In this study, we investigated the changes in LA electro-mechanical and diastolic cardiac functions after T3 replacement in patients with low T3. The most important finding of the current study was a significant reduction was found in LAVI and total atrial conduction time after T3 replacement with an increase at T3 levels and without any significant change in diastolic function.
Hypothyroidism causes an impairment at relaxation of vascular smooth muscle cells and increases systemic vascular resistance and arterial stiffness, without apparent clinical significance [9]. LA phasic function and mechanics are significantly impacted by hypothyroidism. LA regularizes left ventricular filling with its reservoir, conduit and booster pump functions. Increased LA volume is a marker of LV diastolic dysfunction and is associated with further risk of atrial fibrillation (AF) [10]. Total atrial conduction time reflects the extent of both electrical and structural remodeling of the atria and an independent predictor of future AF, which is associated with a fivefold higher risk of stroke [11]. Trials of LT4 in subclinical hypothyroidism have shown improvements in left ventricular, cardiac mitochondrial and vascular endothelial function [12, 13]. Moreover, LT4 significantly, but not completely, improved the LA function and mechanics in these patients [6].
Ozturk et al. evaluated LA mechanical function using only phasic LAV changes in the patients with clinical and subclinical hypothyroidism and they found significant deterioration in LA mechanics in both two groups patients compared to the healthy controls [6]. However, studies which investigated the effect of combined T3 and T4 therapy in hypothyroid patients on the change of diastolic and LA volume and function were insufficient. Recent studies showed no significant differences in heart rate, systolic and diastolic function between the LT4 monotherapy vs. combined therapy [14–16]. Although we did not compare combined therapy versus single LT4 therapy in this study, a significant decrease was observed in LAVI and total atrial conduction time without any changes in systolic and diastolic parameters after adding T3 to therapy.
To our knowledge, there was no data on the effects of T3 replacement treatment on hypothyroid cardiomyopathy in the literature. Left ventricular mass and mass index did not change after adding T3 in our study, which may be partly explained by the fact that the patient group was consisted of patients with low T3, rather than the overt hypothyroidism patients.
In addition, T3 treatment has not only a beneficial effect on cardiac functions but also has a potentially adverse effect on heart rhythm and heart rate, suggesting that an optimal T4/T3 ratio may support the avoidance of adverse effects. In a review published by Biondi B. & Wartosky L.; they found no significant difference in systolic and diastolic function or heart rate between combined therapy vs T4 monotherapy, but some studies reported atrial arrhythmias with combination therapy [16]. In our follow-up period, we did not observe these aforementioned adverse cardiac effects. This result may explain with, we subtracted some of the total T4 doses and added a fixed low dose of T3 to prevent TH side effects. Avoidance of overtreatment at combination therapy decreases cardiac side effects [2, 17].
Meng et al. showed that, preserved ejection fraction heart failure patients with subclinical hypothyroidism were found to have cardiac diastolic dysfunction as evident by increased E/e’ ratio [18] and E/e’ ratio is an important parameter which shows left ventricular filling pressure. In our study, we could not observe a significant change on E/e’ ratio in our patients, which may be related to the normal cardiac functions at baseline.
There were several limitations to this study. One limitation was the relatively small number of patients. Another limitation was that the study only included women and did not have any control groups. Additionally, more advanced echocardiographic techniques such as strain assessment were not used.
In conclusion, the results of the current study suggest that adding T3 to LT4 treatment may improve LAVI and atrial conduction times in patients with low T3. However, more research with larger patient groups is needed to better understand the effects of combined hypothyroidism treatment on cardiac functions.