Wednesday, January 30, 2019

Hyperthermia and ST Elevation

This was submitted by Alexandra Schick.  Dr. Schick is a PGY3 at the Brown Emergency Medicine Residency in Rhode Island.  I remember Allie well from her days in the Research volunteer program at Hennepin.

The article is edited by Smith.

Title: Is it just hot in here or is it a OMI? 

An elderly woman presents with altered mental status; she was found by her family lying on her bed in her apartment on a hot (103 F) summer day and was last seen three hours before.  She was obtunded, not following commands, hypoxic, and in respiratory distress. She was ventilated by bag-valve-mask by EMS on arrival and was quickly intubated with etomidate and succinylcholine. A rectal temperature was obtained which read 107.9 F. Otherwise vitals after intubation were only notable for tachycardia. 

An initial EKG was obtained: 
Computer read: sinus tachycardia, early acute anterior infarct.

There is sinus tach with rate of 124, normal axis, QRS 92, QTc 460, upsloping STD in I, aVL, V4 – V6 with concave STE in V1 (3mm) and V2 (5mm), and III (1mm) with Q wave in V1, V2, III. T wave inversion III, aVR, TWF in aVF.

Here is her prior EKG:
When compared to the old EKG – Q waves present before, TWI in aVR present before, but all other changes are new. 

What is the differential for this EKG? Is this an OMI? 

We considered OMI, as there are elevations with reciprocal changes (III and aVL), but the STE in III does not fit with this pattern.

The pattern of STE and STD reminded us of Brugada Type 1 morphology.

Smith comment:
1) Brugada ECG may have ST shifts in limb leads as well as precordial leads.  See additional image at the bottom of this post.
2) The STE in V1 and V2 has an R'-wave and downsloping ST segments, very atypical for STEMI.
3)  Similar downsloping ST elevation in V1 and V2 with an rsr' is also found in hyperkalemia (See several cases at this post):

This ECG is NOT Pathognomonic of Brugada Syndrome

Case continued:
A bedside cardiac POCUS did not reveal and regional wall motion abnormalities, LV function was hyperdynamic.

Could this be induced by elevated core temperature? Or possibly a medication or metabolic effect?

We started active cooling of the patient and within one hour her temperature had come down to 101.1 F (rectal).

A repeat EKG was performed at that time and showed this:
The STE had almost completed resolved and the STE depression is improved as well.  All that remains is an incomplete RBBB.

By this time, some labs had returned, which showed a troponin I of 0.348 ng/mL (normal in our lab is less than 0.060)
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The only other abnormal labs were: 
pH 7.18, pCO2 61, K 5.1, Bicarb 20, Lactate 4.2, Ammonia 100.

Cardiology was consulted and they agreed that the EKG had an atypical morphology for STEMI and did not activate the cath lab.

The Troponin I was cycled over time and was 0.353 followed by 0.296.

A formal echocardiogram was completed the next day and again showed a normal ejection fraction without any focal wall motion abnormalities to suggest CAD.  The elevated troponin was attributed to either type 2 MI or to non-MI acute myocardial injury.

There is no further workup at this time.

Smith: Here is a case that was just texted to me today from a former resident.  It was from a patient with chest pain:
Note the obvious Brugada pattern.
Also note that there is also: STE in aVL and inferior reciprocal ST depression.
This patient ruled out for MI. 
The limb lead abnormalities appear to be part of the Brugada pattern, as described in this article:
Inferior and Lateral Electrocardiographic RepolarizationAbnormalities in Brugada Syndrome


Brugada Type 1 ECG changes are associated with sudden cardiac death (SCD) and the occurrence of ventricular dysrhythmias. Patients that develop a Type 1 pattern without any precipitating or provoking factors have a risk of SCD of 0.5-0.8% per year. In patients that only have this pattern induced by a sodium channel blocking agent have a lower rate of SCD (0 - 0.35% per year)[1]. Drugs that have been associated with Brugada ECG patterns include tricyclic antidepressants, anesthetics, cocaine, methadone, antihistamines, electrolyte derangements, and even tramadol. [2]. 

Our patient had a Brugada Type 1 pattern elicited by an elevated core temperature, which is also a documented phenomenon. She was on amitriptyline 50 mg/day but no other medications that would affect the sodium channel. There are many case reports of ST elevation with Brugada pattern related to fevers related to infections [3, 4]. It is hypothesized that the rate of sodium channel inactivation can be temperature sensitive and that fever can impair the conductance through the sodium channels [5, 6]. In the largest study looking at this topic by Mizusawa et al., 88 patients with fever induced Brugada Type 1 ECG changes without history of syncope or VF/VT were analyzed. There was a 0.9% per year incidence of SCD in this cohort [1]. 

Prior to Mizusawa's study, it was thought that the incidence of syncope, arrhythmia, or SCD in this cohort was low [7]. Of those that had fever induced Type 1 pattern, approximately 80% also had drug induced Type 1 changes with provocative testing. Only 26% of the group carried the SCN5A mutation and 20% had family history of SCD [1]. It appears as though having Brugada Type 1 ECG patterns unmasked only by fever portends a similar risk of SCD to spontaneous Brugada syndrome, but the studies on this rare clinical entity are still quite small. For now, the 2017 AHA/ACC/HRS guidelines for asymptomatic patients that have inducible types of Brugada syndrome recommend observation without any specific therapies or interventions [8]. In light of the risk of arrhythmia events observed in the Mizusawa trial, a formal EP study might be reasonable to obtain in those with fever induced asymptomatic Brugada ECG changes to help risk stratify these patients. 

Fever in those with spontaneous Brugada Type 1 syndrome has been known to induce Type 1 EKG changes; it is recommended to aggressively treat any fever in this patients when identified. Recently the rate of true arrhythmic events related to fevers in the classic Brugada Type 1 syndrome was explored by Michowitz et al. In a cohort of 588 patients with diagnosed Brugada syndrome who had an arrhythmic event, 6% were associated with a febrile illness. Pediatric and elderly patients were more predisposed to developing an arrhythmic event in the setting of fever [7]. 

As for our patient, on discharge, her EKG had completed returned to her baseline morphology and she has been doing well in follow-up. She has not had a heart catheterization or after this event so the presence or absence of CAD is still unknown. She has not yet been seen by electrophysiology or had further genetic testing for Brugada syndrome. 

[1]: Mizusawa Y, Morita H, Adler A, Havakuk O, Thollet A, Maury P, Wang DW, Hong K, Gandjbakhch E, Sacher F, Hu D, Amin AS, Lahrouchi N, Tan HL, Antzelevitch C, Probst V, Viskin S, Wilde AA. (2016). Prognostic significance of fever-induced Brugada syndrome. Heart Rhythm, 13(7): 1515-1520.

[2]: Junttila MJ, Gonzalez M, Lizotte E, Benito B, Vernooy K, Sarkozy A, Huikuri HV, Brugada P, Brugada J, Brugada R. (2008). Induced Brugada-type electrocardiogram, a sign for imminent malignant arrhythmias. Circulation, 117, 1890–1893.

[3]: Lamelas P, Labadet C, Spernanzoni F, Lopez Saubidet C, and Alvarez PA. (2012). Brugada electrocardiographic pattern induced by fever. World Journal of Cardiology, 4(3): 84-86.

[4]: Antzelevitch C and Brugada R. (2002). Fever and Brugada syndrome. Pacing Clin Electrophysiol, 25(11), 1537-1539.

[5]: Dumaine R, Towbin JA, Brugada P, Vatta M, Nesterenko DV, Nesterenko VV, Brugada J, Brugada R, Antzelevitch C. (1999). Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. Circ Res, 85(9), 803-809.

[6]: Deschênes I and Laurita KR. (2007). How can a single mutation cause such arrhythmic havoc? Heart Rhythm, 4(2), 198-199.

[6] Michowitz Y, Milman A, Sarquella-Brugada G, Andorin A, Champagne J, Postema PG, Casado-Arroyo R, Leshem E, Juang JJM, Giustetto C, Tfelt-Hansen J, Wijeyeratne YD, Veltmann C, Corrado D, Kim SH, Delise P, Maeda S, Gourraud JB, Sacher F, Mabo P, Takahashi Y, Kamakura T, Aiba T, Conte G, Hochstadt A, Mizusawa Y, Rahkovich M, Arbelo E, Huang Z, Denjoy I, Napolitano C, Brugada R, Calo L, Priori SG, Takagi M, Behr ER, Gaita F, Yan GX, Brugada J, Leenhardt A, Wilde AAM, Brugada P, Kusano KF, Hirao K, Nam GB, Probst V, Belhassen B. (2018). Fever-related arrhythmic events in the multicenter survey on arrhythmic events in Brugada syndrome. Heart Rhythm, 15(9): 1394-1401.

[7] American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. (2017). 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Heart Rhythm, 15(10), e73-e189.

Comment by KEN GRAUER, MD (1/30/2019):
Superb presentation and discussion by Dr. Alexandra Schick (with edits by Dr. Smith) of an elderly woman who was seen in the ED for altered mental status, hyperthermia, and the initial ECG shown above. This case provides an excellent example of a “pseudo-infarction” ECG produced by a hyperthermia-induced Brugada-1 ECG pattern. My comments are limited to a few additional clinical points:
  • It is important to distinguish between a Brugada-ECG pattern (as manifest in leads V1, V2 of the initial ECG in this case— vs the “Brugada Syndrome”. In addition to a spontaneous or induced Brugada-1 ECG pattern, criteria for Brugada Syndrome require one or more of the following: History of cardiac arrest, of polymorphoic VT, or of non-vagal syncope — positive family history of sudden death at an early age — a similar ECG in close relatives.
  • ECG criteria for diagnosis of either a Brugada-1 or Brugada-2 pattern are summarized in Figure-1, which I have excerpted from the Bayés de Luna reference shown at the top of the Figure. Note how leads V1 and V2 in the initial ECG (above) clearly satisfy criteria for a Brugada-1 ECG pattern.
  • It is important to clarify distinction between Brugada Syndrome” vs Brugada Phenocopy”. Many factors may induce a Brugada-1 or Brugada-2 ECG pattern. These include certain drugs (ie, calcium channel blockers; ß-blockers; antianginals; psychotropics; ETOH; cocaine; others …); — acute febrile illness (especially with markedly elevated body temperature); — variations in autonomic tone — hypothermia — electrolyte imbalance (ie, common in hyperkalemia); — ischemia/infarction — bradycardia — after cardioversion or defibrillation. The designation Brugada Phenocopy” is given when an otherwise healthy patient has none of the factors associated with Brugada Syndrome — but only develops a Brugada-1 ECG pattern as a result of one of the above conditions — and, resolves this Brugada-1 pattern once the precipitating condition has been corrected. This appears to be what happened in this case — as Brugada-1 ECG changes resolved once this elderly woman’s core temperature was lowered.
  • The clinical significance of distinguishing between Brugada Phenocopy vs a patient with a Brugada-1 ECG that may be due to a true Brugada Syndrome — is that prognosis appears to be significantly better with the former. That said — risk is still present for any patient with a Brugada-1 ECG pattern, which is why referral is merited for more formal risk assessment by an EP cardiologist.
Our THANKS again to Dr. Schick for sharing this case with us!
Figure-1: ECG criteria for diagnosis of a Brugada-1 or Brugada-2 pattern (See text).
NOTE: There are numerous additional cases regarding Brugada pattern ECGs by Dr. Smith on this blog (Simply search for Brugada Syndrome!).
  • For those wanting more — I’ve summarized “My Take” on the Basics of Brugada Pattern ECGs in an ECG VIDEO on this subject.


  1. I know it was a very warm day, but hyperthermia and Brugada pattern changes make me think of cocaine intoxication. Was that considered?

    1. Good idea, but it was not cocaine. Note I had already put a link in to cases of cocaine brugada in the discussion.

  2. A beautiful example of what I would call "acquired" Brugada ECG pattern, which can also occur from hyperkalemia and several other things.
    K. Wang.


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