Brugada electrocardiographic pattern unmasked by fever Commoner than we think? Shiva Sreenivasan 1 , Zoe Jones 2 , Bogdan Nuta 3, Paul McGlinchey 4 1. 2. 3. 4.
Department of Medicine, Western HSC Trust, Enniskillen, Northern Ireland, UK Department of Acute Medicine, Gloucestershire NHS Foundation Trust, Gloucestershire, UK Department of Cardiology, Gloucestershire NHS Foundation Trust, Gloucestershire, UK Department of Cardiology, Western HSC Trust, Enniskillen, Northern Ireland, UK
We describe 2 patients with Type 1 Brugada morphology noted on 12-lead electrocardiography (ECG), both unmasked by concurrent febrile illness.
A 54-year-old lady was admitted with pyelonephritis. An ECG done when febrile at 39°C revealed Type 1 Brugada morphology, which reverted to normal when afebrile. Subsequent ajmaline provocation testing confirmed an inducible Brugada ECG pattern (Figure 1). Febrile 39˚C
Case 2 A 51-year-old gentleman with type 1 diabetes mellitus presented with a febrile illness which was eventually determined to be due to a urinary tract infection. An ECG taken when febrile at 38.2°C showed Type 1 Brugada morphology, which reverted to incomplete right bundle branch block with defervescence (Figure 2).
Figure 2 ECGs when febrile and afebrile, showing Type 1 Brugada pattern in V1 and V2 and resolution
RBBB morphology with ≥ 2 mm coved ST– segment elevation in V1 – V2 that gradually descends to an inverted T–wave
Saddle-back morphology ST–segment elevation followed by a positive T–wave in V1 – V2
Figure 1A ECG when febrile, showing Type 1 Brugada pattern in V1 and V2, and resolution when afebrile
Figure 1B ECG prior to and during ajmaline infusion, showing induction of Brugada pattern
The previously described Type 3 pattern is now incorporated in the Type 2 classification
Table 1 ECG patterns of Brugada syndrome1
Membrane potential (mV)
NaV1.5 complex Na+
Rapid Na+ influx through open fast Na+ channels
Figure 3 Influx of Na+ during Phase 0 of the cardiac action potential via the NaV1.5 channel complex
Abnormalities that can lead to ST–segment elevation in V1 – V3 Differential diagnosis Atypical right bundle branch block Acute myocardial infarction (especially of RV) Acute pericarditis/myocarditis Haemopericardium Pulmonary embolism Dissecting aortic aneurysm Central and autonomic nervous system disorders Duchenne muscular dystrophy Friedreich ataxia LV hypertrophy Arrhythmogenic RV cardiomyopathy Mechanical compression of RVOT Mediastinal tumours Pectus excavatum After electrical cardioversion Early repolarisation, especially in athletes Hypothermia
NaV1.5 inactivators/genetic predisposition Hyperkalaemia Hypercalcaemia Cocaine intoxication/alcohol intoxication Fever Treatment with I. Antiarrhythmic drugs: Sodium-channel blockers (class 1C, class 1A) Calcium-channel blockers Beta-adrenergic receptor blockers II. Antianginal drugs Calcium-channel blockers Nitrates III. Psychotropic drugs Tricyclic antidepressants Tetracyclic antidepressants Phenothiazines Selective serotonin reuptake inhibitors Lithium IV. Anaesthetic agents Propofol Bupivacaine Lidocaine Table 2 Differential diagnosis of Brugada ECG morphology and postulated inactivators of NaV1.5 (Adapted from Benito, et al.2, Yap, et al.3, and Brugada, et al.7)
Written consent was received from both patients for reproduction of the cases and images
Brugada syndrome (BS) is a potentially fatal arrhythmogenic condition with characteristic ECG appearances (Table 1), thought to most commonly result from a delayed Phase 0 fast inward sodium current (INa) in the NaV1.5 voltage-gated cardiac sodium channel encoded by the SCN5A gene (Figure 3).2 ECG changes are often dynamic, and can be unmasked by certain drugs and metabolic conditions (Table 2).3 Fever has also been reported to unmask the Brugada ECG pattern in susceptible individuals, and this is thought to be due to INa delay from temperature-dependent NaV1.5 inactivation.4 The Brugada ECG pattern is estimated to be 20 times more prevalent during fever and has a benign long-term prognosis when inducible.5 There is increased risk of malignant ventricular arrhythmias during febrile episodes, so vigorous antipyretic measures are recommended.6
Conclusion Inducible Brugada syndrome with no high-risk features is generally benign, but increased risk of ventricular arrhythmia during febrile episodes warrants anti-pyretic therapy. In view of the relatively common incidence of a feverinduced Brugada ECG pattern, we recommend opportunistic ECG recording of hospital inpatients when febrile.
References 1. Bayés de Luna A, Brugada J, Baranchuk A, et al. Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report. J Electrocardiol. 2012;45(5):433–42. 2. Benito B, Brugada R, Brugada J, et al. Brugada syndrome. Prog Cardiovasc Dis. 2008;51(1):1–22. 3. Yap YG, Behr ER, Camm AJ. Drug–induced Brugada syndrome. Europace 2009;11(8):989–94. 4. Dumaine R, Towbin JA, Brugada P, et al. Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. Circ Res. 1999;85(9):803–9. 5. Adler A, Topaz G, Heller K, et al. Fever-induced Brugada pattern: how common is it and what does it mean? Heart Rhythm 2013;10(9):1375–82. 6. Junttila MJ, Gonzalez M, Lizotte E, et al. Induced Brugada–type electrocardiogram, a sign for imminent malignant arrhythmias. Circulation 2008;117(14):1890–3. 7. Brugada P, Brugada R, Campuzano O, et al. 2013. Brugada Syndrome 1992 – 2012: Twenty Years of Scientific Progress. In: Zipes DP, Jalife J. ed. Cardiac Electrophysiology: from Cell to Bedside, Expert Consult – Online and Print: Elsevier Health Sciences, pp. 925–33.