6-lead ECG device simplifies QT interval monitoring in RR-TB

A handheld, 6-lead electrocardiographic (ECG) device may be an effective triage test that could reduce the need for 12-lead ECG monitoring in resource-limited, rifampin-resistant tuberculosis (RR-TB) treatment settings, according to a diagnostic prospective cohort study.

RR-TB involves treatment with drugs that can prolong QT interval (time from ventricular depolarization to complete repolarization).  Corrected QT (QTc)  greater than 500 ms is associated with an increased risk for torsade de pointes, a polymorphic ventricular tachycardia that can cause sudden death. ECG is recommended to detect torsades. 

In the study, researchers assessed the diagnostic accuracy, repeatability, and feasibility of 6-lead ECG QTc measurements compared with the standard 12-lead ECG measurements within the phase III BEAT Tuberculosis trial of 191 patients with TB who were initiated on a 6-month TB regimen consisting of bedaquiline, delamanid, linezolid, levofloxacin, and clofazimine. [JAMA Network Open 2024;7(6):e2415576]

High negative predictive value

The 6-lead ECG device accurately estimated the longitudinal mean QTc interval. At a QTc interval threshold of 500 ms, the 6-lead device (KardiaMobile 6L) had a high negative predictive value (NPV) of 99.8 percent (95 percent confidence interval [CI], 98.8–99.9 percent ) and a low positive predictive value (PPV) of 16.7 percent (95 percent CI, 0.4–64.1 percent).

“At a 500-ms QTc interval cut point, false negatives are more problematic than false positives because the latter would theoretically trigger a 12-lead assessment before changing clinical management,” said the authors led by Dr John Metcalfe from the Zuckerberg San Francisco General Hospital and Trauma Center, University of California, San Francisco, California, US.

With concurrent administration of up to four QT-prolonging anti-TB drugs, 98 percent of the patients’ QTc measurements remained at <500 ms over 6 months of treatment.

“Clinical trialists and national TB programmes should consider the use of handheld, 6-lead ECG devices for triage purposes and to extend the reach of 12-lead monitoring when needed,” Metcalfe added.

Importance of the study

Currently, most clinics use formal 12-lead ECG devices, which require a consistent power supply, specialized equipment, and personnel to place the leads accurately. This limits clinical capacity and presents a barrier to scaling up newer RR-TB regimens in some settings.

The researchers said the 6-lead ECG device could potentially simplify QTc monitoring. It has circuitry (amplifiers and filtering) and an algorithm simulating that of a formal 12-lead ECG device but uses a portable handheld platform. 

The 6-lead ECG device consists of a single sensor with stainless steel electrodes, allowing for three contact points and generating a 6-lead measurement. Recordings were transmitted via Bluetooth to a smartphone. The device calculates the QT interval using a clinically validated EK12 algorithm that assesses 10 seconds of waveform data at 5-second intervals.

“This 6-lead ECG device performed well in estimating mean QTc,” said the researchers.  “To our knowledge, this was the first large-scale validation of a simple, handheld 6-lead ECG device in a resource-constrained setting.”

They said the findings justify using a 6-lead ECG device as an alternative to a 12-lead ECG for monitoring QT interval-based cardiac risk in patients taking complex TB regimens with QTc-prolonging effects.