Project Title

Persistent elevation of troponins in the setting of Epstein-Barr Viral infection: A Case Report

Authors' Affiliations

Meredith St.Clair, PGY1 Department of Pediatrics, East Tennessee State University, Johnson City, TN Nathaniel Justice, Department of Pediatrics, East Tennessee State University, Johnson City, TN Jerry Walkup, Pediatric Cardiologist

Location

Mt Mitchell

Start Date

4-12-2019 9:00 AM

End Date

4-12-2019 2:30 PM

Poster Number

143

Faculty Sponsor’s Department

Other - please list

Pediatric Medicine

Name of Project's Faculty Sponsor

Dr. Nathan Justice

Type

Poster: Competitive

Classification of First Author

Medical Resident or Clinical Fellow

Project's Category

Diseases

Abstract Text

Introduction:

In pediatrics, ninety-eight percent of all chest pain complaints are non-cardiac in origin, with the leading cause being muscular skeletal pain. Of the two percent that are cardiac in origin, troponin levels are helpful in detecting cardiac muscle ischemia, most commonly present in myocardial infarction, pulmonary embolism, pericarditis, myocarditis, aortic dissection, heart failure, and cardiac contusion. There are multiple different troponin assays that detect troponin, usually using a two-site immunoezematic assay. Although values obtained may differ slightly between assays, there is not a statistically significant difference between assays. Several endogenous substances, such as rheumatoid factor, excess fibrin, alkaline phosphatase, and heterophile antibodies can cause statistically significant, though falsely increased troponin levels that do not rise and fall in the typical pattern seen in cardiac ischemia due to cross reactivity with the assays. We present the case of a fifteen-year-old male with chest pain and elevated troponins, but otherwise benign workup. It highlights the falsely elevated troponin levels seen with the cross-reactivity of heterophile antibodies and various troponin assays.

Case Presentation:

A 15-year-old male presents with a two-day history of intermittent, stabbing, 5/10 left sided chest pain, as well as substernal chest pressure that radiates to his left upper chest and shoulder. He is unable to identify any triggers of the pain or alleviating factors. Review of systems is negative for nausea, vomiting, diaphoresis, and shortness of breath. His past medical history is significant for pectus excavatum that has been corrected with Nuss bar procedure. He also reports being treated for strep pharyngitis two weeks prior. The patient presents to emergency department after having an irregular heart rate noted by the school nurse’s office.

His vital signs are stable, and his physical exam is notable for a regular heart rate and rhythm. Pectus excavatum with well healed midline scar is present. A basic metabolic panel is normal. In the emergency department, serum troponins are elevated between 0.24-0.25 ng/ml (normal range 0.00-0.02), and a D-dimer is elevated at 500 ng/ml (normal range 0-230). Cardiology is consulted, and following an algorithm for chest pain in pediatric patients,1 a series of additional tests are performed. His electrocardiogram shows a normal sinus rhythm with minimal left axis deviation. Chest x-ray shows intact Nuss bars and is, otherwise, normal. Ventilation-Perfusion (VQ) scan is normal. An echocardiogram shows normal ventricular output and valvular function with an incidental finding of slight angulation of aortic arch with no significant gradient. Cardiology recommends trending troponins every 6 hours. A repeat EKG the following day shows normal sinus rhythm without evidence of ischemia or arrhythmia. Serial troponins remain elevated for the following 48 hours ranging 0.22-0.24 ng/ml. The patient denies any further cardiac symptoms despite the persistently elevated troponins, and he is discharged home with close follow-up with pediatric cardiology as well as a thirty-day looping event monitor.

One week after discharge, in the cardiology clinic, troponin levels are still 0.23ng/ml. Creatine kinase MB level is obtained and is within normal limits. Due to persistently elevated troponins within a narrow range, a literature search is performed to determine if there are other causes for elevated troponins that neither rise nor fall. Several articles are found confirming cross reactivity between various antibodies and troponin assays that lead to falsely elevated troponin levels.2,3 Rheumatoid factor, antinucleic antibodies, and Epstein-Barr virus antibody titers are obtained. RF and ANA levels return within normal limits. However, EBV IgM levels are elevated , while EBV IgG levels are within normal limits, supporting the theory that the patient has a current infection of mononucleosis. The thirty day looping event monitor is uneventful, showing no dysrhythmia or ectopy. Serial echocardiograms continue to remain unchanged from the initial echo during the patient’s hospitalization. Serum samples are analyzed on four different troponin assays, and a vast variation in troponin levels is found, ranging from < 0.015 ng/ml (normal value) on the Siemens Vista/ cTnl to 0.23 ng/ml (significantly elevated) on Beckman Access/ AccuTnI+3. Serial dilution studies are performed on a Beckman Dxi800 instrument and reveal decreasing troponin values with increasingly diluted serum samples.

Discussion:

In pediatrics, ninety-eight percent of all chest pain complaints are non-cardiac in origin, with the leading cause being muscular skeletal pain.4 Of the two percent that are cardiac in origin, troponin levels are helpful in detecting cardiac muscle ischemia, most commonly present in myocardial infarct, pulmonary embolism, pericarditis, myocarditis, aortic dissection, heart failure, and cardiac contusion, over exertion, and rhabdomyolysis. Most troponin assays use a two-site immunoenzymatic assay. One study in 2016 found that various assays reported different troponin levels; however the 99th percentile cutoff values were in agreeance with each other.5 Heterophilie antibodies in the serum have been found to falsely elevate troponin levels due to cross-reactivity between the antibodies and troponin assays. Rheumatoid factor, fibrin, and alkaline phosphatase can also cause false positive results.2

Conclusions:

Elevated troponins are commonly interpreted as a sign of myocardial injury that prompts an extensive cardiac evaluation. This case illustrates that a common pediatric illness, infection with Epstein-Barr virus, can cause a false elevation in serum troponins. Infectious mononucleosis, as well as autoimmune diseases, should be considered in the differential of patients who present with elevated troponins without an apparent cardiac source.

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Apr 12th, 9:00 AM Apr 12th, 2:30 PM

Persistent elevation of troponins in the setting of Epstein-Barr Viral infection: A Case Report

Mt Mitchell

Introduction:

In pediatrics, ninety-eight percent of all chest pain complaints are non-cardiac in origin, with the leading cause being muscular skeletal pain. Of the two percent that are cardiac in origin, troponin levels are helpful in detecting cardiac muscle ischemia, most commonly present in myocardial infarction, pulmonary embolism, pericarditis, myocarditis, aortic dissection, heart failure, and cardiac contusion. There are multiple different troponin assays that detect troponin, usually using a two-site immunoezematic assay. Although values obtained may differ slightly between assays, there is not a statistically significant difference between assays. Several endogenous substances, such as rheumatoid factor, excess fibrin, alkaline phosphatase, and heterophile antibodies can cause statistically significant, though falsely increased troponin levels that do not rise and fall in the typical pattern seen in cardiac ischemia due to cross reactivity with the assays. We present the case of a fifteen-year-old male with chest pain and elevated troponins, but otherwise benign workup. It highlights the falsely elevated troponin levels seen with the cross-reactivity of heterophile antibodies and various troponin assays.

Case Presentation:

A 15-year-old male presents with a two-day history of intermittent, stabbing, 5/10 left sided chest pain, as well as substernal chest pressure that radiates to his left upper chest and shoulder. He is unable to identify any triggers of the pain or alleviating factors. Review of systems is negative for nausea, vomiting, diaphoresis, and shortness of breath. His past medical history is significant for pectus excavatum that has been corrected with Nuss bar procedure. He also reports being treated for strep pharyngitis two weeks prior. The patient presents to emergency department after having an irregular heart rate noted by the school nurse’s office.

His vital signs are stable, and his physical exam is notable for a regular heart rate and rhythm. Pectus excavatum with well healed midline scar is present. A basic metabolic panel is normal. In the emergency department, serum troponins are elevated between 0.24-0.25 ng/ml (normal range 0.00-0.02), and a D-dimer is elevated at 500 ng/ml (normal range 0-230). Cardiology is consulted, and following an algorithm for chest pain in pediatric patients,1 a series of additional tests are performed. His electrocardiogram shows a normal sinus rhythm with minimal left axis deviation. Chest x-ray shows intact Nuss bars and is, otherwise, normal. Ventilation-Perfusion (VQ) scan is normal. An echocardiogram shows normal ventricular output and valvular function with an incidental finding of slight angulation of aortic arch with no significant gradient. Cardiology recommends trending troponins every 6 hours. A repeat EKG the following day shows normal sinus rhythm without evidence of ischemia or arrhythmia. Serial troponins remain elevated for the following 48 hours ranging 0.22-0.24 ng/ml. The patient denies any further cardiac symptoms despite the persistently elevated troponins, and he is discharged home with close follow-up with pediatric cardiology as well as a thirty-day looping event monitor.

One week after discharge, in the cardiology clinic, troponin levels are still 0.23ng/ml. Creatine kinase MB level is obtained and is within normal limits. Due to persistently elevated troponins within a narrow range, a literature search is performed to determine if there are other causes for elevated troponins that neither rise nor fall. Several articles are found confirming cross reactivity between various antibodies and troponin assays that lead to falsely elevated troponin levels.2,3 Rheumatoid factor, antinucleic antibodies, and Epstein-Barr virus antibody titers are obtained. RF and ANA levels return within normal limits. However, EBV IgM levels are elevated , while EBV IgG levels are within normal limits, supporting the theory that the patient has a current infection of mononucleosis. The thirty day looping event monitor is uneventful, showing no dysrhythmia or ectopy. Serial echocardiograms continue to remain unchanged from the initial echo during the patient’s hospitalization. Serum samples are analyzed on four different troponin assays, and a vast variation in troponin levels is found, ranging from < 0.015 ng/ml (normal value) on the Siemens Vista/ cTnl to 0.23 ng/ml (significantly elevated) on Beckman Access/ AccuTnI+3. Serial dilution studies are performed on a Beckman Dxi800 instrument and reveal decreasing troponin values with increasingly diluted serum samples.

Discussion:

In pediatrics, ninety-eight percent of all chest pain complaints are non-cardiac in origin, with the leading cause being muscular skeletal pain.4 Of the two percent that are cardiac in origin, troponin levels are helpful in detecting cardiac muscle ischemia, most commonly present in myocardial infarct, pulmonary embolism, pericarditis, myocarditis, aortic dissection, heart failure, and cardiac contusion, over exertion, and rhabdomyolysis. Most troponin assays use a two-site immunoenzymatic assay. One study in 2016 found that various assays reported different troponin levels; however the 99th percentile cutoff values were in agreeance with each other.5 Heterophilie antibodies in the serum have been found to falsely elevate troponin levels due to cross-reactivity between the antibodies and troponin assays. Rheumatoid factor, fibrin, and alkaline phosphatase can also cause false positive results.2

Conclusions:

Elevated troponins are commonly interpreted as a sign of myocardial injury that prompts an extensive cardiac evaluation. This case illustrates that a common pediatric illness, infection with Epstein-Barr virus, can cause a false elevation in serum troponins. Infectious mononucleosis, as well as autoimmune diseases, should be considered in the differential of patients who present with elevated troponins without an apparent cardiac source.