Efficacy And Safety Of Levothyroxine Replacement In Chronic Heart Failure Patients With Subclinical Hypothyroidism

Background:Subclinical hypothyroidism(SCH)is a common condition in patients with heart failure.Evidence on the effect of thyroid hormone treatment is lacking.We aimed to determine whether levothyroxine provided clinical benefits in patients with chronic heart failure complicated with subclinical hypothyroidism.Methods:We conducted a prospective,open-label,multi-centre,randomized,controlled clinical trial involving 117 adults who were18 to 80 years of age,with systolic heart failure with New York Heart Association(NYHA)class Ⅱ-Ⅲ,left ventricular ejection fraction≤40%,and subclinical hypothyroidism(TSH within ULN to 10 mIU/mL and FT4 level within reference range).A total of 58 patients were assigned to receive levothyroxine(at a starting dose of 12.5μg daily,and will be titrated until TSH is within the normal range.59 patients were assigned to receive standard CHF therapy.The primary endpoints include the difference in distance of the six-minute walk test between 24 weeks and baseline.The secondary endpoints include differences in the plasma NT-proBNP levels and serum lipid profiles,changes in the NYHA classification,cardiovascular death,re-hospitalization,differences in echocardiographic and cardiac magnetic resonance imaging measures,and Minnesota Living With Heart Failure Questionnaire(MLHFQ)results between 24 weeks and baseline.Results:The mean age of the experimental group was 56.69±16.13 years,with 18 females(31%),and the control group was 58.27±14.49 years,with 12 females(20.3%).The average level of thyrotropin(TSH)was 6.66±1.86mIU/ml in the experimental group and 7.16±2.73mIU/ml in the control group.All demographics of subjects in the two groups were comparable.At week 24,the distance improvement value Δ(m)of 6MWT in the experimental group was statistically different from that in the control group[median 60(30,50)m vs-10(-25,41)m,P=0.01].There were significant differences in the Minnesota quality of life score(MLHFQ)between the groups.at month 6,17.22 ± 12.17 points of the experimental group,and 28.57 ± 28.33 points of the control group(P=0.01).After 24-week follow-up,NT-proBNP,left ventricular end diastolic diameter in echocardiography,left ventricular systolic function EF were no significant differences between two groups(P>0.05).There were 5 cases of clinical death in the test group(9.6%)and 7 cases of clinical death in the control group(13.7%).There was no significant difference between the two groups(P=0.51).Conclusions:This study indicates that in heart failure patients with subclinical hypothyroidism,small dose of thyroid hormone supplementation can improve the symptoms of heart failure in these patients,improve their activity tolerance,and lead to better quality of life,with good safety within the 6-month treatment window.