São Paulo, November 2002

Dear Colleagues from the World,

As President of the Scientific Committee for the "First Virtual Symposium about the Brugada Syndrome" "10 years of history 1992/2002," I must point that I feel deeply honored to preside the work for this historical event and to open thus, the tasks and papers over the whole month of this year, thanks to the "miracle" of Internet that definitely democratized the information, and that allows us to get in touch with the main exponents that made the history of this disease, the last one described in Cardiology in the last century.
Pedro and Josep Brugada published in 1992 a small series of eight cases of sudden cardiac death in patients with structurally normal hearts and carriers of a highly suggestive electrocardiographic "hallmark:" right bundle branch block of His bundle –sometimes atypical- associated to persistent elevation, convex to the top, of J point and ST segment from V1 to V2 or V3. Surprisingly the old technology of ECG, with more than 100 years of existence, became the key for the discovery of a new entity in Cardiology thanks to the acute power of observation of these scientists, who make Cardiology proud all over the world, in Europe and in Spain.
The impact of the discovery was so significant, that in a short time many publications reached a true "feverish" and "in crescendo" rhythm, and additionally the eponym "Brugada syndrome" –coined by doctors Gan-Xin and Charles Antzelevitch- became the one most used by investigators, and today is deeply rooted –quite fairly- just as many other eponyms in literature.
After the identification of the gene since 1998 by Cheng et al, in the a subunit of the sodium channel in the SCN5A gene of chromosome 3, the existing doubts vanish and it becomes possible to differentiate the entity from minor forms of right ventricle arrhythmogenic dysplasia.
Without the least shadow of doubt, these ten years of history were a decade of unimaginable progress and advancement, with new papers appearing regarding the entity in several fields of scientific knowledge, such as genetics, ionic channels, molecular and cellular aspects, arrhythmology, electrophysiology and two supplementary methods, such as accessory derivations, surface electrocardiographic mapping, vectorcardiogram, high resolution ECG, stress test, long-term ECG to study possible arrhythmic events or dynamic modifications in ventricular repolarization, variability or RR, QT dispersion, QTc measurement, microvolt T-wave alternans (TWA). More sophisticated techniques were also improved, such as ultra-fast computed tomography, magnetic nuclear resonance, and neurocardiac imaging.
In this decade, the allelic entities were identified, especially its mirror image, i.e. familial long QT syndrome variant 3 or LQT3, the mixed forms LQT3/Brugada syndrome, or the dromotropic progressive disorder of the His-Purkinje system, known as Lenègre syndrome.
Additionally, it was verified that in some cases of sudden cardiac death in infants, known as SIDS ("SUDDEN INFANT DEATH SYNDROME"), these could correspond to Brugada syndromes, due to alterations having been mapped in the SCN5A gene in these individuals.
There has been a recent genetic verification that the so called SUNDS ("SUDDEN UNEXPLAINED DEATH SYNDROME") , an entity with high prevalence in men in the South East of Asia, and the Brugada syndrome are allelic entities since phenotypically, genotypically and functionally they turn out to be the same entity.
Finally, idiopathic ventricular fibrillation shares with Brugada disease the same locus (3p24-p21), it affects the same SCN5A gene, it happens in structurally normal hearts and it is more prevalent in the male sex and it occurs preferentially in middle-aged individuals. Today, it is considered that Brugada disease is a variant of idiopathic ventricular fibrillation that we call genuine ventricular fibrillation.
Regrettably, to this date the only safe treatment is the automatic implantable cardioverter defibrillator, since none of the drugs of the therapeutic armory provide security. This fact, evil for Third World poor countries, lead us to think it is extremely necessary to test new drugs, such as, for instance, cilostazol, which in a recent work was proven promising. Maybe the association of quinidine with this new drug must be the subject of new research protocols, with the aim of finding a less expensive solution in countries with few resources.
As regards the future, personally, I am one of those who believe that it lays on pharmacogenomics, defined as the impact of the genome diversity in individuals or of the population on their response to treatment with drugs. This is a new branch of medicine that promises to reduce failures in treatment by the adjustment of medications to the genetic codes of each patient. The pharmacogenomics tries to solve a great problem of medicine, the fact that all drugs are produced as "one-sized" clothes, although the response to drugs varies from individual to individual. Every year 100 thousand patients die because of the collateral effects of medications, and another two millions get severely ill. It is thought that in just five years the patients will undergo genetic tests before their physicians would decide what drug to prescribe, and in what doses.
The genetic therapy is founded in the capacity of modifying the genetic background of the patient. Several human genetic entities caused by a lesion in just one gene, have been considered as candidates for genetic therapy. Regrettably, the fundamental problem for this therapy is the distribution method of the gene (transfection), which until today, has not been effective. The vectors used until now, include adenoviruses and retroviruses, but the stage of development of the methodology still does not allow this technique to be widely applied, mostly due to the efficiency of transduction and genetic expression regulation after transduction.

I want to thank from the heart to the Brugada brothers –Pedro, Josep and Ramon- who provided their unconditional support, receiving our initiative with the greatest good will.
Finally, I want to express my eternal gratitude, most especially to my great colleague and friend at all hours, and President of the Steering Committee, Dr. Edgardo Schapachnik, who was the motor and ideologist of this venture. Without him, none of this would have been possible.

Andrés Ricardo Pérez Riera MD
President of the Scientific Committee
riera@uol.com.br

Buenos Aires, November 2002

More than a year ago, when the Professor Pedro Brugada filled the Main Lecture Hall of the National Academy of Medicine in Buenos Aires, in the Course "One day with the arrhythmias", organized by Dr. Jorge González Zuelgaray, we outlined the idea of making the First Virtual Symposium about the Brugada Syndrome, on the internet.
That idea, still in its early stage, gathered several stimuli, among which it stood out the enthusiasm inspired by my friend, Dr. Andrés R. Pérez Riera, an in-depth scholar and expert on the Syndrome.
This young entity would be just 10 years old in 2002, since its identification as right bundle branch block with ST elevation in V1-V3, and tendency to sudden cardiac death in patients with structurally normal hearts. Additionally, there was the fact that in such scant period of time there was an advancement from clinical description to the accurate knowledge of the genetic alteration that characterize it, going through the description of the operation of ionic channels, similarities and differences with allelic diseases, such as the LQT3 or the Lenègre disease, and others such as right ventricle arrhythmogenic dysplasia. Thus, the entity deserved –regardless of the cases presented-, to be considered as a model where clinicians, electrophysiologists, geneticists, pharmacologists, and so on, joined with the aim of scientific knowledge advancement.
In line with this fast-paced knowledge, the decade that stands between us and 1992, also allowed us to be eye witnesses of another phenomenon unimagined before in the area of communications, that is to say, the Internet.
Our experience in the area of Medical Education using the Internet tools that we initiated in 1998 with different academic activities in Spanish, the First Course on Arrhythmias over the Internet that from its very beginning has gathered more than 3,000 participants, the First University Course on Pain from the National University of La Plata (Argentina), which got together 1,200 physicians from Latin America, Spain and Portugal, the Course for Clinical Investigators Education over the Internet, from the National University of the North-East (Argentina), the organization of the First Virtual Congress of Cardiology and the Second Virtual Congress of Cardiology in three languages (Spanish, Portuguese and English) in which there were 7,500 and 11,000 registered participants from 107 countries, and the experiences from the First Virtual Symposium on Chagas Disease, the First Virtual Symposium on Pain, Palliative Medicine and Advancements in Pharmacology of Pain and the recently finished Second International Symposium on Chagas Disease on the Internet, the activity of the "Latidos por Minuto" Radio exclusively devoted to Continuing Medical Education over the Internet, constituted another force that encouraged us to organize this novel experience that begins today, and in which we are privileged players.
Internet will allow us for a month to actively interact by exchanging information and knowledge, which otherwise would be very difficult, if not impossible, to achieve.
Our goal is that through November, and even later, the scientific papers presented to this Symposium as Lectures of the Honorary Committee Members, Lectures by Experts and Roundtables will make up and indispensable body of consultation material for the study of the Brugada Syndrome, as it was known until today, and which we will propose to rise to the indisputable category of Brugada Disease.
We hope that this Forum will become a channel for fluid dialogue, with questions, answers, opinions, replies and counter-replies. To achieve this, the participation by all of you will be necessary, and now I call you for this task.
I must tell you about the titanic activity by Dr. Pérez Riera, President of the Scientific Committee, who managed to get together a panel of first international level experts, whose scientific papers will provide an indisputable splendor to this event.
We must thank all of them.
I extend the thanks to the distinguished members of the Scientific Committee, whose presence and participation in the Symposium make us proud.
To the participants, native from places so different and distant in the five continents, who are precisely the ones to turn the chance to share this activity into a fantastic one, without having to move from their dwellings.
My admiration and respect to Pedro, Josep and Ramón Brugada, whose clinical shrewdness made this decade possible, with its unstoppable flow of knowledge in the scientific and cardiologic areas.
My thanks to the Argentine Society of Cardiology and the Argentine Federation of Cardiology for providing scientific sponsorship to this event, and to the Mexican Society of Cardiology for including this Symposium in the schedule of activities of their web site.
My thanks to Guidant Co, our official sponsor, and Cardiolab, its exclusive distributor in Argentina, whose contribution makes this experience possible.
Finally, my thanks to the technical team of young persons from different non-medical disciplines whose work you are enjoying: María Isabel Ayala, Ariel Guebel, Alejo Schapachnik, Fernando Pablo Schapachnik, Omar Staiano, Susana Torok, Martín Vidal.

I now open the deliberations of the First Virtual Symposium about the Brugada Syndrome.

Dr. Edgardo Schapachnik
President of the Steering Committee

Sao Paulo, November 2002

Dear Colleagues of the World:

As President of the Scientific Committee of the "First Virtual Symposium about the Brugada Syndrome: 10 years of history 1992/2002," I express with great sentiment that I feel deeply thankful and honored by the active presence of numerous and illustrious colleagues from all the corners of the world, who have the highest scientific level, and who ennobled our Symposium, turning it into an historical event; a framework that marks the passage of a decade from the brilliant initial description by the brothers Pedro and Josep Brugada. The result could not have been better, both by the significance and topicality of the subject, and for having widely exceeded our expectations by the great participation and the quality of lectures, papers and brief communications presented. We celebrate the talent, aptitude and dedication of the personalities that made up this Virtual Symposium, all highly committed to the study of this fascinating entity that will ultimately result in an instrument of progress to reach the highest aim: the well-being of our dear patients. It is fundamental for physicians to perceive that the patient is their goal, and that the great scientific and technologic development must be devoted to the service of the ill. In my point of view, it is essential for us, fervent lovers of science, to get rid of the constant ghost of prioritizing science at the expense of the medical activity in benefit of the patient. Physicians must not be a mere spectator: they have to be protagonists. It is our duty to be an example. This is not the best way to influence others. It is the only way. It is my belief that no society can fully progress if it does not create favorable conditions for the advancement of knowledge and scientific and technologic innovation.

We think that the third millennium should be characterized by a valorization of genetics, a fundamental issue in the disease that we are dealing with, both for unequivocal confirmation in diagnosis, and with a high probability to find the final road for a definitive therapeutic solution. A clear proof of this tendency is that over the last decade, seven Nobel prizes were granted to studies in the area of genetics, pointing to the direction of the future way to follow. In October 7, 2002, the world knew those award winners of the Nobel Prize 2002, the British John Sulston and Sydney Brenner, who worked together to enlighten the secrets of cell division, using as model the first animal to have its genome totally sequenced. In this sense, in the dawn of the XXI century, we have to prioritize bioethics as an essential instrument for a balanced and fair advancement of science.

The Symposium became a simple homage to the Brugada brothers, an example and pride for the international scientific community, due to their brilliant and permanent contributions for science development. To the eldest of the three, Pedro, of whom I am honored to be a sincere friend, I tell this in a loud and clear voice: my friend, thank you very much for being what you are: a tireless fighter, with a high sense of humanity and respect for your pairs, particularly the humbler ones. To Josep, an example of a distinguished electrophysiologist, and to the youngest one, Ramon, concerned in the search for a clarification of the foundation of the entity within the meanders of genetics. To the three of them, great scientists, on my behalf and that of the President of the Steering Committee, Dr. Edgardo Schapachnik, we thank you very much.
Finally, I have to thank my tireless co-worker, Edgardo, the initiator of this enterprise, on whose shoulders rested the whole weight of this wonderful organization, provoking in us a feeling of permanent wonder for his huge capacity for work and disposition to face the inevitable unexpected events. To him, my most sincere thanks.

Andrés Ricardo Pérez Riera MD
President of the Scientific Committee
riera@uol.com.br

Buenos Aires, November 2002

Closing speech by Dr. Edgardo Schapachnik, President of the Steering Committee

Thirty days have gone by of intense academic activity where the reason that gathered clinical cardiologists, electrophysiologists, pediatricians, geneticists, biologists, researchers, was to pay homage to the 10 years of existence of the entity we nowadays know as Brugada Syndrome. For this, we used an unusual means, but which we vindicate as a powerful tool for communication, that is to say the Internet environment. When the scientific quality of the lecturers called converges with the interest of the participants, and when to give life to this meeting the proper means of exchange are used, the final product we achieve is one with the characteristics shown in this First Virtual Symposium about the Brugada Syndrome, that is to say, a scientific event in which all of the parts involved did their best, and the assessment of which must be done by each one, according to degree and impact in which the concepts presented influenced on them.

These exciting 30 days were like the tip of the iceberg; the expression of more than a year of work, where the wisdom of Andres R. Perez Riera gathered the most representative group of researchers, who contributed to the knowledge of the syndrome… His own personal contribution in his plentiful texts will remain as a permanent sign of the dedication he devoted to study this entity and cardiology as a whole. Internet, as the ideal means to develop this kind of activities, has not yet received from the academic world all the recognition that its power deserves. The possibility of making medical Symposia and Conferences through the Internet is still seen with some distrust, and the meetings made with these goals are scant.

Maybe, the experience of this Symposium and the participation in it by distinguished personalities from the scientific field, will provide qualified opinions in this sense, if their vision is shared with ours about considering the goal as met. These will be our only thoughts on the experience carried out. The true balance of what was done must spring from everyone and each one of you. All the presented lectures and papers will remain for analysis, as well as all the opinions expressed in this Forum, the Round Table broadcast through the Radio, and all the imagination put into the www site that gathered us. Once again, and as I stated in the Symposium's opening, I want to thank Andres Perez Riera, and Pedro, Josep and Ramon Brugada, all the lecturers and authors, members of the Scientific Committee, participants, Guidant Co. and Cardiolab from Argentina, and most of all the foundation of the iceberg that made it possible: Maria Isabel Ayala, Ariel Guebel, Martin Vidal, Omar Staiano, Fernando Pablo Schapachnik, Alejo Schapachnik, and particularly to our co-worker and secretary, Mrs. Susana Torok, my wife.

Dr. Edgardo Schapachnik
President of the Steering Committee