From,

Dr. Lulu Cyriac,

Post Graduate in Department of General Medicine,

A.J. Institute of Medical Sciences,

Mangalore 575004

To,

The Registrar,

Rajiv Gandhi University of Health Sciences,

Bangalore

(through proper channel)

Respected Sir,

Subject: Submission of Synopsis of Dissertation

Herewith I am submitting synopsis of my dissertation work “ROLE OF ISCHEMIA MODIFIED ALBUMIN IN ACUTE CORONARY SYNDROME” for the registration in Rajiv Gandhi University of Heath Sciences, Bangalore.

Kindly accept the same and oblige.

Thanking you,

Yours faithfully,

(Dr.Lulu Cyriac)

Place:

Date:

CURRICULAM VITAE

Dr’s Name : Dr. Lulu Cyriac

Date of Birth & Age : May 8th 1988, 25 years

Present Designation : PG

Department : General Medicine

College : A.J. Institute of Medical Sciences

City : Mangalore

Residential Address : AJ Girls Residents’ Hostel,

Room no 705, Kuntikana,

Mangalore.

Phone Number : Mobile No : 8123108678

E-mail address:

Qualifications:

Qualifications / College / University / Year / Registration No. of UG & PG with date / Name of the Medical Council
MBBS / Co-operative Medical College, Kochi,Kerala. / CUSAT / February 2012 / 45596,
6/7/2012 / Travancore-Cochin Medical Council

Details of previous appointments/teaching experience

Designation / Department / Name of Institution / From
DD/MM/YY / To
DD/MM/YY / Total experience in years & months
PG / General Medicine / A.J. Institute of Medical Sciences,
Mangalore / June10, 2013 / Till Date

CURRICULAM VITAE

Name : Dr.Uday B Nayak

Date of birth & Age : May 14,1970, 43Years

Present Designation : Professor

Department : General Medicine

College : A.J. Institute of Medical Sciences

City : Mangalore

Residential Address : A-201,Crest Apartment

Anegundi Road

Bejai,

Mangalore-575004

Phone & Fax Number with code : Office : 0824-2225533

Residence : 0824-2214390

Mobile number : 9845079262

1. Date of joining present institution: October 22, 2013 as Professor

2. Qualifications:

Qualification / College / University / Year / Registration No.of UG & PG with date / Name of the State Medical Council
MBBS / Kasturba Medical College,Mangalore / Mangalore University / 1993 / 35628,
dt.March31, 1993 / Karnataka Medical council
MD
(General Medicine) / Govt.Medical College,Nagpur / Nagpur
University / 1997 / 35628,
dt.Jan22, 2007 / Karnataka Medical council
DM/M.Ch / NA


CURRICULAM VITAE

Details of the previous appointments /teaching experience

Designation / Department / Name of Institution / From
DD/MM/YY / To
DD/MM/YY / Total Experience in years and months
Assistant Professor / General Medicine / Kasturba Medical College,
Manipal / Aug 05,1997 / Feb 28,2001 / 3 Years
6months
23days
Assistant Professor / General Medicine / K.S.Hegde Medical Academy,
Mangalore / Feb 28,2001 / Aug 04,2002 / 1 year
5months
4days
Associate
Professor / General Medicine / K.S.Hegde Medical Academy,
Mangalore / Aug 05,2002 / Aug 07,2004 / 2years,
2days
Associate
Professor / General Medicine / Kasturba Medical College,
Mangalore / Aug 08,2004 / Oct 21,2013 / 9Years
2 months
13 days
Professor / General Medicine / A.J Institute of Medical Sciences,
Mangalore / Oct 22,2013 / Till date /


CURRICULAM VITAE

Name : Dr.Ashok Kumar J

Date of birth & Age : May 15,1969, 44Years

Present Designation : Professor & HOD

Department : Biochemistry

College : A.J. Institute of Medical Sciences

City : Mangalore

Residential Address : Rathna Jyothi

Dr.Shivarama Karanth Nagar Layout

PlotNo.47, 3rdCross Konchady,

Mangalore- 575 008

Phone & Fax Number with code : Office : 0824-2211876

Residence : 0824-6565641

Mobile number : 9481848582

1. Date of joining present institution: September 23, 2010 as Professor & HOD

2. Qualifications:

Qualification / College / University / Year / Registration No.of UG & PG with date / Name of the State Medical Council
MBBS / Govt.Medical College,Bellary / Gulbarga
University / 1992 / 35665,
dt.April 01, 1993 / Karnataka Medical council
MD
(Biochemistry) / Kasturba Medical College,Mangalore / MAHE
University / 1997 / 35665,
dt.Feb29, 2004 / Karnataka Medical council
DM/M.Ch / NA

CURRICULAM VITAE

Details of the previous appointments /teaching experience

Designation / Department / Name of Institution / From
DD/MM/YY / To
DD/MM/YY / Total Experience in years and months
Tutor / Biochemistry / Kasturba Medical College,
Mangalore / May 1994 / April 1997 / 3 Years
Assistant Professor / Biochemistry / Manipal College of Medical Sciences,Pokhara,
Nepal / June 1,1997 / June 15,2002 / 5years
15days
Associate
Professor / Biochemistry / A.J Institute of Medical Sciences,
Mangalore / June 16,2002 / Aug 18,2002 / 2months,
3days
Associate
Professor / Biochemistry / Fr.Muller Medical College,
Mangalore / Aug 19,2002 / Jun15,2006 / 3Years
9months
28days
Professor & HOD / Biochemistry / Fr.Muller Medical College,
Mangalore / Jun16,2006 / Oct 14,2008 / 2years
4months
Professor / Biochemistry / Fr.Muller Medical College,
Mangalore / October 15,2008 / Sept 22,2010 / 1year
11months
8days
Professor
& HOD / Biochemistry / A.J Institute of Medical Sciences,
Mangalore / Sept 23,2010 / Till Date

SYNOPSIS

“ROLE OF ISCHEMIA MODIFIED ALBUMIN IN ACUTE CORONARY SYNDROME”

Name of the candidate : Dr. Lulu Cyriac

Guide : Dr. Uday B Nayak

Co-Guide : Dr.Ashok Kumar J

Course and Subject : M.D. General Medicine

Department of General Medicine,

A.J. INSTITUTE OF MEDICAL SCIENCES,

Kuntikana, Mangalore – 575004

2013

1. Name of the candidate

address:

(In block letters)

2. Name of the Institute:

3. Course of study and Subject: M.D. GENERAL MEDICINE

4. Date of admission to course: 10th JUNE 2013

5. Title of the Topic:

“ROLE OF ISCHEMIA MODIFIED ALBUMIN IN ACUTE CORONARY SYNDROME”

BRIEF RESUME OF THE INTENDED WORK:

6.1 Need for the study:

New markers capable of identifying early myocardial ischaemia before it progresses to the irreparable myocardial cell damage might play an important role in the clinical setting because they will give the emergency physician the opportunity to intervene and prevent progression to infarction.Therefore, the ideal biochemical marker of myocardial ischaemia should be released solely from the myocardium and should achieve high concentrations and rapid release into the blood stream at the time of ischaemia. Furthermore, its concentrations should be related to the extent of injury and should be detectable in the blood for long enough to be measured even in late-presenting patients. 3

Another feature of the ideal biochemical marker is a steep decrease after a period of 24 h, so that recurrent ischaemia can easily be detected. The test should also be rapid, easy and cheap.4 Currently, three markers have been proposed: choline, free fatty acids and ischaemia-modified albumin (IMA). Of these, only IMA is currently available as a licensed test for routine clinical application.

Ø  IMA is a US FDA-approved biomarker that can detect myocardial ischaemia within minutes and continues to increase for 4–6h, after which its level returns to normal. Myocardial ischaemia results in reduction of the ability of albumin to bind cobalt, which is the basis of the albumin cobalt-binding test for IMA.1

Ø  Ischemia-modified albumin is a new ischemia marker and has been proposed as a useful marker for the diagnosis of severe ischemic heart disease and ACS. Ischemia-modified albumin represents a new class of markers that depend on the ischemia preceding myocardial necrosis. The goal is to have a biomarker challenging the electrocardiogram (ECG) as the fastest diagnostic tool in cardiac ischemia.5

Ø  6.2 Review of literature:

Studies over the past few years have shown that ischemia modified albumin (IMA) is a biomarker of ischemia in several clinical scenarios. Ischemia-modified albumin levels have been shown to increase in the presence of myocardial ischemia associated with percutaneous coronary intervention(PCI) and are also high in conditions of increased oxidative stress. In the emergency department (ED) setting IMA was shown to be useful for the diagnosis of myocardial ischemia.2

In a study conducted in CMC Ludhiana,serum IMA in four sequential samples was estimated from 25 patients admitted to ICCU. Twenty five healthy volunteers formed the control group from which the normal range was derived. IMA was significantly raised in ischemia patients than in controls as well as compared to the patients who did not have cardiac ischemia.6

In a study done in St.George’s Hospital, London, elevated IMA levels at presentation in patients with typical acute chest pain were independently associated with an adverse 1-month and 1-year outcome. Thus, IMA

may help identifying patients with a worse prognosis among

those with suspected ACS. Their results suggest that patients with acute chest pain and high IMA levels on arrival to the ED should be evaluated and followed up carefully, even if cTn and clinical tests are negative in the emergency

department.

The French Nationwide Opera study concluded that in patients with AMI, IMA measured within 24 hours is a strong and independent predictor of cardiac outcome at 1 year and may help identify those requiring more aggressive medical management.

6.3 Objectives of the study:

*To evaluate the added diagnostic value of biomarkers beyond clinical assessment to reliably detect myocardial ischemia in the absence of necrosis.

*Role of IMA in differentiating unstable angina versus MI.

*Role of IMA in providing clinical utility complementary to that of cardiac troponins,CKMB the established markers of necrosis in NSTEMI & STEMI.

*Role of IMA In predicting in-hospital mortality.

Materials: Manual BP apparatus, Stethoscope, ECG machine,Spectrophotometer, Calorimeter, Centrifuge (Cooling), - 20 deep freezer, Syringe & needle destroyer, Syringes, Stationary (ECG paper, Etc), Kits for Troponin T,CKMB, Ischemia modified albumin.

Methodology:

Albumin Cobalt Binding (ACB) test.

This involves addition of a known amount of cobalt to a serum sample, addition of dithiothreitol to bind the unbound cobalt and measuring the colorimetric change. As normal albumin will bind cobalt, the amount of free cobalt, and hence the absorbance, will be proportional to the amount of IMA present. Normal values range from 6 – 80 u/ml.7

Initial IMA levels will be measured from venous blood samples taken from the patients admitted with chest pain and suspected ACS. Data including history, physical examination, serial 12-lead ECG and troponin-T measurement at 0 and 6 hours after admission will be collected .Based on hospital diagnosis algorithm (troponin repeated measurements, treadmill test or other ischemia detection, coronary angiography if necessary) patients will be classified as UA,NSTEMI or STEMI. Sensitivity, specificity, positive and negative predictive values will be determined for each marker and in combined analysis.

7.1 Source of data.

`It will be a prospective study, comprising of patients who come to AJ IMS & HRC, Mangalore with c/o chest pain.

7.2 Method of collection of data (including sampling procedure, if any)

Sample and sampling technique:

·  Study design: Prospective study.

·  Set-up: AJ IMS & HRC,Mangalore.

·  Study Period:1year

·  Age group: 18 years and above.

·  Sample size:120

·  Study type:1 year prospective study.

Sampling Technique: All patients coming to casualty with complaints of chest pain,dyspnoea,palpitation,syncope and other symptoms within 6 hours suggestive of an anginal equivalent are taken for the study.Cardiac biomarkers Troponin,CKMB measured along with IMA and ECG taken in the ED within 30mins as part of the standard care.

Inclusion criteria:

All consecutive patients admitted in the hospital with a primary complaint of chest pain evolving within 6 hours and suspected as acute coronary syndrome.

Exclusion criteria:

1) Presence of renal diseases.

2) Presence of cirrhosis.

3) Presence of stroke, skeletal muscle injury, malignancy,trauma.

4) Critically ill patients.

5) Ongoing infectious diseases.

6) Serum albumin < 2 gms/dl .

7) Patient younger than 18 years old.

8) Patients with complaints lasting more than 6 hours, as IMA levels usually return to normal 8–12 hours after onset of myocardial ischemia.

9). Patients whose symptoms had ceased 2 hrs previously,because IMA levels fall rapidly once an ischaemic event has ended.

Plan for data analysis:

The various measures of central tendencies and graphical representations will be used to analyze the data.

7.3 Does the study require any investigations or interventions to be conducted on patients ? If so, please describe briefly.

This study requires the following investigations:

RFT,LFT,USG abdomen,IMA,Troponin,CKMB,12 lead ECG,CAG(if needed).

7.4 Has ethical clearance been obtained from your institution in case of 7.

Ethical clearance obtained.

8. References:

1.R. Duseja and J.A. Feldman, Missed acute cardiac ischemia in the ED: limitations of diagnostic testing. Am J Emerg Med, 22 (2004), pp. 219–225

2.D. Roy, J. Quiles and G. Aldama, et al. Ischemia modified albumin for the assessment of patients presenting to the emergency department with acute chest pain but normal or non-diagnostic 12-lead electrocardiograms and negative cardiac troponin T. Int J Cardiol, 97 (2004), pp. 297–301.

3.F. Peacock, D.L. Morris and S. Anwaruddin, et al. Meta-analysis of ischemia-modified albumin to rule out acute coronary syndromes in the emergency department. Am Heart J, 152 (2006), pp. 253–262.

4.J.H. Pope, T.P. Aufderheide and R. Ruthazer, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med, 342 (2000), pp. 1163–1170.

5.M. Montagnana, G. Lippi and G.C. Guidi, New perspectives in the diagnostic approach to ACS.Recenti Pro Med,96 2005,pp.171-177.

6.M. Rajappa and A. Sharma, Biomarkers of cardiac injury: an update. Angiology, 56 (2005), pp. 677–691. |

7.G.B. Green, Green SF markers of myocardial injury in the evaluation of the emergency department patient with chest pain, A.H.B. Wu, Editor, Cardiac markers, Humana Press, Totawa, NJ (1998), pp. 75–89.

9. Signature of the candidate:

10. Remarks of the guide:

11. Name and Designation of (in block letters):-

11.1 Guide:

11.2 Signature:

11.3 Co-Guide: Dr.ASHOK KUMAR J

PROFESSOR & HOD,

DEPARTMENT OF BIOCHEMISTRY,

A.J.INSTITUTE OF MEDICAL SCIENCES,

MANGALORE-575004

11.4 Signature:

11.5 Head of Department:

11.6 Signature:

12. Remarks of the Chairman and Principal: