CASE PRESENTATION

Patricia Baile – PL1December 16, 2009

16 year old male presents to the ER with chest pain

HPI

•Chest pain x 6 days▫Sharp, stabbing sensation on left side of

chest▫Constant ▫PS 7/10▫Worse when lying on left side and on

inspiration▫Radiating to back▫Mild improvement with aspirin and

acetaminophen

HPI

•Chest pain▫Associated with nausea, dizziness and

blurring of vision 2 days prior▫No diaphoresis

•On day of admission, chest pain persistent, no improvement with acetaminophen hence BIB EMS to ER

ROS

•Denies recent strenuous physical activity•No fever•No URI symptoms•No sick contacts•No joint pains•No dyspnea

Past Medical History

•Asthma▫9 previous hospitalizations, last 1 year

prior▫No ICU, no intubation▫Advair BID▫Singulair 10 mg PO QD▫Albuterol PRN

Family History

•+ Asthma•+ DM•+ Hypertension•+ CAD•No sudden death•No CVA•No connective tissue disorders

•Birth History▫FT, NSVD, no complication

•Immunization History▫Up to date

•Adolescent History▫Currently in 9th grade (behind 2 years)▫Lives with mother, stepfather and older

brother▫No sport or after-school activity▫Denies drugs, alcohol, tobacco▫Sexually active, has had 8 partners, uses

condoms, no STD history (never tested)

Physical Examination• BP 102/58 HR 72 RR 18 O2 100%RA T 98.3• Pain score: 6-7/10• Wt: 76.9 kg (90%) Ht: 185 cm (90%)

• GS: non-toxic appearing• HEENT: NCAT, congested turbinates, TMI, mild

erythema OP, no CLAD• C/L: SCE, good air entry b/l, CTAB, no crackles,

no rales, no tenderness on palpation of chest• CV: RRR, no m/r/g• Abdomen: soft, ND, NT, no organomegaly• Ext: well-perfused, good distal pulses

EKG

Labs

•CBC: 6.9 > 13.7/39.1< 251 N 68 L 20

•BMP: 138/3.8/100/26/7/0.6/104/8.3•LFT: 3.9/6.9/25/109/0.7/74•Lipase: 12•CPK: 1751•CKMB: 168.8•Troponin T: 8.77

Labs

•Lipid profile▫Cholesterol: 106▫TG: 49▫HDL: 31 ▫LDL: 65

•CRP: 7.5•Urine Drug Screen: Negative

Labs

•RSV/Flu: Negative•Rapid strep test: negative•Throat culture•ASO: 165•Streptozyme: Positive•Respiratory viral panel: Negative

Ancillary Tests

•Chest Radiograph▫Normal chest

Ancillary Tests

•Initial Echo▫Normal LV ejection fraction▫Normal RV function▫Mild inferolateral akinesis▫Inferior wall akinesis▫Small pericardial effusion

Initial Impression

•16 year old male with Juvenile pattern pericarditis; Asthma exacerbation

Hospital Course

•Admitted to PICU•Cardiac enymes gradually decreased •Repeat Echo done•Cardiac catheterization done

Ancillary Tests

•Repeat Echo▫Myocarditis with LV inferior/posterior wall

motion abnormality: persistent abnormal LV wall motion

▫Suboptimal LV shortening fraction▫Normal diastolic LV function▫Trace inferior and posterior pericardial

effusion

Ancillary Tests

•Cardiac catheterization▫Clear vessels▫Decreased ejection fraction▫Decreased motion of LV

FINAL DIAGNOSIS

•16 year old male with chest pain secondary to Myocarditis; Asthma exacerbation

MYOCARDITIS

Introduction

•Clinical syndrome characterized by inflammation of myocytes resulting from infectious, toxic, and autoimmune etiologies.

•Ongoing viral infection, myocardial destruction, and adverse remodeling can lead to persistent ventricular dysfunction and dilated cardiomyopathy.

Introduction

•Infectious etiologies, particularly viral, are most common in children.

•The most common causes of viral myocarditis are enterovirus (coxsackie group B) and adenovirus

Incidence

•Incidence of myocarditis in children is unknown

▫Inflammatory infiltrates and myocardial cell damage were found at autopsy in 3 to 40% of infants and children who died suddenly unrelated to trauma

▫17 percent of infants who died of SIDS had histopathologic evidence of myocarditis

Incidence• In one retrospective study from a single

tertiary Canadian center, the estimated prevalence of myocarditis presenting to their emergency department was 0.5 cases per 10,000 visits

•A review of all the autopsies performed at a single English pediatric tertiary center over a ten-year period (1996 to 2005) identified 28 of 1516 cases with myocarditis (1.8 percent)

Pathophysiology

•In susceptible patients: ▫Viral RNA uptake cytotoxic necrosis

rapid cell death•More common presentation

▫4-14 days post-infection immune response (macrophage activation and cytokine expression) natural killer cells target myocardium expressing the viral RNA and continue myocyte necrosis

Pathophysiology▫TNF is involved in rapidly clearing virus

and signals additional proinflammatory cells, activates endothelial cells, and has direct negative inotropic effects

▫Cytotoxic T lymphocytes infiltrate myocytes and trigger lysis of these cells

Pathophysiology

•In the chronic phases, the effects of either inadequate or inappropriately abundant immune response can lead to the long-term sequelae of dilated cardiomyopathy and heart failure

Pathophysiology

•Ongoing study has demonstrated the presence of antimyosin autoantibodies and other immunomodulators long after initial viral infection

Clinical Manifestation

•Nonspecific illness ▫Fatigue▫Mild dyspnea▫Myalgias▫Fever (20%)

•Chest pain (35%)▫most commonly described as a pleuritic,

sharp, stabbing precordial pain▫may be substernal and squeezing

Clinical Manifestation

•In a 6-year study of pediatric ED patients, the most common presenting symptom was dyspnea and more than half of patients were initially diagnosed with asthma or pneumonia.

•May be asymptomatic

Clinical manifestation

•Symptoms of heart failure•Dyspnea on exertion•Orthopnea•Shortness of breath•Palpitation

Physical Findings

•Tachypnea and retractions•S3 and occasionally S4 gallops may be

present and are important signs of impaired ventricular function

•If the right or left ventricular dilation is severe, auscultation may reveal murmurs of functional mitral or tricuspid insufficiency

Physical Findings•Signs of low cardiac output •Pericardial friction rub and effusion may

become evident in some patients with myopericarditis

•A widely inflamed heart shows the classic signs of ventricular dysfunction including the following:▫Jugular venous distention▫Bibasilar crackles▫Ascites▫Peripheral edema

Causes

•Infectious•Toxic•Immunologic

Infectious Causes

•Viral myocarditis is the most common▫Parvovirus B19, 36.6%▫Enterovirus, 32.6% ▫Human herpesvirus 6 (HHV-6), 10.5% ▫Adenovirus, 8.1% ▫Co-infection with HHV-6 and parvovirus

B19, 12.6%•HIV

Infectious Causes

•Bacterial causes▫Most common worldwide is Diphtheria▫Streptococcal and staphylococcal species

and Bartonella, Brucella, Leptospira, and Salmonella species can spread to the myocardium as a consequence of severe cases of endocarditis

•Chagas disease•Parasitic myocarditis from

trypanosomiasis

Toxic Causes

•Numerous medications (eg, lithium, doxorubicin, cocaine, numerous catecholamines, acetaminophen) may exert a direct cytotoxic effect on the heart

•Zidovudine (AZT) has been associated with myocarditis

Toxic causes

•Environmental toxins include lead, arsenic, and carbon monoxide

•Wasp and scorpion stings and spider bites, specifically black widows, may cause myocarditis

•Radiation therapy

Immunologic Etiology

•Connective tissue disorders ▫Systemic lupus erythematosus (SLE) ▫Rheumatoid arthritis ▫Scleroderma▫Dermatomyositis

•Idiopathic inflammatory and infiltrative disorders such as Kawasaki disease, sarcoidosis, and giant cell arteritis may be a cause

Differential Diagnoses

•Acute Coronary Syndrome•Pneumonia•Congestive Heart Failure •Aortic Dissection•Pulmonary Embolism•Esophageal Perforation, Rupture and

Tears•Viral syndrome

Diagnostic Studies

•EKG•CXR•Cardiac enzymes•Echo•MRI with contrast•Cardiac catheterization•Other tests

EKG

•Classical triad ▫Sinus tachycardia (>100 in a child; >120 in

an infant; >150 in a neonate)▫Low voltage complexes ▫ST segment and T wave changes

•Other abnormalities like, varying AV blocks, bundle branch blocks, both supraventricular and ventricular arrhythmias and an even an anterior wall myocardial infarction pattern

Chest Radiograph

•Typically include cardiomegaly, although heart size may be normal

•Pulmonary vascular congestion is often present

Cardiac Enzymes

•Elevation reflects myocardial necrosis•Seen in some patients with myocarditis

•Experimental and clinical findings in adults suggest that elevations of cardiac troponin I or T (cTnI or cTnT) levels may be more common than CK-MB elevations in patients with biopsy-proven myocarditis

Echocardiography

•Enlarged Left Ventricular (LV) dimensions, left atrial enlargement and impaired ejection fraction (EF) and shortening fraction

•Normal EF in children is 64+4%•2D echo reveals a large, hypo contractile

LV which is globular, with thin walls, mild pericardial effusion and occasional regional wall motion abnormalities

MRI

•Said to pick up earliest abnormality in Myocarditis

•Document the location and extent of inflammation

•Gadolinium enhancement was greater in patients with myocarditis than in normal controls

Cardiac Catheterization

•Reveals depressed cardiac index, elevated left ventricular end diastolic pressure, and elevated mean atrial pressure

•Angiography shows decreased left ventricular function with or without mitral regurgitation

•Main purpose is to obtain samples by endomyocardial biopsy (EMB) for pathologic and microbiologic analysis

Endomyocardial Biopsy (EMB)

•Gold standard for the diagnosis of myocarditis

•Dallas criteria▫Active myocarditis is defined as "an

inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of the ischemic damage associated with coronary heart disease"

EMB

•Dallas criteria▫Borderline myocarditis is the term used if

lymphocytic infiltration is present without myocyte destruction

▫Ongoing Myocarditis – both inflammation and necrosis present.

▫Resolving Myocarditis – inflammation may be present; cell necrosis not

▫Resolved Myocarditis – No inflammation / cell necrosis.

EMB• The American Heart Association, the American

College of Cardiology, and the European Society of Cardiology released a scientific statement on the role of EMB

▫Limited data are available on EMB in children▫EMB is reasonable in the setting of unexplained

cardiomyopathy in children. ▫ Indications include fulminant or acute

unexplained heart failure, cardiac transplant rejection monitoring, certain unexplained arrhythmias, and idiopathic dilated cardiomyopathy

Treatment

•Mainstays of therapy for acute or fulminant myocarditis are monitoring, supportive care, and standard regimens for heart failure

•Patients should be monitored in a pediatric intensive care unit

Treatment of Heart Failure

•In the acute phase, diuretics, afterload reducing agents, and inotropic drugs are used to treat heart failure

•Dopamine, dobutamine, and milrinone are used to prevent circulatory collapse in the case of acute fulminant myocarditis

Treatment of Heart Failure

•Mechanical ventilation•ECMO•Ventricular Assist Device

•For patients who progress from acute myocarditis to chronic heart failure, diuretics, angiotensin inhibitors, digoxin, and aldosterone inhibitors (ie, spironolactone) are well-accepted therapies

Anti-arrhythmic Drugs

•Most antiarrhythmic drugs have negative inotropic activity and may therefore worsen cardiac function and lead to acute hemodynamic instability

•Should be used only when the expected benefit exceeds the risk, and only in consultation with a pediatric cardiologist

Immunosuppressive Therapy• Myocardial damage in infectious

myocarditis is thought to be due to both direct viral damage and the immune response to infection.▫Myocarditis Treatment Trial:

111 patients with a histopathologic diagnosis of myocarditis and a left ventricular ejection fraction (LVEF) of less than 45 percent were randomly assigned to receive conventional therapy alone or immunosuppression with either cyclosporine or azathioprine for 28 weeks [7]. There was no difference in outcome in the two treatment groups.

Immunosuppressive Therapy

•Corticosteroids

▫ Case series and a small trial are inconclusive with respect to the beneficial effects of prednisone and/or other immunosuppressive agents (azathioprine, cyclosporine) on left ventricular function and ventricular arrhythmias in children with myocarditis, but definitive data are lacking

Immunosuppressive Therapy

•IVIG▫use is supported by experimental data in

which polyclonal immunoglobulin protects against myocardial or arterial damage in mouse models of viral and autoimmune myocarditis

▫no randomized controlled trials of IVIG for the treatment of myocarditis in children have been reported, some clinical evidence suggests it may be beneficial

Pain control

•Narcotic analgesic•Avoid NSAIDs which are relatively

contraindicated in this condition

PROGNOSIS

•Most cases are believed to be clinically silent and resolve spontaneously without sequelae

•Patients who present with CHF experience morbidity and mortality based on the degree of left ventricular dysfunction.

•Patients who do not fully recover cardiac function may develop dilated cardiomyopathy.

OUTPATIENT FOLLOW UP

•Recovered patients should have restricted activity for 6 months because rapid return to activity has provoked recurrent inflammation in animal models

•Follow-up visits with a cardiologist