Considerations for early acute myocardial infarction rule-out for emergency department chest pain patients: the case of copeptin

Abstract The evaluation of patients admitted at the emergency department (ED) for chest pain is challenging and involves many different clinical specialists including emergency physicians, laboratory professionals and cardiologists. The preferable approach to deal with this issue is to develop joint protocols that will assist the clinical decision-making to quickly and accurately rule-out patients with non life-threatening conditions that can be considered for early and safe discharge or further outpatient follow-up, rule-in patients with acute coronary syndrome and raise the degree of alert of the emergency physicians on non-cardiac life-threatening emergencies. The introduction of novel biomarkers alongside the well-established troponins might support this process and also provide prognostic information about acute short-term or chronic long-term risk and severity. Among the various biomarkers, copeptin measurement holds appealing perspectives. The utility of combining troponin with copeptin might be cost-effective due to the high negative predictive value of the latter biomarker in the rule-out of an acute coronary syndrome. Moreover, in the presence of a remarkably increased concentration (e.g., more than 10 times the upper limit of the reference range), to reveal the presence of acute life-threatening conditions that may not necessarily be identified with the use of troponin alone. The aim of this article is to review current evidence about the clinical significance of copeptin testing in the ED as well as its appropriate placing within diagnostic protocols.

[1]  Benjamin R. McClintic,et al.  Approach to the Patient with Chest Pain , 2012 .

[2]  H. Katus,et al.  Combined testing of high-sensitivity troponin T and copeptin on presentation at prespecified cutoffs improves rapid rule-out of non-ST-segment elevation myocardial infarction. , 2011, Clinical chemistry.

[3]  Alan S Maisel,et al.  Short-term mortality risk in emergency department acute heart failure. , 2011, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[4]  P. Ponikowski,et al.  Increased 90-Day Mortality in Patients With Acute Heart Failure With Elevated Copeptin: Secondary Results From the Biomarkers in Acute Heart Failure (BACH) Study , 2011, Circulation. Heart failure.

[5]  U. Lotze,et al.  Combined determination of highly sensitive troponin T and copeptin for early exclusion of acute myocardial infarction: first experience in an emergency department of a general hospital , 2011, Vascular health and risk management.

[6]  J. Köhrle,et al.  Copeptin and peroxiredoxin-4 independently predict mortality in patients with nonspecific complaints presenting to the emergency department. , 2011, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[7]  W. Rottbauer,et al.  Copeptin does not add diagnostic information to high-sensitivity troponin T in low- to intermediate-risk patients with acute chest pain: results from the rule out myocardial infarction by computed tomography (ROMICAT) study. , 2011, Clinical chemistry.

[8]  S. Anker,et al.  Comparison of the temporal release pattern of copeptin with conventional biomarkers in acute myocardial infarction , 2011, Clinical Research in Cardiology.

[9]  Brandy Drake A 2-h Diagnostic Protocol to Assess Patients with Chest Pain Symptoms in the Asia-Pacific region (ASPECT): A Prospective Observational Validation Study , 2011 .

[10]  Leong L Ng,et al.  C-terminal provasopressin (copeptin) as a prognostic marker after acute non-ST elevation myocardial infarction: Leicester Acute Myocardial Infarction Peptide II (LAMP II) study. , 2011, Clinical science.

[11]  B. Riou,et al.  High-sensitivity versus conventional troponin in the emergency department for the diagnosis of acute myocardial infarction , 2011, Critical care.

[12]  J. Rehfeld,et al.  Association of copeptin and N-terminal proBNP concentrations with risk of cardiovascular death in older patients with symptoms of heart failure. , 2011, JAMA.

[13]  A. Hall,et al.  The RATPAC (Randomised Assessment of Treatment using Panel Assay of Cardiac markers) trial: a randomised controlled trial of point-of-care cardiac markers in the emergency department. , 2011, Health technology assessment.

[14]  S. Kristensen,et al.  A third troponin T blood sample is not cost-effective in patients with suspected non-ST segment elevation acute coronary syndrome , 2011, Scandinavian journal of clinical and laboratory investigation.

[15]  K. Wahbi,et al.  Combination of copeptin and high-sensitivity cardiac troponin T assay in unstable angina and non-ST-segment elevation myocardial infarction: a pilot study. , 2011, Archives of cardiovascular diseases.

[16]  A. Khera,et al.  Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. , 2010, JAMA.

[17]  N. Morgenthaler,et al.  Copeptin and risk stratification in patients with acute dyspnea , 2010, Critical care.

[18]  James McCord,et al.  Testing of low-risk patients presenting to the emergency department with chest pain: a scientific statement from the American Heart Association. , 2010, Circulation.

[19]  Mario Plebani,et al.  Recommendations for the use of cardiac troponin measurement in acute cardiac care. , 2010, European heart journal.

[20]  N. Morgenthaler,et al.  Copeptin: a biomarker of cardiovascular and renal function. , 2010, Congestive heart failure.

[21]  H. Litt,et al.  Evaluation of the patient with acute chest pain. , 2010, Radiologic clinics of North America.

[22]  Mario Plebani,et al.  The “hospital central laboratory”: automation, integration and clinical usefulness , 2010, Clinical chemistry and laboratory medicine.

[23]  A. Jaffe,et al.  Biological and analytical variability of a novel high-sensitivity cardiac troponin T assay. , 2010, Clinical chemistry.

[24]  S. Sandberg,et al.  Can changes in troponin results be useful in diagnosing myocardial infarction? , 2010, Clinical chemistry.

[25]  Alan S. Go,et al.  Population trends in the incidence and outcomes of acute myocardial infarction. , 2010, The New England journal of medicine.

[26]  A. Jaffe,et al.  Being rational about (im)precision: a statement from the Biochemistry Subcommittee of the Joint European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation Task Force for the definition of myocardial infarction. , 2010, Clinical chemistry.

[27]  S. Blankenberg,et al.  Copeptin improves early diagnosis of acute myocardial infarction. , 2010, Journal of the American College of Cardiology.

[28]  A. Maisel,et al.  The utility of biomarkers in sorting out the complex patient. , 2010, The American journal of medicine.

[29]  L. Rydén,et al.  Copeptin, IGFBP-1, and Cardiovascular Prognosis in Patients With Type 2 Diabetes and Acute Myocardial Infarction , 2010, Diabetes Care.

[30]  M. Kontos,et al.  Emergency department and office-based evaluation of patients with chest pain. , 2010, Mayo Clinic proceedings.

[31]  Nader Rifai,et al.  What is a biomarker? Research investments and lack of clinical integration necessitate a review of biomarker terminology and validation schema , 2010, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[32]  D. Bruns,et al.  Assessing the impact of biomarkers on patient outcome: An obligatory step , 2010, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[33]  M. Scott When do new biomarkers make economic sense? , 2010, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[34]  E. Dobos,et al.  Guidelines for the use of biomarkers: Principles, processes and practical considerations , 2010, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[35]  D. Morrow Clinical application of sensitive troponin assays. , 2009, The New England journal of medicine.

[36]  A. Gass,et al.  Copeptin: A novel, independent prognostic marker in patients with ischemic stroke , 2009, Annals of neurology.

[37]  N. Morgenthaler,et al.  Incremental value of copeptin for rapid rule out of acute myocardial infarction. , 2009, Journal of the American College of Cardiology.

[38]  F. Apple,et al.  Role of monitoring changes in sensitive cardiac troponin I assay results for early diagnosis of myocardial infarction and prediction of risk of adverse events. , 2009, Clinical chemistry.

[39]  Filippo Ottani,et al.  Percorso di valutazione del dolore toracico. Valutazione dei requisiti di base per l'implementazione negli ospedali italiani , 2009 .

[40]  M. Plebani,et al.  Cardiac troponins: what we knew, what we know – where are we now? , 2009, Clinical chemistry and laboratory medicine.

[41]  A. Giannoni,et al.  Measurement of circulating concentrations of cardiac troponin I and T in healthy subjects: a tool for monitoring myocardial tissue renewal? , 2009, Clinical chemistry and laboratory medicine.

[42]  A. Wu,et al.  Short- and long-term biological variation in cardiac troponin I measured with a high-sensitivity assay: implications for clinical practice. , 2009, Clinical chemistry.

[43]  D. Cohen,et al.  Interpreting the results of cost-effectiveness studies. , 2008, Journal of the American College of Cardiology.

[44]  J. Struck,et al.  C-terminal provasopressin (copeptin) is associated with left ventricular dysfunction, remodeling, and clinical heart failure in survivors of myocardial infarction. , 2008, Journal of cardiac failure.

[45]  G. Filippatos,et al.  Natriuretic peptides in acute coronary syndromes: prognostic value and clinical implications. , 2008, Congestive heart failure.

[46]  N. Morgenthaler,et al.  Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level. , 2008, Neuro endocrinology letters.

[47]  M. Christ-Crain,et al.  Copeptin: a new and promising diagnostic and prognostic marker , 2008, Critical care.

[48]  J. Struck,et al.  Copeptin: clinical use of a new biomarker , 2008, Trends in Endocrinology & Metabolism.

[49]  J. Alpert,et al.  Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction , 2008 .

[50]  M. Emdin,et al.  Distribution of plasma cardiac troponin I values in healthy subjects: pathophysiological considerations , 2008, Clinical chemistry and laboratory medicine.

[51]  Jeroen J. Bax,et al.  Universal definition of myocardial infarction. , 2007 .

[52]  J. Struck,et al.  COPEPTIN, A STABLE PEPTIDE OF THE ARGININE VASOPRESSIN PRECURSOR, IS ELEVATED IN HEMORRHAGIC AND SEPTIC SHOCK , 2007, Shock.

[53]  G. Lippi,et al.  How many troponins should we measure to get a clinically significant result? , 2007, QJM : monthly journal of the Association of Physicians.

[54]  J. Struck,et al.  C-Terminal Provasopressin (Copeptin) as a Novel and Prognostic Marker in Acute Myocardial Infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) Study , 2007, Circulation.

[55]  Fred S Apple,et al.  National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical characteristics and utilization of biochemical markers in acute coronary syndromes. , 2007, Circulation.

[56]  Robert H Christenson,et al.  National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. , 2007, Clinical chemistry.

[57]  W. Gibler,et al.  The role of cardiac risk factor burden in diagnosing acute coronary syndromes in the emergency department setting. , 2007, Annals of emergency medicine.

[58]  R. Redberg,et al.  The prognostic value of normal exercise myocardial perfusion imaging and exercise echocardiography: a meta-analysis. , 2007, Journal of the American College of Cardiology.

[59]  Maureen Chase,et al.  Prospective validation of the Thrombolysis in Myocardial Infarction Risk Score in the emergency department chest pain population. , 2006, Annals of emergency medicine.

[60]  Jawahar Kalra,et al.  Impact of the cardiac troponin testing algorithm on excessive and inappropriate troponin test requests. , 2006, American journal of clinical pathology.

[61]  Harry P. Selker,et al.  Presentations of Acute Myocardial Infarction in Men and Women , 1997, Journal of General Internal Medicine.

[62]  J. Struck,et al.  Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. , 2006, Clinical chemistry.

[63]  J. Struck,et al.  Copeptin, a stable peptide derived from the vasopressin precursor, is elevated in serum of sepsis patients , 2005, Peptides.

[64]  M. Gheorghiade,et al.  Vasopressin antagonism in heart failure. , 2005, Journal of the American College of Cardiology.

[65]  A. Jeremias,et al.  Narrative Review: Alternative Causes for Elevated Cardiac Troponin Levels when Acute Coronary Syndromes Are Excluded , 2005, Annals of Internal Medicine.

[66]  C. S. Gal,et al.  Non-peptide vasopressin V1b receptor antagonists as potential drugs for the treatment of stress-related disorders. , 2005, Current pharmaceutical design.

[67]  Fred S Apple,et al.  Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome. , 2005, Clinical chemistry.

[68]  Jeroen J. Bax,et al.  Seven-year follow-up after dobutamine stress echocardiography: impact of gender on prognosis. , 2005, Journal of the American College of Cardiology.

[69]  R. Hendel,et al.  Acute resting myocardial perfusion imaging in patients with diabetes mellitus: results from the emergency room assessment of sestamibi for evaluation of chest pain (ERASE Chest Pain) trial , 2004, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[70]  R. Lima,et al.  Incremental prognostic value of myocardial perfusion 99m-technetium-sestamibi SPECT in the elderly. , 2004, International journal of cardiology.

[71]  S. Dixon,et al.  Randomised controlled trial and economic evaluation of a chest pain observation unit compared with routine care , 2004, BMJ : British Medical Journal.

[72]  S. Goodacre,et al.  Cost effectiveness of diagnostic strategies for patients with acute, undifferentiated chest pain , 2003, Emergency medicine journal : EMJ.

[73]  R. Davey Troponin testing: an audit in three metropolitan hospitals , 2003 .

[74]  H. Joller-jemelka,et al.  Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes. , 2003, Journal of the American College of Cardiology.

[75]  E. Amsterdam,et al.  Immediate Exercise Testing to Evaluate Low-Risk Patients Presenting to the Emergency Department with Chest Pain. , 2003 .

[76]  C. S. Gal,et al.  The vasopressin V1b receptor as a therapeutic target in stress-related disorders. , 2003, Current drug targets. CNS and neurological disorders.

[77]  I. Olivotto,et al.  Effectiveness of a multidisciplinary chest pain unit for the assessment of coronary syndromes and risk stratification in the Florence area. , 2002, American heart journal.

[78]  S. Campbell,et al.  A prospective, observational study of a chest pain observation unit in a British hospital , 2002, Emergency medicine journal : EMJ.

[79]  M. Runge,et al.  Randomized comparison of a strategy of predischarge coronary angiography versus exercise testing in low-risk patients in a chest pain unit: in-hospital and long-term outcomes. , 2001, Journal of the American College of Cardiology.

[80]  V. Roger,et al.  Prognostic value of exercise echocardiography in 2,632 patients > or = 65 years of age. , 2001, Journal of the American College of Cardiology.

[81]  R Ruthazer,et al.  Missed diagnoses of acute cardiac ischemia in the emergency department. , 2000, The New England journal of medicine.

[82]  E. Antman,et al.  The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. , 2000, JAMA.

[83]  E W Steyerberg,et al.  Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. , 2000, Circulation.

[84]  J. McMurray,et al.  “Chest pain—please admit”: is there an alternative? , 2000, BMJ : British Medical Journal.

[85]  E. Amsterdam,et al.  Evaluation of chest pain suspicious for acute coronary syndrome: use of an accelerated diagnostic protocol in a chest pain evaluation unit. , 2000, The American journal of cardiology.

[86]  S. Zarich,et al.  The Goldman algorithm revisited: prospective evaluation of a computer-derived algorithm versus unaided physician judgment in suspected acute myocardial infarction. , 1999, American heart journal.

[87]  E. Amsterdam,et al.  Immediate exercise testing of low risk patients with known coronary artery disease presenting to the emergency department with chest pain. , 1999, Journal of the American College of Cardiology.

[88]  H. Schunkert,et al.  Evidence for a vasopressin system in the rat heart. , 1999, Circulation research.

[89]  R. Walls,et al.  Clinical correlates and prognostic significance of early negative exercise tolerance test in patients with acute chest pain seen in the hospital emergency department. , 1998, The American journal of cardiology.

[90]  C. Heeschen,et al.  Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. , 1997, The New England journal of medicine.

[91]  L. Graff,et al.  Impact on the care of the emergency department chest pain patient from the chest pain evaluation registry (CHEPER) study. , 1997, The American journal of cardiology.

[92]  J. Muhlestein,et al.  An emergency department-based protocol for rapidly ruling out myocardial ischemia reduces hospital time and expense: results of a randomized study (ROMIO). , 1996, Journal of the American College of Cardiology.

[93]  R B D'Agostino,et al.  Missed diagnoses of acute myocardial infarction in the emergency department: results from a multicenter study. , 1993, Annals of emergency medicine.

[94]  R. Conroy,et al.  Does intensive medical therapy influence the outcome in unstable angina? , 1990, Clinical cardiology.

[95]  J. Cohn Neuroendocrine activation after acute myocardial infarction. , 1990, The American journal of cardiology.

[96]  I. Sand Litigation against the emergency physician. Common features in cases of missed myocardial infarction , 1990 .

[97]  E F Cook,et al.  A computer protocol to predict myocardial infarction in emergency department patients with chest pain. , 1988, The New England journal of medicine.

[98]  G. So The prognostic importance of asymptomatic ischemic episodes in patients with unstable angina pectoris. , 1987 .

[99]  M. Weisfeldt,et al.  Silent ischemia predicts infarction and death during 2 year follow-up of unstable angina. , 1987, Journal of the American College of Cardiology.

[100]  G W Rouan,et al.  Clinical characteristics and natural history of patients with acute myocardial infarction sent home from the emergency room. , 1987, The American journal of cardiology.

[101]  S. Gottlieb The prognostic importance of asymptomatic ischemic episodes in patients with unstable angina pectoris. , 1987, Herz.

[102]  F. Harrell,et al.  The prognosis for patients with new-onset angina who have undergone cardiac catheterization. , 1983, Circulation.

[103]  R. Gokal,et al.  The syndrome of inappropriate antidiuretic hormone secretion associated with acute myocardial infarction. , 1977, Postgraduate medical journal.