Hội Tim mạch học Việt Nam

Hội Tim mạch học Việt Nam tài liệu, giáo án, bài giảng , luận văn, luận án, đồ án, bài tập lớn về tất cả các lĩnh vực ki...

Some points updated on

myocarditis

Nguyen Ngoc Quang, MD, FASCC

Dept of Cardiology, Hanoi Medical University

Vietnam National Heart Institute

IDCM Myocarditis Ischemic Infiltrative Peripartum HTN HIV CTD Abuse

3 3

4 4

4 5

7 9

50

1 Epidemiology

✓ True incidence of myocarditis in community is unknown

✓ Greatest burden of myocarditis (chronic DCM, then die

or require orthotopic heart transplantation) may not be apparent for 6-12 years after diagnosis

Underlying Causes and Long-Term Survival in Patients with Initially

Unexplained Cardiomyopathy.

Felker GM, et al N Engl J Med 2000; 342:1077-1084

Coxsackie B

Coxsackie A

Other Enterovirus

Many Uncommon Viruses

Adenovirus

HCV

PVB19

HHV6 EBV

Enteroviruses

Non-Enteroviruses

2010 1948

✓ Viral & postviral myocarditis: major causes of acute and chronic dilated cardiomyopathy

✓ Spectrum of viruses (EMB samples) shifted from coxsackie-

virus B to adenovirus to parvovirus B19 and other viruses

✓ Less frequent viruses: hepatitis C, EBV, CMV and HIV

2 Etiology

Many injuries can cause

• Bacterial, fungal, protozoal Infections

Some special etiology

✓ Hypersensitivity myocarditis: anticonvulsants,

antibiotics, and antipsychotics.

✓ Eosinophilic myocarditis: Churg–Strauss syndrome, Loffler’sendomyocardial fibrosis, cancer, and parasitic, helminthic, or protozoal infections and with vaccination for several diseases, including smallpox.

✓ Giant-cell myocarditis (acute dilated

cardiomyopathy): thymoma, autoimmune disorders,

ventricular tachycardia, or high-grade heart block.

✓Catecholamines, Anthracyclines, Cyclophosphamide,

✓ Heavy metals (copper, lead, iron), Arsenic,

✓ Alcohol, Cocaine, Carbon monoxide,Methysergide

✓ Inflammatory bowel disease (Crohn's disease, ulcerative colitis)

✓ Radiation

3 Pathophysiology

Progression from acute injury to chronic DCM: 3-stage process:

✓ Acute injury leads to cardiac damage (myocyte death) within hours of viral cell entry, results from direct viral damage tomyocytes

✓ Exposure of intracellular antigens (cardiac myosin) and an innate immune response comprised of altered regulatory T cell function, NK cells, interferon gamma, nitric oxide…

✓ Heart specific immune response characterized by antibodies

to pathogen, host cardiac proteins and autoreactive T cells

Most recover with few consequences, a minority die from arrhythmias or progress onto chronic HF

Pathogenesis of DCM After Enteroviral Infection

Coxsackie B virus

“Normal heart”

Myocyte infection

Chronic dilated cardiomyopathy

Myocyte cell death

Acute dilated cardiomyopathy

• Autoantibodies

• Autoreactive

• T lymphocytes

Hemodynamic remodeling

Neurohumoral activation

Sequestered viral genome

Cooper LT, Gersh BJ Am J Card, 2002

Myocyte cytoskeletal damage Direct cytopathic effect

CP1184045-6

4 Clinical Presentations

✓ Viral prodrome and highly variable symptoms

✓ Children often have fulminant presentation.

✓ Common clinical presentation

✓ Acute Heart Failure with Dilated Cardiomyopathy

✓ Syncope: poor prognosis if related with VT or AVB

✓ Fulminant heart failure after viral syndrome:

better prognosis but require hemodynamic support

✓ Chest pain: good prognosis

5 Diagnostic procedures

✓ Troponin I: specificity 89%, sensitivity 34%

✓ ECG: sensitivity: 47%

✓ Endomyocardial biopsy

✓ Echocardiography: to distinguished fulminant myocarditis

✓ Cardiovascular magnetic resonance

✓ Analysis of messenger RNA and protein markers

✓

US Centers for Disease Control Case Definitions for Myocarditis

• Possible - Clinical syndrome with typical EKG

changes, and troponin rise or abnormalities on echocardiogram

• Probable - Criteria for possinle myocarditis and NEW changes on echocardiogram

• Confirmed - Positive histology

MMWR 2003

2:1 Second degree HB and Q waves

In Acute Myocarditis

Nakashima 1998

Comparison of the Sensitivity and Specificity of

Troponin and Heart Biopsy for Myocarditis

Skouri et al: JACC 48(10):2085, 2006

CP1256539-1

Positive Negative Sensitivity Specificity predictive predictive Technique No (%) (%) value value

EMB Indication (Class I, LOE B)

• New onset heart failure

• of 2 weeks to 3 months duration

• assoct w a dilated left ventricle,

• new ventricular arrhythmias,

• 2nd or 3rd degree heart block

• failure respond to usual care within 1 to 2 weeks

Cooper, LT, et al Circulation 2007

Endomyocardial Biopsy

Histologic “Dallas” Criteria

Aertz, et al Am J Pathol 1986

Sampling error, Variation in interpretation, Low

sensitivity, Lack of correlation with outcome

Baughman, K, Circulation 2006

Endomyocardial Biopsy

Giant Cell Myocarditis

When to Suspect Giant Cell Myocarditis

• Failure to Respond to Usual Care

• Ventricular Tachycardia

• High-grade Heart Block

Cooper, LT, et al AHJ Dec 2008

Giant Cell versus Lymphocytic Myocarditis

Transplant-Free Survival

0 0.2

Death or Transplant

0 0.2

Consensus Criteria on the CMR

Diagnosis of Myocarditis

Endorsed by SCMR Myocardial Inflammation Requires 2 of 3

1 IR prepared T2 weighted images (body coil),

the regional or global intensity ratio of myocardium

to skeletal muscle exceeds 2SD (1.9)

2 T1 global enhancement ratio is greater than 2SD (4.5)

3 T1 “Late enhancement” post-contrast has

at least one focal lesion with

non-ischemic distribution

Friedrich, M., Presented ESC September 2008, JACC 2009

CMR in Acute Myocarditis

Triple-inversion-recovery T2 weighted Spin echo CMR

T1 weighted fast spin echo

Skouri et al: JACC 48(10):2085, 2006

T1 inversion recovery

Antimyosin and Gallium Imaging in

Rheumatic Carditis

Gallium-67

Indium-111 Antimyosin

Aschoff Nodule, 10x, 40x

Enteroviral Infection & Clinical Outcome

Why HJ: Circ, 1994

Terasaki F: J Card Surg, 1999

Detection of enteroviral RNA in pt with myocardial disease is associated with an adverse prognosis and

is an independent predictor of outcome

0 5 10 15 20 25

Enteroviral RNA+ Enteroviral

Enterovirus negative

P=0.02

Proportion Surviving

Recent Predictors of Outcome in Patients

with Myocarditis

1.0 0.8 0.6 0.4 0.2

Virus negative

P=0.893

Viral Genome Detection

β 1 -AR Antibodies Predict

Mortality in DCM

Stork, Am Heart J 2006

N=105

6 Treatment

✓ Supportive therapy for LV dysfunction: mainstay of treatment

✓ Antiviral therapy

✓ Benefit in acute viral myocarditis (?) dute to late prognosis

✓ IV Ig routine use for acute myocarditis: not recommended

(Intervention in Myocarditis and Acute Cardiomyopathy trial)

✓ Interferon beta: maybe effective in viral persistence chronic, stable DCM

Recent Treatment Strategies for Chronic Dilated Cardiomyopathy

• Targeted cytokine blockade- 2 Negative RCT

• Case Control Series, RCT underway

• Antiviral Therapy- Interferon β, Pleconaril.

Interferon β1b for Chronic Viral Cardiomyopathy

Schultheiss, H-P AHA November 11 th , 2008

Changes in LV measurements following immunosuppressive therapy

Frustaci A ESC Congress 2008; Munich, Germany.

End point Baseline 6 mo LVEF (%) 26.4 48.0 LVEDD (mm) 68.6 52.8

Randomized 85 patients with active lymphocytic myocarditis

Immunosuppression (prednisone 1 mg/kg daily * 4 weeks, followed by 0.33 mg/kg daily dose for five months) + azathioprine (2 mg/kg daily for six months) versus control

Immunosuppression improves LV function in virus-negative inflammatory

cardiomyopathy

Thank you very much

for your attention

✓ Imaging modalities: CMRI replace EBM

✓ Immunopression vs Immunostimulation