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Mastitis unmasks Brugada syndrome
International Journal of Cardiology 132 (2009) e94 – e96 www.elsevier.com/locate/ijcard
Letter to the Editor
Mastitis unmasks Brugada syndrome Amrut V. Ambardekar, Laurent Lewkowiez, Mori J. Krantz ⁎ Division of Cardiology, Denver Health Medical Center and University of Colorado Health Sciences Center, Mail Code 0960, 777 Bannock Street, Denver, CO 80204-4507, USA Received 25 May 2007; received in revised form 7 July 2007; accepted 8 July 2007 Available online 26 November 2007
Abstract The Brugada syndrome is an important cause of sudden cardiac death primarily among males without structural heart disease. Although not widely known, it may be unmasked by an acute febrile illness. An association between mastitis and Brugada syndrome has not been previously reported. We describe an 18-year-old postpartum female who developed mastitis, fever, and syncope. Electrocardiography revealed type 1 Brugada pattern, which disappeared once her fever resolved. Although the role of pregnancy in this syndrome is unknown, clinicians should be aware that fever may precipitate Brugada syndrome among peripartum women. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Brugada syndrome; Fever; Mastitis; Pregnancy
1. Case report Since its initial description in 1992 [1], there has been growing concern regarding the Brugada syndrome given that it is implicated in N 20% of sudden deaths among patients without structural heart disease [2]. Moreover, in countries where the condition is endemic, it is a leading cause of death in men b 40 years old — second only to automobile accidents [2]. Although there have been occasional reports of fever precipitating this syndrome in adults, fever is the most frequent trigger for syncope and sudden death among children with occult Brugada syndrome [3]. An 18-year-old female 1 week postpartum presented with abrupt loss of consciousness. She denied prodromal symptoms of chest pain, dizziness, palpitations, or seizures; however, she did complain of an unrelenting fever. The patient had no prior cardiovascular disease and denied a family history of sudden death. Her only medication was dicloxacillin — started 1 day prior for mastitis, and she denied illicit substance abuse. Upon arrival, her temperature was 39.0 °C, pulse was 120 beats/min, and blood pressure was 104/74 mmHg without orthostasis. ⁎ Corresponding author. Tel.: +1 303 436 7818; fax: +1 303 436 7739. E-mail address: [email protected] (M.J. Krantz). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.07.154
Cardiac exam was notable for tachycardia and breast exam revealed erythema and tenderness consistent with mastitis. A 12-lead electrocardiogram (ECG) demonstrated incomplete right bundle branch block with 2 mm of ST elevation with a coved pattern and inverted T-waves in leads V1 and V2 (Fig. 1a). Echocardiography demonstrated normal right and left ventricular function. The ECG findings completely resolved after antipyretic therapy (Fig. 1b) and were not reproduced with intravenous procainamide challenge. Given the abrupt onset of syncope and characteristic ECG findings, a diagnosis of Brugada syndrome was made and a cardiac defibrillator was implanted once the patient's mastitis had resolved. To our knowledge, this is the first reported case of fever from acute mastitis unmasking the Brugada syndrome. Interestingly, this patient did not complain of any chest discomfort even though chest pain has been reported in association with ST elevation and fever induced Brugada syndrome [4]. Mutations in the SCN5A gene encoding the α-subunit of the voltage-gated cardiac sodium channel have been implicated in 10–30% of patients with the Brugada syndrome [2]. Since premature inactivation of the sodium channel in SCN5A mutations is dependent upon body temperature, this provides a plausible mechanism to suggest why a febrile state may unmask the Brugada syndrome [5].
A.V. Ambardekar et al. / International Journal of Cardiology 132 (2009) e94–e96
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Fig. 1. a) Admission ECG. Incomplete right bundle branch block with ST elevation (arrows) and inverted T-waves in leads V1 and V2 consistent with type 1 Brugada pattern. b) Follow up ECG. Resolution of ECG findings with antipyretic treatment.
These genetic defects often have an autosomal dominant mode of inheritance — with males and females inheriting these defective genes equally. It is therefore surprising that males are 8–10 times more likely to have phenotypic manifestations and may suggest a sex hormone effect. In support of this, testosterone has been implicated in this syndrome given the disappearance of the Brugada-type ECG pattern after surgical castration [6]. Further support for the role of testosterone is suggested by the lack of gender predominance
in the Brugada syndrome in prepubescent children whose testosterone levels are low [3]. In our patient, it is unclear whether the hormonal changes of pregnancy predisposed to this syndrome. It is provocative, however, since testosterone levels are elevated in pregnancy attributable to estrogen-induced increases in hepatic synthesis of sex hormone-binding globulin. Regardless of the role of sex hormones in the pathogenesis of Brugada syndrome, this case reinforces the critical role of hyperthermia in precipitating both
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A.V. Ambardekar et al. / International Journal of Cardiology 132 (2009) e94–e96
the electrocardiographic manifestations of the disorder and subsequent arrhythmic events. Indeed, hyperthermia may be a stronger precipitant than Class IA anti-arrhythmic drugs as seen in this case. Future investigations should focus on the mechanisms for sex differences, the role of pregnancy in unmasking the phenotype, and better diagnostic tools for this intermittently silent yet life-threatening syndrome. References [1] Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol 1992;20:1391–6.
[2] Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference. Circulation 2005;111:659–70. [3] Probst V, Denjoy I, Meregalli PG, et al. Clinical aspects and prognosis of Brugada syndrome in children. Circulation 2007;115:2042–8. [4] Aramaki K, Okumura H, Shimizu M. Chest pain and ST elevation associated with fever in patients with asymptomatic Brugada syndrome: fever and chest pain in Brugada syndrome. Int J Cardiol 2005;103:338–9. [5] 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;85:803–9. [6] Matsuo K, Akahoshi M, Seto S, Yano K. Disappearance of the Brugadatype electrocardiogram after surgical castration: a role for testosterone and an explanation for the male preponderance. Pacing Clin Electrophysiol 2003;26:1551–3.
Letter to the Editor
Mastitis unmasks Brugada syndrome Amrut V. Ambardekar, Laurent Lewkowiez, Mori J. Krantz ⁎ Division of Cardiology, Denver Health Medical Center and University of Colorado Health Sciences Center, Mail Code 0960, 777 Bannock Street, Denver, CO 80204-4507, USA Received 25 May 2007; received in revised form 7 July 2007; accepted 8 July 2007 Available online 26 November 2007
Abstract The Brugada syndrome is an important cause of sudden cardiac death primarily among males without structural heart disease. Although not widely known, it may be unmasked by an acute febrile illness. An association between mastitis and Brugada syndrome has not been previously reported. We describe an 18-year-old postpartum female who developed mastitis, fever, and syncope. Electrocardiography revealed type 1 Brugada pattern, which disappeared once her fever resolved. Although the role of pregnancy in this syndrome is unknown, clinicians should be aware that fever may precipitate Brugada syndrome among peripartum women. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Brugada syndrome; Fever; Mastitis; Pregnancy
1. Case report Since its initial description in 1992 [1], there has been growing concern regarding the Brugada syndrome given that it is implicated in N 20% of sudden deaths among patients without structural heart disease [2]. Moreover, in countries where the condition is endemic, it is a leading cause of death in men b 40 years old — second only to automobile accidents [2]. Although there have been occasional reports of fever precipitating this syndrome in adults, fever is the most frequent trigger for syncope and sudden death among children with occult Brugada syndrome [3]. An 18-year-old female 1 week postpartum presented with abrupt loss of consciousness. She denied prodromal symptoms of chest pain, dizziness, palpitations, or seizures; however, she did complain of an unrelenting fever. The patient had no prior cardiovascular disease and denied a family history of sudden death. Her only medication was dicloxacillin — started 1 day prior for mastitis, and she denied illicit substance abuse. Upon arrival, her temperature was 39.0 °C, pulse was 120 beats/min, and blood pressure was 104/74 mmHg without orthostasis. ⁎ Corresponding author. Tel.: +1 303 436 7818; fax: +1 303 436 7739. E-mail address: [email protected] (M.J. Krantz). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.07.154
Cardiac exam was notable for tachycardia and breast exam revealed erythema and tenderness consistent with mastitis. A 12-lead electrocardiogram (ECG) demonstrated incomplete right bundle branch block with 2 mm of ST elevation with a coved pattern and inverted T-waves in leads V1 and V2 (Fig. 1a). Echocardiography demonstrated normal right and left ventricular function. The ECG findings completely resolved after antipyretic therapy (Fig. 1b) and were not reproduced with intravenous procainamide challenge. Given the abrupt onset of syncope and characteristic ECG findings, a diagnosis of Brugada syndrome was made and a cardiac defibrillator was implanted once the patient's mastitis had resolved. To our knowledge, this is the first reported case of fever from acute mastitis unmasking the Brugada syndrome. Interestingly, this patient did not complain of any chest discomfort even though chest pain has been reported in association with ST elevation and fever induced Brugada syndrome [4]. Mutations in the SCN5A gene encoding the α-subunit of the voltage-gated cardiac sodium channel have been implicated in 10–30% of patients with the Brugada syndrome [2]. Since premature inactivation of the sodium channel in SCN5A mutations is dependent upon body temperature, this provides a plausible mechanism to suggest why a febrile state may unmask the Brugada syndrome [5].
A.V. Ambardekar et al. / International Journal of Cardiology 132 (2009) e94–e96
e95
Fig. 1. a) Admission ECG. Incomplete right bundle branch block with ST elevation (arrows) and inverted T-waves in leads V1 and V2 consistent with type 1 Brugada pattern. b) Follow up ECG. Resolution of ECG findings with antipyretic treatment.
These genetic defects often have an autosomal dominant mode of inheritance — with males and females inheriting these defective genes equally. It is therefore surprising that males are 8–10 times more likely to have phenotypic manifestations and may suggest a sex hormone effect. In support of this, testosterone has been implicated in this syndrome given the disappearance of the Brugada-type ECG pattern after surgical castration [6]. Further support for the role of testosterone is suggested by the lack of gender predominance
in the Brugada syndrome in prepubescent children whose testosterone levels are low [3]. In our patient, it is unclear whether the hormonal changes of pregnancy predisposed to this syndrome. It is provocative, however, since testosterone levels are elevated in pregnancy attributable to estrogen-induced increases in hepatic synthesis of sex hormone-binding globulin. Regardless of the role of sex hormones in the pathogenesis of Brugada syndrome, this case reinforces the critical role of hyperthermia in precipitating both
e96
A.V. Ambardekar et al. / International Journal of Cardiology 132 (2009) e94–e96
the electrocardiographic manifestations of the disorder and subsequent arrhythmic events. Indeed, hyperthermia may be a stronger precipitant than Class IA anti-arrhythmic drugs as seen in this case. Future investigations should focus on the mechanisms for sex differences, the role of pregnancy in unmasking the phenotype, and better diagnostic tools for this intermittently silent yet life-threatening syndrome. References [1] Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol 1992;20:1391–6.
[2] Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference. Circulation 2005;111:659–70. [3] Probst V, Denjoy I, Meregalli PG, et al. Clinical aspects and prognosis of Brugada syndrome in children. Circulation 2007;115:2042–8. [4] Aramaki K, Okumura H, Shimizu M. Chest pain and ST elevation associated with fever in patients with asymptomatic Brugada syndrome: fever and chest pain in Brugada syndrome. Int J Cardiol 2005;103:338–9. [5] 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;85:803–9. [6] Matsuo K, Akahoshi M, Seto S, Yano K. Disappearance of the Brugadatype electrocardiogram after surgical castration: a role for testosterone and an explanation for the male preponderance. Pacing Clin Electrophysiol 2003;26:1551–3.