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Now that the US Food and Drug Administration has granted Emergency Use Authorization (EUA) for hydroxychloroquine (and its derivative, chloroquine) to treat COVID-19, many cardiologists have been quick to urge caution before prescribing the medications for all affected patients.

That's because of the drugs' track record of inducing prolonged QT interval, an adverse and potentially fatal effect that impacts certain patients' heart rhythms. Fortunately, ECG can help physicians monitor for prolonged QT intervals in patients who may need the medication despite its risks—and a new paper from Mayo Clinic gives guidance on how.

Here's what cardiologists need to know.

The Risks and Benefits of Hydroxychloroquine for COVID-19

The arrhythmia risks of hydroxychloroquine were known long before the SARS-CoV-2 outbreak.

The therapy, which had already been FDA-approved for malaria and some autoimmune disorders and was starting to get off-label uptake for the novel coronavirus before the EUA, contributes to drug-induced ventricular arrhythmias much like other medications, such as antidepressants, antipsychotics, and antibiotics (including azithromycin, which is often used with hydroxychloroquine).

In the most serious cases, these problems can lead to sudden cardiac death. While that's rare, these fatal side effects still stand to affect thousands of lives, given the prevalence of the novel coronavirus. As one physician told The Washington Post, even though just 1% of people face a high risk of prolonged QTc, if the virus infects one million people, that's 10,000 patients in the greatest danger.

Still, the Wall Street Journal reports that physicians have applauded the benefits of the drug in treating severe cases of COVID-19, even though large-scale, peer-reviewed data won't surface for a while. In in vitro studies, including those from Clinical Infectious Diseases and Cell Research, hydroxychloroquine and chloroquine have demonstrated antiviral properties that help prevent the novel coronavirus from binding with and invading cells.

In the absence of empirical evidence and enough time to gather it, physicians should use their discretion to weigh the potential benefits and risks of hydroxychloroquine for their patients.

Young and otherwise healthy patients with existing long QT intervals may be able to ride out the virus without the medication, while older or more immunocompromised patients may benefit from hydroxychloroquine because they are at higher risk of poor respiratory outcomes, as the Mayo Clinic reports in its guidance intended to help practitioners make the risk-benefit assessment.

By monitoring ECG changes, physicians can watch for prolonged QT intervals as they make this determination.

A Pocket Guide System for Monitoring Prolonged QT Interval

The clinical guidance recommends performing a baseline ECG measurement before starting therapy so specialists can track changes over time. Check page 19 of the Mayo Clinic Proceedings manuscript for a flow chart of hydroxychloroquine indications and baseline directions. Pay special attention to the "Pre-Initiation Checklist" box for a list of things to do at the outset.

The authors suggest the following courses of action based on ECG performance:

• If QTc is 500 milliseconds or higher (seen 1% of the time), this is known as a red zone. Proceed only with certain precautions, such as electrolyte abnormality corrections or telemetry placement. Stop drugs that prolong QTc if you see signs of torsades de pointes.
• If QTc is between 470 milliseconds in adult men or 480 milliseconds in adult women but less than 500 milliseconds (seen 9% of the time), this is known as a cautionary zone. Proceed with certain precautions.
• If QTc is under 470 milliseconds in adult men or 480 milliseconds in adult women (seen 90% of the time), this is known as a green zone. Move forward with treatment if you determine it would be helpful.

If you do proceed with therapy, the authors also suggest a post-initiation checklist that repeats ECG readings to track progress and identify any changes that may develop. Limit the urge to perform ECG measurements daily, however, as this could expose ECG technicians to added infection risk and unnecessarily waste precious PPE.

Exercise Discretion to Find the Best Path Forward

Of course, COVID-19 is still an evolving public health situation, and research regarding the potential therapeutic effects of hydroxychloroquine—as well as strategies for mitigating its known adverse effects—will likely continue to emerge. Cardiologists should exercise discretion in identifying the best path forward for each patient's care plan.

But you don't have to go at it alone. Use the tools you have available to monitor progress throughout treatment. A standard 12-lead ECG is certainly in your arsenal, and it's a tool that many clinicians are likely well equipped to use, but there are others, including telemetry and smartphone-enabled mobile ECG.

Whatever you do, know that it is essential to remain diligent about the risks of hydroxychloroquine, and it is as critically important not to miss out on the potential benefits of promising therapies. They may save a life, or thousands.