Not A Reject – A Falsely Elevated Cardiac Troponin in a Heart
Transplant Recipient
Nicholas Wettersten, MD; Kathleen Tong, MD
University of California, Davis Medical Center; Sacramento, CA
Investigational Studies
Introduction
Medications
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Mycophenolate 360 mg BID
•  Fludrocortisone 0.1 mg daily
Tacrolimus 3.5 mg BID
•  Duloextine 30 mg daily
Carvedilol 3.125 mg BID
•  Mirtazapine 30 mg qhs
Aspirin 81 mg daily
•  Lamotrigine 75 mg daily
Trimethoprim/Sulfamethoxazole 160/800 mg M, W, F
Past Medical History
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Catecholamine Mediated Polymorphic Ventricular Tachycardia
Orthotopic Heart Transplantation (with daclizumab induction)
Asthma
Polysubstance Abuse
Mood Disorder, NOS
Family History
•  Non-contributory
Social History
•  Smokes 0.5-1 packs every day for 5 years
•  Occasional alcohol use
•  Intermittent use of marijuana and methamphetamine after transplantation
Physical Exam
Blood pressure: 112/50 mmHg; Heart Rate: 70/min
General: No acute distress.
Cardiac exam: Regular rate and rhythm, S1 and S2
Lung exam: Clear to auscultation bilaterally
Extremities: No edema or cyanosis
Luminescent Signal
No Troponin Present
Heterophilic Antibody Found
Steroid Burst Started
“Capture” Antibody
Repeat Biopsy
30
Troponin
20
10
9/2/12
8/2/12
7/2/12
6/2/12
5/2/12
4/2/12
3/2/12
2/2/12
1/2/12
12/2/11
11/2/11
10/2/11
9/2/11
8/2/11
7/2/11
6/2/11
5/2/11
Confirmed Interference
4/2/11
“Signal” Antibody
Heterophilic Antibody
First Cardiac Catheterization and Biopsy
0
History
•  A 23 year old man presented with chest pain to an outside ER where his
first troponin was <0.01 ng/ml and he was transferred to our institution
for further evaluation
•  Five years prior he had undergone orthotopic heart transplantation for
catecholamine mediated polymorphic ventricular tachycardia
•  Post-transplant he displayed maladaptive behavior with intermittent
compliance to immunosuppressive therapy and frequent presentations to
Emergency Rooms (ER) with syncope and chest pain. Evaluations did
not identify any cause for these recurrent symptoms.
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3/2/11
Case Presentation
Troponin I/T Molecule
50
2/2/11
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To recognize the implications of a positive troponin in a heart transplant
patient
To learn how heterophilic antibodies interfere with immunoassays
To learn other causes of interference in the troponin assay
Repeat Catheterization, Biopsy, and more Steroids
1/2/11
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60
12/2/10
Learning Objectives
Average Troponin Value For Date of Evaluation
Troponin Measured (ng/ml)
In cardiac transplant medicine, an elevated troponin may be a sign of organ
rejection. This may prompt invasive testing and increased
immunosuppression with significant risks and side effects. This series of
events stems from a positive troponin, which can sometimes be falsely
elevated.
Assay Container
Date of Evaluation
Graph displaying mean troponin value measured during different presentations to our hospital.
Highlighted on graph are key events.
Cardiac Catheterization 11/11: No coronary artery disease
Endomyocardial Biopsy 11/11: Mild to moderate rejection
Tacrolimus level: 5.7 (target 8.5-10)
Endomyocardial Biopsy 12/11: Mild chronic rejection
Cardiac Catheterization 3/12: No coronary artery disease
Endomyocardial Biopsy 3/12: Mild chronic rejection
Tacrolimus level: 12.5
Troponin - UCD: 40.33 ng/ml; Heterophil Antibody Block: 0.06 ng/ml
Troponin - UCD : 1.41 ng/ml; Other Hospital (different assay): <0.01 ng/ml
Multiple echocardiograms over admissions showed preserved LV function
Clinical Course
•  11/11: Initial troponin 22.9 ng/ml, patient underwent cardiac catheterization
and endomyocardial biopsy and tacrolimus level measured. Augmentation of
immunosuppression deferred after discussion with transplant center.
•  12/11: Repeat endomyocardial biopsy at transplant institution
•  1/12: Elevated troponin, steroid burst of prednisone 60 mg started
•  3/12: Troponin higher than measurable, repeat cardiac catheterization and
endomyocardial biopsy performed and second steroid burst started
•  5/12: Troponin measured 40 ng/ml, suspicion of assay interference and sample
sent for testing with a heterophilic antibody blocking reagent, which measured
troponin at 0.06 ng/ml strongly suggesting heterophilic antibody interference.
•  7/12: Presented to outside ER with troponin of 0.1 ng/ml then 0.04 ng/ml.
Transferred to UC Davis. Troponin measured 1.4 ng/ml. Sample sent to first
hospital for measurement. No troponin detected confirming interference.
Potentially Interfering Conditions Causing
False Positive Troponin
Heterophilic Antibodies
Alkaline Phosphatase
Fibrin
Inadequate Washing
Hemolysis
Macrotroponin
Rheumatoid Factor
Infection with Legionella
Table
Conditions and substances that can interfere with troponin assay and cause a false positive.
Figure
Left: Example of normal immunoassay function with troponin captured by one antibody and a
second antibody binds captured troponin to signal presence.
Right: With a heterophilic antibody, it can bind both capture and signal antibody making it
seem troponin is present when it is not.
Discussion
•  Elevated cardiac troponin in a heart transplant recipient may be from:
•  Ischemia
•  Rejection with injury of vasculature and ischemia
•  Rejection with injury to myocardium
•  Troponin is measured by an immunoassay
•  Immunoassays commonly use a “two-site sandwich”
•  A “capture” antibody binds troponin floating in serum
•  A “signal” antibody is added and binds the captured troponin to
signal the presence of troponin
•  The intensity of light emitted correlates with the amount of
troponin present
•  Immunoassays are prone to various forms of interference
•  Multiple different substances and conditions have been shown to
cause false positive troponins (see Table)
•  It is estimated between 0.4 and 3.1% of troponin measurements are
false positives
•  A heterophilic antibody describes a type of antibody that displays weak
and non-specific binding, often with broad reactivity
•  Sometimes they display stronger targeted binding, often in
individuals previously exposed to a specific antigen
•  Provoking factors that can induce a heterophilic antibody include:
•  Clinical therapeutics
•  Blood transfusions
•  Vaccinations
•  Exposure to animals
•  Ingestions
•  The patient had Daclizumab, a humanized mouse anti-interleukin-2receptor antibody, at time of transplantation potentially inducing
heterophilic antibodies
•  This case highlights the need to consider laboratory interference when
other clinical parameters do not support laboratory results
References
•  McNeil A. The trouble with Troponin. Heart, lung & circulation. 2007;16 Suppl 3:S13-16.
•  McClennen S, Halamka JD, Horowitz GL, Kannam JP, Ho KK. Clinical prevalence and ramifications of falsepositive cardiac troponin I elevations from the Abbott AxSYM Analyzer. Am J Cardiol. May 1 2003;91(9):
1125-1127.
•  Fleming SM, O'Byrne L, Finn J, Grimes H, Daly KM. False-positive cardiac troponin I in a routine clinical
population. Am J Cardiol. May 15 2002;89(10):1212-1215.
•  Kricka LJ. Human anti-animal antibody interferences in immunological assays. Clinical chemistry. Jul
1999;45(7):942-956.
•  Garcia-Mancebo ML, Agullo-Ortuno MT, Gimeno JR, Navarro-Martinez MD, Ruiz-Gomez J, Noguera-Velasco
JA. Heterophile antibodies produce spuriously elevated concentrations of cardiac Troponin I in patients with
Legionella pneumophila. Clinical biochemistry. Jun 2005;38(6):584-587.