Persistent Increase of Cardiac Troponin I in Plasma without Evidence of Cardiac Injury Lindsay A. Legendre-Bazydlo, 1 Doris M. Haverstick, 1 Jamie L.W. Kennedy, 2 John M. Dent, 2 and David E. Bruns 1* CASE A 69-year-old man with diabetes mellitus type II, hy- pertension, dyslipidemia, and prior ischemic strokes presented to the emergency department with com- plaints of balance difficulties and inability to stand un- assisted of 2 weeks’ duration. The patient’s home medication regimen included atenolol, lisinopril, am- lodipine, metformin, and glipizide. He is a retired chef and a former smoker (20 pack-years). He has 2 broth- ers, both of whom had myocardial infarctions in their 50s. The patient’s physical examination was remark- able for frequent premature contractions, left lower ex- tremity weakness, and impaired coordination. His electrocardiogram revealed sinus rhythm with fre- quent premature ventricular contractions and diffuse nonspecific T-wave abnormalities. Results of a comprehensive metabolic chemistry panel were within the reference intervals except for in- creases in glucose (158 mg/dL; reference interval, 74 –99 mg/dL) and creatinine (1.5 mg/dL; reference in- terval, 0.7–1.3 mg/dL). The hemoglobin A 1c value was 7.4% (reference interval, 6.0%). Cardiac troponin I (cTnI) 3 concentrations were increased at 0.27, 0.22, and 0.25 g/L (Abbott Architect assay; 99th percentile, 0.03 g/L) over a span of approximately 8 h. The patient was admitted to the cardiology service on the basis of these abnormal results. A transthoracic echocardiogram revealed a pre- served left ventricular systolic function with evidence of impaired diastolic filling. A cardiac catheterization evaluation revealed an ulcerated plaque in the left an- terior descending artery with 70% stenosis, which was treated with a bare-metal stent. The presenting symptom of balance difficulty failed to resolve after the coronary intervention, and the patient remained un- able to stand unassisted. A neurologic evaluation in- cluded magnetic resonance imaging, which found no evidence of an acute stroke. He was discharged with a diagnosis of orthostatic hypotension. Three months later, the patient presented to the emergency department with several days of balance difficulty. The initial cTnI value was increased at 0.10 g/L, prompting admission to the cardiology service. Over the subsequent 12 h, cTnI values for 2 additional samples remained stable at 0.10 g/L. Other laboratory tests included a comprehensive metabolic panel and a complete blood count, with results within reference in- tervals except for a hemoglobin concentration of 12.5 g/dL (reference interval, 14.0 –18.0 g/dL) and a hemat- ocrit of 35.5% (reference interval, 40.0%–52.0%). The patient’s symptoms were not consistent with a car- diac etiology, and no further cardiac evaluation was pursued. A neurologic evaluation again found no evidence of acute stroke, and his symptoms were be- lieved to reflect a combination of orthostatic hypo- tension, pontine gliosis, and cerebellar atrophy. The unexplained abnormal troponin results prompted the attending cardiologist to contact the director of clinical chemistry. DISCUSSION Cardiac troponins play a central role in diagnosis and risk stratification in acute coronary syndromes (1), but troponins are recognized as markers of cardiac myo- cyte injury, not of the etiology of injury. A wide range of clinical conditions has been associated with increased 1 Department of Pathology and 2 Division of Cardiovascular Medicine, Depart- ment of Medicine, University of Virginia School of Medicine and Health Science Center, Charlottesville, VA. * Address correspondence to this author at: Department of Pathology, University of Virginia Health Science Center, Charlottesville, VA 22908. Fax 434-924-2574; e-mail DEB6J@virginia.edu. Received October 6, 2009; accepted December 8, 2009. DOI: 10.1373/clinchem.2009.138164 3 Nonstandard abbreviations: cTnI, cardiac troponin I; HAMA, human antimouse antibody; CK-MB, creatine kinase isoenzyme MB; cTnT, cardiac troponin T. QUESTIONS TO CONSIDER 1. Describe common pathologic reasons for increased plasma concentrations of cardiac troponins in the ab- sence of an acute coronary syndrome. 2. What analytical interferences increase measured cTnI concentrations? 3. How would you investigate the abnormal cTnI results in this patient? Clinical Chemistry 56:5 702–707 (2010) Clinical Case Study 702