Heart Lecture 2 PDF

Heart and Muscle Damage Dr Karan Rana  Learning Outcomes You will be aware of the different biomarkers of heart damage and the isoforms which are specific to disease. The role of Pro-BNP as a biomarker of heart damage Biomarkers  Could we use a biomarker of cardiac tissue...

Heart and Muscle Damage Dr Karan Rana  Learning Outcomes You will be aware of the different biomarkers of heart damage and the isoforms which are specific to disease. The role of Pro-BNP as a biomarker of heart damage Biomarkers  Could we use a biomarker of cardiac tissue damage to differentiate unstable angina, STEMI and NSTEMI? Chest pain ECG Biomarker of tissue damage Unstable angina STEMI  NSTEMI       Serum troponins as biomarkers Isoforms (coded for by different genes) Troponin T (three Fast Slow twitch Heart isoforms) twitch muscle Binds to tropomyosin muscle Troponin C (two Fast Slow twitch isoforms) twitch muscle, binds Ca2+ muscle Heart Troponin I (three Fast Slow twitch Heart isoforms) twitch muscle prevents myosin binding muscle to actin unless Ca2+ is bound to C  Which ones can be used as biomarkers for AMI? Serum troponins as biomarkers  Use of troponin I and troponin T has caused a redefinition of AMI.  Assay of Troponins  All assays use a capture antibody and a detection antibody with some sort of label attached.  Only one Troponin T assay (Roche patent).  Several Troponin I assays using different antibodies.  Lack of primary reference troponin I makes standardisation difficult. NICE guidance on troponins  Recommended biochemical marker for diagnosing AMI is troponin (I or T).  Take at least two samples: one on admission and one 10-12 hours after the onset of symptoms.  One component alongside evidence from the nature and timing of clinical symptoms, ECG, or imaging tests, to make a diagnosis.  Other causes of troponin release include myocarditis (inflammatory disease of the myocardium) or pulmonary embolism (which leads to right ventricular dysfunction). Are troponins good biomarkers?  Tissue specific (i.e. only present within one tissue).  Rapid release in response to damage. Mean  Very low in serum of normal individuals. URL: upper  Easily measured and with clear and universal reference limit reference values. 95%  Main problem is in deciding what is an abnormal 2.5% 2.5% -1.96 S.D. +1.96 S.D. result.  Each laboratory should ideally establish the 99th percentile reference limit. Isoforms of Creatine Kinase  Three genes: CK-M, CK-B and CK-Mt (mitochondrial enzyme)  Enzymes exist as dimers, which one would you use for AMI detection?  Creatine kinase MB may be specific for heart, but the proportion of CK-MB can increase in muscle in trauma, extreme exercise training or in disease (muscular dystrophy). Is creatine kinase MB a good biomarker?  Enzyme assay with immuno-inactivation of the M subunit so that only the B subunit activity is measured.  Better is a mass immunoassay using monoclonal antibodies.  Tissue specific (i.e. only present within one tissue).  Rapid release in response to damage.  (Very) low in serum of normal individuals.  Easily measured and with clear and universal reference values. Heart Failure  Failure of the heart to fill (diastolic) or eject (systolic) blood.  Can use B-type naturetic peptides as biomarkers. Is a BNP a good biomarker?  Serum level predominantly reflects stress on the atrial and ventricle wall.  Production and release induced in heart failure. BNP acts a hormone to reduce the ‘load’ on the heart.  Raised NT-proBNP or BNP should lead to echocardiography (ultrasound) to confirm diagnosis.  Increase in naturetic peptides can occur other than in heart failure (e.g. aortic stenosis).  A normal NT-proBNP or BNP results has strong negative predictive value for heart failure.  NB: this is a biomarker which is induced not released.  Summary  Principles of using serum enzymes, other proteins and metabolites as diagnostic tools.  Methods involved in measuring the above.  Apply such principles to the diagnosis of the conditions acute myocardial infarction and heart failure. Recommended Reading.  Chapter 7 Clinical Enzymology and Biomarkers in: Clinical Biochemistry ed. Nessar Ahmed (2011).  Apply the criteria to assessing the following as diagnostic indicators of AMI:  Myoglobin.  ‘Heart-specific’ lactate dehydrogenase.  Any questions?? [email protected]