The working diagnoses that were considered based on the patient's presentation were as follows:
In this case, 12 year-old boy had elevated cTnI along with ECG change. Although most of these findings are consistent with AMI, very rapid decline of cardiac enzymes (especially cTnI), the young age of the patient, the echocardiogram finding, the concurrent LLL pneumonia and the rapid recovery in the clinical course made the diagnosis of AMI unlikely, however, myocardial ischemia/infarction was not completely ruled out.
The boy has a very strong family history of hypertension and cardiac disease, in that "paternal great grandfather died suddenly of heart attack at 26 years of age.". However, detailed information about it is unobtainable, and whether his great grandfather died of acute MI or other diseases such as a fatal arrhythmia, is uncertain.
LDL-C was only marginally elevated, and TG and VLDL-C were elevated in this case. Elevated LDL-C or TC and low levels of HDL-C are well known risk factors of cardiovascular disease. Recently, the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III) by the National Cholesterol Education Program (NCEP) released the updated recommendations for cholesterol testing and management, in that TG and lipoprotein remnants or VLDL-C are listed as "Emerging Cardiovascular Risk Factors" (1). This patient has elevated TG and VLDL-C and these are considered as cardiac risk factors under the new guideline.
Despite of the presence of these cardiac risk factors, there were several points contradictory to the diagnosis of myocardial ischemia/infarction in this case.
First, it is extremely unusual for 12 year-old boy developing myocardial ischemia/infarction, unless the child has other morbidities such as Kawasaki disease, or mucocutaneous lymph node syndrome. Patients with Kawasaki disease can develop arrhythmia, myocarditis and coronary aneurysm as long term cardiac sequelae (2). Echocardiogram should reveal the presence of aneurisms in coronary arteries, and ECG should detect arrhythmia, both of which were absent in this case. Besides, the patient lacks the constellation of symptoms of Kawasaki disease.
The hospital course is also inconsistent with the diagnosis of myocardial infarction. The symptoms subsided very rapidly with inhalation of 2 agonist, which should not have resolved symptoms of myocardial ischemia/infarction. The alleviation of chest pain by inhalation of 2 agonist suggests the involvement of respiratory system as a source of chest pain rather than cardiac origin. cTnI stays elevated up to a week in myocardial infarction, and the rapid decline of cTnI is also against myocardial infarction.
Myocarditis is cardiac inflammation that is most commonly the result of an infectious process. Clinically significant acute myocarditis in the United States is caused most commonly by viruses, especially coxsackievirus B (3). Clinical presentations of myocarditis are variable, ranging from an asymptomatic to profound cardiogenic shock. The most obvious symptom suggesting myocarditis is an antecedent viral syndrome with fever, myalgias, and malaise. Chest pain may occur in up to 35 percent of patients and may be typically ischemic, somewhat atypical, or pericardial in character. Occasionally patients will present with a clinical syndrome identical to an acute myocardial infarction, with ischemic chest pain and ST-segment elevations on the ECG (4). Although the presence of antecedent viral syndrome and the association between his left lower lobe pneumonia and myocarditis are unclear, the symptoms of this patient could be explainable by myocarditis.
Laboratory findings of myocarditis include leukocytosis, eosinophilia, and an elevated erythrocyte sedimentation rate (ESR). Although virus infection is the most common cause of myocarditis, a rise in virus antibody titer only demonstrates the response to a recent viral infection and is not necessarily indicative of active myocarditis (4). Endomyocardial biopsy is the critical test to confirm the diagnosis, but the procedure is quite invasive and its limited sensitivity and specificity have been pointed out (5). In this case, the blood counts, ESR, viral titer, and endomyocardial biopsy were not performed, and the confirmation of myocarditis was not obtained.
Smith and her colleagues studied the experimental and clinical correlations between elevated cardiac troponin I and myocarditis (6). In this Myocarditis Treatment Trial, they measured values of cTnI and CK-MB in the sera of patients with a histological diagnosis of myocarditis and compared with values measured in patients with unexplained congestive heart failure (CHF) but no evidence of myocarditis on endomyocardial biopsy. Among myocarditis patients, 18 out of 53 patients (34%) were found to have elevated cTnI values, but only 3 out of 53 patients (5.7%) had elevated CK-MB values (P =0.001), whereas 4 out of 35 unexplained CHF patients (11%) were found to have an elevated cTnI level, and none of these 35 patients had elevated CK-MB values (P = 0.07). cTnI values were significantly greater in patients with myocarditis than in control patients (P=0.01), whereas CK-MB values were not significantly greater in patients with myocarditis than in control patients (P=0.27). The sensitivity of an elevated cTnI for the diagnosis of myocarditis is 0.34, the specificity is 0.89, and the positive predictive value is 0.82. They also showed that cTnI elevations did not correlate with the histological severity of myocarditis either in patients or in mice with autoimmune myocarditis.
Troponin complex is on the thin filament of skeletal and myocardial muscles, and the current guidelines from the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction (MI) recommend cTnI as a preferred marker due to its high sensitivity (7). cTnI elevations indicate the presence of myocardial injuries, not necessarily acute ischemia. Various conditions, such as myocarditis, acute pericarditis, heart failure and pulmonary embolism are known to cause cTnI elevations, and it is critical to correlate cTnI elevations with clinical information for accurate diagnosis (8). Based on the discussions above, the elevation of cTnI in this case is thought to be caused from myocarditis rather than myocardial is infarction.
As discussed above, laboratory results alone do not confirm the correct diagnosis in this case, and this case reminds laboratory physicians of the importance of clinical correlation for interpretation of laboratory results.
Contributed by Kenichi Tamama, MD, PhD and Mohamed A. Virji, MD, PhD