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Drug-Induced long QT syndrome affects about thousands of people per year, and can have deadly consequences. The condition can lead to a number of serious conditions, including arrhythmia or even sudden death.

Thankfully, clinicians can keep tabs on QT intervals with continuous monitoring, which has made tremendous advances in recent years. Ian Rowlandson, GE Healthcare Chief Engineer and Scientist for Diagnostic Electrocardiography, has helped to develop algorithms that go into GE Healthcare’s ECG diagnostic carts and bedside monitors – including those that examine the complex and often overlooked problem of long QT. Clinical View sat down with Ian to discuss long QT epidemiology and signs, long QT measurement and reversal strategies, and the advantages GE Healthcare delivers to the QT monitoring landscape.

Question: What is long QT?

Ian Rowlandson: An electrocardiogram (ECG) measures the QT interval from the earliest onset of depolarization (the start of the Q wave) to the latest offset of repolarization (the end of the T wave)—or in simpler terms, the time it takes the heart to recharge between beats. A QT interval corrected for heart rate results in the QTc value (corrected QT).

Prolongation of the QT/QTc interval, also referred to as long QT, occurs when the heart takes longer than usual to recharge between beats. Long QT sets the stage for TdP, an abnormal and potentially fatal heart rhythm.

Q: What causes long QT?

Ian Rowlandson: There are two types of long QT: congenital and acquired. Congenital long QT cases don’t generally come to light unless a patient exhibits symptoms such as fainting or blacking out, which would lead to diagnosis and treatment, often of the patient’s entire family.

Acquired long QT may be either drug-induced or triggered by clinical conditions such as electrolyte imbalances, arrhythmias, poor liver or heart function.

Drug-induced long QT is a dire concern, particularly in hospital settings, where use of QT-prolonging drugs is prevalent. QT-prolonging drugs literally poison the ion channels in the heart membrane. The list of drugs likely to prolong QT continues to grow and includes anti-arrhythmics such as Sotalol as well as anti-psychotics, anti-depressants, antibiotics and some anesthetics. (Note: Sites such as crediblemeds.org categorize drugs by their potential to cause long QT and/or TdP.)

Q: How prevalent is long QT?

Ian Rowlandson: That depends on the type. Up to one in 2,000 individuals may have congenital long QT^1, although we are learning that these genetic abnormalities might be more common than originally thought.

Acquired long QT is thought to be even more common than congenital long QT.

A nationwide study from Denmark found that of 1,363 SCDs, nearly 20 percent of the deceased had received a QT-prolonging drug less than 90 days before death.²

Unfortunately, when clinicians are confronted with long QT, they don't know whether it is acquired, congenital or drug-induced. They must simply deal with it.

Q: What are signs of long QT?

Ian Rowlandson: There are no hard and fast rules, but an American Heart Association (AHA) and American College of Cardiology Foundation (ACCF) joint statement on TdP prevention in hospital settings³ views QTc prolongation to greater than 500 milliseconds as a prime ECG risk factor for TdP. However, additional factors such as advanced age, female gender, administration of a QT-prolonging drug, poor electrolytes, poor cardiac health, etc. increase the TdP risk.

This 500-millisecond long QT threshold is important, particularly as a benchmark for hospitals in the defense of SCD cases. However, the ACC-ACCF also concede that, particularly for drug-induced long QT, the change in QT over time may be more important than the absolute QT.³ That is why precise and consistent QT monitoring matters, and why a single ECG may not be sufficient for patients prescribed a QT-prolonging drug.

Q: What are the clinical concerns of long QT?

Ian Rowlandson: Long QT is extremely serious. Long QT causes death and, in cases of drug-induced long QT, is often initiated by a clinician prescribing a QT-prolonging drug. When long QT goes unnoticed, it creates a perfect storm for a life-threatening TdP event.

The irony is that long QT is preventable and reversible. Clinicians must be educated on QT measurement as well as signs and treatment of long QT.

Q: Why is long QT sometimes overlooked?

Ian Rowlandson: Long QT is sometimes overlooked because a fair number of physicians, even cardiologists, have difficulty measuring the QT interval on the ECG. Some QT correction formulas require a calculator. A Heart Rhythm Society (HRS) study found that of 800 physicians, less than one fourth of cardiologists and non-cardiologists correctly classified all QT intervals as either ‘long’ or ‘normal.’⁴

Mistakes in QT measurement occur for a number of reasons, including technically suboptimal ECGs. Another factor is that besides the ability to recognize long QT on the ECG, clinicians must also be skilled at reading T- and U-wave shapes. A distorted T-wave—one that is flat, asymmetric and notched—is another TdP red flag. In drug-induced long QT, the distorted T-wave may merge with a bigger U-wave. Some clinicians have never seen a true prolonged QT or distorted T-wave on the ECG of a TdP patient, but they can be taught to recognize and distinguish abnormal T- and U-wave shapes.

Q: What is the recommended approach to monitoring long QT?

Ian Rowlandson: Step one is taking a thorough medical history, including any prescribed QT-prolonging drugs and previously mentioned TdP risk factors.

Ideally, before administering any QT-prolonging drug, particularly a high-risk drug such as Sotalol, the clinician should test the patient’s tolerance to the drug. To do so, the clinician should first conduct a diagnostic resting 12-lead ECG to baseline the QT. Then, once the drug is administered, the patient should be placed on a monitor to track the QT.

The clinician should watch for signs of arrhythmia. These include an increase in the QT interval by more than 60 milliseconds from pre-drug baseline, QT prolongation to greater than 500 milliseconds, a distorted T-U wave, and other markers. Should any warning signs occur, another 12-lead ECG should be taken to clarify the reading.

These readings can be taken over a six- or 12-hour period and may include additional 12-lead ECGs. With high-risk drugs like Sotalol, the patient might require admission and monitoring for up to three days to ensure safe tolerance.

I recommend this combination ECG-monitoring approach because QT monitoring alone sometimes results in false positives. Remember that the monitor typically uses fewer leads. Also, during a diagnostic resting 12-lead ECG, the patient is truly at rest. Monitoring doesn't always provide that assurance. Patient movement during monitoring can cloud the signal.

Finally, for QT monitoring consistency, the AHA-ACCF recommend the use of the same recording device, ECG lead, heart rate correction formula, etc. both before and after drug administration.³

Q: How do you reverse drug-induced long QT?

Ian Rowlandson: The clinician has multiple options, including discontinuing the QT-prolonging drug, adjusting electrolytes, administering magnesium sulfate, or considering a temporary pacemaker. These patients should remain in the hospital unit with the highest level of ECG monitoring surveillance and available defibrillation.

Q: How does GE Healthcare help clinicians monitor QT?

Ian Rowlandson: A number of factors distinguish GE Healthcare's QT monitoring solutions, including QT measurement accuracy and precision, consistency of QT measurement across platforms and conformance to global QT measurement recommendations.

In developing its GE Marquette™ 12SL™ ECG analysis program, GE Healthcare fine-tuned the algorithm’s QT measurements by participating in studies to determine drugs’ QT prolongation and TdP risk. The 12SL algorithm received such high marks for accuracy and precision that no manual intervention was required in selected drug tests.⁵

Unlike some other manufacturers, GE Healthcare has evidence to quantify accuracy of QT measurement in its ECG algorithm, especially when QT is long, a measurement where vendors’ algorithms differ most.⁶ In a study of QT measurement precision by advanced ECGs, for QTc values greater than 500 milliseconds (AHA/ACCF benchmark for long QT), the correlation between manually and automatically measured QTc values was 0.97.⁵

To support consistency of QT measurement, GE Healthcare has implemented its 12SL ECG algorithm across all diagnostic ECGs and monitoring systems. As an added feature, the monitor can interface with patients’ historical ECGs that were done on a resting electrocardiograph. That's important, because the installed base of historical access of prior ECGs is much larger in GE Healthcare versus in other.

And finally, GE Healthcare conforms to the AHA/ACC/HRS global recommendation to average QT measurement across all twelve ECG leads, from earliest onset to latest onset.³ GE Healthcare’s 12SL algorithm measures ten beats across all twelve leads, overlays them and then takes the median sample in each sample time. This generally results in clean and
consistent measurements compared to methods that use averaging or eliminate selected leads from the calculation.

Q: Before we end, what’s on the horizon for GE Healthcare's QT monitoring?

Ian Rowlandson: First, we are taking a closer look at T-wave morphology as a marker for long QT and TdP risk. Clinicians have requested more advanced tools for this purpose. A second related priority is looking at T-wave shapes in the presence of atrial fibrillation, which is treated with Sotalol, with its attendant risks for QT prolongation and TdP risk.

References

Professor Dr. med. Patrick Friederich, Monitoring of the QT interval in perioperative and critical care. GE Healthcare white paper. Accessed May 21, 2019.
Risgaard, B., et al., Sudden Cardiac Death: Pharmacotherapy and Proarrhythmic Drugs: A Nationwide Cohort Study in Denmark. JACC: Clinical Electrophysiology, 2017. 3(5): p. 473-481. Accessed May 21, 2019.
Drew, B.J., et al., Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation, 2010. 121(8): p. 1047-60. Accessed May 20, 2019.
Viskin, S., et al., Inaccurate electrocardiographic interpretation of long QT: the majority of physicians cannot recognize a long QT when they see one. Heart Rhythm Society, 2005. 2(6): p. 569-74. Accessed May 20, 2019.
Hnatkova, K., et al., Precision of QT Interval Measurement by Advanced Electrocardiographic Equipment. Pacing Clin Electrophysiol, 2006. 29(11): p. 1277-84. Accessed May 21, 2019.
Kligfield, P., et al., Comparison of automated interval measurements by widely used algorithms in digital electrocardiographs. American Heart Journal, 2018. Accessed May 19, 2019.