Letter by Santangeli et al Regarding Article, “High-Density Substrate Mapping in Brugada Syndrome: Combined Role of Conduction and Repolarization Heterogeneities in Arrhythmogenesis”
To the Editor:
In their article on high-density substrate mapping in Brugada syndrome, Lambiase and colleagues reported striking endocardial conduction delays in such patients predominantly in the anterolateral right ventricular outflow tract.1 Complex and interesting electrophysiological data are presented, giving new insights into Brugada syndrome features. However, we feel that some methodological flaws in patient characterization, mapping procedure, and data interpretation give different perspectives to their conclusions.
It is clear that concealed myocardial diseases, such as arrhythmogenic right ventricular cardiomyopathy and myocarditis, may cause a Brugada syndrome-like echocardiogram pattern.2,3 Thus, cardiac magnetic resonance imaging and even additional invasive studies, such as endomyocardial biopsy, appear necessary to rule out cardiac structural abnormalities.3,4 However, in Lambiase’s article,1 neither magnetic resonance imaging nor additional tests other than genetic testing were included in the baseline evaluation of the patients with Brugada syndrome, possibly leading to a patient selection bias.
With regard to the mapping procedure, because the authors did not perform bipolar voltage and dynamic substrate mapping, it is our opinion that the reported isochronal maps used to demonstrate areas of delayed conduction are, from a pathophysiological standpoint, incomplete findings.
Indeed, isochronal maps provided by the Ensite array system are not sufficient alone to distinguish a functional from an anatomic area of conduction block. In fact, the areas of delayed conduction observed by Lambiase et al may be caused by areas of conduction boundaries, such as fibrosis or active inflammation,5 or they may be the result of decreased conduction velocity due to ion channel dysfunction. The distinction between these 2 phenomena carries important diagnostic and prognostic information because areas of anatomic conduction block may mask underlying pathological processes (ie, fibrosis, fibrofatty tissue, or inflammation),3 suggesting that a concealed myocardial disease is the underlying cause of the Brugada-like electrocardiographic pattern. Also to this purpose, magnetic resonance imaging is an essential baseline evaluation for these patients.4
Moreover, the authors’ findings of fractionated electrograms, conduction delay, and dispersion actually reinforce the suspicion of a cardiomyopathic substrate.
In conclusion, the authors should be praised for their elegant contribution in reporting an in vivo mechanism of arrhythmogenesis in Brugada syndrome. However, due to the lack of a detailed baseline evaluation and a thorough substrate analysis, we believe that their results are only partially interpretable and worthy of further investigation.
Lambiase PD, Ahmed AK, Ciaccio EJ, Brugada R, Lizotte E, Chaubey S, Ben-Simon R, Chow AW, Lowe MD, McKenna WJ. High-density substrate mapping in Brugada syndrome: combined role of conduction and repolarization heterogeneities in arrhythmogenesis. Circulation. 2009; 120: 106–117.
Corrado D, Basso C, Buja G, Nava A, Rossi L, Thiene G. Right bundle branch block, right precordial ST-segment elevation, and sudden death in young people. Circulation. 2001; 103: 710–717.
Frustaci A, Priori SG, Pieroni M, Chimenti C, Napolitano C, Rivolta I, Sanna T, Bellocci F, Russo MA. Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation. 2005; 112: 3680–3687.
Catalano O, Antonaci S, Moro G, Mussida M, Frascaroli M, Baldi M, Cobelli F, Baiardi P, Nastoli J, Bloise R, Monteforte N, Napolitano C, Priori SG. Magnetic resonance investigations in Brugada syndrome reveal unexpectedly high rate of structural abnormalities. Eur Heart J. 2009; 30: 2241–2248.