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Effect of Levothyroxine Treatment on Heart Rate Variability in Hypothyroidism: Systematic Review and Meta-Analysis

Valentin Brusseau, Igor Tauveron, Reza Bagheri, Ukadike Chris Ugbolue, Valentin Magnon, Valentin Navel, Jean-Baptiste Bouillon, Frederic Dutheil

Introduction: We performed a systematic review and meta-analysis of the effect of levothyroxine treatment on Heart Rate Variability (HRV) in hypothyroidism. Indeed, abnormalities of HRV exist in hypothyroidism, but their reversibility after treatment remains contradictory.

Methods: We searched for articles related to HRV parameters in treated and untreated hypothyroidism in different databases (pubmed, cochrane, embase, and google scholar) until November 15, 2022. We performed a meta-analysis for each HRV parameter, stratified according to the degree of hypothyroidism: RR intervals (or Normal to Normal intervals-NN), SDNN (Standard Deviation of RR intervals), RMSSD (square root of the mean difference of successive RR intervals), pNN50 (percentage of RR interval with more than 50 ms of variation), Total Power (TP), LFnu (Low-Frequency normalized unit), HFnu (High-Frequency normalized unit), VLF (Very Low Frequency) and LF/HF ratio.

Results: We included 10 studies with a total of 269 untreated hypothyroid patients, 184 treated hypothyroid patients and 348 healthy controls. After treatment, there was an increase in SDNN (ES=0.72, 95% CI 0.27 to 1.16), RMSSD (1.37, 0.34 to 2.39), pNN50 (3.04, 1.29 to 4.79), and a decrease in LFnu (-1.26, -2.46 to -0.06) and LF/HF ratio (-0.78, -1.42 to -0.15) (p<0.05), without significant difference for RR intervals, TP and HFnu. However, abnormalities persisted after treatment compared to controls (p<0.05) with lower SDNN (-0.72, -1.22 to -0.23) and HFnu (-0.83, -1.46 to -0.21) and higher LF/HF (0.35, 0.11 to 0.59).

Conclusion: After treatment, there is an improvement in the parameters of the HRV, hence a beneficial effect of levothyroxine substitution, particularly for monitoring the evolution of cardiovascular morbidity. However, this reversibility of abnormalities remains partial.