Left ventricular global longitudinal strain impairment during long-term hydroxychloroquine exposure

AIMS: Antimalarial-induced cardiomyopathy (AMIC) is a rare but severe and under-recognized condition. Although screening for ocular toxicity is recommended, this is not the case for cardiac damage. After observing three successive cases of AMIC, we aimed to study the association of chronic hydroxychloroquine (HCQ) intake on echocardiographic parameters in asymptomatic patients. METHODS AND RESULTS: After analyzing the characteristics of the 3 patients diagnosed with AMIC, we systematically investigated patients treated with HCQ and referred for routine transthoracic echocardiography between September 2017 and April 2025. Patients with known heart disease or decreased left ventricular ejection fraction (LVEF) were excluded. Patients were divided into tertiles of HCQ-exposure duration (ED). Eighty-two patients were included with a median HCQ-ED of 132 months (72-204) and a cumulative HCQ dose of 1414 g (864-2358). Global longitudinal strain (GLS) was significantly different among the three tertiles of HCQ-ED (p = 0.048) whereas there was no difference in LVEF, left ventricular mass or diastolic function. GLS values were significantly correlated with HCQ-ED (r = 0.395, p < 0.001) and HCQ cumulative dose (r = 0.402, p < 0.001). GLS remained significantly associated in multivariate linear regression analysis adjusted for age, female sex, creatinine and hypertension. A threshold of 1994 g had 78.6% sensitivity and 76.5% specificity for impaired GLS (> - 18%). CONCLUSION: This is the first study highlighting the association between long-term HCQ-ED and systolic dysfunction assessed by GLS in asymptomatic patients. Because of its poor prognosis, early detection of AMIC is necessary, and GLS could be an interesting tool in the screening strategy for the detection of pre-clinical alterations.