Electrocardiographic methods for diagnosis and risk stratification in the Brugada syndrome

Abstract

The Brugada syndrome (BrS) is a malignant, genetically-determined, arrhythmic syndrome manifesting as syncope or sudden cardiac death (SCD) in individuals with structurally normal hearts. The diagnosis of the BrS is mainly based on the presence of a spontaneous or Na + channel blocker induced characteristic, electrocardiographic (ECG) pattern (type 1 or coved Brugada ECG pattern) typically seen in leads V1 and V2 recorded from the 4th to 2nd intercostal (i.c.) spaces. This pattern needs to be distinguished from similar ECG changes due to other causes (Brugada ECG phenocopies). This review focuses mainly on the ECG-based methods for diagnosis and arrhythmia risk assessment in the BrS. Presently, the main unresolved clinical problem is the identification of those patients at high risk of SCD who need implantable cardioverter-defibrillator (ICD), which is the only therapy with proven efficacy. Current guidelines recommend ICD implantation only in patients with spontaneous type 1 ECG pattern, and either history of aborted cardiac arrest or documented sustained VT (class I), or syncope of arrhythmic origin (class IIa) because they are at high risk of recurrent arrhythmic events (up to 10% or more annually for those with aborted cardiac arrest). The majority of BrS patients are asymptomatic when diagnosed and considered to have low risk (around 0.5% annually) and therefore not indicated for ICD. The majority of SCD victims in the BrS, however, had no symptoms prior to the fatal event and therefore were not protected with an ICD. While some ECG markers such as QRS fragmentation, infero-lateral early repolarisation, and abnormal late potentials on signal-averaged ECG are known to be linked to increased arrhythmic risk, they are not sufficiently sensitive or specific. Potential novel ECG-based strategies for risk stratification are discussed based on computerised methods for depolarisation and repolarisation analysis, a composite approach targeting several major components of ventricular arrhythmogenesis, and the collection of large digital ECG databases in genotyped BrS patients and their relatives.

Keywords: AP, action potential; ARI, activation-recovery intervals; BrS, Brugada syndrome; Brugada syndrome; ECG, electrocardiogram; EPS, electrophysiology study; Electrocardiogram; Genetic arrhythmic syndromes; ICD, implantable cardioverter-defibrillator; IHD, ischaemic heart disease; LBBB, left bundle branch block; MAP, monophasic action potential; MI, myocardial infarction; PCA, principal component analysis; RVOT, right ventricular outflow tract; Risk stratification; SAECG, signal-averaged electrocardiogram; SCD, sudden cardiac death; SNP, single-nucleotide polymorphism; Sudden cardiac death; VF, ventricular fibrillation; VT, ventricular tachycardia; WT, wavelet transform.

Figure 1

Leads V1–V3 from a resting 12 lead ECG in a 32-year-old man with the BrS. Note the typical type 1 pattern in leads V1 and V2 and type 2 patterns in lead V3. In this one and in all subsequent figures, ECGs are displayed at 25 mm/s, 1 cm/mV, unless stated otherwise. All ECGs presented on this one and all subsequent figures have been originally acquired with high-pass filter of 0.05 Hz.

Figure 2

Resting ECG in a 45-year-old asymptomatic man with BrS, with simultaneous recording of leads V1 and V2 from the 4th, 3rd and 2nd intercostal (i.c.) space (leads V1, V2, V13, V23, V12 and V22, respectively) as well as lead V3 in standard position and one (V33) and two (V32) i.c. spaces higher. Note that for all three leads (V1, V2 and V3), Brugada type 1 pattern appears either only or more clearly in the ‘high’ positions (3rd and 2nd i.c. spaces) compared to their standard locations. For example, lead V3 shows no Brugada type pattern in the standard position, clear type 2 pattern is one i.c. space higher, and marked type 1 pattern, when the electrode is moved, is two i.c. spaces higher. See the text for details.

Figure 3

Snapshot from a positive diagnostic ajmaline test in an asymptomatic 50-year-old man with BrS and non-diagnostic resting 12-lead ECG. Lead V1 and V2 leads from the 3rd and 2nd i.c. space were not recorded because the test was performed before the diagnostic value of the ‘high’ right precordial leads was established. The ECG on the figure was recorded four minutes after the start of the test. The standard unipolar lead V2 still displays non-diagnostic type 2 pattern, whereas the bipolar leads between the V2 electrode (positive pole) and V4, V5 or V6 electrode (leads V2_4, V_5, V2_6, respectively) display typical type 1 pattern. One minute later, diagnostic type 1 pattern appeared in lead V2 as well (not shown).

Figure 4

Type 2 (lead V2) and type 3 (lead V1) Brugada ECG pattern. Note that both ECG patterns are characterised by the same general shape of the J-ST-T wave, but the ST segment elevation in lead type 3 pattern (lead V1) is slightly less than 0.1 mV.

Figure 5

ECGs recorded at baseline (left panel) and six minutes after the start of diagnostic ajmaline test (right panel) with positive outcome in an asymptomatic 35-year-old man who was investigated because his resting ECG (acquired for different reasons) had shown changes suspicious of the BrS. In both panels, the leads from top are V1, V2, V3 and V1 from 3rd i.c. space (lead V13), V2 from 3rd i.c. space (lead V23) and V3 from one i.c. space higher than the standard position (lead V33). Note the presence of type 2 pattern in lead V2 (3rd i.c. space) at baseline which is subsequently converted to typical type 1 pattern following ajmaline administration. During the test, type 1 pattern is also seen in lead V1 (3rd i.c.) whereas in lead V2, the normal ECG configuration is transformed by the drug into type 2 pattern.

Figure 6

Examples of typical type 1 Brugada ECG pattern with (left panel) and without QRS notching/fragmentation. Lead V1 from the 4th, 3rd and 2nd i.c. space is shown. (A) Fractionated QRS complex in a 25-year-old asymptomatic male patient with BrS (ajmaline-induced type 1 Brugada ECG pattern); (B) Spontaneous type 1 Brugada ECG pattern in a 53-year-old man with aborted cardiac arrest, implanted ICD, and subsequently multiple appropriate shocks of the device. No considerable fractionation of the QRS complex can be seen. See the text for details. The examples above suggest that although the presence of QRS notching/fragmentation is linked to increased risk of sudden cardiac death in the BrS, its sensitivity and specificity may not be very high. See the text for details.

Figure 7

(A) A signal-averaged ECG (SAECG) with abnormal late potentials in a 60-year-old man with no previous history of arrhythmic symptoms and spontaneous type 1 Brugada ECG pattern. The total filtered QRS duration, the duration of the high frequency low amplitude (HFLA) <40 μV and the root-mean-square voltage (RMS) in the terminal 40 ms of the QRS are 137 ms, 55 ms and 15 μV, respectively (all three parameters are abnormal). The noise level is 0.25 μV, the number of averaged complexes is 214 and the filter settings are 40–240 Hz. (B) Resting ECG of the same patient. Only lead V1–V3 from 4th to 2nd i.c. space are shown. Note the presence of typical type 1 Brugada ECG pattern in many leads, with QRS fractionation in leads V1 (4th and 3rd i.c. space) and V2 (3rd and 2nd i.c. space). Note also that the type 1 Brugada pattern generally becomes more pronounced when moving the recording electrodes cranially from 4th to 2nd i.c. space (it is present even in lead V3 when recorded 2 i.c. spaces higher (lead V32), which is a relatively rare finding).

Figure 8

Principal component analysis (PCA) of the ST-T wave (from the J point to the end of the T wave) in the right precordial leads of ECGs recorded during diagnostic ajmaline test. (A) Positive ajmaline test in a 15-year-old girl with the BrS and a past history of syncope of presumable arrhythmic origin. (B) Negative ajmaline test in a 67-year-old asymptomatic man with a family history of BrS and sudden cardiac death. Each bar represents the PCA value (ratio of the 2nd/1st eigenvalue) from analysis of one 10-s ECG recording. Two to five 10-s ECGs were recorded during the test. On the X-axis, time is shown in minutes from the beginning of the test. ECGs were recorded at baseline (b) as well as up to 15 min after the start of the drug administration. PCA has been applied to the V1–V3 leads (blue diamonds) and to leads V1–V3 recorded from the 3rd i.c. space (red diamonds). Data are presented as mean ± standard deviation (SD) of all complexes within one 10-s ECG. Generally, higher values reflect more heterogeneous (and, hence, more abnormal and potentially more arrhythmogenic) ventricular repolarisation. The figures show that the appearance of diagnostic type 1 Brugada ECG pattern during the positive test (A) is accompanied by a striking increase in the PCA ratio, whereas during a negative test, there is practically no change in PCA (the SD deviation bars are hidden within the diamond bars). Adapted from .

Figure 9

PCA of the QRS complex of leads V1–V3 from the 3rd i.c. space recorded during positive ajmaline test in patients with previous history of arrhythmia-related symptoms (n = 6, brown bars), during positive ajmaline test in asymptomatic patients (n = 17, yellow bars) and in patients with negative ajmaline tests (n = 73, blue bars). Data are presented as mean ± standard error (SE) of all ECG complexes recorded during one minute of the tests as well as at baseline. Note the distinctly different pattern of PCA of the QRS in symptomatic and asymptomatic BrS patients with positive ajmaline test. In the latter group, PCA of the QRS is similar to those with negative ajmaline tests. See the text for details. Adapted from .