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Elevated Cardiac Troponin Levels in Patients With Submassive Pulmonary Embolism
James D. Douketis, MD, FRCP;
Mark A. Crowther, MD, MSc, FRCP;
Eric B. Stanton, MD, FRCP, FACC;
Jeffrey S. Ginsberg, MD, FRCP
Arch Intern Med. 2002;162:79-81.
ABSTRACT
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Background Cardiac troponins are reliable markers of myocardial injury that are
being used increasingly in patients presenting with undifferentiated chest
pain or dyspnea to diagnose an acute coronary syndrome. If elevated cardiac
troponin levels also occur in patients with pulmonary embolism because of
right ventricular dilation and myocardial injury, such patients could be misdiagnosed.
We performed a prospective cohort study to determine the prevalence of elevated
cardiac troponin I (cTnI) levels in patients with submassive pulmonary embolism.
Methods Consecutive patients with objectively confirmed submassive pulmonary
embolism and no previous history of ischemic heart disease, other cardiac
disease, or renal insufficiency were included. Creatine kinase and cTnI levels
were measured within 24 hours of clinical presentation on 2 occasions 8 to
12 hours apart.
Results Of 24 patients with submassive pulmonary embolism, 5 (20.8%) had elevated
cTnI levels of 0.4 µg/L or higher (95% confidence interval, 7.1-42.2%).
One of these patients had a cTnI level higher than 2.3 µg/L that was
suggestive of myocardial infarction.
Conclusion Pulmonary embolism should be considered in the differential diagnosis
of patients presenting with undifferentiated chest pain or dyspnea and an
elevated cardiac troponin level.
INTRODUCTION
CARDIAC troponins, which include cardiac troponin I (cTnI) and cardiac
troponin T (cTnT), are highly sensitive and specific markers of myocardial
injury that are being used increasingly in the assessment of patients presenting
with undifferentiated chest pain or dyspnea to diagnose an acute coronary
syndrome.1-3 Cardiac
troponins are more sensitive and specific markers of myocardial ischemia than
the creatine kinase myocardial isoenzyme and, in general, are not influenced
by acute skeletal muscle injury.4 However,
elevated cardiac troponin levels also occur in patients with renal insufficiency5 and/or nonischemic cardiac conditions, such as severe
congestive heart failure, myocarditis, and infiltrative cardiomyopathy.3
Massive pulmonary embolism, defined as pulmonary embolism associated
with systemic hypotension, cardiogenic shock, or respiratory failure,6 is another condition that results in myocardial injury
and elevated creatine kinase levels,7-10
probably as a result of acute right ventricular dilation and strain that is
caused by a large embolus.11 However, because
cardiac troponins are highly sensitive to minor myocardial injury that occurs
in patients with unstable angina,12 it is biologically
plausible that elevated cardiac troponins might also occur in patients with
submassive pulmonary embolism who are hemodynamically stable. In support of
this contention, prospective cohort studies have found that 40% to 55% of
patients with pulmonary embolism have right ventricular dilation documented
by echocardiography, which might result in transient right ventricular strain
and myocardial injury.13-14 If
elevated cardiac troponin levels occur frequently in patients with submassive
pulmonary embolism, this could result in the misdiagnosis of patients presenting
with undifferentiated chest pain or dyspnea. Therefore, we performed a prospective
cohort study to determine the prevalence of elevated cTnI levels in patients
with submassive pulmonary embolism.
PATIENTS AND METHODS
PATIENTS
Consecutive patients with submassive pulmonary embolism who were diagnosed
at St Joseph's Hospital, Hamilton, Ontario, between March 1, 1999, and May
30, 2000, were considered for this study. Patients were included if pulmonary
embolism was confirmed by a high-probability ventilation-perfusion lung scan,
pulmonary angiography, spiral computed tomography of the chest, or a nondiagnostic
lung scan and deep vein thrombosis confirmed by findings from a duplex ultrasound
or venography. Patients were excluded if they had massive pulmonary embolism
associated with systemic hypotension (ie, systolic blood pressure <90 mm
Hg), cardiogenic shock, respiratory failure that required mechanical ventilation,
a history of confirmed ischemic heart disease, congestive heart failure or
cardiomyopathy, or renal insufficiency (ie, serum creatinine level >150 mmol/L).
MEASUREMENT OF cTnI AND CREATINE KINASE AND ANALYSIS
As part of the patients' regularly scheduled blood testing, measurement
of cTnI and creatine kinase was performed within 24 hours of presentation
on 2 occasions 8 to 12 hours apart. Myocardial ischemia was defined by an
elevated cTnI level of 0.4 µg/L or higher, and myocardial infarction
was defined by a cTnI level higher than 2.3 µg/L. An elevated creatine
kinase level was defined as higher than 220 U/L in men and higher than 150
U/L in women. A quantitative immunofluorescent enzyme assay was used to measure
cTnI, and creatine kinase was measured by an enzymatic rate reaction assay
(both assays by Abbott Diagnostics, Abbott Park, Ill).The prevalence of an
elevated cTnI level in patients with submassive pulmonary embolism was expressed
as a proportion, with a corresponding 95% confidence interval.
RESULTS
PATIENTS
During the 15-month study period, 26 patients were identified with submassive
pulmonary embolism that was confirmed by a high-probability ventilation-perfusion
lung scan (n = 19), spiral computed tomography of the chest (n = 3), or a
nondiagnostic lung scan and deep vein thrombosis on duplex ultrasound (n =
4). Two patients were excluded because they were transferred to another institution
prior to cTnI testing, leaving 24 patients in the study. Patients received
initial treatment with low-molecular-weight heparin (n = 14), unfractionated
heparin (n = 8), or a thrombolytic drug (n = 2), followed by warfarin, which
was administered to achieve an international normalized ratio of 2.0 to 3.0.
OUTCOMES
Of the 24 patients with submassive pulmonary embolism, 5 (20.8%) had
an elevated cTnI level of 0.4 µg/L or higher (95% confidence interval,
7.1-42.2). In one of these patients, the cTnI level higher than 2.3 µg/L
was suggestive of myocardial infarction, and another patient had an elevated
creatine kinase level of 890 U/L (normal,  220 U/L). The clinical characteristics
of the 5 patients with elevated cTnI levels are provided in Table 1. At presentation, one of these patients had transient hypotension
that resolved following the administration of intravenous fluids, and 2 patients
had a right ventricular strain pattern on the 12-lead electrocardiogram. No
patient with normal cTnI levels had electrocardiographic evidence of right
ventricular strain.
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Clinical Characteristics of Patients With Pulmonary Embolism and Elevated
Cardiac Troponin I Levels*
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COMMENT
In this small study of 24 patients with submassive pulmonary embolism,
5 (20.8%) had elevated cTnI levels. This finding is clinically relevant because
pulmonary embolism and acute coronary syndromes are common diseases that can
present with nonspecific and overlapping clinical features. The potential
for misdiagnosis, which may be influenced by elevated troponin levels, was
illustrated in a recent report in which a patient with presenting symptoms
caused by pulmonary embolism was initially considered to have a myocardial
infarction because of elevated cTnT levels and suggestive electrocardiographic
findings.15
To our knowledge, 2 other prospective cohort studies have investigated
the prevalence of elevated cardiac troponin levels in patients with pulmonary
embolism.16-17 In these studies,
the study populations seemed to have more extensive pulmonary embolism than
our patients. In the first study,16 elevated
cTnT levels occurred in 18 (32%) of 56 patients with pulmonary embolism. However,
17 patients (30%) were classified as having massive pulmonary embolism and
11 (20%) had a previous myocardial infarction. Such patients were excluded
from our study. In the second study,17 elevated
cTnI levels occurred in 2 (7%) of 29 patients with pulmonary embolism. Although
details about the patients' clinical presentation were not provided, 7 patients
presented with cardiogenic shock or syncope, 6 patients received thrombolytic
therapy, and 4 patients underwent pulmonary thrombectomy, thereby suggesting
a more unstable clinical presentation than the patients in our study.
There are potential limitations of this study. First, patients were
not investigated to determine if they had subclinical coronary artery disease
that would have predisposed them to myocardial ischemia when pulmonary embolism
occurred. However, even if some patients did have underlying coronary artery
disease, this would not change our conclusion that pulmonary embolism should
be considered in patients with undifferentiated chest pain or dyspnea and
elevated cTnI levels. Second, we did not investigate the prognostic significance
of elevated cTnI levels in patients with pulmonary embolism, as elevated troponins
might identify patients who are at increased risk of death.16
Third, this study was small and we cannot exclude that the prevalence of elevated
cTnI levels in patients with pulmonary embolism may be as high as 42% or as
low as 7%. Additional studies are needed in large heterogeneous populations
with pulmonary embolism to provide accurate estimates of the prevalence and
clinical importance of elevated cTnI levels in such patients.
In the meantime, clinicians should be aware of conditions such as pulmonary
embolism that are associated with elevated cardiac troponin levels in the
absence of an acute coronary syndrome. Pulmonary embolism should be considered
in the differential diagnosis of patients presenting with undifferentiated
chest pain or dyspnea and an elevated cTnI level.
AUTHOR INFORMATION
Accepted for publication April 9, 2001.
Dr Douketis is the recipient of a research scholarship from the Heart
and Stroke Foundation of Canada; Dr Crowther is the recipient of a research
scholarship from the Canadian Institutes of Health Research, Ottawa, Ontario;
and Dr Ginsberg is the recipient of a career investigator award from the Heart
and Stroke Foundation of Canada.
Corresponding author and reprints: James D. Douketis, MD, FRCP, St
Joseph's Hospital, Room F-538, 50 Charlton Ave E, Hamilton, Ontario, Canada
L8N 4A6 (e-mail: jdouket{at}mcmaster.ca).
From the Department of Medicine, McMaster University (Drs Douketis,
Crowther, Stanton, and Ginsberg) and St Joseph's Hospital (Drs Douketis, Crowther
and Stanton), Hamilton, Ontario.
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