Debate endomyocardial biopsy aldia

Debate:

All patients with clinically suspected

myocarditis shall be biopsied

YES Alida LP Caforio, MD, PhD, FESC

Dept Cardiological ,Thoracic and Vascular Sciences

University of Padova, Italy

E-mail: [email protected]

mailto:[email protected]

ESC REPORT

Current stateofknowledgeonaetiology,diagnosis,

management, and therapy of myocardit is:

a posit ion statement of the European Society

of Cardiology W orking Group on Myocardial

and Pericardial Diseases

Alida L. P. Cafor io1†*, Sabine Pankuweit 2†, Eloisa Arbust ini3, Cr ist ina Basso4,

Juan Gimeno-Blanes5, Stephan B. Felix6, Michael Fu7, TiinaHelio8, Stephane Heymans9,

Roland Jahns10, Kar in Klingel11, AlesLinhart 12, Bernhard Maisch2, W illiam McKenna13,

JensMogensen14, Yigal M. Pinto15, Arsen Rist ic16, Heinz-Peter Schultheiss17,

Hubert Seggewiss18, Luigi Tavazzi19, Gaetano Thiene4, Ali Yilmaz20,

Philippe Charron21, and Perry M. Elliot t 13

1Division of Cardiology, Department of Cardiological Thoracic and Vascular Sciences, University of Padua, Padova, Italy; 2UniversitatsklinikumGießen und Marburg GmbH, Standort

Marburg,Klinik fur Kardiologie,Marburg, Germany; 3Academic Hospital IRCCSFoundation Policlinico, San Matteo, Pavia, Italy; 4Cardiovascular Pathology,Department of Cardiological

Thoracic and Vascular Sciences, University of Padua, Padova, Italy; 5Servicio de Cardiologia, Hospital U. Virgen de ArrixacaCtra. Murcia-Cartagena s/n, El Palmar, Spain; 6Medizinische

Klinik B, University of Greifswald, Greifswald, Germany; 7Department of Medicine, Heart Failure Unit, Sahlgrenska Hospital, University of Goteborg, Goteborg, Sweden; 8Division of

Cardiology, Helsinki University Central Hospital, Heart & LungCentre, Helsinki, Finland; 9Center for Heart Failure Research, Cardiovascular Research Institute, University Hospital of

Maastricht, Maastricht, The Netherlands; 10Department of Internal Medicine, Medizinische Klinik und Poliklinik I, Cardiology, Wuerzburg, Germany; 11Department of Molecular

Pathology,University Hospital Tubingen,Tubingen,Germany; 122ndDepartment of Internal Medicine, 1st School of Medicine, CharlesUniversity, Prague2,CzechRepublic; 13TheHeart

Hospital,University College, London, UK;14Department of Cardiology, Odense University Hospital,Odense, Denmark; 15Department of Cardiology (Heart FailureResearch Center),

Academic Medical Center, Amsterdam, The Netherlands; 16Department of Cardiology, Clinical Center of Serbiaand Belgrade University School of Medicine, Belgrade, Serbia;17Department of Cardiology and Pneumology, Charite Centrum 11 (Cardiovascular Medicine), Charite–Universitatsmedizin Berlin, CampusBenjamin Franklin, Berlin, Germany;18Medizinische Klinik 1, LeopoldinaKrankenhaus Schweinfurt, Schweinfurt, Germany; 19GVM Care and Research, MariaCeciliaHospital, Cotignola, RA, Italy; 20Robert-Bosch-

Krankenhaus, Stuttgart, Germany; and 21UPMC Univ Paris6, AP-HP, Hopital Pitie-Salpetriere, Centre de Reference Maladiescardiaques hereditaires, Paris, France

Received 14 December 2012; revised 19 April 2013;accepted 23 May2013; online publish-ahead-of-print 3 July2013

In thisposition statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviewsthe current

knowledge on clinical presentation, diagnosisand treatment of myocarditis, and proposesnew diagnostic criteria for clinically suspected myo-

carditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to

improve management and provide acommon reference point for future registries and multicentre randomised controlled trials of aetiology-

driven treatment in inflammatory heart muscle disease.- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -Keywor ds Myocarditis † Cardiomyopathy † Diagnosis † Therapy

Int roduct ion

Myocarditisisachallengingdiagnosisduetotheheterogeneityofclinical

presentations.1–3Theactual incidenceofmyocarditisisalso difficult to

determineasendomyocardial biopsy(EMB),thediagnosticgoldstand-

ard,1–3 isused infrequently.2,3 Studiesaddressing the issue of sudden

cardiac death in young people report a highly variable autopsy

prevalenceof myocarditis, rangingfrom2 to 42%of cases.4,5Similarly,

biopsy-provenmyocarditisisreported in9–16%of adult patientswith

unexplained non-ischaemic dilated cardiomyopathy (DCM)6,7 and in

46%ofchildrenwithanidentifiedcauseofDCM.8Inpatientspresenting

with mild symptomsand minimal ventricular dysfunction, myocarditis

often resolves spontaneously without specific treatment.9 However,

in up to 30% of cases, biopsy-proven myocarditis can progress to

†A.L.P.C. and S.P. contributed equally to the document.

* Correspondingauthor.DivisionofCardiology,Department ofCardiological ThoracicandVascular Sciences,PaduaUniversityMedical School,Policlinico Universitario,ViaN Giustinani,

2, 35128 Padova, Italy. Tel: + 39 (0)498212348, Fax: + 39 (0)498211802, Email: [email protected]

Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissionsplease email: [email protected]

European Heart Journal (2013) 34,2636–2648

doi:10.1093/eurheartj/eht210

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Debate:



YES: Why?

1) Can we reach the

diagnosis of certainty

without a biopsy? NO

What is myocarditis?

• Definition (Circulation, 1995 WHO/ISFC classification; Eur Heart J, 1999; AHA statement 2006; ESC 2008)

– Myocarditis is an inflammatory disease of the myocardium and is diagnosed by established histological, immunological and immunohistochemical criteria

• Histological features (Dallas criteria on EMB)

• Myocarditis forms

– idiopathic,

– Infectious (mainly viral) and/or autoimmune

Debate:



YES: Why?

2) Do we have a typical clinical presentation? NO

Myocarditis:clinical presentation

• Mild symptoms • Palpitation, atypical chest pain, SOB

• Minor ECG abnormalities • Conduction disturbances, ST-T changes

• Major arrhythmia • SVT, complete A-V block, VT-VF

• Syncope, sudden cardiac death

• Cardiogenic shock • Fulminant myocarditis

• Unexplained heart failure with or without DCM features

• Onset of symptoms: days or up to several years

• Peri-partum

• Infarct-like with normal coronary arteries

Chimenti et al, JACC 2004; 43: 2305

EMB in 30 pts with sporadic ARVC and similar clinical, ECG, Echo,

angiographic and MRI findings differentiates ARVC (fatty tissue and myocyte%

area) from myocarditis

30% ARVC 70%

Myocarditis

Miocarditis mimicking ARVC

CD45

B 021150 I BEM

• Active Autoimmune Myocarditis (T Lymphocytes, few B cells)

• Virus negative by PCR

•AHA pos

Z.V. 32 F, (peri-partum DCM,

cardiogenic shock )

CD45

Suspected myocarditis in a 36-year woman with acute DCM, normal coro’s www.escardioorg

European Society of CardiologyWorking Group onMyocardial & Pericardial Diseases

Newsletter Issue 34 – April 2011

Presented by: ^Martina Perazzolo Marra, MD, PhD *Marny

Fedrigo, PhD and ^Alida LP Caforio, MD, PhD

The clinical case of the month: What isyour diagnosis?

Biopsy-proven giant cell myocarditis in a 36-year woman with acute DCM, normal coro’s

Cooper LT, 2013 Heart Fail Rev

CD68

Courtesy of Prof A Angelini, Cardiac

Pathology, University of Padova, Italy

The clinical case of the month: What isyour diagnosis?

Caforio et al, Eur J Heart Fail 2009

Caforio et

al, Eur J

Heart Fail

2009

Myocarditis, mimicking Takotsubo cardiomyopathy

a, b:

inflammation

and necrosis

(HE);

c,d=positive T

lymph.

activated

(CD45RO);

f=positive

cytotoxic T

lymph

Caforio et al,

Eur J Heart

Fail 2009

Myocarditis, mimicking Takotsubo cardiomyopathy

Suspected myocarditis, 65 yr, male, pseudo-infarct

presentation (TnI, 20 μg/L) preserved LVEF


presentation (TnI, 20 μg/L) preserved LVEF, normal coro’s


presentation, preserved LVEF, normal coro’s: 3-D echo at

discharge

65 yr, male, pseudo-infarct presentation, normal LVEF and

coro’s, biopsy-proven autoimmune eosinophilic myocarditis

Cardiovascular Pathology, University of Padua A B

A: eosinophilic infiltrate, B: Thrombus

Table 3 Possible presentations in clinically suspected myocarditis

Caforio et al. Eur Heart J 2013; 34:2636-48

Clinical presentations*:

1) acute chest pain, pericarditic or pseudo-ischaemic

2 ) new-onset (days up to 3 months) or worsening of: dyspnoea at rest or exercise, and/or fatigue,

with or without left and/or right heart failure signs

3 ) subacute/chronic (>3 months) or worsening of: dyspnoea at rest or exercise, and/or fatigue, with

or without left and/or right heart failure signs

4 ) palpitation, and/or unexplained arrhythmia symptoms and/or syncope, and/or aborted sudden

cardiac death

5) unexplained cardiogenic shock

Table 3 Diagnostic criteria for clinically suspected myocarditis


Diagnostic criteria:

I. ECG/Holter/stress test features

1) newly abnormal 12 lead ECG and/or Holter and/or stress testing, any of the following: I to III

degree atrioventricular block, or bundle branch block, ST/T wave change (ST elevation or non

ST elevation, T wave inversion), sinus arrest, ventricular tachycardia or fibrillation and asystole,

atrial fibrillation, reduced R wave height, intraventricular conduction delay (widened QRS

complex), abnormal Q waves, low voltage, frequent premature beats, supraventricular

tachycardia

II. Myocardiocytolysis markers

2 ) elevated TnT/TnI by local criteria (high-sensitivity assay, where available)

III. Morphofunctional abnormalities at cardiac imaging (echo/angio/CMR)

3) new, otherwise unexplained LV and/or RV structure and function abnormality (including

incidental finding finding in apparently asymptomatic subjects): regional wall motion or global

systolic or diastolic function abnormality, with or without ventricular dilatation, with or without

increased wall thickness, with or without pericardial effusion, with or without endocavitary

thrombi.

IV. Tissue characterization by CMR

oedema and/or LGE of classical myocarditic pattern (see text)

Table 3 Diagnostic criteria for clinically suspected myocarditis


Clinically suspected myocarditis if >1 clinical presentation and >1 diagnostic criteria from

different categories, in the absence of: - 1) angiographically detectable coronary artery disease

(coronary stenosis ≥ 50%) –2) known pre-existing cardiovascular disease or extra-cardiac causes that

could explain the syndrome (e.g. valve disease, congenital heart disease, hyperthyroidism, etc.) (see

text). Suspicion is higher with higher number of fulfilled criteria. *If the patient is asymptomatic >2

diagnostic criteria should be met.

Diagnostic criteria and proposed diagnostic approach for clinically suspected myocarditis


Debate:



YES: Why?

3) Is EMB dangerous for the patient?

NO

ESC REPORT

Current stateof knowledgeonaet iology,diagnosis,






Juan Gimeno-Blanes5, Stephan B. Felix6, Michael Fu7, T iinaHelio8, Stephane Heymans9,

Roland Jahns10, Kar in Klingel11, Ales Linhart 12, Bernhard Maisch2, W illiam McKenna13,


Huber t Seggewiss18, Luigi Tavazzi19, Gaetano Thiene4, Ali Yilmaz20,


1Division of Cardiology, Department of Cardiological Thoracic and Vascular Sciences, University of Padua, Padova, Italy; 2Universitatsklinikum Gießen und Marburg GmbH, Standort

Marburg, Klinik fur Kardiologie, Marburg, Germany; 3Academic Hospital IRCCSFoundation Policlinico, San Matteo, Pavia, Italy; 4Cardiovascular Pathology, Department of Cardiological

Thoracic and Vascular Sciences, University of Padua, Padova, Italy; 5Servicio de Cardiologia, Hospital U. Virgen de Arrixaca Ctra. Murcia-Cartagena s/n, El Palmar, Spain; 6Medizinische

Klinik B, University of Greifswald, Greifswald, Germany; 7Department of Medicine, Heart FailureUnit, Sahlgrenska Hospital, University of Goteborg, Goteborg, Sweden; 8Division of



Pathology,University Hospital Tubingen, Tubingen, Germany;122nd Department of Internal Medicine,1st School of Medicine, CharlesUniversity, Prague2,CzechRepublic; 13TheHeart

Hospital, University College, London, UK;14Department of Cardiology, Odense University Hospital, Odense, Denmark; 15Department of Cardiology (Heart FailureResearch Center),

Academic Medical Center, Amsterdam, The Netherlands; 16Department of Cardiology, Clinical Center of Serbia and Belgrade University School of Medicine, Belgrade, Serbia;17Department of Cardiology and Pneumology, Charite Centrum 11 (Cardiovascular Medicine), Charite–Universitatsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany;18Medizinische Klinik 1, LeopoldinaKrankenhaus Schweinfurt, Schweinfurt, Germany; 19GVM Care and Research, Maria CeciliaHospital, Cotignola, RA, Italy; 20Robert-Bosch-

Krankenhaus, Stuttgart, Germany; and 21UPMC Univ Paris6, AP-HP, Hopital Pitie-Salpetriere, Centre de Reference Maladies cardiaques hereditaires, Paris, France

Received 14 December 2012; revised 19 April 2013; accepted 23 May2013


knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposesnew diagnostic criteria for clinically suspected myo-




Int roduct ion

Myocarditisisachallengingdiagnosisdueto theheterogeneityofclinical


determineasendomyocardial biopsy(EMB), thediagnosticgold stand-

ard,1–3 is used infrequently.2,3 Studies addressing the issue of sudden


prevalenceof myocarditis, rangingfrom 2 to 42%of cases.4,5Similarly,

biopsy-provenmyocarditisisreported in9–16%ofadult patientswith







* Correspondingauthor.Division ofCardiology,Department ofCardiological ThoracicandVascular Sciences,PaduaUniversityMedical School,Policlinico Universitario, ViaN Giustinani,


Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: journals.per [email protected]

European Heart Journal


European Heart Journal Advance Access published July 3, 2013

by

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, 20

13

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Jacc 2007 Eur Heart J 2013; 34:2636-48

Debate:



YES: Why?

4) Do we have a common aetiology

and similar treatment? NO

5) Do we have non-invasive

alternative tools to identify

aetiology? NO

Etiology of human myocarditis

INFECTIOUS IMMUNE-MEDIATED TOXIC

Bacterial Allergens: e.g. penicillin Drugs: e.g

catecholamine

cocaine

Spirochetal

Fungal Alloantigens: e.g. heart-

transplant rejection

Heavy

metals

Protozoal

Parasitic Physical

agents

Rickettsial

Viral: coxsackievirus, cytomegalovirus, dengue

virus, echovirus, encephalomyocarditis, Epstein–

Barr virus, hepatitis A, hepatitis C virus, herpes

simplex virus, herpes zoster, HIV, influenza A and

B, Junin virus, lymphocytic choriomeningitis,

measles, mumps, parvovirus, poliovirus, rabies,

respiratory syncytial, rubella, rubeola, vaccinia,

varicella–zoster, variola, and yellow fever virus

Autoantigens: e.g. myosin

in giant-cell myocarditis and

in virus-negative myocarditis ,

myocarditis associated to

organ and non-organ-specific

autoimmune diseases

Various

Agents, e.g

sting bites

Caforio A and McKenna WJ, Drugs 1996

From Task Force on Myocarditis-WG Position Statement, Eur Heart J 2013

Mar

ker

Aden

ovir

us

Cyto

meg

alovir

us

Epst

ein

-Bar

r vir

us

Infl

uen

za v

irus

A/B

Par

vovir

us

B19

Ente

rovir

us

Par

amix

ovir

us

Mark

er

Adenov

irus

Cyto

megalo

vir

us

Epst

ein

-Barr

vir

us

Herp

es

Sim

ple

x v

irus

Infl

uen

za v

irus

A/B

Parv

ovir

us

B19

Ente

rovir

us

Para

mix

ov

irus

Hepati

tis

C v

irus

*Calabrese et al.,Diagn Mol Pathol 2002; 11(4):212-21

Organ-specific (O-S) AHA and AIDA

Positive diffuse O-s and AIDA

pattern on human myocardium

(X40)

Negative pattern on human

skeletal muscle (X40)

Caforio et al. J Am Coll Cardiol 1990; 15 : 1527-34; Heart 2010; 96:779-84


Etiological forms of biopsy-proven myocarditis

ESC REPORT

Current stateofknowledgeonaetiology,diagnosis,






Juan Gimeno-Blanes5, Stephan B. Felix6, Michael Fu7, TiinaHelio8, Stephane Heymans9,

Roland Jahns10, Karin Klingel11, AlesLinhart 12, Bernhard Maisch2, W illiam McKenna13,


Hubert Seggewiss18, Luigi Tavazzi19, Gaetano Thiene4, Ali Yilmaz20,



Marburg, Klinik fur Kardiologie, Marburg, Germany; 3Academic Hospital IRCCSFoundation Policlinico, San Matteo,Pavia, Italy; 4Cardiovascular Pathology, Department of Cardiological

Thoracic and Vascular Sciences,University of Padua, Padova, Italy; 5Servicio de Cardiologia, Hospital U. Virgen de ArrixacaCtra. Murcia-Cartagena s/n, El Palmar, Spain; 6Medizinische

Klinik B, University of Greifswald, Greifswald, Germany; 7Department of Medicine, Heart Failure Unit, Sahlgrenska Hospital, University of Goteborg, Goteborg, Sweden; 8Division of

Cardiology, Helsinki University Central Hospital,Heart & LungCentre, Helsinki, Finland; 9Center for Heart Failure Research, Cardiovascular Research Institute, University Hospital of


Pathology,UniversityHospital Tubingen,Tubingen,Germany;122ndDepartment of Internal Medicine,1st School ofMedicine, CharlesUniversity,Prague2,CzechRepublic;13TheHeart


Academic Medical Center, Amsterdam, The Netherlands; 16Department of Cardiology, Clinical Center of Serbiaand Belgrade University School of Medicine, Belgrade, Serbia;17Department of Cardiology and Pneumology, Charite Centrum 11 (Cardiovascular Medicine), Charite–Universitatsmedizin Berlin, CampusBenjamin Franklin, Berlin, Germany;18Medizinische Klinik 1, LeopoldinaKrankenhaus Schweinfurt, Schweinfurt, Germany; 19GVM Care and Research, MariaCeciliaHospital,Cotignola, RA, Italy; 20Robert-Bosch-




knowledge on clinical presentation, diagnosisand treatment of myocarditis, and proposesnew diagnostic criteria for clinically suspected myo-




Int roduct ion

Myocarditisisachallengingdiagnosisduetotheheterogeneityofclinical


determineasendomyocardial biopsy(EMB),thediagnosticgoldstand-

ard,1–3 isused infrequently.2,3 Studiesaddressingthe issue of sudden


prevalenceof myocarditis, rangingfrom2 to 42%of cases.4,5Similarly,








* Correspondingauthor.DivisionofCardiology,Department ofCardiological ThoracicandVascular Sciences,PaduaUniversityMedical School,Policlinico Universitario,ViaN Giustinani,


Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissionsplease email: [email protected]




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Debate:



YES: Why?

6) Are biopsy data are prognostically

relevant? YES

AM: Actuarial survival

and PCR result

AM: Actuarial survival

and histology type

0 20 40 60 80 100

Follow up (months)

0,0

0,2

0,4

0,6

0,8

1,0

Pro

po

rtio

n S

urv

ivin

g

PCR result

PCR negative

PCR positive

P= 0.02

0 100 200 300

Follow up (months)

0,0

0,2

0,4

0,6

0,8

1,0

Pro

po

rtio

n S

urv

ivin

g

Histological type

Active lymphocytic

Borderline myocarditis

Giant cell myocarditis

Others

P= 0.004

P= 0.004

Caforio et al, Eur Heart J 2007; 28:1326-33

Figure 3. Unadjusted survival free from cardiac death and heart transplantation according to the findings of endomyocardial biopsy.

Kindermann I et al. Circulation 2008;118:639-648

Copyright © American Heart Association

Debate:



YES: Why?

7) Do biopsy data change clinical

management? YES

Hemodinamically unstable myocarditis


Major Criteria of Autoimmune Disease

• Mononuclear cell infiltrate and abnormal HLA expression in the target organ (organ-specific disease) or in various organs (nonorgan-specific disease) in the absence of infectious agents

• Circulating autoantibodies (Abs) and/or autoreactive lymphocytes in patients (pts) and family members

• Abs and/or autoreactive lymphocytes within the affected organ

• Identification and isolation of autoantigen(s) (Ags) involved

• Disease induction in animals after immunization with Ags and/or passive transfer of serum, Abs and/or lymphocytes

• Efficacy of immunosuppression/immunomodulation in pts

• Autoimmune disease= fullfillment of 2 or more major criteria

Witebsky E, Rose NR

ESC recommendations for immunosuppression in myocarditis

European Society of CardiologyWorking Group onMyocardial & Pericardial Diseases

Newsletter Issue 34 – April 2011


ACUTE MYOCARDITIS: DIAGNOSTIC AND MANAGEMENT PROTOCOL

Clinically Suspected Myocarditis

Haemodynamically stable

Preserved LV function

No eosinophilia

No significant rhythm or conduction disturbances

Not associated with systemic immune disease#

History, Examination, ECG, Echo, Laboratory tests: Troponin, CRP, ESR, Blood Cell Count, BNP,

CMR; if Available, Serum Cardiac Autoantibodies

Consider coronary angiography and EMB

No coronary disease

General Supportive Therapy

Haemodynamically

unstable, Decreased LV

Function,

Cardiogenic Shock

Pharmacological & if needed

Mechanical support (ECMO,

LVAD/Bi-VAD, Bridge to heart

transplant or to recovery)

Lymphocytic Giant cell, Eosinophilic,

Sarcoidosis (acute

decompensation)

General Supportive Therapy

Immunosuppression if

unresponsive & virus negative

EMB

Immunosuppression if

infection negative EMB

# If myocarditis is associated with systemic immune disease exacerbation, therapy overlaps with treatment of the background disease (usually immunosuppression).

“There are three phases to

treatment: diagnosis,

diagnosis and

diagnosis.”

William Osler. Principles

and Practice of Medicine,

1892

Debate:


myocarditis shall be biopsied:

YES

ESC REPORT

Current stateof knowledgeonaet iology,diagnosis,






Juan Gimeno-Blanes5, Stephan B. Felix6, Michael Fu7, T iinaHelio8, Stephane Heymans9,

Roland Jahns10, Kar in Klingel11, Ales Linhart 12, Bernhard Maisch2, W illiam McKenna13,


Huber t Seggewiss18, Luigi Tavazzi19, Gaetano Thiene4, Ali Yilmaz20,



Marburg, Klinik fur Kardiologie, Marburg, Germany; 3Academic Hospital IRCCSFoundation Policlinico, San Matteo, Pavia, Italy; 4Cardiovascular Pathology, Department of Cardiological

Thoracic and Vascular Sciences, University of Padua, Padova, Italy; 5Servicio de Cardiologia, Hospital U. Virgen de Arrixaca Ctra. Murcia-Cartagena s/n, El Palmar, Spain; 6Medizinische

Klinik B, University of Greifswald, Greifswald, Germany; 7Department of Medicine, Heart FailureUnit, Sahlgrenska Hospital, University of Goteborg, Goteborg, Sweden; 8Division of



Pathology,University Hospital Tubingen, Tubingen, Germany;122nd Department of Internal Medicine,1st School of Medicine, CharlesUniversity, Prague2,CzechRepublic; 13TheHeart


Academic Medical Center, Amsterdam, The Netherlands; 16Department of Cardiology, Clinical Center of Serbia and Belgrade University School of Medicine, Belgrade, Serbia;17Department of Cardiology and Pneumology, Charite Centrum 11 (Cardiovascular Medicine), Charite–Universitatsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany;18Medizinische Klinik 1, LeopoldinaKrankenhaus Schweinfurt, Schweinfurt, Germany; 19GVM Care and Research, Maria CeciliaHospital, Cotignola, RA, Italy; 20Robert-Bosch-




knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposesnew diagnostic criteria for clinically suspected myo-




Int roduct ion

Myocarditisisachallengingdiagnosisdueto theheterogeneityofclinical


determineasendomyocardial biopsy(EMB), thediagnosticgold stand-

ard,1–3 is used infrequently.2,3 Studies addressing the issue of sudden


prevalenceof myocarditis, rangingfrom 2 to 42%of cases.4,5Similarly,








* Correspondingauthor.Division ofCardiology,Department ofCardiological ThoracicandVascular Sciences,PaduaUniversityMedical School,Policlinico Universitario, ViaN Giustinani,


Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: journals.per [email protected]




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Clinical case 1 • 37 yr old male, agonist sport activity (cycling, soccer), negative family and

personal history

• March 2010: prolonged palpitation unrelated to effort

• 24 h Holter monitoring 10/2010: 4771 polymorphic VEBs, 887 in couples, 86 NSVT runs (longest 5 beats, max 120 bpm), SR, mean HR 72 (43-143)

• Negative LP, normal 2D echo, 11/2010 cardiological consultation (EPS/ARVC specialist): arrhythmia in normal heart, ARVC excluded, starts propafenone 150 mg tid, adviced to reduce sport activity

• December 2010: after training session, prolonged palpitation, epigastric pain, increased with respiratory acts, admission to local hospital:normal ECG, increased TnI, angiographically normal coronary arteries, normal biventricular function, sporadic frequent VEBs, stable increase in TnI (2-3 ng/mL, flat curve, normal CK-MB, Reactive C Protein), suggested CMRI

• February 2011: referred to Myocarditis/cardiomyopathy OPD (Padova) as clinically suspected myocarditis, normal coronary arteries

Clinical case 1 • April 2011: therapy: atenolol 100 mg, TNI high sensitivity 4,214 microg/L

(normal 0,00-0,045). Holter: Rs, mean HR 69 (46-103), 4345 VEBs, 711 couplets, 150 NSVT (longest 3 beats)

• High titre ANA (1/5000), AHA positive, AIDA positive

• Claustrophobic (refuses CMRI), 2D-echo: normal, LVEF 67%

• Young adult, good education, motivated to get a diagnosis and treatment, 2 young children

• What to do? – f/u

– EPS

– ICD as primary prevention

– Treat with NSAIDs, colchicine?

– EMB

Clinical case 1 • May 2011: admitted to our hospital to get a diagnostic EMB

• CMRI: compatible with previous myocarditis, preserved biventricular function, intramural LGE (mid septal), epicardial LGE (mid septal inferior); T2 not diagnostic (frequent VEBs)

• Constantly abnormal TnI (4-5 microg/L, normal 0.00-0.045), normal C3,C4, RCP

• 2D echo: mildly reduced LVEF = 50% (global hypokinesis), normal RV, no pericardial effusion

• Coronary flow reserve on AD by 2 D echo-adenosine: normal

• while in hospital on telemetric monitoring (cardiology ward)… – Prolonged SVT, haemodinamically stable, treated with amiodarone I.V. bolus

– Switched from beta-blocker to sotalol

• Right catheter: normal pulmonary pressures (PA mean 11 mmHg, mean wedge 7 mmHg), normal cardiac index (3.65 ml/min/m2); performed RV biopsy (4 samples, no complications)

Histology: focal

lymphomonocytic

myocarditis, initial

DCM (perinuclear

halos,dysmetric

nuclei)

ImmunoHx: focal

CD3pos, CD68 pos

and CD 20 cells

(>7/mm2) associated

with necrosis)

Negative PCR,

NT PCR for

cardiotropic

viruses:

adenov, HSV,

EBV,HHV6;

PVB19; CMV;

influenza A, B;

EV.

Clinical case 1 • What to do?

– EPS: no, Sotalol 80 mg tid

– ICD as primary prevention: no, Loop recorder implanted

– Treat with NSAIDs, colchicine: no

– Immunosuppression (IS) (started May 2011): prednisone 1 mg/kg then taper; Azathioprine 2 mg/Kg/d

• July 2011 (2 mo IS): TNI high sensitivity 0,47 microg/L (normal 0,00-0,045). Holter: Rs, mean HR 66 (44-107), 1618 VEBs, 34 couplets, no NSVT ; Echo: LVEF 60%

• September 2012 (15 mo IS) during tapering: Holter: Rs, mean HR 65 (44-105), 52 77 VEBs, 71 couplets, 6 NSVT longest 6 beats, 193 bpm; Echo: LVEF 64%; stop IS tapering; TnI negative.

• July/2014 (36 mo IS): TnI negative, LP: no arrhythmia; Echo: LVEF 64%; tapering IS, stop October/2014

• March 2015: TnI negative, LP: no arrhythmia; Echo: LVEF 64%; off IS

“There are three phases to

treatment: diagnosis,

diagnosis and

diagnosis.”

William Osler. Principles

and Practice of Medicine,

1892

Debate:


myocarditis shall be biopsied:

YES

Thank you for your attention!

Debate endomyocardial biopsy aldia

Healthcare

Transcript of Debate endomyocardial biopsy aldia