Hydroxychloroquine cardiotoxicity presenting as a rapidly evolving biventricular cardiomyopathy: key diagnostic features and literature review

Abstract

Cardiotoxicity is a rare but serious complication of hydroxychloroquine, a 4-aminoquinoline increasingly used in the treatment of rheumatological disorders. We describe typical clinical, echocardiographic, and histological features of this rare condition according to the currently available literature, illustrated with a recent new biopsy-proven case of hydroxychloroquine cardiotoxicity in a 52-year-old female with rheumatoid arthritis. Presentation in this case was of a rapidly progressive decompensated biventricular cardiomyopathy associated with recurrent biomarker elevations, conduction system disease, and possibly neuromyotoxicity. Death occurred suddenly 2 months after diagnosis despite drug discontinuation and clinical improvement. The potential role of cardiac magnetic resonance delayed gadolinium enhancement imaging in the prognosis of this toxic cardiomyopathy is also introduced. This case-based literature review highlights that, although rare, hydroxychloroquine cardiotoxicity can be fatal, particularly if irreversible histopathological changes have occurred prior to drug discontinuation. Given this, regular screening with 12-lead electrocardiography and transthoracic echocardiography to detect conduction system disease and/or biventricular morphological or functional changes should be considered in hydroxychloroquine-treated patients in addition to recommended ophthalmological screening.

Drugs That May Cause or Exacerbate Heart Failure

“…More than 70 cases of cardiotoxicity have been reported with these agents in which chloroquine has primarily been implicated. 278 Cardiotoxicity manifests as restrictive or dilated cardiomyopathy or with conduction system abnormalities such as atrioventricular and bundle-branch block. 279,280 Because both chloroquine and hydroxychloroquine are cationic amphiliphilic drugs, they are hypothesized to bind to phospholipids within the myocyte, accumulating in the lysosomes and inhibiting lysosomal enzymes.…”

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

“…However, lifetime treatment with doxycycline may lead to development of resistance (205), and it is not clear whether this treatment is sufficient for every clinical manifestation of T. whipplei infection (199). Both doxycycline and hydroxychloroquine are known to have adverse effects when used for a longer period (228,229). For hydroxychloroquine, the main complication is retinal toxicity and to a lesser extent, cardiotoxicity and neuromyotoxicity (228).…”

“…Both doxycycline and hydroxychloroquine are known to have adverse effects when used for a longer period (228,229). For hydroxychloroquine, the main complication is retinal toxicity and to a lesser extent, cardiotoxicity and neuromyotoxicity (228). Long-term side effects of doxycycline use include mainly gastrointestinal and skin manifestations (229).…”

Hydroxychloroquine-induced restrictive cardiomyopathy: a case report

“…Risk factors for development of HCQ-induced cardiotoxicity include old age, female sex, long duration of therapy (>10 years), high dose HCQ, pre-existing cardiac disease and renal impairment. [1][2][3][4][5] Diagnostic modalities for HCQ-induced cardiomyopathy are 2D echocardiography, CMR and endomyocardial biopsy. On echocardiography, the hallmark finding of HCQ cardiotoxicity is diffusely thickened ventricular wall.…”