes During Exercise.

Notably, the median increase in right atrial pressure per unit cardiac output (ΔRAP/ΔCO) was marginally higher in the AL group, reflecting a potential difference in central venous pressure dynamics during stress between the amyloidosis types. Nonetheless, the ratio of ΔRAP to ΔPAWP remained consistent across both groups, suggesting a uniform relationship between right atrial pressures and left-sided filling pressures during exercise, regardless of amyloid type (p=0.08) Table 2.

Table 2. Hemodynamic Variables at Rest and During Exercise.

Hemodynamic Variable	Rest ATTR	Exercise ATTR	Rest AL	Excercise AL
Heart Rate (b.p.m)	70 ± 12	85 ± 15	72 ± 11	88 ± 14
Arterial 02 saturation (%)	95 ± 3	96 ± 2	94 ± 4	95 ± 3
Cardiac output (L/min)	4.6 ± 1.1	6.5 ± 1.2	4.4 ± 1.0	6.2 ± 1.3
Stroke volume (ml)	65 ± 15	75 ± 18	63 ± 14	73 ± 17
Right atrial pressure (mmHg)	8 [S-12]	10 [7-14]	7 [4-11]	9 [6-13]
Systolic pulmonary artery pressure (mmHg)	35 ± 10	40 ± 12	33 ± 11	38 ± 13
Diastolic pulmonary artery pressure (mmHg)	15 ± 5	20 ± 6	14 ± 6	18 ± 7
Mean pulmonary artery pressure (mmHg)	25 ± 8	30 ± 10	24 ± 9	28 ± 11
Pulmonary capillary wedge pressure (mmHg)	12 [8-16]	15 [10-20]	11 [7-15]	14 [9-19]
Pulmonary vascular resistance (Wood units)	1.5 [1.2-2.0]	1.3 [1.0-1.7]	1.6 [1.3-2.1]	1.4 [1.1-1.8]
Pulmonary arterial compliance (mL/mmHg)	3.0 [2.5-3.S]	2.8 [2.3-3.2]	3.1 [2.6-3.7]	2.9 [2.4-3.4]

These findings illuminate the pathophysiological divergence in exercise response between ATTR and AL amyloidosis, underscoring the need for tailored clinical management strategies.

Discussion

This study's findings reveal a complex interplay between cardiac amyloidosis subtypes and pulmonary hypertension (PH), particularly under exercise conditions.⁸ The higher prevalence of exercise-induced PH in ATTR compared to AL amyloidosis may reflect the distinct pathophysiological mechanisms at play.⁹ ATTR amyloidosis, with its non-mutant and mutant variants, often leads to stiffer ventricular walls, predisposing patients to a higher incidence of PH during stress.⁷

The marginal differences in hemodynamic responses, such as ΔmPAP/ΔCO and ΔPAWP/ΔCO, suggest a possible disparity in how each amyloid subtype affects cardiac and vascular function.¹⁰ These disparities could be attributed to the differential myocardial infiltration patterns and the resultant impact on ventricular compliance and contractility. The similar ΔRAP/ΔPAWP ratios between the groups might indicate a shared mechanism in the way increased left heart pressures are transmitted back to the right heart, despite the differences in amyloid fibril composition anetd deposition.

The borderline statistical significance observed in PH prevalence and hemodynamic responses warrants further investigation. A larger sample size could elucidate whether the trends observed are consistent and statistically robust across a broader population.

Clinically, these findings emphasize the importance of personalized management strategies for PH in patients with cardiac amyloidosis.⁴ They also raise questions about the potential benefits of targeted therapies for PH that consider the specific amyloidosis subtype. Prospective studies might investigate whether treatments that are effective for PH in one subtype may be less so in another, due to the underlying molecular and structural differences.

This research contributes to a growing body of evidence that suggests cardiac amyloidosis, particularly ATTR, is an underrecognized etiology in patients presenting with PH.¹⁰ Recognition of this relationship is critical, as it may guide the timing of diagnostic procedures like RHC, especially when noninvasive assessments are inconclusive or suggest PH. It also underscores the need for heightened clinical awareness of amyloidosis as a differential diagnosis in PH patients.

Conclusion

The hemodynamic response to exercise in cardiac amyloidosis patients with PH presents a multifaceted challenge. Our study adds to the understanding of this response, providing a foundation for future research and clinical practice that could improve outcomes for this patient population.

Ethical approval committee

0839-21-CB (12/2/2021).

Author contributions statement

Authors AA & KS were involved in the conception and design, and author HA was involved in the analysis and interpretation of the data; the drafting of the paper, revising it critically for intellectual content; and the final approval of the version to be published. All authors agree to be accountable for all aspects of the work.

Ethics and consent

Description of data restrictions

Our study involves data that are sensitive in nature due to [patient confidentiality, proprietary information]. To protect the privacy and rights of the individuals involved and to comply with [local institute regulations and guidelines], access to the complete dataset is restricted.

Information required for data access application

Researchers or reviewers interested in accessing the dataset must:

1. Submit a formal request to [specify the authority, e.g., the principal investigator, a specific department, or an institutional review board] outlining the purpose of the data request.
2. Provide a detailed research proposal, including objectives, methodology, and expected outcomes.
3. Agree to abide by all ethical guidelines, including [specify any specific requirements, such as data handling procedures, confidentiality agreements, etc.].
4. Obtain approval from their own institutional review board (IRB) or ethics committee, if applicable.

Conditions for data access

Access to the data will be granted under the following conditions:

1. The data will be used solely for the purposes outlined in the approved research proposal.
2. Any publication or dissemination of results derived from the data must acknowledge the source of the data.
3. The data must not be shared with third parties or used to identify individual participants.
4. All researchers accessing the data agree to comply with [specify any additional conditions, such as data security measures, reporting requirements, etc.].

We believe these measures are necessary to ensure the ethical use of the data and to protect the privacy and security of the individuals and entities involved. Should you require any further information or clarification, please do not hesitate to contact us.

Data availability statement

Data available upon request by contacting the correspondence author via dr.albulushi@gmail.com. Due to ethical restrictions and the sensitive nature of the clinical data, these are not publicly deposited but are available under conditions that preserve the privacy of individuals involved.

References

1. Meaney E, Shabetai R, Bhargava V, et al.: Cardiac amyloidosis, constrictive pericarditis, and restrictive cardiomyopathy. Am. J. Cardiol. 1976; 38(5): 547–556. Publisher Full Text
2. Akatsuka T, Fujimoto N, Ishiyama M, et al.: Trajectory of left ventricular geometry and diastolic dysfunction in hereditary transthyretin cardiac amyloidosis. ESC Heart Fail. 2021; 8(4): 3422–3426. PubMed Abstract | Publisher Full Text | Free Full Text
3. Porcari A, et al.: Cardiac amyloidosis: do not forget to look for it. Eur. Heart J. Suppl. 2020; 22(Suppl_E): E142–E147. PubMed Abstract | Publisher Full Text | Free Full Text
4. Dingli D, Utz JP, Gertz MA: Pulmonary hypertension in patients with amyloidosis. Chest. 2001; 120(5): 1735–1738. Publisher Full Text
5. Slivnick J, et al.: Prevalence and haemodynamic profiles of pulmonary hypertension in cardiac amyloidosis. Open Heart. 2022; 9(1): e001808. PubMed Abstract | Publisher Full Text | Free Full Text
6. Banydeen R, et al.: Diagnostic and prognostic values of cardiopulmonary exercise testing in cardiac amyloidosis. Front Cardiovasc Med. 2022; 9: 898033. PubMed Abstract | Publisher Full Text | Free Full Text
7. Holt MF, Flø A, Ravnestad H, et al.: Invasive haemodynamics at rest and exercise in cardiac amyloidosis. ESC Heart Fail. 2023 Dec 29; 11: 1263–1268. Publisher Full Text
8. Cantone A, Serenelli M, Sanguettoli F, et al.: Cardiopulmonary exercise testing predicts prognosis in amyloid cardiomyopathy: a systematic review and meta-analysis. ESC Heart Fail. 2023; 10(4): 2740–2744. PubMed Abstract | Publisher Full Text | Free Full Text
9. Bustamante JG, Zaidi SRH: Amyloidosis. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023 Jul 31.
10. Longinow J, et al.: Significance of Pulmonary Hypertension in Cardiac Amyloidosis. Am. J. Cardiol. 2023; 192: 147–154. PubMed Abstract | Publisher Full Text

Comments on this article Comments (0)

Version 1

VERSION 1 PUBLISHED 08 Jul 2024

Author details Author details

Arif Albulushi
Roles: Conceptualization

Amna Al-Busaidi
Roles: Supervision

Kumayl Al-Lawatia
Roles: Investigation, Supervision, Validation

Thuraiya Al-Rawahi
Roles: Methodology, Supervision

Matlooba Al-Zadjali
Roles: Resources, Validation

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

Article Versions (1)

version 1

Published: 08 Jul 2024, 13:769

https://doi.org/10.12688/f1000research.148652.1

© 2024 Albulushi A et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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how to cite this article

Albulushi A, Al-Busaidi A, Al-Lawatia K et al. Comparative hemodynamics of ATTR and AL amyloidosis with exercise-induced pulmonary hypertension: A retrospective analysis [version 1; peer review: 1 not approved]. F1000Research 2024, 13:769 (https://doi.org/10.12688/f1000research.148652.1)

NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.

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Open Peer Review

Version 1

VERSION 1

PUBLISHED 08 Jul 2024

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Reviewer Report 04 Sep 2024

Selda Murat, Eskisehir Osmangazi University, Eskisehir, Turkey

Not Approved

https://doi.org/10.5256/f1000research.162992.r314999

The methodology of the study is not suitable for retrospective data recording studies.
It should be explained for which indications right catheter and exercise-induced catheter were performed after diagnosis.

If these interventional procedures were performed within the scope of this study, the study design should be stated prospectively.

The study ethics committee date is written as 2021, but the data collecting intervals in which the study was performed are stated as 2015-2023. This is confusing.

The discussion is very insufficient.

It would be appropriate to provide information about the patients' right heart functions (TAPSE, RV area, RV strain ..).

Is the work clearly and accurately presented and does it cite the current literature?

No
Is the study design appropriate and is the work technically sound?

No
Are sufficient details of methods and analysis provided to allow replication by others?

Yes
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Partly
Are the conclusions drawn adequately supported by the results?

No

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: cardiomyopathy

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

CITE

Report a concern

Author Response 05 Sep 2024

SS DM2020, Division of Adult Cardiology, National Heart Center, The Royal Hospital, Muscat, Oman

05 Sep 2024

Author Response
1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may ... Continue reading
1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may have caused some confusion in the presentation. The study involved a review of existing patient data where right heart catheterization (RHC) and exercise-induced RHC were performed as part of routine clinical care after diagnosing cardiac amyloidosis. We will update the methodology section to clarify that these procedures were not part of a prospective study but rather data were gathered retrospectively from patients who had undergone RHC as part of their diagnostic workup. This will ensure the distinction between retrospective data collection and prospective study designs is clear.

2. It should be explained for which indications right heart catheterization and exercise-induced catheterization were performed after diagnosis.
Response:
We appreciate your comment and agree that this needs to be clarified. We will add a detailed explanation regarding the indications for performing RHC and exercise-induced catheterization. Typically, these procedures were performed in patients with suspected or established pulmonary hypertension (PH) based on non-invasive imaging findings, worsening symptoms, or unexplained dyspnea, especially during exertion. We will include this information in the revised manuscript to better explain the rationale behind the selection of patients for these procedures.

3. If these interventional procedures were performed within the scope of this study, the study design should be stated prospectively.
Response:
We acknowledge the confusion caused by the presentation of the study design. As noted earlier, this was a retrospective study, and no interventional procedures were conducted specifically for the purpose of the study. The data were gathered from patients who had already undergone RHC and exercise-induced catheterization as part of their clinical care. We will explicitly state this in the study design section to avoid any ambiguity.

4. The study ethics committee date is written as 2021, but the data collection intervals in which the study was performed are stated as 2015-2023. This is confusing.
Response:
You are correct in identifying this inconsistency. We will revise the manuscript to explain that the data collection was retrospective, spanning from 2015 to 2023, and that ethical approval was obtained in 2021 for the retrospective review of these data. This clarification will make the timeline more transparent.

Thank you for sharing the reviewer's feedback. Below is a structured response to each of the concerns raised, which you can use as a guide to address the reviewer's comments effectively.
Reviewer Concerns and Suggested Responses
1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may have caused some confusion in the presentation. The study involved a review of existing patient data where right heart catheterization (RHC) and exercise-induced RHC were performed as part of routine clinical care after diagnosing cardiac amyloidosis. We will update the methodology section to clarify that these procedures were not part of a prospective study but rather data were gathered retrospectively from patients who had undergone RHC as part of their diagnostic workup. This will ensure the distinction between retrospective data collection and prospective study designs is clear.
2. It should be explained for which indications right heart catheterization and exercise-induced catheterization were performed after diagnosis.
Response:
We appreciate your comment and agree that this needs to be clarified. We will add a detailed explanation regarding the indications for performing RHC and exercise-induced catheterization. Typically, these procedures were performed in patients with suspected or established pulmonary hypertension (PH) based on non-invasive imaging findings, worsening symptoms, or unexplained dyspnea, especially during exertion. We will include this information in the revised manuscript to better explain the rationale behind the selection of patients for these procedures.
3. If these interventional procedures were performed within the scope of this study, the study design should be stated prospectively.
Response:
We acknowledge the confusion caused by the presentation of the study design. As noted earlier, this was a retrospective study, and no interventional procedures were conducted specifically for the purpose of the study. The data were gathered from patients who had already undergone RHC and exercise-induced catheterization as part of their clinical care. We will explicitly state this in the study design section to avoid any ambiguity.
4. The study ethics committee date is written as 2021, but the data collection intervals in which the study was performed are stated as 2015-2023. This is confusing.
Response:
You are correct in identifying this inconsistency. We will revise the manuscript to explain that the data collection was retrospective, spanning from 2015 to 2023, and that ethical approval was obtained in 2021 for the retrospective review of these data. This clarification will make the timeline more transparent.
5. The discussion is very insufficient.
Response:
We appreciate your feedback on the discussion. To address this, we will expand the discussion to include:

A deeper analysis of the differences in hemodynamic responses between ATTR and AL amyloidosis during exercise.

A comparison with other studies on cardiac amyloidosis and pulmonary hypertension to put our findings into context.

Clinical implications of our results, particularly how they might inform tailored management strategies for ATTR and AL amyloidosis patients. This revision will aim to provide a more comprehensive interpretation of the findings and their significance in current clinical practice.

6. It would be appropriate to provide information about the patients' right heart functions (TAPSE, RV area, RV strain).
Response:
Thank you for this important suggestion. We agree that including parameters of right heart function such as tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) area, and RV strain would add valuable insight to the study. Although this study primarily focused on "invasive" pulmonary hemodynamics, we will re-examine the dataset to extract information on these parameters. If available, we will present these data in the results section and discuss the relevance of right heart function in the context of exercise-induced PH and amyloidosis.

7. Is the work clearly and accurately presented and does it cite the current literature?
Response:
We acknowledge that the manuscript may not have fully addressed the current literature. In the revised version, we will ensure that recent and relevant studies on cardiac amyloidosis, PH, and exercise-induced hemodynamics are cited. This will provide a stronger foundation for our discussion and interpretation of the results.

8. Are the conclusions drawn adequately supported by the results?
Response:
We recognize that the conclusions may not be fully supported by the current results due to the limitations of sample size and some borderline statistical findings. In the revision, we will adjust our conclusions to more cautiously reflect the data, emphasizing trends and the need for further research to confirm our findings. We will also include a clearer discussion of the study’s limitations.
1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may have caused some confusion in the presentation. The study involved a review of existing patient data where right heart catheterization (RHC) and exercise-induced RHC were performed as part of routine clinical care after diagnosing cardiac amyloidosis. We will update the methodology section to clarify that these procedures were not part of a prospective study but rather data were gathered retrospectively from patients who had undergone RHC as part of their diagnostic workup. This will ensure the distinction between retrospective data collection and prospective study designs is clear.

2. It should be explained for which indications right heart catheterization and exercise-induced catheterization were performed after diagnosis.
Response:
We appreciate your comment and agree that this needs to be clarified. We will add a detailed explanation regarding the indications for performing RHC and exercise-induced catheterization. Typically, these procedures were performed in patients with suspected or established pulmonary hypertension (PH) based on non-invasive imaging findings, worsening symptoms, or unexplained dyspnea, especially during exertion. We will include this information in the revised manuscript to better explain the rationale behind the selection of patients for these procedures.

3. If these interventional procedures were performed within the scope of this study, the study design should be stated prospectively.
Response:
We acknowledge the confusion caused by the presentation of the study design. As noted earlier, this was a retrospective study, and no interventional procedures were conducted specifically for the purpose of the study. The data were gathered from patients who had already undergone RHC and exercise-induced catheterization as part of their clinical care. We will explicitly state this in the study design section to avoid any ambiguity.

4. The study ethics committee date is written as 2021, but the data collection intervals in which the study was performed are stated as 2015-2023. This is confusing.
Response:
You are correct in identifying this inconsistency. We will revise the manuscript to explain that the data collection was retrospective, spanning from 2015 to 2023, and that ethical approval was obtained in 2021 for the retrospective review of these data. This clarification will make the timeline more transparent.

Thank you for sharing the reviewer's feedback. Below is a structured response to each of the concerns raised, which you can use as a guide to address the reviewer's comments effectively.
Reviewer Concerns and Suggested Responses
1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may have caused some confusion in the presentation. The study involved a review of existing patient data where right heart catheterization (RHC) and exercise-induced RHC were performed as part of routine clinical care after diagnosing cardiac amyloidosis. We will update the methodology section to clarify that these procedures were not part of a prospective study but rather data were gathered retrospectively from patients who had undergone RHC as part of their diagnostic workup. This will ensure the distinction between retrospective data collection and prospective study designs is clear.
2. It should be explained for which indications right heart catheterization and exercise-induced catheterization were performed after diagnosis.
Response:
We appreciate your comment and agree that this needs to be clarified. We will add a detailed explanation regarding the indications for performing RHC and exercise-induced catheterization. Typically, these procedures were performed in patients with suspected or established pulmonary hypertension (PH) based on non-invasive imaging findings, worsening symptoms, or unexplained dyspnea, especially during exertion. We will include this information in the revised manuscript to better explain the rationale behind the selection of patients for these procedures.
3. If these interventional procedures were performed within the scope of this study, the study design should be stated prospectively.
Response:
We acknowledge the confusion caused by the presentation of the study design. As noted earlier, this was a retrospective study, and no interventional procedures were conducted specifically for the purpose of the study. The data were gathered from patients who had already undergone RHC and exercise-induced catheterization as part of their clinical care. We will explicitly state this in the study design section to avoid any ambiguity.
4. The study ethics committee date is written as 2021, but the data collection intervals in which the study was performed are stated as 2015-2023. This is confusing.
Response:
You are correct in identifying this inconsistency. We will revise the manuscript to explain that the data collection was retrospective, spanning from 2015 to 2023, and that ethical approval was obtained in 2021 for the retrospective review of these data. This clarification will make the timeline more transparent.
5. The discussion is very insufficient.
Response:
We appreciate your feedback on the discussion. To address this, we will expand the discussion to include:

A deeper analysis of the differences in hemodynamic responses between ATTR and AL amyloidosis during exercise.

A comparison with other studies on cardiac amyloidosis and pulmonary hypertension to put our findings into context.

Clinical implications of our results, particularly how they might inform tailored management strategies for ATTR and AL amyloidosis patients. This revision will aim to provide a more comprehensive interpretation of the findings and their significance in current clinical practice.

6. It would be appropriate to provide information about the patients' right heart functions (TAPSE, RV area, RV strain).
Response:
Thank you for this important suggestion. We agree that including parameters of right heart function such as tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) area, and RV strain would add valuable insight to the study. Although this study primarily focused on "invasive" pulmonary hemodynamics, we will re-examine the dataset to extract information on these parameters. If available, we will present these data in the results section and discuss the relevance of right heart function in the context of exercise-induced PH and amyloidosis.

7. Is the work clearly and accurately presented and does it cite the current literature?
Response:
We acknowledge that the manuscript may not have fully addressed the current literature. In the revised version, we will ensure that recent and relevant studies on cardiac amyloidosis, PH, and exercise-induced hemodynamics are cited. This will provide a stronger foundation for our discussion and interpretation of the results.

8. Are the conclusions drawn adequately supported by the results?
Response:
We recognize that the conclusions may not be fully supported by the current results due to the limitations of sample size and some borderline statistical findings. In the revision, we will adjust our conclusions to more cautiously reflect the data, emphasizing trends and the need for further research to confirm our findings. We will also include a clearer discussion of the study’s limitations.
Competing Interests: None Close
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COMMENTS ON THIS REPORT

Author Response 05 Sep 2024

SS DM2020, Division of Adult Cardiology, National Heart Center, The Royal Hospital, Muscat, Oman

05 Sep 2024

Author Response
1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may ... Continue reading
1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may have caused some confusion in the presentation. The study involved a review of existing patient data where right heart catheterization (RHC) and exercise-induced RHC were performed as part of routine clinical care after diagnosing cardiac amyloidosis. We will update the methodology section to clarify that these procedures were not part of a prospective study but rather data were gathered retrospectively from patients who had undergone RHC as part of their diagnostic workup. This will ensure the distinction between retrospective data collection and prospective study designs is clear.

2. It should be explained for which indications right heart catheterization and exercise-induced catheterization were performed after diagnosis.
Response:
We appreciate your comment and agree that this needs to be clarified. We will add a detailed explanation regarding the indications for performing RHC and exercise-induced catheterization. Typically, these procedures were performed in patients with suspected or established pulmonary hypertension (PH) based on non-invasive imaging findings, worsening symptoms, or unexplained dyspnea, especially during exertion. We will include this information in the revised manuscript to better explain the rationale behind the selection of patients for these procedures.

3. If these interventional procedures were performed within the scope of this study, the study design should be stated prospectively.
Response:
We acknowledge the confusion caused by the presentation of the study design. As noted earlier, this was a retrospective study, and no interventional procedures were conducted specifically for the purpose of the study. The data were gathered from patients who had already undergone RHC and exercise-induced catheterization as part of their clinical care. We will explicitly state this in the study design section to avoid any ambiguity.

4. The study ethics committee date is written as 2021, but the data collection intervals in which the study was performed are stated as 2015-2023. This is confusing.
Response:
You are correct in identifying this inconsistency. We will revise the manuscript to explain that the data collection was retrospective, spanning from 2015 to 2023, and that ethical approval was obtained in 2021 for the retrospective review of these data. This clarification will make the timeline more transparent.

Thank you for sharing the reviewer's feedback. Below is a structured response to each of the concerns raised, which you can use as a guide to address the reviewer's comments effectively.
Reviewer Concerns and Suggested Responses
1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may have caused some confusion in the presentation. The study involved a review of existing patient data where right heart catheterization (RHC) and exercise-induced RHC were performed as part of routine clinical care after diagnosing cardiac amyloidosis. We will update the methodology section to clarify that these procedures were not part of a prospective study but rather data were gathered retrospectively from patients who had undergone RHC as part of their diagnostic workup. This will ensure the distinction between retrospective data collection and prospective study designs is clear.
2. It should be explained for which indications right heart catheterization and exercise-induced catheterization were performed after diagnosis.
Response:
We appreciate your comment and agree that this needs to be clarified. We will add a detailed explanation regarding the indications for performing RHC and exercise-induced catheterization. Typically, these procedures were performed in patients with suspected or established pulmonary hypertension (PH) based on non-invasive imaging findings, worsening symptoms, or unexplained dyspnea, especially during exertion. We will include this information in the revised manuscript to better explain the rationale behind the selection of patients for these procedures.
3. If these interventional procedures were performed within the scope of this study, the study design should be stated prospectively.
Response:
We acknowledge the confusion caused by the presentation of the study design. As noted earlier, this was a retrospective study, and no interventional procedures were conducted specifically for the purpose of the study. The data were gathered from patients who had already undergone RHC and exercise-induced catheterization as part of their clinical care. We will explicitly state this in the study design section to avoid any ambiguity.
4. The study ethics committee date is written as 2021, but the data collection intervals in which the study was performed are stated as 2015-2023. This is confusing.
Response:
You are correct in identifying this inconsistency. We will revise the manuscript to explain that the data collection was retrospective, spanning from 2015 to 2023, and that ethical approval was obtained in 2021 for the retrospective review of these data. This clarification will make the timeline more transparent.
5. The discussion is very insufficient.
Response:
We appreciate your feedback on the discussion. To address this, we will expand the discussion to include:

A deeper analysis of the differences in hemodynamic responses between ATTR and AL amyloidosis during exercise.

A comparison with other studies on cardiac amyloidosis and pulmonary hypertension to put our findings into context.

Clinical implications of our results, particularly how they might inform tailored management strategies for ATTR and AL amyloidosis patients. This revision will aim to provide a more comprehensive interpretation of the findings and their significance in current clinical practice.

6. It would be appropriate to provide information about the patients' right heart functions (TAPSE, RV area, RV strain).
Response:
Thank you for this important suggestion. We agree that including parameters of right heart function such as tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) area, and RV strain would add valuable insight to the study. Although this study primarily focused on "invasive" pulmonary hemodynamics, we will re-examine the dataset to extract information on these parameters. If available, we will present these data in the results section and discuss the relevance of right heart function in the context of exercise-induced PH and amyloidosis.

7. Is the work clearly and accurately presented and does it cite the current literature?
Response:
We acknowledge that the manuscript may not have fully addressed the current literature. In the revised version, we will ensure that recent and relevant studies on cardiac amyloidosis, PH, and exercise-induced hemodynamics are cited. This will provide a stronger foundation for our discussion and interpretation of the results.

8. Are the conclusions drawn adequately supported by the results?
Response:
We recognize that the conclusions may not be fully supported by the current results due to the limitations of sample size and some borderline statistical findings. In the revision, we will adjust our conclusions to more cautiously reflect the data, emphasizing trends and the need for further research to confirm our findings. We will also include a clearer discussion of the study’s limitations.
1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may have caused some confusion in the presentation. The study involved a review of existing patient data where right heart catheterization (RHC) and exercise-induced RHC were performed as part of routine clinical care after diagnosing cardiac amyloidosis. We will update the methodology section to clarify that these procedures were not part of a prospective study but rather data were gathered retrospectively from patients who had undergone RHC as part of their diagnostic workup. This will ensure the distinction between retrospective data collection and prospective study designs is clear.

2. It should be explained for which indications right heart catheterization and exercise-induced catheterization were performed after diagnosis.
Response:
We appreciate your comment and agree that this needs to be clarified. We will add a detailed explanation regarding the indications for performing RHC and exercise-induced catheterization. Typically, these procedures were performed in patients with suspected or established pulmonary hypertension (PH) based on non-invasive imaging findings, worsening symptoms, or unexplained dyspnea, especially during exertion. We will include this information in the revised manuscript to better explain the rationale behind the selection of patients for these procedures.

3. If these interventional procedures were performed within the scope of this study, the study design should be stated prospectively.
Response:
We acknowledge the confusion caused by the presentation of the study design. As noted earlier, this was a retrospective study, and no interventional procedures were conducted specifically for the purpose of the study. The data were gathered from patients who had already undergone RHC and exercise-induced catheterization as part of their clinical care. We will explicitly state this in the study design section to avoid any ambiguity.

4. The study ethics committee date is written as 2021, but the data collection intervals in which the study was performed are stated as 2015-2023. This is confusing.
Response:
You are correct in identifying this inconsistency. We will revise the manuscript to explain that the data collection was retrospective, spanning from 2015 to 2023, and that ethical approval was obtained in 2021 for the retrospective review of these data. This clarification will make the timeline more transparent.

Thank you for sharing the reviewer's feedback. Below is a structured response to each of the concerns raised, which you can use as a guide to address the reviewer's comments effectively.
Reviewer Concerns and Suggested Responses
1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may have caused some confusion in the presentation. The study involved a review of existing patient data where right heart catheterization (RHC) and exercise-induced RHC were performed as part of routine clinical care after diagnosing cardiac amyloidosis. We will update the methodology section to clarify that these procedures were not part of a prospective study but rather data were gathered retrospectively from patients who had undergone RHC as part of their diagnostic workup. This will ensure the distinction between retrospective data collection and prospective study designs is clear.
2. It should be explained for which indications right heart catheterization and exercise-induced catheterization were performed after diagnosis.
Response:
We appreciate your comment and agree that this needs to be clarified. We will add a detailed explanation regarding the indications for performing RHC and exercise-induced catheterization. Typically, these procedures were performed in patients with suspected or established pulmonary hypertension (PH) based on non-invasive imaging findings, worsening symptoms, or unexplained dyspnea, especially during exertion. We will include this information in the revised manuscript to better explain the rationale behind the selection of patients for these procedures.
3. If these interventional procedures were performed within the scope of this study, the study design should be stated prospectively.
Response:
We acknowledge the confusion caused by the presentation of the study design. As noted earlier, this was a retrospective study, and no interventional procedures were conducted specifically for the purpose of the study. The data were gathered from patients who had already undergone RHC and exercise-induced catheterization as part of their clinical care. We will explicitly state this in the study design section to avoid any ambiguity.
4. The study ethics committee date is written as 2021, but the data collection intervals in which the study was performed are stated as 2015-2023. This is confusing.
Response:
You are correct in identifying this inconsistency. We will revise the manuscript to explain that the data collection was retrospective, spanning from 2015 to 2023, and that ethical approval was obtained in 2021 for the retrospective review of these data. This clarification will make the timeline more transparent.
5. The discussion is very insufficient.
Response:
We appreciate your feedback on the discussion. To address this, we will expand the discussion to include:

A deeper analysis of the differences in hemodynamic responses between ATTR and AL amyloidosis during exercise.

A comparison with other studies on cardiac amyloidosis and pulmonary hypertension to put our findings into context.

Clinical implications of our results, particularly how they might inform tailored management strategies for ATTR and AL amyloidosis patients. This revision will aim to provide a more comprehensive interpretation of the findings and their significance in current clinical practice.

6. It would be appropriate to provide information about the patients' right heart functions (TAPSE, RV area, RV strain).
Response:
Thank you for this important suggestion. We agree that including parameters of right heart function such as tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) area, and RV strain would add valuable insight to the study. Although this study primarily focused on "invasive" pulmonary hemodynamics, we will re-examine the dataset to extract information on these parameters. If available, we will present these data in the results section and discuss the relevance of right heart function in the context of exercise-induced PH and amyloidosis.

7. Is the work clearly and accurately presented and does it cite the current literature?
Response:
We acknowledge that the manuscript may not have fully addressed the current literature. In the revised version, we will ensure that recent and relevant studies on cardiac amyloidosis, PH, and exercise-induced hemodynamics are cited. This will provide a stronger foundation for our discussion and interpretation of the results.

8. Are the conclusions drawn adequately supported by the results?
Response:
We recognize that the conclusions may not be fully supported by the current results due to the limitations of sample size and some borderline statistical findings. In the revision, we will adjust our conclusions to more cautiously reflect the data, emphasizing trends and the need for further research to confirm our findings. We will also include a clearer discussion of the study’s limitations.
Competing Interests: None Close
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Version 1 08 Jul 24	read

Selda Murat, Eskisehir Osmangazi University, Eskisehir, Turkey

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Reviewer Report

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04 Sep 2024 | for Version 1

Selda Murat, Eskisehir Osmangazi University, Eskisehir, Turkey

4 Views Cite this report Responses(1)

Not Approved

Is the work clearly and accurately presented and does it cite the current literature?

No
Is the study design appropriate and is the work technically sound?

No
Are sufficient details of methods and analysis provided to allow replication by others?

Yes
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Partly
Are the conclusions drawn adequately supported by the results?

No

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

cardiomyopathy

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Responses (1)

Author Response

05 Sep 2024

SS DM2020, Division of Adult Cardiology, National Heart Center, The Royal Hospital, Muscat, Oman

1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may have caused some confusion in the presentation. The study involved a review of existing patient data where right heart catheterization (RHC) and exercise-induced RHC were performed as part of routine clinical care after diagnosing cardiac amyloidosis. We will update the methodology section to clarify that these procedures were not part of a prospective study but rather data were gathered retrospectively from patients who had undergone RHC as part of their diagnostic workup. This will ensure the distinction between retrospective data collection and prospective study designs is clear.

2. It should be explained for which indications right heart catheterization and exercise-induced catheterization were performed after diagnosis.
Response:
We appreciate your comment and agree that this needs to be clarified. We will add a detailed explanation regarding the indications for performing RHC and exercise-induced catheterization. Typically, these procedures were performed in patients with suspected or established pulmonary hypertension (PH) based on non-invasive imaging findings, worsening symptoms, or unexplained dyspnea, especially during exertion. We will include this information in the revised manuscript to better explain the rationale behind the selection of patients for these procedures.

3. If these interventional procedures were performed within the scope of this study, the study design should be stated prospectively.
Response:
We acknowledge the confusion caused by the presentation of the study design. As noted earlier, this was a retrospective study, and no interventional procedures were conducted specifically for the purpose of the study. The data were gathered from patients who had already undergone RHC and exercise-induced catheterization as part of their clinical care. We will explicitly state this in the study design section to avoid any ambiguity.

4. The study ethics committee date is written as 2021, but the data collection intervals in which the study was performed are stated as 2015-2023. This is confusing.
Response:
You are correct in identifying this inconsistency. We will revise the manuscript to explain that the data collection was retrospective, spanning from 2015 to 2023, and that ethical approval was obtained in 2021 for the retrospective review of these data. This clarification will make the timeline more transparent.

Thank you for sharing the reviewer's feedback. Below is a structured response to each of the concerns raised, which you can use as a guide to address the reviewer's comments effectively.
Reviewer Concerns and Suggested Responses
1. Methodology of the study is not suitable for retrospective data recording studies.
Response:
Thank you for pointing this out. We recognize that the retrospective nature of our study may have caused some confusion in the presentation. The study involved a review of existing patient data where right heart catheterization (RHC) and exercise-induced RHC were performed as part of routine clinical care after diagnosing cardiac amyloidosis. We will update the methodology section to clarify that these procedures were not part of a prospective study but rather data were gathered retrospectively from patients who had undergone RHC as part of their diagnostic workup. This will ensure the distinction between retrospective data collection and prospective study designs is clear.
2. It should be explained for which indications right heart catheterization and exercise-induced catheterization were performed after diagnosis.
Response:
We appreciate your comment and agree that this needs to be clarified. We will add a detailed explanation regarding the indications for performing RHC and exercise-induced catheterization. Typically, these procedures were performed in patients with suspected or established pulmonary hypertension (PH) based on non-invasive imaging findings, worsening symptoms, or unexplained dyspnea, especially during exertion. We will include this information in the revised manuscript to better explain the rationale behind the selection of patients for these procedures.
3. If these interventional procedures were performed within the scope of this study, the study design should be stated prospectively.
Response:
We acknowledge the confusion caused by the presentation of the study design. As noted earlier, this was a retrospective study, and no interventional procedures were conducted specifically for the purpose of the study. The data were gathered from patients who had already undergone RHC and exercise-induced catheterization as part of their clinical care. We will explicitly state this in the study design section to avoid any ambiguity.
4. The study ethics committee date is written as 2021, but the data collection intervals in which the study was performed are stated as 2015-2023. This is confusing.
Response:
You are correct in identifying this inconsistency. We will revise the manuscript to explain that the data collection was retrospective, spanning from 2015 to 2023, and that ethical approval was obtained in 2021 for the retrospective review of these data. This clarification will make the timeline more transparent.
5. The discussion is very insufficient.
Response:
We appreciate your feedback on the discussion. To address this, we will expand the discussion to include:

A deeper analysis of the differences in hemodynamic responses between ATTR and AL amyloidosis during exercise.
A comparison with other studies on cardiac amyloidosis and pulmonary hypertension to put our findings into context.
Clinical implications of our results, particularly how they might inform tailored management strategies for ATTR and AL amyloidosis patients. This revision will aim to provide a more comprehensive interpretation of the findings and their significance in current clinical practice.

6. It would be appropriate to provide information about the patients' right heart functions (TAPSE, RV area, RV strain).
Response:
Thank you for this important suggestion. We agree that including parameters of right heart function such as tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) area, and RV strain would add valuable insight to the study. Although this study primarily focused on "invasive" pulmonary hemodynamics, we will re-examine the dataset to extract information on these parameters. If available, we will present these data in the results section and discuss the relevance of right heart function in the context of exercise-induced PH and amyloidosis.

7. Is the work clearly and accurately presented and does it cite the current literature?
Response:
We acknowledge that the manuscript may not have fully addressed the current literature. In the revised version, we will ensure that recent and relevant studies on cardiac amyloidosis, PH, and exercise-induced hemodynamics are cited. This will provide a stronger foundation for our discussion and interpretation of the results.

8. Are the conclusions drawn adequately supported by the results?
Response:
We recognize that the conclusions may not be fully supported by the current results due to the limitations of sample size and some borderline statistical findings. In the revision, we will adjust our conclusions to more cautiously reflect the data, emphasizing trends and the need for further research to confirm our findings. We will also include a clearer discussion of the study’s limitations.

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Competing Interests

None

Alongside their report, reviewers assign a status to the article:

Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested

Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.

Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions

[1] 1. Meaney E, Shabetai R, Bhargava V, et al.: Cardiac amyloidosis, constrictive pericarditis, and restrictive cardiomyopathy. Am. J. Cardiol. 1976; 38(5): 547–556. Publisher Full Text

[2] 2. Akatsuka T, Fujimoto N, Ishiyama M, et al.: Trajectory of left ventricular geometry and diastolic dysfunction in hereditary transthyretin cardiac amyloidosis. ESC Heart Fail. 2021; 8(4): 3422–3426. PubMed Abstract | Publisher Full Text | Free Full Text

[3] 3. Porcari A, et al.: Cardiac amyloidosis: do not forget to look for it. Eur. Heart J. Suppl. 2020; 22(Suppl_E): E142–E147. PubMed Abstract | Publisher Full Text | Free Full Text

[4] 4. Dingli D, Utz JP, Gertz MA: Pulmonary hypertension in patients with amyloidosis. Chest. 2001; 120(5): 1735–1738. Publisher Full Text

[5] 5. Slivnick J, et al.: Prevalence and haemodynamic profiles of pulmonary hypertension in cardiac amyloidosis. Open Heart. 2022; 9(1): e001808. PubMed Abstract | Publisher Full Text | Free Full Text

[6] 6. Banydeen R, et al.: Diagnostic and prognostic values of cardiopulmonary exercise testing in cardiac amyloidosis. Front Cardiovasc Med. 2022; 9: 898033. PubMed Abstract | Publisher Full Text | Free Full Text

[7] 7. Holt MF, Flø A, Ravnestad H, et al.: Invasive haemodynamics at rest and exercise in cardiac amyloidosis. ESC Heart Fail. 2023 Dec 29; 11: 1263–1268. Publisher Full Text

[8] 8. Cantone A, Serenelli M, Sanguettoli F, et al.: Cardiopulmonary exercise testing predicts prognosis in amyloid cardiomyopathy: a systematic review and meta-analysis. ESC Heart Fail. 2023; 10(4): 2740–2744. PubMed Abstract | Publisher Full Text | Free Full Text

[9] 9. Bustamante JG, Zaidi SRH: Amyloidosis. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023 Jul 31.

[10] 10. Longinow J, et al.: Significance of Pulmonary Hypertension in Cardiac Amyloidosis. Am. J. Cardiol. 2023; 192: 147–154. PubMed Abstract | Publisher Full Text

Comparative hemodynamics of ATTR and AL amyloidosis with exercise-induced pulmonary hypertension: A retrospective analysis

Abstract

Background

Methods

Results

Conclusions

Keywords

Introduction

Methods

Study population

Hemodynamic assessment

Statistical analysis

Ethical considerations

Results

Table 1. Clinical Parameters of the Study Cohort.

Figure 1. Prevalence of Pulmonary Hypertension in ATTR vs. AL Amyloidosis.

Figure 2. Hemodynamic Changes During Exercise.

Table 2. Hemodynamic Variables at Rest and During Exercise.

Discussion

Conclusion

Ethical approval committee

Author contributions statement

Ethics and consent

Description of data restrictions

Information required for data access application

Conditions for data access

Data availability statement

References

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