Jeffrey Michel

Overuse of Troponin? A Comprehensive Evaluation of Testing in a Large Hospital System.

&NA; Troponin assays are integral to the diagnosis of acute myocardial infarction (AMI), but there is concern that testing is over utilized and may not conform to published guidelines. We reviewed all testing performed at 14 hospitals over 12 months and associated troponin values with the primary and secondary diagnoses for each visit. Troponin was determined to be negative, indeterminate or elevated based on reference ranges. The majority of troponin measurements were single, not serial (64%). The rate of AMI was low, with only 3.5% of tested patients having a primary or secondary diagnosis of AMI. Sensitivity, specificity and negative predictive value were excellent, exceeding 90%. However, positive predictive value was low, suggesting testing of populations with diseases known to be associated with elevated troponin levels in the absence of AMI. The majority (79%) of elevated troponin values were associated with primary diagnoses other than AMI. Only 28% of elevated troponins were associated with a primary or secondary diagnosis of AMI. These data suggest possible overuse of troponin testing in our healthcare system.

Dual antiplatelet compared to triple antithrombotic therapy in anterior wall acute myocardial infarction complicated by depressed left ventricular ejection fraction

Current guidelines recommend triple antithrombotic therapy (TT) consisting of warfarin, aspirin, and a P2Y12 inhibitor following an anterior ST elevation myocardial infarction (STEMI) complicated by extensive wall motion abnormalities. This recommendation, however, is based on data collected before percutaneous coronary intervention (PCI) became the standard of care for the treatment of STEMI. We designed a retrospective study of patients who received PCI for anterior STEMI over an 8-year period to compare rates of thromboembolic and bleeding events between patients receiving dual antiplatelet therapy (DAPT) and those receiving TT, including warfarin. Patients were included if the predischarge echocardiogram showed extensive wall motion abnormality and an ejection fraction ≤35%. Patients with known left ventricular thrombus were excluded. A total of 124 patients met the criteria, with 80 patients in the DAPT group and 44 in the TT group. The median age was 58 years in the TT group and 64 years in the DAPT group (P < 0.04), with an average ejection fraction of 31%. Thromboembolic events occurred in 4 patients (5%) in the DAPT group compared with 3 patients (6.8%) in the TT group (P = 0.70). Bleeding occurred in 2 patients in the DAPT group and 4 patients in the TT group (2.5% in DAPT vs. 9.1% in TT group, P = 0.18). No differences in rates of clinical embolism or left ventricular thrombus were found. Our data support recent findings that warfarin may not be indicated for patients following PCI for anterior STEMI, even when significant wall motion abnormalities and reduced ejection fraction ≤35% are present.

The trouble with troponin

D iagnostic tests are double-edged swords. They typically have good sensitivity when illness is likely but can contribute to misdiagnosis when disease prevalence is low. In cardiology, troponin has become an essential tool to diagnose or exclude acute myocardial infarction (AMI). However, discovery of elevated serum troponin in patients without AMI can confuse physicians and lead to poor decision making. An example is an 85-year-old woman with a urinary tract infection and an elevated serum troponin level defined as>99th percentile. Is the patient having a heart attack? Should heparin and dual antiplatelet therapy be started? Should she be taken to the cardiac catheterization lab for urgent coronary angiography? Should treatment of her urinary tract infection be modified? Does she have a poor prognosis? All too often this patient is admitted to a cardiac intensive care unit, is anticoagulated, and undergoes cardiac catheterization followed by percutaneous coronary intervention of coronary stenoses that are identified. Troponin testing to diagnose AMI developed in the early 1990s as an alternative to the creatinine kinase (CK) assays then in use. Interpretation of CK results required evaluating both the quantity and percentage of the cardiac-specific isoform (MB-CK). MB-CK can be produced by injured skeletal muscle, making AMI diagnosis difficult in patients with trauma or rhabdomyolysis. Troponins are proteins that exist in both skeletal and cardiac muscle as a ternary complex of I, T, and C subunits. They function to mediate the calcium-regulated interaction between actin and myosin. Cardiac-specific isoforms of the I and T isoforms exist that can be differentiated from skeletal muscle isoforms using monoclonal antibodies. These antibodies have been incorporated into assays for cardiac troponin testing that are now in widespread clinical use and are integral to the current third international universal definition of MI. Only ST-elevation MI can be diagnosed acutely in the absence of a myocardial biomarker elevation. However, research has shown that troponin is not a specific marker for AMI or ischemia and frequently accompanies noncardiac diseases including stroke, sepsis, and renal failure. The exact pathophysiology is unclear. Though some patients with ischemic heart disease suffer ischemic injury driven by increased cardiac performance, ischemic heart disease is not required for troponin elevation. Troponin elevation in hospitalized pediatric populations without ischemic heart disease has been documented, and development of high-sensitivity troponin assays has led to recognition that serum cardiac troponin can be detected in populations without acute disease. There is even evidence that troponin can be released from cardiac myocytes in the absence of cell death. In addition, recent studies suggest that a small amount of circulating troponin may be normal. When blood samples from over 150,000 individuals were tested using new very high-sensitivity assays, 80% had detectable troponin. Troponin elevation in the absence of AMI can create cognitive dissonance for physicians on the front lines of patient care. Under current guidelines, detecting troponin elevation provides half of the information needed to make a diagnosis of AMI. All that is then needed is a clinical setting consistent with acute myocardial ischemia and symptoms of ischemia. Patients with sepsis, pneumonia, cholecystitis, and acute gastrointestinal diseases often have nausea, shortness of breath, and pain. Many have known coronary artery disease or risk factors for ischemic heart disease. Many patients, including diabetic patients and women, have atypical symptoms when experiencing myocardial ischemia and infarction. To make matters worse, patients with elevated troponin are known to have worsened clinical outcomes in many non-AMI disease states. Physicians detecting troponin elevation in their patients have reason for concern. Data from our health care system indicate that 30% of hospitalized patients have troponin testing as part of their inpatient management. Fewer than 3% of hospitalized patients are diagnosed with AMI, many with ST elevation allowing diagnosis by electrocardiographic criteria alone. More than 70% of elevated troponin values identified in our health care

Rates of Echocardiography, Coronary Angiography, and Coronary Intervention Associated With Troponin Testing in Hospitalized Patients

Diagnosis of acute myocardial infarction (AMI) often depends on detection of cardiac troponin elevation >99th percentile. However, troponin elevation is commonly found in patients without AMI. We have previously reported an association between troponin elevation and rates of electrocardiogram (ECG), echocardiography (ECHO), and coronary angiography (CAG) in patients with a primary diagnosis of sepsis. We hypothesized that elevated troponin might be associated with greater use of ECHO and CAG in primary diagnoses other than sepsis and that this correlation might also include percutaneous coronary intervention (PCI). We reviewed all inpatient admissions to nine hospitals in Texas in 2016 collecting primary International Statistical Classification of Diseases and Related Health Problems (International Classification of Diseases-10) diagnoses, troponin test data, and the presence of ECHO, CAG, or PCI during hospitalization. We identified 56,895 unique inpatient admissions, of which 14,326 (25.2%) were associated with troponin testing. Of patients tested, 26.1% had one or more troponin I values ≥0.1 ng/ml (99th percentile). Primary ICD-10 diagnoses were grouped into (1) AMI, (2) primary diagnosis other than AMI (non-AMI), (3) congestive heart failure (CHF), (4) sepsis, and (5) Other excluding AMI, CHF, or sepsis. Troponin testing was itself associated with greater utilization of ECHO, CAG, and PCI in all groups except CHF. Troponin I values ≥0.1 ng/ml were associated with increased rates of ECHO, CAG, and PCI across all groups.

St-Elevation Acute Myocardial Infarction Due to Arterial Thrombosis in a 29-Year-Old Woman with Normal Coronary Arteries

Acute myocardial infarction (AMI) is rare in young adults. We present a case of a 29-year-old black woman who presented with an acute onset of chest pain while sleeping. Anterior wall ST-elevation AMI was diagnosed based on clinical presentation, electrocardiographic findings, and elevated cardiac biomarkers. Coronary angiography revealed a totally occluded proximal left anterior descending artery. The obstructing lesion, thrombus, was removed. There was no evidence of atherosclerotic disease or dissection. An evaluation for a hypercoagulable state was unrevealing. Echocardiography 1 year later revealed normal left ventricular wall motion and systolic function.

Usefulness of Released Cardiac Myosin Binding Protein-C as a Predictor of Cardiovascular Events

Cardiac myosin binding protein-C (cMyBP-C) is a heart muscle-specific thick filament protein. Elevated level of serum cMyBP-C is an indicator of early myocardial infarction (MI), but its value as a predictor of future cardiovascular disease is unknown. Based on the presence of significant amount of cMyBP-C in the serum of previous study subjects independent of MI, we hypothesized that circulating cMyBP-C is a sensitive indicator of ongoing cardiovascular stress and disease. To test this hypothesis, 75 men and 83 women of similar ages were recruited for a prospective study. They underwent exercise stress echocardiography to provide pre- and poststress blood samples for subsequent determination of serum cMyBP-C levels. The subjects were followed for 1 to 1.5 years. Exercise stress increased serum cMyBP-C in all subjects. Twenty-seven primary events (such as death, MI, revascularization, invasive cardiovascular procedure, or cardiovascular-related hospitalization) and 7 critical events (CE; such as death, MI, stroke, or pulmonary embolism) occurred. After adjusting for sex and cardiovascular risk factors with multivariate Cox regression, a 96% sensitive prestress cMyBP-C threshold carried a hazard ratio of 8.1 with p = 0.041 for primary events. Most subjects (6 of 7) who had CE showed normal ejection fraction on echocardiography. Pre-stress cMyBP-C demonstrated area under receiver operating curve of 0.91 and multivariate Cox regression hazard ratio of 13.8 (p = 0.000472) for CE. Thus, basal cMyBP-C levels reflected susceptibility for a variety of cardiovascular diseases. Together with its high sensitivity, cMyBP-C holds potential as a screening biomarker for the existence of severe cardiovascular diseases.

TROPONIN TESTING IN PATIENTS HOSPITALIZED FOR SEPSIS IS ASSOCIATED WITH INCREASED CARDIOVASCULAR TESTING AND LENGTH OF STAY

The 2012 ACCF expert opinion recommends against testing for troponins in sepsis. We recently reviewed troponin use in our system and found evidence of significant testing in septic patients. We hypothesized that such testing might be associated with an increased use of cardiovascular resources. We

COMPARING EMERGENCY ROOM AND INPATIENT TROPONIN TESTING: TOO MUCH AND TOO OFTEN?

Diagnosis of acute myocardial infarction (AMI) remains the only indication for troponin testing that is guideline based and has been shown to improve outcomes. We hypothesized that troponin testing in both the emergency room (ER) and inpatient (IP) settings is likely to include significant numbers