[ARVD-FORUM] EXPERTS ASK, EXPERTS ANSWER. Dr. Wlodarska

Fri Apr 15 16:54:14 ART 2005

English - Spanish

Dear Dr Perez Riera,
let me desagree with you again. May I ask you some practical questions?
Could you frankly answer me if you perform biopsy in all your patients with
ARVC? Even in those with typical changes in ECG, Echo and MRI? Even in
patients with  well controled arrhythmia without syncope? What about
patients with paper thin RV wall? How the result of a biopsy influence your
therapeutical decisions when you don't have any doubts that a patient should
have ICD inserted?
Yours sincerely,

Katarzyna Wlodarska

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

Estimado Dr. Perez Riera:
Dejeme discrepar con Ud. nuevamente. Podria hacerle algunas preguntas
practicas? Podria responderme en forma franca si Ud. realiza biopsias en
todos sus pacientes con DAVD? Incluso en aquellos con cambios tipicos en
ECG, Eco y IRM? Incluso en pacientes con arritmia bien controlada sin
sincope? Que pasa con los pacientes con paredes del VD delgadas como un
papel? Como influye el resultado de una biopsia en sus decisiones
terapeuticas cuando no tiene ninguna duda de que un paciente deberia tener
un CDI implantado?
Atentamente,

Katarzyna Wlodarska

Katarzyna Wlodarska

_______________________________________

>
> 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.
> >
> > _______________________________________________
> > Arvd-forum mailing list
> > Arvd-forum at ishne.org
> > http://www.ishne.org/mailman/listinfo/arvd-forum

-- 
Dr. Sergio Dubner
Director

Dr. Edgardo Schapachnik
Director