NAME OF THE CANDIDATE AND ADDRESS
/ DR. ASHA KRPOST-GRADUATE,
GENERAL MEDICINE,
VYDEHI INSTITUTE OF MEDICAL SCIENCES AND RESEARCH CENTRE,
#82, EPIP AREA NALLURAHALLI,WHITEFIELD
BANGALORE-560066
2.
/NAME OF INSTITUTION
/ VYDEHI INSTITUTE OF MEDICAL SCIENCES AND RESEARCH CENTRE,#82, EPIP AREA,
NALLURAHALLI,WHITEFIELD,
BANGALORE-560066
3.
/COURSE OF STUDY AND SUBJECT
/M.D. GENERAL MEDICINE
4.
/DATE OF ADMISSION OF THE COURSE
/05 June 2013
5.
/TITLE OF THE TOPIC:
STUDY OF CARDIAC FUNCTION IN PATIENTS WITH SEVERE IRON DEFICIENCY ANAEMIA.
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION.
6.1 NEED FOR THE STUDY
Iron deficiency is the commonest nutritional deficiency worldwide, affecting more than one-third of the population. Iron Deficiency is more prevalent and its economic consequences are relevant. Although not commonly acknowledged, Iron Deficiency adversely affects the function and limits the survival of living organisms at every complexity level .
In the last decade, anemia was recognized as an important co-morbidity in Heart Failure, a factor limiting physical activity, responsible for a poor quality of life, and a predictor of unfavourable outcomes.
Iron deficiency was hypothesized to be the cause of erythropoietin resistance in Heart Failure which could be responsible for the unsatisfactory effects of erythropoietin therapy in Heart Failure 7. Most of the available literature have studied the effects of chronic anemia of any etiology on the cardiac function and have use M mode parameters for the same1,4.
There are numerous studies on Heart Failure in Iron Deficiency anemia but there is lack of sufficient data regarding left ventricular mass , wall thickness and volume in iron deficiency anemia . Hence I would like to emphasize on these parameters based on clinical, ECG and Echocardiographic findings in iron deficiency anemia for early detection of heart failure.
6.2 REVIEW OF LITERATURE
Mohammed A-Biltagi concluded that IDA( Iron Deficiency Anemia) was associated with diastolic dysfunction. There was significant increase in Left Atrial volume, decrease in LA longitudinal peak strain and increase in LA stiffness. Assessment of e/a ratio by TDI(Tissue Doppler Imaging) was more sensitive than E/A ratio assessed by conventional Doppler as it can differentiate the normal and pseudo normal mitral inflow pattern. Tissue Doppler imaging was able to detect even subclinical structural and functional alteration of the atrial myocardium. Results in our study denote that atrial dysfunction in iron deficiency anemia patients was due to hemodynamic abnormality. Primary and secondary prevention of iron deficiency anemia should be done in infants, toddlers and children to avoid cardiac complications. Recent echocardiography modalities (Tissue Doppler & speckle tracking) are useful in early detection of subclinical myocardial deformation1.
Alvarez et al evaluated the cardiac functions before and after total dose iron (TDI) therapy . In their series of thirty patients cardiac function was evaluated using M mode echocardiogram. The baseline echo was done before total dose iron therapy and repeated five days later. Significant difference was found in the ejection fraction , which improved after iron therapy. The fractional shortening did increase after total dose iron therapy but this difference was not found to be significant. In this study impaired ventricular performance was observed in patients with iron deficiency anemia. After total dose iron therapy the left ventricular function improved before there was a significant rise in hemoglobin level proving the theory that correction of the abnormalities of the heart in iron deficiency patient by total dose iron therapy may be the result of correction of iron at the tissue level2.
Nikita Hegde in her study concluded that with severe iron-deficiency anemia, however, subtle echocardiographic indices suggest that left ventricular function deteriorates. Myocardial contractility, as determined by the fractional shortening percentage, decreases as hemoglobin drops below 7 g/dL. The ratio of end-systolic wall stress to end-systolic volume index (ESS/ESVI) has also been used to evaluate cardiac contractility. This ratio is reduced—implying functional compromise—in patients with hemoglobin levels of less than 6 g/dL. Hence Left ventricular dysfunction may result from iron deficiency, particularly when the hemoglobin level is less than 5 g/dL3.
Simsek H Included 97 patients who had iron deficiency anemia and 50 healthy subjects. The cases were evaluated with a clinical examination and diagnostic tests that included 12‐lead electrocardiography and transthoracic echocardiography. Compared to the control group, patients with iron deficiency anemia showed significantly longer maximum P wave duration (Pmax) , P wave dispersion (PWD, mitral inflow deceleration time and isovolumetric relaxation time (IVRT); they also showed increased heart rate and frequency of diastolic dysfunction. Correlation analysis revealed that P wave dispersion was significantly correlated withisovolumetric relaxation time, DT, heart rate, the presence of anemia and hemoglobin level. These findings suggest that iron deficiency anemia may be associated with prolonged P wave duration and dispersion and impaired diastolic left ventricular filling4.
Suk Sohn et al studied cardiac hypertrophy in a patient with severe iron deficiency anaemia associated with long-term bloodloss leading to iron deficiency anemia, is discussed using chest electrocardiographic and radiographic images. With iron supply, the patient showed remarkable improvement of cardiomegaly, which is a unique feature of chronic severe iron deficiency anaemia. 3 months following intravenous iron therapy the study group showed reduced signs and symptoms of cardiac failure. Haemoglobin and haematocrit levels had normalized. Marked cardiomegaly on the chest radiograph also had regressed . A follow up echocardiogram revealed normalized left ventricular wall thickness and dimension with scanty pericardial effusion and trace mitral regurgitation5.
Vitthal HK included 30 non-pregnant females with severe iron deficiency anaemia, haemoglobin<6gm% and low serum ferritin levels and were subjected to the ECG test. The QTc of each subject was calculated by using Bazzet’s formula and this was compared with that of an equal number of sex and age matched controls .A significantly shortened QTc was observed in severe iron deficiency anemia(390±23ms) as compared to that in the controls (419±19ms) (P>0.001). There was a significant positive correlation between the serum ferritin levels and the QTc interval. This study suggested that a shortened QTcwas observed in the severe iron deficiency anemia group because of the sympathetic over activity which was secondary to the hyper dynamic circulation6.
Cristina Opasich enrolled one hundred and forty-eight consecutive patients with haemoglobin concentration <13 g/dL (if males) or <12 g/dL (if females) . Factors responsible for anaemia were investigated by evaluating endogenous erythropoietin (Epo) production, serum cytokines levels, body iron status, and iron supply for erythropoiesis. Most patients (57%) presented anaemia of chronic disease and among them, 92% showed evidence of a defective endogenous Epo production. This was indicated by an observed/predicted log(serum Epo) ratio less than 0.8 and/or a defective iron supply for erythropoiesis diagnosed by low transferrin saturation and/or increased value of soluble transferrin receptor. According to regression analysis sex and serum Epo were correlated with anaemia. These findings suggested that about half of anaemic CHF patients showed anaemia of chronic disease with blunted endogenous Epo production and/or a defective iron supply for erythropoiesis. Determination of the individual mechanisms of anaemia in CHF could justify a rational therapeutic approach to anaemia7.
Ewa A. Jankowskastudied 443 patients with stable systolic CHF , New York Heart Association Class I/II/III/IV with severe iron deficiency anemia were included.He concluded that iron deficiency independently predicts exercise intolerance in patients with systolic CHF. Whether iron supplementation would improve exercise capacity in iron-deficient subjects requires further studies8.
Mohammed Abd Abdul Hussein enrolled 200 participants and classified into two groups; anemic and non-anemic (n=100 for each) according to the definition of WHO.Anemia was identified to correlate well with the development of left ventricular hypertrophy and with the resultant diastolic dysfunction. The severity of diastolic dysfunction was unrelated to the severity of anemia and sex of the patients9.
6.3 OBJECTIVES OF THE STUDY
(1) To study the clinical and hematological profile in patients with severe iron deficiency anemia.
(2) To evaluate in detail the ECG and Echocardiographic abnormalities and left ventricular function in patients with severe iron deficiency anemia.
7 MATERIALS AND METHODS
7.1 SOURCE OF DATA
All patients diagnosed with severe Iron deficiency anemia in the department of general medicine , Vydehi institute of medical sciences and research center Bangalore will be taken as subjects and who satisfy the inclusion criteria.
7.2 Method of collection of data:
Patients with iron deficiency anemia with hemoglobin less than 6gm% will be included after applying the exclusion criteria. Detailed history will be taken for all patients , which included history of palpitation , chest pain , breathlessness and swelling of legs. The clinical; examination included resting pulse , blood pressure , nail changes , jugular venous pressure , pedal edema , heart sounds , murmurs heard, liver and spleen size and features of congestive heart failure. All patients will have a complete hematological examination and peripheral smear examination. Estimation of serum iron , serum ferritin will be done in all cases. Electrocardiogram will be recorded for all patients in the resting state. Routine postero anterior chest roentgenogram will be taken in all cases. All the patients will have echocardiogram recorded. All Echos will be done using hewllet Packard image point with 3.7, 5 MHz and 2.0, 2.5 MHz probe. The various Echo parameters will be analyzed.
Sample size : 100 cases.
Sample design : cross sectional study.
INCLUSION CRITERIA
Ø Age > 18 years in medical wards
Ø Hemoglobin < 6gm% ( according to WHO criteria)
Ø Microcytic , Hypochromic blood picture in peripheral smear
Ø Red cell indices suggestive of iron deficiency anemia.
If patients had congestive cardiac failure due to anemia, they were included in the study two weeks after the failure was controlled ( For baseline hemodynamics to be stabilized)
EXCLUSION CRITERIA
Ø Chronic renal failure
Ø Chronic liver disease
Ø Anemia in pregnancy
Ø Dimorphic anemia
Ø Other cardiac diseases ( Ischemic heart disease, Rheumatic heart disease and Infections related)
Statistical analysis : percentage and proportion is used .
7.3 Does the study require any Investigations or interventions to be conducted on patients or other animals?
PARAMETERS STUDIED
Ø Clinical features
Ø Hemogram, peripheral smear, red cell indices
Ø Serum ferritin
Ø Bone marrow study in selected cases
Ø Electrocardiogram
Ø Echocardiogram
7.4 Has ethical clearance been obtained from institution In case of 7.2
Yes .
8LIST OF REFERENCES
(1) Mohammed A-Biltagi, Osama Tolba, Mohammed Elshanshory, Ibrahim Badraia and SaharM.Hazaa . Atrial Function and Glutathione in Children with Iron Deficiency Anemia- Tanta-Egypt-2012. International Blood Research & Reviews .2013Aug;1(2): 72-86
(2) Alvarez JF, Oak JL , Pathare A V . Evaluation of cardiac function in iron deficiency anemia before and after total dose therapy. J Assoc Physicians India. 2000 Feb;48(2):204-6.
(3) Nikita Hegde, Michael W. Rich, CharinaGayomali.The Cardiomyopathy of Iron Deficiency. Tex Heart Inst J. 2006; 33(3): 340–344.
(4) Simsek H, Gunes Y, Demir C, Sahin M, Gumrukcuoglu HA, Tuncer M. The effects of iron deficiency anemia on p wave duration and dispersion.Clinics.2010 Aug;65(11):1067-1071.
(5) Suk Sohn ,Eun-Sun Jin, Jin-Man Cho, Chong-Jin Kim, Jong-HoaBae, Ju-Young Moon et al;Bloodletting-induced cardiomyopathy: reversible cardiac hypertrophy in severe chronic anaemia from long-term bloodletting with cupping. Eur J Echocardiogr.2008Jan; 9 (5): 585-586.
(6) Vitthal HK, Kammar KF; QTc Changes in Non-pregnant Females
with Severe iron deficiency anaemia. Journal of Clinical and Diagnostic Research. 2012 Jun;6(5): 777-779.
(7) Cristina Opasich, Mario Cazzola, Laura Scelsi, Stefania De Feo, EnzoBosimini, Rocco Lagioia et al. Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure.Eur Heart J. 2005Nov; 26 (21): 2232-2237.
(8) Ewa A. Jankowska, PiotrRozentryt, AgnieszkaWitkowska, Jolanta Nowak, Oliver Hartmann, BeataPonikowska , et al . Iron Deficiency Predicts Impaired Exercise Capacity in Patients With Systolic Chronic Heart Failure. 2011Nov;17(11): 899–906.
(9) Mohammed Abd Abdul Hussein.Relationship between Anemia and Diastolic Dysfunction
of the Heart.Medical journal of Babylon .2012 ;9( 1):166-181
910
11 / Name and Designation
(in block letters)
9.1 Guide
9.2 Signature
9.3 REMARKS
Head of Department
10.1 Signature
Remarks of the Principal.
11.1 Signature / DR.B.SHASHIDHARAN.
MD(GENERAL MEDICINE)
PROFESSOR,
VYDEHI INSTITUTE OF MEDICAL SCIENCES AND RESEARCH CENTRE, WHITEFIELD, BENGALURU-560066.
VERY FEW STUDIES DONE ON THIS TOPIC . NOT DONE PREVIOUSLY . HENCE A GOOD STUDY.
DR.SOMASEKAR D.S.
MD(GENERAL MEDICINE)
PROFESSOR & HOD,
VYDEHI INSTITUTE OF MEDICAL SCIENCES AND RESEARCH CENTRE, WHITEFIELD, BENGALURU-560066.