Cardiac Spectacular

Mayura Phadtare, PGY-3

Emergency Medicine

Question

What is a sufficient interval of serial

biomarkers to exclude MI and/or ACS for

patients presenting to ED with chest pain?

Question

Which biomarkers?

What interval?

What is negative (zero or trend)?

Objectives

- Troponins

- Brief overview

- History

- Assays

- Other biomarkers

It’s all about the biomarkers…

Overview

-A complex of 3 contractile regulatory proteins

-released into circulation in response to myocardial necrosis

The biology of troponin

3-unit troponin complex (troponin I, T and C)

1 cardiac troponin I

4 cardiac troponin T isomers

Can be expressed in diseased skeletal muscle

tissue

Brief history

1999

National Academy of Clinical Biochemistry

2000

European Society of Cardiology (ESC) and American College of Cardiology (ACC) - recommend 99th percentile should be measurable with an imprecision (coefficient of variation) of 10% or less.

2004

First assay created to meet standards

Characteristics of troponin

assaysCystolic pool of unbound protein

6% trop T; 3% trop I

13–15-fold increased amount of troponin per gram of myocardium is mostly complexed

Half-life is about 2hours

Huge variability in assay sensitivity

heterogeneity of the antibodies and matrix components of the assays

various fragments of troponin circulate; antibodies used in the various assays detect these fragments differently

Troponin I vs Troponin T

Assessing the Requirement for the 6-Hour Interval

between Specimens in the American Heart Association

Classification of Myocardial Infarction in Epidemiology

and Clinical Research StudiesAndrew R. MacRae, Peter A. Kavsak, Viliam Lustig,Rakesh Bhargava, Rudy Vandersluis,Glenn E. Palomaki,

Marie-Jeanne Yerna, and Allan S. Jaffe

Here at Henry Ford

- Ultra cTnI (Centaur Instrumentation)

- 0.2 ng/mL (detect 0.04 ng/mL)

- Turn around time 30min

- use green top (lithium heparnized) tubes

2007 Guidelines:ACCF 2012 Expert Consensus Document

- A rise and/or fall of biomarkers (preferably

troponin)

- Elevations in biomarkers after PCI in patient

having normal pre-intervention troponin

levels

- Elevations in biomarkers in patients

following CABG and with normal baseline

troponin levels

Third universal definition of MI published

The 2012 document sets out the levels of

troponin required for a diagnosis of

procedural related myocardial infarction

after percutaneous coronary intervention

(PCI), coronary bypass (CABG), other

cardiac procedures, and non-cardiac

procedures

Other biomarkers

Myelopyroxidase (MPO)

Ischemia-induced alubim (IMA)

CRP

NT-proBNP

Mid-regional pro-adrenomedullin peptide (MR-

proADM)

Mid-regional pro-atrial natriuretic peptide (MR-

proANP)

Final Thoughts

- Troponins play a pivotal role in defining MI

- Higher sensitivity assays allowing for

decreased intervals

- Importance of rise/fall of troponins

- Future of biomarkers

References

Aldous, Sally et al. A 2hr thrombolysis in myocardial infarction score outperforms other risk stratification tools in patients presenting with possible acute coronary syndromes: Comparison of chest pain risk stratification tools. American Heart Journal. v 164 (4). pp 209-218. Oct 2012.

Aldous, Sally et al. High-sensitivity troponin T for early rule-out of myocardial infarction in recent onset chest pain. Emerg Med J. v 29. pp 805-810. Nov 2011.

Goodacre, Steve et al. The Randomised Assessment of Treatment using Panel Assay of Caridac Markers (RATPAC) trial: a randomised controlled trial of point-of-care cardiac markers in the emergency department. Heart. v 97. pp 190-196. Sept 2010.

Hamm, Christian et al. Emergency Room Triage of Patients with Acute Chest Pain by Means of Rapid Testing for Cardiac Troponin T or Troponin I. The New England Journal of Medicine. v 337 (23). pp 1648-1653. Dec 1997.

Keller, Till et al. Serial Changes in Highly Sensitive Troponin I Assay and Early Diagnosis of Myocardial Infarction. JAMA. v 306 (24). pp 2684-2693.

MacRae, Andrew et al. Assessing the Requirement for the 6-hour Interval between Specimens in the American Heart Association Classification of Myocardial Infarction in Epiddemiology and Clinical Research Studies. Clinical Chemistry. v 52 (5). pp 812-818. 2006.

Mueller, Matthias et al. Absolute and Relative Kinetic Changes of High-Sensitivity Cardiac Troponin T in Acute Coronary Syndrome and in Patient with Increased Troponin in the Absence of Acute Coronary Syndrome. Clinical Chemistry. v 58 (1). pp 209-218. 2012.

Newby, L. Kristin et al. ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations. Journal of the American College of Cardiology. v 60 (23). 2012.

Reichlin, Tobias et al. One-Hour Rule-out and Rule-in of Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin T. Arch Intern Med. v 172 (16). pp 1211-1218. Aug 2012.

Than, Martin et al. 2-Hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker. Journal of the American College of Cardiology. v 59 (23). pp 2091-2098. 2012.

Than, Martin et al. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): aprospective observational validation study. Lancet. v 377. pp 1077-1084. March 2011.