[ARVD-FORUM] Personal message. Dr. Escape

Thu Apr 7 13:42:34 ART 2005

English - Spanish

Dear colleague Dra. Isabel Escape from Barcelona.
Yes I confirm.  Methylphenidate is used in the treatment of
attention-deficit/hyperactivity disorder (ADHD). ADHD are associated with
minor, but statistically significant, changes in heart rate and blood
pressure that were often observed in those receiving placebo. Given the
minor
pressor and chronotropic effect of these medications, patients with ADHD
should have their blood pressure and heart rate checked at baseline and
periodically during treatment. Wilens TE, Hammerness PG, Biederman J,  et al
Blood pressure changes associated with medication treatment of adults with
attention-deficit/hyperactivity disorder. J Clin Psychiatry.
2005;66:253-259.

Methylphenidate-induced increases in blood pressure are in part due to its
central dopaminergic effects.  Methylphenidate's pressor effects may be in
part mediated by dopamine-induced increases in peripheral
epinephrine.(Volkow
ND, Wang GJ, Fowler JS,  et al Cardiovascular effects of methylphenidate in
humans are associated with increases of dopamine in brain and of epinephrine
in plasma.Psychopharmacology (Berl). 2003;166:264-270).

In ARVC/D we observe catecholamines facilitation. The induction of the VT
generally is dependent of the infusion of isoproterenol. Catecholamines
increase the ST segment elevation.

ARVC/D Type 2 an autosomal dominant pattern of inheritance mapped to the
long arm of chromosome 1. Cytogenetics is 1q42-q43 and the OMIN number is 
600996 is characterized by presenting as a minor or "concealed phase", 
showing PVT induced by strain. Since both loci, ARVD1 and ARVD2, were mapped 
near the alpha-actin gene, it is possible to involve it with these 
myofibrillar proteins in the pathogenesis of ARVC/D (Rampazzo A, Nava A, Erne 
P, Eberhard M, Vian E, Slomp P, Tiso N, Thiene G, Danieli GA.A new locus for
arrhythmogenic right ventricular cardiomyopathy (ARVD2) maps to chromosome
1q42-q43. Hum Mol Genet. 1995;  4:2151-2154.).  A  RYR2 mutation has been
identified in four independent families. The RyR2 protein in myocardial
cells activated by ion calcium Ca2+ induces cation release from the 
sarcoplasmic reticulum to cytosol. The RyR2 protein is the equivalent to the 
ryanodine receptor protein of the skeletal muscle, known as RyR1. The 
skeletal muscle ryanodine receptor has a role in malignant hyperthermia and 
in susceptibility in the so-called central core disease (CCD) (Tiso N, 
Stephan DA, Nava A, et al. identification of mutations in the cardiac 
ryanodine receptor gene in families affected with arrhythmogenic right 
ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet 2001;10:189-94.) 
(Tiso N, Bauce B, Rampazzo A, Bagattin A, Nava A, Danieli GA. Gene symbol: 
RYR2. Disease: Arrhythmogenic right ventricular cardiomyopathy type 2.Hum 
Genet. 2004; 114:405.)
Clinically it causes PVT induced by strain or emotional adrenergic stress in a 
similar way to familial catecholaminergic PVT without structural heart 
disease (Bagattin A, Bauce B, Rampazzo A, Tiso N, Nava A, Danieli GA.Gene 
symbol: RYR2. Disease: Effort-induced polymorphic ventricular arrhythmias. 
HumGenet. 2004;114:406.).

FinaI conclusion: I think that is dangeours to use Methylphenidate in first
degree relatives of ARVD patients.

You ask: would like to ask you, what is the recommended age to make studies
on them? How frequently?. Please read Dr Marcus recomendations in this forum.

Best

Andres Perez Riera

-----------------------

Estimada colega, Dra. Isabel Escape de Barcelona:
Si, se lo confirmo. El metilfenidato se emplea en el tratamiento del
trastorno por deficit de atencion con hiperactividad (TDAH). El TDAH se
asocia con cambios menores, pero estadisticamente significativos, en la
frecuencia cardiaca y la presion sanguinea, que se observan con frecuencia
en quienes reciben placebo. Dado el efecto menor presor y cronotropico de
estos medicamentos, los pacientes con TDAH deben verificar su presion
sanguinea y su frecuencia cardiaca en condiciones basales y periodicamente
durante el tratamiento.
Wilens TE, Hammerness PG, Biederman J,  et al
Blood pressure changes associated with medication treatment of adults with
attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2005;66:253-259.

Los aumentos de la presion sanguinea inducidos por metilfenidato se deben en
parte a sus efectos centrales dopaminergicos. Los efectos presores del
metilfenidato pueden ser mediados en parte por aumentos inducidos por
dopamina en la epinefrina periferica. (Volkow ND, Wang GJ, Fowler JS,  et al
Cardiovascular effects of methylphenidate in humans are associated with
increases of dopamine in brain and of epinephrine in plasma. 
Psychopharmacology (Berl). 2003;166:264-270).

En la M/DAVD observamos facilitacion de catecolaminas. La induccion de las
TV generalmente depende de la infusion de isoproterenol. Las catecolaminas
aumentan el supradesnivel del segmento ST.

La M/DAVD tipo 2 presenta un patron autosomico dominante de herencia,
mapeado en el brazo largo del cromosoma 1. La citogenetica es 1q42-q43 y el
numero OMIM es 600996, y se caracteriza por presentarse como una "etapa
oculta" o menor, que muestra TVP inducida por esfuerzo. Puesto que ambos
locus, DAVD1 y DAVD2 se mapearon cerca del gene de la alfa actina, es
posible involucrarlo con estas proteinas miofibrilares en la patogenesis de
la M/DAVD (Rampazzo A, Nava A, Erne P, Eberhard M, Vian E, Slomp P, Tiso N, 
Thiene G, Danieli GA. A new locus for arrhythmogenic right ventricular 
cardiomyopathy (ARVD2) maps to chromosome 1q42-q43. Hum Mol Genet. 1995;  
4:2151-2154).
Una mutacion RYR2 se ha identificado en cuatro familias independientes. La
proteina RyR2 en las celulas miocardicas, activada por el ion calcico Ca2+,
induce la liberacion de cationes desde el reticulo sarcoplasmatico en el
citosol. La proteina RyR2 es el equivalente del receptor de rianodina del
musculo esqueletico, conocido como RyR1. El receptor de rianodina del
musculo esqueletico tiene un papel en la hipertermia maligna y en la
susceptibilidad en la llamada enfermedad del nucleo central (ENC) (Tiso N,
Stephan DA, Nava A, et al. identification of mutations in the cardiac 
ryanodine receptor gene in families affected with arrhythmogenic right 
ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet 2001;10:189-94.) 
(Tiso N, Bauce B, Rampazzo A, Bagattin A, Nava A, Danieli GA. Gene symbol: 
RYR2. Disease: Arrhythmogenic right ventricular cardiomyopathy type 2.Hum 
Genet. 2004; 114:405).
Clinicamente, causa TVP inducida por esfuerzo o estres adrenergico
emocional, de manera similar a la TVP catecolaminergica familiar sin
cardiopatia estructural. (Bagattin A, Bauce B, Rampazzo A, Tiso N, Nava A,
Danieli GA.Gene symbol:
RYR2. Disease: Effort-induced polymorphic ventricular arrhythmias. Hum
Genet. 2004;114:406).

Conclusion final: creo que es peligroso usar el metilfenidato en parientes
en primer grado de pacientes con DAVD.

Ud. pregunta: Quisiera preguntarles a ¿que edad se recomienda  estudiarles?
, ¿con que frecuencia? Por favor lea las recomendaciones del Dr. Marcus en
este foro.

Saludos,

Andrés Ricardo Pérez Riera

t _____________________________________
>
> English - Spanish
>
> Dear colleagues,
>
> Before anything, I want to thank you for the organization and the
> possibility of being able to participate in this forum about ARVD.
> My specialty is not cardiology, but radiology, but I find myself in the
> hard situation of facing my husband's death five months ago because of this
> disease. It could not be diagnosed, though he had been through several
> studies, including an electrophysiological study, which was negative. I
> have three children of 11, 14, and 16 years old.
>
> I would like to ask you, what is the recommended age to make studies on
> them? How frequently? And I also would like to know whether the medication
> indicated for an attention deficit disorder with hyperactivity
> (Methylphenidate) is counterindicated o it could have side effects. I have
> seen on some of the comments I have been reading these days, that it is
> necessary to include the partners as well in the screening. I also wanted
> to confirm this opinion.
>
> Thank you very much.
>
> Sincerely,
>
> Dra. Isabel Escape
> Barcelona
>
> Spain.
>
> ---------------------------
>
> Apreciados colegas.
>
> Ante todo queria agradecerles la organización y la posibilidad de poder
> participar en este forum sobre ARVD.
> Mi especialidad no es la cardiologia, sino la radiología,  pero me
> encuentro ante la difícil situación de hacer frente a la muerte de mi
> marido hace 5 meses a causa de esta enfermedad. No pudimos diagnosticarla a
> pesar de haberle hecho numeros estudios, incluído un estudio
> electrofisiólogico, que fue negativo.
> Tengo tres hijos de 11, 14, y 16 años.
>
> Quisiera preguntarles a ¿que edad se recomienda  estudiarles? , ¿con que
> frecuencia? y tambien saber si la medicacion que se administra para un
> deficit de atencion con hiperactividad (Metilfenidato)  esta contraindicada
> o puede tener efectos secundarios. En alguno de los comentarios que he ido
> leyendo estos días tambien se comenta que es necesario incluir en el
> screenig a los conyugues. Tambien querria confirmar esa opinión.
>
> Muchas gracias
>
> Atentamente
>
> Dra. Isabel Escape
> Barcelona
>
> Spain.