What are the causes of elevated troponin (troponin) levels in pediatric patients?

Causes of Elevated Troponin in Pediatric Patients

Unlike adults where troponin elevation typically indicates acute coronary syndrome requiring urgent catheterization, elevated troponin in children reflects a broad spectrum of cardiac and non-cardiac pathologies, with myocarditis being the most common cause, and coronary artery disease being exceedingly rare. 1, 2

Cardiac Causes

Inflammatory/Infectious Conditions

• Myocarditis is the most common cardiac cause of troponin elevation in previously healthy children, accounting for approximately 50% of cases in pediatric series 1, 2
• Myopericarditis and perimyocarditis together represent another significant proportion of inflammatory cardiac causes 1, 2
• These inflammatory conditions can be diagnosed through clinical history (chest pain, recent viral illness), physical examination, ECG changes, and echocardiographic findings without requiring cardiac catheterization 1, 2

Structural and Congenital Abnormalities

• Anomalous coronary artery origins can cause troponin elevation, typically presenting with exertional symptoms rather than rest symptoms 2
• Severe congenital heart disease with hemodynamic compromise can elevate troponin levels 3
• Valvular heart disease can increase wall stress leading to troponin elevation 4

Acute Cardiac Stress

• Tachyarrhythmias cause myocardial stress and subsequent troponin release 4
• Acute heart failure from any cause can result in wall stress and myocyte damage 4
• Cardiac trauma and contusion from blunt chest trauma frequently elevate troponin, with values >2.0 ng/ml suggesting significant injury 3

Iatrogenic Causes

• Cardiac procedures including surgery, catheterization, ablation, and cardioversion can cause troponin elevation 4

Non-Cardiac Causes

Toxicologic/Pharmacologic

• Drug intoxications represent a major cause of pediatric troponin elevation, accounting for approximately 11% of cases in large series 1
• Coronary vasospasm secondary to illicit drug use (particularly cocaine and amphetamines) accounts for approximately 22% of myocardial injury cases in some pediatric cohorts 2
• Carbon monoxide poisoning is a significant cause, representing nearly 10% of cases 1
• Intensive β-agonist use during acute asthma exacerbations and lower respiratory tract infections can elevate troponin 1
• Cardiotoxic chemotherapy agents can cause troponin elevation 5

Respiratory Conditions

• Severe respiratory distress or hypoxemia can cause type 2 myocardial infarction through oxygen supply-demand mismatch 4
• Pulmonary embolism causes right ventricular strain and troponin elevation 4
• Pulmonary hypertension, particularly severe cases, can cause chronic right heart strain 4, 3

Critical Illness

• Sepsis causes troponin elevation through inflammatory mediators and demand ischemia 4
• Shock states of any etiology can result in myocardial injury 4
• Systemic illness with multiorgan dysfunction is associated with troponin elevation and poor prognosis 3

Other Systemic Conditions

• Renal dysfunction (both acute and chronic) reduces troponin clearance and is associated with baseline elevations 4, 5
• Acute neurological events including stroke can cause troponin elevation 4
• Endocrine disorders such as thyroid dysfunction can elevate troponin 4

Diagnostic Approach in Pediatric Patients

Initial Assessment

• A single troponin measurement is insufficient; serial measurements at 6-12 hour intervals are essential to establish rising/falling patterns characteristic of acute injury 5, 2
• Clinical history focusing on chest pain, exertional symptoms, recent viral illness, drug exposure, and trauma is the fundamental screening tool 1, 2
• Urine drug screen should be obtained routinely as it identifies coronary vasospasm from drug use in approximately 20-22% of cases where performed 2

Electrocardiographic Findings

• ECG abnormalities are present in approximately 84% of pediatric patients with elevated troponin 2
• ECG changes help distinguish ischemic from inflammatory etiologies 1, 2

Echocardiographic Evaluation

• Echocardiography is abnormal in approximately 56% of cases and helps identify structural abnormalities, wall motion abnormalities, and ventricular dysfunction 2
• Normal echocardiography does not exclude significant pathology, as nearly half of patients with elevated troponin have normal studies 2

Advanced Imaging

• Cardiac MRI with gadolinium enhancement is the most useful test when initial evaluation is non-diagnostic, showing abnormalities in approximately 50% of cases where performed 2
• MRI can distinguish myocarditis from other causes and assess extent of myocardial involvement 2

Role of Cardiac Catheterization

• Cardiac catheterization is rarely indicated in pediatric troponin elevation and shows abnormalities in only 13% of cases 2
• Catheterization does not typically change management and should be reserved for specific indications such as suspected anomalous coronaries with exertional symptoms 1, 2
• Unlike adults, emergency catheterization is not routinely required for troponin elevation in children 1

Interpretation of Troponin Values

Magnitude and Patterns

• For diagnosis of acute myocardial necrosis, a troponin value above the 99th percentile with evidence of serial increase or decrease ≥20% is required 6
• In pediatric myocarditis, median peak troponin levels reach 506.5 ng/L, significantly higher than non-cardiac causes 7
• A high-sensitivity troponin cutoff of 90 ng/L provides 100% sensitivity and 95% specificity for myocarditis diagnosis 7
• Initial troponin levels and progression patterns are not reliably diagnostic or prognostic for specific etiologies in children 2

Prognostic Significance

• Abnormal troponin in the first 72 hours of hospitalization for myocarditis is associated with ECMO requirement (25.6% vs 7.1%) but not with mortality 8
• Troponin values >8.0 ng/ml in the context of severe systemic illness are associated with poor survival 3
• Even minor elevations carry prognostic significance and should not be dismissed 4

Critical Pitfalls to Avoid

• Do not assume coronary artery disease as the primary etiology as it is exceedingly rare in previously healthy children 1, 2
• Do not proceed directly to cardiac catheterization without completing non-invasive evaluation including drug screen, ECG, and echocardiography 1, 2
• Do not rely on a single troponin measurement; serial values are mandatory 5, 2
• Do not overlook toxicologic causes; obtain urine drug screen routinely 2
• Recognize that stable congenital or acquired heart disease does not typically cause troponin elevation in the absence of acute decompensation 3
• Remember that troponin may remain elevated for up to 2 weeks after injury, complicating assessment of recurrent events 5