**6. Risk assessment based on biomarkers of myocardial injury**

Cardiac troponins I and T as well as NT-pro brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) have emerged as promising tools for risk stratification.

#### **6.1 Cardiac troponins**

Cardiac troponins may be increased in patients with PE, even in the absence of coronary artery disease. The presumed mechanism is acute right heart overload attributed to myocardial ischemia and from oxygen supply-demand mismatch. The elevation usually resolves within 40 hours following PE in contrast to more prolonged elevation after an acute myocardial infarction. The peak level is usually lower than in acute myocardial infarction (Müller-Bardorff et al., 2002).

Patients with an elevated troponin I or troponin T levels had an increased risk for short-term mortality (OR 5.24, 95% CI 3.28 – 8.38) or PE-related deaths (OR 9.44, 95% CI 4.14 – 21.49). Elevated troponin levels even among patients who are hemodynamically stable are associated with higher mortality (Becattini et al., 2007; Jimenez et al., 2008).

Irrespective of various methods and cut-off values applied, most trials reported a low positive predictive value for PE-related mortality in the range of 12% to 44%, but with a very high negative predictive value between 99% and 100%.

#### **6.2 Brain natriuretic peptide**

Right ventricular dysfunction is associated with increased myocardial stretch which leads to the release of BNP and its amino terminal portion, NT-proBNP.

In acute PE, increasing levels of BNP or NT-proBNP predict the severity of RV dysfunction and mortality (Cavallazzi et al., 2008; Klok et al., 2008; Lega et al., 2009). Although elevated concentrations are related to worse outcome, the positive predictive value is low. On the other hand, low levels of BNP or NT-proBNP can be used reliably to identify patients with a good prognosis (Table 5).

#### **6.3 Novel biomarker**

Heart-type fatty acid binding protein (H-FABP), a protein released earlier than troponins during myocardial ischemia, has been evaluated as a prognostic marker in acute PE. The studies have reported a high sensitivity (78% to 100%) and negative predictive value (96% to 100%), but these studies are small and such measurements are not widely available (Puls et al., 2007; Kaczynska et al., 2006).

#### **6.4 Summary of evidence on the prognostic value of biomarkers**

Many studies did not perform an extensive comparison between all the available biomarkers, thus it remains debatable which biomarker will yield the best prognostic value. Another limitation is biomarker thresholds were determined retrospectively, thus no consistent cut-off values were used in the studies. Despite this, it appears BNP/NT-proBNP and cardiac troponins could be used as rule-out tests.

Perfusion defects due to PE increase with the number and size of emboli, without corresponding ventilation compromise ("mismatch" defects). However, the prognostic implications of the number and size of defects on a V/Q scan have not been investigated.

Cardiac troponins I and T as well as NT-pro brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) have emerged as promising tools for risk stratification.

Cardiac troponins may be increased in patients with PE, even in the absence of coronary artery disease. The presumed mechanism is acute right heart overload attributed to myocardial ischemia and from oxygen supply-demand mismatch. The elevation usually resolves within 40 hours following PE in contrast to more prolonged elevation after an acute myocardial infarction. The peak level is usually lower than in acute myocardial infarction

Patients with an elevated troponin I or troponin T levels had an increased risk for short-term mortality (OR 5.24, 95% CI 3.28 – 8.38) or PE-related deaths (OR 9.44, 95% CI 4.14 – 21.49). Elevated troponin levels even among patients who are hemodynamically stable are

Irrespective of various methods and cut-off values applied, most trials reported a low positive predictive value for PE-related mortality in the range of 12% to 44%, but with a very

Right ventricular dysfunction is associated with increased myocardial stretch which leads to

In acute PE, increasing levels of BNP or NT-proBNP predict the severity of RV dysfunction and mortality (Cavallazzi et al., 2008; Klok et al., 2008; Lega et al., 2009). Although elevated concentrations are related to worse outcome, the positive predictive value is low. On the other hand, low levels of BNP or NT-proBNP can be used reliably to identify patients with a

Heart-type fatty acid binding protein (H-FABP), a protein released earlier than troponins during myocardial ischemia, has been evaluated as a prognostic marker in acute PE. The studies have reported a high sensitivity (78% to 100%) and negative predictive value (96% to 100%), but these studies are small and such measurements are not widely available (Puls et

Many studies did not perform an extensive comparison between all the available biomarkers, thus it remains debatable which biomarker will yield the best prognostic value. Another limitation is biomarker thresholds were determined retrospectively, thus no consistent cut-off values were used in the studies. Despite this, it appears BNP/NT-proBNP

**6. Risk assessment based on biomarkers of myocardial injury** 

associated with higher mortality (Becattini et al., 2007; Jimenez et al., 2008).

high negative predictive value between 99% and 100%.

the release of BNP and its amino terminal portion, NT-proBNP.

**6.4 Summary of evidence on the prognostic value of biomarkers** 

and cardiac troponins could be used as rule-out tests.

**6.1 Cardiac troponins** 

(Müller-Bardorff et al., 2002).

**6.2 Brain natriuretic peptide** 

good prognosis (Table 5).

al., 2007; Kaczynska et al., 2006).

**6.3 Novel biomarker** 


(a-cTests used: aShionoria, CIS Bio International; bElecsys, Roche Diagnostics; cTriage, Biosite Technologies. eAdverse events include the need for resuscitation, mechanical ventilation, inotropic support, thrombolytics, or embolectomy)

Table 5. Prognostic value of BNP or NT-proBNP in acute pulmonary embolism

Due to the high negative predictive value for PE-related mortality and adverse events, a potential approach consists of a combination of biomarker testing and echocardiography. In the setting of an acute PE, further risk stratification with echocardiography is warranted in patients with elevated cardiac biomarkers due to limited specificity of the assays for predicting RV dysfunction. Conversely, in patients with levels below cut-off, echocardiography will likely not add prognostic information.

This approach was demonstrated in a prospective study of 124 patients diagnosed with acute PE. The presence of RV dysfunction on echocardiography in patients with elevated NT-proBNP (cut-off of 1000 pg/mL) or cardiac troponins (cut-off of 0.04 ng/mL) is associated with a 10-fold increase in complication risk compared with patients biomarker levels below threshold (Binder et al., 2005).
