Study Reveals Potential Dangers, Application of QTc Monitoring for COVID-19

A recent study published in Mayo Clinic Proceedings has detailed information on the potential dangers and the application of QTc monitoring, an indicator of the health of the heart’s electrical recharging system, to guide treatment when using drugs that can cause heart rhythm changes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the coronavirus disease 2019 (COVID-19), has been spreading worldwide, leading to more than 20,000 deaths in less than 4 months. Although efforts are progressing to develop a COVID-19 vaccine, it is still likely to be more than a year away. The pandemic, meanwhile, is driving researchers to find safe and effective therapies for patients with COVID-19. Although new and repurposed drugs are being tested in clinical trials, some of these promising drugs are simultaneously being used off-label for compassionate use to treat patients, according to the study.

These medications are known to cause drug-induced prolongation of the QTc of certain patients, according to the researchers. Patients with dangerously prolonged QTc are at increased risk for potentially life-threatening ventricular rhythm abnormalities that can culminate in sudden cardiac death. Correctly identifying which patients are most susceptible to adverse events and knowing how to safely use these medications, therefore, is imperative for this pandemic, according to the study.

Hydroxychloroquine is a long-standing preventive and treatment drug for malaria and is used to manage and minimize symptoms of inflammatory immune disease, such as lupus and rheumatoid arthritis. In laboratory tests, hydroxychloroquine can prevent the SARS-CoV and SARS-CoV-2 viruses from attaching to and entering cells.

On a cellular level, potential QT-prolonging medications, such as hydroxychloroquine, block 1 of the critical potassium channels that control the heart’s electrical recharging system. This interference increases the possibility that the heart’s rhythm could degenerate into dangerous erratic heart beats, resulting ultimately in sudden cardiac death, according to the study.

Cardiologists and physician-scientists at the Mayo Clinic have provided urgent guidance on how to use a 12-lead ECG, telemetry or smartphone-enabled mobile ECG to determine the patient’s QTc as a vital sign to identify those patients at increased risk and how to ultimately minimize the chance of drug-induced sudden cardiac death.

Guidelines for QTC Monitoring During Treatment

The antimalarial drugs chloroquine and hydroxychloroquine, as well as the HIV drugs lopinavir and ritonavir, all carry a known or possible risk of drug-induced ventricular arrhythmias and sudden cardiac death. Prior to starting treatment with these medications, it is important to get a baseline ECG to be able to make changes, according to the study authors.

When starting treatment with these medications, it is important to get a baseline ECG to be able to measure changes, the researchers said. This starting point measurement could be from a standard 12-lead ECG, telemetry or a smartphone-enabled mobile ECG device. The FDA has granted emergency approval of AliveCor’s Kardia 6L mobile ECG device as the only FDA-approved mobile device for QTc monitoring with COVID-19.

The mobile device’s ability to remotely provide the patient’s heart rhythm and QTc value does not require an extra ECG technician to take the measurement in person, thus saving increased exposure to COVID-19 and the need for more personal protective equipment.

Using this algorithm, the potential risk of drug-induced arrhythmias can be rated and used to modify treatment accordingly. Patients with a baseline QTc value greater than or equal to 500 milliseconds from baseline after starting treatment with 1 or more QTc-prolonging drugs are at greatest risk for drug-induced arrhythmias. Simple QTc countermeasures can be implemented for patients with a cautionary “red light” QTc status if the decision is made to proceed with the intended COVID-19 therapies.

Information Guides Decisions

There are a number of considerations around the use of off-label drugs to treat COVID-19. The drugs may or may not be available in large enough supply to treat a worldwide pandemic, even at the current compassionate use of testing. It will take careful consideration of COVID-19 patients’ circumstances for the care team to decide on the use of drugs or drug combinations that may treat their infection, but which potentially could cause harmful drug-induced adverse events, according to the study.

Patients under the age of 40 years with mild symptoms and a QTc greater than or equal to 500 milliseconds may choose to avoid treatment altogether, as the arrhythmia risk may far outweigh the risk of developing COVID-19-realted acute respiratory distress syndrome. However, for patients with COVID-19 with a QTc greater than or equal to 500 milliseconds who have progressively worsening respiratory symptoms or are at greater risk of respiratory complications due to advanced age, immunosuppression, or having another high-risk condition, the potential benefit of QTc-prolonging medicines may exceed the arrhythmia risk.

Ultimately, the weighing of risks to benefits depends on whether hydroxychloroquine, with or without azithromycin, is an effective treatment against COVID-19.

Reference

• Guidance on patients at risk of drug-induced sudden cardiac death from off-label COVID-19 treatments [news release]. Mayo Clinic website. Published March 25, 2020. https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-provides-urgent-guidance-approach-to-identify-patients-at-risk-of-drug-induced-sudden-cardiac-death-from-use-of-off-label-covid-19-treatments/. Accessed March 30, 2020.