Author + information
- aDepartment of Clinical and Experimental Cardiology, Heart Centre Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
- bDepartment of Medicine, Columbia University Irving Medical Centre, New York, New York
- ↵∗Address for correspondence:
Dr. Arthur A.M. Wilde, Department of Cardiology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
The definition of the diagnosis of Brugada syndrome (BrS) has undergone a number of modifications over the years. The electrocardiography (ECG) signature, that is, the right precordial coved type ST-segment elevation, has been key for the diagnosis in all consensus documents, but the number of required positive leads, the position of the leads (2nd, 3rd, or 4th intercostal space) and the circumstances under which the ECG sign is picked up, have varied. In the last consensus document, by analogy with the long QT syndrome, for the first time a score system was proposed in which a spontaneous appearance of the characteristic ECG (3.5 points) would be sufficient for the probable or definite diagnosis of BrS (≥3.5 points; possible BrS and nondiagnostic were assigned scores of 2 or 3 and <2 points, respectively) (1). The proposed scoring system, referred to as the Shanghai BrS Score, was based on the studies available at that time and on the opinion of 17 experts gathered together in a 5-day meeting in Shanghai in April 2015 (1). The most important deviation from the immediately preceding Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society guidelines (2) is that the presence of a fever-induced or drug-induced ECG (respectively, 3 and 2 points) does require additional clinical criteria for the diagnosis of BrS. In that document, it was explicitly stated that “As with all such recommendations, they will need to undergo initial and ongoing validation in future studies” (1). Notably, in the Shanghai document the drug- or fever-induced ECG was again discriminated from a spontaneous type 1 ECG, as it used to be in the preceding consensus document from 2005 (3).
In this issue of JACC: Clinical Electrophysiology, the Okayama, Japan, group, which has published important papers on BrS previously, is the first to challenge the Shanghai scoring system (4). A cohort of 393 BrS patients was divided into 4 groups with varying scores (<3.5, 3.5, 4.0 to 5.0, and ≥5.5). Of the 348 patients with a definite diagnosis of BrS (88%), 81 had a score of ≥5.5, and all patients with prior ventricular fibrillation were in this group (which is no surprise because the presence of a spontaneous type 1 ECG and documented arrhythmia already equals 6.5 points). Forty-five patients had a score of <3.5 (possible or nondiagnostic for BrS), and by definition, none of these patients could have had a spontaneous type 1 ECG. The intermediate groups consisted of 186 patients (with 3.5 points) and 81 patients (with 4.0 to 5.0 points), respectively. Because genetic testing was only performed in 167 patients (42%) and a positive test provides 0.5 point, a small shift toward higher scores could have been expected if all these patients had been genotyped.
More importantly, the authors also tested whether the scoring system might be useful for risk stratification. Indeed, risk stratification in BrS is ill-defined, and many potential parameters are disputed based on noncoherent results in different cohorts (5). The Shanghai risk score includes several of these parameters, including the presence of a spontaneous type 1 ECG, symptoms, and the presence of SCN5a carrying a mutation. It is therefore no surprise that the risk score seems to bear prognostic information as well. Indeed, the highest score group has the highest event rate on follow-up (±25% events within 5 years). Importantly, no events occurred in the group with the lowest score (follow-up duration for this particular subgroup was not indicated but in ±36 of 45 patients, more than 10 years), emphasizing the benign course of asymptomatic patients with drug-induced BrS who constituted the majority of the patients in this subgroup (6). The intermediate groups (i.e., groups 2 and 3) are in between, as to future events, with an important difference between group 2 (3.5 points) and group 3 (4.0 to 5.0 points) early during follow-up. The authors conclude that “Our study provides validation for the use of the Shanghai Score System for the diagnosis as well as risk stratification of patients with BrS” (4). Both conclusions, with which I agree, are for the reasons indicated, rather obvious, yet it is interesting to see that the risk for (recurrent) events relates directly to the risk score.
One may even take this one step further. In principle, the risk score could serve as a continuous time-dependent variable, changing over time (i.e., increasing). Eventually this could be useful in determining the moment of implantable cardioverter-defibrillator implantation, in particular in the group with 3.5 points (group B), which is the largest group and includes mainly asymptomatic patients with a spontaneous type 1 ECG (see Table 4 in the paper by Kawada et al. ). Indeed, some of the variables in the Shanghai score are prone to time-dependent changes, including the ECG pattern itself, the symptoms, and the family history. However, during the review process, it became clear that over time there were actually no changes in the Shanghai Score for this group of patients (not reported in the paper). Additional criteria as the appearance of fractionated signals or other ECG markers known to affect risk, although almost all are debated (5), may need to be added to the scoring system to make this a reliable option.
Finally, an interesting aspect of many of these studies (7,8) is the apparent immediate onset of events during follow-up (see Figures 2A and 2B in in the Kawada et al. paper ), even in the patients without prior ventricular fibrillation (see Figure S1 in the online version of the Kawada et al. paper ). Indeed, approximately one-third of the patients in the high-risk groups (≥4 points) who developed an event during follow-up seemed to experience this event within days or weeks after the start of the follow-up period. It is likely that most of these patients, if not all, had an implantable cardioverter-defibrillator, and one may wonder whether the implant itself relates to these events (i.e., “proarrhythmogeneity” of the implant). Obviously, the present data do not allow for such a conclusion, but it may be worthwhile to have a closer look.
The present study (4) is important because it is the first to validate the Shanghai scoring system for the diagnosis of BrS. In addition, the study provides evidence for some potential in the prediction of future events. In my view, further studies should focus on the latter because that is where the need is. We will learn most when a prospective study is started with the Shanghai risk score as the main determinant for implantable cardioverter-defibrillator implantation.
↵∗ Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology.
Dr. Wilde has received support from Netherlands CardioVascular Research Initiative, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organisation for Health Research and Development, and Royal Netherlands Academy of Sciences (PREDICT; AAMW). The funding sources had no role in manuscript preparation or decision to submit for publication.
The author attests he is in compliance with human studies committees and animal welfare regulations of the author’s institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- 2018 American College of Cardiology Foundation
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