Long-term hydroxychloroquine exposure impairs the left ventricular longitudinal strain

Introduction

Antimalarial drugs are commonly used in connective tissue and rheumatologic diseases. Hydroxychloroquine (HCQ) impairs the lysosomal function leading to intracellular accumulation of metabolic degradation products. Retinopathy is the best-known complication of long-term HCQ use, but rare severe cardiac side effects have also been reported (heart failure, conduction disorders leading exceptionally to transplantation). To date, no prospective clinical research to detect cardiac HCQ-related toxicity has been conducted.

Objective

We aimed to evaluate whether chronic HCQ intake impairs the left ventricular systolic function assessed by global longitudinal strain (GLS).

Method

We prospectively investigated patients treated with HCQ and referred for a routine trans-thoracic echocardiography (TTE) in the Dijon university hospital between September 2017 and June 2023. Patients with a history of heart disease or heart failure, a decreased LVEF, or an abnormal ECG were excluded. Demographic data, duration of HCQ exposure, associated diseases and echocardiographic data (LVEF, LV diastolic function, global and regional strain) were collected. Patients were divided in tertile of HCQ-exposure duration (ED).

Results

Sixty-three patients were studied with a mean HCQ ED of 135.3 (± 81.1) months. The mean age was 50.4 years, 90% were women and 63.5% were treated for a lupus. The mean left ventricular GLS was −21.2% (± 3.0) and the mean LVEF was 65.5% (± 6.4). The mean corrected QT interval according to Bazett was 405.9 ms (± 37.7) with no differences among the three tertiles. There was a positive correlation between HCQ ED and GLS (Pearson r 0.32, P = 0.012, Fig. 1), whereas no significant correlations were found between HCQ ED and both LVEF and diastolic function. GLS was significantly different among the three tertiles (P = 0.020). Post hoc tests identified significant differences in mean GLS between the 1st tertile (mean ED 48 ± 23.5 months, mean GLS −22.4 ± 2.1%) and the 3rd tertile (mean ED 240 ± 23.5 months, mean GLS −19.9 ± 2.8%) (P = 0.018).

Conclusion

This is a princeps study demonstrating a significant correlation between the duration of HCQ exposure and left ventricular GLS alteration. Further studies are needed to determine the relevance of systematic TTE for the detection of cardiac HCQ- related toxicity.