American Heart Journal
Volume 145, Issue 5 , Pages 751-753, May 2003

Diagnosing and managing acute pulmonary embolism: role of cardiac troponins

  • Victor F. Tapson, MD

      Affiliations

    • Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, NC, USA
    • Corresponding Author InformationReprint requests: Dr Victor F. Tapson, Duke University Medical Center, Division of Pulmonary and Critical Care Medicine, 353D Bell Bldg, Durham NC 27710, USA.

Article Outline

 

See related article on page 821.

Acute pulmonary embolism (PE) accounts for between 60,000 and 200,000 deaths in the United States every year, and in many patients it is undiagnosed before death.1, 2 Because the symptoms and signs of acute PE are nonspecific, the diagnosis is frequently overlooked. Issues of substantial concern include recognizing PE when it is present and risk-stratifying for aggressive therapy. Diagnostic imaging studies are essential to accomplish each of these, but they are often delayed or nondiagnostic. Approaches that will facilitate these processes are essential. PE needs to be diagnosed quickly, and the decision regarding thrombolytic therapy needs to made as early as possible.

In the setting of acute coronary syndromes, cardiac troponins have proven useful in determining both diagnosis and prognosis.3 Subsequently, several prospective cohort studies have established that these enzymes may be elevated in acute PE.4, 5, 6, 7, 8 Because troponin level elevation is quite specific for cardiac myocyte damage, the heart remains the source of the enzyme elevation in acute PE. Not surprisingly, both cardiac troponin T (cTnT) and troponin I (cTnI) levels have been found to be elevated in acute PE and, in particular, in more massive PE in which myocyte injury caused by right ventricular strain might be expected. In this issue of the Journal, Mehta et al6 have expanded on the available data about the usefulness of cardiac troponin measurements in acute PE.

Four years ago, a French report of 29 patients with acute PE revealed that cTnI levels were elevated in 2 patients, both with submassive PE, and both patients survived.4 More recently, Giannitsis et al5 demonstrated that patients with more massive emboli often had elevated troponin levels. They examined 56 patients with PE that was, in most cases, confirmed by high-probability ventilation-perfusion scanning or pulmonary angiography (in 71% of cases). The remainder of cases were documented by less acceptable, but occasionally necessary, methods, such as echocardiographic right ventricular dysfunction with clinical presentation in the absence of pre-existing lung disease. Of the 56 patients, 76% had at least moderate-to-large emboli, and 30% of emboli were described as massive. A positive cTnT was demonstrated in 18 patients (32%) and only in those with moderate to large emboli. In addition, right ventricular dysfunction was found more often in patients with elevated cTnT levels. In 4 (7.1%) patients who were cTnT positive, acute myocardial infarction (MI) without characteristic electrocardiographic changes was suggested by creatine kinase (CK)/CK-MB values. Although it might appear possible that cTnT levels would be more likely to be elevated in acute PE in the setting of coronary artery disease, significant disease was revealed by coronary angiography to be in an equal distribution of cTnT-positive and cTnT-negative patients. The data from this study also demonstrated that patients with elevated cTnT values were at a higher risk for subsequent inhospital death. Not surprisingly, however, there were also marked mortality differences in patients with moderate versus massive PE (41.1% vs 7.7%). In a logistic regression analysis, cTnT remained the only independent predictor of inhospital death (adjusted odds ratio 15.2, 95% CI 1.22–190.37). This is interesting, but the broad CI suggests that larger numbers of patients should be studied.

As Mehta et al6 point out, another group recently reported on the association of cTnI with acute right ventricular dysfunction in patients with acute PE.7 In their patients, Meyer et al7 found that a significant minority with acute PE (39%) had elevated cTnI levels. In the cTnI-positive group, 63% had right ventricular dilation, compared with 27% in the cTnI-negative group. The cTnI-positive group also had significantly more segmental defects on ventilation-perfusion scanning than the cTnI-negative group. Finally, Douketis et al,8 from Hamilton, Ontario, Canada, reported on 26 patients with submassive PE (patients with hypotension or respiratory failure associated with the need for mechanical ventilation were excluded). In that study, 5 of 24 patients (20.8%) had elevated cTnI levels. One patient with PE had a level of 2.3 μg/L, which was suggestive of myocardial infarction. It was concluded that PE should be considered in the setting of a consistent clinical picture and elevated cTnI levels. Although these patients were not examined for subclinical coronary disease, it would not change the author’s opinion that PE should be considered in this setting.

Mehta et al6 have added more information to the pool of cTnI data. They studied 38 patients with acute PE, of whom 18 (47%) had elevated cTnI levels. Of these 18 patients, 12 (67%) had right ventricular dilation/hypokinesis, compared with only 3 of 20 patients (15%) without elevated cTnI levels (P = .004). Furthermore, patients with elevated cTnI levels had significantly higher right ventricular systolic pressures and a higher chance of developing cardiogenic shock (33% vs 5%, P = .01). The odds ratio for the latter was 8.8 (CI 2.5–21.0). This information supports the earlier data suggesting that cardiac troponin levels are often elevated in acute PE and that although the elevations may occur with smaller PEs, they are more common with more massive PEs and they seem to be associated with a poorer prognosis. So which test should be used? And how should they be used in clinical practice?

Whether cTnT or cTnI levels are used may be less important as long as it is realized that the cTnT assays are produced by a single manufacturer and have relatively uniform cutoff concentrations and a high degree of precision at the low end of the measuring range when used for acute MI.9 In contrast, the interassay variability for cTnI and variations in the cutoff concentrations for abnormal levels means that when cTnI levels are used, clinicians must refer to the cutoff values on the basis of the assay used in their hospital laboratory. This principle, which applies to acute coronary syndromes, would also apply when acute PE is considered. It would appear that elevated cardiac troponin levels could potentially contribute to risk-stratification of acute PE for aggressive therapy and to improved prognostication. There is the potential for hastening the diagnosis of acute PE and the diagnosis of early recurrence of PE.

It seems evident that massive PE associated with hypotension, and probably PE associated with extreme hypoxemia, are poor prognostic signs. It is often obvious when a patient with acute PE is severely ill and requires aggressive supportive care and thrombolytic therapy. Such patients are also the ones most likely to have elevated cTnT and cTnI values; in such settings, an elevated cardiac troponin level may add little to the diagnostic or therapeutic plan. Right ventricular dysfunction has been established as a predictor of increased likelihood of death from PE.10 Thrombolytic therapy in this setting may improve right ventricular function and potentially reduce mortality in patients with acute PE.10 In addition, in 1 study, the extent of perfusion abnormality has been shown to correlate with right ventricular dysfunction.11 However, the presence of bleeding risk and the diversity of the clinical presentation has prevented widespread acceptance of criteria for administering thrombolytic therapy. Certain clinical settings, such as mild to moderate right ventricular dysfunction or anatomically large emboli without severe hypoxemia or hypotension, have been less convincing of poor prognosis or the need for thrombolytic therapy. Thus, the troponins may be useful in helping us to better risk-stratify patients for thrombolytic therapy in 1 of these settings when hypotension or more severe right ventricular dysfunction are absent. They also might be a useful means of predicting deterioration in patients with smaller emboli. Once PE is diagnosed, a rise in serum troponin level might predict subsequent right ventricular failure and hypotension. It would seem, however, that on the basis of the presumed pathophysiology of a troponin “leak” caused by right ventricular damage from PE, that the elevated cardiac troponin level would be more a result of the latter, rather than a predictor. However, it is feasible that an increasing troponin level might occur with right ventricular strain before overt hypotension and, thus, be potentially useful in determining more aggressive therapy.

Certainly, troponin levels cannot be used like D-dimer testing; that is, they are not sensitive enough to rule out PE when clinical suspicion is relatively low, without additional diagnostic testing.12 Still, at present, perhaps the most important aspect of elevated cardiac troponin levels lies not in their prognostic value, but in their diagnostic value. The single most vexing problem involving acute PE is probably the failure to diagnose it. When patients have the usual nonspecific symptoms and signs of acute PE, such as dyspnea, chest pain, tachypnea, and tachycardia, the differential diagnosis is considerable, particularly in older patients with underlying cardiopulmonary disease. PE may not be initially considered, and this may have devastating consequences. Although an elevated cardiac troponin level cannot be considered diagnostic of acute PE, even in the absence of acute MI, elevated cardiac troponin levels might help clinicians to at least consider acute PE earlier in the diagnostic evaluation and then proceed to the necessary confirmatory diagnostic imaging.

It is important to also realize that patients who do not die within the first hour after having acute PE generally survive that PE, unless there is a recurrence. Although cTnT and cTnI levels remain elevated for days after acute MI (and likely after acute PE), perhaps subsequent rises might help in identifying recurrent emboli that would need to be confirmed by means of an imaging study to permit the appropriate therapeutic action (eg, inferior vena cava filter). This requires further study.

Future clinical studies should evaluate larger numbers of patients with PE and determine more precisely the sensitivity and specificity for PE and attempt to prognosticate and risk-stratify in less obvious settings. Larger studies are necessary to verify the data aforementioned and the often wide confidence limits. More information about acute PE and associated coronary artery disease with elevated troponin levels would be useful, although these elevations can occur in the absence of significant coronary disease.5 Prognosticating may never be simple, even with these markers, because the role of residual lower extremity thrombus after acute PE has occurred remains a poorly explored area. Patients with persistent, extensive deep venous thrombosis may have a higher mortality rate than patients without residual clots in the legs. Although this remains unproven, it is an area in which troponin levels wouldn’t be expected to help because they cannot reflect the residual thrombus burden. Additional studies could potentially clarify the role of cTnT and cTnI in suspecting early recurrence of PE.

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References 

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PII: S0002-8703(02)94705-8

doi:10.1016/S0002-8703(02)94705-8

American Heart Journal
Volume 145, Issue 5 , Pages 751-753, May 2003

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