What is the role of troponin I (troponin I) levels in patients with pulmonary embolism?

Role of Troponin I in Pulmonary Embolism

Troponin I is essential in pulmonary embolism for risk stratification and prognostication, as elevated levels identify patients at significantly higher risk of short-term mortality and adverse clinical outcomes, even among hemodynamically stable patients.

Primary Prognostic Function

Troponin I serves as a marker of right ventricular myocardial injury resulting from acute pressure overload in pulmonary embolism, with elevated levels strongly predicting mortality and clinical deterioration 1.

Mortality Risk Prediction

• Elevated troponin I increases mortality risk 5-17 fold depending on the cutoff used and patient population 1, 2.
• In acute PE, elevated troponin levels (using various cutoffs from 0.03-1.5 ng/mL) are associated with in-hospital mortality odds ratios ranging from 6.5 to 16.91 1.
• A meta-analysis of 1,985 patients demonstrated that elevated cardiac troponin concentrations were associated with an odds ratio of 9.44 (95% CI 4.14-21.49) for death in unselected patients and 5.90 (95% CI 2.68-12.95) specifically in hemodynamically stable patients 1, 2.

Risk Stratification in Normotensive Patients

The critical clinical value lies in identifying high-risk patients among those who appear hemodynamically stable 1.

• In normotensive acute PE patients, troponin I >0.03 μg/L predicts hemodynamic instability with a hazard ratio of 9.8 (95% CI 1.2-79.2), independent of clinical, echocardiographic, and other laboratory data 1, 3.
• Troponin I >0.07 ng/mL in normotensive patients yields a hazard ratio of 12.1 (95% CI 1.3-112.0) for in-hospital death or clinical deterioration 1.
• The positive predictive value for PE-related early mortality ranges from 12-44%, while the negative predictive value is exceptionally high at 99-100% 1.

Combined Risk Assessment Strategy

Troponin I provides maximum prognostic value when combined with imaging or natriuretic peptides, creating a multimodal risk stratification approach 1.

Troponin + Echocardiography

• The combination of troponin I ≥0.10 μg/L with RV/LV ratio >0.9 on echocardiography identifies patients with 30-day mortality hazard ratio of 7.17 (95% CI 1.6-31.9) 1.
• When both troponin I >0.4 ng/mL and RV/LV ratio >1 are present, 1-year mortality hazard ratio reaches 2.584 (95% CI 1.451-4.602) 1.
• Patients with preserved RV function and normal troponin have excellent prognosis with mortality approaching 1% 1.

Troponin + Natriuretic Peptides

• Combined elevation of troponin T and NT-proBNP >1000 pg/mL yields hazard ratio of 10.00-12.16 for in-hospital death or complications 1.
• PE-related 40-day mortality exceeds 30% when both cardiac troponin T and NT-proBNP are elevated, compared to excellent prognosis when both are low 1.

Identification of Low-Risk Patients

Undetectable or very low troponin I has exceptional negative predictive value for adverse outcomes 1, 4.

• Highly sensitive troponin I <0.012 ng/mL identifies patients with zero in-hospital deaths and no hard events (death, CPR, thrombolysis) in a cohort of 137 patients 4.
• These patients are potential candidates for outpatient management or early discharge, regardless of clinical risk scores 1, 4.
• Low troponin combined with absence of RV dysfunction identifies the lowest-risk group with short-term mortality rates approaching 1% 1.

Clinical Application Algorithm

Use troponin I measurement in all confirmed PE patients for the following decision pathway:

1. Measure troponin I on admission (and consider repeat at 6-12 hours if initially negative, as conversion to positive has prognostic implications) 1.

2. If troponin I is undetectable or very low (<0.03-0.10 ng/mL depending on assay):

   • Patient has excellent short-term prognosis 1, 4
   • Consider early discharge or outpatient management if clinically stable 4
   • Standard anticoagulation is appropriate 1

3. If troponin I is elevated (>0.03-0.10 ng/mL):

   • Obtain echocardiography to assess RV function 1
   • Measure BNP or NT-proBNP for additional risk stratification 1
   • Admit for monitoring due to 5-10 fold increased mortality risk 1, 2

4. If both troponin I and RV dysfunction are present:

   • Patient is at highest risk (10-38% mortality) 1, 5
   • Requires intensive monitoring 5
   • Consider escalation of therapy if clinical deterioration occurs 5
   • Current data do not support routine thrombolysis based solely on biomarkers, but these patients warrant close observation 1, 5

Important Caveats

Several factors limit troponin interpretation in PE:

• No universally accepted cutoff values exist; thresholds range from 0.01 to 1.5 ng/mL across studies 1.
• Troponin elevation reflects RV myocardial injury but does not distinguish between acute PE and other causes of RV strain 1.
• Some studies show troponin I elevation is not statistically significant for mortality when clinical scores (like PESI) are included in multivariate analysis 1.
• The positive predictive value is modest (12-44%), meaning many patients with elevated troponin will not experience adverse outcomes 1.
• Biomarkers alone should not dictate thrombolytic therapy decisions in normotensive patients; ongoing trials are evaluating this question 1.