Grippe und Kardiomyopathie - Herz Kurs€¦ · 58 reported cases of myocarditis associated with...

Carsten Tschöpe, Berlin

Kardiologie, Charite, CVK

Grippe und Kardiomyopathie

„A. zieht nach Berlin für ein Praktikum.

48 Stunden später ist er tot,

gestorben an einer Herzmuskelentzündung,

obwohl er hier noch

zwei Rettungsstellen und einen Arzt aufsuchte.“

Der Tagesspiegel VOM 19.04.2014

„Herz und Versagen“

German register of

sport-related sudden deaths

Bohm et al Eu J Precv Cardiol 2016

Pathogenesis of

inflammatory cardiomyopathies

Trachtenberg et al Circ Res. 2017;121:803-818

Blauwet L et al, Pro Cardiovascu Dis 2010

Pathogenesis of viral myocarditis

Ammirati et al Circulation 138:1088-1099; 2018

Impaired prognosis of

complicated Myocarditis

Complicated:

Changes in EF

or

Abnormal ECG

or

Trop T pos

or

hemodynamically compromised

54%

recover

* No specific

treatment

due to viral

persistence

19,4%

stay at risk

27%

Defect

healing

Kühl et al

Spontaneous Course of biopsy proven MC/DCMi *

(clinical mean follow-up: 30 months, n=922)

Despite HF standard therapy

45% will patients with MC/DCMi will not recover

ESC Recommendations

Caforio et al, Eur Heart J 2013

Chronic Viral Cardiomyopathy versus Controls (n=669)

negative EV PVB19 HHV6 PVB/HHV

260 54 210 89 56

Infection 48% 45% 49% 35% 42%

Tiredness 69% 82% 72% 59% 82%

Angina pectoris ( atypical ) 40% 10% 47% 36% 40%

Dyspnoe on exertion 55% 50% 60% 64% 77%

Pericardial effusion 6% 2% 7% 5% 13%

Impaired contractility (global) 68% 71% 68% 69% 69%

Impaired contractility (region.) 43% 24% 31% 44% 25%

Rhythm disturbances 46% 50% 51% 38% 62%

SVES 7% 9% 11% 4% 6%

VES 23% 9% 24% 19% 18%

Atrial fibrillation 19% 25% 16% 18% 23%

Ventricular tachycardia 9% 0% 13% 4% 7%

Charite - CBF

No viral specfic symptoms in patients

with suspected myocarditis

Diagnostics

• ECG

• hsTroponin, CRP

• No virusserology

• Echocardiography

• MRI (Lake-Louise Criteria)

• Endomyocardial biopsy


Myocarditis

Mimicking Acute Myocardial Infarction

Kühl et al Circulation 2003

6 months later

Shahid et al JACC 2016

Diagnostics

• ECG

• hsTroponin, CRP

• No virus serology





Diagnostics

• ECG

• hsTroponin, CRP

• No virus serology

-> To excude a systemic infection

(Herpesvirus, Hepatitis C, Parvovirus B19)

-> anti bodies (IgMs) do not reflect the cardiac disease


Diagnostics

• ECG

• hsTroponin, CRP






Wall oedema

Echocardiography

EchocardiographyWall oedema

EchocardiographyPericardial Effusion

MCpEF

Echocardiography

Myocarditis with preserved ejection Fraktion

Escher et al 2013 Kasner et al IJC 2016

MCpEF

Echocardiography

Myocarditis with preserved ejection Fraktion

Escher et al 2013 Kasner et al IJC 2016

Fibrosis and MRI in MCpEF

Aquaro et al JACC 2017

2nd y

Diagnostics

• ECG

• hsTroponin, CRP






Indicate myocarditis, if 2 out of 3 criteria are positive

quantitative

Yes/no

T2 – ER ≥ 2

quantitative

T1 – gRE ≥ 4

qualitative

LGE T2W

Yes/no

T1W

Friedrich et al JACC 2009

MRT Lake – Louise Kriterien

zur Diagnostik der Myokarditis

MRT Lake Louise Kriterien zur

akuten und chronischen MyokarditisLurz P et al.: JACC 2012

= acute myocarditis

Moderen MRI:

T1-, T2-Mapping

von Knobelsdorff-Brenkenhoff et al. Circ Cardiovasc Imaging. 2017

New MRI – Louise criteria for

acute but not chronic Myocarditis

Ferreira et al JACC 72:3158-3176; 2018

Lurz P et al.: JACC 2016

New MRI – Louise criteria for

acute but not chronic Myocarditis

Kindermann et al. Circulation 2008

Immunohistology criteria –

have a prognostic significance

MRI and virus presence

Gutberlet et al 2008 Friedrich JACC CVI 2008 (Review)

T1 und T2 Mapping zur Verlaufsbeurteilung einer

Myokarditis

Bohnen et al Eu Heart J Cardiovasc Imaging 2017

Diagnostics

• ECG

• hsTroponin, CRP



• MRI (Lake-Louise Criteria/T1/T2) – a negative result

does not exclude a myocarditis – a positive does

not clarify the viral situation

• Endomyocardial biopsy - Goldstandard


Ammirati et al Circulation 138:1088-1099; 2018

Impaired prognosis of

complicated Myocarditis

Complicated:

Changes in EF

or

Abnormal ECG

or

Trop T pos

or

hemodynamically compromised

Bio

psie

MR

T

Ammirati et al Current Cardiology Reports 2018

MRI or Biopsy

in suspected myocarditis

A RV-Biopsy in 20 sec ?

„ Get it ! „

The requirement for a specific treatment strategy for

myocarditis is a comprehensive diagnostic by an

endomyocardial biopsy

Coxsackie


Noutsias et al 2011

Histology Immuno-

Histology

Molecular-

biology

Flow diagram illustrating clinical scenarios described in

AHA/ACC/ESC Scientific Statement.

Francis et al heartjnl-2017

Class 1

Eosinophilic

Myocarditis

(EF: 30%,)

Fulminant

Myocarditis

(EF: 32%) (EF: 32%)

Giant cell

Myocarditis

Moderate

Prognosis

Poor

Prognosis

Poor

Prognosis

Severe unexplained acute new onset HF

Initial defect size and

type of inflammatory response

Flow diagram illustrating clinical scenarios described in

AHA/ACC/ESC Scientific Statement.

Francis et al heartjnl-2017

Class I

Class IIA

Immunosuppression in virus-negative DCMi:

6 months Follow-up – TIMIC Study

Randomized, double-blind, placebo-

controlled study

n=85 patients

Placebo: n= 42 patients

Immunosuppression: n= 43 patients

Prednisone / Azathioprine

* P<0.05

Immunosuppres. placebo

Immunosuppres. placebo

Frustaci et al. Eur Heart J 2009

Empfehlungen zur TherapieImmunsuppression in virus-negativer komplizierter Myokarditis

Merken et al Circ Heat Fail 2018

Dominguez F et al, Rev. Esp Cardiol 2016

Current Therapeutic Options in

Chronic forms of myocarditis

After Exclusion of

viral persistence

Viral genomes epidemiology

Dominguez et al, Rev Esp Cardiol 2015

Shauer et al, IMAJ 2013

Can

be cleared

Cannot

be cleared

Coxsackievirus B3 and Adenovirus

Yoder et al, J of Virol 2012

Pankuweit et al, Heart Failure Rev 2013

- Single stranded (ss) RNA

- Nonenveloped, icosahedral

- 6 serotypes of CVB: 1, 3 & 5 cardiotropic

- Clear association with MC

- Infects cardiomyocytes

- Double-stranded (ds) DNA

- Nonenveloped, icosahedral

- Human 51 serotypes: 2 & 5 cardiotropic

- Clear association with MC

- Infects among others cardiomyocytes

Zhang et al, J of Virology 2005; McCarthy et al, J of Virology 2014

Blailock et al, Exp & Molec Pathol 1968

Coxsackievirus B3 Adenovirus

Kühl et al JACC, 2012

Enterovirus

Cardiac Coxsacki virus

persistence and prognosis

50%

EV Spontan-

elimination

ß-Interferon in Chronic Adeno Viral

Cardiomyopathy: RCT Phase II – BICC Study

Schultheiss et al CRC 2016




Hepatitis C virus and restrictiveCardiomyopathy

Fall in BNP

Drop in PAP

improvement

in NAYH

Poller et al Clin Card 2017

45 % of patients with HCV have HF

Effect of DAA –Therapy on HCV copies

IIyas et al Viral Immunol 2017

Hepatitis C virus and Myocarditis




EBV CMV HHV-6

Life-long latency X X X

Reactivation in

immunocompromised

patients/geriatrics

X X X

Cardio/vasculotropism X X X

Treatment Foscarnet Gancyclovir Acyclovir/

Ganclovir

Herpes viruses

Herpes viruses

Cardiotropism

Long-life (latent) persistence - > Bystanders

-> no specific treatment / not to clear

-> in doubt: treat inflammation

Re-activatable

–> Antiviral treatment target in severe HF with and cardiac

inflammation

-> Antiviral therapy in ciHHV-6 with high copy numbers




22.07% Virus negative0.34% CVB369.31% PVB191.03% EBV2.24% HHV60.17% CMV0.52% CVB3/PVB190.52% HHV6/PVB193.45% EBV/PVB190.17% HHV6/PVB19/EBV0.17% CVB3/PVB19/EBV

69.3% PVB19

22.1% Virus negative

Distribution of viral genomes 2015-2019

Charite – Campus Virchow

Tschöpe et al 2019, unpublished

N = 580

Adamson-Small LA et al, Virus Research 2014

Persistent B19V DNA in non-erythroid tissues:

possible role in inflammatory and disease process

Parvovirus B19 in Endomyocardial Biopsy of Patients

With Idiopathic Dilated Cardiomyopathy

Hjalmarsson, C., et al. (2019). J Card Fail 25(1): 60-63.

B19V-DNA is a common finding in both patients

with IDCM and in healthy donor hearts,

not affecting prognosis

CAPACITY Trial

Cortison in PVB positive DCMi

Tschöpe et al EJHF 2019

Improved

EF

Reduced

Inflammation

No change

In viral load

Cardiac viruses:

To be a bystander or not be a bystander

Adenovirus Coxsackie virus B3

Virulent Cardiotropic

PVB19

HCV

HCV positive with HF – treat, independent of

EMB result

HHV-6/ciHHV6EBV

Latent; undetectable DNA in EMB;

no Inflammation

DNA+ EMB; active: needs to be treated

in ciHHV-6 or in severe HF

Inactive persistent; DNA (<500 copies/µg);

no inflammation

High copy numbers/systemic viraemia

Bystander

Virluent

Bystander

Virluent

Virluent

Virluent

Influenza-associated Myocarditis

58 reported cases of myocarditis associated with H1N1

2009 pandemic in Japan

Ukimura, A., et al. (2012). Influenza Res Treat 2012: 351979.

Influenza-associated Myocarditis

• Acute fulminant form of myocarditis.

• The true prevalence remains unknown.

• Influenza A virus–associated fulminant

myocarditis is rare.

• The treatment is based on hemodynamic and

ventilatory support beside neuraminidase

inhibitors.

Zusammenfassung der Therapie

bei Myokarditis

1. Symptomatische Therapie

2. Kausale Therapie

Tschöpe et al 2019


bei Myokarditis


2. Kausale Therapie

Tschöpe et al 2019

1. ACEI/ARB/ARNI

2. Beta Blocker

3. MRA (EF <35%)

4. Diuretics

5. Ivabradine (HF > 74 bpm)

6. No Sport (for 6 months)

7. Devices

Chronic phase: GL

2015 ESC Guidelines:

Conventional

standard therapy


bei Myokarditis


2. Kausale Therapie

Tschöpe et al 2019

Inflammation negative

Virus negative

EMB-

results

Differential

diagnosis

Therapy

options

Post MC

DCM

HF therapy

Risk adjusted therapy

Proposal for Biopsy- guided therapy options in viral

– induced myocarditis 2019

Tschöpe et al 2019

Inflammation positive

Virus negative


Virus negative

EMB-

results

Differential

diagnosis

Therapy

options

Post MC

DCM

HF therapy


Lymphocytic MC

Giant Cell MC

Sarcoid

Eosinophilic MC

Immuno-

suppression



Tschöpe et al 2019


Virus positive


Virus negative

Adenovirus Enterovirus Immunmodulation**


Virus negative

EMB-

results

Differential

diagnosis

Therapy

options

Post MC

DCM

HF therapy


Lymphocytic MC

Giant Cell MC

Sarcoid

Eosinophilic MC

Immuno-

suppression

Herpesvirus, HIV, HCV,

Ifluenza

Parvovirus B19

Antiviral***

Immunosuppression*



Tschöpe et al 2019

Zusammenfassung

Inflammatorische Kardiomyopathien

Diagnostik

-> neue MRT Kriterien zur akuten Myokarditis

-> Biopsie-geführte Diagnose bei V. a. chronische oder

„komplizierter“ Myokarditis (> 30 Tage / Schock)

Therapie

-> Prognose Verbesserung durch Immunsuppression

bei virus-negativen kardialen Entzündungen

-> Spezielle Therapie Ansätze bei Viruspersistenz

Prognose -> Meist gut unter konservativer Therapie und Schonung

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Grippe und Kardiomyopathie - Herz Kurs€¦ · 58 reported cases of myocarditis associated with...

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