Elsevier

Clinica Chimica Acta

Volume 371, Issues 1–2, September 2006, Pages 117-123
Clinica Chimica Acta

Plasma heart-type fatty acid binding protein is superior to troponin and myoglobin for rapid risk stratification in acute pulmonary embolism

https://doi.org/10.1016/j.cca.2006.02.032Get rights and content

Abstract

Background

Irreversible right ventricular (RV) failure with myocardial damage may precipitate fatal outcome in acute pulmonary embolism (APE). Cytoplasmic heart-type fatty acid binding protein (H-FABP) is a sensitive and specific biomarker of myocardial damage. We assessed which biomarker of myocardial damage or RV stretching is the most useful for short-term risk stratification in APE.

Methods

We analyzed 77 patients (51 F, 26 M) aged 65.3 ± 16.0 years with confirmed APE. On admission, systemic blood pressure and transthoracic echocardiography (for RV overload) were recorded and plasma concentrations of myoglobin (Mb), cardiac troponin T (cTnT), N-terminal fragment of proBNP (NT-proBNP) and H-FABP were evaluated.

Results

Fifteen (19.5%) patients died and 24 (31.2%) experienced complicated clinical course (CCC)-death/thrombolysis/cardiopulmonary resuscitation/intravenous vasopressors. Hazard ratio analysis demonstrated that plasma H-FABP, Mb, cTnT and NT-proBNP concentrations predicted fatal outcome. When only APE-related deaths were considered, plasma H-FABP concentrations indicated fatal outcome. Multivariate hazard ratio analysis revealed H-FABP as the only 30-day mortality predictor (HR 1.02 CI 95% 1.01–1.05).

Conclusions

H-FABP measured on admission is useful for short-term risk stratification in APE. It appears to be superior to cTnT, NT-proBNP and Mb in the prediction of 30-day APE-related mortality.

Introduction

Acute pulmonary embolism (APE) is a major cause of cardiovascular mortality. Risk assessment and appropriate patient treatment still remain, however, a difficult task, due to the variable clinical presentation and degree of hemodynamic instability in APE [1]. Ongoing myocardial injury has been found to precipitate fatal outcome in APE, since elevated plasma levels of cellular proteins released after tissue injury–cardiac troponins and myoglobin–were observed in some patients with APE. Brain natriuretic peptides released upon myocardial stretch were also found to be elevated in APE, especially APE accompanied by right ventricular dysfunction. Importantly, all these biomarkers were proven to be helpful for short-term risk stratification of APE patients [2], [3], [4], [5], [6], [7], [8].

Recently, cytoplasmic fatty acid-binding protein (H-FABP) was recognized as a more sensitive marker of minor myocardial damage than troponin T (cTnT) or myoglobin (Mb) [9]. This relatively small (15 kDa) cytoplasmic protein is abundantly expressed in tissues with an active fatty acid metabolism, such as heart and liver, and primarily facilitates the intracellular transport of long-chain fatty acids [10], [11]. Because of its small weight it appears in the circulation shortly after cell damage [9] and demonstrates both high sensitivity and specificity in the detection of myocardial injury [12], [13], [14], [15], [16], [17]. Therefore, we tried to assess which of the biomarkers of myocardial injury and overload is the most useful for short-term risk stratification in patients with APE.

Section snippets

Patients

We analyzed 77 patients (51 female, 26 male) aged 65.3 ± 16.0 years with APE confirmed by contrast-enhanced computed tomography [18] or lung ventilation/perfusion scintigraphy (PIOPED). Medical history was obtained on admission (concomitant diseases: coronary artery disease—CAD, congestive heart failure—CHF and renal insufficiency—RI with plasma creatinine levels > 2.0 mg/100 ml). On admission prior to treatment implementation transthoracic echocardiography (TTE) was performed using the

Treatment and clinical outcome

The characteristics of all patients are presented in Table 1. Nine (11.7%) patients suffered clinically massive APE, submassive APE was diagnosed in 43 (55.8%) patients, while the remaining 25 (32.5%) patients formed the group of nonmassive APE. Seventy one (92.2%) patients were anticoagulated, using either intravenous unfractionated heparin or subcutaneous low molecular weight heparin. Six (7.8%) patients initially presenting with clinically massive or deteriorating submassive APE received

Discussion

Right ventricular dysfunction is an independent predictor of fatal outcome in APE [22]. RV strain and systemic hypotension may cause hypoperfusion and hypoxia of the RV myocardium, resulting in myocardial stretch and damage, even in patients with normal coronary arteries. We observed higher plasma concentrations of the biochemical markers of RV strain–NT-proBNP–and myocyte damage–Mb, cTnT and H-FABP–in patients who died in the course of APE or had CCC. Importantly, Cox's multivariate regression

Acknowledgements

This study was partially supported by grant KBN2PO5B06927 of Polish State Committee for Scientific Research and by the Dutch Ministry of Economic Affairs, BTS grant 97.188 and the Dutch Technology Foundation grant GGN4680. Jan F.C. Glatz is Netherlands Heart Foundation Professor of Cardiac Metabolism.

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