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Myocarditis, Viral: Differential Diagnoses & Workup

Author: Edwin Rodriguez-Cruz, MD, Assistant Professor, Department of Pediatrics, San Juan Bautista Medical School and Medical Center; Consulting Interventional/Clinical Pediatric Cardiologist, Department of Prediatrics, Hospital El Maestro and San Juan Bautista Medical Center; Consulting Interventional/Clinical Pediatric Cardiologist, Department of Cardiology, Cardiovascular Center of Puerto Rico and the Caribbean and Veterans Affairs Hospital and Medical Center of Puerto Rico
Coauthor(s): Robert D Ross, MD, Co-Director of Pediatric Cardiology Fellowship Program, Department of Pediatrics, Division of Pediatric Cardiology, Professor, Children's Hospital of Michigan and Wayne State University
Contributor Information and Disclosures

Updated: Oct 9, 2008

Differential Diagnoses

Aortic Stenosis, Valvar
Endocardial Fibroelastosis
Cardiac Tumors
Enteroviral Infections
Cardiomyopathy, Dilated
Glycogen-Storage Disease Type I
Carnitine Deficiency
Glycogen-Storage Disease Type II
Coarctation of the Aorta
Myocarditis, Nonviral
Coronary Artery Anomalies
Pericarditis, Viral

Other Problems to Be Considered

Medial necrosis of the coronary arteries
Shock

Workup

Laboratory Studies

  • CBC with differential
    • Acute anemia of any origin may cause heart failure, and chronic anemia exacerbates heart failure; both respond to blood transfusion.
    • The presence of lymphocytosis or neutropenia supports diagnosis of a viral infection.
  • Blood cultures: Ruling out any bacterial infection is important.
  • Sedimentation rate and C-reactive protein: These nonspecific markers of inflammation are usually elevated. However, a normal value does not rule out myocarditis, particularly in the presence of congestive heart failure, which may lower the sedimentation rate.
  • Viral cultures: Nasopharyngeal and rectal swabs may help identify etiology.
  • Viral titers: A 4-fold increase in a specific titer from the acute to convalescent phase is strong evidence of infection.
  • In situ hybridization
    • This process identifies viral RNA in myocardial tissue of patients believed to have myocarditis.
    • The incidence of false-negative results is high.
  • Polymerase chain reaction (PCR)5
    • PCR is used to find the viral genome in myocardial cells.
    • It is rapid, sensitive, and may become the test of choice for the diagnosis of viral myocarditis.
  • Creatinine kinase–MB isoenzyme (CK-MB): These markers of myocardial damage are elevated most commonly when associated elevation of the ST segment on the ECG is present.
  • Lactate dehydrogenase isoenzyme 1: This may be elevated in idiopathic myocarditis.
  • Troponin I
    • This is another indicator of myocardial damage.
    • It is usually elevated up to a month after infection but is not specific for this disease.

Imaging Studies

  • Echocardiography
    • This is the most cost-effective test used for evaluation of myocardial function.
    • It is sensitive but not specific.
    • 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 fraction
      • Segmental wall motion abnormalities
      • Pericardial effusion
  • Chest radiography
    • Cardiomegaly and pulmonary edema may be depicted.
    • Incidentally noted cardiomegaly on chest radiography may be the initial presentation.
  • Radionuclide imaging
    • This may be helpful as a screening tool.
    • Gallium citrate Ga 67 myocardial scintigraphy is useful to reveal chronic inflammatory processes. It is a sensitive test but is limited by its low specificity and predictive value.
    • Indium In 111 antimyosin antibody imaging is highly sensitive for myocardial necrosis, but has a high incidence of false-positive results. However, absence of antimyosin uptake is highly predictive of negative biopsy findings (92-98%).
    • Myocardial perfusion imaging with technetium Tc 99m–labeled labeled methoxyisobutyl isonitrile single-photon emission computed tomography (99mTc-MIBI SPECT) is usually a tool used to evaluate the severity of myocardial ischemia.6 Because the uptake and clearance of 99mTc-MIBI is affected by cell viability and membrane integrity, clinicians have recently used it as a marker for the severity of myocardial necrosis and inflammation in patients with myocarditis, with results comparable to those obtained with enzymatic cell damage markers.
  • MRI: MRI with gadolinium is a newer technology to evaluate the cardiac muscle inflammation via a special protocol for myopericarditis.

Other Tests

  • Electrocardiography (ECG)
    • In some patients with mild cardiac involvement, ECG changes may be the only abnormal findings suggestive of myocarditis.
    • Low-voltage QRS (<5 mm throughout the limb leads) is the classic pattern. Pseudoinfarction patterns with pathologic Q waves and poor progression of R waves in the precordial leads may also be present.
    • T-wave flattening or inversion is a common finding associated with small or absent Q waves in V5 and V6.
    • Left ventricular hypertrophy with strain may be present.
    • Other nonspecific findings include prolonged PR segment and prolonged QT interval.
    • Sinus tachycardia is the most common finding. Premature ventricular contractions and atrial tachycardias have been reported. Junctional tachycardia is common and may worsen congestive heart failure. Occasional second-degree and third-degree atrioventricular block may be present, requiring temporary pacing.
    • Ventricular tachycardia is commonly associated and may be the initial presentation.
  • Other techniques: Other techniques are under investigation to determine a specific viral etiology of myocarditis, such as immunohistochemical stains, inflammatory mediators, and autoantibody measurements.

Procedures

  • Biopsy is the criterion standard for the diagnosis of myocarditis.7 Myocardial biopsy findings establish diagnosis and classify disease stage.
  • Biopsy is a relatively safe and effective way to sample heart muscle in older children; however, a risk of perforation in sick or younger infants is observed.
  • The use of endomyocardial biopsy is controversial because of the possibility of a high false-negative result rate and because no proven therapy is available, even when a positive biopsy finding is obtained.
  • Some advocate using radionuclide imaging techniques as screening tools before considering endomyocardial biopsy.
  • Biopsy specimens may be useful for PCR diagnosis of viral etiology.

Histologic Findings

  • Gross evaluation of the heart reveals flabby and pale muscle with petechiae. Ventricular muscle is usually thin and may be hypertrophied. Heart valves and the endocardium are not usually involved, but in cases of chronic myocarditis, they might appear as they appear in endocardial fibroelastosis. Some experts believe that endocardial fibroelastosis is a result of viral myocarditis.
  • The microscopic hallmark of acute myocarditis is focal or diffuse interstitial infiltrate of mononuclear cells, lymphocytes, plasma cells, and eosinophils. Viral particles are rarely seen unless searched with special techniques (ie, PCR). Necrosis and disarrangement of the myocytes are typical and often are seen with coxsackievirus infection. In the chronic and healing stages, myocytes are replaced by fibroblasts (scar tissue).
  • In adenoviral myocarditis, less severe infiltrate can be seen histologically than is seen in cases of enteroviral infection.

More on Myocarditis, Viral

Overview: Myocarditis, Viral
Differential Diagnoses & Workup: Myocarditis, Viral
Treatment & Medication: Myocarditis, Viral
Follow-up: Myocarditis, Viral
References
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References

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Further Reading

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Keywords

viral myocarditis, myocardium, adenovirus, enterovirus, coxsackievirus, active myocarditis, borderline myocarditis, drug hypersensitivity, Starling law, congestive heart failure, cardiac failure, chronic myocarditis, dilated cardiomyopathy, arrhythmia, pericarditis, heart murmur, atrioventricular valve regurgitation, hepatomegaly, sepsis, somnolence, seizures, oliguria, failure to thrive, diaphoresis, end organ damage, chest pain, cytomegalovirus, Epstein-Barr virus, hepatitis C, herpes, HIV, human immunodeficiency virus, influenza, measles, mumps, parvovirus B19, poliomyelitis virus, rubella, varicella

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Contributor Information and Disclosures

Author

Edwin Rodriguez-Cruz, MD, Assistant Professor, Department of Pediatrics, San Juan Bautista Medical School and Medical Center; Consulting Interventional/Clinical Pediatric Cardiologist, Department of Prediatrics, Hospital El Maestro and San Juan Bautista Medical Center; Consulting Interventional/Clinical Pediatric Cardiologist, Department of Cardiology, Cardiovascular Center of Puerto Rico and the Caribbean and Veterans Affairs Hospital and Medical Center of Puerto Rico
Edwin Rodriguez-Cruz, MD is a member of the following medical societies: American College of Cardiology, American College of Physicians-American Society of Internal Medicine, American Heart Association, American Medical Association, American Society of Echocardiography, Puerto Rico Medical Association, Society of Cardiac Angiography and Interventions, and Society of Pediatric Echocardiography
Disclosure: Nothing to disclose.

Coauthor(s)

Robert D Ross, MD, Co-Director of Pediatric Cardiology Fellowship Program, Department of Pediatrics, Division of Pediatric Cardiology, Professor, Children's Hospital of Michigan and Wayne State University
Robert D Ross, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, and Society of Pediatric Echocardiography
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey Allen Towbin, MD, MSc, FAAP, FACC, FAHA, Professor, Departments of Pediatrics (Cardiology), Cardiovascular Sciences, and Molecular and Human Genetics, Baylor College of Medicine; Chief of Pediatric Cardiology, Foundation Chair in Pediatric Cardiac Research, Texas Children's Hospital
Jeffrey Allen Towbin, MD, MSc, FAAP, FACC, FAHA is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Cardiology, American College of Sports Medicine, American Heart Association, American Medical Association, American Society of Human Genetics, Cardiac Electrophysiology Society, Heart Rhythm Society, New York Academy of Sciences, Society for Pediatric Research, Texas Medical Association, and Texas Pediatric Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Ameeta Martin, MD, Clinical Associate Professor, Department of Pediatric Cardiology, University of Nebraska College of Medicine
Ameeta Martin, MD is a member of the following medical societies: American College of Cardiology
Disclosure: Nothing to disclose.

CME Editor

Gilbert Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College
Gilbert Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Chief Editor

Stuart Berger, MD, Professor of Pediatrics, Division of Cardiology, Medical College of Wisconsin; Chief of Pediatric Cardiology, Medical Director of Pediatric Heart Transplant Program, Medical Director of The Heart Center, Children's Hospital of Wisconsin
Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American College of Chest Physicians, American Heart Association, and Society for Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

 
 
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