Download RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE,
KARNATAKA
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
01
Name of the Candidate and Address
Dr. Ravikumar B.H.
c/o M. Bellarappa “Asare Nilaya”
KHB Colony, Horohalli Extension
Kolar, Karnataka State
02
Name of the Institution
M.S. Ramaiah Medical College
Bangalore 54
03
Course of the Study and Subject
M.D General Medicine
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Date of Admission
23rd September 2011
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Title of the Topic
“Heart-type fatty acid binding protein” a comparison
with cardiac troponin-T and Creatinine kinasemyofibrin band(CK-MB) as an early biochemical
marker for diagnosis of myocardial infarction”.
1
Introduction
In patients presenting with acute chest pain, early and correct diagnosis of acute myocardial infarction
(AMI) enables interventions to reduce the mortality rate which is of paramount importance. It is also
important to identify patients who are not suffering from AMI, who can be sent home safely which
results in considerable gains for both patients and hospitals.
Heart-type fatty acid binding protein (h-FABP) is a small cytoplasmic protein (15kDa) that is abundant in
cardiac tissue. Its main function is to regulate the transportation of free fatty acids with in the myocardial
cells. When myocardium is damaged, h-FABP immediately leaks into the bloodstream, Causing rapid
elevation in the concentration of h-FABP. So it is a highly sensitive biomarker for early diagnosis of
AMI. h-FABP levels rise as early as 1-3 h after the onset of AMI, peak at 4-6 h, and return to normal
within 24-30h.
A one–step h-FABP immunochromatographic test designed to detect h-FABP in whole blood samples is
now commercially available. The test result is available within 15 min after addition of blood samples. It
requires no sample pretreatment and thus can be applied in emergency situation. Combined with the well
established markers like troponins, it may allow early and accurate targeting of appropriate therapy
compared to the currently available diagnostic tests.
Need for the Study
According to available data, coronary heart disease is responsible for 1 in 5 deaths in the united states. It
is becoming more common in the developing world such that in India,cardiovascular disease(CVD) is
leading cause of death. In these patients no single specific test is available for early diagnosis.
Presently available cardiac markers like ck-mb and Trop-T have got a sensitivity of 75.4% and 65.3%
respectively in acute myocardial infarction. And both do not peak until 6-12 hrs of onset. Where as a
novel new biomarker h-FABP has got a sensitivity of 89.3% and specificity of 87.5%.In acute
myocardial infarction, The h-FABP is immediatly released after myocardial injury, and that is detectable
as early as 1 ½ hrs after symptom onset. A peak level is reached after 4 to 6 hour and due to rapid renal
clearance, the level returns to base line with in 30 hours.
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Review of Literature
 Assessment of h-FABP with in the first 4 hrs of symptoms is superior to cardiac troponin-T for
detection of MI, and is an useful additional biomarker for patients with acute chest pain 1
 Qualitative h-FABP test has excellent sensitivity, higher than measurement of CK-MB and cardiac
troponin-T on hospital admission, and high specificity in the patient group with non ST segment
elevation ACS. And also h-FABP seems to be an excellent biochemical cardiac marker for
diagnosing non ST segment elevation MI 2
 Studies shows that a combined measurement of two cardiac markers, an early one such as h-FABP
and a later marker such as cardiac troponin-T may provide the optimum diagnostic data 3,7
 Heart-Fatty acid binding protein(h-FABP) predicts long term mortality after ACS and identifies
high-risk patients 4
 CK-MB has only 50% sensitivity when measured at the time of presentation. Maximum sensitivity
is achieved by analysis of a second sample 6 to 12 hrs after admission 5
 The new biomarker(h-FABP) test result is available within 15 minutes, it require no sample
pretreatment 6
Objective of the Study
 To assess the Specificity and Sensitivity of Heart-fatty acid binding protein,In diagnosis of acute MI
 Qualitative assay of h-FASBP, in comparison with cardiac Trop T and CK-MB
as an early
biochemical marker for myocardial infarction.
Materials and Methods
Study subjects
 Patients presenting with ischemic Chest pain to the emergency department at M.S. Ramaiah Medical
Hospitals, with suspected MI will be enrolled
 Patients symptoms and past medical history will be documented at admission using a pre- defined
protocol
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Diagnostic Criteria
 The Standard diagnosis will be made after critical review of all clinical pictures
 AMI is defined as detection of initial or 12h cTn-T >0.1ng/L together with evidence of
myocardial ischemia with suggestive one of the following
1. Symptoms of ischemia
2. ECG changes indicative of new ischemia (new ST-T changes)
3. Development of pathological Q wave in the ECG
4. Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality
Diagnostic outcomes will be first categorized into following groups
I.
II.
III.
ST-elevation myocardial infarction(STEMI)
Non ST-elevation myocardial infarction(NSTEMI)
Non myocardial infarction(NMI)
 Quantitative assay of cardiac Trop-T and CK-MB will be performed at presentation,
 Heart- fatty acid binding protein qualitative assay will be measured at presentation
 Cardiac troponin-T will be re determined at least 12h from the onset of chest pain to full fill a final
diagnosis
Lab Methods
 Trop-T:- Electrochemiluminescence immunoassay- 2 antibodies sandwich principle(ECLIA)>0.1n/L
 CK-MB:-Electrochemiluminescence immunoassay 2 antibodies sandwich principle, Short turn
around time(STAT) >25/L
 h- FABP:- Rapid chromatographic immunoassay designed for qualitative determination of h-FABP
in blood samples with a cut –off level of >7ng/L (QuickSens @ , 8sens . diognostic GmbH, Berlin ,
Germany). The test is based on a dual monoclonal antibody sandwich method , using two distinct
monoclonal antibodies and the gold labeled method and requires 100-120 microL of blood sample
and the result will be interpreted within 15 minute after sample application.
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Duration of Study: -
November-2011-october 2013
Inclusion Criteria
 Patients presenting with acute onset chest pain of less than 12 hours duration
 Age > 18 Years
Exclusion Criteria
 Patients presenting after 12 hours of symptom onset
 Chronic renal failure
 Acute muscle disease
 Suspected pulmonary thrombo embolism or pericarditis
Statistical Analysis of data: Sample size for this intended study is minimum of 50
 Sensitivity , specificity, positive predictive value , negative predictive value will be calculated for
diagnostic tests namely h-FABP , CK-MB, Trop-T
 ROC curve will be employed to assess the sensitivity and specificity and to find out appropriate cut
of level for various bio-marker
 Descriptive statistics will be employed to summarise the data regarding qualitative and quantitative
variable.
Does the study require any investigation or intervention to be conducted on patients or other
humans or animals?
Yes
 Electrocardiography
 Creatinine Kinase –Myofibrin band(ck-mb)
 Cardiac Troponin-T
 Echocardiography
 Fasting lipid profile
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 Fasting blood sugars, post prandial blood sugar
 Renal Function test
 Liver function test
Has the ethical clearance been obtained from your institution?
Yes Ref.No STD-/EC/0488/2011 Dated 23/11/2011
References
1. Conor J. McCann, Ben M. Glaver. et al Novel biomarker in early diagnosis of acute myocardial
infarction compared with cardiac troponin T. European heart journal, 2008, 29, 2843-2850.
2. Figiel L. Kasprzak JD , Peruga j, Lipiec p, et al Heart type fatty acid Binding protein –a reliable
marker of myocardial necrosis in Heterogeneous group of patient with acute coronary syndromes
without persistent ST elevation. Kardiol Pol, 2008; 66(3):253-9.
3. Chan, C.P., Wan T.S., Watkins K.L., et al Rapid analysis of fatty acid-binding protein with
immunosensors and immunotests for early monitoring of tissue injury. Biosens and
Bioelectronics,2005,20(12):2566-80
4. Kilcullen N Vishwanathan K Das R,Marrell C. et al Heart type fatty acid binding protein predicts
long- term mortality after acute coronary syndrome .J Am Coll Cardiol, 2007 20;50(21):2061-7.
5. Mauro Panteghini, Franca Pagani. and Graziella Bonetti et al The sensitivity of cardiac marker: an
evidence based Approach Clin Chem Lab Med, 1999;37(11/12):1097-1106
6. Cangel P .Y. Chan, Matthias Lehmann, llka Renneberg, et al A novel Credit-card Style assay for
bed side determination of fatty acid-binding protein. IVD Technology Magazine, 2006;12:51
7. Chun-jian Li, Jie-qi Li, Xiao-fang Liang et al point of care test of heart type fatty acid binding
protein for early diagnosis of myocardial infarction Acta pharmacologica sinica, 2010 31:307312;doi:10.1038/aps.2010.2;
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Signature of the Candidate
08
Name and Designation of the Guide
Dr. Sudhir
Professor
Dept. of Medicine
08.1
Remarks of the Guide
08.2
Signature of the Guide
09
Head of the Department
Study may help to identify
Patients with acute Myocardial
Infarction early for Intervention
Dr. Arun Narayan
Professor & Head
Dept. of Medicine
09.1
Signature
10
Principal
Dr. Saraswathi G. Rao
10.1
Remarks of the Principal
Forwarded to RGUHS
10.2
Signature
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