SYNOPSIS

RajivGandhiUniversity of Health Sciences, Karnataka,

Bangalore.

N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE AS A PREDICTOR OF SHORT TERM OUTCOMES IN ST SEGMENT ELEVATION MYOCARDIAL INFARCTION

Name of the candidate:Dr. Madhu Kumar. R

Guide:Dr. Venkatesha. B. M

Course and Subject :M.D (General Medicine)

Department of General Medicine

FatherMullerMedicalCollege,

Kankanady, Mangalore – 575002.

August – 2009

RAJIVGANDHIUNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA

PROFORMA FOR REGISTRATION OF THE SUBJECT FOR

DISSERTATION

1. / NAME OF THE CANDIDATE AND ADDRESS / DR. MADHU KUMAR. R
P.G. RESIDENT
FR. MULLER MEDICAL COLLEGE, KANKANADY,
MANGALORE – 575002.
2. / NAME OF THE INSTITUTION / FR. MULLER MEDICAL COLLEGE, KANKANADY, MANGALORE – 575002
3. / COURSE OF STUDY AND SUBJECT / M.D (GENERAL MEDICINE)
4. / DATE OF ADMISSION TO COURSE / 25-05-2009
5. / TITLE OF THE TOPIC:
N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE AS PREDICTOR OF SHORT TERM OUTCOMES IN ST SEGMENT ELEVATION MYOCARDIAL INFARCTION
6. / Brief Resume of the Intended Work:
6.1. Need for the study:
Optimal risk stratification of patients with acute myocardial infarction (AMI) is of paramount importance to deliver appropriate care. Risk prediction based on clinical, ECG, and biochemical parameters (cardiac troponin, CK-MB) is relatively inaccurate.¹ Brain natriuretic peptide (BNP) is a circulating cardiac hormone released mainly from the ventricles in response to myocyte stretch. It is synthesized as an inactive prohormone that is split into the active hormone BNP and the inactive N-terminal fragment (NT-pro-BNP). The measurement of BNP has been shown to be useful in detecting LV dysfunction, particularly after AMI.¹ Elevated levels of BNP and N-terminal pro-BNP may indicate the extent or severity of the ischaemic insult correlating with adverse outcomes.² Many of the studies have concentrated on the role of NT-pro-BNP levels in predicting the long term morbidity and mortality of AMI.
This study intends to determine the relationship between NT-pro-BNP levels and short term complications of ST segment elevation myocardial infarction (STEMI) and the role of NT-pro-BNP in predicting the short term outcome of STEMI.
6.2 Review of Literature
Brain(B-type) natriuretic peptide(BNP) is a peptide hormone, first isolated from porcine brain but released primarily from the cardiac ventricles in response to myocyte stretch. It is synthesized as an inactive prohormone that is split into the active hormone BNP and the inactive N-terminal fragment (NT-pro-BNP). BNP has a number of systemic effects, including vasodilatation, increase in urinary volume and sodium output and inhibition of the sympathetic nervous system and the renin-angiotensin-aldosterone system. It is widely believed that predominant pathophysiological process underlying increased circulating levels of BNP and NT-pro-BNP is regional or global impairment of left ventricular systolic or diastolic function leading to left ventricular wall stretch. In addition, their increased levels may also result directly from cardiac ischaemia. It appears that ischaemic or injured myocardial tissue releases extra BNP irrespective of haemodynamic factors.³ Assessing NT-pro-BNP is easier than BNP. The clearance of BNP is rapid by way of several mechanisms. The clearance of NT-pro-BNP is mainly by passive kidney excretion, and hence it remains elevated for longer time.
A study done in Massachusetts, USA, in 2004 showed that increased concentrations of BNP at initial presentation, in patients with STEMI are associated with higher short term risk of mortality.4
A multicentric study in Italy inferred that NT-pro-BNP levels, measured at admission early after the onset of the ischaemic episode, improve the early risk stratification of patients with acute coronary syndrome and are strongly predictive of short term mortality.¹
A study in Lucknow, India in 2003-2004 concluded that NT-pro-BNP has the strongest predictive value to assess the risk of adverse events including death in patients with ACS. Information provided by this biomarker is incremental to that offered by conventional risk markers in patients with ACS.²
In a multimarker study comparing NT-pro-BNP with nine inflammatory markers and microalbuminuria, NT-pro-BNP was the only marker shown to improve risk stratification of recurrent cardiovascular events. 5
6.3 Objectives of the study:
The objectives are:
  1. To assess the relationship between N-terminal pro-Brain natriuretic peptide levels on admission in ST elevation myocardial infarction (STEMI) and its short term complications.
  2. To determine the role of plasma NT-pro-BNP levels in predicting short term outcome in patients with STEMI.

7. Materials and Methods
7.1 Source of data:
A minimum of 30 patients, in the age group of 40-80 years, who are admitted in FatherMullerHospital with acute ST elevation myocardial infarction, will be included in this study. The study period would be 1 year.
7.2. Method of collection of data:
A minimum of 30 patients, who present with acute ST elevation myocardial infarction to FatherMullerMedicalCollegeHospital, will be included in this study. The study is a cross sectional study and the method of sampling used is purposive or judgmental.
The patients will be evaluated as per the history, general physical examination, systemic examination, ECG, ECHO cardiography and investigations.Plasma NT-pro-BNP levels are measured by electro-chemi-luminiscence method. The included patients are followed up over a period of 5 days for development of various short term complications of acute MI.
Inclusion Criteria
  1. Those admitted in ICCU of Father Muller Hospital having typical ischaemic symptoms, and ST segment elevation of at least 1 mm in limb leads and 2 mm or more in chest leads of ECG.
  2. Admitted within 12 hours after onset of symptoms.
  3. Patients within the age group of 40-80 years.
Exclusion Criteria
  1. STEMI patients with previous chronic heart failure.
  2. STEMI patients with previous chronic kidney disease.
  3. STEMI patients with cardiogenic shock at presentation.
  4. STEMI patients who present 12 hours after the onset of symptoms.
  5. STEMI patients who are taken up for angioplasty within 5 days of study period.
  6. STEMI patients of age < 40 years or > 80 years.
  7. Patients with non ST segment elevation MI and unstable angina.
Data Analysis
Data will be analyzed for the statistical significance using Karl Pearson correlation coefficient, t’ test, and by Receiver Operating Curve (ROC) analysis. A p value of <0.05 will be considered significant.
7.3. Does the study require any investigations or interventions to be conducted on patients or other humans or animals?
Yes. The following tests are done – ECG, ECHO cardiography, CK-MB, Troponin-I, Renal function tests, Fasting lipid profile, and NT-pro-BNP levels.
7.4. Has ethical clearance been obtained from your institution in case of 7.3?
Yes.
8. / List of References:
  1. Galvani M, Ottani F, Oltrona L, Ardissino D, Gensini GF, Maggioni AP, et al. N-Terminal Pro-Brain Natriuretic Peptide on Admission Has Prognostic Value Across the Whole Spectrum of Acute Coronary Syndromes. Circulation. 2004;110:128-134.
  2. Puri A, Narain V, Mehrotra S, Dwivedi S, Saran R, Puri V. N-Terminal-Pro Brain Natriuretic Peptide as a Predictor of Short-Term Outcomes in Acute Myocardial Infarction. Ind Heart J 2005;57:304-310.
  3. Goetze JP, Christofferson C, Perko M, Arendrup H, Rehfeld JF, Kastrup J, et al. Increased cardiac BNP expression associated with myocardial ischaemia. FASEB J 2003;17:1105-7.
  4. Mega JL, Morrow DA, de Lemos JA, Sabatine MS, Murphy SA, Rifai N, et al. B-type natriuretic peptide at presentation and prognosis in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2004;44:335-9.
  5. Blankenberg S, McQueen MJ, Smieja M, Pogue J, Balion C, Lonn E, et al. Comparative impact of multiple biomarkers and N-Terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation. 2006;114:201-208.

9. / SIGNATURE OF THE CANDIDATE:
10. / REMARKS OF THE GUIDE: / APPROVED
11. / NAME & DESIGNATION OF GUIDE / DR. VENKATESHA. B. M
PROFESSOR
DEPARTMENT OF GENERAL MEDICINE
FR. MULLERMEDICALCOLLEGE
MANGALORE – 575002
11.2SIGNATURE
11.3 HEAD OF DEPARTMENT / DR. B. NARASIMHA HEGDE
PROFESSOR AND H O D OF MEDICINE DEPARTMENT OF GENERAL MEDICINE FR. MULLER MEDICAL COLLEGE MANGALORE – 575002
11.6SIGNATURE
12.1 REMARKS OF THE CHAIRMAN AND PRINCIPAL
12.2 SIGNATURE

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