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Hydroxychloroquine Cardiotoxicity: A Rare But Potentially Deadly Adverse Effect

The antimalarial drug hydroxychloroquine (HCQ) has been promoted by President Trump as a game-changing treatment for coronavirus infection. Of the drug, Trump declared “What do you have to lose? Take it! Try it if you’d like.”

As with any drug treatment one should consider the risks and the benefits of HCQ before “trying.” For expert virologists and infectious disease doctors, HCQ has not been proven to be beneficial in the treatment of coronavirus infection despite a glimmer of hope from early, small, poorly controlled trials from China and France.

The Chinese and French papers which reported on the use of HCQ with or without azithromycin in patients with coronavirus did not clearly show a clinical benefit. The most recent information suggests no benefits and potential harms to HCQ use.

With benefit unproven, we must be particularly cognizant of the adverse effects of any proposed or experimental treatment, and both HCQ and azithromycin (AZ) have well documented potentially lethal cardiac adverse effects.

I wrote about the risk of QT prolongation and sudden death with azithromycin here

A patient of mine with known left bundle branch block and cardiomyopathy recently contacted me because he had been prescribed HCQ for a rheumatologic disease. To determine if he should take this drug I reviewed the literature on HCQ cardiotoxicity.

Hydroxychloroquine Cardiotoxicity

HCQ is primarily utilized now for the treatment of rheumatologic disorders, most commonly systemic lupus erythematosus ( SLE.)

A recent review of  HCQ use in SLE concluded

HCQ may reduce the risk of flares, allow the reduction of the dosage of steroids, reduce organ damage, and prevent the thrombotic effects of anti-phospholipid antibodies. The drug is generally safe and may be prescribed to pregnant women. However, some cautions are needed to prevent retinopathy, a rare but serious complication of the prolonged use of HCQ

The Johns Hopkins Lupus Center section devoted to “Treating Lupus with Anti-Malarial Drugs” mentions a dozen side effects but does not mention cardiotoxicity.

However, the scientific literature contains numerous case reports of patients with SLE who developed either severe heart failure or conduction abnormalities (sometimes both) with strong evidence that HCQ was responsible.

Joyce, et al, (Hydroxychloroquine cardiotoxicity presenting as a rapidly evolving biventricular cardiomyopathy: key diagnostic features and literature reviewdescribed a case of HCQ cardiotoxicity in 2013 and reviewed the literature on the topic. They emphasized typical findings on cardiac biopsy and concluded:

“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”

The most recent review of HCQ was published in 2018 and identified 127 patients from case reports or case series with cardiac complications from HCQ or chloroquine.

Two-thirds of these patients were female and the majority were treated with chloroquine (58%.)

Patients had been on drug treatment from 3 days to 35 years (median 7 years.)

The median cumulative dose was 1.235 grams for HCQ.

Conduction disorders were the most common adverse cardiac effect noted with 85% of patients

Other non-specific adverse cardiac events included ventricular hypertrophy (22%), hypokinesia (9.4%), heart failure (26.8%), pulmonary arterial hypertension (3.9%), and valvular dysfunction (7.1%).

For 78 patients reported to have been withdrawn from treatment, some recovered normal heart function (44.9%), while for others progression was unfavorable, resulting in irreversible damage (12.9%) or death (30.8%)

To summarize:

  1. HCQ and chloroquine have associated and well-documented, albeit rare cases of potentially lethal cardiotoxicity.
  2. The benefit of these drugs in the treatment of coronavirus infection is currently unproven.
  3. Data from high-quality randomized trials of HCQ treatment in patients with coronavirus is needed before we can assess whether the drug benefits outweigh its risk in COVID-19 patients.

Much has been written in the cardiology literature recently about QT prolongation with HCQ and ECG monitoring and I will publish a separate post on that topic shortly.

Skeptically Yours,


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