RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA

BANGALORE

ANNEXURE – II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 / Name of the candidate and address ( in block letters) / : / DR. SURAPANENI JANARDHANA RAO
M.D. GENERAL MEDICINE
MAHADEVAPPA RAMPURE MEDICAL COLLEGE
GULBARGA-585105
KARNATAKA.
Permanent address / : / DR. SURAPANENI JANARDHANA RAO
S/O Dr. S. RAMAKRISHNA
3-6-535 SRI NILAYAM
STREET NUMBER 7
HIMAYATNAGAR
HYDERABAD- 500029
ANDHRA PRADESH.
2 / Name of the institution / : / H.K.E. SOCIETY’S MAHADEVAPPA RAMPURE MEDICAL COLLEGE,
GULBARGA – 585105.
3 / Course of study and subjects / : / m.d.(General Medicine)
4 / Date of admission to the course / : / 31st MAY 2013
5 / Title of Topic / : / STUDY OF LEVELS OF “N TERMINAL - PRO BRAIN NATRIURETIC PEPTIDE” (NT-Pro BNP) AND ASSOCIATED RISK FACTORS IN SYSTOLIC HEART FAILURE CONSEQUENTIAL TO ISCHAEMIC HEART DISEASE.
6 / Brief Resume of the intended work
6.1 / Need for the study
The 20th century saw unparalleled increases in life expectancy and a major shift in the causes of illness and death throughout the world. During this transition, cardiovascular disease (CVD) became the most common cause of death worldwide.
A century ago, CVD accounted for less than 10 per-cent of all deaths. Today, it accounts for approximately 30 percent of deaths worldwide including nearly 40 percent in high-income countries and about 28 percent in low- and middle-income countries. Driven by industrialization, urbanization, and associated lifestyle changes, this ongoing transition is occurring around the world among all races, ethnic groups, and cultures at an even faster rate than last century.
People from the Indian Subcontinent have the infamous distinction of having the highest prevalence of Coronary Artery Disease amongst all ethnic groups of the world, with projected 100% rise in mortality over the next 25 years.
Heart failure on the other hand is the common end point of many cardiovascular diseases. Cardiomyopathies, Coronary Artery Disease, Hypertension and many other conditions all lead to Heart Failure.
In Ischaemic Heart Diseases like in most other Cardiac Pathologies the end stage is represented by Heart Failure. Early and accurate diagnosis of this stage facilitating prompt treatment is of utmost importance.
A lot of research is being done in the field of Cardiology with respect to pathology, acute and long term therapeutic modalities as well as diagnostics. All of them aiming to better our management of cardiac conditions in any hospital setting.
Echocardiography has revolutionized the management of heart failure. As a result of its ability to provide an accurate diagnosis of Heart Failure. However it is severely limited by its need to have present a highly trained Specialist to make optimal use of it. This is not possible in a developing nation such as India.
To fill this void we should make use of accurate biochemical markers. NT-proBNP is such a marker, which can provide us with not only an accurate diagnosis of onset of Heart Failure but also can be used for follow up.
Hence making our management of Heart failure simpler. In Heart Failure as in any critical care condition, early and accurate diagnosis is always the key to minimizing morbidity and mortality.
6.2 / Review of Literature
Douglas L. Mann. Disorders of Heart, heart Failure and Cor Pulmonale. 18th ed. In Harrison’s Principles of Internal Medicine, Dan L. Longo ed. New York: McGraw-Hill; Pg 1901-15 say:
Heart failure is a common syndrome that is increasing in Incidence and Prevalence. It is primarily a disease of aging, with over 75% of existing and new cases occurring in individuals over 65 years of age. The prevalence of Heart failure rises from < 1% in individuals below 60 years to nearly 10% in those over 80 years of age. In developed countries, CAD with resulting myocardial infarction and loss of functioning myocardium (ischemic cardiomyopathy) is the most common cause of systolic heart failure.
Otto M. Hess, John D. Carroll in Clinical Assessment of Heart Failure, in Braunwalds Heart Disease a Textbook of Cardiovascular Medicine 8th Edition Chapter 23 say:
Patients with left heart failure have symptoms of low cardiac output and elevated pulmonary venous pressure; Dyspnoea is the predominant feature.
STARS-BNP Multicenter Study. J Am Coll Cardiol. 2007 Apr 24;49(16): 1733–9. [PMID: 17448376] says:
Brain Natriuretic Peptide is a circulating hormone released mainly from the ventricles in response to myocyte stretch. It was isolated originally from porcine brain extracts abut was soon defined as a cardiac natriuretic peptide. The nomenclature hence is a misnomer. The measurement of BNP has been shown to be useful in detecting LV dysfunction, particularly after Acute Myocardial Infarction, and to be related to poor outcome. Elevated levels of BNP and N-Terminal pro BNP may indicate the extent or severity of Heart Failure post an Ischaemic Attack in the heart.15
Pfister R in NT-pro-BNP for differential diagnosis in patients with syncope. Int J Cardiol - 20-MAR-2009 says
BNP acts on distant tissues and causes diuresis, vasodilation and decreased renin and aldosterone secretion. Known mechanisms of BNP clearance from plasma include binding to the natriuretic peptide clearance receptor type-c and proteolysis by peptidase NEP 24.11. NT-proBNP has a longer half life and thus higher plasma concentration than BNP. It probably is cleared from the plasma by renal excretion and possibly other unknown pathways. 5
The main findings of a study by Mayr and other in Austria were:
Significant Correlation of NT-proBNP measurement on days 3 after admission with acute and chronic infarct size, ejection fraction and segmental wall thickening after Acute Myocardial Infarction assessed by Cardiac Magnetic resonance imaging as well as with biomarkers of Myocardial Necrosis.
Ikonomidis I. in Association of left ventricular diastolic dysfunction with elevated NT-pro-BNP in general intensive care unit patients with preserved ejection fraction: a complementary role of tissue Doppler imaging parameters and NT-pro-BNP levels for adverse outcome in Shock - 01-FEB-2010; 33(2): 141-8 says:
NT-pro BNP levels tend to be higher in patients with systolic heart failure than in those with heart failure with preserved ejection fraction. An NT-pro-BNP greater than 941 pg/mL was a reliable predictor of LV diastolic dysfunction defined as a composite of E' less than or equal to 8 cm/s and/or mean E/E greater than or equal to 13 (area under the curve, 75%; P = 0.03). Patients with combined NT-pro-BNP greater than 941 pg/mL and abnormal TDI markers had increased creatinine levels and a lower MAP, P(O2)/Fi(O2), and survival rate than those with abnormal TDI or NT-pro-BNP alone or patients with normal TDI markers and NT-pro-BNP (25%, 60%, 70%, and 84%, respectively; P < 0.05). The addition of abnormal TDI in a model including NT-pro-BNP and sepsis increased the model's value for in-hospital mortality (P for change = 0.01). In ICU patients with preserved EF, LV diastolic dysfunction and sepsis determine NT-pro-BNP levels. Tissue Doppler imaging markers and NT-pro-BNP have a complementary value for in-hospital mortality.
An international pooled analysis of 1256 patients of acute destabilised heart failure cases, showed
That with age related cut offs of 450, 900 and 1800 pg/ml for ages of <50, 50-75 and >75 years of age the NT proBNP level measurement yielded a sensitivity of 90% and a specificity of 84% for acute heart failure. 14
Another study showed that plasma NT-pro BNP levels correlated well with the unloading of left ventricle and clinical improvement of patients in end stage heart failure. So this marker can be used to follow up cases in end stage heart failure. 13
A study by Morrow and de-Lemos JA classifies:
NT-pro BNP as a useful biomarker in Heart Failure meaning it is:
1)  Accurate, affordable and with short turn around period.
2)  Provides information that is not available from clinical assessments
3)  Aids in making clinical decisions
This study aims to study the levels of N-Terminal Pro BNP levels in systolic heart failure which is a specific consequence of Ischaemic Heart Disease alone on the basis of above literature.
6.3 / Objectives of the Study
1.  To study levels of NT-pro BNP in Systolic Heart Failure consequential to Ischaemic Heart Disease.
2.  To study the correlation between the levels of NT-pro BNP and Systolic Heart Failure consequential to Ischaemic Heart Disease
3.  To study the risk factors in patients presenting with Heart Failure consequential to Ischaemic Heart Disease and their correlation to NT-proBNP Levels.
7 / Materials and methods
7.1 / Source of data
All Patients admitted in Basaveshwar Teaching and General Hospital, attached to Mahadevappa Rampure Medical college, Gulbarga, diagnosed with Heart Failure.
7.2 / Methods of collection of data ( including sampling procedure, if any)
SAMPLE SIZE:
100 PATIENTS
INCLUSION CRITERIA :
All patients diagnosed with Systolic Heart Failure (Ejection Fraction <40%) subsequent to Ischaemic Heart Disease.
EXCLUSION CRITERIA:
1.  Patients who present with Heart failure with preserved Ejection Fractions.
2.  Patients who present with Heart Failure consequential to any other etiology other than Ischaemic Heart Disease, such as Rheumatic Heart Disease, Restrictive Cardiomyopathies, Cor-Pulmonale, Endo-Myocardial Disorders, etc.
3.  Patients with any other known causes which lead to elevated NT-pro BNP levels such as Chronic and Acute Kidney injuries, Acute Pulmonary Embolism, Primary or Secondary Pulmonary Hypertension, COPD, Respiratory Failure, Hyperthyroidism, Sepsis.
STUDY PROTOCOL :
A previously designed proforma will be used to collect data on cases admitted into Basaveshwara Teaching and General Hospital, Gulbarga. Complete detailed history and clinical examination will be taken and performed, requisite investigations will be sent and their respective result values noted, and finally analysis of collected data will be performed.
STUDY DESIGN:
It is a cross sectional, single center study involving patients diagnosed with Systolic Heart Failure in Basaveshwara Teaching and General Hospital, Gulbarga. Clinical history, Investigations-Particularly NT-proBNP levels, ECG, Troponin I, CPK-MB, Echocardiography and others where available will be collected until said sample size is achieved.
PERIOD OF STUDY
DECEMBER 2013 – AUGUST 2015
STATISTICAL ANALYSIS :
Data will be analysed by using SPSS software (11.5 Version).
Large sample “Z” test, T – Tests, Chi – Square test, ANOVA, etc tests are used for ascertaining significance.
7.3 / Does the study require any investigation or intervention to be conducted on patients or other humans or animals? if so please describe briefly
1.  NT - pro BNP LEVELS
2.  RANDOM BLOOD GLUCOSE
3.  FASTING LIPID PROFILE
4.  ECG
5.  2D-ECHO
6.  TROPONIN I
7.  CkMb
7.4 / Has ethical clearance been obtained from your institution in case of 7.3 ?
Yes. Ethical clearance has been obtained from Ethical clearance committee of the institution.
8. / List of References

1.  Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.

Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA; Breathing Not Properly Multinational Study Investigators. N Engl J Med Jul 2002

2.  Predictive value of NT-pro-BNP for the non-cardiologist. A study on 573 hospitalized patients with cardiovascular disease
Pfister R - Dtsch Med Wochenschr - 01-MAR-2008
3.  Relative role of NT-pro BNP and cardiac troponin T at 96 hours for estimation of infarct size and left ventricular function after acute myocardial infarction.
Steen H - J Cardiovasc Magn Reson - 01-JAN-2007
4.  A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction.
Atisha D, Bhalla MA, Morrison LK, Felicio L, Clopton P, Gardetto N, Kazanegra R, Chiu A, Maisel AS. - Am Heart J. 2004 Sep
5.  NT-pro-BNP for differential diagnosis in patients with syncope.
Pfister R - Int J Cardiol - 20-MAR-2009
6.  The Characteristic and Prognostic importance of NT Pro BNP concentration in critically ill patients.
Shah KB, Nolan MM, Rao K, Wang DJ – The American Journal of Medicine 2007;120 (12):1071-7
7.  Use of NT proBNP peptide assay for etiologic diagnosis of acute dyspnoea in elderly patients.
Berdague P, Caffin PY, Barazer I, Vergnes C, Sedighian S. – American Heart Journal 2006;151(3):690-8
8.  Natriuretic peptides: Measurements and relevance in heart failure.
Palazzuoli A, Gallota M, I Quatrini, Nutri R. - Vascular Health Risk Management 2010;6:411-8
9.  Page number 509 of Braunwald’s Heart disease 8th edition
10.  Douglas L. Mann. Disorders of Heart, heart Failure and Cor Pulmonale. 18th ed. In Harrison’s Principles of Internal Medicine, Dan L. Longo ed. New York: McGraw-Hill; Pg 1901-15
11.  Application of Nt-proBNP measurements in cardiac case: a more discerning marker for detection and evaluation of heart failure.
Yoshiko Seino, Akio Ogawa, Tenyo Yamashita, Masato Fukushima – European Journal of Heart Failure 2003;6(3):295-300
12.  N-Terminal Pro Brain Natriuretic Peptide on admission has prognostic value across the whole spectrum of acute coronary syndromes.
Galvani M, Ottani F, Oltrona L, Ardissino D, Gensini GF, Maggioni AP, et al. – Circulation 2004;110(2):128-134
13.  Prognostic impact of plasma NT-proBNP in severe chronic heart failure.
Franz Hartmann, Milton Packer, Andrew JS Coats, Michael B fowler. – Copernicus SubStudy – European Journal of Heart Failure 2004;6(3):343-50
14.  Time course of B-type Natriuretic Peptide (BNP) and N-Terminal Pro BNP changes in patients with Decompensated Heart Failure.
Alifons Gegenhuber, Thomas Mueller, Fritz Firlinger, Kurt Lenz, - Clinical Chemistry 2004;50(2):454-6
15.  Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure:
The STARS-BNP Multicenter Study. J Am Coll Cardiol. 2007 Apr 24;49(16): 1733–9. [PMID: 17448376]
16.  Association of left ventricular diastolic dysfunction with elevated NT-pro-BNP in general intensive care unit patients with preserved ejection fraction: a complementary role of tissue Doppler imaging parameters and NT-pro-BNP levels for adverse outcome.
Ikonomidis I. - Shock - 01-FEB-2010; 33(2): 141-8 says:
9 / Signature of Candidate
10 / Remarks of guide / This is a pioneering study being performed in our institution in the field of early rapid diagnosis of heart failure which arises as a complication of Ischaemic Heart Disease. It is of immense benefit to the patients enabling a quick diagnosis and initiation of therapy, thereby significantly decreasing mortality and morbidity in our setup.