Impact of Female Gender on Acute and Mid-Term Mortality in Patients with ST-Segment Elevation Myocardial Infarction during the Pandemic Era
, Carlo Avallone 1, Andrea D’Errico 1, Domitilla Gentile 2, Dagnachew Cigno Membo 1, Gabriele Tumminello 1 and Stefano Carugo 1
Round 1
Reviewer 1 Report
Dear authors, thank you for the interesting study
There are several points to be addressed.
Mention in which region the study was carried out. And, probably, discuss your finding in comparison of data of Spadea T (https://doi.org/10.1038/s41598-021-00982-4).
Where are patients symptomatic or not? Their condition (PaO2; peripheral O2 saturation; chest X-ray) could affect the results.
What drugs were used for treatment (as hydroxychloroquine in COVID-19 patients can prolong QTc).
Where COVID-19 patients were considered ill during the time of interventions as they could be considered healed only after resolution of symptoms and two consecutive negative tests for SARS-CoV-2 at 24-h intervals.
Please briefly describe the possible reasons and pathological mechanisms leading to increased mortality (10.3390/ijms23031716).
Author Response
The reviewer’s comments have been highly appreciated and very useful in the revision of the manuscript.
Response to Reviewer 1
Reviewer #1: Dear authors, thank you for the interesting study. There are several points to be addressed.
- Mention in which region the study was carried out. And, probably, discuss your finding in comparison of data of Spadea T (https://doi.org/10.1038/s41598-021-00982-4).
Reply. We thank the reviewer for the suggestion. Our study was carried out in Milan, Lombardy, one of the most affected region during the pandemic period. As reported also by Spedea and colleagues, in-hospital mortality was significantly higher respect to the historical trends, especially in the first and darkest period of pandemic. We now better specify this issue in the discussion, see page 6 lines 26-28.
- Where are patients symptomatic or not? Their condition (PaO2; peripheral O2 saturation; chest X-ray) could affect the results.
Reply. We thank the reviewer for the suggestion. We have not reported data about gas exchanges at baseline and during the hospitalization but there are no differences in term of incidence of COPD in the two subgroups neither they have no differences in term of COVID infection and need of ventilatory support. Consequently, the two subgroups did not have different incidence of ventilatory complication rate. Even if we have no data it is supposable that there is an homogenous distribution of respiratory condition in the two subgroups not affecting the final results.
What drugs were used for treatment (as hydroxychloroquine in COVID-19 patients can prolong QTc).
Reply. We thank the reviewer for the suggestion. No COVID-19 patients were treated with hydroxychloroquine.
Where COVID-19 patients were considered ill during the time of interventions as they could be considered healed only after resolution of symptoms and two consecutive negative tests for SARS-CoV-2 at 24-h intervals.
Reply. We thank the reviewer for the comment. Because all the patients were hospitalized in emergency conditions, they were all considered potentially ill until the first nasopharyngeal swab test was performed. After the diagnosis of COVID-19 infection they were considered and treated as ill until the resolution of symptoms and two consecutive negative swab tests according to guidelines.
Please briefly describe the possible reasons and pathological mechanisms leading to increased mortality (10.3390/ijms23031716).
Reply. We thank the reviewer for the suggestion. The high mortality rate in our population was mainly driven by a 6 times greeter incidence of respiratory complications among COVID-19 patients without any differences in term of cardiovascular mortality. We now specify this issue in the discussion, see page 6 lines 28-30.
Reviewer 2 Report
The authors studied 283 consecutive STEMI patients undergoing urgent coronary angiography and pPCI, a total of 25 patients (8.6%) resulted positive for COVID-19 among them. They found that in the acute phase, the only other independent predictor of mortality was COVID-19 infection, secondary to the higher rate of respiratory complications, without any difference in terms of MACE. The impact of COVID-19 infection on mortality was completely lost at 1-year follow-up. The manuscript is structured and well written, and the clinical question is of great importance.
Author Response
The reviewer’s comments have been highly appreciated and very useful in the revision of the manuscript.
Response to Reviewer 2
Reviewer #2: The authors studied 283 consecutive STEMI patients undergoing urgent coronary angiography and pPCI, a total of 25 patients (8.6%) resulted positive for COVID-19 among them. They found that in the acute phase, the only other independent predictor of mortality was COVID-19 infection, secondary to the higher rate of respiratory complications, without any difference in terms of MACE. The impact of COVID-19 infection on mortality was completely lost at 1-year follow-up. The manuscript is structured and well written, and the clinical question is of great importance.
Reply. We thank the reviewer for the comment.
Reviewer 3 Report
Dear Authors,
first of all I would like to congratulate you the interesting study. However I hove some major and minor comments:
- I suggest adding the another parameter apart from the hemoglobin levels - the number of patients with the diagnosis of anemia to the analysis
- Could you describe the reasons of DOACs administration and the prevalence of this disorders (I.e. atrial fibrillation)
- In my opinion in this study that analyze the women patients the analysis of GFR instead of creatinine is more appopriate
- Did you analyze the another end-points beside overall mortality?
- I think the flow-chart describing the study population would be a good idea to present the methods of study.
- The more detailed analysis of COVID subgroups is necessary
- The limitations should be expanded
- The additional analysis of pre-pandemic group of patients and the difference in comparison of pandemic group would be another point providing better quality of data and improving the paper.
Author Response
The reviewer’s comments have been highly appreciated and very useful in the revision of the manuscript.
Response to Reviewer 3
Reviewer #3: Dear Authors, first of all I would like to congratulate you the interesting study. However I hove some major and minor comments:
- I suggest adding the another parameter apart from the hemoglobin levels - the number of patients with the diagnosis of anemia to the analysis
Reply. We thank the reviewer for the suggestion. We re-analyzed data focusing on anemia and we found as expected a higher incidence of anemia among female. We specified the issue in methods and results, see page 2 lines 18-20, page 3 line 12 and Table 1.
- Could you describe the reasons of DOACs administration and the prevalence of this disorders (i.e. atrial fibrillation)
Reply. We thank the reviewer for the comment. All the DOACs prescribed were for atrial fibrillation. The higher incidence in female gender may be probably explained by the older age of the group, see Table 1.
- In my opinion in this study that analyze the women patients the analysis of GFR instead of creatinine is more appropriate
Reply. We thank the reviewer for the suggestion. We calculate eGFR and report in the Table 1. The result confirm the previous findings with creatinine with a significant lower renal function in the female gender group, see page 2 lines 19, 20; page 3 lines 14,15 and Table 1.
- Did you analyze the another end-points beside overall mortality?
Reply. We thank the reviewer for the comment. The size of the population and the retrospective type of the study forced us to focalize only on mortality.
- I think the flow-chart describing the study population would be a good idea to present the methods of study.
Reply. We thank the reviewer for the suggestion. The flow-chart of the study is a good idea to show graphically the structure of the study but because it is a retrospective study, we included all consecutive patients admitted for STEMI in our hospital during the defined period.
- The more detailed analysis of COVID subgroups is necessary
Reply. We thank the reviewer for the suggestion. We performed several statistical analyses on the COVID subgroups but the small sample size limited all the power of the findings. For that reason, we did report these analyses.
- The limitations should be expanded
Reply. We thank the reviewer for the suggestion. We now insert a dedicated limitation section accordingly. See page 8 lines 3-8.
- The additional analysis of pre-pandemic group of patients and the difference in comparison of pandemic group would be another point providing better quality of data and improving the paper.
Reply. We thank the reviewer for the suggestion. The analysis of pre-pandemic group is a very idea but we are not able to perform this kind of analysis because in the pre-pandemic period we were not an Hub-center and the two populations are not comparable.
Round 2
Reviewer 3 Report
Dear Authors,
thank you very much for considering my suggestions. In my opinion in this form this study is applicable for publish in Women.
Yours faithfully
Author Response
We thank the reviewer for the comment
