Professional Documents
Culture Documents
The recent development of sensitive and specific assay pro- dial infarction, especially in postoperative patients, and-in the
cedures for the cardiac troponins has markedly improved the detection of cardiac contusion where the MB isoenzyme of
diagnosis of myocardial injury in adults.I, 2 Cardiac troponin
I measurements have proved useful in diagnosing myocar- See commentary, p. 853.
Submitted for publication June 21, 1996; accepted Nov. 15, 1996.
Dr. Jaffe and Dr. Ladenson are consultants to Dade International. I cTnI Cardiactroponin I [
CK-MB Creatine kinase, MB isoenzyme
Reprint requests: Michael Landt, PhD, Department of Pediatrics,
Washington University School of Medicine, One Children's Place,
St. Louis, MO 63110. creatine kinase can be elevated as a result of skeletal muscle
Copyright © 1997 by Mosby-Year Book, Inc. damage. 2-6
0022-3476/97/$5.00 + 0 9/21/79370 The reason for this improved accuracy is that release of
872
The Journal of Pediatrics Hirsch et al. 873
Volume 130, Number 6
cTIfl into the blood appears to be highly specific for cardiac ities of varying severity; and group B3, 7 patients (4 boys/3
injury. Cardiac troponin I is found only within the myocar- girls, mean age 126 months, range 44 to 220 months) with
dial cell and is a potent inhibitor of the process of actin-my- blunt chest trauma. These patients were suspected of having
osin cross-bridge formation] Fetal hearts contain two cTnI sustained cardiac contusions based on the nature of their in-
isoforms: the adult cardiac isoform and an isoform similar jury (obvious blunt trauma to the chest area, pulmonary
to that found in adult slow-twitch skeletal muscle. The contusion on chest radiograph, and hemodynamic instabil-
slow-twitch isoform is the predominant form in both rat and ity). They were classified as high likelihood or low likeli-
human fetal hearts, but with maturation, the slow-twitch hood of contusion by a clinician, unaware of their cTnI val-
isoform is replaced until at birth only the adult cardiac iso- ues, on the basis of their injuries and echocardiographic and
form is detectable, s This serves as the basis for a growing electrocardiographic findings.
number of literature reports about the specificity and sensi- Blood samples from these patients were collected when
tivity of cTnI as a marker for cardiac injury. 9 specimens for other laboratory evaluations were being
There is a need in pediatrics for a sensitive and specific obtained, and within 36 hours of admission.
test that would allow for the identification of myocardial cell All studies were conducted in accordance with a protocol
damage in either isolated conditions or associated with other approved by the Human Studies Committee of Washington
pathologic conditions. The clinical tests routinely used for University.
adults may not have the same sensitivity or specificity in Cardiac troponin I. Concentration of cTnI was assayed
children. The utility of measuring serum cTnI for diagnostic by a sandwich immnnoassay in a preliminary research
or screening purposes in a pediatric population is not yet application that recognizes two different epitopes of cTnI
known. Normal values have not been established, and the and has no detectable cross-reactivity with skeletal muscle
impact of congenital or acquired heart disease on serum cTnl troponin I. J The limit of detection for this assay is 1.5 ng/ml.
values is unclear. This study was conducted to clarify these This value is equivalent to a value of 0.4 ng/ml with the
issues. commercially available assay (Dade International). Labora-
tory personnel performing the assay were unaware of the
METHODS clinical status of the patients.
Patient population. Initial studies surveyed cTnI con- Echoeardiography. Apart from the ambulatory pediatric
centrations in two broad population groups (designated A patients (group A1), all patients had two-dimensional
and B) in relation to a variety of general pediatric diseases echocardiograms (Hewlett-Packard Sonos model 1500) per-
between Janum2¢ 1994 and December 1995. formed with standard views recommended by the American
Group A patients included ambulatory pediatric patients, Society of Echocardiography.10 Patients in the intensive care
further subdivkied into two groups: group A1, 120 ambula- unit (group B) had these evaluations performed within 24
tory pediatric patients (73 boys/47 girls, mean age 11.6 hours of admission, and usually within 12 hours of blood
months, range 0 to 29 months) without apparent heart dis- sampling for cTnI. Echocardiographic interpretation was
ease, but with a variety of other pediatric diseases (clinic pa- performed by a senior staff cardiologist who was unaware of
tients); and group A2, 96 patients (50 boys~46 girls, mean age the indication for the test or knowledge of patients' inclusion
47 months, range 0 to 228 months) with known congenital in the study.
and acquired cardiac diseases at various stages during their Electrocardiography. Patients with suspected cardiac
courses (patients in nonacute condition arriving for ongoing contusion underwent 12-lead electrocardiography (Mar-
therapy or surgical repair). qnette Electronics, Mac Vu electrocardiogram) within 24
Blood samples from these patients were collected when hours of admission, with standard 12-lead placement. Inter-
either routine laboratory tests were performed or in con- pretation was performed by a senior staff cardiologist
junction with preoperative evaluations. unaware of inclusion criteria for the study.
Group B patients included 59 inpatients in a multidisci- Statistical analysis. Statistical differences were assessed
plinary pediamc intensive care or neonatal intensive care by the Wilcoxon Rank Sum Test (significant values p <0.05).
setting who were included after the performance of echocar-
diography. The decision to request an echocardiogram in any RESULTS
patient was made,, by clinicians independent of knowledge of Serum cTnI values were less than 2.0 ng/ml in 117 of the
the study. Group B was further subdivided into three groups 120 ambulatory patients without cardiac disease (group A1)
according to the results of their echocardiograms: group B1, and were frequently below the level of detection for the as-
16 patients (10 boys/6 girls, mean age 26.2 months, range 0 say, regardless of diagnosis (Table IA). There was no age
to 204 months) shown to have no anatomic cardiac abnor- dependency evident in the cTnI values in these patients.
malities; group B2, 36 patients (17 boys/19 girls, mean age Three patients from this group had levels measured between
3.1 months, range 0 to 96 months) with cardiac abnormal- 2.0 and 4.8 ng/mi. Review of the patients' medical histories
874 Hirsch et al. The Journal of Pediatrics
June 1997
Table IA. Ambulatory pediatric patients (group A1) Table lB. Ambulatory cardiology patients (group A2)
(n = 120) (n = 96)
Table IIA. Intensive care patients with normal Table lIB. Intensive care patients with abnormal
echocardiograms (group B1) (n = 16) echocardiograms (group B2) (n = 36)
14. Langer JC, Winthrop AL, Wesson DE,'Spence L, Pearl RH, 18. Click RL, Holmes DR, Vlietstra RE, Kosinski AS, Kronmal
Hoffman MA, et al. Diagnosis and incidence of cardiac injury RA. Anomalous coronary arteries: location, degree of athe-
in children with blunt thoracic trauma. J Pediatr Surg 1989; rosclerosis and effect on survival a report from the coro-
24:1091-4. nary artery surgery study. J Am Coll Cardiol 1989;13:
15. Cummins B, Auckland ML, Cummins P. Cardiac-specific 531-7.
troponin-I radioimrnunoassay in the diagnosis of acute myo- 19. Eppenberger HM, Eppenberger M, Richterich R, Aebl H. The
cardial infarction. Am Heart J 1987;113:1333-44. ontogeny of creatine kinase isoenzymes. Dev Biol 1964; 10:1-
16. Nakamura Y, Fujita Y, Nagai M, Yanagawa H, Imada Y, 16.
Okawa S, et al. Cardiac sequelae of Kawasaki disease in chil- 20. Grant JW, Canter CE, Spray TL, Landt Y, Saffitz JE, Laden-
dren: statistical analysis. Pediatrics 1991; 88:1144-7. son JH, et al. Elevated donor cardiac troponin I, a marker of
17. Goorin AM, Borow KM, Goldman A, Wilfiams RG, Hender- acute graft failure in infant heart recipients. Circulation 1994;
son IC, Sallan SE, et al. Congestive heart failure due to adri- 90:2618-21.
amycin cardiotoxicity. Cancer 1981; 47:2810-6.