Biomarkers in acute pulmonary embolism

Biomarkers in acute pulmonary embolism

Biomarkers of myocardial injury may be elevated in acute pulmonary embolism. They are due to right ventricular ischemia and can influence early outcome. Elevated cardiac troponins are associated with worse prognosis in acute pulmonary embolism. It is a supply demand mismatch as in type 2 myocardial infarction. Systemic hypotension reduces the coronary perfusion pressure in an overloaded right ventricle. Yet elevated cardiac troponins have a low specificity and positive predictive value for early mortality in normotensive patients with acute pulmonary embolism [1]. But highly sensitive troponin T assay in normotensive patients with acute pulmonary embolism has been shown to have a high negative predictive value [2].

Heart-type fatty acid-binding protein (H-FABP) is another early and sensitive marker of myocardial injury which has been found to be useful in acute pulmonary embolism. There was value in both unselected and normotensive patients with pulmonary embolism. Boscheri A et al found that it predicts mortality in patients with pulmonary embolism at intermediate risk [3]. Another study of 126 consecutive normotensive patients with confirmed pulmonary embolism showed that it is a useful biomarker for risk stratification [4].

Right ventricular pressure overload in acute pulmonary embolism causes stretching of myocardium and release of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP). Similar to cardiac troponins, natriuretic peptides also have low specificity and positive predictive value for early mortality in normotensive patients with acute pulmonary embolism. But there is a high negative predictive value for low blood levels of natriuretic peptides [5].

D-dimer is of course the first biomarker which comes to your mind when you think of pulmonary embolism. For long it has been used mainly as a negative predictive test as positive predictive value is low especially in hospitalized patients. This is because there are several alternate reasons for D-dimer elevation in hospitalized patients other than acute pulmonary embolism including cancer, infections, inflammation and pregnancy.

Now there is a concept of D-dimer cut-off values adjusted for age or clinical probability as an alternative to fixed cut-off values [1]. In an analysis of 1029 consecutive patients presenting to the emergency department with clinically suspected pulmonary embolism, sensitivity of D-dimer testing was 100% in all age groups. But the specificity decreased markedly with age, being 67% in those aged 40 years or lower and 10% in those aged 80 years or more [6]. In a study of 3346 patients with suspected pulmonary embolism, compared with a fixed D-dimer cutoff of 500 microgram/liter, the combination of pretest clinical probability and age-adjusted D-dimer cutoff was associated with a larger number of patients in whom pulmonary embolism could be ruled out with low likelihood of subsequent clinical venous thromboembolism.

YEARS study evaluated the YEARS clinical decision rule incorporating differential D-dimer cutoff values at presentation to be fast, compatible with clinical practice and to reduce the number of CT pulmonary angiograms in all age groups [8]. Clinical items in the YEARS decision rule were clinical signs of deep vein thrombosis, hemoptysis, and whether pulmonary embolism was the most likely diagnosis. In those without any of the clinical items, D-dimer less than 1000 ng/ml excluded pulmonary embolism. In those with one or more items and D-dimer less than 500 ng/ml also pulmonary embolism could be excluded. The main advantage projected was that YEARS algorithm could reduce CT pulmonary angiograms by 14% in all age groups.

References

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