We have read with interest the scientific letter published by Santiago-Cortés et al.1 The distinction between Brugada phenocopies and Brugada syndrome can sometimes be a complex diagnostic challenge. This differential diagnosis requires restraint and precision, as these entities differ not only in their etiology, but also in the potential prognostic implications for patients.1,2

The scientific letter by Santiago-Cortés et al. describes the case of a 12-year-old adolescent with a type 1 Brugada electrocardiographic pattern in the context of febrile syndrome (pediatric multisystem inflammatory syndrome associated with SARS-CoV-2) that resolved after stabilization and improvement of the infectious-inflammatory condition.3 Outpatient provocation testing with flecainide and genetic testing were both negative and, therefore, Brugada phenocopy was diagnosed.3

First, we agree with the authors that the overall findings were consistent with Brugada phenocopy, namely, a Brugada electrocardiographic pattern induced by a clearly identifiable condition that reverts after correction, low pretest probability of Brugada syndrome, and negative results in induction and genetic tests.1 However, in this particular patient, we believe that the fact that inflammatory syndrome plus fever were considered a potential reversible condition when diagnosing Brugada phenocopy deserves special attention. The clinical conditions traditionally reported to exhibit Brugada pattern in phenocopies are related to: a) metabolic conditions; b) mechanical compression; c) ischemia and pulmonary embolism; d) myocardial and pericardial disease, and e) electrocardiogram-amplitude modulation.4 Fever is not usually listed among the conditions, as elevated body temperature outside the physiologic range is considered a genuine trigger for uncovering true Brugada patterns because the arrhythmogenic potential of cardiac sodium channels is increased at high temperatures.5,6 Additionally, from a clinical rather than pathophysiologic standpoint, numerous reports and case series have shown that patients with fever that induced a Brugada-like electrocardiogram have later experienced malignant arrhythmia.7

Induction and genetic tests were used in this patient to support the Brugada phenocopy diagnosis. However, the sensitivity of induction tests is only 70% to 80%, and this specific patient experienced slight QRS widening after flecainide administration, although with no clear ST-segment changes.8 Only a few Brugada syndrome cases are due to known gene mutations, and patients who have exhibited Brugada pattern in the context of fever could later experience malignant arrhythmia despite no genetic predisposition.7,9 Therefore, in the event of an unusual predisposing factor for the diagnosis of Brugada phenocopy, as seen on this occasion, the ability of these tests to define the condition is somewhat debatable, as negative results are not too useful. An alternative diagnostic approach could include serial tests with increasing doses of sodium channel blockers to improve the diagnostic accuracy of provocation tests if there is diagnostic uncertainty.

Accurate differentiation between Brugada syndrome and Brugada phenocopies has major prognostic implications for patients. The diagnostic process should include a careful assessment of all established criteria for both entities while considering that the current information available seems to indicate that triggering factors of Brugada-like electrocardiographic pattern seem to have varying molecular and pathophysiologic consequences as well as different implications for the clinical prognosis. This will ensure an appropriate approach to therapy and follow-up for each individual patient.10