Tag Archives: troponin

PEM Playbook – Big Labs, Little People: Troponin, BNP, D-Dimer, and Lactate

Originally published at Pediatric Emergency Playbook on April 1,
2016 – Visit to listen to accompanying podcast. Reposted with permission.

Follow Dr. Tim Horeczko on twitter @EMTogether

It’s a busy shift.  Today no one seems to have a chief complaint.

Someone sends a troponin on a child.  Good, bad, or ugly, how are you going to interpret the result?

And while we’re at it – what labs do I need to be careful with in children – sometimes the normal ranges of common labs can have our heads spinning!

Read on for bread-and-butter pediatric blood work and further, to answer the question – what’s up with troponin, lactate, d-dimer, and BNP in kids?


A fundamental tenet of emergency medicine:

We balance our obligation to detect a dangerous condition with our suspicion of the disease in given patient.

Someone with a cough and fever may simply have a viral illness, or he may have pneumonia.  Our obligation is to evaluate for the pneumonia.  It’s ok if we “miss” the diagnosis of a cold. It could be bad if we don’t recognize the pneumonia.

How do we decide?  Another fundamental concept:

The threshold.

Depending on the disease and the particular patient, we have a threshold for testing, and a threshold for treating.  Every presentation – and every patient for that matter – has a complicated interplay between what we are expected to diagnose, how much we suspect that particular serious diagnosis, and where testing and treating come into play.

What’s wrong with “throwing on some labs”?

Easy to do right?  They are but a click away…

Often a good history and physical exam will help you to calibrate your investigational thresholds.  This is especially true in children – the majority of pediatric ambulatory visits do not require blood work to make a decision about acute care.  If your patient is ill, then by all means; otherwise, consider digging a bit deeper into the history, get collateral information, and make good use of your general observation skills.

First, a brief word about basic labs.

The punchline is, use a pediatric reference.

If you don’t have a trusted online reference available during your shift, make sure you have something like a Harriett Lane Handbook accessible to you. Don’t rely on your hospital’s lab slip or electronic medical record to save you, unless you are sure that they use age-specific pediatric reference ranges to flag abnormal values. Believe it or not, in this 21st century of ours, some shops still use adult reference ranges when reporting laboratory values on children.

Notable differences in basic chemistries

Potassium: tends to run a bit higher in infants, because for the first year of life, your kidneys are inefficient in excreting potassium.

BUN and creatinine: lower in children due to less muscle mass, and therefore less turnover (and usually lack of other chronic disease)

Glucose: tends to run lower, as children are hypermetabolic and need regular feeding (!)

Alkaline phosphatase: is always high in normal, growing children, due to bone turn over (also found in liver, placenta, kidneys)

Ammonia: high in infancy, due to immature liver, trends down to normal levels by toddlerhood

ESR and CRP: low in healthy children, as chronic inflammation from comorbidities is not present; both increase steadily with age

Thyroid function tests: all are markedly high in childhood, not as a sign of disease, but a marker of their increased metabolic activity

Big Labs


Reliably elevated in myocarditis, and may help to distinguish this from pericarditis (in addition to echocardiography)

Other causes of elevated troponin in children include: strenuous activity, status epilepticus, toxins, sepsis, myocardial infarction (in children with congenital anomalies).  Less common causes of troponemia are: Kawasaki disease, pediatric stroke, or neuromuscular disease.

Don’t go looking, if you won’t do anything with the test.

Brain natriuretic peptide (BNP)

In adults, we typically think of a BNP < 100 pg/mL as not consistent with symptoms caused by volume overload.

Luckily, we have data in children with congenital heart disease as well.  Although each company’s assay reports slightly different cut-offs, in general healthy pediatric values match healthy adult values.

One exception is in the first week of life, when it is high even in healthy newborns, due to the recent transition from fetal to newborn circulation.

Use of BNP in children has been studied in both clinic and ED settings. Cohen et al. in Pediatrics used BNP to differentiate acute heart failure from respiratory disease in infants admitted for respiratory distress. They compared infants with known CHF, lung disease, and matched them with controls.

Later, Maher et al. used BNP in the emergency department to differentiate heart failure from respiratory causes in infants and children with heart failure and those with no past medical history.

The bottom line is:

BNP reliably distinguishes cardiac from respiratory causes of shortness of breath in children with a known diagnosis of heart failure.


To cut to the chase: d-dimer for use as a rule-out for pulmonary embolism has not been studied in children.

The only data we have in using d-dimer in children is to prognosticate in established cases. It is only helpful to track therapy for children who have chronic clots.

This is where our adult approach can get us into trouble. Basically, think of the d-dimer in children like it doesn’t even exist. It’s not helpful in our setting for our indications.   An adult may have an idiopathic PE – in fact, up to a third of adults with PE have no known risk factor, which makes decision tools and risk stratification important in this population.

Children with PE almost always have a reason for it.


There is at least one identifiable risk factor in up to 98% of children with pulmonary embolism. The majority have at least two risk factors.

If you’re suspecting deep venous thrombosis, perform ultrasonography, and skip the d-dimer.

If you’re worried about PE, go directly to imaging. In stable patients, you may elect to use MR angiography or VQ scan, but most of us will go right to CT angiography. Radiation is always a concern, but if you need to know, get the test.

This is yet another reminder that your threshold is going to be different in children when you think about PE – they should have a reason for it. After you have excluded other causes of their symptoms, if they have risk factors, and you are still concerned, then do the test you feel you need to keep this child safe.

You are the test.

Risk factors only inform you, and you’ll have to just pull the trigger on testing in the symptomatic child with risk factors.


A sick child with sepsis syndrome?

The short answer – yes.

In the adult literature, we know that a lactate level above 4 mmol/L in patients with severe sepsis was associated with the need for critical care. This has been studied in children as well, and an elevated lactate in children – typically above 4 – was a predictor of prolonged ICU course and mortality in septic patients.

The acute recognition and treatment of sepsis is first and foremost, clinical.

Our goal is to promote perfusion and provide oxygen to the tissues. Laboratory testing is not a substitute for clinical assessment – it should be used as an extension of your assessment.  There are two main reasons for an elevated lactate: the stress state and the shock state.

The stress state is due to hypermetabolism and an increase in glycolysis, as an example, in early sepsis. The shock state is due to tissue hypoxia, seen in septic shock. The confusion and frustration with lactate is that we often test the wrong people for it.

We could use it to track treatment, and see if we can clear the lactate; decreased lactate levels are associated with a better outcome in adults. Serial clinical assessments are even more useful to gauge your success with treatment.

We should use lactate to detect occult shock. Children compensate so well for shock, that subtle tissue hypoxia may not be detected until later. It may inform your decision for level of care, intensive care versus some other lower level.

Have you every been in this situation:

“Why, oh why, did we send a lactate?”

There are times when a lactate is ordered – maybe by protocol or maybe accidentally – or maybe in retrospect, the patient didn’t need it. Here is a quick mnemonic to remember the reasons for an elevated lactate: LACTATES


Lliver – any liver disease affects how lactate is metabolized by the Cori cycle
Aalbuterol (or for our international friends, salbutamol), beta-agonists like albuterol, increase lactate production via cyclic amp
C“can’t breathe” – respiratory distress and increased work of breathing shifts the ratio of aerobic and anerobic repiration
Ttoxins – all kinds of wonder drugs and recreational drugs do it – look up your patient’s list if you’re suspicious
Aalcohol, not an infrequent offender
Tthiamine deficiency – think of this in your cachectic or malnourished patients
Eepinephrine – a by-product of the Cori cycle, how lactate is metabolized. Difficult to interpret lactates when a patient is on an epinephrine drip.
Sseizure or shock – most commonly septic, but can be any type: cardiogenic, bstructive, hypovolemic, distributive.

Bottom line: high serum lactate levels have been associated with morbidity and mortality in children with sepsis and trauma, the two best-studied populations.

A summary of how labs can help you – or hurt you – in pediatric emergency medicine:

  1. Have a good reference for normal values and always be skeptical of how your lab reports them.
  2. Troponin testing is great for the child with suspected cardiogenic shock, myocarditis, or in unwell children with congenital heart disease.
  3. BNP in children can be used just like you do in adults – to get a sense of whether the presenting symptoms are consistent with heart failure.
  4. D-dimer is mostly a waste of time in the PED.
  5. Lactate can be useful in the right patient – use it to risk-stratify the major trauma patient or the patient with sepsis that may be suffering from occult shock.
  6. And lastly, make sure that you are mindful of your threshold for testing, and our threshold for treatment. If will vary by disease and by the patient at hand.



Gupta SK, Naheed Z. Chest Pain in Two Athletic Male Adolescents Mimicking Myocardial Infarction. Pediatr Emer Care. 2014;30: 493-495.

Kelley WE, Januzzi JL, Christenson RH. Increases of Cardiac Troponin in Conditions other than Acute Coronary Syndrome and Heart Failure. Clinical

Chemistry. 2009; (55) 12:2098–2112.

Kobayashi D, Aggarwal S, Kheiwa A, Shah N. Myopericarditis in Children: Elevated Troponin I Level Does Not Predict Outcome. Pediatr Cardiol. 2012; 33:1040–1045.

Koerbin G, Potter JM, Abhayaratna WP et al. The distribution of cardiac troponin I in a population of healthy children: Lessons for adults. Clinica Chimica Acta. 2016; 417: 54–56.

Liesemer K, Casper TC, Korgenski K, Menon SC. Use and Misuse of Serum Troponin Assays in Pediatric Practice. Am J Cardiol. 2012;110:284 –289.

Newby KL et al. for the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations. J Am Coll Cardiol. 2012; 60(23): 2427-2463.

Schwartz MC, Wellen S, Rome JJ et al. Chest pain with elevated troponin assay in adolescents. Cardiology in the Young; 2013. 23: 353–360.


Auerbach SR, Richmond ME, Lamour JM. BNP Levels Predict Outcome in Pediatric Heart Failure Patients Post Hoc Analysis of the Pediatric Carvedilol Trial. Circ Heart Fail. 2010;3:606-611.

Cohen S, Springer C, Avital A et al. Amino-Terminal Pro-Brain-Type Natriuretic Peptide: Heart or Lung Disease in Pediatric Respiratory Distress? Pediatrics. 2005;115:1347–1350.

Fried I, Bar-Oz B, Algur N et al. Comparison of N-terminal Pro-B-Type Natriuretic Peptide Levels in Critically Ill Children With Sepsis Versus Acute Left Ventricular Dysfunction. Pediatrics. 2006; 118(4): 1165-1168.

Koch A, Singer H. Normal values of B type natriuretic peptide in infants, children, and adolescents. Heart. 2003;89:875–878.

Maher KO, Reed H, Cuadrado A et al. , B-Type Natriuretic Peptide in the Emergency Diagnosis of Critical Heart Disease in Children. Pediatrics. 2008;121:e1484–e1488.

Mir TS, Marohn S, Laeer S, Eistelt M. Plasma Concentrations of N-Terminal Pro-Brain Natriuretic Peptide in Control Children From the Neonatal to Adolescent Period and in Children With Congestive Heart Failure. Pediatrics. 2002;110(6)1:6.

Mir TS, Laux R, Hellwege HH et al. Plasma Concentrations of Aminoterminal Pro Atrial Natriuretic Peptide and Aminoterminal Pro Brain Natriuretic Peptide in Healthy Neonates: Marked and Rapid Increase After Birth. Pediatrics. 2003;112:896–899.


Goldenberg NA, Knapp-Clevenger RA, Manco-Johnson MJ. Elevated Plasma Factor VIII and d-Dimer Levels as Predictors of Poor Outcomes of Thrombosis in Children for the Mountain States Regional Thrombophilia Group. Pediatrics. 2003;112:896–899.

Manco-Johnson MJ. How I treat venous thrombosis in children. Blood. 2006; 107(1)21-31.

Naqvi M, Miller P, Feldman L, Shore BJ. Pediatric orthopaedic lower extremity trauma and venous thromboembolism. J Child Orthop. 015;9:381–384.

Parasuraman S, Goldhaber SZ. Venous Thromboembolism in Children. Circulation. 2006;113:e12-e16.

Strouse JJ, Tamma P, Kickler TS et al. D-Dimer for the Diagnosis of Venous Thromboembolism in Children. N Engl J Med. 2004;351:1081-8.


Andersen LW, Mackenhauer J, Roberts JC et al. Etiology and therapeutic approach to elevated lactate. Mayo Clin Proc. 2013; 88(10): 1127–1140.

Bai et al. Effectiveness of predicting in-hospital mortality in critically ill children by assessing blood lactate levels at admission. BMC Pediatrics. 2014; 14:83.

Scott HF, Donoghue AJ, Gaieski DF et al. The Utility of Early Lactate Testing in Undifferentiated Pediatric Systemic Inflammatory Response Syndrome. Acad Emerg Med. 2012; 19:1276–1280.

Shah A, Guyette F, Suffoletto B et al. Diagnostic Accuracy of a Single Point-of-Care Prehospital Serum Lactate for Predicting Outcomes in Pediatric Trauma Patients. Pediatr Emer Care. 2013; 29:715-719.

Topjian AA, Clark AE, Casper TC et al. for the Pediatric Emergency Care Applied Research Network. Early Lactate Elevations Following Resuscitation From Pediatric Cardiac Arrest Are Associated With Increased Mortality. Pediatr Crit Care Med. 2013; 14(8): e380–e387.

This post and podcast are dedicated to Daniel Cabrera, MD for his vision and his leadership in thinking ‘outside the box’.


Troponin     |     BNP     |     D-Dimer     |     Lactate

Powered by #FOAMed — Tim Horeczko, MD, MSCR, FACEP, FAAP

Elevated Troponin in the Setting of Supraventricular Tachycardia: Is it Clinically Significant?

Author: Erica Simon, DO, MHA (EM Resident Physician, SAUSHEC) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Stephen Alerhand, MD (@SAlerhand)

A 33 year-old male presents to your emergency department with the chief complaint of shortness of breath. As you walk into the patient’s room to greet him, you glance at his monitor which displays: HR 152, SBP 127/82, RR 22, SpO2 98% on room air. You begin your history taking, noting the absence of respiratory distress. The patient speaks in full sentences, explaining that he noticed the onset of palpitations and acute shortness of breath while watching television and smoking a cigarette one hour prior to arrival. The patient denies any past medical history. Family history is remarkable only for a maternal grandmother with DM II. Review of systems is negative for recent travel, history of DVT/PE, thyroid pathology, and lower extremity edema.

As you scroll through the triage note, you come across the patient’s EKG, demonstrating the absence of p-waves, and a narrow regular QRS complex with a ventricular rate of 154. Suspecting supraventricular tachycardia (SVT) as the etiology of the patient’s palpitations and potentially his shortness of breath, you attempt vagal maneuvers. After failed modified Valsalva technique, you administer 6 mg IV adenosine, which results in conversion to normal sinus rhythm.

While gathering your thoughts regarding the various labs and radiologic studies that you would like to order, you contemplate sending a troponin. The patient is a young male without chest pain; he has one cardiac risk factor. Is the troponin needed for risk stratification? Is the troponin likely to be elevated in the setting of SVT? Should a troponin be included in the standard evaluation of not just this patient’s SVT, but all patients presenting with SVT?

If you have pondered questions such as these, the following provides a discussion of the research on the topic, in addition to tips regarding the tailoring of your personal practice.

Troponin Levels – A Quick Pathophysiologic Review

Cardiac troponin T (cTnT), cardiac troponin I (cTnI), and cardiac troponin C (cTnC), in addition to actin and myosin, compose the myocardial sarcomere.1-5 At the molecular level, cardiac contraction is mediated by the entrance of calcium into the myocyte sarcolemma. When calcium binds to cTNC, a conformational change results, triggering the dislocation of troponin I from actin, and tropomyosin from myosin, allowing for actin and myosin interaction and subsequent contraction.6 (See the Annals of Clinical Biochemistry (reference 6) figure below for a quick review. Note: Red component = calcium.

components of the myocardial sarcomere

Figure 1. Components of the Myocardial Sarcomere6

Programmed proteolytic degradation of the sarcomeric unit results in a steady-state level of cTnT (6-8%) and cTnI (2-4%); hence the normal laboratory reference values. 1,2 Myonecrosis, occurring in the setting of ischemic versus non-ischemic cardiac myocyte injury, is evidenced by elevated circulatory levels of cTnT and cTnI.1-7 As cTnT and cTnI are localized to the cardiac myocyte, elevations of these proteins are sensitive indicators of myonecrosis. 1-7

Troponin Sensitivity and Specificity

Cardiac troponin assays are utilized as the gold standard in the detection of acute cardiovascular events, however, elevated troponins are not synonymous with myocardial infarction.1-3,5,7-11 Current cardiology literature details numerous studies citing varying etiologies of, and settings in which, cardiac troponins may be elevated in the absence of coronary artery disease. The following figure includes a summary of such etiologies and is adapted from Mahajan et al.’s and Clark’s works cited below. For a complete list of references utilized by Mahajan et al. and Clark, please view these respective publications directly.

 elevated Trop

        Figure 2. Etiologies of Elevated Troponin in Patients with Normal Coronary       Arteries1,4

Note: Troponin elevations secondary to these pathophysiologic mechanisms are not isolated to the adult population. Case reports have identified cTnI elevation s/p SVT in children with and without underlying cardiac pathology (HOCM).12,13

Go here for further reading: http://www.emdocs.net/the-elevated-troponin-what-else-besides-acs-could-cause-troponin-elevation/

What Does the Literature Say About Elevated Troponin Levels and SVT?

The following chart is a summary of relevant literature. The articles contained within are also cited in the Best Evidence Topic (BET) Summary, published in the Emergency Medicine Journal in 2010.

(Note: In seeking to assess the appropriateness of the routine use of troponin levels in the evaluation of SVT, the authors of the BET summary performed a Medline search (dates) using the Pubmed interface [SVT] and [troponin levels] and [evaluation of CAD]. Based upon their findings, the authors concluded that there was not sufficient research to support the routine utilization of troponin levels in the evaluation of uncomplicated SVT.14)

Author Study Type Subjects Presenting Symptom(s) CAD Risk Factor(s) Outcomes Findings
Patane et al., 20093 Case Study 49F with SVT. Cardiac risk factor: current smoker. Palpitations Current Smoker. Elevated cTnI Echo with mitral regurgitation and septal hypertrophy. Troponin normalized.                               Note: Confounding factor: History of multinodular goiter and paroxysmal SVT. Anti-TPO antibodies elevated and TSH low during hospital stay.
Miranda et al., 20065 Case Study 49F with SVT and elevated troponin. Retrosternal pain, nausea, diaphoresis, shortness of breath, palpitations None reported. PMHx of tachycardia with propranolol therapy. Elevated cTnI Coronary angiography without findings.
Zellweger et al., 20037 Case Series Four patients (ages 44-57) with SVT and elevated troponins. 44M: Chest pain and shortness of breath                          48F: Atypical chest pain         50M: Dizziness, lightheadedness, shortness of breath, nausea.                           57F: Dizziness, chest pain. 44M: None reported. PMHx of SVT.                         48F: None reported. PMHx of SVT.                     50M: None reported.         57F: None reported. Elevated cTnI for all. 57F with ST depression in infero-lateral leads s/p adenosine. Myocardial perfusion imaging (48 F, 50 M), stress echocardiography (50 M), coronary angiography (44 M, 57 F); all without findings of coronary artery disease.
Bakshi et al., 20028 Prospective Cohort Three patients (ages 37-49) presenting with SVT and elevated troponin. (Note: Study included 21 patients with elevated troponins who underwent coronary angiography for suspected CAD) 37F: Non-anginal chest discomfort. 45 year-old male: Atypical chest pain.       49F: Typical chest pain and diaphoresis. All: No PMHx reported. Elevated cTnI. EKG of 49F with ST depressions. Two patients with EKG changes suspicious for ACS: coronary angiography unremarkable. One patient with normal EKG with unremarkable coronary angiography.
Redfearn et al., 200510 Retrospective Cohort Three patients (ages 22-72) with SVT and elevated troponin. 22M, 56M, 72M: no presenting symptoms reported. All: No PMHx reported. Elevated cTnI All patients with unremarkable coronary angiography.
Yeo et al., 200611 Case Series Three patients (ages 22-58) with SVT and elevated troponins. 22M: Palpitations and dyspnea.

45M: Asymptomatic.                 58M: Asymptomatic.

22M: No CAD risk factors.

45M: No CAD risk factors but PMHx of non-ischemic cardiomyopathy, VT and COPD.

58M: HTN. PMHx also significant for CKD.

All patient with elevated cTnI. 45 year-old male EKG: VT. 58 year-old male EKG: RBB, VT. All patients with unremarkable coronary angiography.

-Legend: M = Male, F = Female, PMHx = Previous Medical History
-Note: Unless otherwise indicated, all patient EKGs consistent with narrow complex tachycardia (SVT).
-Cardiac risk factors: DM, Smoking, HTN, HLD, Family Hx of CAD <55 years of age.

Is there Prognostic Significance of cTnI Levels in Hospitalized Patients Presenting with SVT?

To date, only one study published out of Johns Hopkins has collected data on this topic. Chow et al. retrospectively screened patient records given an ICD-9 discharge diagnosis of SVT from 2002-2006. Patients included in the study were those who had been evaluated and treated in the emergency department, possessed an EKG demonstrating SVT, had at least one cTnI level and creatinine recorded, and received follow-up within one year of discharge. Patients excluded included those who ultimately received a diagnosis of atrial fibrillation or flutter, those who presented with a severe concurrent illness, and those who died within 30 days of discharge due to unrelated causes.

In total, 78 patients met criteria for the study (54% female; mean age 62.2 ±15.8 yrs) and 29 patients had an elevated cTnI. Univariate predictors of elevated cTnI included: LVEF <50%, renal dysfunction, ST segment depression, LBBB on EKG, and mod/severe valvular regurgitation.

Multivariable adjustment identified the presence of elevated cTnI with SVT as being associated with increased risk of death, MI, or cardiovascular re-admission (hazard ratio: 3.67; 95% CI 1.22-11.1; p = 0.02).15

Note: Hospitalized individuals with an elevated troponin more commonly possessed medical co-morbidities as compared to their counterparts presenting without elevated troponins. Please see the reference below if interested in further reading/evaluation.15

What Can We Conclude?
  • Cardiac troponins are sensitive in terms of locale – they are found only in the myocardium. Troponin elevation is NOT specific for myocardial infarction or coronary artery pathology. Cardiology literature has identified numerous etiologies of troponin elevation in the absence of coronary angiographic findings. Case reports in the pediatric population have also demonstrated the same.
  • Current research regarding the utilization of troponin levels in the evaluation and management of SVT is limited to small cohort studies (low n), case series, and case reports. One Best Evidence Topic Summary published in the Emergency Medicine Journal in 2010 recommends against the routine use of troponin levels in the setting of uncomplicated SVT (a presentation undefined in the BET summary), due to the potential for unnecessary testing and treatments.14
  • A study out of Johns Hopkins has demonstrated an increased risk of death, MI, and CV re-admission in patients requiring hospitalization following an ED presentation of SVT with elevated troponin (these individuals were more likely to have numerous medical co-morbidities [CAD, DM, COPD, CrCl <60ml/min, etc.]).15
Bottom Line

Given this review and the aforementioned findings, it is reasonable to infer that the decision to send a troponin should be based on a thorough H&P – if the history is concerning, anginal equivalents are present, there are cardiac risk factors, major medical comorbidities exist, or there are findings on physical exam concerning for cardiac pathology (new murmurs, signs/symptoms of new onset CHF, etc.), a troponin should be sent.

Is troponin elevation in the setting of SVT significant? In the appropriate clinical setting, yes, it can be.


References / Further Reading

  1. Mahajan N, Mehta Y, Rose M, Shani J, and Lichstein E. Elevated troponin level is not synonymous with myocardial infarction. Int J Cardiol 2006; 111: 442-449.
  2. Hein S, Scheffold T, Schaper J. Ischemia induces early changes to cytoskeletal and contractile proteins in diseased human myocardium. J Thorac Cardiovasc Surg 1995; 110: 89-98.
  3. Patane S, Marte F, Di Bella G. Abnormal troponin I levels after supraventricular tachycardia. Int J Cardiol 2009; 132: e57-e59.
  4. Clark M. Elevated cardiac troponins: Their significance in acute coronary syndrome and noncardiac conditions. J Okla State Med Assoc 2006; 99(6): 363-367.
  5. Miranda R, Machado M, Takakura I, da Mata P, da Fonseca C, Mouco O, et al. Elevated troponin levels after prolonged supraventricular tachycardia in patients with normal coronary angiography. Cardiology 2006; 106: 10-13.
  6. Gaze D, Colinson P. Multiple molecular forms of circulating cardiac troponin: Analytical and clinical significance. Ann Clin Biochem 2008; 45(Pt 4): 349-55
  7. Zellweger M, Schaer B, Cron T, Pfisterer M, Osswald S. Elevated troponin levels in the absence of coronary artery disease after supraventricular tachycardia. Swiss Med Wkly 2003; 133: 439-441.
  8. Bakshi T, Choo M, Edwards C, Scott G, Hart H, Armstrong P. Causes of elevated troponin I with a normal coronary angiogram. Int Med J 2002; 32:520-525.
  9. Costabel J, Urdapilleta M, Lambardi F, Campos R, Vergara J, et al. High-sensitivity cardiac troponin levels in supraventricular tachyarrhythmias. Pacing Clin Electrophysiol 2016. doi: 10.1111/pace.12851. [Epub ahead of print]
  10. Redfearn D, Ratib K, Marshal H, et al. Supravantricular tachycardia promotes release of troponin I in patients with normal coronary arteries. Int J Cadiol 2005; 102:521-22.
  11. Yeo K, Cruz L, Hong R. Tachycardia-induced elevations in cardiac troponin in the absence of coronary artery disease. Hawaii Med J 2006; 65:86-87.Luna C, Adie M, Tessle I, Acherman R.
  12. Luna C, Adie M, Tessler I, Acherman R. Troponin I elevation after supraventricular tachycardia in a child with hypertrophic cardiomyopathy. Pediatr Cardiol 2001; 22:147-149.
  13. Moore J, Arcilla L, Wang S, Lee M, Shannon K. Characterization of cardiac troponin elevation in the setting of pediatric supraventricular tachycardia. Pediatr Cardiol 2016; 37: 392-398.
  14. Carley S. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Emerg Med J 2010; 27(2): 141-142.
  15. Chow G, Hirsch G, Spragg D, Cai J, Cheng A, et al. Prognostic significance of cardiac troponin I levels in hospitalized patients presenting with supraventricular tachycardia. Medicine 2010; 89(3):141-147.

The Elevated Troponin: What else besides ACS could cause troponin elevation?

Author: Christina Smith, MD (EM Resident Physician, UTSW/Parkland Memorial Hospital) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Chief Resident at SAUSHEC, USAF)


Case Presentation

A 62 year-old male with PMH significant for CAD, CHF, COPD, ESRD, and prior PE presents with worsening shortness of breath since this morning. He called EMS after he noticed he was experiencing difficulty catching his breath. He is on several medications that he cannot remember, but one “blood thinner” and “some sort of puffer.” He also receives hemodialysis three times a week, and he states he has been compliant.

On first appearance, he is diaphoretic in a hunched over position trying his best to breath. His vital signs include: HR 121, BP 190/107, RR 25, Temp 38, and O2 Saturation 94% on room air.

An ECG is obtained and shows no change compared to prior: sinus rhythm with tachycardia to 120 and no ST or T wave abnormalities. CXR shows mild bilateral pulmonary edema. BNP is mildly elevated to 1,200 (baseline on prior labs 500). Troponin is 0.05 (baseline on prior labs is 0.03).

The differential for dyspnea and his laboratory findings is extensive, and this patient could have numerous confounders contributing to his elevated troponin. But first, what is troponin, and what does an elevation mean?



Cardiac troponins consist of three proteins: cTnC, cTnI, and cTnT1. These proteins interact with tropomyosin to form a complex that functions as the backbone of striated muscle. This functions in the excitation and contraction coupling of the heart through modulation of actin-myosin interaction in muscle.

Screen Shot 2016-02-02 at 11.01.21 AM

How do these types of troponin differ? Cardiac troponin I is specific for cardiac tissue, as it is not expressed in injured or regenerating skeletal muscle elsewhere. cTnT and cTNI are comparable for use in cardiac ischemia, but cTnT is more likely to be elevated with renal failure.

Troponin elevation can occur immediately after cardiac injury, but labs may only pick it up after one hour of injury. Peak level is reached at 24 hours, and troponin will often stay positive for one week.

What about other causes of troponin elevation? Did CKD, COPD exacerbation, sepsis, pericarditis, aortic dissection, even pulmonary embolism cross your mind as a possibility for his elevated troponin, or did tunnel vision of ACS take over? Not every troponin elevation is due to ACS, and we must understand the pitfalls of troponin, causes of elevation, and appropriate uses of troponin to broaden our differential.(1) Sample causes of elevated troponin are shown in table 1.

Table 1 – Causes of Elevated Troponin

Noncardiac Causes Cardiac Causes
Acute Noncardiac Critical Illness Acute and Chronic Heart Failure
Acute Pulmonary Edema Acute Inflammatory Myocarditis or Endocarditis/Pericarditis
Acute Pulmonary Embolism Aortic Dissection
Cardiotoxic Drugs Aortic Valve Disease
Stroke, Subarachnoid hemorrhage Apical Ballooning Syndrome
Chronic Obstructive Pulmonary Disease Bradyarrhythmia, Heart Block
Chronic renal failure Cardiac contusion from trauma
Extensive Burns Cardiac surgery, Post-percutaneous Coronary Intervention, Endomyocardial biopsy
Infiltrative Disease (Amyloidosis) Cardioversion
Rhabdomyolysis with Myocyte Necrosis Direct Myocardial Trauma
Sepsis Hypertrophic Cardiomyopathy
Severe Pulmonary Hypertension Tachycardia/Tachyarrhythmia, Bradyarrhythmia
Strenuous Exercise/Extreme Exertion  


Noncardiac Causes

Acute Noncardiac Critical Illness(2,3,4,5)

Patients in the intensive care unit are by definition critically ill. These patients may be ventilated, on inotropic support, have a high core temperature, tachycardic, hyper- or hypotensive, and most likely are not healthy at baseline. All of this increased myocardial demand leads to a pathologic process. And in result, troponin elevation can be seen with increased cardiac demand (type II NSTEMI) and unfortunately is associated with higher morbidity and mortality rates.

Pitfall: Do not conclude that patients with noncardiac critical illness and elevated troponin without other manifestations of ACS have AMI. ECG and history are vital.

Pearl: Troponin elevation in the critically ill has a correlation with mortality and morbidity. However, utilization of ECG and history are important in differentiating demand ischemia and another cardiac event.


Acute Pulmonary Embolism (PE) (2,3,6)

Cardiac troponin elevation can occur anywhere from 10-50% of pulmonary embolism patients and can signify the degree of myocardial injury likely from right heart strain, hypoxia, release of endothelial mediators, and decreased coronary blood flow. Increase in troponin correlates with increased morbidity and mortality in patients with acute PE.

Pitfall: Do not conclude in a patient with positive troponin that they have an NSTEMI without considering the diagnosis of PE. Strongly consider patient risk factors and your history and exam. If suspicious of PE, use a clinical scoring system to risk stratify the patient and consider imaging.

Pearl: Troponin elevation in setting of PE signifies a worse clinical picture. These patients with PE and elevated troponin likely warrant admission for close monitoring and treatment.


Stroke and Subarachnoid hemorrhage (SAH) (2,3,7)

In patients with intracranial bleeding, catecholamine release, either in plasma concentration or stimulated specifically in cardiac nerves, causes “contraction band necrosis” in the myocardium. This necrosis of cardiac cells releases troponin. It has also been suggested that the higher level of troponin elevation in subarachnoid hemorrhage suggests a higher severity of injury and a poorer prognosis. However, in patients with ischemic strokes, there are not as strong of studies to correlate with prognosis.

Pitfall: When you see an elevated troponin result, do not forget to consider stroke or SAH as the cause in the right clinical setting.

Pearl: Remember the catecholamine hypothesis. Sudden neurologic deficit or headache that points to stroke or SAH are key.


Chronic Obstructive Pulmonary Disease (COPD)( 3,8,9)

Myocardial damage occurs during a COPD exacerbation secondary to increased left ventricular afterload, increased RV demand, pulmonary hypertension, hypercapnia, and hypoxia that puts more demands on energy needs from the body. Elevated troponin in this setting has actually been proven to be a strong independent predictor of mortality in those admitted and following discharge. It is also a predictor of increased need for noninvasive mechanical ventilation. Unfortunately, these patients often have other comorbidities that predispose them to ACS.

Pitfall: Do not fall into the trap that an elevated troponin in a COPD flare is of no significance. These patients must be monitored closely for decompensation.

Pearl: Elevated troponin in COPD is predictive of mortality and need of further intervention such as noninvasive ventilation. Carefully evaluate these patients for chest pain as well, and look closely at the ECG for other signs of ischemia.


Chronic renal failure(2,3,6)

There are many possibilities as to why the troponin is elevated in this patient population including decreased clearance of normal cardiac myocyte loss, heart failure without evidence of ischemia or infarct, chronic inflammation or damage to skeletal muscle, or a combination of them all. So how are we supposed to approach this clinically?

Providers must consider the entire picture of the patient from their presenting symptoms to their ECG and labs with comparison to prior if available.

It is thought that cardiac troponin I holds advantages over troponin T because it is cleared more by dialysis and undergoes more chemical conversions in serum due to its instability. Troponin I should be less elevated than troponin T in the setting of chronic renal failure.

Pitfall: Do not make a clinical decision on troponin alone in a CKD patient. Scrutinize the ECG and take a careful history. Look at baseline labs if possible.

Pearl: Troponin can be elevated in patients with CKD in the absence of acute coronary syndrome, especially troponin T. There is not an easy solution to this conundrum. ECG and lab results cannot be trusted and therefore you have to keep your clinical suspicion high. Carefully evaluate the clinical picture with history, exam, and ECG.



Sepsis results in an inflammatory response, releasing mediators that depress the myocardium. Myocardial depression may lead to increased membrane permeability, resulting in troponin leak. Fortunately, this damage is usually not due to necrosis and is reversible. In other instances, a troponin increase can result from increased oxygen demand on the myocardium in the setting of reduced oxygen supply that does in fact lead to myocardial injury. Overall, increased troponin in the setting of sepsis is associated with increased morbidity and mortality.

Pitfall: Do not conclude that a positive troponin is ACS in the setting of sepsis.

Pearl: Troponin leak in the setting of sepsis is associated with increased morbidity and mortality.


Cardiac Causes

Acute and Chronic Heart Failure(3,6,10)

Troponins may be elevated in acute or chronic heart failure patients in the absence of ischemia. Previous studies have suggested that chronically damaged myocardium leaks proteins, specifically muscle contraction proteins, when subjected to further stress. Other injuries to the myocardium including global wall stretch, coronary malperfusion, or hypoxemia are also responsible for troponin elevation. Although it might not be useful to determine if this patient is having ACS, high sensitivity troponin I can be useful to determine the mortality rate.

Pitfall: Do not fall into the trap of thinking an elevated troponin means an acute ischemic event in a heart failure patient.

Pearl: Troponin elevation in chronic heart failure is still significant, as there is likely myocardium protein damage, but it does not always mean ACS. If possible, compare to an old troponin level and evaluate for change. A significant change from baseline may be true ACS. Evaluate the ECG for changes from a baseline ECG.


Aortic Dissection(2,3,11)

The reason as to why troponin is elevated in aortic dissection is not fully understood, although coronary compromise and increased demand have been proposed as the most likely causes. And as one may predict, aortic dissection is frequently misdiagnosed as ACS. This has dangerous consequences including delay in diagnosis or treating for ACS with antithrombotic agents that cause increased bleeding in an aortic dissection patient. Studies have shown elevated troponin associated with type A aortic dissection, signifying myocardial loss, may indicate hemodynamic compromise.

Pitfall: Do not forget to consider aortic dissection in patients presenting with ACS-type signs and symptoms.

Pearl: Always consider aortic dissection as a possible cause of elevated troponin. Ask patients about pain that is sudden in onset, ripping/sharp/tearing pain, pain that moves or changes, chest pain with neurologic symptoms, or pain above and below the diaphragm.


Acute Inflammatory Pericarditis, Myocarditis, or Endocarditis(2,3,6)

Myocarditis closely resembles ACS, not just clinically but pathologically with necrosis being the cause of troponin elevation in both. Troponin elevation can correlate with heart failure one month after primary infection, as well as inflammation severity based on continued elevation.

Pericarditis also can resemble ACS, but normally there is a history of a recent viral illness. Troponins are found in the myocardium, but are not found in the pericardium. However, you can still see a troponin elevation if the epicardium, or even if the myocardium, is involved in the inflammatory process of pericarditis. Troponin elevation in this instance however does not correlate with poor prognosis.

In patients with endocarditis, troponin elevation does correlate with morbidity and mortality.

Pitfall: Do not conclude in a patient with positive troponin that they have an NSTEMI without considering diagnosis of endocarditis, pericarditis, and myocarditis.

Pearl: ACS can be seen simultaneously in patients with endocarditis, pericarditis, or myocarditis.



A troponin elevation does not mean it’s ACS. At the end of the day, troponin is a tool and nothing more. Physicians must take into account the entire clinical picture: history, exam, ECG, baseline labs, response to treatment, clinical gestalt, etc. Several studies have suggested that in ACS, the initial troponin I on average is higher than elevations in non-ACS cases, with a median troponin of 0.14 ng/mL.(12) This can be just another tool to decipher the diagnosis causing an elevated troponin in our patients.

However, the critical step is to realize that not every elevated troponin is cardiac in nature. We must be wary of tunnel vision and broaden our differential because if we don’t, we risk missing high morbidity/mortality entities.


References/Further Reading

[1] Mahajan, V. S., and P. Jarolim. “How to Interpret Elevated Cardiac Troponin Levels.” Circulation 124.21 (2011): 2350-354. Web.

[2] Kelley, W. E., J. L. Januzzi, and R. H. Christenson. “Increases of Cardiac Troponin in Conditions Other than Acute Coronary Syndrome and Heart Failure.” Clinical Chemistry 55.12 (2009): 2098-112. Web.

[3] Tanindi, Asli, and Cemri. “Troponin Elevation in Conditions Other than Acute Coronary Syndromes.” VHRM Vascular Health and Risk Management (2011): 597. Web.

[4] Koshkina, EV, MIa Krasnosel’skiĭ, NM Fedorovskiĭ, EV Goriacheva, AA Polupan, AA Aref’ev, and AG Katrukha. “Diagnostic Value of Cardiac Troponin T Increase in Critically Ill Patients.” Anesteziol Reanimatol 6 (2009): 42-46. Print.

[5] Guest, Thomas M. “Myocardial Injury in Critically Ill Patients.” Jama 273.24 (1995): 1945. Web.

[6] Korff, S. “Differential Diagnosis of Elevated Troponins.” Heart 92.7 (2006): 987-93. Web.

[7] Miketic, J. K., M. Hravnak, S. M. Sereika, and E. A. Crago. “Elevated Cardiac Troponin I and Functional Recovery and Disability in Patients After Aneurysmal Subarachnoid Hemorrhage.” American Journal of Critical Care 19.6 (2010): 522-28. Web.

[8] Fruchter, Oren, and Mordechai Yigla. “Cardiac Troponin-I Predicts Long-Term Mortality in Chronic Obstructive Pulmonary Disease.” COPD: Journal of Chronic Obstructive Pulmonary Disease 6.3 (2009): 155-61. Web.

[9] Baillard, C., M. Boussarsar, JP Fosse, E. Girou, P. Le Toumelin, C. Cracco, and S. Jaber. “Cardiac Troponin I in Patients with Severe Exacerbation of Chronic Obstructive Pulmonary Disease.” Intensive Care Med 29.4 (2003): 584-89. Print.

[10] Missov, E., C. Calzolari, and B. Pau. “Circulating Cardiac Troponin I in Severe Congestive Heart Failure.” Circulation 96.9 (1997): 2953-958. Web.

[11] Bonnefoy, Eric, Patrick Godon, Gilbert Kikorian, Sylvie Chabaud, and Paul Touboul. “Significance of Serum Troponin I Elevation in Patients with Acute Aortic Dissection of the Ascending Aorta.” Acta Cardiologica 60.2 (2005): 165-70. Web.

[12] Harvell, Bryan, Nathan Henrie, Amy A. Ernst, Steven J. Weiss, Scott Oglesbee, Dusadee Sarangarm, and Lorenzo Hernandez. “The Meaning of Elevated Troponin I Levels: Not Always Acute Coronary Syndromes.” The American Journal of Emergency Medicine (2015): n. pag. Web.