Usefulness of C₂HEST Score in Predicting Clinical Outcomes of COVID-19 in Heart Failure and Non-Heart-Failure Cohorts

Round 1

Reviewer 1 Report

The authors present an interesting study analyzing the usefulness of the C2HEST score in predicting the Clinical 2 Outcomes of COVID-19 in Heart Failure and Non-Heart Failure Cohorts.

The authors should briefly define the C2HEST score in the abstract.

The ESC stands for European Society of Cardiology.

I am not sure all the information on previous medication is needed. Some medication linked (although with many doubts) with prognosis could be included, but otherwise, there is a lot of information that does not add anything to the manuscript.

Is there any information on the left ventricular ejection fraction of the patients? I understand not doing ultrasound during the COVID period if strictly needed, but I assume patients with HF should have a previous measure of the left ventricular ejection fraction.    

The section in the Result where the authors discuss the Cox results is difficult to understand.

There are too many tables. The authors give a lot of information, but I doubt it is relevant to the present manuscript.

Reference 16 might be a mistake.

 

The discussion is difficult to understand. 

Author Response

Reviewer #1:

 

We would like to thank the Reviewer for an in-depth analysis of the manuscript and for the pivotal comments provided, which have resulted in a significant improvement of this manuscript.

Ad. 1. As the Reviewer suggested, a brief summary regarding the C2HEST score in the abstract section has been done.

Ad 2 We would like to thank the Reviewer for finding a typo in the Introduction section regarding the ESC abbreviation. As result, we have fixed this error.   

Ad.3 and 6.  In order to clarify the manuscript and improve readability, in accordance with the Reviewer recommendation, we have removed several tables presenting excessive details from the main text and transferred them to Supplementary File .

Ad 4. Another vailed remark from Reviewer is focused on left ventricular ejection fraction measurement. We added a short comment focused on this issue in to the limitations section “Additionally, the study protocol did not include a routine in-hospital assessment of the LVEF (mainly due to safety concern), and the TTE was performed only in deteriorating/decompensating subjects, when needed. Hence, the allocation to the HF cohort was made on the basis of past medical history - the diagnosis of HFrEF or HFmrEF  had been made based on the TTE done prior admission to the hospital. Therefore, we decided not to present the data collected during hospitalization, based mostly on the deteriorating subjects, as they could not reflect the whole studied cohort.”

Ad. 5. We would like to thank the Reviewer for pointing out that the part of the Results section regarding the Cox analysis was difficult to interpret. As result, we have changed this section in order to be clearer in that matter.

 

Ad. 7. We would like to thank the Reviewer for finding an error in the reference number 16 we fixed it

 

Ad. 8. We would like to thank the Reviewer for a suggestion regarding the readability of the Discussion – this part of the manuscript was re-edited and subsequently read by an English speaker familiar with English in medical writing.

Author Response File: Author Response.docx

Reviewer 2 Report

The authors aimed at investigating the Usefulness of the C2HEST Score to predict the clinical outcomes of COVID-19 in patients with and without heart failure. The paper is really interesting, as few studies are investigating the C2HEST score in COVID-19 patients so far.

Some issues, however, raised by reading the manuscript:

There is a lack of information about patient' follow-up. The paper could be improved if any information of clinical outcome at 6 and 12 months of follow-up are reported.

The acronym for C2HEST Score should be reported.

The discussion should be improved. Information about CV comorbidity and therapy should be discussed more in depth, in particular the potential (or not) impact of heart failure treatments should be discussed (Arch Med Sci Atheroscler Dis. 2022 Mar 28;7:e5-e23.

Front Cardiovasc Med . 2020 Oct 9;7:585866.).

 

Growing evidence is showing how some ultrasound parameters, in particular the LUS score are predictor of worse outcome and increased risk of mortality in COVID-19 patients (Respiration. 2022;101(2):122-131. doi: 10.1159/000518516.

J Ultrasound Med. 2021 Oct 26:10.1002/jum.15849.

Respir Med. 2022 Jun;197:106826.) Since ultrasound could be a good method to stratify the prognosis of COVID-19 patients along with the C2HEST score, are there any studies evaluating this association ? If not, it could be interesting to discuss this feature as a clinical perspective.

 

Author Response

Reviewer #2:

 

We would like to thank the Reviewer for an in-depth analysis of the manuscript and for the pivotal comments provided, which have resulted in a significant improvement of this manuscript.

 

Ad.1  We are pleased to inform that in accordance with the COLOS study protocol, as a part of long-term follow up we collected data regarding  3-month, and 6-month all-cause mortality. All mentioned data is presented in the Results section (Figure 3 and Figure 4 with appropriate comment in the text). At this moment, no longer follow-up is available, we intend to collect it in July 2022 and perform subsequent detailed analysis, as June 2021 was the last month included to the study protocol.

 

Ad. 2  We would like to thank the Reviewer for a suggestion that the definition of C2HEST requires an extension. In the introduction, we have explained it as follows: C₂HEST (C2: CAD/COPD; H: Hypertension; E: Elderly [Age ≥75]; S: Systolic HF; T: Thyroid disease)

 

Ad 3. We would like to thank the Reviewer for a suggestion regarding the role of cardiovascular disorders and cardiovascular treatment in COVID-19 subjects. Therefore, the following comment in the discussion section has been added: “However, this therapy was associated with a reduction in mortality and re-hospitalization in patients with cardiovascular disease- and particularly with heart failure and coronary artery disease. Nevertheless, in terms of patients with active SARS-COV 2 infections, some safety concerns are still rising, and a intense debate is ongoing in this matter [21,22,23]. Some recently published large-population studies on COVID-19 [24, 25] have proven that the number of cardiovascular comorbidities appears to be independently associated with increased COVID-19-related death.  Noteworthy, no relationship between commonly-used CVD medications and increased risk of death due to COVID-19 was identified. Furthermore, some data suggests that specific cardiovascular drugs should be continued in order to reduce potential unfavorable cardiovascular events in the course of SARS-COV 2 infection, particularly in subjects with heart failure.”

 

Ad 4 Another valid point mentioned by the Reviewer is a remark regarding the Lung Ultrasound Score and it potential usefulness, as an addition to C2HEST risk score stratification. As result, we have commented on it as following: “… a growing number of evidence indicates that some diagnostic tools including Lung Ultrasound (LUC) can be useful for diagnosis, optimizing of treatment, and risk stratification in COVID-19 patients [32,33,34]. Therefore, an interesting approach might be a multidimensional assessment of risk factors for an unfavorable outcome of Covid-19, including the data from imaging diagnostics. A merger of the C2HEST risk score with LUC might be valuable and increase the discriminatory performance of the C2HEST score in predicting the outcomes, without an unnecessary increase in complexity of scale. Nevertheless, further studies evaluating the value of such a modified C2HEST score scale are necessary.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

The authors have resolved the issues