Multilead QT Screening Is Necessary for QT Measurement: Implications for Management of Patients in the COVID-19 Era.

During the current coronavirus disease-2019 (COVID-19) pandemic, there has been increased interest in using off-label medications for treatment of the novel severe acute respiratory syndrome-coronavirus-2, including drugs with a propensity for QT interval prolongation, such as hydroxychloroquine and azithromycin (1). With the increasing availability of handheld electrocardiographic devices, these devices have been proposed as a means to evaluate and manage the QT interval in patients undergoing therapy (2,3).

This study received ethical approval from the University of British Columbia clinical research ethics board. We performed a prospective evaluation of the handheld electrocardiographic device and standard 12-lead electrocardiographic QT intervals in patients undergoing routine evaluation for inherited arrhythmia syndromes. Patients underwent a comprehensive evaluation, including 12-lead electrocardiography (ECG), exercise treadmill testing, cardiac imaging, and genetic testing when indicated. Following 12-lead ECG, eligible research participants recorded sequential single-lead electrocardiograms in the lead I, lead II, and precordial lead positions using a handheld electrocardiographic device (Kardia, AliveCor, Mountain View, California; leads III, aVR, aVL, and aVF were not recorded). The precordial lead electrocardiogram was recorded by placing the handheld device on the upper precordium (V1 and V2 positions) (4). Blinded QT interval measurements on the handheld device and 12-lead ECG used the maximum slope technique and were corrected using Bazett’s formula. The longest QT interval measured across all leads on the 12-lead electrocardiogram was used. Corrected QT (QTc) intervals were compared using paired Students’ t-tests and a Bland-Altman plot.

Twenty-two research participants performed the handheld electrocardiographic recordings. Patients had histories of unexplained cardiac arrest (n = 2), syncope (n = 3), or palpitations (n = 2) and were asymptomatic probands (n = 3) or first-degree family members (n = 12). The median age was 38 years (interquartile range [IQR]: 26 to 52 years), and 32% were women. One-half of patients (n = 11) were deemed unaffected or normal after comprehensive evaluation. One participant was excluded because of an unmeasurable QT interval using the handheld device because of flattened T waves (in all recorded leads), and 1 participant was excluded because of ventricular bigeminy throughout all handheld electrocardiographic recordings.

The median QRS duration was 92 ms (IQR: 89 ms to 103 ms), and the median QTc interval measured by 12-lead ECG was 400 ms (IQR: 385 ms to 414 ms). The median QTc interval measured using the handheld device in lead I was 360 ms (IQR: 344 ms to 376 ms), in lead II was 366 ms (IQR: 354 ms to 386 ms), and in a precordial lead was 354 ms (IQR: 340 ms to 392 ms). There was no difference in the maximal QTc interval measured by 12-lead ECG compared with the maximal QTc interval measured across all positions using the handheld device (401 ms vs. 404 ms; p = 0.259) (Figure 1 ). The QTc interval measured by 12-lead ECG was significantly longer than the lead I QTc interval on the handheld device (+23 ms; 95% confidence interval: 13 ms to 34 ms; p < 0.001) and the precordial lead QTc interval on the handheld device (+11 ms; 95% confidence interval: 1 to 20 ms; p = 0.018). The QTc interval measured by 12-lead ECG was not significantly different from the lead II QTc interval on the handheld device (+5 ms; 95% CI: −10 to 20 ms; p = 0.244). The longest QTc interval measured by 12-lead ECG was frequently in the precordial leads.

Figure 1

Bland-Altman Plot Comparing QTc Intervals Measured Using 12-Lead ECG and Maximum QTc Measured on Handheld Device, Across Various Positions

ECG = electrocardiography; QTc = corrected QTc.

We demonstrate that QTc intervals can be measured reproducibly using a single-lead handheld device in a cohort of patients undergoing evaluation for inherited arrhythmia syndromes, but this requires capture of multiple vectors with the handheld device and not a single-lead electrocardiographic capture alone. The QTc interval measured by 12-lead ECG was no different than the maximal QTc interval measured using the handheld device across multiple positions but was consistently longer than the QTc interval measured in any single lead position alone.

Studies have shown that administration of QT interval–prolonging drugs is associated with an almost 3-fold increased risk for sudden arrhythmic death (5). Prior to initiation of QT interval–prolonging medications, a baseline 12-lead electrocardiogram should be obtained, in addition to exercise treadmill testing when congenital long-QT syndrome is suspected (6). Although a larger systematic evaluation is required to determine how much single-lead ECG will underestimate the QTc interval, our pilot data in ambulatory patients suggested that the QTc interval measured by 12-lead ECG was numerically longer than any single position alone (lead I, lead II, precordial) and significantly longer in 2 of 3 positions. Although the lead II QTc interval on the handheld device was not significantly shorter, systematic measurement of QTc intervals in a single position may lead to underreporting of the QTc interval, particularly in patients with abnormal QT configurations.

It is appealing to use the handheld electrocardiographic device as a QT screening tool in patients with COVID-19. In the context of off-label medications that prolong the QT interval, handheld devices should be used in multiple lead positions to determine baseline QTc intervals. The practical application of these results is to perform 12-lead ECG, multilead handheld ECG, or single-lead handheld ECG in at least 3 lead positions. This may be challenging for patients but is clearly necessary on the basis of the presented data. The maximum QTc interval can be used as a baseline and for surveillance when patients with COVID-19 receive QT interval–prolonging medical therapies. Measuring the change (delta) in QTc interval with therapy will augment risk stratification but also should not be performed alone, as both the absolute and delta QTc intervals are required to establish baseline risk and proarrhythmia. These are important considerations both in hospitalized patients who had serial electrocardiographic studies pose exposure hazard to patients and providers and in ambulatory patients undergoing medical therapy at home.