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• Challenged by "flecainide challenge"
  Isidoros P Gavaliatsis
  Published on: 9 January 2022
• We need more than genetics alone in Brugada syndrome
  Pedro Brugada
  Published on: 9 January 2022
• No single ECG pattern for Brugada syndrome
  Pedro Brugada
  Published on: 9 January 2022
• There is not a single typical ECG pattern for the syndrome of sudden death, RBBB, and ST elevation
  Bortolo Martini
  Published on: 9 January 2022

• Published on: 9 January 2022

  Challenged by "flecainide challenge"

  • Isidoros P Gavaliatsis, Cardiologist

  Dear Editor:

  In the July 2000 issue of Heart, in an Editorial by Brugada,[1] about a paper by Viskin et al,[2] it is stated:
  "The most important conclusion of the study by Viskin and colleagues is, however, that patients with syncope of unknown origin should be pharmacologically tested for Brugada syndrome, a suggestion made by the authors on the basis of their results."

  However, in th...

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  Dear Editor:

  In the July 2000 issue of Heart, in an Editorial by Brugada,[1] about a paper by Viskin et al,[2] it is stated:
  "The most important conclusion of the study by Viskin and colleagues is, however, that patients with syncope of unknown origin should be pharmacologically tested for Brugada syndrome, a suggestion made by the authors on the basis of their results."

  However, in the conclusions of the Abstract by Viskin et al, it is stated:
  "A definite Brugada sign is a specific marker for arrhythmic risk. However, less than obvious ECG abnormalities have little diagnostic value, as a 'questionable' Brugada sign was observed in 1% of healthy controls. In this series of concecutive patients with idiopathic ventricular fibrillation, most had normal ECGs".

  Most importanly, in the Results, it is stated:
  "Six patients received intravenous ajmaline or procainamide and 26 patients received oral treatment with class 1A drugs (mainly quinidine but also disopyramide) following the diagnosis of idiopathic ventricular fibrillation. Class 1A drugs did not unmask a Brugada sign in any patient".

  Furthermore, in the Discussion, it is stated:
  "It should be noted, however, that the specificity of ST elevation following class 1 drug administration is not at all clear. This point cannot be overemphasised in view of anecdotal reports suggesting that ECG features indistinguishable from a Brugada sign may apper in patients without documented or suspected ventricular arrhythmias following administration of class 1C drugs".

  After all these, and not very convincingly, in an Addendum, based on Brugada et al data,[3] it is stated:
  "This new evidence underscores the need for systematic performance of a 'flecainide challenge' in patients with idiopathic ventricular fibrillation and apparently normal ECG, and in patients with questionable symptoms and a questionable Brugada sign".[2]

  I also "question the validity of pharmacological testing for the Brugada syndrome".[4]

  I also "agree that genetics will provide a definitive diagnosis".[4]

  Isidoros P. Gavaliatsis, MD, FESC
  Senior Registrar, Cath Lab
  Evangelismos Hospital
  Athens, Greece

  References

  (1) Brugada P. Brugada syndrome: an electrocardiographic diagnosis not to be missed. Heart 2000;84:1-2.

  (2) Viskin S, Fish R, Eldar M, et al. Prevalence of the Brugada sign in idiopathic ventricular fibrillation and healthy controls. Heart 2000;84:31-6.

  (3) Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000;101:510-15.

  (4) Wilde AAM, Priori SG. Brugada syndrome and sudden death. [Letter and Reply]. Eur Heart J 2000;21:1483-4.

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  Conflict of Interest:
  None declared.

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• Published on: 9 January 2022

  We need more than genetics alone in Brugada syndrome

  • Pedro Brugada, Cardiologist

  Dear Editor:

  Dr Gavaliatsis points out the severe limitations that we still face in the exact diagnosis of monogenic diseases causing ventricular arrhythmias, like Brugada syndrome and the long QT syndrome. In Brugada syndrome it seems that we have a pharmacologic challenge (iv flecainide, ajmaline or procainamide) to unmask the phenotype. Unfortunately, that is not so in the long QT syndrome. But even with the ph...

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  Dear Editor:

  Dr Gavaliatsis points out the severe limitations that we still face in the exact diagnosis of monogenic diseases causing ventricular arrhythmias, like Brugada syndrome and the long QT syndrome. In Brugada syndrome it seems that we have a pharmacologic challenge (iv flecainide, ajmaline or procainamide) to unmask the phenotype. Unfortunately, that is not so in the long QT syndrome. But even with the pharmacologic challenge I agree with Dr Gavaliatsis that there may exist a problem of sensitivity and specificity in the diagnosis that will only be uncovered by exact knowledge of the genotype. But we need more than genetic analysis to make the correct correlations.

  It starts with
  1. The correct clinical diagnosis (something no that easy sometimes, particularly in the long QT syndrome), it continues by
  2. Showing a change in the genetic code - for instance in the gene SCN5A encoding for the human cardiac sodium channel - and ends by
  3. Expressing the mutation to show its functional consequences.

  Of course, the diagnostic chain is only closed at the time that the functional consequences of the mutation turn out to make sound pathophysiologic sense, that is, they correlate with the clinical diagnosis and the known consequences of the disease. Mutation "hunters" seem to forget more and more frequently step 3. They report results that rather confuse instead of clarifying the many scientific questions that still remain. Publication of "mutations" without functional analysis to exclude among others, polymorphisms and non-significant changes in DNA sequences should be avoided by all serious scientific journals.

  The points by Dr Gavaliatsis are well taken but a simple answer will not become available instantaneously. Meanwhile it remains the duty of the physician to protect patients with a Brugada phenotype against sudden death. It is a matter of medical phylosophy: When we do not know the patient should not become the victim of our ignorance. Implanting a defibrillator too much is not nice, but seeing a young individual succumb suddenly to ventricular fibrillation because a defibrillator was not implanted is much worse.

  Prof Dr Pedro Brugada

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  Conflict of Interest:
  None declared.

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• Published on: 9 January 2022

  No single ECG pattern for Brugada syndrome

  • Pedro Brugada, Professor of Cardiology

  Dear Editor:

  Nava and coworkers[1] and Martini and coworkers[2] described a single patient with the diagnois of right ventricular dysplasia who, retrospectively analyzed by the same authors, may have suffered from the syndrome of right bundle branch block, ST segment elevation and sudden death, now known as Brugada disease.

  As they have no genetic analysis on that patient (to exclude among others Naxos syndrome) t...

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  Dear Editor:

  Nava and coworkers[1] and Martini and coworkers[2] described a single patient with the diagnois of right ventricular dysplasia who, retrospectively analyzed by the same authors, may have suffered from the syndrome of right bundle branch block, ST segment elevation and sudden death, now known as Brugada disease.

  As they have no genetic analysis on that patient (to exclude among others Naxos syndrome) their recent letter to Heart[3] ads only confusion to an excellent study by Viskin and coworkers.[4] Their speculations on the mechanisms of right ventricular dysplasia and Brugada disease are no more than speculations and devoid of any scientific basis.

  Prof Dr Pedro Brugada
  Cardiovascular Research and Teaching Institute Aalst
  Belgium

  References

  (1) Nava A, Canciani B, Schiavinato ML, Martini B, Buja GF, La repolarisation precoce dans le precordiales droites: trouble de la conduction intraventriculaire droite? Correlations de l'electrocardiographie- vectorcardiographie avec l'electro- physiologie. Mises a Jour Cardiologiques 1988;17:157-9.

  (2) Martini B, Nava A, Thiene G, et al. Ventricular fibrillation without apparent heart disease: description of six cases. Am Heart J 1989;11:1203-9.

  (3)Martini B, Nava A, Cannas S. There is not a single typical ECG pattern for the syndrome of sudden death, RBBB, and ST elevation [Rapid response]. Heart 15 August 2000.

  (4) Viskin S, Fish R, Eldar M, et al. Prevalence of the Brugada sign in idiopathic ventricular fibrillation and healthy controls. Heart 2000;84:31-6.

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  Conflict of Interest:
  None declared.

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• Published on: 9 January 2022

  There is not a single typical ECG pattern for the syndrome of sudden death, RBBB, and ST elevation

  • Bortolo Martini, Cardiologist

  Dear Editor:

  The article by Viskin et al[1] adds some confusion to the definition of "the typical" electrocardiographic pattern associated with the syndrome of sudden death and right bundle branch delay described by Nava and Martini in 1988-1989,[2, 3] by Aihara in 1990, and by Brugada in 1992. As clearly documented,[3] three (and not one as discussed by Viskin et al) of six patients with aborted sudden death showed differe...

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  Dear Editor:

  The article by Viskin et al[1] adds some confusion to the definition of "the typical" electrocardiographic pattern associated with the syndrome of sudden death and right bundle branch delay described by Nava and Martini in 1988-1989,[2, 3] by Aihara in 1990, and by Brugada in 1992. As clearly documented,[3] three (and not one as discussed by Viskin et al) of six patients with aborted sudden death showed different degrees of right bundle branch block, left axis deviation, prolonged PR interval and ST segment elevation. Two more patients had mild isolated ST elevation with T inversion. The same polymorphic patterns were lately documented either with standard electrocardiography or after class 1C drugs (in subjects with normal ECG or minor ST-T abnormalities), either in Brugada's or other series.[4] Thus a typical sign of the syndrome is a fascinating but not confirmed statement.

  Viskin probably wants to emphasise the first and the most popular electrocardiogram of the syndrome, which is the one published in 1988[1] and 1989 (patient 3 of figure 1 in reference 2), and reprocessed by Brugada on his web site.

  This electrocardiogram shows an R' wave in V1 (incorrectly called J wave), very similar to an incomplete right bundle branch block, followed by a coved ST elevation. It must be remembered that the typical J wave is those recorded in leads II, III, aVF, V5-V6 in vagotonia, and other pathological conditions.[5] Thus R' in V1 is an atypical J wave, or something else.

  Different from a right bundle branch delay, the atypical J wave seen in V1 shows neither a late and slurred S wave in V6, or the typical vectorcardiographic terminal loop.[1] Late potentials often characterise this pattern, but are absent in pure incomplete right bundle branch block. Thus the trace proposed by Viskin et al in figure 2 as the typical sign of the syndrome is, in reality, a typical incomplete right bundle branch block, while the trace presented in figure 3A closely resembles a true atypical J wave with coved ST elevation, and not a questionable sign.

  This does not means that Viskin et al's patients do not have the syndrome, because this is not characterised by a single electrocardiographic pattern, but by polymorphic right bundle branch delays with ST elevation.[2] The latter can be the only basal abnormality, with the atypical J wave appearing spontaneously, or being induced after class 1C drugs.

  The significance of all the electrocardiographic patterns of the syndrome, particularly of the atypical J wave and coved ST elevation, is strongly debated. Brugada favours a functional repolarisation abnormality, while we think, according to electrical and anatomic demonstration, that it represents an organic depolarisation abnormality.[4] This can be easily demonstrated by recording late potentials. As mentioned before, in patients with the discussed "typical" electrocardiogram late potentials are almost always present, clearly demonstrating that the atypical J wave and coved ST elevation is due to a delayed QRS activity, probably of the outflow tract of the right ventricle.[4]

  Please contact Dr Martini for a copy of the figure described below (unfortunately we cannot support illustrations in Rapid Responses)
  The atypical J wave with coved ST elevation in V1, is identical in these two subjects with the syndrome. The trace on the left is the patient of Brugada described in Heart[6] after ajmaline; this pattern was ascribed to a functional repolarisation abnormality. The trace on the right is that of an apparently normal patient, belonging to a family affected by a minor form of right ventricular cardiomyopathy. This patient has a very positive late potentials study, indicating that the atypical J wave and ST elevation, both spontaneous and drug inducible, represents a late depolarisation abnormality of the cardiac activity, probably at the right ventricular outflow tract level. A repolarisation abnormality can never induce late potentials.

  Bortolo Martini MD*
  Andrea Nava MD+
  Sergio Cannas MD*
  *Department of Cardiology, Ospedale Civile di Thiene
  +Department of Cardiology, University of Padua

  Correspondence to:
  Bortolo Martini MD
  Via Gioberti 9
  36016 Thiene (VI), Italy
  Fax +39 445 368537

  References

  (1) Viskin S, Fish R, Eldar M, et al. Prevalence of the Brugada sign in idiopathic ventricular fibrillation and healthy controls. Heart 2000;84:31-6.

  (2) Nava A, Canciani B, Schiavinato ML, Martini B, Buja GF, La repolarisation precoce dans le precordiales droites: trouble de la conduction intraventriculaire droite? Correlations de l'electrocardiographie- vectorcardiographie avec l'electro- physiologie. Mises a Jour Cardiologiques 1988;17:157-9.

  (3) Martini B, Nava A, Thiene G, et al. Ventricular fibrillation without apparent heart disease: description of six cases. Am Heart J 1989;11:1203-9.

  (4) Martini B, Corrado D, Nava A, Thiene G. Syndrome of right bundle branch block, ST segment elevation and sudden death: evidence of an organic substrate. In: Nava A, Thiene G, eds. Arrhythmogenic right ventricular cardiomyopathy. Elsevier 1997:438-53.

  (5) Yan GX, Antzelevitch C. Cellular basis for the electrocardiographic J wave. Circulation 1996;93:372-9.

  (6) Brugada P. Brugada syndrome: an electrocardiographic diagnosis not to be missed. Heart 2000;84:1-3.

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  Conflict of Interest:
  None declared.

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