Feature | Coronavirus (COVID-19) | March 24, 2020| Marianne Pop, Pharm.D, BCPS

COVID-19 Hydroxychloroquine Treatment Brings Prolonged QT Arrhythmia Issues

QT prolongation assessment and monitoring when using hydroxychloroquine 

Hydroxychloroquine causes prolonged QT intervals and cardiac arrhythmias, so this needs to be considered in patients being treated with this drug for COVID-19. #COVID19 #SARScov2 #coronavirus

Hydroxychloroquine causes prolonged QT intervals and cardiac arrhythmias, so this needs to be considered in patients being treated with this drug for COVID-19.

It has been more than three months since the word coronavirus was uttered on everyone’s lips and all over the social media, but over the last month the focus has moved from fear to hope in the form of treatment for novel coronavirus (also referred to as COVID-19 and SARS-CoV-2).However, the drug therapy brings with it a set of negative side effects. 

Hydroxychloroquine and chloroquine are the new “medical miracles” being lauded by letters to the editor and anecdotal in-vitro/vivo studies.[1,2,3] A recent open-label study by Gautret et al. showed significant reduction in viral “carriage” in patients receiving hydroxychloroquine and azithromycin.[4] This led to the off-label recommendation to use hydroxychloroquine for COVID-19.[5,6]  Hydroxychloroquine is used to prevent or treat malaria infections caused by mosquitos and to treat auto-immune diseases such as lupus and rheumatoid arthritis when other medications have not worked or cannot be used.[6]

It may take months to know the true outcomes from larger trials,[4,5] but what we do know is the safety profiles of these medications. Both hydroxychloroquine and chloroquine have been U.S. Food and Drug Administration (FDA) approved for lupus erythematosus, rheumatoid arthritis, and malaria.[6] Years of safety data show that these medications can cause cardiac ECG QT prolongation and subsequent arrhythmias, including torsade de pointes.[9] These medications can prolong the QT correction (QTc), even when taken as recommended.[9] With limited treatment options how can providers proceed with treatment options?

QT Prolongation Assessment and Monitoring With Hydroxychloroquine and Chloroquine

The QT interval in electrocardiograms (ECG) is the time from the beginning of the QRS complex, representing ventricular depolarization, to the end of the T wave, resulting from ventricular repolarization.[8]

In general, the normal QT interval is below 400 to 440 milliseconds (ms), or 0.4 to 0.44 seconds. Women can have a longer QT interval than men. Due to the effects of heart rate, the corrected QT interval (QTc) is frequently used.

Due to the effects of heart rate, the term "corrected QT interval" (QTc) is frequently used. The QTc is considered prolonged if greater than 450 ms in males and 470 ms in females.[8]

According to Tisdale et al. (2013), there are risk factors associated with QTc prolongation. They have been developed into a risk score tool (Figure 1) that takes age, sex, diuretic use, potassium level, baseline QTc, acute myocardial infarction, use of QTc prolonging drugs, sepsis and heart failure into account.[7] 

For those considering hydroxychloroquine and chloroquine for COVID-19 infected patients, consider the following modifiable options [9]:    
   • ECG with QTc evaluation
   • Avoidance of non-essential QT-prolonging medications    
   • Identifying and correcting electrolyte imbalances (potassium, magnesium, calcium)  
   • Discontinuing non-essential QTc-prolonging medications In addition, consider co-morbidities that may increase therapeutic levels such as acute kidney injury or liver disease. 

Lastly, adopt a relevant resource for interpretation and drug interactions. Credible Meds provides in-depth review of QTc prolonging medications and is free.[9] Although we do not have many tools in the COVID-19 treatment arsenal, we can arm ourselves with the knowledge of how to assess patients for QTc prolongation.

 

According to Tisdale et al. (2013), those with low risk scores (<7) had a 15% incidence for QTc prolongation. Those with moderate (7-10) or high (>11) risk scores incidence of QTc prolongation was 37% and 73%, respectively (Tisdale et al., 2013). #COVID19 #SARScov2

FIGURE 1 — According to Tisdale et al. (2013), those with low risk scores (<7) had a 15% incidence for QTc prolongation. Those with moderate (7-10) or high (>11) risk scores incidence of QTc prolongation was 37% and 73%, respectively (Tisdale et al., 2013).

 

Read the related article ESC Council on Hypertension Says ACE-I and ARBs Do Not Increase COVID-19 Mortality.
 

Editor’s note: Marianne Pop, Pharm.D., BCPS, is a clinical pharmacist and clinical assistant professor with the regional pharmacy program, University of Illinois at Chicago College of Pharmacy. She specializes in emergency medicine pharmacy as part of the regional pharmacy program at OSF Saint Anthony Medical Center in Rockford, Ill.

References:
1. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020 Mar 4:105932. doi: 10.1016/j.ijantimicag.2020.105932. [Epub ahead of print]

2. Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. pii: ciaa237. doi: 10.1093/cid/ciaa237. [Epub ahead of print]

3. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73

4. Gautret P, Lagier J, Parola P, Hoang V, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents. In Press.

5. Kupferschmidt K., Cohen J. WHO launches global megatrial of the four most promising coronavirus treatments. Science. March 22, 2020. Accessed March 23, 2020 https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments.

6. Hydroxychloroquine. Lexi-drugs. Lexicomp. Wolters Kluwer Health Inc. Riverwoods, IL. http://online.lexi.com.  Accessed March 23, 2020.

7. Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016 May;149(3):139-52. doi: 10.1177/1715163516641136.

8. ECG review, ECG Basics, QT Interval. Healio. https://www.healio.com/cardiology/learn-the-heart/ecg-review/ecg-interpretation-tutorial/qt-interval. Accessed March 24, 2020. 

9. Woosley RL, Heise CW , Gallo T, Tate J, Woosley D and Romero KA,  www.CredibleMeds.org,  QTdrugs List, Accessed March 23, 2020. AZCERT Inc. 1822 Innovation Park Dr., Oro Valley, AZ  85755. 

Related Content

OTC ECG devices

OTC ECG devices can help detect abnormal heart rhythms in the general population, and this technology will continue to improve.

Feature | ECG | March 11, 2020
Apple created a stir when it...
Several wearable, less-obtrusive ECG monitors fhave been cleared by the FDA for longer wear. This example is Cardiac Insight’s Cardea SOLO device. 

Several wearable, less-obtrusive ECG monitors have been cleared by the FDA for longer wear. This example is Cardiac Insight’s Cardea SOLO device. 

Feature | ECG | February 19, 2020
When the patients of Michael Boler, M.D. need cardiac monitoring, the Holter monitor is no longer his first choice. “...
The Bittium Faros uses a 4-in-1 ECG technology. It is a lightweight, waterproof and can be configured for different patient monitoring needs. Bittium Faros Holter monitoring.

The Bittium Faros uses a 4-in-1 ECG technology. It is a lightweight, waterproof and can be configured for different patient monitoring needs. 
 

News | ECG | January 22, 2020
January 22, 2020 – Bittium is exhibiting solutions for cardiology at...
Cardiologs
News | ECG | December 12, 2019
December 12, 2019 — Cardiologs, a global leader in artificial intelligence (AI)
FDA Clears AliveCor's KardiaMobile 6L as First Six-Lead Personal ECG Device
Technology | ECG | May 13, 2019
AliveCor announced its third U.S. Food and Drug Administration (FDA) clearance in three months, making KardiaMobile 6L...
One innovation in ECG is its use in the customer wearable market, which will tie more closely into the clinical world either with using the data to triage patients and/or patients seeking medical attention prior to acute symptoms appearing.

One innovation in ECG is its use in the customer wearable market, which will tie more closely into the clinical world either with using the data to triage patients and/or patients seeking medical attention prior to acute symptoms appearing.

Feature | ECG | May 03, 2019 | Sanket Solanki
Technology has made its way into the healthcare sector and brought a drastic transformation.
Videos | ECG | March 05, 2019
This is a quick demo of the Schiller Cardiovit FT-1 electrocardiograph (ECG) system displayed at the ...
EKG With Artificial Intelligence Reliably Detects Heart Failure Precursor
News | ECG | January 08, 2019
January 8, 2019 — A Mayo Clinic study finds that applying...
Use of traditional Holter monitor leads can be an issue for patient compliance and comfort. The newer generation ambulatory cardiac monitors use an adhesive patch that sticks directly on the patient's chest and allows them to shower and go about daily activities without a belt mounted monitor or leads getting in the way. This is especially important for longer term monitoring of seven days or longer.

Use of traditional Holter monitor leads can be an issue for patient compliance and comfort. The newer generation ambulatory cardiac monitors use a small, adhesive patch that sticks directly on the patient's chest and allows them to shower and go about daily activities without a belt mounted monitor or leads getting in the way. This is especially important for longer term monitoring of seven days or longer. 

Feature | ECG | September 27, 2018
Advances in the technology of wearable cardiac monitors are improving both the experience of the patient and the effe
HeartSciences MyoVista ECG Device Shows Promise in Detecting Abnormal Cardiac Function
News | ECG | April 27, 2018
HeartSciences announced the results of a clinical study of its electrocardiography device that applies continuous...
Overlay Init