Case Report: The importance of initial assessment in acute pulmonary embolism

This is a case report on a case of acute pulmonary embolism with a focus on the initial assessment, risk stratification, and risk-based management. It is very well written and presents a balanced mix of typical and atypical features. The typical features make the case interesting for the young physician, while the atypical ones will interest the experienced physician. 

The typical features include the antecedent risk factor - orthopaedic surgery, the vital signs, and the symptoms. While it is uncommon for chest pain, hemoptysis, and pre-syncope to co-occur, these are all typical signs and it is interesting to find them in the same patient. 
The atypical features include the relatively young age. 

There is one major problem throughout the article that needs to be corrected. In pulmonary embolism, "high-risk probability of PE" and "high-risk PE" are two completely different things (note the words "probabality" and "of"). The first refers to the result of the assessment of the pre-test (or clinical) probability that a patient has PE at all before the gold standard test (CTPA or ventilation/perfusion scan) has been performed, and is used to decide whether to perform CTPA, because this may return false positive and may also unnecessarily expose patients to radiation. In contrast, "high-risk PE" refers to the assessment of risk of early (in-hospital or 30-days) death that occurs AFTER (or: at the same time as) a diagnosis has been made (using CTPA or ventilation/perfusion scan) based on a series of clinical, laboratory, and echocardiographic parameters, and is used to decide how to manage the patient (to sum up, low-risk patients can go home immediately, intermediate-risk patients may require only medium- or intensive-care monitoring, high-risk patients may require systemyc thrombolysis and intensive care monitoring). There is confusion between these two points in the Abstract and the Discussion. But to the PE clinician "high risk of PE" and "high-risk PE" mean, and should mean, two totally different things belonging to two separate stages of the management process. I detail below where the wording needs to be adapted to prevent this potentially dangerous misunderstanding. 

There is also a very important missing point: an explicit statement of the risk stratification class. This must be made as clear as possible, because it guides the management of acute PE according to all current guidelines. In particular, it should be stated very explicitly that this patient was eligible for intravenous thrombolysis (which was indeed performed) because its risk class was high (high-risk PE) according to the European (ESC) guidelines, or, alternatively, massive according to the US guidelines. This point is of utmost importance, as this is the key element for the decision-making in acute PE. 

Recommendations

ABSTRACT
1) even among clinicians working with patients with pulmonary embolism and devoting their career to clinical research in pulmonary embolism and, to the best of my experience, in most countries, it is very uncommon to refer to the S1Q3T3 pattern in the electrocardiogram as "McGinn-White Sign". It is much more common to refer to it as, indeed, "S1Q3T3 sign". I therefore suggest that the Authors write "S1Q3T3 pattern (McGinn-White sign)" instead of "McGinn-White sign"; that is, the eponymic form should be enclosed between parentheses after the more traditional one. For instance, the way the sign is described in the Case Presentation is entirely understandable. If the word limit for the Abstract is reached, just write "S1S3T3 pattern" without eponymic. 
2) similarly, "Palla's sign" is relatively uncommon and I suggest to instead write "enlarged right pulmonary artery (Palla's sign)". Again, much better in the Case presentation. If the word limit for the Abstract is reached, just write "enlarged right pulmonary artery". 
3) the exact spelling of the echocardiographic sign the Authors refer to is "McConnell sign" rather than "McConneal sign" (see for instance (Konstantinides SV.et.al., 2020 ref 2 ). Please correct.
4) This sentence cannot be correct: "CTPA was performed due to the moderate-high risk PE". The sentence suggests that, "because of" ("due to") a moderate-high risk PE, a CTPA was performed; that is, that it was known that the patient had a moderate-high risk PE before the CTPA was even performed. But it is impossible for a diagnosis of PE to be posed without imaging (CTPA or ventilation/perfusion scan). Therefore, the Authors must have meant either "due to the moderate-high risk pre-test risk of PE" or "A CTPA showed hyperattenuating and partial filling defect, confirming a moderate-high risk PE". In the latter case, "moderate-high" would refer to the PE risk stratification and would not be correct (in the European guidelines, the naming "intermediate-high" is used; in the US guidelines, the naming "submassive" is used). In the case presentation, a correct sentence is used: "(...) Wells' score of 7 showed a moderate-high risk for PE" (the "for" makes all of the difference!), revealing that the sentence in the Abstract fell in the first of the cases I described. Please correct accordingly.
5) "adequate anticoagulation" does not describe exactly what is adequate in this context. It would be more informative to write "therapeutic" anticoagulation (as opposed to prophylactic or sub-therapeutic). 

KEYWORDS
6) I suggest that the keyword "Risk stratification" is added. 

INTRODUCTION
7) For the sentence in the Introduction, a more recent and direct reference for the numbers of deaths in Europe is Barco S.et.al., 2020 ref 1 which should replace ref. 3. However, current reference 3 may be kept for the first sentence of the Discussion ("...helps provide better outcomes (3)"). 
8) It is not entirely correct to write "Computed Tomography Pulmonary Angiography (CTPA) has been proposed as a standard imaging modality to diagnose PE." because CTPA has not merely been proposed: it is in fact the current recommended standard, and has been for a long time now (over 20 years). This formulation may be misleading to younger doctors. I suggest the Authors write "Computed Tomography Pulmonary Angiography (CTPA) is the current standard imaging modality to diagnose PE." 

CASE PRESENTATION
9) The sentence "we used PE’s risk assessment to better diagnose the involvement of PE." is linguistically very unclear (one does not "diagnose" an "involvement" in medicine, but only a disease; also, one does not diagnose "better" or "worse" - one either diagnoses or does not diagnoses). I think that the Authors should write clearly what they did: "We assessed the pre-test probability of PE based on the patient's clinical presentation". This sentence describes exactly the meaning and purpose of scores such as the Geneva score, the Wells score, or the Leiden score: establishing the probability a patient has a PE based solely on clinical and laboratory parameters and not on the diagnostic test CTPA (pre-test probability) in order to assess whether it is meaningful to perform a CTPA to diagnose PE. 
10) "referring hospital" would be more common word usage than "referrer hospital". 
11) please correct "before referred to our hospital" into either "before he was referred to our hospital" or "before referral to our hospital". 
12) I believe it should be Norepinephrine rather than Norepinefrin - unless the latter is a commercial name for the active ingredient/active principle?
13) For the sake of conciseness, the Authors may write "Laboratory testing revealeed incraed D-dimer (...)" instead of "We performed laboratory examination, which resulted in (...)". 
14) The numbers between brackets here are quite crowded: "(Class II, low risk 1.7-3.5% 30-days mortality rate)". It may be clearer if rewritten as "(Class II, low risk; 30-days mortality rate 1.7 to 3.5%)".

DISCUSSION
15) The sentences "However, clinical features and baseline findings often cannot unequivocally rule out PE, whereas follow-up examination (CTPA) is not cost-effective. This causes a follow-up examination to be carried out only in intermediate-high risk PE.2,3" does not seem to be correct. CTPA is not a "follow-up examination" in PE: it is the gold standard for diagnosis! In medicine, the wording "follow-up" is reserved for the long-term (chronic) monitoring of patients who have already a diagnosis and are currently stable; it is not used in acute/emergency medicine. The sentences may be misleading, as they suggest to the reader that CTPA is only performed in intermediate-high risk PE. This is absolutely not the case - even low-risk PE must have been diagnosed before it can be assessed as being low risk, and this must absolutely have occurred with either CTPA or ventilation/perfusion scan. I checked references 2 and 3 at the end of the second sentence, and I think there is a misunderstanding: CTPA should be carried out only in patients with a "intermediato to high pre-test probability of PE", NOT in patients with "intermediate-high risk PE" (the latter means that one already knows that the patients has PE because the CTPA has already been carried out, and that the patient has a high probability of DYING from PE, not of HAVING PE). I think rewriting the two sentences as follows would solve the issue: "However, clinical features and baseline findings often cannot unequivocally rule out PE, whereas CTPA, that can diagnose a PE, is not cost-effective in all patients, as it may lead to false positives and unnecessarily expose them to radiation. This causes the CTPA to be considered appropriate only in patients with a intermediate to high clinical risk of having a PE (2, 3).". In addition, please refer the reader, for maximum clarity, to a discussion of the latest guidelines where this point is examined explicitly, such as ref 1  (in addition to existing references 2 and 3). Note that the following paragraph is written in a perfectly correct way - the point is the SUSPICION of PE.  
16) "Tachycardia is followed by S1Q3T3 pattern (...) is a strong predictor of PE": first, please remove the "is" (probably a type); second, it is not entirely true that this pattern is a strong predictor of PE; it is not very specific; to the best of my knowledge, less than 30% (I just noticed that you indeed write 25-30% in the next sentence, confirming what I thought). In biostatistics, usually, only positive predictive values above 90% justify the wordisng "strong prediction". I would rather write "strongly suggests PE". 
17) "We found patients with (...)" supposedly refers to the patient described in this report; then, it would better be written as "In the patient we described in this Report, clinical signs, ECG and CXR findings all supported a moderate to high pre-test risk of PE (...)" (note that, once again, it would be wrong to write "moderate-high risk PE", because this wording would refer to the risk of early death).
18) "Most patients will not survive within the first hours of the event.": this is quite misleading, as the overall case fatality of PE does not go beyond 5%, and that hardly qualifies as "most patients". Only the subset of patients assessed as high-risk have a higher fatality. Please correct into "Patients with a high-risk PE may not survive beyond the first hours of the event". 
19) Please correct "McConneal" into "McConnell sign".  
20) In tthe sentence "Following an acute embolic event, the patient is at risk for fatal circulatory collapse due to right-sided heart failure and subsequent embolism.", please remove "subsequent embolism", because this is simply plainly wrong - the pulmonary embolism itself (the one already there) causes right-sided heart failure, and not a new, "subsequent" embolism following the right-sided heart failure. Please add a sentence detailing that therefore, once PE has been diagnosed, the risk of death from right-sided heart failure must be assessed based on several clinical and imaging parameters, so that the patient is assigned to a formal class that in turn determines; for the appropriate word use read and cite the 2019 ESC guidelines (Konstantinides SV.et.al., 2020 ref 2 
) and/or, for a shorter practical example, Gallo A.et.al.,2019  ref 3 
21) "CTPA is mandatory in cases of high-risk PE. ": once again, this is very misleading, because "high-risk PE" means "PE with high risk of death" and not "high pre-test probability of having PE". Please write "CTPA is mandatory in patients with a high pre-test probability of PE" or "CTPA is mandatory in patients with a high clinical probability of PE".  
22) There is duplication of information and some kind of circularity in the DIscussion, because there are two separate paragraphs both on the diagnostic value of CTPA: the paragraph suarting with "most patients will not survive within the first hours (...)" and again the paragraph starting with "CTPA is manadatory in cases of high-risk PE". Note how they both report the same piece of information on the sensitivity and specificity of CTPA! Please merge the two paragraphs into a single paragraph that should precede the paragraph on the death risk stratification (which is the one starting with "Following an acute embolic event"). This is the most obvious and logical order: first, discuss the problem of diagnosis (pre-test probability to decide whether to perform CTPA); then, discuss the problem of risk of death/prognosis assessment. 
23) The two sentences "Pulmonary embolism blocks pulmonary blood flow, resulting in right heart failure. Acute right heart failure due to lack of systemic output is the leading cause of death in high-risk PE." repeats for the second or third time what has already been said. This paragraph should re-focus on the current case and discuss treatment. Please remove the two sentences. 

CONCLUSIONS
24) Once again, correct "moderate-high risk PE and was supported by clinical (...)" into "moderate to high pre-test probability of PE as suppored by (...)". 
25) Correct "The use of PE’s risk assessment will help determine the needs of CTPA" into "The assessment of clinical (pre-test) probability of PE helps to decide on the need of CTPA". 
26) Correct "in the Acute Cardiac Care Setting" into the more general and appropriate "in case of suspicion of PE in the acute setting". 
27) Correct "Utilization of CTPA for the immediate diagnosis of pulmonary embolism patients helps determine the patient management accurately. Adequate therapy can reduce the risk of mortality and morbidity from pulmonary embolism." into "If a PE is diagnosed, CTPA also supports the subsequent assessment of the risk of early death from PE, guiding the choice of adequate therapy and ultimately reducing the risk of mortality and morbidity from PE".