Brugada ECG patterns in athletes

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ScienceDirect Journal of Electrocardiology xx (2015) xxx – xxx www.jecgonline.com

Review

Brugada ECG patterns in athletes Eugene H. Chung, MD, FACC, FHRS, FAHA⁎ Division of Cardiology, Cardiac Electrophysiology, UNC School of Medicine, 160 Dental Circle, CB 7075, Chapel Hill, NC

Abstract

Brugada syndrome is responsible for up to 4% of all sudden cardiac deaths worldwide and up to 20% of sudden cardiac deaths in patients with structurally normal hearts. Heterogeneity of repolarization and depolarization, particularly over the right ventricle and the outflow tract, is responsible for the arrhythmogenic substrate. The coved Type I ECG pattern is considered diagnostic of the syndrome but its prevalence is very low. Distinguishing between a saddle back Type 2 Brugada pattern and one of many “Brugada-like” patterns presents challenges especially in athletes. A number of criteria have been proposed to assess Brugada ECG patterns. Proper precordial ECG lead placement is paramount. This paper reviews Brugada syndrome, Brugada ECG patterns, and recently proposed criteria. Recommendations for evaluating a Brugada ECG pattern are provided. © 2015 Elsevier Inc. All rights reserved.

Keywords:

Brugada pattern; High lead ECG; Athletes

Introduction Distinguishing a Brugada ECG pattern from a “Brugada like” pattern can be challenging. This paper aims to briefly review Brugada syndrome (BrS), Brugada ECG patterns (BrEP), and criteria for evaluating screening ECGs in athletes.

Background: Brugada syndrome The ECG pattern comprised of a coved-type rSr’ pattern, ST-segment elevation, and inversion of the terminal portion of the T waves in the right precordial leads, has been the hallmark of BrS since 1992 [1–3]. BrS is responsible for up to 4% of all sudden cardiac deaths (worldwide) and up to 20% of sudden cardiac deaths in patients with structurally normal hearts [4,5]. Manifestations include syncope, atrial arrhythmias, ventricular arrhythmias, and sudden cardiac death in the absence of myocardial ischemia or overt heart disease. The vulnerability to sudden cardiac death seems to occur mostly during sleep or when vagal tone is increased. Inheritance is variable but 15%–30% of cases are attributable to pathogenic variants in the sodium channel gene SCN5A [6–8]. It predominantly affects males and has a predilection for men under 40 in Southeast Asia [5,8,9]. Increased vagal tone, fever, electrolyte disturbances, and ⁎ Division of Cardiology, Cardiac Electrophysiology, UNC School of Medicine, 160 Dental Circle, CB 7075, Chapel Hill, NC 27599. E-mail address: [email protected] http://dx.doi.org/10.1016/j.jelectrocard.2015.05.001 0022-0736/© 2015 Elsevier Inc. All rights reserved.

sodium channel blocking medications can accentuate the ECG pattern. Class I antiarrhythmic agents, such as ajmaline, flecainide, and procainamide, can “provoke” the BrEP and are used in evaluation of suspected BrS patients. Isoproterenol (isoprenaline) and quinidine can normalize the pattern [8]. The pathophysiology behind the BrEP is ascribed to two main hypotheses [10,11]. The first implicates abnormal repolarization: loss of Na current due to mutations in SCN5A results in “unopposed” outward K current by Ito, creating a voltage gradient (from dispersion of refractoriness) between the epicardium and endocardium in the right ventricle (RV) and RV outflow tract, where there are fewer M cells, causing the BrEP changes [12]. The second hypothesis, and not necessarily mutually exclusive of the first, implicates delayed depolarization and structural alterations in the RV and RV outflow tract [5,12,13]. A recent small but intriguing study utilizing electrocardiographic imaging (ECGI) showed that both repolarization and conduction (or depolarization) abnormalities are present in BrS patients [11]. The heterogeneity of repolarization and depolarization generates the arrhythmogenic substrate for polymorphic ventricular tachycardia or ventricular fibrillation.

Brugada ECG pattern While diagnosing BrS should include both clinical history and ECG findings, the Type 1 BrEP alone is now considered diagnostic [12,14]. Classically, the Type 1 BrEP has a coved

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Fig. 1. Classic Brugada ECG patterns. Type 1 is considered diagnostic of Brugada syndrome. Types 2 and 3 were grouped together as Type 2 in a recent consensus report. From Ref. [7].

ST segment elevation ≥ 2 mm, negative T wave and no isoelectric separation of T wave (Fig. 1); Type 2 BrEP has a saddleback appearance with an ST segment elevation of ≥ 2 mm, trough that is still ≥ 1 mm ST elevation and a positive or biphasic T wave; Type 3 BrEP is also saddleback but has an ST segment elevation of b 1 mm. A consensus report combined Type 2 and 3 as Type 2 [12]. Another recent expert consensus statement states: “[Brugada syndrome] is definitively diagnosed when a Type 1 ST-segment elevation is observed either spontaneously or after intravenous administration of a sodium channel blocking agent (e.g. ajmaline, flecainide, pilsicainide, or procainamide) in at least one right precordial lead (V1 and V2), which are placed in a standard or a superior position (up to the 2nd intercostal

space)”[15]. The prevalence of the BrEP is very low: in a cohort of approximately 12,000 apparently healthy Europeans, only 23 (0.19%) had any BrEP; of these, only 2 had the Type 1 pattern [16].

Distinguishing and evaluating “Brugada-like” ECGs Distinguishing between a BrEP and “Brugada-like” (also called rSr’, non Type 1, Type 2 Brugada type) pattern can be challenging, especially in athletes. A recent new term, “Brugada phenocopy”, has been proposed to describe a BrEP, in a person without true BrS, provoked by agents or clinical situations not expected to unmask true BrS, such as

Fig. 2. Electrocardiographic differential diagnosis for Brugada-like ECG patterns. From Ref. [12].

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Fig. 3. Comparison of V1 and V2 in standard (4th intercostal space) and high lead (2nd intercostal space) in a screening ECG on a varsity basketball player. From Ref. [35].

hyperkalemia [10]. “Brugada-like” is used here as it encompasses potential true Type 1 and 2 patterns as well as the Brugada phenocopies.) Differential diagnosis includes both physiologic (eg normal variant, incomplete right bundle branch block) and pathologic causes (eg right ventricular hypertrophy, arrhythmogenic right ventricular cardiomyopathy (ARVC), pulmonary hypertension, hyperkalemia) [12,13] (Fig. 2). Exercise stress testing might reveal transient augmentation of ST segment elevation that is diagnostic of BrS [17,18]. Intravenous adrenoreceptor stimulation can also augment Type 1 ST elevation [19]. First degree AV block, left axis deviation, and atrial fibrillation are additional ECG findings that could be suggestive of BrS [15,20]. Patients with known or suspected BrS can display normal or non-diagnostic ECG findings [10]. In these cases, administration of a sodium channel blocker may produce a Type 1 pattern and support the diagnosis [10,21,22]. In asymptomatic patients without known BrS or family history of sudden death (ie, a potential case of concealed BrS), a BrEP can be “acquired” by exposure to both cardiac and non-cardiac drugs with sodium channel blocking properties. Offending noncardiac agents that have been reported include tricyclic antidepressants, lithium, cocaine, and bupivacaine [10,21,22]. Fever can precipitate the BrEP and may be the precipitating symptom approximately 20% of the time [23,24]. Management of the asymptomatic patient with a spontaneous Type 1 pattern remains controversial [13,15,25]. In screened athletes this scenario is rare but warrants a cardiac consultation. In the largest registry to date from 11 European referral centers, asymptomatic patients with sodium channel blocker induced Type 1 pattern had a low event rate of 0.55%, but other studies have reported higher rates [25,26]. Although the data are limited, subjects in whom the Type 1 ECG normalizes once the offending agent has been discontinued or febrile illness resolved may still represent a high risk group [27]. For instance, if the BrEP was attained after amitriptyline use or a febrile illness, one should

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consider the presence of concealed BrS [10,22]. Workup is not indicated for an asymptomatic patient with a Type 2 pattern. An rSr’ pattern is less than 10% common in the general population but is seen in up to 50% of highly trained athletes [28,29]. Endurance athletes, particularly male, have a higher prevalence of an rSr’ pattern and it may be due to slowing of conduction from exercise-induced RV enlargement [30,31]. Incomplete right bundle branch block pattern is not common in ARVC but in conjunction with T wave inversions could be suggestive of ARVC. Early repolarization in athletes is highly prevalent, generally benign, and remains the subject of much debate and investigation [14,32]. There are features common to BrS and early repolarization including male predominance, vagal influence, and normalization with quinidine [14]. Typically, an rSr’ pattern in an athlete is characterized by a narrow r’ and minimal ST elevation compared to the broader r’ in BrS patients [29]. However, the rSr’ (or rSR’ if right bundle branch block pattern) in patients without BrS can appear “Brugada-like”. One potential etiology of Brugada-like patterns is improper recording of ECG tracings. High pass filtering has also been shown to provoke an rSr’ reminiscent of a BrEP [33]. High placement of the precordial leads (placing V1 and V2 in the 2nd or 3rd intercostal space) accentuates a Type I pattern in a known Brugada patient but can also cause an rSr’ pattern in general patients [34]. A number of groups, including ours, have reported commonly obtaining (up to a third) Brugada-like patterns when V1 and V2 ECG leads are purposely placed high in both athlete and non-athletes [35–41]. Classic Type 2 or Type 3 (now grouped as Type 2) was noted in approximately 12% of athletes over two years or pre-participation screening in our study when V1 and V2 were purposely placed in the second intercostal space [35] (Fig. 3). No baseline Type 1 patterns were seen, and no Type 1 patterns were produced with high lead tracings. In an analysis of 8 male football and basketball players with a Brugada-like high lead ECG, we did not identify any abnormal point of maximal impact (PMI) or echo chamber measurements to explain the rSr’ recordings

Fig. 4. The “Corrado Index” for distinguishing anterior early repolarization from Brugada ECG pattern. From Ref. [43].

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Fig. 5. Criteria for evaluating Brugada-like rSr’ patterns that appear. From Ref. [46].

(unpublished data). The subjects were asymptomatic and did not undergo pharmacologic provocation to attempt to induce a Type 1 BrEP. Our findings, which were most significant in tall and heavy male athletes, underscore the importance of proper ECG lead placement. Misplaced leads can generate misdiagnosis and unnecessary activity restriction and cardiac testing. A number of criteria have been proposed to help distinguish between BrEP and Brugada-like ECGs, especially in athletes. The Type 1 BrEP should be distinguishable from the ST segment elevation of early repolarization by recognizing differences in the morphology of the r’ and ST segment. Corrado et al. described the “Corrado index” which measures the height of the ST elevation at the beginning of the ST segment (ST-J) and 80 ms after (ST-80) [31,42]. Type 1 BrEPs will have an ST-J:ST-80 ratio N 1, reflecting the downsloping nature of r’, whereas early repolarization patterns will have an ST-J:ST-80 ratio b 1, reflecting the upsloping nature of the ST segment (32, Fig. 4). Although it has been shown that the high take-off of the QRS-ST does not always coincide with the J point, Zorzi et al. recently reported the high accuracy of the Corrado index in a small cohort of athletes and Brugada patients [10,43]. Similarly, Okhubu et al. and Chevalier et al. both observed that the angle formed by the ascending and descending limbs of r’ is significantly larger in patients with Type 2 BrEP [44,45]. Chevalier specifically noted a β angle of 58° as the optimal cutoff [44]. Serra et al. recently compared the β angle with three additional criteria that form triangles using the upslope and downslope of the r’ wave [46] (Fig. 5). The length of the triangle measured 5 mm below the peak of r’ was deemed the easiest [46]. While all of these criteria are intriguing, they have been studied in small series of patients and need to be tested further in larger cohorts. Recommendations 1. When presented with an athlete’s screening ECG with a Brugada-like pattern, it is paramount to ensure that the precordial leads were placed properly and to repeat the ECG if necessary. 2. The diagnosis of BrS should be strongly considered if the baseline ECG or a high precordial lead ECG (with V1 and V2 placed as high as the 2nd intercostal space) reveals a Type 1 pattern [15]. The 2010 European Society of Cardiology recommendations, the 2012

3.

4.

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Seattle Criteria, and the most recent Refined Criteria recommend referral of patients with Type 1 BrEPs to cardiac specialists [29,47,48]. A patient with a BrEP consistent with Type 2 and has a Type 1 BrEP induced by drug provocation with a sodium channel blocker is considered to have BrS [15]. Patients with a transient Type 1 BrEP brought on by a known offending agent (such as a tricyclic antidepressant) and/or fever may be at higher risk for a cardiac event and should be further evaluated by a cardiac specialist. Asymptomatic patients with a Type 2 BrEP and no concerning family history do not require further workup. This group likely represents a low risk group [49]. Evaluation of Brugada-like ECG patterns in athletes that are not clearly Type 1 or Type 2 should involve confirmation of lead placement, clinical history (including family history) and application of published ECG criteria. The ST segment in true BrEP is more downsloping than in early repolarization patterns. The r’ in true BrEP is broader than that in Brugada-like patterns and relatively new algorithms for evaluation have been proposed [43–46].

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