Case Report: Wellens syndrome in acute critical coronary occlusion saved by collateral

Background It is important and challenging to distinguish between acute myocardial infarction and Wellens syndrome due to its time to intervention. Difficulties in differentiating between subtypes could mean the patients are overtreated or receive undertreatment. Case report A 57-year-old man was referred to our emergency ward with acute onset of chest pain. Electrocardiograms changes were suggestive of type A Wellens syndrome. Nitroglycerin was administrated, the patient's chest pain disappeared, and we planned an early invasive strategy. He had a previous documented electrocardiogram before he went for catheterization and based on the second electrocardiogram changes were suggestive of an ST-elevation. As the result of the invasive strategy, it was found that there was single-vessel disease, critical occlusion in the middle of the left anterior descending artery coronary artery with collateral from the right coronary artery. After two days of observation in the Intensive Cardiovascular Care Unit, the patient improved and was transferred to Low Care Unit. Conclusions The case highlights Wellens syndrome in acute critical occlusion with collateral artery.


Introduction
Acute ST-elevation myocardial infarction (STEMI) equivalents represent coronary occlusion without meeting the traditional ST-elevation criteria.It's important to recognize these patterns in a timely fashion, since STEMI equivalent patterns often require emergent or urgent percutaneous coronary intervention (PCI) to minimize morbidity and mortality.One of the most common STEMI equivalent is Wellens syndrome.
Wellens syndrome is characterized by specific an electrocardiogram profiles in the precordial lead, particularly deeply inverted or biphasic T waves in leads V2-V3, that is highly specific for critical, proximal stenosis of the left anterior descending (LAD) coronary artery. 1 The incidence rate is 10-15% of all patients with acute coronary syndrome. 2pical Wellens syndrome usually presents to the emergency department with pain-free symtomps and normal or slightly elevated troponin level.However, it is important to recognize the electrocardiogram patterns as these patients are at high risk for impending large anterior wall myocardial infarction.Thus, Wellens syndrome has often been considered an STEMI equivalent.
On the other hand, the presence of coronary collateral circulation can change an electrocardiogram picture that should be STEMI due to total or near total occlusion of the left anterior descending artery, turning into an electrocardiogram of Wellens syndrome.
In this case, we present Wellens syndrome in acute total occlusion saved by collateral.Significant collateral circulation is believed to improve clinical outcomes, especially in patients with acute coronary syndrome.

Case report
A 57-year-old man presented at Dr. Soetomo General Hospital, Surabaya, Indonesia, with sudden chest pain that started half an hour after eating and lasted two hours.He had a history of poorly controlled type 2 diabetes mellitus, poorly controlled hypertension, hypercholesterolemia, and a history of angina three years ago without undergoing a revascularization procedure.There was no social history of smoking nor drinking.He was brought to the emergency department with acute onset of substernal chest pain and diaphoresis.The chest pain started two hours before he was brought to the emergency ward.His chest pain score was four on the visual analogue scale (VAS).Nitroglycerin was administrated then the patient's chest pain disappeared.Physical examination on admission revealed a temperature of 36.7°C, a pulse of 99 beats/min, blood pressure of 170/100 mmHg, respiration of 22/min and oxygen saturation was 95% on room air.He was overweight with a BMI of 29.4 kg/m 2 .Others physical examination were unremarkable.

Timeline
On day one, the patient was admitted to our emergency ward due to abrupt and sudden onset chest pain with visual analogue scale 4/10, that was not relieved by nitroglycerine.Electrocardiogram showed a biphasic T wave in V2-V4 (type A Wellens) (Figure 1).The patient was diagnosed with non-ST elevation myocardial infarction.On day two, transthoracic echocardiography revealed regional wall motion abnormality with reduced ejection fraction.Electrocardiogram changed into an anterior acute ST-elevation myocardial infarction.Then, we planned to perform early invasive strategy.Coronary angiography revealed a total occlusion in the middle left anterior descending coronary artery.We performed percutaneous coronary intervention and stenting in the lesion.On day four, the patient improved significantly during the critical period and was transferred to low care.On day five, Electrocardiogram revealed an inverted T wave in V2-V6 (type B Wellens) (Figure 2), and then the patient was discharged without any sequelae.

Investigations
Significant laboratory findings suggested significant raised of highly sensitive troponin I (hs-TnI) levels 2,058 ng/ml (normal value: <0.02), HbA1c 8.5% (normal value: <6.5%), and complete blood count, renal function test, liver function test and serum electrolyte were within normal limits.Electrocardiography in the emergency department (Figure 1) showed an ST segment of less than 1 mm, and there was a biphasic T wave in V2-V4 (type A Wellens) (Figure 2); REVISED Amendments from Version 2 -Deleted for several repeated words -Minor changes for case presentation to make it fully comprehendible -Minor changes for Video 1 and Video 2 (anonymous patient identity) Any further responses from the reviewers can be found at the end of the article echocardiography was therefore performed showed ejection fraction was 48%, there was left ventricular dilatation (left ventricular internal diameter end diastole 6.1cm) and eccentric left ventricular hypertrophy (left ventricular mass index: 132.62 g/m 2 ; relative wall thickness: 0.320); from segmental analysis, it was found that there was hypokinetic in the anteroseptal (basal-mid) region, septal (apical) region; others regions were within normal limits.
Before the invasive strategy was done, the patient had another electrocardiography eight hours after the first electrocardiogram, based on the second (Figure 2).The electrocardiogram showed ST-segment elevation changes that were greater than 1 mm.The early invasive strategy (Figure 3 and Figure 4; Extended data: Video 1 and Video 2) 3,4 showed that the left anterior descending artery had a critical occlusion of 99% in the middle of left anterior descendants coronary artery  (Figure 3).The left circumflex coronary artery had non-significant stenosis of 40% proximal and 65% distal, and right coronary artery had non-significant stenosis of 55% distal.The right coronary artery had Rentrop grade 2 collateral arteries that supply blood to the middle of left anterior descending coronary artery (Figure 4).

Differential diagnosis
• Other STEMI equivalent patterns: Hyperacute T-waves, de Winter T-waves, Isolated posterior MI, T waves upright in V1.It is important to remember that an electrocardiogram is not 100% sensitive for coronary occlusion and that the absence of STE does not rule out an MI.
• Persistent juvenile T-wave pattern: patients are typically under 30 years old with asymmetrically inverted T-waves in V1-V3.
• Digitalis effect: diagnosis of digitalis toxicity can be ruled out since there are no history of digitalis consumption.• Acute myocarditis: no history of viral illness nor influenza-like illness.
• Preexcitation syndromes: no delta waves nor prominent R waves in V1-3, no shortening PR intervals.Concealed pathway can't be rule out, however, our patient never experiences any tachyarrhythmias episode.
• Later stages of pericarditis: physical examination didn't find any friction rub.Echocardiography didn't find any pericardial effusion nor constrictive pattern.
• Pulmonary embolism: has symptoms of chest pain, but the electrocardiogram shows S1Q3T3.It means the presence of an S wave in lead I (indicating a rightward shift of the QRS axis) with a Q wave and T inversion in lead III.
• Cocaine users: has electrocardiogram patterns like Wellens, called "pseudo-Wellens syndrome", due to vasospasm of the coronary arteries.
• Central nervous system disorders: disorders of the central nervous system usually cause abnormalities in ventricular repolarisation.However in this case, no history of central nervous system trauma, stroke, tumor or infection.

Treatment
In accordance with the 2020 European Society of Cardiology Guidelines for Acute Coronary Syndrome, 5 our patient received an acetylsalicylic acid loading dose of 300 mg followed by 100 mg once daily, high dose statin with Atorvastatin 40 mg once daily at night, Bisoprolol 2.5 mg once daily, Ramipril 5 mg once daily in the morning, Fondaparinux injection 2.5 mg subcutaneous once daily, IV nitroglycerine 20 μg/minute for hypertension; the patient's angina subsided.He was also receiving basal insulin bolus for his diabetes.An early invasive strategy was carried out and the patient was then moved to the ICCU.

Outcome and follow up
Our patient improved significantly during the critical period.After two days in the ICCU, he had no complaints.Based on physical examination, he was afebrile.His heart rate was 70 beats per minute, with blood pressure 123/70 mmHg, respiratory rate 18 breaths per minute, and peripheral oxygen saturation was 95% with a nasal cannula of three litres per minute.Our patient was no longer using nitroglycerine pump and anticoagulant, and he was transferred to the low-care unit.After three days in the hospital, the results of the ECG examination showed an inverted T wave in V2-V6, and then the patient was discharged without any sequelae.After one month, the patient was well controlled for his disease without any sequelae.

Discussion
Current STEMI criteria leaves the clinician restricted in early-decision making processes if specific measurements are not met.Under the STEMI/NSTEMI paradigm, up to 30% of patients we classify as NSTEMI are consistently found to have missed acute coronary occlusion. 6Although these patients often end up receiving intervention at a later stage (24-72 hours) into admission, it is usually too late to salvage ischaemic or infarcted tissue and they are exposed to significant increases in morbidity and mortality.The term "STEMI-equivalent" is outdated.Patients with acute occlusion not meeting STEMI criteria may be an underserved, underidentified subgroup of acute coronary syndrome patients who would benefit from emergent intervention. 7erefore, in 2018, Meyers, Weingart and Smith introduced the concept of Occlusion Myocardial Infarction through the Manifesto. 8Since this, there has been gaining awareness that ST-elevation on electrocardiogram is most likely an unreliable tool for detecting patients that will benefit from PCI, and that a shift is required to a more reliable paradigm for detecting acute coronary occlusion.Occlusion Myocardial Infarction is a branch of the acute coronary syndrome algorithm representing near or total occlusion with insufficient collateral circulation causing active infarction.On the other hands, Non-Occlusion Myocardial Infarction (NOMI) explains no occlusion nor sufficient collateral circulation to avoid active infarction.Patients with Occlusion Myocardial Infarction are those with benefit from emergent reperfusion therapy, and in which the benefits outweigh the risks of this invasive procedure. 9ellens electrocardiogram pattern is commonly found in a patient with total or near total occlusion in the proximal left anterior descending coronary artery.It is commonly associated with NSTE-ACS, followed by new onset angina CCS III-IV or crescendo angina, without increased cardiac markers. 10The spontaneous transformation from Wellens type A ECG pattern into Wellens type B ECG pattern is a rare case.It reflects a pattern of electrocardiogram that sometimes changes due to occlusion and spontaneous reperfusion from the collateral coronary artery.Type A and type B Wellens particular for critical, proximal stenosis of the left anterior descending (LAD) coronary artery. 11Criteria for diagnosing Wellens syndrome include all of the following 12,13 : • Type A Wellens describes a pattern of electrocardiogram that shows biphasic T wave in the lead V2-V4 • Type B Wellens describes a pattern of electrocardiogram that shows T inverted in the lead V2-V4 • History of angina • An electrocardiogram without Q wave • Normal or minimally elevated troponin levels • ST segment isoelectric or minimally elevated (<1 mm) In this case, the first electrocardiogram showed a biphasic T wave in lead V1-V4 (Wellens type A) and it was minimally elevated (<1 mm).After a few hours before the invasive procedure, the second ECG showed a change in ST-segment elevation of more than 1 mm.In this case, the patient's ECG and troponin level showed Wellens syndrome.However, after a few hours the patient's electrocardiogram showed dynamic changes, namely an increase in elevation in the ST segment (>1 mm).An abnormal T wave ischemic pattern may persist, remaining between hours to weeks, even when the patient is asymptomatic without chest pain. 7T wave abnormalities can be normalized or evolved into ST-segment elevation in the symptomatic patient with Wellens syndrome.The mechanism responsible for these electrocardiogram findings is repolarization heterogeneity resulting from reperfusion of a briefly occluded left anterior descending.This could explain the evolution of T-wave modifications. 14,15In this case, there was complete occlusion in the middle left anterior descendents coronary artery, but the patient received collateral artery supply from the right coronary artery so that the electrocardiogram feature mimicked the critical occlusion picture in the proximal left anterior descending coronary artery.
The collateral of the coronary artery is classified into five grades.Collateral grade 0 reveals no flow between the collateral of the coronary artery.This condition can occur when several collateral arteries are visible yet not angiographically apparent at any other time.Collateral grade 1 flow reveals a barely apparent collateral coronary artery.Sometimes, there might be an unclear connection with the significant epicardial coronary artery.Collateral grade 2 flow reveals a moderately opaque collateral coronary artery but it was only present through 75% of the cardiac cycle.Collateral grade 3 flow reflects a well-opacified collateral coronary artery while the column of dye is well defined (i.e., >0.5 mm in diameter), but it was <0.7 mm wide throughout most of its length.Collateral grade 4 flow mimics collateral grade 3. The collateral is very well opacified, fills antegrade, and is very large.It was >0.7 mm in diameter throughout its length. 16,17e cardiac catheterization results found that a collateral artery originating from the right coronary artery supplied the mid-distal left anterior descending coronary artery.Therefore the heart muscle that should have been severely damaged due to not getting blood supply from the left anterior descending could still survive due to the presence of the collateral artery.Previous data has established that enough collaterals can prevent ischemia and directly induce spontaneous reperfusion in one-third of NSTE-ACS patients.Spontaneous reperfusion with well-developed coronary collateral circulation is associated with a better prognosis in cardiovascular mortality reduction. 18 ischemic conditions, collateral circulations are a good predictor of prognosis.Collateral circulation may support cardiac function and decrease cardiac mortality and morbidity rate.Collateral circulations are inter arterial anastomoses that exist neonatally and grow more significant because of many mechanisms like cytokines and growth factors induced by shear stress and ischemia and pressure gradient changes. 19The collateral circulation artery may appear several weeks after occlusion. 18

Conclusions
This case shows Wellens syndrome, which can change into ST-elevation myocardial infarction.Wellens can also occur in the left anterior descending artery that is in total occlusion but gets its blood supply from a branch of the right coronary collateral artery.Based on this case report, an early invasive strategy is recommended, with favourable clinical outcomes.Failing to recognize Wellens syndrome or T-wave dynamic changes on electrocardiogram could lead to significant mortality and morbidity, such as underestimating the seriousness of the electrocardiogram finding in a pain-free patient, failing to properly admit or consult cardiology leads to delay percutaneous coronary intervention, ordering unnecessary stress test which may provoke a large anterior wall myocardial infarction.

Consent
Written informed consent for publication of their clinical details and clinical images was obtained from the patient.
Video 1: Angiography revealed total occlusion at mid left anterior descending coronary artery.

Zahid Khan
Barts Health NHS Trust, London, UK Thank you for inviting me to review the revised version.Please make the following changes to the article.
He was overweight with a pained grunt and he occasionally clutched his chest.Others physical examination were unremarkable.The overweight part should come in the past medical history.
Differential diagnosis should make sense and should not be just random differentials.Please rewrite these and the differentials ideally should be in a paragraph form.
Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Intervention cardiology and General internal Medicine
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Dhan Bahadur Shrestha
Department of Internal Medicine, Mount Sinai Hospital, Chicago, Illinois, USA This version is better; however, there are still many instances requiring improvements.Prior comments regarding writing have not been totally addressed, and the writing needs further revisions.For example, "It's important important to recognize", important is to repetition by mistake in the abstract!"He was overweight with a pained grunt and he occasionally clutched his chest." not fully comprehendible Occlusion Myocardial Infarction (OMI) abbreviated with full form in multiple instances, its recommended to use full form with abbreviations in first use in body of manuscript and only abbreviations in subsequent use.Other similar cases include ECG, LAD, RCA, etc

Thank you
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: General Cardiology, Arrythmia and electrophysiology, Sudden cardiac death/Cardiac arrest I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Author Response 30 Jun 2024

Ricardo Adrian Nugraha
Reviewer Comment: This version is better; however, there are still many instances requiring improvements.Prior comments regarding writing have not been totally addressed, and the writing needs further revisions.
Author response: Thank you for your help.We've got the manuscript better and better from your feedback and suggestions.We really appreciate your perspective and will take it into consideration.

Reviewer Comment:
For example, "It's important important to recognize", important is to repetition by mistake in the abstract!Author response: Thank you for your feedback, we deleted that repeated word.

Reviewer Comment:
"He was overweight with a pained grunt and he occasionally clutched his chest." not fully comprehendible Author response: Thank you for your feedback, we replaced it with "He was overweight with a BMI of 29.4 kg/m 2 "

Reviewer Comment:
Occlusion Myocardial Infarction (OMI) abbreviated with full form in multiple instances, its recommended to use full form with abbreviations in first use in body of manuscript and only abbreviations in subsequent use.Other similar cases include ECG, LAD, RCA, etc.
Author response: Thank you for your suggestion.Since OMI is popular for the abbreviation of Old Myocard Infarct, then we decided not to abbreviate the term of Occlusion Myocardial Infarction.
Once again, thank you for taking the time to share your suggestions with us.

Zahid Khan
Barts Health NHS Trust, London, UK The introduction should provide some more information about Wellens syndrome and why early intervention is important.
Please exclude any patient identifiable information such as location of the patient/hospital provided in the case report section.Please use the term poorly controlled rather uncontrolled for both hypertension and diabetes.I would suggest to use either recent history or history of angina three years ago rather than using both.
There was no history of cocaine use (This is not required and it should be part of the social history along with smoking and drinking) On physical examination on the emergency ward (in the emergency ward , oxygen saturation of 95% on room air) The trop rise of this level does not really fit with Wellens syndrome.Wellens syndrome patients tend to have mild trop rise The differential diagnosis are poorly constructed and please include more relevant differential diagnosis.

General comments.
The case report is about a patient presenting with chest pain and the authors claim that the patient had wellens syndrome.The case report has significant grammatical errors that need rectifying.The presentation lacks flow and is disjointed.The high level of trop does not really fit with wellens syndrome type picture.Please remove all patient's identifiable information from the case report.The introduction and case presentation sections need significant revision.

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Partly

Is the case presented with sufficient detail to be useful for other practitioners? Partly
Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Intervention cardiology and General internal Medicine
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.
Please exclude any patient identifiable information such as location of the patient/hospital provided in the case report section.Authors response: thank you for your constructive feedback.We have removed any patient identifiable information In our 2 videos.
Please use the term poorly controlled rather uncontrolled for both hypertension and diabetes.
Authors response: thank you for your suggestion.We have used the term poorly controlled hypertension and diabetes.
I would suggest to use either recent history or history of angina three years ago rather than using both.Authors response: thank you for your suggestion.We have used the term history of angina three years ago.
There was no history of cocaine use (This is not required and it should be part of the social history along with smoking and drinking) Authors response: thank you for your suggestion.We have used the term social history of smoking or drinking.
On physical examination on the emergency ward (in the emergency ward , oxygen saturation of 95% on room air) Authors response: thank you for your suggestion.We have used the term as you have suggested.
The trop rise of this level does not really fit with Wellens syndrome.Wellens syndrome patients tend to have mild trop rise Authors response: thank you for your suggestion.Unfortunately, our case has significant raised of troponin level which may be unsuitable for Wellens syndrome.We have tried to search for any literatures regarding cardiac enzyme among Wellens syndrome, and found that troponin may be falsely reassuring in patients with Wellens syndrome.Only 12% of patients with Wellens syndrome had elevated cardiac enzymes, and these elevations were less than twice the upper limit of normal.Increase of cardiac enzymes in our case may indicates that cardiac myonecrosis have already been occurred at the time of diagnosis.General comments.The case report is about a patient presenting with chest pain and the authors claim that the patient had wellens syndrome.The case report has significant grammatical errors that need rectifying.

Figure 3 .
Figure 3. Angiography: A and B LAD projection view showed total occlusion of 100% in the middle LAD.The left circumflex coronary artery (LCx) had non-significant stenosis of 40% at proximal and 65% at distal.

Figure 4 .
Figure 4. Angiography RCA projection View RAO, CRA.It is revealed that there is grade II collateral from distal right coronary artery to distal left anterior descending coronary artery.(Notes: RAO CRA = right anterior oblique + cranial view, a radiographic projection).
The differential diagnosis are poorly constructed and please include more relevant differential diagnosis.Authors response: thank you for your suggestion.We have added several differential diagnosis: Hyperacute T-waves, de Winter T-waves, Isolated posterior MI, T waves upright in V1, Persistent juvenile T-wave pattern, Digitalis toxicity, Acute myocarditis, Preexcitation syndromes, Later stages of pericarditis, and Central nervous system disorders.
discussion, which may be less relevant in mentioning detailed classifications of collaterals in half of the discussion section.Authors response: thank you for your feedback.We have added several background of Wellens syndrome in the Introduction section.We have added the reason to a new MI classification considering vascular occlusion (OMI vs. N-OMI) in the Discussion section.4.It's unclear to me whether the authors reported HS-troponin or just troponin.The AHA 2021 chest pain guideline recommends an HS-troponin assay.Authors response: thank you for your questions.It was HS-troponin I.5.The relevance of this paragraph "The patient felt that his treatment at the hospital was excellent and fast, especially when he felt chest pain.After the medication was taken, his chest pain gradually disappeared.The patient was also very grateful for the direct action of inserting a catheter into the heart in less than 24 hours.The patient hopes that the publication of cases of diseases like his will help paramedics handle them in the future." is uncertain to me, rather more objective mention of patient care timeline (door to cath lab/balloon) and its alignment with recent 2018 ESC or 2021 AHA/ACC revascularization guideline would be more appropriate.Authors response: after reviewing it carefully, we decided to delete this irrelevant paragraph.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.This is an open access peer review report 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.