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Thank you for revising Figure 3. This paper is now acceptable for publication. Congratulations.
Thank you for addressing the previous concerns. I note that there are errors in the KM graphs and statistics in Figure 3A and 3B. Please rectify.
Thank you for your revised work. However, residual concerns remain that prevent acceptance in its current form. Please refer to the reviewer's comments and the following:
1. LM disease has been left out of the abstract. Please address.
2. Introduction section of the manuscript is too abbreviated. Please expand to give more context to the study.
3. It appears in the method that inpatients with atypical chest pain were also included. Other parts of this manuscript did not seem to reference this and focus on patients from the ER?
4. Line 289-291 (last sentence in conclusion) appears redundant and out of place.
5. KM curves: Curtailment of follow-up duration is needed as the numbers are too few at the far right of the curves. Please respond with statistical reasoning and back-up.
Line 119-120 - 'Briefly, diagnostic catheterization and intervention were performed within 72 hours as possible after the diagnosis of NSTEMI was confirmed' does not make sense. Should read 'as soon as possible'?
Line 264 - should read 'A previous study....'
No comment
No comment
The authors have satisfactorily responded to previous concerns. Specifically, I am satisfied that revascularisation strategies were largely standardized across groups and therefore unlikely to contribute to significant differences in long-term outcomes. In addition, post-PCI treatment also seems to be standardized and appropriate. The clinical applicability of these results have also been addressed in the discussion section.
Thank you for making changes. As a dataset descriptor, it would still be good to know about the gender breakdown of the entire study population and state this. It can be seen that there were 77.5%, 68.1% and 65.7% males in the groups with no ST change, inverted T wave and ST depression respectively, which means the proportion of males in the total group must be in the low 70s, but I think putting this in early in the results is best. This kind of descriptor makes it easier to compare data across studies.
As a slight grammatical comment, we would usually say 'an' ST depression/decrease rather than 'a' ST depression/decrease in spoken and written English, so this could be changed where it appears in the manuscript for easier reading.
There are a few parts of the corrections that would benefit from other slight grammatical corrections, if they could be proof-read again.
The design is adequate for the question being asked.
Thank your for including a description of the total revascularisation vs incomplete revascularisation proportions in the overall group. It would be ideal to see if incomplete revascularisation was a predictor of the primary or secondary end-point as well, if you have this data.
Overall this is an improved manuscript.
Your manuscript underwent independent peer reviews and both reviewers have highlighted several important issues for you to address.
In particular, details on how these patients are managed in the follow-up period is of importance to address. Were the risk factors treated? Glucose, lipids and blood pressure? Did their medications differ?
In the survival graphs, the authors are encouraged to include numbers at risk at different time-points during follow-up.
Given the mean follow-up duration was 66 months, why are the survival curves shown beyond this to 96 months?
More details on PCI and residual disease ought to be presented.
• The manuscript is generally well-written with appropriate use of professional English language throughout.
• The title does not match the abstract and manuscript – the title states the population is NSTEMI patients who underwent coronary angiography. However, the rest of the manuscript says the study population is NSTEMI patients who underwent PCI.
• The introduction is short but adequately identifies absence of contemporaneous data on ECG morphology and long-term mortality in NSTEMI patients. It is appropriately referenced.
• The manuscript conforms to PeerJ standards.
• Figures are relevant to the study and are well-formatted and well-presented.
• The full raw data .csv file has been supplied.
• The research question is well-defined in the introduction. It is an interesting question and it is indeed surprising that ECG morphology in NSTEMI has not been evaluated before in the PCI era.
• The study appears to have been carried out in a rigorous and replicable manner. Ethical approval has been sought and referenced. The population studied is well-defined. However, the inclusion and exclusion criteria could be more explicitly stated. For example, patients undergoing PCI after 72 hours were excluded from the study but this has not been written in the ‘Setting and patient population’ section of the manuscript.
• ECG definitions of ST depression and T wave inversion appear to be appropriate.
• A number of baseline characteristics have been included in the analysis but the methods for collecting these baseline characteristics have not been included in the methods section. For example, at what point were bloods for creatinine and eGFR taken and when was baseline echocardiography done?
• Methods section lacks detail regarding angiography and stenting procedures. What was involved in the decision making process for placing stents? Were only culprit lesions stented or were all radiographically significant stenoses treated?
• Post-PCI management has not been outlined. Were patients treated according to current clinical guidelines? 9 months of dual antiplatelets were given but what about secondary prevention medications. Were all patients referred for cardiac rehabilitation? How was compliance?
• Statistical methods are appropriate for the study.
• The raw data provided is adequate and the data collection appears to have been robust.
• There are some potentially confounding factors which have not been assessed. For example, time to angiography has not been assessed. All patients underwent PCI within 72 hours but was there a difference in outcomes in patients who underwent PCI within 24 hours compared with those who underwent PCI after 48 hours? Furthermore, bystander coronary artery disease has not been reported. The presence of any untreated bystander disease may influence long-term outcomes in these patients. Was it assessed and could it be included in the analysis?
• The clinical importance of these results have not been adequately outlined in the discussion and conclusion sections. ST depression is independently associated with poor long-term outcomes. This is despite (presumably) optimal medical and interventional treatment as per current clinical guidelines. Can anything be done, therefore, to improve the outcomes associated with ST depression or is the association simply due to the other risk factors also associated with ST depression such as advanced chronic kidney disease and diabetes?
• This retrospective observational study explores the relationship between presenting ECG morphology and long-term mortality in patients with non-ST elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). The study identifies ST depression as a significant independent risk factor for long-term mortality.
• Whilst the idea is novel and the study is well carried-out, the paper suffers from significant confounding making interpretation of the results difficult. Although it is interesting to note that ST depression is associated with significant risk factors and poor long-term outcomes when compared with T wave inversion and non-specific ECG changes, there are a lot of confounding factors which obscure the real effect of ST depression. The effect of ST depression seen in this study may simply be due to the association of risk factors which are known to be important in long-term outcomes. Poorer outcomes may also be related to factors such as bystander disease which has not been assessed in this study.
• In addition, there does not seem to be significant clinical applicability of these findings. How will this study change clinical management of patients with ST depression? Management of risk factors such as diabetes is already a key pillar of guideline-directed management of coronary artery disease.
• The methodology described within the manuscript is lacking important details particularly pertaining to the PCI procedures.
Ideally state the number of male patients in the overall data-set as part of descriptors in the abstract.
Line 164: sentence needs rephrasing.
Line 200: can take the word 'significantly' out of the sentence.
Lines 87 and 107: Were patients with some ST elevation, but that did not meet STEMI criteria (and were not attributed to eg LBBB/LVH/male pattern etc) all included in the 'no significant ST-T change' group, or were patients with these kinds of ST changes excluded from this study? This may be worth clarifying.
Exclusion of patients with PCI delayed >72 hours for other aetiologies - were the patients too sick or eg kidney function too poor for angiography, or were there other diagnoses suggested as the cause for troponin rise? It might be worth explaining in more detail why these patients were excluded.
Are ACS patients treated with DAPT for 9 months rather than 12 months in local guidelines?
While not absolutely essential, it would be good to know a bit about how many patients had complete revascularisation at the index procedure presenting with NSTEMI, vs culprit only +/- staged procedures, as recent data has emerged in STEMI patients. It is noted the stent number does appear similar in all 3 groups.
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