myocarditis an update in treatment and - ... • underdiagnosed • 9% (myocarditis treatment trial,...

MyocarditisAn update in treatment andAn update in treatment and 

managementDr Rahaf Waggass

Consultant Pediatric CardiologistConsultant Pediatric CardiologistKAMC‐WR

MyocarditisMyocarditis

• DefinitionDefinition• Etiology

id i l• Epidmiology• Clinical presentations• Diagnosis• TraetmentTraetment• Outcome and prognosis

DefinitionDefinition

• A process characterized by inflammatoryA process  characterized  by inflammatory  infiltrate  of the myocardium with necrosis  and/or degeneration of adjacent myocytesand/or degeneration of adjacent  myocytes  not typical of the ischemic damage  associated with coronary artery diseasewith coronary artery disease.

Wynn J, Braunwald E. Hear disease: A textbook of cardiovascular medicine. 1997

EtiologyEtiology

• Infectious:Infectious:Viral

i lBacterial             ParasiticFungalTBTB

EtiologyEtiology

• Non‐infectious:Non infectious:Drugs and toxins

iAutoimmuneCollagen‐vascular diseasesIdiopathic

Viral MyocarditisViral Myocarditis

• The most commonThe most common• Usually sporadicC b id i• Can be epidemic

Viral MyocarditisViral Myocarditis

• 1980s: Coxsackievirus1980s: Coxsackievirus• 1990s: Adenovirus2000 i 9• 2000s: Parvovirus B19

Breinholt et al, JHLT 2010; Moulik et al, JACC 2010

EpidemiologyEpidemiology

• UnderdiagnosedUnderdiagnosed• 9% (Myocarditis Treatment Trial, 1995)• 4‐5% ( obtained from young men dying of trauma)4 5% ( obtained from young men dying of trauma)• 16‐21% ( found in autopsy series of children dying suddenly)suddenly)

• WHO reported 1‐4% of cardiac involvement after enteroviral infection

Clinical presentationsClinical presentations

• Seen at all agesSeen at all ages• Presents typically with heart failure

i di l ll• May present in cardiovascular collapse• May present with bradycardia and AV Block• May present with VT or other forms of     arrhythmiay

• May present with nonspecific symptoms

DiagnosisDiagnosis

• ClinicalClinical• Lab:Viral culturesViral culturesPCRECGECGCXRECHOCARDIOGRAPHYECHOCARDIOGRAPHYBiopsy

EchocardiographyEchocardiography

– Findings include the following:Findings include the following: • Global hypokinesis (the most common finding)• Increased left ventricular end diastolic and systolic dimensions

• Left ventricular dysfunction, primarily systolic with decreased ejection fraction and shortening fractiondecreased ejection fraction and shortening fraction

• Segmental wall motion abnormalities• Pericardial effusionPericardial effusion

Cardiac BiopsyCardiac Biopsy

• Endomyocardial biopsy:Endomyocardial biopsy:The inflammatory infiltrate is usually patchy and scattered in the ventricular myocardiumand scattered in the ventricular myocardium.Sensitive in 3% to 63% of cases.Chow et al. and Hauck et al reported that to identify 80% of cases 17 or more specimens must be obtained.

• Endomyocardial biopsy:Endomyocardial biopsy:Because of the risk of associated with biopsy especially in young children or those withespecially in young children or those with severe ventricular dilation, many centers have abandoned this procedureabandoned this procedure.

Dallas CriteriaDallas Criteria

• Active myocarditisActive myocarditisinflammatoy infiltrate+ myocyte degeneration or necrosisor necrosis

• Borderline myocarditistoo sparse an infiltrate or no degeneration

• No myocarditisyno infiltrate and degeneration

Management of myocarditisManagement of myocarditis

• Includes management of:Includes management of:Shock

f il d i l d f iHeart failure and ventricular dysfunctionArrhythmiasSpecific treatment for certain etiologies (e.g TB))

Inotropic supportInotropic support

• Low dose dopamine (2‐5 mcg/kg/min) toLow dose dopamine (2 5 mcg/kg/min) to support BP

• Plus phosphodiestrease inhibitor (Milrinone)• Plus phosphodiestrease inhibitor (Milrinone) 0.125‐ 1 mcg/kg/min to diminish afterload and augment cardiac outputand augment cardiac output

• If more inotropic support needed dobutamine 1 10 /k / i b d1‐10 mcg/kg/min can be used

• Further afterload reduction may be achievedFurther afterload reduction may be achieved with sodium nitroprusside 0.3‐ 4 mcg/kg/min provided that BP is maintainedprovided that BP is maintained.

R l i h i i h i• Rarely epinephrine or norepinephrine are required.

DiuresisDiuresis

• IV diuretics are used to augment diuresis andIV diuretics are used to augment diuresis and improve congestive symptoms

• Continuous IV Furosemide have been used i h i di i i hwith success in pediatric patients when 

intermittent dosing has failed to result in d di iadequate diuresis

If the patient stabilized and there is end‐organIf the patient stabilized and there is end organ perfusion improvement:

• Weaning off milrinone and introduction of• Weaning off milrinone and introduction of ACE inhibitorIf l i k l d hif ll IV l R• If oral intake tolerated shift all IV to oral Rx

• Digoxin can be started

• Rezkalla S et al 1990Rezkalla S. et al. 1990Proved the beneficial effects of captopril in acute coxcackievirus B3 myocarditisacute coxcackievirus B3 myocarditis

B‐BlockersB Blockers

• In a multi‐institutional experience Shaddy, et al.In a multi institutional experience Shaddy, et al.reviewed the results with metoprolol in 15 childrenwith cardiomyopathy of different etiologieswith cardiomyopathy of different etiologies.after a mean of 23 months on metoprolol there was a statisticallysignificant and clinically importanta statisticallysignificant and clinically important increase in EF from 27% to 41%.

• Bruns, et al. reviewed the,use of carvedilol in 46 infants and children with cardiomyopathy(80%) or congenital heart disease (20%) at 6centers.After 3 months of therapy, modified NYHA class improvedin 67% of patients and worsened in 11%in 67% of patients and worsened in 11%.Shortening fraction improved slightly, from 16.2% to19 0%19.0%.

• In a single center study Rusconi et alIn a single center study Rusconi, et al. reviewed theresults in 24 pediatric patients with dilatedresults in 24 pediatric patients with dilated cardiomyopathy who received carvedilol.Th l f i l j i f iThe mean left ventricular ejection fraction improved from 25% to 42%

If No ImprovementIf No Improvement

• If HF is not responsive to medicalIf HF is not responsive to medical management, institution of of mechanical circulatory support must be consideredcirculatory support must be considered.

• ECMO or VAD for short duration or as a bridge to heart transplantto heart transplant.

ECMO and MyocarditisECMO and Myocarditis

• Satish K et al, Crit Care Med 2010 Vol. 38, No. 2Satish K et al, Crit Care Med 2010 Vol. 38, No. 2Reviewed the ELSO registry database from1995‐200619348 (<18y) in 116 centers19348 (<18y) in 116 centers260 runs for patients with myocarditis (1.3%)61% survival to hospital discharge61% survival to hospital discharge3% had heart transplantIn the patients who did not survive:In the patients who did not survive:arrhythmia, renal failure and female gender found to be associated risk factorsbe associated risk factors.

Other treatment modalitiesOther treatment modalities

IVIG:IVIG:                                                                        The use was based on Drucker et al study in 19941994.IVIG in 21/46 children with myocarditis.B LV f i f 6 h f F/U dBetter LV function after 6 months of F/U and less mortality after 1 year.It did not reach statistical significance due to low volume.

• Systematic review did not show significantSystematic review did not show significant improvement with IVIG use based on RCT but some case series and small uncontrolled trialsome case series and small uncontrolled trial showed improvement of ventricular function.

Steroids and immunosuppressionSteroids and immunosuppression

• The Myocarditis Treatment Trial 1995 :The Myocarditis Treatment Trial,1995 :showed no difference among 111 patients treated with azathioprine and prednisonetreated with azathioprine and prednisone, cyclosporine and prednisone, and conventional therapyconventional therapy.

InterferonInterferon

• Kuhl et al 2003Kuhl et al, 2003Used interferon‐B in 22 patients with proven enteroviral or adenovirus infection by PCRenteroviral or adenovirus infection by PCR with chronic LV dysfunction.Gi 3 / f 6 h l d h i dGiven 3x/w for 6 months cleared the virus and improved LV function.

• Daliento et al 2003Daliento et al, 2003similar success with alpha interferon in patients with enterovirus myocarditispatients with enterovirus myocarditis.

AnticoagulationAnticoagulation

• Should be considered to reduce the likelihoodShould be considered to reduce the likelihood of thrombotic/embolic phenomenon especially in more than mild ventricularespecially in more than mild ventricular dysfunction.

Predictors of OutcomePredictors of Outcome 

• Foerster et al circ heart fail 2010;3:689Foerster, et al, circ heart fail 2010;3:689found worse outcome associated with:

S ( 0 03)LV FS (P=0.03)LVEDD z‐score>2 (P=0.001)

PrognosisPrognosis

• Poor in newborn with 75% mortality rate inPoor in newborn with 75% mortality rate in infants with coxsackievirus B.

• Older children have better prognosis with• Older children have better prognosis with mortality rate between 10‐25%Ab 25% f i ill i h• About 25% of patients will continue to have ECG abnormalities.

ConclusionsConclusions

• Viral myocarditis can be acute or chronicViral myocarditis can be acute or chronic disorder.

• Treatment of heart failure and ventricular• Treatment of  heart failure and ventricular dysfunction is a cornerstone in treatment of myocarditismyocarditis.

• Despite the frequent use of IVIG and/or id li i l isteroids, recent clinical experience suggests 

their use has no impact on outcomes.