<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">Dr. Gabriel Pellegrini from La Plata. Argentina. I´m Andrés Ricardo Pérez Riera from Sao Paulo Brazil.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Risk stratification in HCM should include a complete clinical-cardiological evaluation that should also consider new diagnostic features, e. g. MRI. Risk stratification should also include genetic testing, since some gene mutations seem to be associated with a higher risk for SCD than others. However, genetic testing in HCM in not yet available on a routine basis. </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"> </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Major risk factors for SCD include (1):</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"> </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">1) A SURVIVED CARDIAC ARREST (VF): The implantation of a ICD is first-line therapy in patients with documented VT/VF or patients who have survived SCD(Secondary prevention of SD). SCD is the most devastating presenting manifestation of HCM. It has the highest incidence in preadolescent and adolescent children and is particularly related to extreme exertion. The risk of SD in children is as high as 6% per year. In more than 80% of cases, the arrhythmia that causes sudden death is VF. Many of these cases degenerate into VF from rapid atrial arrhythmias, such as fibrillation, supraventricular tachycardia, or WPW syndrome, while others result from VT and low cardiac output hemodynamic collapse.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"> </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">2) NON-SUSTAINED AND SUSTAINED VT IN HOLTER MONITORING;</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"> </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"> </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">3) FAMILIAL HISTORY OF SD AT A YOUNG AGE: SCD at children, preadolescent and adolescent is not infrequently the first symptom of an inherited cardiac disease. Because these diseases usually inherit as an autosomal dominant trait, first-degree family members have a 50% chance of carrying the same genetic defect. Besides clinical cardiologic examination of the remaining family members, post-mortem molecular genetic investigation can be of value in reaching a diagnosis and in determining the subsequent therapeutic options for immediate relatives(2);</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"> </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">4) UNEXPLAINED SYNCOPE:It occurs more commonly in children and young adults with small LV chamber size and evidence of VT upon ambulatory monitoring. Syncope resulting from inadequate cardiac output upon exertion or from cardiac arrhythmia;</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"> </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">5) AN ABNORMAL BLOOD PRESSURE RESPONSE ON EXERCISE;</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"> </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">6) LEFT VENTRICULAR THICKNESS GREATER OR EQUAL THAN 30mm: Surgical myectomy is effective in reducing symptoms in children with LV obstruction who are unresponsive to drugs. The percutaneous septal ablation can also be regarded as a feasible alternative;</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"> </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">7) THE PRESENCE OF "MALIGNANT" MUTATIONS: mutations (R403Q, R453C, G716R and R719W) are highly malignant defects in the beta-myosin heavy chain (MYH7). In the cardiac troponin T gene (TNNT2), a specific mutation (R92W) has been associated with high risk of SD (3). Genetic testing is not widely available at this time but is becoming increasingly available in this disease setting. In research situations or in larger pedigrees, genotyping is informative for the identification of additional family members once the proband's genotype has been determined. Genetic studies have defined HCM as a disease of the sarcomere caused by mutations in any of 11 genes that encode different elements of the contractile apparatus in cardiac myocytes. Over 200 individual mutations have been identified. With a prevalence estimated to be ~1/500-1/1000 in the general population, HCM is the most common monogenic cardiac disorder. </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Each factor has a low positive predictive accuracy, but patients having two or more of these risk factors have high risk. The presence of two or more risk factors is associated with a 6-year SCD survival rate of 72%, justifying the consideration of prophylactic therapy.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Invasive EPS appear to carry little advantage over non-invasive risk stratification. Other uses for EPS include the investigation and treatment of individuals with conduction disease and/or WPW syndrome, atrial flutter and fibrillation and MVT. Appropriate management may then involve radiofrequency ablation(4).</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"> </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">References</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">1) Pellnitz C, Geier C, Perrot A, et al. Sudden cardiac death in familial hypertrophic cardiomyopathy. Identification of high-risk patients Dtsch Med Wochenschr. 2005;130:1150-1154.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">2) Wilde AA, van Langen IM, Mannens MM, Sudden death at young age and the importance of molecular-pathologic investigation Ned Tijdschr Geneeskd. 2005;149:1601-1604;</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">3) Ackerman MJ, Van Driest SL, Ommen SR, et al. Prevalence and age-dependence of malignant mutations in the beta-myosin heavy chain and troponin T genes in hypertrophic cardiomyopathy: a comprehensive outpatient perspective. J Am Coll Cardiol. 2002; 39:2042-2048.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">4) Behr ER, Elliott P, McKenna WJ. et al. Role of invasive EP testing in the evaluation and management of hypertrophic cardiomyopathy. Card Electrophysiol Rev. 2002; 6:482-486.</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"> </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">All the best</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, ABC Faculty of Medicine (FMABC), Foundation of ABC (FUABC) - Santo André - Sao Paulo - Brazil. 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><DIV><FONT class="Apple-style-span" face="Arial">--</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Dr. Sergio Dubner</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">President of Scientific Committee</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"><BR></FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Dr. Edgardo Schapachnik</FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">President of Steering Committee</FONT></DIV><FONT class="Apple-style-span" face="Arial"><BR class="Apple-interchange-newline"></FONT></DIV><FONT class="Apple-style-span" face="Arial"><BR></FONT><DIV><BLOCKQUOTE type="cite"><DIV><FONT class="Apple-style-span" face="Arial"><BR></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">Good afternoon. </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">I would like to read opinions about: what patient with hypertrophic cardiomyopathy should undergo a genetic study? </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial"><BR></FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Thank you very much, </FONT></DIV><DIV><FONT class="Apple-style-span" face="Arial">Dr. Gabriel Pellegrini. La Plata. Argentina.</FONT></DIV></BLOCKQUOTE></DIV></BODY></HTML>