<HTML><BODY style="word-wrap: break-word; -khtml-nbsp-mode: space; -khtml-line-break: after-white-space; "><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">Dear Silvano Diangelo from Argentina,</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">I'm Andres Ricardo Perez Riera from Brazil, and I'll answer your question.</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">A young adult (35 years old), male, with electrocardiographic pattern of IRBBB with superior axis and that presents a crisis of paroxysmal AF with no apparent cardiac or extracardiac cause (I am certain that you investigated hyperthyroidism and other causes for AF), falls in the category of idiopathic AF: essential, primary, lonely, or as Anglo-Saxon literature call it, "lone atrial fibrillation", which is defined as AF that appears with no evidence (clinical or lab) of structural heart disease or systemic disease. It represents 6% to 10% of the cases of AF, and in many cases it translates an increase of vagal tone, generally during the night (AF of vagotonic type), transitory and in rest. These apparently idiopathic cases may have a genetic basis, and stop being so. AF apparently without cause has been mapped in several chromosomes:</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">1) Dominant autosomal chromosome 10 in region 10q22-q23 (1);</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">2) One of the mapped genes, 10q22 in region DLG5, is a member of the family of the proteins called MAGUKs (Membrane Associated Gyanylate Kinase). This family mediates intracellular signs with function in the formation of cellular binds, in maintenance of cell form, and clustering of protein channels in cell surface (2);</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">3) A family with the mutation (S140G) in gene KCNQ1 (KvKQT1) of chromosome 11p15.5 was also identified. This KCNQ1 gene, encodes the pore that makes up the alpha subunit of I(Ks) channel. The analysis of this mutation revealed a gain in function in KCNQ1/KCNE1 and KCNQ1/KCNE channels. This fact is in contrast with the negative effect or loss of function in KCNQ1 observed in long QT syndrome. Thus, the S140G mutation starts and maintains AF by reducing the duration of AP, and the refractory period of atrial cardiomyocytes (3).</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">First conclusion: in this patient it is necessary to perform a genetic study. Not only because of suspicion of Brugada syndrome, but to determine if AF is idiopathic or genetic. </FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; font: normal normal normal 13px/normal GB18030 Bitmap; min-height: 17px; "><FONT class="Apple-style-span" face="Arial" size="3"><SPAN class="Apple-style-span" style="font-size: 12px;"><BR></SPAN></FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">This patient may have a cancelled from of Brugada that was unmasked by use of endovenous propafenone. Several papers show that Brugada syndrome may be unmasked with propafenone in this way (4). </FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">Propafenone in Brugada syndrome may unmask VT crisis, both polymorphic and monomorphic (5).</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">It may cause J wave in inferior lead when injected in patients carriers of the so-called variant Brugada syndrome (6).</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">A case very similar to yours was presented last year (2005) by Aksay et al in Turkey, in which the patient presented acute AF, and when propafenone was administered to reverse AF, Brugada pattern appeared (7). A similar situation was observed by Beldner et al (8) in patients with AF treated with propafenone or with flecainide. </FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">Second conclusion: your patient seems to have Brugada syndrome, and should be electrophysiologically studied. "It looks like a lion, and it is a lion." If positive, ICD.</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; font: normal normal normal 13px/normal Lucida Grande; min-height: 16px; "><FONT class="Apple-style-span" face="Arial" size="3"><SPAN class="Apple-style-span" style="font-size: 12px;"><BR></SPAN></FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">References </FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">1) Brugada R, Tapscott T, Czernuszewic GZ, et al. Identification of a genetic locus for familial atrial fibrillation N Engl J Med 1997; 336:905-911);</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">2) Shah G, Brugada R, Gonzalez O, et al. The cloning, genomic organization and tissue expression profile of the human DLG5 geneBMC Genomics 2002 3: 6.</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">3) Chen YH, Xu SJ, Bendahhou S, et al. KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science 2003; 299:251-254.</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">4) Matana A, Goldner V, Stanic K, et al. Unmasking effect of propafenone on the concealed form of the Brugada phenomenon. PACE 2000;23:416-418.</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">5) Karaca M, Dinckal MH.Successful radiofrequency catheter ablation of idiopathic ventricular fibrillation presented as recurrent syncope and diagnosed by an implanted loop recorder. Acta Cardiol. 2006;61:481-484.</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">6) Ozeke O, Aras D, Celenk MK, Exercise-induced ventricular tachycardia associated with J point ST-segment elevation in inferior leads in a patient without apparent heart disease: a variant form of Brugada syndrome? J Electrocardiol. 2006; 39:409-412.</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">7) Aksay E, Okan T, Yanturali S.Brugada syndrome, manifested by propafenone induced ST segment elevation. Emerg Med J. 2005;22:748-750.</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">8) Beldner S, Lin D, Marchlinski FE.Flecainide and propafenone induced ST-segment elevation in patients with atrial fibrillation: clue to specificity of Brugada-type electrocardiographic changes. Am J Cardiol. 2004;94:1184-5.</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">Cordially, </FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">Andrés Ricardo Pérez Riera</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">Jefe del Sector de Electro-Vectocardiologia de la disciplina de Cardiologia del ABC. Facultad de Medicina del ABC (FMABC), Foundación del ABC (FUABC) - Santo André - Sao Paulo - Brasil. Rua Sebastiao Afonso 885 - Zip Code: 044417-100- Jardim Miriam S.P Brazil</FONT></DIV><FONT class="Apple-style-span" face="Arial"><BR></FONT><DIV> <SPAN class="Apple-style-span" style="border-collapse: separate; border-spacing: 0px 0px; color: rgb(0, 0, 0); font-family: Helvetica; font-size: 12px; font-style: normal; font-variant: normal; font-weight: normal; letter-spacing: normal; line-height: normal; text-align: auto; -khtml-text-decorations-in-effect: none; text-indent: 0px; -apple-text-size-adjust: auto; text-transform: none; orphans: 2; white-space: normal; widows: 2; word-spacing: 0px; "><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">--</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">Dr.</FONT><SPAN class="Apple-converted-space"><FONT class="Apple-style-span" face="Arial"> </FONT></SPAN><FONT class="Apple-style-span" face="Arial">Sergio</FONT><SPAN class="Apple-converted-space"><FONT class="Apple-style-span" face="Arial"> </FONT></SPAN><FONT class="Apple-style-span" face="Arial">Dubner</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">President</FONT><SPAN class="Apple-converted-space"><FONT class="Apple-style-span" face="Arial"> </FONT></SPAN><FONT class="Apple-style-span" face="Arial">of</FONT><SPAN class="Apple-converted-space"><FONT class="Apple-style-span" face="Arial"> </FONT></SPAN><FONT class="Apple-style-span" face="Arial">Scientific</FONT><SPAN class="Apple-converted-space"><FONT class="Apple-style-span" face="Arial"> </FONT></SPAN><FONT class="Apple-style-span" face="Arial">Committee</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; font: normal normal normal 13px/normal Lucida Grande; min-height: 16px; ; font-family: Lucida Grande; font-size: 13px; "><FONT class="Apple-style-span" face="Arial" size="3"><SPAN class="Apple-style-span" style="font-size: 12px;"><BR style="font-family: Lucida Grande; font-size: 13px; "></SPAN></FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">Dr.</FONT><SPAN class="Apple-converted-space"><FONT class="Apple-style-span" face="Arial"> </FONT></SPAN><FONT class="Apple-style-span" face="Arial">Edgardo</FONT><SPAN class="Apple-converted-space"><FONT class="Apple-style-span" face="Arial"> </FONT></SPAN><FONT class="Apple-style-span" face="Arial">Schapachnik</FONT></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; "><FONT class="Apple-style-span" face="Arial">President</FONT><SPAN class="Apple-converted-space"><FONT class="Apple-style-span" face="Arial"> </FONT></SPAN><FONT class="Apple-style-span" face="Arial">of</FONT><SPAN class="Apple-converted-space"><FONT class="Apple-style-span" face="Arial"> </FONT></SPAN><FONT class="Apple-style-span" face="Arial">Steering</FONT><SPAN class="Apple-converted-space"><FONT class="Apple-style-span" face="Arial"> </FONT></SPAN><FONT class="Apple-style-span" face="Arial">Committee</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"><BR class="khtml-block-placeholder"></FONT></DIV><DIV><BR class="khtml-block-placeholder"></DIV></SPAN></DIV><DIV><BLOCKQUOTE type="cite"><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; min-height: 14px; "><BR></DIV> <DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">I would like to ask Dr. Andres Perez Riera about a 35-year-old, male patient, with no structural heart disease or family history of SCD, baseline ECG with incomplete right bundle branch block with superior axis, who presents for the first time with Paroxysmal Atrial Fibrillation, which after being reverted with oral propafenone 600 mg (UD), induces ECG with Brugada pattern.<SPAN class="Apple-converted-space"> </SPAN></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">What is the prognosis? Therapeutics?<SPAN class="Apple-converted-space"> </SPAN></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">Does he need an additional screening (genetic, EPS)?</DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">Is he really a Brugada patient or is this just the effect of the drug, producing Brugada-like pattern?</DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; min-height: 14px; "><BR></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">Thank you very much.<SPAN class="Apple-converted-space"> </SPAN></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; min-height: 14px; "><BR></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">Kind regards,<SPAN class="Apple-converted-space"> </SPAN></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">Dr. Silvano Diangelo</DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">Argentina</DIV><DIV><BR class="khtml-block-placeholder"></DIV><BR></BLOCKQUOTE></DIV><BR></BODY></HTML>