Marked PR interval variability in a patient with Brugada syndrome.

To the Editor The authors present a clinical case of a 54-year-old woman without relevant medical history other than Brugada type 1 pattern in the electrocardiogram, without chronic medication, who was referred for the cardiology outpatient clinic with palpitations. She had a strong family history of Brugada syndrome, but no history of sudden death, and she never had syncope. A transthoracic echocardiogram was performed, ruling out structural heart disease. Blood samples were analyzed, without thyroid function or electrolyte abnormalities. A 24-hour Holter examination was performed (digital Philips Zymed Holter, Model 1810 Plus Software, Philips Medical Systems) that revealed nocturnal periods of first-degree atrioventricular block (AVB) with a markedly variable PR interval and without nonconducted P waves; no other abnormalities were seen; the patient was asymptomatic. The P wave and QRS morphology were the same throughout the examination. The PR interval either increased or decreased, but it was always followed by a QRS complex. The number of P waves was the same as the QRS complexes. There was no relation between the PR interval variability and heart rate or circadian predominance. The patient is kept under follow-up in the outpatient clinic, uneventful. No genetic test was performed. First-degree AVB is typically a benign situation1; however, it is associated with increased incidence of atrial fibrillation, heart failure, and mortality during follow-up.2 In some clinical settings, it can even be associated with markedly decreased survival.3 Some data point out that first-degree AVB on a basal ECG is an independent predictor of malignant arrhythmic events in Brugada syndrome (although this association was only demonstrated with first-degree AVB on basal ECG and not on Holter examination).4,5 The PR interval is highly affected by the autonomic nervous system.6-9 Sympathetic activation results in a decrease of the PR interval, whereas parasympathetic activation originates an increase of the PR interval.6,7 Previous studies showed that the increase in PR interval in response to vagal stimulation is well correlated with vagal stimulation frequency and can be regarded as linear.7 The Brugada syndrome is diagnosed in the presence of a spontaneous type 1 pattern in patients without other heart disease, regardless of symptoms.10 It is a genetic sodium-related (INa) channelopathy.10 The most common gene involved is the SCN5A, which is also associated with conduction diseases.11 Sodium currents are responsible for propagation of action potential through the myocardial cells. As patients with Brugada syndrome have reduced INa current, conduction disease is not unexpected to occur, if the SCN5A gene is involved.12 First-degree AVB could represent a marker of increased risk because of a stronger phenotype of INa reduction, leading to increased myocardial electrical instability.5 Other identified risk markers are the localization of type 1 Brugada pattern (Figs. 1 and 2), atrial fibrillation, fragmented QRS, QRS duration >120 ms, R wave in lead aVR, S wave in lead I (≥40 ms, amplitude ≥0.1 mV, area ≥1 mm2), early repolarization pattern in inferolateral leads, ST segment depression, T‐wave alternans, dispersion of repolarization, and Tzou criteria.11 In another recent study, the S wave in lead I was the only independent predictor of persistent risk of life-threatening arrhythmic events.13Figure 1.: ECG revealing sinus rhythm with type 1 Brugada pattern.Figure 2.: (A) Holter revealing sinus rhythm with type 2 Brugada pattern and first-degree AVB with a progressive PR interval prolongation; (B) continuation of previous Holter stripe; and (C) variable PR interval, always followed by a QRS complex. A type 1 Brugada pattern was not present in this examination.The significance of this PR interval variability, with a “harmonic” appearance, is not yet known, as well as its clinical implications.