Rebuttal leslie cooper

Debate:

All patients with clinically suspected

myocarditis shall be biopsied

YES:

Rebuttal

ESC REPORT

Current stateof knowledgeonaet iology,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, T iinaHelio8, Stephane Heymans9,

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

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

Huber t 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; 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

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;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 Paris 6, AP-HP, Hopital Pitie-Salpetriere, Centre de Reference Maladies cardiaques hereditaires, Paris, France

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

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

knowledge on clinical presentation, diagnosis and 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

Myocarditisisachallengingdiagnosisdueto theheterogeneityofclinical

presentations.1–3Theactual incidenceofmyocarditisisalso difficult to

determineasendomyocardial biopsy(EMB), thediagnosticgold stand-

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

cardiac death in young people report a highly variable autopsy

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

biopsy-provenmyocarditisisreported in9–16%ofadult 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.Division ofCardiology,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 permissions please email: journals.per [email protected]

European Heart Journal

doi:10.1093/eurheartj/eht210

European Heart Journal Advance Access published July 3, 2013

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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

Clinical case 2 • 18 yr old female, agonist sport activity (canoeing), negative family and

personal history

• 12-19/06/2014: admitted to hospital, pericarditic chest pain, TnI 23,96 microg/L, negative CRP, 2D Echo: normal biventricular function, no pericardial effusion, CMRI suggesting myocarditis, discharged with ibuprofen 600 mg tid

• 24/06: readmission to hospital, chest pain, peak TnI 18 microg/L at admission, negative CRP, reduced TnI and second peak after few days. Echo: preserved LVEF, septal hypokinesis, no pericardial effusion. Angio TC: negative for CAD. New CMRI suggests increased myocarditis changes (lateral and inferior LV walls. Discharged 4/07 TnI reduced but not normal on Ibuprofen 800 mg tid, colchicine 1 mg day, esomeprazole 40 mg

• 02/08: readmission to hospital, chest pain, peak TnI 50 microg/L at admission, ECG: low voltages, mild inferolateral STE, Echo: preserved biventricular function, no pericardial effusion. In CCU short NSVT runs, improved on bisoprolol 1.25 mg. Coronary angiography: normal, EMB (RV, no complications).

Clinical case 2 • EMB Dgn: relapsing focal lymphocitic virus-negative (adeno, EBV, PVB19,

EV, CMV,influenza A, B, HHV6 weak pos), myocarditis; negative HHV6 IgM, negative

• What to do? – Immunosuppression (IS)?: Yes (started 15/08/2014, Prednisone 1 mg/Kg/d for 2 wks,

subsequent tapering + azathioprine 2 mg/kg)

• During medical consultation at OPD (20/08) chest pain and inverted T waves in from V2 to V6, D1, AVL, flat inferior leads positive AVR leads, admitted to our hospital

– 20/08 (TNI 0.20 ng /ml (normal <0.045); Eco; LVEF: 57%, hypokinesis posterior septum, basal mid inferior wall; discharged 29/08 TnI 0.05 (normal <0.045)

– CMRI 22/9: subacute myocarditis, preserved biventricular function (LVEF 60%, Rvef 53%), no LVWMA

• Outcome – Relapse 28/10/14: TnI 2.1; relapse 13/1/15: TnI 12, second peak 1, HHV6 DNA in blood:

detectable; ECG: neg T waves Inferolat leads; Echo: LVEF 65%

– 28/01/15 Tni neg; LVEF 65%; IVIG infusion, prednisone 25 mg (tapering), azathioprine 50 mg bid

– March 2015, TnI neg, LVEF 65%, prednisone 25 mg (tapering), azathioprine 50 mg bid, awaiting HHV6 DNA in blood

T2-weighted T1-weighted Inversion Recovery

post-Gd

Mid short-axis view: note the epicardial bright signal in the inferior and infero-lateral wall

due to myocardial edema (white arrows)

Mid short-axis view: note the epicardial Late Gadolinium

Enhancement (white arrows) in the same region of edema. Note

the greater extent of LGE compared to edema, due to a

subacute inflammatory process

M Perazzolo Marra

T1-weighted Inversion Recovery post-Gd

Long axis 4-chamber view: note the epicardial Late Gadolinium Enhancement (white arrows) in lateral LV wall, apex and also

the right side of interventricular septum

M Perazzolo Marra

If: preserved LV/RV function,

normal coro’s, prolonged troponin

(weeks, months) with or without

arrhythmia: EMB

If: preserved LV/RV functions,

normal coro’s, troponin release,

patient consent (research) and

experienced tertiary centre: EMB

EORP Cardiomyopathy and Myocarditis Registry - Protocol V1.0 – 10 June 2014 Page 1 of 29

Protocol

Cardiomyopathy and Myocarditis Registry

10/June/2014

Version 1.0

Study Sponsored by the European Society of Cardiology

in conjunction with the Working Group on

Myocardial & Pericardial Disease

Coordinating centre:

EURObservational Research Programme

European Society of Cardiology

Les Templiers, 2035 Route des Colles - CS 80179 Biot

06903 Sophia Antipolis Cedex - France

Tel: +33(0)492 94 76 00

Fax: +33(0)492 94 76 29

Email: [email protected]

Chairman of the Executive Committee

Professor Perry Elliott

Property of European Society of Cardiology (ESC)

Confidential May not be used, divulged, published, or otherwise disclosed without the written consent of ESC


Protocol


10/June/2014

Version 1.0









Tel: +33(0)492 94 76 00

Fax: +33(0)492 94 76 29




Property of European Society of Cardiology (ESC) Confidential

May not be used, divulged, published, or otherwise disclosed without the written consent of ESC


Protocol


10/June/2014

Version 1.0









Tel: +33(0)492 94 76 00

Fax: +33(0)492 94 76 29







Protocol


10/June/2014

Version 1.0









Tel: +33(0)492 94 76 00

Fax: +33(0)492 94 76 29







Protocol


10/June/2014

Version 1.0









Tel: +33(0)492 94 76 00

Fax: +33(0)492 94 76 29




Property of European Society of Cardiology (ESC)

Confidential May not be used, divulged, published, or otherwise disclosed without the written consent of ESC

Take-home message: the future

• Promote a European Myocarditis Treatment Trial

– multicentre

– placebo-controlled

– double-blind

– randomised

– viral and autoimmune diagnosed according to the ESC WG Task Force criteria.

“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!

Rebuttal leslie cooper

Healthcare

Transcript of Rebuttal leslie cooper