Plasma heart-type fatty acid binding protein is superior to troponin and myoglobin for rapid risk stratification in acute pulmonary embolism
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.
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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.
References (30)
- et al.
Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry
Lancet
(1999) - et al.
Myoglobin stratifies short-term risk in acute major pulmonary embolism
Clin Chim Acta
(2003) - et al.
Cardiac troponin T monitoring identifies high-risk group of normotensive patients with acute pulmonary embolism
Chest
(2003) - et al.
Fatty acid-binding proteins as plasma markers of tissue injury
Clin Chim Acta
(2005) - et al.
Cellular fatty acid-binding proteins: their function and physiological significance
Prog Lipid Res
(1996) - et al.
The fatty acid transport function of fatty acid-binding proteins
Biochim Biophys Acta
(2000) - et al.
Release of fatty acid-binding protein from isolated rat heart subjected to ischemia and reperfusion or to the calcium paradox
Biochim Biophys Acta
(1988) - et al.
Cardiovascular risk stratification of pulmonary embolism
Am J Cardiol
(1996) - et al.
Pericardial fluid level of heart-type cytoplasmatic fatty acid-binding protein is an indicator of severe myocardial ischemia
Int J Cardiol
(2004) - et al.
Prognostic value of elevated circulating heart-type fatty acid binding protein in patients with congestive heart failure
J Card Fail
(2005)
Leakage of heart fatty acid binding protein with ischemia and reperfusion in the rat
J Mol Cell Cardiol
Importance of cardiac troponins I and T in risk stratification of patients with acute pulmonary embolism
Circulation
Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism
Circulation
Prognostic role of brain natriuretic peptide in acute pulmonary embolism
Circulation
N-terminal pro-brain natriuretic peptide or troponin testing followed by echocardiography for risk stratification of acute pulmonary embolism
Circulation
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