What clinical scenario fits best?

Below are 4 ECGs from the same patient. Accompanying the ECGs is some clinical information. Look at the ECGs and consider the timeline and other information. At the bottom will be five alternative clinical scenarios to explain the findings. Which one do you think fits better with the ECGs and their timeline? 

The patient is a 60 something female. She was admitted to the hospital with clinical signs of infection. She was febrile and hypotensive at presentation. As part of her work up in the ED an ECG was recorded. What do you think?

ECG#1 - day 1

The above ECG shows sinus rhythm with a narrow QRS and normal axis. There is Brugada type I STE in lead V1-V2. The patient was admitted with a suspicion of sepsis. Within 36 hours blood cultures grew a gram neg bacteria typically associated with UTI. Over the next couple of days the patient improved on iv antibiotics and infection control was achieved, On day four she developed SOB, and ECG#2 was obtained. What is going on now?

ECG#2 - day 4.

ECG#2 shows extensive ST Elevation in the anterior leads. There is loss of R wave in V3. There are no real reciprocal ST depression. This ECG could represent OMI of a type III wrap-around LAD. The ECG could as well fit with acute myopericarditis. Takotsubo cardiomyopathy is also a possible explanation. Both myopericarditis and takotsubo are very difficult and sometimes impossible to distinguish from OMI based solely on the ECG. 

An echo was done and decision was made to pursue cath lab the following day as the echocardiography was interpreted as consistent with Takotsubo Cardiomyopathy. The following day in the cath lab a borderline significant mid LAD stenosis was found. (FFR 0,80). Decision was made to stent the lesion. 

ECG#3 -day 6, 1 day after PCI

ECG#3 shows T wave inversions in anterolateral leads. Are these reperfusion T waves from transient OMI? Maybe it is T wave inversion of Takotsubo Cardiomyopathy? Or perhaps T inversion stems from evolution of myopericarditis?  

ECG#4 (below) was recorded about one year after the hospital stay described above. The ECG shows sinus rhythm. There is reconstitution of R waves V3-V6. N-terminal proBNP at the time of this ECG was normalized.

ECG#4 

What clinical scenario do you think fits best in this case? There is maybe no definite answer and arguments can be made for the different scenarios. 

Alternative 1) Patient has Brugada syndrome and also had an LAD OMI

Alternative 2) Patient had LAD OMI that mimicked Brugada syndrome

Alternative 3) Patient has Brugada phenocopy, later developed Takotsubo Cardiomyopathy, no OMI.

Alternative 4) Patient has Brugada phenocopy, and also had an LAD OMI.

Alternative 5) Patient has Brugada phenocopy later ECGs show evolution of myopericarditis.

Would you change you interpretation if the following information was added?

* During ECG #1 patient was febrile with a temperature of 40°C, (104°F)

* Maximum Troponin I was 4210ng/L. N-terminal-proBNP peaked at 18.000, then normalized.

* There was never any severe chest pain. Echo before cath revealed a large WMA.

Clinical course: The patient was admitted due to UTI. She was febrile at the time of the first ECG. There are a number of triggers that can provoke Brugada type I ST-elevation. Hyperkalemia, fever and sodium channel blockers are probably the most common ones. During the course of the next 48 hours the Brugada pattern disappeared with drop in body temperature. 

At the time of the second ECG the patient complained of shortness of breath. The infection was under control. Echocardiography showed a septal and apical WMA, but also hypokinesis of the apex of the RV. WMA not typical of LAD territory. Findings were interpreted as consistent with Takotsubo cardiomyopathy therefore cath lab was not rushed.

At cath the following day there was a borderline significant stenosis of the mid LAD with FFR 0,8. Decision was made to treat the lesion. Troponin I peaked at 4210ng/L.

======================================= 

Magnus’ comment: Putting all the information together, to me the most likely explanation in this case is that fever unmasked Brudgada type I morphologic ST-elevation V1-V2 consistent with Brugada phenocopy. Then the patient, due to severe infection developed Takotsubo Cardiomyopathy producing extensive ST pathologic changes but with rather modest troponin release. I would  expect higher troponin if the "extensive WMA" on echo was from myopericarditis or OMI. The 4th ECG was done at a separate visit to the hospital about one year later and shows reconstitution of R waves in the precordium which i think fits best with alternative three. An MRi was not done for this patient and a definite answer maybe cannot be obtained.

Smith's comment:  Fever-induced Brugada for sure.  But whether the additional findings are due to takotsubo or myocarditis could only have been differentiated with cMRI.  So we will never know, nor do we need to (since both only require supportive care).

Pendell's comment: I vote for brugada on the first one, and then I don’t think I have enough information to figure out whether the second one was OMI vs takotsubo vs myocarditis. I would assume LAD OMI prospectively and only be proven wrong after Angio etc. 

Jesse's comment: Cool case. I’m not sure Takotsubo is the most likely explanation. Isn’t it just as likely there was 1) OMI in context of infection 2) no inferior reciprocal changes because LAD was occluded mid vessel, 3) borderline stenosis because artery reperfused by time of delayed cath 4) TWI look more like reperfusion than the very deep TWI and very long Qt from tako 5) acute Q waves can regress and R waves can reappear after OMI reperfusion. I like the take home that tako often can’t be distinguished by ecg or echo. Surprising they didn’t activate cath lab based on second ECG 

Ken's comment: Intriguing case! — with the important message that sometimes (especially in retrospect!) — a definite diagnosis can not be made. 

• Unfortunately — no MRI was done (which would have been revealing! — especially regarding the possibility of myocarditis). Also unfortunate is the lack of more serial ECGs more closely spaced during the patient's acute illness.
• I thought the clinical scenario in association with ECG #1 was diagnostic of Brugada Phenocopy (especially given that 3 days later with resolution of the fever — the typical Brugada-1 pattern in leads V1,V2 was gone!).
• In place of the Brugada-1 pattern — we see in ECG #2 anterior QS complexes with marked ST elevation, if not hyperacute ST-T waves in multiple leads. While potentially this ECG could be consistent with LAD OMI — or Takotsubo Cardiomyopathy — or Myocarditis — I thought LAD OMI to be the least likely because: i) The clinical scenario of infection, and without CP; ii) With an Echo suggestive of Takotsubo; iii) With an ECG that I thought favored the other entities (lack of reciprocal ST depression; ST-T wave findings too generalized); and, iv) Cath showing only a "borderline significant mid-LAD stenosis" ...
• 
  
• While this patient clearly could have had acute Myocarditis (and she was admitted for acute infection!) — I thought ECGs #2 and #3 were more consistent with Takotsubo because: i) We really have diffuse ST-T wave findings that look fairly similar in multiple leads — really without localization — and with a long QTc on ECG #3; ii) I thought the evolution to diffuse T wave inversion with long QTc more consistent with Takotsubo (though clearly myocarditis could do the same thing); iii) I thought the overall clinical scenario more consistent with Takotsubo (though clearly myocarditis could do the same); and, iv) Assuming accurate interpretation — the Echo was read as consistent with Takotsubo.
• We review ECG findings in Takotsubo Cardiomyopathy in the March 25, 2020 post of Dr. Smith's ECG Blog.

==========================================================

Learning points:

1. Brugada phenocopy can be unmasked several different triggers, pyrexia being one of them. 
2. Takotsubo OMI mimic is very difficult and sometimes impossible to distinguish from OMI. 
3. Takotsubo may manifest transient Q waves and later R-wave recurrence.
4. Takotsubo is much less likely than OMI to have reciprocal changes in the limb leads
5. The work up of Takotsubo cardiomyopathy generally warrants cath lab investigation

Electrocardiographic Findings in Takotsubo Cardiomyopathy: ECG Evolution and Its Difference from the ECG of Acute Coronary Syndrome - PMC (nih.gov)