Cardiomyopathy Related to Antimalarial Therapy with Illustrative Case Report

Abstract

The antimalarial agents, chloroquine (CQ) and hydroxychloroquine (HCQ) are used in long-term treatment of connective tissue diseases and dermatological disorders and are generally regarded as safe. We present one case of cardiotoxicity in a 59-year-old woman treated with antimalarials during 13 years for a discoid lupus erythematosus. She progressively developed conduction disturbances and congestive heart failure (CHF). When the diagnosis of antimalarials toxicity was suspected, CQ was withdrawn. However, heart transplantation had to be performed in the following 4 months for severe CHF. Indeed, rare but severe cardiotoxicity may develop following prolonged use of antimalarials with both conduction disturbances (45 patients) and CHF (25 patients). These cardiac toxic effects have been reported with CQ and less frequently with HCQ use alone. Diagnoses are often delayed since the toxicity of the drug might be misattributed to other factors in these patients. The endomyocardial biopsy, or in some cases the muscle biopsy, are essential to confirm the antimalarials toxicity. Antimalarials have been stopped in 12 cases of CHF, leading to improvement in 8 cases (within 3 months to 5 years) and to deaths or to heart transplantation in 4 cases (within 1 week to 3 months). In the latter cases, as in our patient, the lack of improvement may have been explained by the severity of the cardiomyopathy at diagnosis and the short delay since withdrawal. As a consequence, the potential for reversibility and the severity in undiagnosed cases of these toxic cardiomyopathies emphasize the importance of recognizing early signs of toxicity in order to withdraw antimalarials before the occurrence of life-threatening CHF.

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

“…20 Echocardiography plays a key adjunctive role in the diagnosis of HCQ cardiotoxicity. Diffusely thickened ventricular walls on transthoracic echocardiography are one of the hallmarks of this form of cardiomyopathy 7,12,13,[17][18][19][20] and were seen from earlier on in our patient's course. In one report where the patient went on to undergo successful orthotopic heart transplantation, interventricular septal thickness in the explanted heart measured 20 mm.…”

“…7,10 Indication in both cases was refractory congestive heart failure 3 months after drug discontinuation. In the review by Costedoat-Chalumeau et al, 7 of the 25 congestive heart failure cases described, death occurred in 11 (46%) and partial or complete improvement was seen in eight out of 12 cases where the drug was discontinued. Meanwhile regression of conduction disease appears to be rare -out of 15 patients with conduction disorders in which the causative agent was discontinued, only three had resolution of the disturbance.…”

“…In a new case reported by the same authors, concerning severe cardiotoxicity leading to heart transplantation due to use of both HCQ and CQ over a 9-year period, retinal toxicity and neuromyotoxicity were also present. 7 The most common manifestation of neuromyotoxicity is a bilateral progressive proximal weakness of the lower extremities with variable polyneuropathy. 7,11 Proximal myopathy was present in this case, although muscle biopsy to confirm antimalarial toxicity as the cause of this finding had not been performed.…”

“…7 The most common manifestation of neuromyotoxicity is a bilateral progressive proximal weakness of the lower extremities with variable polyneuropathy. 7,11 Proximal myopathy was present in this case, although muscle biopsy to confirm antimalarial toxicity as the cause of this finding had not been performed. Retinopathy, the most well-known complication of these drugs, may manifest as a spectrum of changes from asymptomatic and reversible pigment changes to visual loss persisting or progressing after drug discontinuation.…”

“…5,7,8,10,11,[13][14][15][16][17][18][19][20][24][25][26] Two case reports have described successful orthotopic heart transplantation. 7,10 Indication in both cases was refractory congestive heart failure 3 months after drug discontinuation. In the review by Costedoat-Chalumeau et al, 7 of the 25 congestive heart failure cases described, death occurred in 11 (46%) and partial or complete improvement was seen in eight out of 12 cases where the drug was discontinued.…”