Cardiac enzymes. 2 – Non enzyme proteins The Troponins Dr Muhammad Ramzan

Cardiac Troponin – the definition A muscle protein Cardiac Troponins are the regulatory proteins that control the Calcium mediated interactions B/W Actin and Myosin Cardiac Troponin consists of 2 subunits and include Troponin I (cTnI) and Troponin T (cTnT)) www.merriam – Webster.com – J Clin Pathol.2004

Cardiac Troponins (cTn) – the background non enzyme proteins Troponin is a muscle protein of 3 subunits (cTnI, cTnT and cTnC) and a part of native Tropomycin (Tc is for Ca binding .SK muscles) Cardiac Troponin are low/absent in smooth muscles Have different AA sequence for their detection through Monoclonal antibody assay Troponins are released into the plasma in response to cardiac (MI) and skeletal muscle damage Alpert et al,2000

Cardiac Troponins – the properties bound and free floating cTn are coded by specific genes and are unique to Cardiac muscles Have shorter half life of 90 min. appears 3-4 hours after symptoms Majority of the cTn are bound to myofilaments but remainder is free floating in the cytoplasm This is in comparison to the CKMB which is fully Cytosolic cTn levels are normally too low to be detected in plasma Have no base line Alpert et al,2000 (Tunstall- Paedo et al. 1994) – www.wikepedia.com

Cardiac Troponins – 2 Peaks and clearance cTn has 2 peaks – an early and late Early Peak / Cytosolic pool of cTn is released first in the blood Late peak / level is maintained by the degradation of myofilaments cTn has no base line with slow clearance (7- 14 days), to the CKMB which get cleared in 3- 4 days Neumayr et al,2001

Elevation of Troponins in MI

Release of cTn – the mechanism injury to the car. Cell membrane Cardiac injury occurs when membrane of normal cardiac myocyte is damaged ( Ischaemic cell death) It results in the loss of intracellular and structural proteins like Troponins; CK, LDH,blood, and Myoglobin into : Extra cellular space - the biomarkers The subsequent release is maintained by the degradation of the Actin and Myosin filaments

Injury to Card. Cell - Release of cTn

Cardiac Troponin – 2 Types There are 2 types of Troponins, present in cardiac muscles with certain differences Cardiac Troponin T - cTnT Cardiac Troponin I - cTnI Major cause for their elevation is CAD/ MI

Elevated cTn – Non CAD conditions1 Elevated levels of cTn are also found in non coronary artery (CAD) related conditions Like: Critically ill patients with non CAD – 50% Tachycardia - 28% Pancreatitis/heavy exercise - 10% Heart failure - 5% Bakshi et al; 2002 – Korff et al;2006

Diagnostic value of cTn Detection and monitoring of the cTn is the new standard in the differential diagnosis of the of the : Unstable angina and non ST elevation MI in ACS patients 1 It is also significant in the following conditions: Acute MI; Myocardial re- infarction, post procedural MI and 2 diagnosis of MI after non cardiac surgery 3 Braunwald et al;2000 -

Cardiac biomarkers - significance the features These are the molecules released into blood after myocardial damage and enhance the ability of the clinician: to manage the patient after chest pain (blood, urine and tissues) The important cardiac biomarkers are : The Typical rise and gradual fall in cTn or : 1 A more rapid rise and fall in CKMB and others 2 Rama Chandran Vasan ;2006

Myocardial infarction (MI) - the definition It is the death of an area of myocardium as a result of sudden and complete obstruction of blood supply Most common cause of the MI is the occlusion of the coronary artery or one of its branches MI is characterized by the history; Physical examination,ECG, cardiac imaging and cardiac biomarkers

Criteria for MI – 2 Classes Expert consensus document Criteria for the diagnosis of MI is divided into 2 according to the Expert Consensus Document This document was agreed upon by the experts from the : European Society of Cardiology (ESC), American College of Cardiology (ACC) and American Heart Association (AHA) 1. Criteria for an acute, evolving or recent MI 2. Criteria for the established MI

Diagnosis of MI - acute /recent / evolving MI. A. one of the biomarkers Criteria for acute, evolving or recent MI Either one of the following criteria, satisfies the diagnosis for acute/evolving/recent MI 1. Cardiac Biomarkers: Typical rise and gradual fall of cTn or More rapid rise and fall (CKMB) (one of cardiac bio markers- cTn – CKMB )

Diagnosis of MI . Acute/recent. B ECG changes/symptoms At least one of the followings: 1.Ischaemia symptoms – severe pain/pressure in the chest 2. Development of pathological Q waves on ECG, 3. ECG changes indicative of Ischaemia like ST segment elevation or depression 4.Coronary artery intervention (Coronary angioplasty) J Am Coll Cardiol Sep;36(3): 959- 69 –ESC/ACC/AHA

Normal Electrocardiogram - ECG

Pathological Q wave

MI – ST segment elevation

MI- ST segment depression

Diagnosis of MI - Established MI 2 ECG and structural heart changes Criteria for the established MI Any one of the following criteria satisfies the diagnosis for the established MI 1.Patient may or may not remember the symptoms 1 2.. Development of new pathological Q waves on serial ECG 2 3.Biochemical markers of MI may have normalized-with time 4. Pathological findings of a healed/healing MI (Echo .Imaging) 3 (1. New patho.Q wave 2. echo +imaging of healed infarcts)

Difference B/W Cardiac Troponins (cTn) and Creatine Kinase (CK- CKMB) Serial NO Cardiac Troponins CKMB 1 Are non enzyme proteins Are enzyme proteins 2 Are specific to cardiac myosites Also present in skeletal muscles 3 Normal serum levels are too low to be detected, has no base line Normal serum levels are detected – has base line 4 Majority is bound to cardiac myofilaments Majority is unbound and fully Cytosolic 5 Rapid rise and gradual fall with Late clearance Rapid rise and fall in MI early clearance 6 Elevated levels Predicts the adverse out come in CAD No such property 7 Predicts the infarct size Do not predict

Cardiac biomarkers- the time table