Fever-induced Brugada pattern: How common is it and what does it mean?

doi:10.1016/j.hrthm.2013.07.030

Heart Rhythm

Volume 10, Issue 9, September 2013, Pages 1375-1382

https://doi.org/10.1016/j.hrthm.2013.07.030 Get rights and content

Background

Fever is known to unmask the Brugada pattern on the electrocardiogram (ECG) and trigger ventricular arrhythmias in patients with Brugada syndrome. Genetic studies in selected cases with fever-induced Brugada pattern have identified disease-causing mutations. Thus, “fever-induced Brugada” is a recognized clinical entity. However, its prevalence has not been systematically evaluated.

Objective

The purpose of this study was to assess the prevalence of Brugada pattern in consecutive patients with fever.

Methods

ECGs of patients with fever admitted to the emergency department were evaluated for the presence of Brugada pattern and compared with ECGs of consecutive nonfebrile patients.

Results

ECGs of 402 patients with fever and 909 without were evaluated. Type I Brugada pattern was 20 times more common in the febrile group than in the afebrile group (2% vs 0.1%, respectively, P = .0001). All patients with fever-induced type I Brugada pattern were asymptomatic and remained so during 30 months of follow-up.

Conclusion

Type I Brugada pattern is definitively more common among patients with fever, suggesting that asymptomatic Brugada syndrome is more prevalent than previously estimated.

Section snippets

Febrile and afebrile groups

Between January 2010 and August 2012, we prospectively collected ECG recordings of all febrile patients (defined as oral temperature >38°C [>100.4°F]) who were evaluated in our emergency medicine department. Because our hospital has a separate pediatric emergency room, only adults were studied. Also, to ensure that all patients presenting with fever in a given day were included in the study, we studied only those who presented to the emergency room during the morning shift of weekdays when

Results

ECG recordings from 402 febrile and 909 afebrile patients were compared. Febrile and afebrile patients were of similar age (62 ± 22 years vs 61 ± 19 years, P = NS), but males were overrepresented in the febrile group (60% vs 49%, P <.001).

Eight of 402 patients with fever, but only 1 of 909 afebrile patients, had a type I Brugada pattern (Figure 1). Thus, a type I Brugada pattern was 20 times more prevalent among febrile patients (2% vs 0.1%, P = .0001). The estimated 95% confidence intervals

Discussion

Fever-induced Brugada is the term used to describe the aggravation of clinical and/or ECG characteristics of this syndrome during febrile states in susceptible individuals. Although the existence of this phenomenon is well accepted, there is more than 1 proposed mechanism for its pathophysiology (see below). Moreover, little is known about the true prevalence of this phenomenon. Therefore, we studied consecutive febrile patients in order to learn how frequently fever exposes a type I Brugada

Conclusion

Our study shows that the prevalence of type I Brugada ECG in patients with fever is 20 times higher than in afebrile patients, emphasizing the potency of fever in uncovering this ECG phenomenon. These findings also may imply that the number of asymptomatic Brugada patients diagnosed today is only the tip of the iceberg, as many more would have been discovered if their ECGs were recorded during febrile illnesses. This has possible implications regarding the number of patients who are potentially

Acknowledgments

We are indebted to Shelly Piterman, Nina Volensky, Ribal Kashkush, and Zinaida Reiscin, who helped collect the ECGs for the study.

References (41)

J. Ortega-Carnicer
Transient right bundle branch block unmasking anterior myocardial infarction
Resuscitation
(2003)
H.L. Tan et al.
Lethal ECG changes hidden by therapeutic hypothermia
Lancet
(2007)
P. Chockalingam et al.
The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children
Heart Rhythm
(2012)
A. Bayes de Luna et al.
Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report
J Electrocardiol
(2012)
Y. Take et al.
Spontaneous electrocardiogram alterations predict ventricular fibrillation in Brugada syndrome
Heart Rhythm
(2011)
G.W. Abbott et al.
MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis
Cell
(2001)
P.G. Postema et al.
Drugs and Brugada syndrome patients: review of the literature, recommendations, and an up-to-date website
Heart Rhythm
(2009)
O. Erdogan et al.
Frequency of Brugada type ECG pattern in male subjects with fever
Int J Cardiol
(2013)
A.A. Wilde et al.
The pathophysiological mechanism underlying Brugada syndrome: depolarization versus repolarization
J Mol Cell Cardiol
(2010)
P.G. Postema et al.
Arrhythmias in Brugada syndrome: changing throughout day and season?
Heart Rhythm
(2008)

M. Takigawa et al.

Seasonal and circadian distributions of ventricular fibrillation in patients with Brugada syndrome

Heart Rhythm

(2008)

S. Viskin et al.

Inaccurate electrocardiographic interpretation of long QT: the majority of physicians cannot recognize a long QT when they see one

Heart Rhythm

(2005)

C. Veltmann et al.

Insights into the location of type I ECG in patients with Brugada syndrome: correlation of ECG and cardiovascular magnetic resonance imaging

Heart Rhythm

(2012)

C. Antzelevitch et al.

Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association

Circulation

(2005)

S. Richter et al.

Variability of the diagnostic ECG pattern in an ICD patient population with Brugada syndrome

J Cardiovasc Electrophysiol

(2009)

R. Dumaine et al.

Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent

Circ Res

(1999)

J.M. Porres et al.

Fever unmasking the Brugada syndrome

Pacing Clin Electrophysiol

(2002)

L.C. Kum et al.

Brugada syndrome unmasked by febrile illness

Pacing Clin Electrophysiol

(2002)

A. Baranchuk et al.

Brugada syndrome coinciding with fever and pandemic (H1N1) influenza

CMAJ

(2011)

M. Suzuki et al.

Fever-induced ST-segment elevation in a syncopal patient with Brugada syndrome

Am J Emerg Med

(2012)

Cited by (123)

Contributions of Israel to the field of clinical cardiac electrophysiology and implantable devices
2024, Heart Rhythm O2
Phase 2 Re-Entry Without I<inf>to</inf>: Role of Sodium Channel Kinetics in Brugada Syndrome Arrhythmias
2023, JACC: Clinical Electrophysiology
In Brugada syndrome (BrS), phase 2 re-excitation/re-entry (P2R) induced by the transient outward potassium current (I_to) is a proposed arrhythmia mechanism; yet, the most common genetic defects are loss-of-function sodium channel mutations.
The authors used computer simulations to investigate how sodium channel dysfunction affects P2R-mediated arrhythmogenesis in the presence and absence of I_to.
Computer simulations were carried out in 1-dimensional cables and 2-dimensional tissue using guinea pig and human ventricular action potential models.
In the presence of I_to sufficient to generate robust P2R, reducing sodium current (I_Na) peak amplitude alone only slightly potentiated P2R. When I_Na inactivation kinetics were also altered to simulate reported effects of BrS mutations and sodium channel blockers, however, P2R occurred even in the absence of I_to. These effects could be potentiated by delaying L-type calcium channel activation or increasing ATP-sensitive potassium current, consistent with experimental and clinical findings. I_Na-mediated P2R also accounted for sex-related, day and night–related, and fever-related differences in arrhythmia risk in BrS patients.
Altered I_Na kinetics synergize powerfully with reduced I_Na amplitude to promote P2R-induced arrhythmias in BrS in the absence of I_to, establishing a robust mechanistic link between altered I_Na kinetics and the P2R-mediated arrhythmia mechanism.
Syncope following Pfizer BioNTech (bnt162b2) vaccination unmasking Brugada syndrome
2023, Heliyon
The Brugada syndrome is an uncommon inherited condition associated with increased risk of ventricular tachyarrhythmias and sudden cardiac death. Different triggers including fever are well known to precipitate the Brugada pattern on electrocardiogram. We report a patient who presents with syncope, two days after the first dose of the BNT162b2 vaccine due to fever-related unmasking of Brugada syndrome.
Approach to septic cardiomyopathy as a cause of refractory shock in resource limited settings: case report
2023, Acta Colombiana de Cuidado Intensivo
A nivel mundial se reportan más de 18 millones de casos de sepsis, la cual afecta a todos los grupos de edad, con mayor susceptibilidad en las personas en los extremos de la vida. Dentro del amplio debate sobre la definición de la cardiomiopatía inducida por sepsis se evidencia la depresión de la contractilidad intrínseca inducida por sepsis, que es un hallazgo común en los pacientes con sepsis o choque séptico en las unidades de cuidado intensivo; sin embargo, la inequidad en la distribución regional de los recursos y las dificultades para lograr medicina especializada e imágenes diagnósticas en escenarios de recursos limitados hacen necesario socializar los retos que se encuentran en el manejo del paciente crítico en escenarios de recursos limitados y reflexionar a través de un caso, en el que el paciente ingresa con choque séptico de origen abdominal, alta sospecha de colangitis, electrocardiograma con taquicardia sinusal, bloqueo completo de rama derecha, infradesnivel de ST en DI, R mellada en V1, troponina negativa, en el que se inicia manejo con reanimación hídrica, soporte vasopresor e inotrópico, manejo antibiótico empírico y manejo antiisquémico; con deterioro clínico progresivo, presenta falla ventilatoria con requerimiento de ventilación mecánica invasiva y de aumento de soporte vasopresor. A pesar del manejo, persisten cambios dinámicos electrocardiográficos asociados a hipoperfusión. En el primer día de estancia en UCI, el paciente se encuentra en falla multiorgánica progresiva, con choque séptico refractario, y finalmente el paciente fallece. Posteriormente al fallecimiento del paciente se obtiene reporte de hemocultivos con evidencia de Escherichia coli BLEE. Hay estrategias que podrían haber mejorado el desenlace y evidenciar la necesidad de dotar de herramientas como el POCUS crítico a todas las unidades de cuidado intensivo, en particular en países de bajo y mediano ingreso con escenarios donde no hay acceso a imágenes diagnósticas por cardiología tempranamente.
Worldwide, more than 18 million cases of sepsis are reported, which affects all age groups, with greater susceptibility in people at the extremes of life; within the wide debate on the definition of cardiomyopathy induced by sepsis, the depression of intrinsic contractility induced by sepsis is evident, and it is a common finding in patients with sepsis or septic shock in intensive care units; however, the inequity in the regional distribution of resources and the difficulties in achieving specialized medicine and diagnostic images in settings with limited resources make it necessary to socialize the challenges found in the management of critical patients in settings with limited resources, and reflect through of a case, the strategies that could have improved the outcome and demonstrate the need to provide tools as POCUS to all intensive care units, particularly in low and middle income countries with scenarios where the access to early diagnostic images by cardiology is limited. The inequity in the regional distribution of resources and the difficulties to achieve specialized medicine and diagnostic imaging in scenarios with limited access, make mandatory to socialize the challenges of critical patient management through a case in which the patient is admitted with septic shock of abdominal origin, high suspicion of cholangitis, electrocardiogram with sinus tachycardia, complete right branch block, ST depression in DI, abnormal R in V1, troponin negative, in which the patient is management with fluid resuscitation, vasopressor and inotropic support, empirical antibiotic management and anti-ischemic management; with progressive clinical deterioration, presenting ventilatory failure requiring invasive mechanical ventilation and requiring increased vasopressor support. Despite management, dynamic electrocardiographic changes associated with hypoperfusion persist. On the first day of ICU stay, the patient is in progressive multi-organ failure, with refractory septic shock, and finally the patient died. After the patient's death, blood cultures were reported with evidence of Escherichia coli ESBL. There are strategies that could have improved the outcome and evidenced the need to provide tools such as the critical POCUS to all intensive care units, particularly in low- and middle-income countries where early diagnostic imaging by cardiology is not available.
Fir(e)ing the Rhythm: Inflammatory Cytokines and Cardiac Arrhythmias
2023, JACC: Basic to Translational Science
Inflammatory activation is increasingly recognized as a nonconventional risk factor for arrhythmias, and experimental studies provided robust evidence that this association is mediated by direct arrhythmogenic effects of proinflammatory cytokines on cardiac cells. Additionally, inflammatory cytokines can favor arrhythmias indirectly through multiple systemic effects. Accumulating data confirm the clinical relevance of these mechanisms; the largest evidence being available for atrial fibrillation, acquired long-QT syndrome, and ventricular arrhythmias. However, clinical management of arrhythmias largely neglects inflammatory cytokines. This review integrates basic science and clinical research to present an updated overview of the topic and provides future directions for patient’s management.
Clinical characteristics and electrophysiologic properties of SCN5A variants in fever-induced Brugada syndrome
2023, eBioMedicine
Brugada syndrome (BrS) is a severe inherited arrhythmia syndrome that can be unmasked by fever.
A multicentre clinical analysis was performed in 261 patients diagnosed with fever-induced BrS, including 198 (75.9%) and 27 (10.3%) patients who received next-generation genetic sequencing and epicardial arrhythmogenic substrate (AS) mapping, respectively.
In fever-induced BrS patients, pathogenic or likely pathogenic (P/LP) SCN5A variant carriers developed fever-induced BrS at a younger age, and more often in females and those of Caucasian descent. They exhibited significant electrophysical abnormalities, including a larger epicardial AS area, and more prolonged abnormal epicardial electrograms. During a median follow-up of 50.5 months (quartiles 32.5–81.5 months) after the diagnosis, major cardiac events (MCE) occurred in 27 (14.4%) patients. Patients with P/LP SCN5A variants had a higher ratio of MCE compared with the rest. Additionally, history of syncope, QRS duration, and Tpe interval could also predict an increased risk for future MCE according to univariate analysis. Multivariate analysis indicated that only P/LP SCN5A variants were independent significant predictors of MCE. Computational structural modelling showed that most variants are destabilizing, suggesting that Nav1.5 structure destabilization caused by SCN5A missense variants may contribute to fever-induced BrS.
In our cohort, P/LP SCN5A variant carriers with fever-induced BrS are more prevalent among patients of Caucasian descent, females, and younger patients. These patients exhibit aggressive electrophysiological abnormalities and worse outcome, which warrants closer monitoring and more urgent management of fever.
The current work was supported by the National Natural Science Foundation Project of China (Nos. 82270332 & 81670304), The Fundamental Research Funds for the Central Universities of China - Independent Research Project of Wuhan University (No. 2042022kf1217) from China; the National Institutes of Health of USA [NIH R56 (HL47678), NIH R01 (HL138103), and NIH R01 (HL152201)], the W. W. Smith Charitable Trust and the Wistar and Martha Morris Fund, Sharpe-Strumia Research Foundation, the American Heart Association Postdoctoral Fellowship (20POST35220002) from United States; the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences (PREDICT2) from the Netherlands.

View all citing articles on Scopus

View full text

Fever-induced Brugada pattern: How common is it and what does it mean?

Background

Objective

Methods

Results

Conclusion

Section snippets

Febrile and afebrile groups

Results

Discussion

Conclusion

Acknowledgments

Resuscitation

Lancet

Heart Rhythm

J Electrocardiol

Heart Rhythm

Cell

Heart Rhythm

Int J Cardiol

J Mol Cell Cardiol

Heart Rhythm

Heart Rhythm

Heart Rhythm

Heart Rhythm

Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association

Circulation

Variability of the diagnostic ECG pattern in an ICD patient population with Brugada syndrome

J Cardiovasc Electrophysiol

Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent

Circ Res

Fever unmasking the Brugada syndrome

Pacing Clin Electrophysiol

Brugada syndrome unmasked by febrile illness

Pacing Clin Electrophysiol

Brugada syndrome coinciding with fever and pandemic (H1N1) influenza

CMAJ

Fever-induced ST-segment elevation in a syncopal patient with Brugada syndrome

Am J Emerg Med