[SCD-FORUM] 102E RE: Hypertrophic cardiomyopathy. Dr. Perez Riera

[SCD Symposium]

Dr. Gabriel Pellegrini from La Plata. Argentina. I´m Andrés Ricardo  
Pérez Riera from Sao Paulo Brazil.
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.

Major risk factors for SCD include (1):

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.

2)       NON-SUSTAINED AND SUSTAINED VT IN HOLTER MONITORING;


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);

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;

5)       AN ABNORMAL BLOOD PRESSURE RESPONSE ON EXERCISE;

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;

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.
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.
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).

References
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.
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;
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.
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.

All the best
Andrés Ricardo Pérez Riera
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-

--
Dr. Sergio Dubner
President of Scientific Committee

Dr. Edgardo Schapachnik
President of Steering Committee


>
>
> Good afternoon.
> I would like to read opinions about: what patient with hypertrophic  
> cardiomyopathy should undergo a genetic study?
>
> Thank you very much,
> Dr. Gabriel Pellegrini. La Plata. Argentina.
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