Persistent Increase of Cardiac Troponin I in Plasma without Evidence of Cardiac Injury

Abstract

CASEA 69-year-old man with diabetes mellitus type II, hypertension, dyslipidemia, and prior ischemic strokes presented to the emergency department with complaints of balance difficulties and inability to stand unassisted of 2 weeks' duration. The patient's home medication regimen included atenolol, lisinopril, amlodipine, metformin, and glipizide. He is a retired chef and a former smoker (20 pack-years). He has 2 brothers, both of whom had myocardial infarctions in their 50s. The patient's physical examination was remarkable for frequent premature contractions, left lower extremity weakness, and impaired coordination. His electrocardiogram revealed sinus rhythm with frequent premature ventricular contractions and diffuse nonspecific T-wave abnormalities.Results of a comprehensive metabolic chemistry panel were within the reference intervals except for increases in glucose (158 mg/dL; reference interval, 74 -99 mg/dL) and creatinine (1.5 mg/dL; reference interval, 0.7-1.3 mg/dL). The hemoglobin A 1c value was 7.4% (reference interval, Ͻ6.0%). Cardiac troponin I (cTnI) 3 concentrations were increased at 0.27, 0.22, and 0.25 g/L (Abbott Architect assay; 99th percentile, Ͻ0.03 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 preserved left ventricular systolic function with evidence of impaired diastolic filling. A cardiac catheterization evaluation revealed an ulcerated plaque in the left anterior descending artery with Ͼ70% 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 unable to stand unassisted. A neurologic evaluation included 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 intervals except for a hemoglobin concentration of 12.5 g/dL (reference interval, 14.0 -18.0 g/dL) and a hematocrit of 35.5% (reference interval, 40.0%-52.0%). The patient's symptoms were not consistent with a cardiac etiology, and no further cardiac evaluation was pursued. A neurologic evaluation again found no evidence of acute stroke, and his symptoms were believed to reflect a combination of orthostatic hypotension, pontine gliosis, and cerebellar atrophy. The unexplained abnormal troponin results prompted the attending cardiologist to contact the director of clinical chemistry. DISCUSSIONCardiac troponins play a central role in diagnosis and risk stratification in acute coronary syndromes (1 ),...

An unexpected rise in cardiac troponin I in a patient with multiple myeloma

“…In addition, PEG precipitation does not identify the mechanism of the interaction between the monoclonal peak and cTnI. In addition, we did not demonstrate in the present case cTnI removal by protein A, protein G or antihuman immunoglobulin,3 as the clinical course of the patient including normal coronary angiography, did not motivate us to perform additional analyses. Nevertheless, PEG precipitation of IgG followed by other confirmatory techniques may help unveil the absence of ‘true’ increased serum cTnI concentration and avoid invasive procedures that may be harmful in these frail patients.…”

Probabilistic Bayesian reasoning can help identifying potentially wrong immunoassays results in clinical practice: even when they appear ‘not-unreasonable’

“…11 False-positive case reports have been widely reported in the recent literature though interestingly, the number of false-negative case reports is lower. 11,29 It is important also to re-emphasize that the effects of interference, either negative or positive, may persist for a long time depending on the underlying cause that triggered the production of interfering immunoglobulin antibodies. Protocols such as repeat analysis after 6 -12 h or 6 -18 h from onset may be unhelpful or even misleading if the initial reading is false.…”

False Elevation of Troponin in a Case of Multiple Myeloma

“…Domanski et al reported a case of a 62-year-old with persistently elevated troponin; he had extensive cardiac testing, including an angiogram, that was unrevealing, like our case [2]. Macrotroponin is a complex of immunoglobulin and cardiac troponin rarely reported in myeloma cases, COVID vaccination, and COVID infection and can falsely elevate troponin levels [2][3][4]. Adding polyethylene glycol to the patient's serum precipitates immunoglobulins, frees troponin molecules, and normalizes the troponin value [2][3][4].…”

“…It is also a red flag and a marker of increased mortality and morbidity in almost every condition associated with elevated troponin levels, such as sepsis, pulmonary embolism, tachycardia, anemia, stroke, and congestive heart failure [1]. Heterophil antibodies and autoantibodies can rarely interfere with high-sensitivity troponin assay causing falsely elevated troponin and myocardial infarction misdiagnosis [2][3][4].…”