|Year : 2018 | Volume
| Issue : 1 | Page : 18-21
Ferritin level: Predictor of thalassemia cardiomyopathy
PK Panda, Y Sharma
Department of Cardiology, PGIMER, Chandigarh, India
|Date of Web Publication||27-Apr-2018|
P K Panda
Department of Cardiology, PGIMER, Chandigarh
Source of Support: None, Conflict of Interest: None
Introduction: Thalassemia is the most common genetic disorder worldwide. Regular transfusion therapy, while improving patient quality of life, creates a state of iron overload. Once reticuloendothelial stores saturate, iron deposition increases in parenchymal tissues such as endocrine glands, hepatocytes, and myocardium. Cardiac iron deposition produces arrhythmias, systolic and diastolic dysfunction, and congestive heart failure in the second or third life decade.
Aims and Objective: The present study was planned to find the prevalence of thalassemia cardiomyopathy and to study the spectrum of cardiac disease in thalassemia patients.
Methods: All consecutive patients of thalassemia more than 12-year-old were included in this study. Screening included medical history assessment, focusing on cardiovascular symptomatology, transfusion and chelation history, physical examination, and transthoracic resting echocardiography. Clinical parameters included age, sex, address, height weight, body mass index (BMI), systolic blood pressure (BP), diastolic BP, mean hemoglobin, and mean serum ferritin.
Results: A total of 56 patients of thalassemia were included in the study. Fifty-one patients were of thalassemia major and 5 patients were of thalassemia intermedia. Mean age of patients included in our study was 15.9 ± 4.6 years. Mean duration of thalassemia in our patients was 12.9 ± 3.05 years. Mean hemoglobin of the patients included in our study was 8.7 ± 1.1 g%. The level of mean serum ferritin in our patients was 666.69 ± 325.46 ng/ml. In our study, we had 8 (14.2%) patients out of 56 having systolic dysfunction. Furthermore, our patients with left ventricular systolic dysfunction had younger mean age as compared to those patients who had a normal left ventricular function. We also found a higher ferritin value in patients with left ventricular dysfunction as compared to patients with normal left ventricular dysfunction studies.
Conclusion: In our study, we found out that patients with left ventricular dysfunction had a younger age of onset of disease, higher ferritin levels, lower blood pressure, and paradoxically higher BMI as compared to patients with normal left ventricular dysfunction.
Keywords: Heart failure, iron overload, thalassemia, thalassemia cardiomyopathy
|How to cite this article:|
Panda P K, Sharma Y. Ferritin level: Predictor of thalassemia cardiomyopathy. Heart India 2018;6:18-21
| Introduction|| |
Approximately 7% of the global population is a carrier for hemoglobin disorders. β-thalassemia is the most common single-gene disorder in the Indian population. Ten percent of the total world's thalassemic population are born in India every year. Certain communities in India, such as Sindhis, Gujaratis, Punjabis, and Bengalis, have a high prevalence of beta-thalassemia, the incidence varying from 1% to 17%. It has been estimated that the prevalence of pathological hemoglobinopathies in India is 1.2/1000 live births, and with approximately 27 million births per year, this would suggest the annual birth of 32,400 babies with a serious hemoglobin disorder. Three clinical forms of β-thalassemia are distinguished, depending on clinical severity: thalassemia major, thalassemia intermedia, and thalassemia minor. In β-Thalassemia major, anemia is severe, develops during the 1st year of life, and requires life-long transfusion therapy for survival. Thalassemia intermedia, on the other hand, accounts for up to 25% of cases. The phenotypic spectrum extends between the clinically severe thalassemia major on the one end and the asymptomatic thalassemia carrier state on the other end. Anemia in thalassemia intermedia is generally milder than that of the major form and is not transfusion dependent, whereas the disease has a later clinical onset and is associated with longer survival compared with thalassemia major. Despite the advances in therapeutic management of thalassemia major and the resulting substantial improvement of patients' survival, heart disease always represented and still remains the primary cause of mortality and a major cause of morbidity. Thalassemia cardiomyopathy can present with dilated left ventricular cardiomyopathy or restrictive left ventricular filling. The aim of the present study was to find the prevalence of thalassemia cardiomyopathy and to study the spectrum of cardiac disease in thalassemia patients.
| Methods|| |
This study was conducted in the Department of Cardiology, PGIMER, Chandigarh. All consecutive patients of thalassemia >12 years of age were included in this study. Screening included medical history assessment, focusing on cardiovascular symptomatology, transfusion and chelation history, physical examination, and transthoracic resting echocardiography. Medical history assessment included both patient interview and review of the hematology records of the patients. Clinical parameters included age, sex, address, height weight, body mass index body mass index (BMI), systolic blood pressure (BP), diastolic BP, mean hemoglobin, and mean serum ferritin.
Detailed echocardiography was recorded in all patients on Phillips IE33 ultrasound machine. Complete M-mode, two-dimensional, and Doppler (pulsed wave, continuous-wave, and color) echocardiography was performed at rest. All echo-Doppler studies were carried out by the same observer. Measurements represented the average values of at least three cardiac cycles. During the echocardiographic study, heart rate and BP was also measured; BP was measured in the right arm, using the same cuff sphygmomanometer for all patients. All echocardiographic measurements were done according to ASE guidelines.
Descriptive statistics was calculated for the various variables and presented as percentages, mean ± standard deviation for qualitative and quantitative variables, respectively. Continuous variables were analyzed by Student's t-test and discrete variable was analyzed by Chi-square test and where applicable ANOVA test. For correlation analysis, Pearson's correlation coefficient was calculated for normally distributed variables and Spearman's rank-correlation coefficient for other variables. P < 0.05 was considered statistically significant. All statistical analysis will be done using SPSS version 17 (IBM, USA).
| Results|| |
A total of 56 patients of thalassemia were included in the study. Fifty-one patients were of thalassemia major and 5 patients were of thalassemia intermedia. Mean age of patients included in our study was 15.9 ± 4.6 years. Males predominated the study population (n = 37/66.07%) compared to females (n = 19/33.93%). Mean duration of thalassemia in our patients was 12.9 ± 3.05 years. Mean hemoglobin of the patients included in our study was 8.7 ± 1.1 g%. The level of mean serum ferritin in our patients was 666.69 ± 325.46 ng/ml. Thalassemia major patients were receiving blood transfusion at a mean duration of 20.9 ± 3.13 days, and 21 (37.5%) patients were receiving chelating therapy.
The mean height of the patients included in our study was 148.3 ± 9.09 cm. The mean weight of the patients included in this study was 43.9 ± 9.3 kg. Mean BMI of patients included in our study was 19.7 ± 2.3 kg/m 2. Mean systolic blood pressure of the patients included in our study was 111.8 ± 16.02 mmhg. Mean diastolic blood pressure of the patients included in our study was 73.0 ± 10.3 mmhg. Out of 56 patients 5 (8.93%) patients had hypertension [Table 1].
|Table 1: Demographic profile of thalassemia patients with normal left ventricular function and left ventricular systolic dysfunction|
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All of the 56 patients underwent echocardiographic study. Mean left ventricular diastolic diameter and left ventricular systolic diameter was 44.98 ± 7.03 mm and 31.23 ± 8.6 mm respectively. The mean interventricular septal systolic dimension and diastolic dimension was 9.6 ± 1.3 mm and 8.01 ± 1.1 mm, respectively. The mean posterior wall systolic and diastolic dimension was 8.01 ± 0.9 mm and 7.25 ± 0.8 mm, respectively. The mean fractional shortening was 29.5% ±5.3%. The mean left atrial diameter and mean left atrial volume was 18.08 ± 5.94 mm and 10.75 ± 2.4 mm 2, respectively. The mean Left ventricular mass was 152.8 ± 25.9 mg. Out of 56 patients, 8 (14.29%) patients had left ventricular systolic dysfunction. Mean left ventricular ejection fraction was 59.2% ±9.13% in our patients.
The mean value of E wave velocity was 62.3 ± 19.5 cm/s and the mean A wave velocity was 59.16 ± 17.01 cm/s. The mean E wave deceleration time was 174.96 ± 37.5 ms. The mean E/A ratio was 1.15 ± 0.49. The mean E/e” was 6.4 ± 2.15. The mean intraventricular relaxation time was 54.10 ± 12.05 ms.
Left ventricular diastolic dysfunction was present in 18/56 (32.14%) patients. Grade 1 diastolic was present in 12 patients, Grade 2 and Grade 3 diastolic dysfunction was present in 3 patients each, respectively. Pulmonary artery hypertension was present in 11 (19.6%) patients [Table 2].
|Table 2: Echocardiographic profile of thalassemia patients with normal left ventricular function and left ventricular systolic dysfunction|
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| Discussion|| |
In our study, we had 8 (14.2%) patients out of 56 having systolic dysfunction. Also our patients with left ventricular systolic dysfunction had younger mean age as compared to those patients who had a normal left ventricular function. Mean ejection fraction was higher than previously mentioned study. We also found a higher ferritin valve in patients with left ventricular dysfunction as compared to patients with normal left ventricular dysfunction consistent with the previous studies.
Furthermore, in our study, we found out that patients with left ventricular dysfunction had a younger age of onset of disease, higher ferritin levels, lower blood pressure, and paradoxically higher BMI as compared to patients with normal left ventricular dysfunction. There was no difference in use of chelating agent, duration of thalassemia and frequency of blood transfusion in patients with left ventricular systolic dysfunction and patients without left ventricular dysfunction.
In our study, left ventricular diastolic dysfunction was present in 18/56 (32.14%) patients.
Severe IE, chronic anemia, and hypoxia also cause increased gastrointestinal tract iron absorption. Without transfusion support, 85% of patients with severe homozygous or compound heterozygous beta thalassemia will die by 5 years of age because of severe anemia. However, transfusions lead to progressive iron accumulation because of inadequate excretory pathways. When serum transferrin saturation exceeds 70%, free iron species, such as labile plasma iron, have been found in the plasma as well as labile iron pool in the red blood cells. These iron species are mainly responsible for generating reactive oxygen species with eventual tissue damage, organ dysfunction, and death. Iron chelation therapy has proven to be the only option to reduce morbidities and prolong survival into the fourth and fifth decades of life.
Although in our study, we were not able to demonstrate that patients on chelation therapy had less incidence of thalassemia cardiomyopathy but patients having left ventricular dysfunction had higher ferritin levels. In a published series  of 52 patients with thalassemia major with heart failure, 83% of cases had left-sided heart failure, with left ventricular dilatation and reduced contractility (mean ejection fraction, 36% ± 9%). Earlier studies also have shown that global and segmental left ventricular function remains within normal range until the final stages of the disease. Moreover, patients with right heart failure and left ventricular myocardial restriction had some indications of a higher iron burden, as shown by the higher mean serum ferritin concentration and the greater number of blood units transfused during the past years.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]