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
President of the Scientific Committee
riera@uol.com.br

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, Noviembre de 2002

Discurso de clausura del Dr. Edgardo Schapachnik, Presidente del Comité Organizador

Han transcurrido 30 días de intensa actividad académica donde el motivo que nucleó a cardiólogos clínicos, electrofisiólogos, pediatras, genetistas, biólogos, investigadores, fue el de rendir homenaje a los 10 años de existencia del que hoy conocemos con el nombre de Síndrome de Brugada. Para ello utilizamos un medio inusual, pero al que reivindicamos como poderosa herramienta de comunicación, cual es el entorno Internet. Cuando la calidad científica de los expositores convocados confluye con el interés de los participantes, y cuando para dar vida a ese encuentro se utilizan los medios adecuados de intercambio, el producto final logrado es de las características como las que ha mostrado este Primer Simposio Virtual de Síndrome de Brugada, es decir un evento científico en el cual cada una de las partes puso lo mejor de sí y cuya evaluación deberá ser hecha por cada uno, según la medida y el impacto en que los conceptos vertidos lo hayan influído.

Estos 30 apasionantes días fueron como la punta de un iceberg, expresión de un trabajo de más de un año, donde la sapiencia de Andrés R. Pérez Riera supo congregar a lo más representativo entre los investigadores que aportaron al conocimiento del síndrome.. Su propio aporte personal en sus prolíficos textos deberá quedar como marca indeleble de la dedicación que ha puesto al estudio de esta entidad y de la Cardiología toda. Internet, como medio idóneo para el desarrollo de este tipo de actividades, aún no ha recibido del mundo académico toda la aceptación que su poderío merece. La posibilidad de realizar Simposios y Congresos médicos a través de Internet aún es vista con cierto recelo y son escasas las convocatorias que se realizan con estos fines. Quizás la experiencia de este Simposio y la participación en él de distinguidas personalidades del ambiente científico aporte calificadas opiniones en ese sentido, si su visión comparte la nuestra de considerar el objetivo como cumplido.

Serán sólo éstas nuestras reflexiones sobre la experiencia realizada. El verdadero balance de lo realizado deberá provenir de todos y de cada uno de ustedes. Quedan para ese análisis todas las ponencias presentadas, todas las opiniones vertidas en este Foro, la Mesa Redonda emitida por Radio y toda la imaginación puesta en el site www que nos congregó. Vaya nuevamente, como lo expresé en la apertura del Simposio, mi agradecimiento a Andrés Pérez Riera, a Pedro, Josep y Ramón Brugada, a todos los expositores, a los miembros del Comité Científico, a los participantes, a Guidant Co y Cardiolab de Argentina, y sobre todo a la base del iceberg que lo hizo posible: María Isabel Ayala, Ariel Guebel, Martín Vidal, Omar Staiano, Fernando Pablo Schapachnik, Alejo Schapachnik y en particular a nuestra compañera y secretaria, Licenciada Susana Torok, mi esposa.

Dr. Edgardo Schapachnik
Presidente del Comité Organizador