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). Drugs that have been associated with Brugada ECG patterns include tricyclic antidepressants, anesthetics, cocaine
, methadone, antihistamines, electrolyte derangements, and even tramadol
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 .
Prior to Mizusawa’s study, it was thought that the incidence of syncope, arrhythmia, or SCD in this cohort was low . 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 . 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 . 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 .
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.
: 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.
: 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.
: 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.
: Antzelevitch C and Brugada R. (2002). Fever and Brugada syndrome. Pacing Clin Electrophysiol, 25(11), 1537-1539.
: 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.
: Deschênes I and Laurita KR. (2007). How can a single mutation cause such arrhythmic havoc? Heart Rhythm, 4(2), 198-199.
 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.
 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.