1970 Don "The drug appears to act as a potent myocardial poison" The cardiovascular effects of acute chloroquine intoxication have been described in three patients and in five animal experiments. The drug appears to act as a potent myocardial poison, reducing the output of the heart and causing disturbances of conduction bradycardia, and arrhythmias. As far as we know, the first two human cases ever, which illustrate the electrocardiographic changes induced by acute chloroquine poisoning, are the ones presented (Patients 1 and 3). The sequence of changes in the electrocardiogram in acute poisoning in dogs is described. Adrenaline was found to be an effective antidote, as well as a preventive drug. Appropriate precautions are suggested to prevent the occurrence of accidental death or induced poisoning. These emphasize the administration of the drug on a weight rather than an age basis. The use of small doses similar to quinidine may prevent drug idiosyncrasy but does not seem to be practical. Considering the widespread use of chloroquine and its increasing administration, it is necessary to consider the precautionary measures outlined on an international scale. 1971 Hughes Chloroquine Myopathy Two cases are described of chloroquine myopathy following prolonged courses of chloroquine given in one case for rheumatoid arthritis and in the other case for sarcoidosis. Skeletal muscles were severely affected but there was also clinical evidence in both cases of cardiac involvement and Case 1, in which there was histological evidence of cardiomyopathy, died of heart failure. Muscle biopsy in both cases and skeletal muscle at necropsy in Case 1 showed a striking vacuolar degeneration of about 50 per cent of the muscle-fibres. Histochemical examination showed that the granular (type I) muscle-fibres were preferentially affected. Electron microscopy showed the ultrastructural detail of the extensive degeneration of the muscle-fibres which contain large numbers of myelin figures thought to be a type of lysosome. There were mitochondrial changes which appear to precede the formation of the myelin figures. The literature of other clinical cases and of the experimentally produced myopathy is briefly reviewed. There is evidence that the administration of chloroquine for a long time in high dosage can cause a toxic myopathy. We record here two further cases. The first clinical report of human cases was made by Whisnant, Espinosa, Kierland, and Lambert (1963), but this side effect has been known in animals since the experimental work of Nelson and Fitzhugh (1948). Although there are extensive studies of the myopathy produced by this drug in animals, there are few reports of human cases with examination of the histochemistry or the ultrastructure of the affected muscles. These investigations were made in one of the cases reported in this paper, which also emphasizes the involvement of the heart in chloroquine myopathy and describes the necropsy findings in a fatal case. 1978 Edwards Complete heart block due to chronic chloroquine toxicity managed with permanent pacemaker. 1983 Ladipo Complete heart block in chronic chloroquine poisoning Complete heart block of recent onset is reported and is attributed to chronic chloroquine abuse. Total blood chloroquine was more than two times higher in this patient than in 4 patients following therapeutic doses of chloroquine, and chloroquine basic metabolities were also proportionally higher in this patient's blood. 1983 deGennes Heart conduction disorders in long-term treatment with chloroquine. Two new cases Cardiac complications are exceptional in long-term chloroquine therapy; congestive heart failure and restrictive cardiomyopathy may develop, but disorders of conduction are more frequent. The characteristics of these disorders emerge from 12 cases in the literature and from 2 personal cases. The usual disorder is fascicular block which may become a complete, syncopal, atrioventricular block, as in one of our 2 patients. The time elapsed between the beginning of treatment and the occurrence of these disorders (2 to 30 years) and the total dose of chloroquine received (100 to 2,500 g) are extremely variable. Retinopathy or neuromyopathy is present in 64 and 35 percent of the cases respectively. The diagnosis is confirmed by endomyocardial biopsy with electron microscopic study which shows vaculoar myopathy with numerous large secondary lysosomes containing a dense material of lamellar structure (myelinic figures, curvilinear bodies). Regression of heart conduction disorders after withdrawal of chloroquine seems to be inconstant and incomplete. The rare occurrence of this complication raises the question of genetic predisposition. We believe that chloroquine therapy should be contra-indicated in patients with a history of conduction disorders and that a 6-monthly electrocardiographic control of these patients would... 1989 Ihenacho CHLOROQUINE ABUSE AND HEART BLOCK IN AFRICANS Twelve of 30 Africans with heart block gave a history of chronic chloroquine abuse. Eleven of these had evidence of chloroquine retinopathy whereas four of the 18 nonabusers had abnormal ophthalmologic findings, thought to be senile changes. The chronic chloroquine abusers were all male and were younger (mean age 51.6 years) than the non‐abusers (mean age 61.2), nine of whom were female. Serum chloroquine levels were not helpful diagnostically. In the absence of other etiological factors, chronic chloroquine toxicity is important in the causation of heart block in Africans. (Aust NZ J Med 1989; 19: 17–21.) 1991 Ogola Chloroquine related complete heart block with blindness: case report. A 27-year old African woman with history of regular chloroquine ingestion presented with progressive deterioration of vision, easy fatiguability, dyspnoea, dizziness progressing to syncopal attacks. Ophthalmological assessment revealed features of chloroquine retinopathy, cardiac assessment revealed features of heart failure and a complete heart block with right bundle branch block pattern. The heart block was treated by pacemaker insertion and the heart failure resolved spontaneously following chloroquine discontinuation. She however remains blind. 1993-Cubero Restrictive cardiomyopathy caused by chloroquine A 59 year old white woman who had been treated with chloroquine phosphate for 25 years presented with signs of congestive heart failure and was diagnosed as having restrictive cardiomyopathy by non-invasive methods. Electron microscopy of a biopsy specimen of skeletal muscle showed lesions compatible with chloroquine myopathy. The patient died five weeks after presentation. Electron microscopy of heart tissue showed similar lesions to those of the skeletal muscle.

1998 Veinot Chloroquine related cardiac toxicity Chloroquine, an agent used in treatment and prophylaxis of malaria, and also known for its antiinflammatory effects in dermatological, rheumatological, and connective tissue disorders, has been reported to cause toxicity, most commonly in the retina and the cardiovascular system. We describe a 60-year-old woman with longstanding rheumatoid arthritis receiving multidrug treatment, including prolonged administration of chloroquine. She developed complete heart block requiring a permanent pacemaker, congestive heart failure, and progressive myopathy. During hospital investigations for her myopathy, she died of acute pulmonary thromboembolism. Although hypertension and possibly amyloidosis were thought to be the cause of her cardiac disease, cardiac and skeletal muscle changes characteristic of chloroquine toxicity were observed. Chloroquine may be an important unsuspected contributing cause of cardiac dysfunction in patients with rheumatological disease. Endomyocardial ... 1999 Baguet "The heart failure improved on stopping chloroquine treatment." A 58 year old woman on long term treatment with chloroquine for systemic lupus erythematosus presented with cardiac conduction disorders and heart failure with hypertrophic cardiomyopathy, which was confirmed by histology to be related to chloroquine toxicity. The heart failure improved on stopping chloroquine treatment. 1999 Reusst Borst "...a permanent pacemaker had to be implanted." Antimalarials are well established disease modifying antirheumatic drugs. A rare and underappreciated treatment difficulty is cardiac complication, in particular conduction disturbances. We describe 2 more patients that developed complete heart block after high dose, longterm treatment. Patient 1, a 73-year-old woman with longstanding rheumatoid arthritis, had taken chloroquine (250 mg/day) for 12 years when she developed complete heart block requiring a permanent pacemaker. Patient 2, a 40-year-old woman with discoid lupus erythematosus, was taking chloroquine from 1979 until 1996. Depending on the clinical disease activity, she intermittently increased the dose from 250 to 750 mg/day. In 1994, she developed complete heart block and a permanent pacemaker had to be implanted. Intensive investigations in both cases did not reveal another underlying cause for conduction disturbances; the atrioventricular block was probably due in both cases to chloroquine related cardiac toxicity. This toxicity seems to be restricted to longterm, high dose treatment; however, it should be kept in mind in patients with preexisting conduction disturbances during longterm treatment. 2004 Freihage Heart transplantation in a patient with chloroquine-induced cardiomyopathy We present the first report of a patient who underwent heart transplantation (HT) after endomyocardial biopsy (EMB) and revealed chloroquine-induced cardiomyopathy (CIC). This patient, who was treated with chloroquine for 6 years, developed a restrictive cardiomyopathy that progressed to congestive heart failure (CHF) resistant to medical management. 2005 Naqvi Chloroquine-induced cardiomyopathy-echocardiographic features A 61-year-old woman with a 30-year history of systemic lupus erythematosus treated with chloroquine sulfate presented with complete heart block, congestive heart failure, and findings of restrictive cardiomyopathy on echocardiogram. Thickening of mitral, aortic, and tricuspid valves along with mild to moderate valve regurgitation was also present. Magnetic resonance imaging showed increased gadolinium uptake in the interventricular septum and the left ventricular lateral wall. Endomyocardial biopsy specimen showed marked myocardial cytoplasmic vacuolation and extensive myelin figures. Seven months after discontinuation of chloroquine, she showed significant clinical improvement and reversal of cardiomyopathy on echocardiography. This is the first case report describing a cardiomyopathy with prolonged use of chloroquine involving the conduction system, cardiac valves, and the myocardium with reversal on discontinuation of the drug. 2006 Wozniacka The Cardiac Safety of Chloroquine Phosphate Treatment in Patients with Systemic Lupus Erythematosus: The Influence on Arrhythmia, Heart Rate Variability and Repolarization Parameters Antimalarials are used to treat cutaneous and systemic lupus erythematosus (SLE). Even though cardiac damage is a rare complication, over the last decade several reports have raised the issue of cardiotoxicity associated with antimalarials. Therefore, the aim of study was to evaluate the influence of seven-month chloroquine treatment with a 250 mg daily dose on arrhythmia, conduction disturbances as well as heart rate variability and repolarization parameters assessed in 24-hour Holter monitoring. The studied group included 28 SLE patients treated with chloroquine as a monotherapy. In all the patients standard 12 leads surface ECG (50 mm) and the 24-hour ECG Holter monitoring (Oxford Medilog Excel-2) were performed before and after chloroquine phosphate treatment. All subjects presented sinus rhythm both at the enrollment and after treatment. No episodes of paroxysmal arrhythmias or conduction disturbances were reported during the study. All the patients were characterized by tendency to tachycardia, but no significant differences in mean heart rate were found before and after chloroquine administration. Similarly, no changes in heart rate variability or repolarization parameters were observed. 2020 nyc Family of New York woman blames hydroxychloroquine combo for fatal heart attack The 65-year-old woman was prescribed the malaria drug and an antibiotic by her doctor to treat coronavirus symptoms. April 16, 2020, 3:19 PM EDT By Heidi Przybyla A New York woman with coronavirus symptoms died last week after being prescribed a drug cocktail with known cardiac side effects, and family members say she was not tested for COVID-19 or for heart problems before receiving the medication. The family’s experience suggests that at least some physicians are prescribing hydroxychloroquine and azithromycin — drugs President Donald Trump has promoted to treat the coronavirus — outside of hospital settings, underscoring why major medical organizations including the American Heart Association have issued warnings about the drug’s potential to trigger heart arrhythmia in some patients. In early April, Ligia, a 65-year-old Queens resident, was given the drug by her general practitioner after she reported having a bad cough, fever and shortness of breath. Ligia’s last name is being withheld on the request of her children.