Rajiv Gandhi University of Health Science Karnataka, Bangalore-41

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCE KARNATAKA, BANGALORE-41

PROFOMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

NAME OF THE CANDIDATE JACKSON B

ADDRESS DEPARTMENT OF BIOCHEMISTRY

ST.JOHN’S MEDICAL COLLEGE HOSPITAL,

BANGALORE-560034 COURSE OF STUDY MSC MLT

SUBJECT BIOCHEMISTRY

TITLE CORRELATION OF CARDIAC TROPININ I

WITH ECG FINDINGS IN PATIENTS

SUSPECTED OF ANGINA.

NEED FOR THE STUDY Identification of patients who present with acute chest pain at high risk for major cardiac events is a common and difficult challenge. Until recently, the initial evaluation of such patient relied on data from history, physical examination and electrocardiogram. [1-3] The cardiac markers used were Creatine Kinase (CK), Creatine Kinase MB (CK- MB) and Lactate dehydrogenase (LDH) to assess the severity of Acute Myocardial Infarction (AMI) [4]. Investigation of CK and CK-MB fraction indicate that these tests are of limited prognostic value in the initial evaluation. Furthermore among patient in whom AMI has been excluded, CK-MB has not correlated with subsequent major complications. [4-9] In recent years considerable investigative interest has focused on new markers of myocardial injury, especially on the cardiac troponins. [10-13] Previous studies with small sample sizes have demonstrated the prognostic value of cardiac troponin I (cTnI) for risk stratification in patients with unstable angina. [14-17] Although these data suggest that cTnI is more sensitive and specific than CK-MB and lactate dehydrogenase for detection of myocardial damage at the cellular level, most clinical studies have been restricted to high risk patients with unstable angina or myocardial infraction. [18-20] In this study, I am focusing on correlating the cTnI with ECG finding in patients with suspected angina and further investigating the applicability of cTnI in low risk patient. REVIEW OF LITERATURE

MYOCARDIAL INFARCTION Many patients with AMI may die within the first few hours of onset, while remainder suffers from effects of impaired cardiac function. It may occur particularly in young people, who develop atherosclerosis due to major risk factors like hypertension, diabetes mellitus, cigarette smoking familial hyper cholestrolaemia etc. Males, throughout their life are at a significantly higher risk of developing MI as compared to females. Women during reproductive period have remarkably low incidence of MI, probably due to the protective influence of oestrogen. Infarcts are most frequently located in the left ventricle. Left atrium is protected from infarction because it is supplied by oxygenated blood in the left arterial chamber. Region of infarction Stenosis of the left anterior descending coronary artery. Stenosis of the right coronary artery. Stenosis of the left circumflex coronary artery.

ANGINA It is a clinical syndrome resulting from transient myocardial ischemia. It is characterized by paroxysmal pain in the substernal or pericardial region of the chest which is aggravated by an increase in the demand of the heart and relived by a decrease in the work of the heart , often the pain radiates to the left arm, neck, jaw or right arm. Three overlapping clinical pattern of angina Stable or typical angina. Prinzmetals variant angina. Unstable or crescendo angina.

Stable or typical angina Is characterized by attacks of pain following physical exertion or emotional excitement and it is relived by rest. The pathogenesis of condition lies in chronic stenosis coronary atherosclerosis.

Prinzmetals variant angina This pattern of angina is characterized by pain at rest and has no relationship with physical activity.

Unstable or crescendo angina It is characterized by more frequent onset of pain of prolonged duration and occurring often at rest.

CARDIAC MARKERS Certain protein and enzymes are released into the blood from necrotic heart muscle after myocardial infarction [22].

Aspartate Transaminase (AST) The estimation of AST is of historical important only in current practice because of its non-specificity [22].

LACTATE DEHYDROGENASE (LDH) Total LDH estimation also lacks specificity since these enzymes are present in various tissues besides myocardium such as in skeletal muscle, kidney, liver, lungs and red blood cells. LDH has two isoforms of which LDH-1 is myocardial specific. Estimation of ratio of LDH-1: LDH-2 above 1 is reasonably helpful in making a diagnosis. LDH level begin to rise after 24 hours, reach peak in 3 to 6 days and return to normal in 14 days.

CREATINE KINASE (CK) [22] It has three forms CK-MM derived from skeletal muscle. CK-BB derived from brain and lungs and CK-MB derived from cardiac muscle and insignificant amount from extra cardiac tissue. The total CK estimation lacks specificity while elevation of CK-MB isoenzyme is considerably specific for myocardial damage. CK-MB has further 2 forms-CK-MB2 is the myocardial form while CK-MB1 is extra cardiac form. A ratio of CK-MB2: CK- MB1above 1.5 is highly sensitive for the diagnosis of acute MI after 4-6 hours of onset of myocardial ischemia. CK-MB disappears from blood by 48 hours. Investigation of creatine kinase (CK) and CK-MB fraction indicate that these tests are of limited prognostic value in the initial evaluation [22]. Furthermore, among patients in whom acute myocardial infarction has been excluded CK-MB has not correlated with subsequent major complications [22].

TROPONINS [22] New cardiac serum marker has rendered LDH estimation obsolete. Troponins are contractile muscle proteins present in human cardiac and skeletal muscle. But cardiac troponins are specific for myocardium.

These are two types of cardiac troponin Cardiac troponin T[cTnT] Cardiac troponin I [cTnI] Both are not found in the blood normally. But after myocardial injury their levels rise very high around the same time. When CK-MB is elevated (i.e. after 4 - 6 hours), both troponin levels remains high for much longer duration, cardiac troponin I for 7-10 days and cardiac troponin T for 10-14 days [21]. Increased serum and plasma cardiac troponins in patients with chest pain now aid in the diagnosis of myocardial infarction and in the differentiation and guidance of management of patients with ischemia having unstable angina. OBJECTIVES

1. To correlate cTnI with ECG findings in patients suspected of angina. 2. To study cTnI level in patients with suspected angina. DESIGN OF STUDY It is a retrospective, observational study conducted in Department of Biochemistry, SJMCH A. SOURSE OF DATA In-patients of SJMCH, suspected of acute myocardial infarction with associated presenting complaints of acute chest pain, whose samples were sent to Biochemistry lab for evaluation of their cardiac troponin I were included in the study Since it’s a retrospective study, patients with elevated cardiac troponin I (greater than 0.04 ng/mL) were selected for the study. On review of their medical records, the cardiac outcome (ECG findings) will be used to evaluate and correlate with cTnI

B.SAMPLE SIZE 100 patients would be selected for the study. All patients (n = 1300) who had their cTnI evaluation during the three month period (August 2009 to October 2009) formed the population of interest. A total of 130 patients were selected based on the criteria. Sample size of 100 patients were chosen from 130 patients based on simple random sampling.

C.1. INCLUSION CRITERIA All patients with cTnI > 0.04 ng/mL were included in the study. The initial evaluation of cTnI of the patient was considered. C.2. EXCLUSION CRITERIA All patients with cTnI < 0.04 ng/mL were excluded All those patients who were on follow up for repeat evaluation of cTnI were excluded because the treatment is initiated based on ECG and / with the initial value of the cTnI. The subsequent values are used for further monitoring the patient. Patients with renal insufficiency and end – stage renal disease are excluded. D.METHODOLOGY Cardiac Troponin I (cTnI) Done by technique: Chemiluminescence Analysed on Access 2 from Beckman coulter Principle of Chemiluminescence The Access Accu TnI assay is a two-site immunoenzymatic (sandwich) assay. A sample is added to a reaction vessel along with monoclonal anti-cTnI antibody conjugated to alkaline phosphatase and paramagnetic particles coated with monoclonal anti-cTnI antibody. The human cTnI binds to the anti-cTnI antibody on the solid phase, while the anti-cTnI antibody-alkaline phosphatase conjugate reacts with different antigenic sites on the cTnI molecules. After incubation in a reaction vessel, materials bound to the solid phase are held in a magnetic field while the unbound materials are washed away. Then, the chemilumniscent substrate Lumi-Phos 530 is added to the vessel and the light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of cTnI in the sample. The amount of analyte in the sample is determined from a stored, multi-point calibration curve.

CARDIAC OUT COME Cardiac outcome of interest is ECG findings Type of Instrument: ELI250 MORTARA

E.STATISTICAL ANALYSIS Descriptive statistics is used to summarize the observed data. Logistic regression is used to evaluate the relationship between cTnI and ECG findings Chi-square test will be used to test the significance REFERENCES

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22. Fred SA, Henderson AR. Cardiac Function. In: Burtis AC and Ashwood ER (editors). Tietz Textbook of Clinical Chemistry. 3rd edn. Asia: Harcourt Brace & Company and W B Saunders Company 1999:1178-1203. SIGNATURE OF CANDIDATE

NAME AND DESIGNATION OF Dr. Anitha D GUIDE Associate Professor Department of Biochemistry St. John’s Medical College, Bangalore - 34 SIGNATURE

REMARKS OF THE GUIDE It’s a retrospective study. The student is capable of carrying out the study and it is feasible with the existing infrastructure and facilities. HEAD OF THE DEPARTMENT Dr. Sultana Furruqh Professor & Head; I/c Clinical Biochemistry Department of Biochemistry St. John’s Medical College, Bangalore-34 REMARKS

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