Brugada Syndrome in an Active Duty Air Force Senior Pilot
By Walker, Dennis D Johnson, Monica L; Craig-Gray, Robert W; Loyd, Frank
ABSTRACT Introduction: Brugada syndrome describes a subgroup of patients at risk for polymorphic ventricular tachycardia, ventricular fibrillation, and sudden cardiac death and is likely underdiagnosed among aviators. Case Report: A 40-year-old male pilot presented to the clinic for his physical. He denied any symptoms on initial questioning. Subsequent electrocardiogram (ECG) revealed premature ventricular couplets with ST-segment elevation in V^sub 1^ and V^sub 2^ of the precordial leads with T-wave abnormalities. Discussion: Special care must be taken if ECG demonstrates a Brugada pattern-especially in patients with a history of syncope or a family history of sudden death. Recent studies have confirmed a significant risk reduction in symptomatic patients with type 1 Brugada to as low as 0.8% to 3% with an implantable cardioverter defibrillator. Conclusion: Symptomatic patients displaying type 1 Brugada ECG (spontaneous or after sodium channel blockade) should receive an implantable cardioverter defibrillator and must be permanently disqualified. The Aeromedicai Consultation Service should review all cases of Brugada syndrome and render a return to fly for asymptomatic nondiagnostic Brugada types. INTRODUCTION
Brugada syndrome refers to a disorder caused by defective cardiac ion channels and is characterized by the risk of developing polymorphic ventricular tachycardia (VT), ventricular fibrillation (VF), and death. This case describes a 40-year-old active duty senior pilot who, while undergoing his annual flight physical examination, demonstrated a premature ventricular couplet (PVC) on screening electrocardiogram (ECG). Detailed cardiologic work-up eventually confirmed a diagnosis of type 1 Brugada syndrome. Considered a cardiac ion channel defect, type 1 Brugada syndrome carries a strong probability of permanent disqualification from aviation duties because of the risks associated with sudden cardiovascular incapacitation during flight. Most patients with Brugada syndrome are asymptomatic. Some experts report that sudden cardiac death (SCD) is the presenting symptom in approximately one- third of these patients. It is therefore imperative that a definitive work-up be accomplished to adequately determine the appropriate aeromedicai disposition for patients with these rhythm disturbances despite their benign nature at first glance.
A 40-year-old male senior pilot presented to the flight medicine clinic for his annual flight physical. On initial questioning, he denied any history of chest pain, dyspnea (with or without exertion), orthopnea, dizziness, palpitations, presyncope, or syncope. Additionally, he reported no family history of seizures or SCD. His physical examination was unremarkable except for his ECG, which demonstrated a PVC. He subsequently underwent 24-hour Holter monitor assessment which demonstrated several episodes of asymptomatic five-beat nonsustained VT (nsVT) (Fig. 1). ECG done by the cardiology department revealed several episodes of PVCs with ST- segment elevation in leads V^sub 1^ and V^sub 2^, and associated T- wave abnormalities (Fig. 2).
Since the coronary angiography was normal, an electrophysiological study (EPS) consisting of a ventricular stimulation protocol from both me right ventricular apex as well as the right ventricular outflow tract was then performed. No significant VT/VF could be elicited by EPS. Because there was still a concern regarding the nsVT seen on initial evaluation without definitive diagnosis, a cardiac magnetic resonance imaging was performed which showed nonspecific small areas of fat without associated dilation or dysfunction. It was then decided that an exercise stress test would be used in an attempt to elicit the ventricular ectopy seen on the original Holter monitor tracing. During the stress test, the patient demonstrated several nonsustained runs of complex ventricular ectopy. This did not definitively confirm the diagnosis of Brugada syndrome, and hence a procainamide challenge was performed. This study was significant for STsegment elevation in V^sub 1^ and V^sub 2^ (Fig. 3), and the patient was referred to Dr. R. Brugada for further evaluation. Dr. Brugada felt that the ST-segment change seen on ECG was “very diagnostic” of patients with the type 1 Brugada pattern. He recommended the aviator undergo the implantation of a defibrillator to decrease his risk of SCD from 30% at 3 years to 0.8% to 3%.1 The patient is currently undergoing processing for permanent disqualification from aviation duties as his risk of SCD remains >1% per year.
The diagnosis of Bragada syndrome is based on three main ECG abnormalities as classified by the European Society of Cardiology. Type 1 (coved type) is diagnostic for the syndrome with >2-mm J- point elevation in leads V^sub 1^ to V^sub 3^, down-sloping ST segment, and negative T-waves.2,,3 The severity of the T-wave abnormality tends to correlate with the risk of cardiac events.4 Type 2 (saddle-back type) and type 3 are considered clinically significant if there is a conversion to a type 1 rhythm, either spontaneously or during administration of sodium channel blockers such as procainamide or flecainide. In type 2, the terminal portion of the ST segment is elevated >1 mm and the T-wave may be positive or biphasic, whereas type 3 shows terminal ST elevation <1 mm and the T-wave is positive. Both types 2 and 3 will show the same 2 mm or greater J-point elevation. It is important to remember that type 2 and 3 changes are considered nonspecific for Bragada syndrome unless they convert to a type 1 rhythm after an IC sodium channel blocker challenge. Since types 2 and 3 may give a false positive, abnormalities suggestive of arrhythmogenic right ventricular cardiomyopathy must be ruled out before considering a diagnosis of Bragada syndrome, especially when there is a type I Bragada pattern in response to IC sodium channel blockers. In addition, ST-segment elevation has numerous possible causes, and hence it is important to exclude these other causes before diagnosing patients with Bragada syndrome. Common causes of ST-segment elevation include: acute myocardial infarction, atypical right bundle branch block, hyperkalemia, hypercalcemia, early repolarization, and acute pericarditis.5,6 Other more rare conditions can also mimic Bragada ECG changes, such as hypothermia7 and a mediastinal tumor with mechanical compression on the right ventricle.8
Epidemiological and Clinical Characteristics
The true incidence of Bragada syndrome in the United States is not known. It is thought to be more common in south Asia and is reported to occur in as much as 0.16% of the Japanese population.9 Brugada syndrome is associated with a disorder of sodium ion channels, which normally transport positively charged sodium ions into cardiac myocytes. These “ion channelopathies” have been known to cause arrhythmic heart failure because they reduce the flow of sodium ions into cells, thereby reducing current flow through the cell membrane.10 This disruption in ion transport may be evidenced during periods of increased physical and emotional stress, or fatigue. Mutations in the SCN5A gene have been isolated in ~25% to 30% of index cases. This gene is located on the short arm of the third chromosome (at locus 3p21-23). It alters the structure or function of the channel, and may also affect the regulation of other ion channels (potassium and calcium), further complicating the condition.11,12
Brugada syndrome is often diagnosed in younger, otherwise healthy individuals.13 The typical arrhythmic manifestations begin before the age of 40 and occur predominantly in males.14,15 These patients are prone to life-threatening arrhythmias, leading to symptoms ranging from nightmares resulting in fatigue to syncopal episodes with potential brain damage or death.13 Sudden death is the presenting problem in 30% to 40% of patients.10 Some experts believe that this syndrome is responsible for 4% to 12% of unexplained sudden deaths, as well as up to 20% of all SCD in adults with structurally normal hearts.2 The incidence of Brugada syndrome is estimated at 0.05% to 0.6% in adults, suggesting that the syndrome manifests primarily during adulthood.16
Currently, the only approved treatment for patients with Brugada syndrome is placement of an implantable cardioverter defibrillator (ICD).3,17 This device offers a significant risk reduction in symptomatic type 1 Brugada patients from as high as 30% (per some experts) to as low as 0.8% to 3% annually with the implantable device. There is a general agreement about the high risk of sudden death in some patients: those with a spontaneous type I ECG pattern, those with a history of syncope, and those who are resuscitated from a sudden cardiac arrest. Cardiologists agree that mese patients should receive an ICD, no additional studies indicated. The indication and usefulness of an EPS is debatable for asymptomatic Brugada patients with no family history of SCD; this topic remains the catalyst for debate among the experts.
Brugada syndrome, with its risk of life-threatening arrhythmias, should trigger an extensive investigation based on its potential for VF and SCD. Although there exists a myriad of cardiovascular diseases that are permanently disqualifying in the flying community, patients with Brugada syndrome have an estimated 30% chance of SCD at 3 years by some reports, with some types requiring permanent disqualification. These aviators must be identified early so that appropriate risk stratification and conventional treatment may be offered in a timely manner. To better stratify the risk in patients with the type 1 pattern, three major factors have been suggested: typical ECG pattern, either spontaneous or induced; a history of symptoms, whether syncope or history of VT/VF; and family history of SCD. It is important to remember that the most common clinical presentation of the Brugada syndrome, other than sudden death, is syncope. For this reason, it is paramount that this diagnosis be considered in the differential when a patient experiences syncope.
For patients with type I Brugada syndrome and a personal history of cardiac arrest or syncope, the decision for an ICD is clear. In contrast, only close follow-up is recommended for asymptomatic patients with no family history of SCD. Dissent exists among cardiologists regarding the predictive capacity of EPS when it is used to evaluate individuals who fall in between these two categories, both for risk stratification and as a guide to therapy. However, there is insufficient data to support returning even a low- risk pilot to unrestricted flying without full cardiac evaluation. The controversy surrounding the predictive value of the current risk stratification system reflects a lack of clear data. Dr. R. Brugada believes mat EPS studies may vary because some series have not restricted participation to patients with the diagnostic type 1 ECG. These groups have included patients with type 2 or 3 ECGs (nondiagnostic), which he feels are only a “suggestive” pattern of Bragada,18 type I ECG pattern is the more “lethal” form. Another possible explanation regarding variation in EPS19 results in high- risk patients is the lack of a universally accepted EPS protocol for testing individuals with a genetic defect in SCN5A. Additionally, there are over 80 known SCN5A mutations, making the specific diagnosis difficult. It must be remembered that not all of these gene carriers are at significant risk for clinical disease.
The risk of recurrent tachyarrhythmias, associated hemodynamic symptoms, risk of sudden death, syncope, and presyncopal episodes are all of aeromedicai concern. The identification of these high- risk subjects is one of the major goals in the aeromedicai clinical decision-making process. Often, only an ECG is obtained while evaluating an otherwise asymptomatic patient seen during screening examinations. This ECG can be very dynamic and often conceals the diagnosis, making it difficult to estimate true risk or prevalence in the aeromedicai community. Scanty findings of Brugada syndrome in our aviation population highlight the lack of evidence from which to base a solid aeromedicai decision. Additionally, in evaluating conventional guidelines, there appears to be significant incongruity in evaluating and treating these patients, especially the nondiagnostic Brugada types. It is certain among the experts, however, that SCD is the most compelling concern, which is most notable among the type 1 Brugada pattern. For this reason, symptomatic type 1 Brugada ECG is permanently disqualifying due to risk for sudden death with or without the intervention of an ICD.
The Aeromedicai Consultation Service should review all cases of Brugada-type ECG. Aeromedicai disposition should be granted after the studies have been forwarded to the Aeromedical Consultation Service for review and diagnosis confirmation. First, Symptomatic patients displaying the type 1 Brugada ECG (spontaneous or after sodium channel blockade) should receive an ICD as a class I indication without need for additional studies. Similarly, all type 1 Brugada patients presenting with related history of syncope, seizure, a documented history of VF or polymorphic VT, should undergo ICD implantation after other noncardiac causes have been carefully ruled out. Symptomatic patients with inducible ventricular arrhythmias and a positive family history of SCD may benefit from prophylactic implantation of a defibrillator.20-22 For details about risk stratification and indications for ICD implantation, we recommend that readers review the consensus report by Antzelevitch et al.19
Additionally, second, asymptomatic patients with a nondiagnostic Brugada pattern on routine ECG represent a difficult algorithm. These patients should undergo pharmacological challenge to unmask subclinical primary electrical disease, if there is a family history of SCD which potentially stemmed from Brugada syndrome. If type 1 Brugada ECG is revealed, then the patient should receive an ICD. Asymptomatic patients without family history who have a spontaneous type 1 Brugada ECG or develop a type 1 Brugada ECG after sodium channel blockade should be closely followed-up. Their risk for SCD appears to be low and ICD is not currently recommended for these patients. If a type 1 Brugada ECG is not produced with sodium channel blockade, then recommendation of a regular biannual office assessment by a cardiologist is warranted. These patients, spontaneous or otherwise, should undergo exercise treadmill testing every 6 months with cardiac event monitoring and should be returned to flying status only after omer cardiac and noncardiac causes have been carefully ruled out and if there are no reported cardiac complications after 2 years. In the case of the above patient, some experts would argue that this asymptomatic type 1 Brugada patient, without family history of SCD, is at low risk for SCD and hence ICD is not recommended. Clearly, Dr. Brugada would oppose that sentiment.
In January 2005, the Second Consensus Conference on Brugada Syndrome published its recommendations for ECGbased diagnosis and therapeutic approaches, looking at the use of EPS-namely, programmed electrical stimulation-to better risk-stratify certain patients.19 For symptomatic patients with a type I Brugada rhythm, me guidelines recommend placement of an ICD without further study. Asymptomatic patients with a type I rhythm, whether spontaneous or induced, and wim a family history of SCD, should undergo EPS, with placement of an ICD if positive. There is controversy, however, as to me utility of EPS in asymptomatic patients with a spontaneous type I ECG and no family history of SCD. According to the guidelines, EPS is warranted in these patients and if EPS induces ventricular arrhythmias, then an ICD is indicated. However, if EPS is negative, men ICD is not warranted and close follow-up is recommended. This role for EPS, however, in risk stratification of patients with Brugada syndrome is quite heterogeneous. One major discrepancy has been at the level of the positive predictive value of EPS in asymptomatic individuals.23 Although some authors support it,18,24 others have provided experimental evidence suggesting a poor predictive value and low reproducibility.25 Hence, the results should be viewed with some reservation. A prospective study in Italy, termed PRELUDE (Programmed Electrical Stimulation Predictive) is likely to provide additional insight into mis issue.
ICD placement remains the only definitive therapy for treating VT/ VF in Brugada syndrome; this is not compatible with performance of flying duties. Almough some patients report no symptoms during the general course of the physical evaluation, a more specific line of questioning may be warranted, especially if they meet electrocardiographic criteria for Brugada syndrome and/or report a history of palpitations, syncope, nightmares, or difficulty breathing. The aviator functions in an environment that has inherent psychological stressors (e.g., task saturation and performance of emergency maneuvers) and is exposed to varying degrees of acceleration forces-all of which could pose significant additional cardiovascular and physiological risks for the Brugada patient. Although the prognosis for the type 1 Brugada patient is poor for resumption of a flying career, the aviator may be considered fit for military duties omer than flying after detailed work-up. In either event, it is paramount that a thorough evaluation of each flyer be accomplished to prevent the catastrophic events which may occur during flight.
This article was self-funded; there were no other affiliation or contractual agreements.
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CAPT Dennis D. Walker, USAFMC*; LT COL Monica L. Johnson, USAF MC[dagger]; MAJ Robert W. Craig-Gray, USAF MC[double dagger], MAJ Frank Loyd, USAFR MC[section]
* Element Leader/FSO, 697 Louisiana Drive, Dyess AFB, TX 79607.
[dagger] FS, Chief of Medical Staff/Pediatrician, 697 Louisiana Drive, Dyess AFB, TX 79607.
[double dagger] FS, 1075 West Perimeter Road, Andrews AFB, MD 20762.
[section] FS, 1780 Doolittle Avenue, NAS JRB Fort Worth, TX 76127.
This manuscript was received for review in September 2007. The revised manuscript was accepted for publication in April 2008.
Reprint & Copyright (c) by Association of Military Surgeons of U.S., 2008.
Copyright Association of Military Surgeons of the United States Aug 2008
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