[ARVD-FORUM] EXPERTS ASK, EXPERTS ANSWER. Dr. Perez Riera

Thu Apr 14 23:24:58 ART 2005

English - Portuguese

Excuse me dear Dr Katarzyna Wlodarska, but I disagree with you point of view
because the complications EMB are insignificant, and because of its
important benefit for an accurate diagnosis, the procedure is recommend for
differential diagnosis.(Benedek I, Hintea T.Endomyocardial biopsy in
diagnosis of myocardial diseases.Rom J Intern Med. 1999;37:207-215.)

The diagnosis of ARVC/D is a clinical challenge, and the gold standard for
making the diagnosis has not yet been defined.

EMB is of limited value because the affected area may be missed, and biopsy
of the RV free wall-the region most often affected-is considered hazardous.
(Niroomand F,Carbucicchio C, Riva S, et al. Electrophysiological
characteristics and outcome in patients with idiopathic right ventricular
arrhythmia compared with arrhythmogenic right ventricular dysplasia Heart
2002;87:41-47). Using a flexible bioptome is possible to obtain tissue
samples from RV and LV.

False positives include other conditions with fatty infiltration of the
ventricle, such as chronic alcohol abuse and Duschenne/Becker muscular
dystrophy.

False negatives are common, however, because the disease progresses
typically from the epicardium to the endocardium (with the biopsy sample
coming from the endocardium), and the segmental nature of the disease. Also,
due to the paper-thin RV free wall that is common in this disease process,
most biopsy samples are taken from the ventricular septum, which is commonly
not involved in the disease process.

A biopsy sample that is consistent with ARVC/D would have > 3% fat, > 40%
fibrous tissue, and < 45% myocytes.

Chimenti et al (Chimenti C, Pieroni M, Maseri A, et al. Histologic findings
in patients with clinical and instrumental diagnosis of sporadic
arrhythmogenic right ventricular dysplasia. J Am Coll Cardiol. 2004;
43:2305-2313) studied thirty patients with LBB morphology VT and
echocardiographic, angiographic, and MRI findings diagnostic of ARVC/D. All
patients, besides diagnostic, noninvasive, and invasive cardiac studies,
underwent EMB in the apex, anterior free wall, and inferior wall of the RV
and in the septal-apical region of the LV.  Diagnostic histologic features
of ARVC/D were found only in 30% patients and a myocarditis, according to
the Dallas criteria, in the remaining 70% patients. Morphometric evaluation
of RV samples showed significant differences in fatty tissue and myocyte
percent area between ARVC/D and myocarditis. Conversely, no difference was
found between the two groups in arrhythmic patterns and structural and
functional echocardiographic, angiographic, and MRI RV alterations. MRI
showed hyperintense signals in 67% of ARVC/D and in 62% of myocarditis
group. During follow-up (mean, 23 +/- 14 months), all patients with
myocarditis remained stable on antiarrhythmic therapy while five patients
with ARVC/D required implantation of an ICD. A myocarditis involving the RV
can mimic ARVC/D. An EMB appears the most reliable diagnostic technique,
with significant prognostic and therapeutic implications.  The echo-guided
EMB appears to be a prospective alternative to the conventional approach
under X-ray guidance. Its duration is comparable; it eliminates X-ray
exposure, enables continuous echocardiographic monitoring and can be
performed at the bedside. (Bedanova H, Necas J, Petrikovits E, et al.
Echo-guided endomyocardial biopsy in heart transplant recipients. Transpl
Int. 2004;17:622-625.)

Conclusion: Excuse me dear Dr Katarzyna Wlodarska but sometimes EMB is very
necessary for diagnosis and therapeutics implications...I think.

Best Regards

Andrés Ricardo Pérez Riera

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

Portugues

Perdoe-me Dr Katarzyna Wlodarska, mas descordo com seu ponto de vista,
porque as complicações da BEM são insignificantese porque permite um
diagnóstico apurado e o procedimento é recomendado para diagnóstico
diferencial. (Benedek I, Hintea T.Endomyocardial biopsy in diagnosis of
myocardial diseases.Rom J Intern Med. 1999;37:207-215.)

O diagnóstico da DAVD é um verdadeiro desafio e representada um padrão ouro
na confecção do diagnóstico, quando não está ainda bem definido. A BEM
possui um vaor limitado porque a área afetada pode não ser detectada e a
parede livre de VD (região mais freqüentemente afetada) é considerada
difícil em seu acesso. (Niroomand F,Carbucicchio C, Riva S, et al.
Electrophysiological characteristics and outcome in patients with idiopathic
right ventricular arrhythmia compared with arrhythmogenic right ventricular
dysplasia Heart 2002;87:41-47).

Usando um biótomo flexível, é possível obter amostras do tecido, tanto do VD
como do VE. Falso-positivo incluem outras condições como alcoolismo e as
distrofias musculares de Duschenne/Becker.

Falso-negativos são comuns, por que a doença progride tipicamente de
epicardio a endocárdio (a amostra da biopsia é extraída do endocárdio) e
pode natureza segmentar da doença.

Por outro lado, o afinamento da parede livre do VD é comum, e isso faz com
que as biopsias tenham que ser extraídas do septo, o qual não é comumente
acometido na doença.

A amostra é consistente com o diagnóstico de DAVD quando possui mais de 3%
de gordura, mais de 40% de fibrose e menos de 45% de miócitos. Chimenti e
cols (Chimenti C, Pieroni M, Maseri A, et al. Histologic findings in
patients with clinical and instrumental diagnosis of sporadic arrhythmogenic
right ventricular dysplasia. J Am Coll Cardiol. 2004; 43:2305-2313)
estudando 30 pacientes portadores de TV com morfologia de BCRE pelo
ecocardiograma, angiograma e RNM onde se realizou diagnóstico de DAVD. Todos
os pacientes  realizaram BEM no ápex, parede anterior do VD, parede inferior
do VD e região septo-apical de VE.

Diagnóstico histológico compatível co DAVD foi encontrado em apenas 30% dos
pacientes e miocardite em 70% restante, usando os critérios de Dallas. A
evolução morfométrica das amostras extraídas do VD revelaram diferenças
significativas na quantidade de gordura e na porcentagem dos miócitos quando
comparados a DAVD e a miocardite. Contrariamente, não encontraram diferenças
entre ambos grupos quando foram estudados pelo ecocardiograma, RNM e
angiografia. O VD na RNM mostrou sinais de hiperintensidade em 77% dos casos
de DAVD e em 62% no caso de miocardites, durante um seguimento médio de 23
meses,todos os pacientes com miocardites permaneceram instáveis com
anti-arritmos. Já 5 pacientes com DAVD requeriam implante de CDI. Uma
miocardite comprometendo o VD pode simular uma DAVD e a miocárdio biopsia é
a mais importante técnica diagnóstica com significado prognóstico e
terapêutico.

A BEM guiada pelo ecocardiograma pode ser uma alternativa a abordagem pelo
raio-x e sua duração é comparável alem de eliminar as exposições aos raios e
permitir um monitoramento continuo do ecocardiograma ao lado do leito.
(Bedanova H, Necas J, Petrikovits E, et al. Echo-guided endomyocardial
biopsy in heart transplant recipients. Transpl Int. 2004;17:622-625.)

Conclusão: Perdoe-me prezado Dr Katarzyna Wlodarska mas as vezes a BEM é
muito necessária para o diagnóstico e guia terapêutico...penso eu.

Saudações

Andrés Ricardo Pérez Riera

_______________________________________

>
> English- Spanish
>
> Dear Dr Perez-Riera,
> I agree with you that endomyocardial biopsy is valuable method in diagnosis
> of ARVC, but in my opinion as an invasive one it should be performed only
> when clinically indicated. The histological type of ARVC does not have any
> impact on therapeutical decisions. From scientific point of view it would
> be very usefull to have histopathologic diagnosis in each case, but we can
> not exclude possible complications, even if they are very rare.
> Sincerely yours,
>
> Katarzyna Wlodarska
>
> ------------------------
>
> Estimado Dr. Perez Riera:
> Coincido con Ud. en que la biopsia endomiocardica es un metodo valioso para
> el diagnostico de M/DAVD, pero en mi opinion, como metodo invasivo, se
> deberia realizar solo cuando se indique clinicamente. El tipo histologico
> de M/DAVD no tiene ningun impacto en las decisiones terapeuticas. Desde el
> punto de vista cientifico seria muy util tener un diagnostico
> histopatologico en cada caso, pero no podemos excluir posibles
> complicaciones, aunque sean muy raras.
>
> Atentamente,
>
> Katarzyna Wlodarska
>
>  _____________________________________
>
> > English - Spanish
> >
> > Dr. Enrique Retik from Argentina asks. Dr. Andres Perez Riera from Brasil
> > responds
> >
> > QUESTION
> > - Endomyocardial biopsy should be performed when there is clinical
> > suspicion of ARVD?
> >
> >
> > Dr. Alejandro Cueto from Uruguay asks. Dr. Andres Perez Riera from Brasil
> > responds
> >
> > QUESTION
> > - If the biopsy is not within the diagnostic criteria, in which cases is
> > it indicated?
> >
> >
> > Dr. José Luis González from Argentina asks. Dr. Andres Perez Riera from
> > Brasil responds
> >
> > QUESTION
> > - In what case should you indicate a cardiac biopsy?
> >
> > ANSWER
> > - In all of cases because is important for determination of type: fatty
> > or fibro-fatty form.
> >
> >  Two patterns are described depending on the presence of additional
> > fibrosis: (Thiene G, Nava A, Corrado D, et al. Right ventricular
> > cardiomyopathy and sudden death in young people. N Engl J Med 1988;
> > 318:129-133).  (Nava A, Thiene G, Canciani B, et al. Familial occurrence
> > of right ventricular dysplasia: a study involving nine families. J Am
> > Coll Cardiol. 1988; 12:1222-1228.)
> >
> > (1)     Fatty (40%); Tabib et al. (Tabib A, Loire R, Chalabreysse L, et
> > al Circumstances of death and gross and microscopic observations in a
> > series of 200 cases of sudden death associated with arrhythmogenic right
> > ventricular cardiomyopathy and/or dysplasia. Circulation. 2003;
> > 108:3000-3005) from 200 consecutive cases observed that adipose
> > infiltration of the RV was either isolated (20%) or associated with
> > fibrosis (74.5%) and lymphocytes (5.5%).
> >
> > (2)     Fibro-fatty (60%): the latter is associated to RV wall thinning
> > as a consequence of programmed, non-necrotic cell death (apoptosis) and
> > secondary repair by fibro-fatty tissue mediated by patchy myocarditis. In
> > this variety, the association with focal lymphocytic myocarditis is high,
> > as well as with left ventricle (LV) and septum involvement; and
> > appearance of RV aneurysms and inflammation is almost exclusive to the
> > fibro-fatty variety. Whether inflammation is a primary phenomenon or a
> > spontaneous reaction to apoptosis, still remains to be solved. (Basso C,
> > Thiene G, Corrado D, Angelini A, Nava A, Valente M. Arrhythmogenic right
> > ventricular cardiomyopathy. Dysplasia, dystrophy, or myocarditis?
> > Circulation. 1996; 94:983-991.).
> >
> > Transvenous biopsy (through the internal jugular vein) of the RV can be
> > highly specific for ARVC/D, but it has low sensitivity. The diagnosis of
> > ARVC/D is a clinical challenge, and the gold standard for making the
> > diagnosis has not yet been defined.
> >
> > EMB is of limited value because the affected area may be missed, and
> > biopsy of the RV free wall-the region most often affected-is considered
> > hazardous. (Niroomand F,Carbucicchio C, Riva S, et al.
> > Electrophysiological characteristics and outcome in patients with
> > idiopathic right ventricular arrhythmia compared with arrhythmogenic
> > right ventricular dysplasia Heart 2002;87:41-47). Using a flexible
> > bioptome is possible to obtain tissue samples from RV and LV.
> >
> >  False positives include other conditions with fatty infiltration of the
> > ventricle, such as chronic alcohol abuse and Duschenne/Becker muscular
> > dystrophy.
> >
> > False negatives are common, however, because the disease progresses
> > typically from the epicardium to the endocardium (with the biopsy sample
> > coming from the endocardium), and the segmental nature of the disease.
> > Also, due to the paper-thin RV free wall that is common in this disease
> > process, most biopsy samples are taken from the ventricular septum, which
> > is commonly not involved in the disease process.
> >
> > A biopsy sample that is consistent with ARVC/D would have > 3% fat, > 40%
> > fibrous tissue, and < 45% myocytes.
> >
> > Chimenti et al (Chimenti C, Pieroni M, Maseri A, et al. Histologic
> > findings in patients with clinical and instrumental diagnosis of sporadic
> > arrhythmogenic right ventricular dysplasia. J Am Coll Cardiol. 2004;
> > 43:2305-2313) studied thirty patients with LBB morphology VT and
> > echocardiographic, angiographic, and MRI findings diagnostic of ARVC/D.
> > All patients, besides diagnostic, noninvasive, and invasive cardiac
> > studies, underwent EMB in the apex, anterior free wall, and inferior wall
> > of the RV and in the septal-apical region of the LV.  Diagnostic
> > histologic features of ARVC/D were found only in 30% patients and a
> > myocarditis, according to the Dallas criteria, in the remaining 70%
> > patients. Morphometric evaluation of RV samples showed significant
> > differences in fatty tissue and myocyte percent area between ARVC/D and
> > myocarditis. Conversely, no difference was found between the two groups
> > in arrhythmic patterns and structural and functional
> > echocardiographic, angiographic, and MRI RV alterations. MRI showed
> > hyperintense signals in 67% of ARVC/D and in 62% of myocarditis group.
> > During follow-up (mean, 23 +/- 14 months), all patients with myocarditis
> > remained stable on antiarrhythmic therapy while five patients with ARVC/D
> > required implantation of an ICD. A myocarditis involving the RV can mimic
> > ARVC/D. An EMB appears the most reliable diagnostic technique, with
> > significant prognostic and therapeutic implications.  The echo-guided EMB
> > appears to be a prospective alternative to the conventional approach
> > under X-ray guidance. Its duration is comparable; it eliminates X-ray
> > exposure, enables continuous echocardiographic monitoring and can be
> > performed at the bedside. (Bedanova H, Necas J, Petrikovits E, et al.
> > Echo-guided endomyocardial biopsy in heart transplant recipients. Transpl
> > Int. 2004;17:622-625.)
> >
> > Because the complications of this procedure are insignificant, and
> > because of its important benefit for an accurate diagnosis, the procedure
> > is recommend for different cardiomyopathies.(Benedek I, Hintea
> > T.Endomyocardial biopsy in diagnosis of myocardial diseases.Rom J Intern
> > Med. 1999;37:207-215.)
> >
> > Complications
> >
> > 1)       Pneumothorax;
> >
> > 2)        Atrial or ventricular arrhtymias.
> >
> > -------------------------------------------------------------------------
> >-- -
> >
> > El Dr. Enrique Retik de Argentina pregunta. El Dr. Andres Perez Riera de
> > Brasil, responde
> >
> > PREGUNTA
> > - ¿Debe realizarse biopsia endomiocárdiaca cuando existe sospecha clínica
> > de ARVD?
> >
> >
> > El Dr. Alejandro Cueto de Uruguay pregunta. El Dr. Andres Perez Riera de
> > Brasil, responde
> >
> > PREGUNTA
> > - No estando la biopsia dentro de los criterios diagnósticos, ¿en que
> > casos está indicada?
> >
> >
> > El Dr. José Luis González de Argentina pregunta. El Dr. Andres Perez
> > Riera de Brasil, responde
> >
> > PREGUNTA
> > - ¿En qué caso se debe indicar una biopsia cardíaca?
> >
> > RESPUESTA
> > - En todos los casos porque es importante para la determinación del tipo:
> > forma adiposa o fibroadiposa.
> >
> > Dos patrones se describen, dependiendo de la presencia de fibrosis
> > adicional. (Thiene G, Nava A, Corrado D, et al. Right ventricular
> > cardiomyopathy and sudden death in young people. N Engl J Med 1988;
> > 318:129-133).  (Nava A, Thiene G, Canciani B, et al. Familial occurrence
> > of right ventricular dysplasia: a study involving nine families. J Am
> > Coll Cardiol. 1988; 12:1222-1228).
> >
> > Adiposa (40%): Tabib y cols., (Tabib A, Loire R, Chalabreysse L, et al
> > Circumstances of death and gross and microscopic observations in a series
> > of 200 cases of sudden death associated with arrhythmogenic right
> > ventricular cardiomyopathy and/or dysplasia. Circulation. 2003;
> > 108:3000-3005) de 200 casos consecutivos, observaron que la infiltración
> > adiposa del VD fue o aislada (20%) o asociada con fibrosis (74,5%) y
> > linfocitos (5,5%).
> >
> > Fibroadiposa (60%): ésta se asocia con adelgazamiento de la pared del VD
> > como consecuencia de muerte celular programada no necrótica (apoptosis) y
> > reparación secundaria de tejido fibroadiposo mediada por miocarditis en
> > "parches" (patchy). En esta variedad, la asociación con miocarditis
> > linfocítica focal es alta, así como con compromiso del ventrículo
> > izquierdo (VI) y del septo; y la aparición de aneurismas del VD e
> > inflamación son casi exclusivas de la variedad fibroadiposa. Si la
> > inflamación es un fenómeno primario o una reacción espontánea a la
> > apoptosis, es una cuestión que aun debe resolverse. (Basso C, Thiene G,
> > Corrado D, Angelini A, Nava A, Valente M. Arrhythmogenic right
> > ventricular cardiomyopathy. Dysplasia, dystrophy, or myocarditis?
> > Circulation. 1996; 94:983-991).
> >
> > La biopsia transvenosa (a través de la vena yugular interna) del VD puede
> > ser altamente específica para la M/DAVD, pero tiene una baja
> > sensibilidad. El diagnóstico de M/DAVD es un desafío clínico, y el gold
> > standard para hacer el diagnóstico no se ha definido aun.
> >
> > La BEM es de valor limitado, porque el área afectada se puede pasar por
> > alto, y la biopsia de la pared libre del VD, la región afectada con mayor
> > frecuencia, se considera peligrosa. (Niroomand F,Carbucicchio C, Riva S,
> > et al. Electrophysiological characteristics and outcome in patients with
> > idiopathic right ventricular arrhythmia compared with arrhythmogenic
> > right ventricular dysplasia Heart 2002;87:41-47). El empleo de un catéter
> > bioptome flexible es posible para obtener muestras de tejido del VD y el
> > VI.
> >
> > Los falsos positivos incluyen otras condiciones con infiltración adiposa
> > del ventrículo, como el abuso crónico de alcohol y la distrofia muscular
> > de Duchenne/Becker.
> >
> > Los falsos negativos son comunes, sin embargo, dado que la enfermedad
> > progresa típicamente desde el epicardio al endocardio (la muestra
> > biópsica proviene del endocardio), y la naturaleza segmentaria de la
> > enfermedad. Además, por la pared libre del VD delgada como un papel, que
> > es común en este proceso patológico, la mayoría de las muestras biópsicas
> > se toman del septo ventricular, que comúnmente no está comprometido en el
> > proceso de la enfermedad.
> >
> > Una muestra biópsica que sea consistente con la M/DAVD tendría >3% de
> > adiposidad, >40% de tejido fibroso y <45% de miocitos.
> >
> > Chimenti y cols., (Chimenti C, Pieroni M, Maseri A, et al. Histologic
> > findings in patients with clinical and instrumental diagnosis of sporadic
> > arrhythmogenic right ventricular dysplasia. J Am Coll Cardiol. 2004;
> > 43:2305-2313) estudiaron a treinta pacientes con TV con morfología de BRI
> > y hallazgos ecocardiográficos, angiográficos y de IRM diagnósticos de
> > M/DAVD. Todos los pacientes, además de los estudios diagnósticos, no
> > invasivos e invasivos cardíacos, se sometieron a BEM en el ápice, la
> > pared libre anterior y la pared inferior del VD y en la región
> > septo-apical del VI. Las características histológicas diagnósticas de la
> > M/DAVD se hallaron solamente en el 30% de los pacientes y miocarditis,
> > según el criterio de Dallas, en el 70% restante de los pacientes. La
> > evaluación morfométrica de las muestras del VD mostraron diferencias
> > significativas en el tejido adiposo y el área de porcentaje de miocitos
> > entre la M/DAVD y la miocarditis. Por el contrario, no se encontraron
> > diferencias entre los dos grupos en los patrones arrítmicos y las
> > alteraciones estructurales y funcionales ecocardiográficas, angiográficas
> > y de IRM del VD. La IRM mostró señales de hipertensión en el 67% de la
> > M/DAVD y en el 62% del grupo con miocarditis. Durante el seguimiento
> > (promedio 23 +/-14 meses), todos los pacientes con miocarditis
> > permanecieron estables con terapia antiarrítmica, mientras que cinco
> > pacientes con M/DAVD necesitaron implante de CDI. Una miocarditis que
> > comprometa el VD puede simular M/DAVD. La BEM parece ser la técnica de
> > diagnóstico más confiable, con implicancias pronósticas y terapéuticas
> > significativas. La BEM guiada por eco parece ser una alternativa
> > prospectiva al enfoque convencional bajo la guía
> > radiográfica. Su duración es comparable; elimina la exposición a los
> > rayos X, permite un monitoreo ecocardiográfico continuo y puede
> > realizarse con el paciente en cama. (Bedanova H, Necas J, Petrikovits E,
> > et al. Echo-guided endomyocardial biopsy in heart transplant recipients.
> > Transpl Int. 2004;17:622-625).
> >
> > Puesto que las complicaciones de este procedimiento son insignificantes,
> > y dado el importante beneficio para un diagnóstico preciso, se recomienda
> > el procedimiento para las diferentes miocardiopatías. (Benedek I, Hintea
> > T.Endomyocardial biopsy in diagnosis of myocardial diseases.Rom J Intern
> > Med. 1999;37:207-215).
> >
> > Complicaciones
> > (1)	Neumotórax
> > (2)	Arritmias auriculares o ventriculares.
>
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Dr. Sergio Dubner
Director

Dr. Edgardo Schapachnik
Director