Thyroid hormone plays a crucial role in cardiovascular homeostasis in physiological as well as pathological conditions. Heart failure can trigger changes in metabolism and peripheral thyroid hormone concentration in euthyroid patients. In heart failure, the alteration of thyroid functions is referred to as low-T 3 (triiodothyronine) syndrome or euthyroid sick syndrome marked by a reduction in serum total T 3 and free T 3 with normal levels of T 4 and thyrotropin. This low-T3 syndrome is an adaptive compensatory and beneficial response that decreases the energy consumption of the diseased body. Heart failure is a complex clinical syndrome that could be the result of any structural or functional cardiac disorders that impairs the ability of ventricles to fill or eject blood (reduced ejection). 1 Coronary Artery Disease (CAD) accounts for a substantial portion of patients with chronic heart failure. Survival is markedly shortened in patients with heart failure. 2 The overall 5-year rate of mortality in patients with heart failure is 50% and 1-year mortality in patients with end-stage heart failure can be as high as 75%. 2. Role of various biological and neurohormonal factors in risk assessment of chronic heart failure has been studied in various clinical studies. Noradrenaline, Angiotensin II, Atrial natriuretic peptide (ANP), and Brain Natriuretic Peptide (BNP) have been used as prognostic markers for patients with heart failure. 3 The pathophysiology of low T 3 syndrome is due to impaired peripheral deiodination of T 4 to T 3 secondary todecreased activity of type I deiodinase enzyme, whichdeiodinases T4 to T 3 . Normally 20% of T 3 production comesfrom thyroidal secretion and 80% from peripheral deiodinationof T4. Though the production of T3 by the thyroid gland is normal, the peripheral production of T 3 is decreased. Production of rT3 isunchanged, while its clearance is diminished leading to raisedrT 3 levels.The syndromeaffects both sexes equally and affects people of all ages.Because of the increased incidence of chronic illness atadvanced ages the syndrome is more common in the elderly agegroup. Low T3 (triiodothyronine) levels correlate with increased mortality in chronic heart failure patients and benefits can be gained from thyroid supplementation. 45 Recent are of focus in studies have explored the use of triiodothyronine levels to predict mortality in heart failure patients. They are very few studies done in our area to determine the relation of low T 3 levels and heart failure. Therefore, we conducted the present study to determine the prevalence of low T 3 levels in heart failure and the role of Total T 3 when estimating severity in patientswith chronic heart failure as an adjunct to clinical and functionalparameters.

This prospective study was conducted in the Department of General Medicine and Cardiology, KMC, and MGM Hospital, Warangal from Jan 2017 to June 2019. Institutional Ethical Committee approval was taken for the study. Written permission was obtained from all the patients of the study.

1. Those diagnosed with heart failure for more than 3 months 2. Ventricular ejection fraction levels < 45% 3. LV end diastolic diameter of > 56mm

Exclusion Criteria

Based on the inclusion and exclusion criteria successive patients with heart failure were included in the study. A total of n=100 patients were included in the study. A questionnaire was prepared to note the duration,symptoms, and treatment of heart failure. Questions were asked concerning chest pain, dyspnoea, syncope, cough, smoking, andmedications. All previous clinical records of the patients were analyzed in detail. Based on the degree of effort needed to elicitsymptoms patients were assigned to NYHA (New York HeartAssociation) class I to IV.A detailed physical examination was conducted to assessthe patient's volume status (rales, edema, jugular venous distension),weight, height, body mass index, and orthostatic blood pressurechanges.Complete blood count, blood glucose (fasting and 2 hours postprandial), Fasting serum lipid profile, blood urea, serumcreatinine, and serum electrolytes were measured in all patients.Two-dimensional echocardiography was done in the cardiologydepartment of Mahatma Gandhi general hospital was reviewed for evidence of atrial enlargement, ventricularhypertrophy, evidence of antecedent myocardial infarction, andconduction blocks. Thyroid hormonemeasurements TSH, total T 3 , total T 4 , free T 3 , free T 4 were made inall patients in the same fasting morning sample. All the above datawere obtained between two to five days of enrolment in the study.Chest X-ray posteroanterior view was done in all patients to note pulmonary congestion, pleural effusion, and to estimate cardiothoracic ratio M-mode echocardiography was used to assess the left ventricle dimensions. The left ventricle internal dimension in end-systole N=13 out of total n=28 females were found with low T 3 levels. Similarly, in males n=8 out of total n=72 cases were found with low T 3 levels. The difference of proportions between the two groups is analyzed using the Chi-square test which is not statistically significant.

Total T 3 values of all the n=100 patients were computed. Out of the n=100 patients, n=28 were females and n=72 were male patients. The prevalence of low T 3 is found to be 21% had Total T 3 less than the lower limit of 80 ng/dl. The mean age of patients in the Low T3 group is 62.5 years which is higher than the mean age in patients with the Normal T 3 group 52.0 years.The difference of means between the two groups is analyzed using an independent T-test which is statistically significant.The mean BMI of patients in the Low T 3 group is 25.56 kg/m2which is higherthan the mean BMI in patients with the Normal T 3 group 25.10 kg/m2.Thedifference of means between the two groups is analyzed usingan independent Ttest which is not statistically significant. Analysis of Echocardiography parametersCompared to patients who were alive (n=90),left ventricular end-diastolic diameter was higher in those whodied (n=10). The mean ejection fraction in died and alive groups were27.19% and 35.12% respectively. Persons who died had asignificantly lower ejection fraction than those alive.When the mean ejection fraction was compared betweenpatients with low total T 3 (T 3 <80 ng/dl) and normal T 3 , patients with low T 3 had a mean ejection fraction of 29.2% and those with normal T 3 levels had a mean ejection fraction of 34.78%. Thisindicates mean ejection fraction is lower in patients with low total T 3 levels (table 1) Table 1: Analysis of Echocardiography parameters * Significant N=32 out of n=100 cases were with the history of hypertension of which n=17 cases were in the low T 3 group and the rest were with normal T 3 levels. The comparison of hypertension within low T 3 was done showing the p values as 0.014 as significant given in table 2. A comparison between dyslipidemia, between normal T 3 and low T 3 , shows the values were found to be significant. Out n=10 patients dead n=7 cases were of dyslipidemia of which n=5 cases were with low T 3 and n=2 cases were of normal T 3 . As far as obesity is concerned the comparison between normal T 3 and low T 3 did not reveal any significant values. Similarly, for beta-blockers, the values were not found to be significant and smoking also did not show any significance between the normal T 3 and low T 3 levels. The results show a significant relationship between total T 3 with ejection fraction, indicating patients who have low ejection fraction have low total T 3 levels. Total T 3 levels did not correlate with sex. There is a significant correlation betweenadvancing age and lower total T 3 levels. Using a cutof total T 3 level of 80 ng/dl (the lower limit of normal) two subgroups were identified and Kaplan-Meiersurvival analysis was compiled. Survival at 24 months in a low total T 3 group was found to be less than the group with total T 3 80 ng/dl and above.

The results of the present study showed that the death was significantly related to low T 3 levels, low ejection fraction, and higher left ventricular end-diastolic diameter (LVEDD). Studies have shown that changes in thyroid metabolism characterized by a reduction in biologically active T 3 have been reported in HF and commonly interpreted as a compensatory mechanism.

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In a cohort of 573 unselected cardiac patients, the probability of death was significantly higher in patients with low T 3 syndrome; free (F)T3 resulted also in a powerful independent predictor of cardiac and cumulative death. 6 Kozdag G et al; 7 found a significant correlation between low T 3 values and reduced ejection fraction. We also found a significant negative correlation of low total T 3 levels with advancing age which means as the age of patients increases the prevalence of Low T 3 increases. This contrasts with the study by Pingitore et al; 8 who did not find any correlation between low total T 3 and ejectionfraction.In the current study Kaplan-Meyer survivalcurves of patients with reduced left ventricular ejection fraction (LVEF)and total T3 showed the highest mortality when compared with thatof patients with similar LVEF but normal total T 3 which indicate that low T 3 patients are a greater risk of death. From our study, we found that age, ejection fraction, and T 3 levels are associated with high mortality. And there was a correlation of total T 3 with age and ejection fraction. Opasich et al; 9 found low T 3 syndrome was not an independent negative prognostic factor but has a definite role when used along with other parameters. Echocardiographic alterations, and mortality in patients with dilated cardiomyopathy. Hamilton et al; 10 reinforced previous data in a smaller cohort of patients showing the potential capacity of prognostic stratification of the altered THmetabolism in HF.Zargar et al; 11 studied sick euthyroid syndrome in chronic nonthyroidal illness and found a prevalence of 20.60%. There has been some evidence that HF patients have gained a small but significant benefit when treated with thyroxine. However, there are only a few studies that have tested the use of synthetic T 4 or T 3 in the treatment of cardiac dysfunction. 1213 However, there are also concerns of noncardiac collateral effects of hormone increasing oxygen consumption, heart rate, and negative effects on protein and fat metabolism. An alternative approach is to use TH analogs with fewer side effects such as 3,5-diiodothyropropionic acid (DITPA)with minimal effects on heart rate and metabolic activity. 1415 We in the present study used only a minimal dose of T 4 in cases with low T 3 syndrome. Although it proved to be beneficial in some patients, the presence of other confounding factors was responsible for the death of some patients.

Within the limitations of the present study, it can be concluded that the prevalence of low T 3 syndrome in patients with chronic heart failure is common. It was found that patients with lower T 3 levels were having a lower ejection fraction.The LVEDD diameterwas negatively correlated with total T 3 . Therefore, Total T 3 levels can be used as an adjunct to other parameters for risk stratification and survival estimation in chronic heart failure.