The relevance of electrocardiogram filtering in the differential diagnosis of Brugada syndrome: An illustrative case report

Abstract

We present a clinical case of a teenager in whom a Brugada syndrome electrical pattern was found which was finally diagnosed as a Brugada phenocopy due to a wrong setup of the high-pass filter on the electrocardiogram

Brugada syndrome is a rare (prevalence of 0.01% in children) yet potentially life-threatening channelopathy associated with various gene mutations, being SCN5A the most common in those patients with a positive genotype. ¹ It is characterised by unique electrical features, including two distinctive electrical patterns with ST-segment elevation in right precordial leads (V1–V3): coved (type 1) or saddleback (type 2) (Table 1). ² Only type 1 pattern, spontaneous or induced by the administration of a sodium channel blocker, is associated with arrhythmogenic potential, and enough for final diagnosis. ^2,3

Table 1. Brugada phenocopy categories and diagnostic criteria (adapted from Anselm et al.) ⁵

The increasing awareness of Brugada syndrome and the use of electrocardiograms in community or school-based pre-sports cardiac screenings have led to increased referrals to paediatric cardiologists for potential cases. ⁴ Diagnosing Brugada syndrome in children is complex due to its low prevalence, the intermittent nature of electrocardiogram patterns, which typically manifest with fever, and the occasional clinical overlap with neurogenic syncope or convulsions. Hormonal influences can further complicate diagnosis due to the potential for electrocardiogram changes if the syndrome manifests during puberty. Furthermore, drug provocation and genetic tests may not be efficient in children. ^3,4 Therefore, definitive diagnosis typically requires continuous observation and a comprehensive evaluation, with accurate electrocardiogram interpretation being essential.

Recently, Brugada phenocopies have been defined as a heterogeneous range of clinical scenarios in which electrocardiogram patterns are indistinguishable from those of Brugada Syndrome, but these patterns disappear when the underlying cause is resolved, with no clear association of these phenocopies with sudden death. ⁵ We present a case of Brugada phenocopy, underlining the critical importance of recognising such cases to prevent unnecessary interventions associated with Brugada syndrome diagnosis.

During cardiac screening event before competitive sports practice, an asymptomatic and previously healthy 10-year-old boy with no relevant family history was found to have a Brugada syndrome type 2 electrical pattern (Fig. 1a, b). He was referred for specialised cardiological evaluation, with temporary contraindication to practice sports, informing the family about the risk of sudden cardiac death. We conducted a physical examination which was normal, also baseline and serial electrocardiograms of the patient and parents (also with the placement of precordial leads V1, V2, and V3 on the chest up to the second and third intercostal spaces), echocardiography, Holter monitoring, and treadmill testing, all of which were normal. Finally, we observed that the only pathological electrocardiogram was performed manually, with a low-frequency high-pass filter of 0.67 Hz on analogical equipment, while all normal electrocardiograms were performed with 0.05 Hz on digital devices (Fig. 1c). Although we could not trace back the exact electrocardiogram machine used, the family confirmed the absence of screens in it, and only printed (not digital) records were available. The strip format, printing 6 leads on one strip followed by another 6 on a separate strip, during a community-level health screening, suggested a non-standard electrocardiogram machine, and this idea is further supported by the 0.67 Hz high-pass filter, common in ambulatory or bedside monitoring settings. Given the very low pre-test probability of Brugada syndrome and the potential technical error of using a non-standard electrocardiogram machine, we categorised the patient as a Brugada phenocopy type 2C. A clinical and electrocardiogram follow-up was conducted, avoiding provocative pharmacological testing and genetic study, allowing the patient to re-engage in sports without incidents for two years so far.

Figure 1. a and b. 12-lead electrocardiogram performed manually at the centre of origin with an analog electrocardiogram with a high-pass filter which had a frequency of 0.67 hz (lower left area of Fig. 1a). Right precordial leads (V2-V3) show convex ST-segment elevations ≥2 mm with respect to the isoelectric line of base, with saddleback morphology. c. 12-lead electrocardiogram performed in our centre with digital electrocardiogram and high-pass filter with a frequency of 0.05 hz (upper right area of Fig. 1c), in which no abnormalities were observed. Note that the applied 45 hz low-pass filter in Figure 1c is also incorrect but did not influence the diagnosis of our patient, American Heart Association recommend a minimum of 150 hz for the low-pass filter. ECM: myogram or muscle filter. DFT0: drift filter. Note that DFT could refer to any filter, but the value 0,67 hz is usually a configuration used for high-pass filters. Hz = hertz.

Electrical filtering is a technical aspect of the electrocardiogram aimed to reduce noise or interference to obtain high-quality tracings. Incorrect filtering cut-off points could have potential clinical implications in conditions like Brugada syndrome, where the electro is a crucial diagnostic and prognostic tool. In 2014, Anselm and colleagues ⁵ proposed an updated classification of causes, diagnostic criteria, and types of Brugada phenocopy (Table 1). Our case exemplifies Brugada phenocopy type 2C, ^5,6 secondary to inadequate electrocardiogram modulation due to the inappropriate application of a high-pass filter > 0.5 Hz instead of the recommended 0.05 Hz by the American Heart Association. ⁷ This filter can be amplified to 0.67 Hz when using linear-phase or zero-phase distortion filters, but not with traditional nonlinear-phase analogic filters like the one used for our patient only pathological electrocardiogram. The application of this filter attenuates low-frequency noise, which appears as baseline oscillation caused, for example, by respiratory movements. ⁶ These artefacts are more frequent in right precordial leads and in the ST segment, which are crucial in the differential diagnosis between Brugada syndrome and Brugada phenocopy, making proper filtering essential to avoid misdiagnoses that lead to interventions that might negatively impact patients’ quality of life, such as avoiding sports activities, additional diagnostic tests, and the emotional burden of communicating a risk of sudden death.

It is noteworthy that, although adequate electrocardiogram surface filtering is one of the 8 diagnostic criteria for Brugada phenocopy, its incorrect application has been described in up to 62% of ambulatory electrocardiograms, ⁸ highlighting the lack of awareness of these parameters in routine clinical practice. We acknowledge that we applied a 45 Hz low-pass filter instead of the recommended 150 Hz filter in the ‘normal’ electrocardiogram shown in Figure 1C. Of note, this error is more common (96%) than incorrect high-pass filter in clinical practice. ⁸ The inadequate low-pass filter might affect R-wave amplitude measurements used in left ventricular hypertrophy criteria and Q-wave measurements used in myocardial infarction diagnosis. Therefore, we believe it did not significantly impact the diagnostic assessment of our patient. Additionally, a controversial aspect of the Brugada phenocopy diagnosis in our case is the absence of a negative provocation test with sodium channel blockers (a mandatory criterion). ⁵ The recent update in Brugada phenocopy types introduces class C for patients with a high suspicion based on the electrocardiogram, but in whom pharmacological testing is not justified due to specific electrocardiographic filter alterations. ^3–5 Furthermore, although it is a safe test, its efficiency and sensibility in the paediatric population is low, with a high rate of false negatives before puberty, especially in asymptomatic cases without family history, and also carries a negative psychological impact. ^1,3,4 We also did not request a genetic study, which is a desirable but not mandatory criterion ³ due to its low efficiency, and it is currently not recommended for patients with isolated Brugada type 2 electrical patterns. ^1,2 Due to the recent description of Brugada phenocopies, there is uncertainty regarding its natural history and the actual risk of sudden death. ⁵ Therefore, clinical and electrical follow-up of these patients is advisable, without lifestyle modifications, with an emphasis on performing electrocardiograms during episodes of fever in paediatrics. ^1,3

Finally, we would like to remark the wide range of implications within cardiac screening programmes conducted in non-clinical settings. Despite ongoing debates regarding the utility of performing electrocardiograms in pre-sport cardiac screenings, there is a growing body of evidence supporting their effectiveness. ⁹ However, the use of electrocardiogram machines with non-standard configurations in community or school events could significantly elevate the rate of false positive results. This can potentially lead to unwarranted follow-up tests, increased anxiety among patients, and augmented healthcare costs. To address this concern, educational programmes for healthcare professionals on the selection of electrical equipment and adequate configurations might be of help, ensuring their appropriateness for the specific screening population is paramount.