<HTML><BODY style="word-wrap: break-word; -khtml-nbsp-mode: space; -khtml-line-break: after-white-space; "><DIV><FONT class="Apple-style-span" face="Arial">Dear Dr Jorge Ruiz Alais here answer Andrés Ricardo Pérez Riera ffrom São Paulo Brazil.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">In apparently healthy men the Manitoba prospective population follow-Up study (1948 to 2004) showed that newly developed complete left bundle branch block (CLBBB) was a highly significant short-term risk to sudden unexpected cardiac death that diminished with time (1).</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Cardiac resynchronization therapy (CRT) has significant positive effects on the quality of life, enables patients to cope more efficiently with cardiopulmonary stress and leads to a reduction of total mortality in patients suffering from congestive HF NYHA classes III and IV, reduced LV function and CLBBB with a QRSd > 150 ms. Prolongation of QRSd > or =120 ms occurs in 14% to 47% of HF patients. LBBB is far more common than RBBB. Left-sided intraventricular conduction delay is associated with more advanced myocardial disease, worse LV function, poorer prognosis, and a higher all-cause mortality rate compared with narrow QRS complex. In a large number of patients suited for CRT, an additional defibrillator function seems to work out well concerning an additional prognostic improvement by means of reducing SCD. Due to partially contradictory study outcomes, it still remains to be discussed whether all patients suited for CRT really need an ICD (2). In ICD patients with HF, a wide underlying QRS complex more than doubles the cardiac mortality compared with a narrow QRS complex. There is a high incidence of an elevated defibrillation threshold at the time of ICD implantation in patients with QRS > or =200 ms. Mechanical LV dyssynchrony potentially treatable by ventricular resynchronization occurs in about 70% of HF patients with left-sided intraventricular conduction delay, a fact that would explain the lack of therapeutic response in about 30% of patients subjected to ventricular resynchronization according to standard criteria relying on QRS duration. The duration of the basal QRS complex does not reliably predict the clinical response to ventricular resynchronization, and QRS narrowing after cardiac resynchronization therapy does not correlate with hemodynamic and clinical improvement. Mechanical LV dyssynchrony is best shown by evolving echocardiographic techniques (predominantly tissue Doppler imaging) currently in the process of standardization (3).</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">The presence of BBB is strongly associated with future high-degree atrioventricular block that was more pronounced for LBBB. Men with LBBB have a substantially increased risk of coronary death, mainly due to SCD outside the hospital setting (4).</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Lènegre disease is the eponym of "idiopathic" progressive disease of the His-Purkinje system. It is also knows as Progressive Cardiac Conduction Defect (PCCD). The disease has been identified as an entity that affect the sodium fast channel (channelopathy entity) occasioned by mutation in the SCN5A gene. It is an allelic of Brugada disease with a different phenotypic expression. The same missence mutation in the SCN5A gene can cause both phenotypes: Brugada and Lènegre disease.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">So, we now ask for scientific community: why Lènegre has disease category and Brugada entity has not?. Is it certain? Both entities, called Progressive Cardiac Conduction Defects (PCCD), are grouped together as primary conduction diseases (Lev-Lenègre). Both Lenègre disease-known as "primary" PCCD (5)-as well as the secondary mechanic lesion-sclerosis of the left "cardiac skeleton" or Lev disease (6)-usually cause LBBB or RBBB, frequently associated with divisional blocks.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"><BR></FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Occasionally, they develop into more advanced degrees of block with a potential to cause SCD due to total AV block, to the extent that they represent the most important cause of pacemaker implantation in the first world: 0.15 per 1,000 inhabitants a year.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"><BR class="khtml-block-placeholder"></FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">The same mutation in novel single SCN5A missense mutation can lead either to Brugada syndrome or to an PCCD. Modifier gene(s) may influence the phenotypic consequences of a SCN5A mutation. A G-to-T mutation at position 4372 was identified by direct sequencing and was predicted to change a glycine for an arginine (G1406R) between the DIII-S5 and DIII-S6 domain of the Na+ channel protein (7).</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"><BR></FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Trimetazidine (TMZ) Vartel a clinically effective antianginal agent with no negative inotropic or vascular properties, acts by optimizing cardiac energy metabolism through inhibition of free faty acid oxidation, shifting substrate utilization from fatty acids to glucose. long-term trimetazidine improves functional class and LV function in patients with HF. This benefit contrasts with the natural history of the disease, as shown by the decrease of EF in patients on standard HF therapy alone. Recently, results have demonstrated that trimetazidine improves radial artery endothelium-dependent relaxation related to its antioxidant properties. Similarly, exercise training has been demonstrated to improve diastolic filling and systolic function in patients with ischemic cardiomyopathy, in relation to enhanced perfusion and contractility of dysfunctional myocardium. Patients with viable myocardium, in theory, should have the greatest benefits because trimetazidine improves contractility of dysfunctional hibernating/stunned myocardium, whereas exercise has documented efficacy in improving endothelial vasomotor response of coronary arteries, stimulating coronary collateral circulation and small vessel growth, improving LV function, and increasing functional capacity.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"><BR></FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">References</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">1) Cuddy TE, Tate RB. Sudden unexpected cardiac death as a function of time since the detection of electrocardiographic and clinical risk factors in apparently healthy men: the Manitoba Follow-Up Study, 1948 to 2004. Can J Cardiol. 2006;22:205-11.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">2) Volkmann H, Bergmann C, Walter M.Cardiac resynchronization therapy: who is suitable? Who requires an additional ICD as a backup? Z Kardiol. 2005; 94:60-64.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">3) Kashani A, Barold SS. Significance of QRS complex duration in patients with heart failure. J Am Coll Cardiol. 2005;46:2183-92.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">4) Eriksson P, Wilhelmsen L, Rosengren A.Bundle-branch block in middle-aged men: risk of complications and death over 28 years. The Primary Prevention Study in Goteborg, Sweden. Eur Heart J. 2005;26:2222-3.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">5) Lenègre J.The pathology of complete atrioventricular block. Progr Cardiovasc Dis 1964; 6:317-323.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">6) Lev M. Anatomic basis of atrioventricular block. Am J Med 196437:742.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">7) Kyndt F, Probst V, Potet F, et. al. Novel SCN5A Mutation Leading Either to Isolated Cardiac Conduction Defect or Brugada Syndrome in a Large French Family. Circulation 2001; 104: 3081-3086</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"><BR></FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">All the best</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"><BR class="khtml-block-placeholder"></FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Andrés Ricardo Pérez Riera</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Chief of Electro-Vectocardiology Sector of the Discipline of Cardiology,</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">ABC Faculty of Medicine (FMABC), Foundation of ABC (FUABC)</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">- Santo André - São Paulo - Brazil.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Rua Sebastião Afonso 885 - Zip Code: 044417-100- Jardim Miriam S.P Brazil-</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"><BR class="khtml-block-placeholder"></FONT></DIV><BLOCKQUOTE type="cite"><DIV><FONT class="Apple-style-span" face="Arial"><BR></FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Dear friends,</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Congratulations on such a novel and scientific symposium on heart</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">pathologies, for I am personally quite surprised with the advanced</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">progresses that help to clarify and understand lots of pathologies</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">still unknown to many colleagues. By the way, I would like to know</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">about the newest advancements about complete left bundle branch block</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">of his bundle; if this may actually be a pathology that may cause</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">sudden death; clarify its etiology, prognosis, proper management,</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">what other complications it may have, and if possible, whether there</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">is some innovative treatment to endure this condition. I would also</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">like to know what is the experience regarding the cardiac ischemia</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">treatment with vastarel (trimetazidine dichlorhydrate).</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Thank you very much for your consideration to this message.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">I remain waiting for your kind response,</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"><BR></FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">JORGE RUIZ ALAIS</FONT></DIV></BLOCKQUOTE><BR><BR><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; ">--</DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">Dr.<SPAN class="Apple-converted-space"> </SPAN>Sergio<SPAN class="Apple-converted-space"> </SPAN>Dubner</DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">President<SPAN class="Apple-converted-space"> </SPAN>of<SPAN class="Apple-converted-space"> </SPAN>Scientific<SPAN class="Apple-converted-space"> </SPAN>Committee</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; "><BR style="font-family: Lucida Grande; font-size: 13px; "></DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">Dr.<SPAN class="Apple-converted-space"> </SPAN>Edgardo<SPAN class="Apple-converted-space"> </SPAN>Schapachnik</DIV><DIV style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; ">President<SPAN class="Apple-converted-space"> </SPAN>of<SPAN class="Apple-converted-space"> </SPAN>Steering<SPAN class="Apple-converted-space"> </SPAN>Committee</DIV><DIV><BR class="khtml-block-placeholder"></DIV><DIV><BR class="khtml-block-placeholder"></DIV><BR class="Apple-interchange-newline"></SPAN> </DIV><BR></BODY></HTML>