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.

Keywords: Cardiomyopathy; cardiotoxicity; endomyocardial biopsy; heart failure; hydroxychloroquine.

Figure 1.

Findings on imaging modalities in support of the diagnosis of hydroxychloroquine cardiomyopathy. (a) Pulse-wave Doppler of mitral inflow on 2-dimensional transthoracic echocardiography shows increased E-wave peak velocity to A-wave peak velocity ratio (E/A) of >1.5 associated with reduced deceleration time of <160 m/s suggestive of restrictive physiology. (b) Pulse-wave tissue Doppler imaging at the septal mitral annulus shows significantly reduced early diastolic relaxation velocity (0.02 m/s) confirming restrictive pattern diastolic dysfunction. In addition, markedly elevated E/E′(ratio of mitral inflow E-wave peak velocity to tissue Doppler early diastolic velocity) of >15 is shown, suggestive of significantly elevated left ventricular filling pressures. (c and d) Cardiac magnetic resonance 4-chamber (c) and 2-chamber (d) delayed gadolinium enhancement imaging illustrating areas of patchy enhancement throughout the mid-wall, particularly in the septum and apical anterior walls (arrows).

Figure 2.

Histological findings from right ventricular endomyocardial biopsy on light microscopy (top panels) and electron microscopy (bottom panels). (a) Myocyte hypertrophy and focal myocyte damage is demonstrated with vacuolization of the some of the cardiomyocytes. Some of these vacuoles contain central nuclei (arrows). (b) Masson’s trichrome stain highlights marked interstitial fibrosis (green/blue staining). (c and d) Electron microscopy showed cytoplasmic inclusion bodies: rounded aggregates of dark osmiophilic staining small bodies, some of which contain curvilinear and lamellar character (so-called ‘myelin bodies’) (arrows).