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Background: Subclinical hypothyroidism has been associated with heart failure, but only small trials assessed whether treatment with levothyroxine has an impact on cardiac function.Methods: In a randomized, double-blind, placebo-controlled, trial nested within the TRUST trial, Swiss participants ages ≥65 years with subclinical hypothyroidism (thyroid-stimulating hormone [TSH] 4.60-19.99 mIU/L; free thyroxine level within reference range) were randomized to levothyroxine (starting dose of 50 µg daily) to achieve TSH normalization or placebo. The primary outcomes were the left ventricular ejection fraction for systolic function and the ratio between mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e' ratio) for diastolic function. Secondary outcomes included e' lateral/septal, left atrial volume index, and systolic pulmonary artery pressure.Results: A total of 185 participants (mean age 74.1 years, 47% women) underwent echocardiography at the end of the trial. After a median treatment duration of 18.4 months, the mean TSH decreased from 6.35 mIU/L to 3.55 mIU/L with levothyroxine (n = 96), and it remained elevated at 5.29 mIU/L with placebo (n = 89). The adjusted between-group difference was not significant for the mean left ventricular ejection fraction (62.7% vs 62.5%, difference = 0.4%, 95% confidence interval -1.8% to 2.5%, P = 0.72) and the E/e' ratio (10.6 vs 10.1, difference 0.4, 95% confidence interval -0.7 to 1.4, P = 0.47). No differences were found for the secondary diastolic function parameters or for interaction according to sex, baseline TSH, preexisting heart failure, and treatment duration (P value >0.05).Conclusion: Systolic and diastolic heart function did not differ after treatment with levothyroxine compared with placebo in older adults with mild subclinical hypothyroidism.

To the Editor, We read with great interest the article by El Aouar et al.1, entitled "Relationship between left atrial volume and diastolic dysfunction in 500 Brazilian patients", which was published in the previous issue of Arquivos Brasileiros de Cardiologia. The authors1 aimed to evaluate the relationship between left atrial volume index and different grades of diastolic dysfunction in Brazilian patients submitted to echocardiogram. Although we commend the authors for the detailed and valuable information that they have provided, some comments may be beneficial. Diastolic dysfunction is associated with adverse outcomes and its prevalence among hypertensive, hyperlipidemic and diabetic adults is very high2. It has been shown that lowering blood pressure and heart rate, management of impaired lipid profile and blood glucose could improve diastolic dysfunction2. Also, thyroid dysfunction has been associated with the development of diastolic dysfunction even in patients without underlying heart disease3. Diuretics, ACE inhibitors and angiotension-II receptor antagonists, nitrates and their derivatives, calcium channel blockers, alpha-blockers, nicardipine and phosphodiesterase inhibitors reduce left ventricular filling pressures2,3. Statins could ameliorate diastolic dysfunction by attenuating myocardial interstitial fibrosis and angiogenesis independently of their lipid lowering effects4. Thyroid hormonotherapies increase cardiac output by affecting stroke volume and heart rate, and reduce systemic vascular resistance by activating the renin-angiotensin-aldosterone system; resulting in an improvement in diastolic dysfunction3. It has been demonstrated in diabetic cardiomyopathy that eplerenone, the mineralocorticoid receptor blocker, has anti-fibrotic effects which could attenuate cardiac steatosis, apoptosis and remodelling as well as diastolic dysfunction5. In conclusion, if the medication details which can be associated with diastolic dysfunction had been given, the study would have been more valuable.