An explainable algorithm for detecting drug-induced QT-prolongation at risk of torsades de pointes (TdP) regardless of heart rate and T-wave morphology

Safety and effectiveness of drug therapy for the acutely agitated patient (Part I)

Italian Journal of Medicine ◽

10.4081/itjm.2010.127 ◽

2013 ◽

pp. 127-136

Author(s):

Gianluca Airoldi

Keyword(s):

Heart Rate ◽

Qt Interval ◽

Physical Restraint ◽

Safety Data ◽

Surrogate Marker ◽

Diagnostic Procedures ◽

Torsades De Pointes ◽

Long Qt ◽

Drug Induced ◽

Qt Interval Prolongation

Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the first in a 2-part series) is to review the extensive safety data published on the antipsychotic medications currently available for managing situations of this type, including older neuroleptics like haloperidol, chlorpromazine, and pimozide as well as a number of the newer atypical antipsychotics (olanzapine, risperidone, ziprasidone). Particular attention is focused on the ability of these drugs to lengthen the QT interval in surface electrocardiograms. This adverse effect is of major concern, especially in light of the reported relation between QT interval and the risk of sudden death. In patients with the congenital long-QT syndrome, a long QT interval is associated with a fatal paroxysmal ventricular arrhythmia knownas torsades de pointes. Therefore, careful evaluation of the QT-prolonging properties and arrhythmogenic potential of antipsychotic drugs is urgently needed. Clinical assessment of drug-induced QT-interval prolongation is strictly dependent on the quality of electrocardiographic data and the appropriateness of electrocardiographic analyses. Unfortunately, measurement imprecision and natural variability preclude a simple use of the actually measured QT interval as a surrogate marker of drug-induced proarrhythmia. Because the QT interval changes with heart rate, a rate-corrected QT interval (QTc) is commonly used when evaluating a drug’s effect. In clinical settings, themost widely used formulas for rate-correction are those of Bazett (QTc=QT/RR^0.5) and Fridericia (QTc=QT/RR^0.33), both of which standardize themeasuredQTinterval to an RRinterval of 1 s (heart rate of 60 bpm).However, QT variability can also be influenced by other factors that are more difficult to measure, including body fat, meals, psycho-physical distress, and circadian and seasonal fluctuations.

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Sensitivity of QTc and T-wave morphology to small drug-induced electrocardiographic changes

Journal of Electrocardiology ◽

10.1016/j.jelectrocard.2008.08.026 ◽

2008 ◽

Vol 41 (6) ◽

pp. 644

Author(s):

C. Graff ◽

J. Matz ◽

M.P. Andersen ◽

J.K. Kanters ◽

E. Toft ◽

...

Keyword(s):

Drug Induced ◽

T Wave ◽

Wave Morphology ◽

Electrocardiographic Changes

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Abstract 14311: Qt Interval Correlation Between Telemetry and 12-lead Electrocardiogram

Circulation ◽

10.1161/circ.142.suppl_3.14311 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Mohamed Farhan Nasser ◽

Ahmad Jabri ◽

Saima Karim ◽

Elizabeth Kaufman

Keyword(s):

Qt Interval ◽

Ventricular Arrhythmias ◽

Qt Prolongation ◽

T Wave ◽

Qt Intervals ◽

Increased Risk ◽

Tangent Method ◽

Wave Morphology ◽

Monitoring Service ◽

Inpatient Units

Introduction: QT prolongation is associated with increased risk of ventricular arrhythmias.As many patients with COVID19 may be started on QT prolonging drugs, measuring and monitoring QT is imperative to prevent fatal ventricular arrhythmias. However, we need to limit exposure of staff to patients with confirmed COVID19 and judiciously use personal protective equipment. Thus, it is important to find alternatives to doing frequent 12-lead ECGs. Hypothesis: We hypothesize that the QT interval measured from telemetry is similar to the QT interval on 12-lead ECG. Methods: Telemetry recordings and 12-lead ECGs were obtained from 15 patients at the same time and identical heart rates. Patients were from two different inpatient units with the same telemetry monitoring service. QT intervals were measured manually using calipers with the tangent method, excluding U waves. Telemetry recordings included lead I and II or a precordial lead. QT from telemetry was compared to the corresponding leads and to the longest QT on the 12-lead ECG. In cases of atrial fibrillation (AF), the QT from all the complexes was averaged. Results: Of 15 patients, 2 were in AF and 2 had RBBB. One patient had abnormal T-wave morphology and QT prolongation (abnormal repolarization). In all patients, QT intervals from the same leads as telemetry matched the QT measured from 12-lead. In 14 of 15 patients, telemetry QT matched the longest QT on the 12-lead ECG. However, in the patient with abnormal repolarization, maximum QT on 12-lead ECG was substantially longer than telemetry QT (Figure 1). Conclusion: When using the same lead, QT intervals were identical on telemetry and 12-lead ECG. However, in the patient with abnormal repolarization, the longest QT on 12-lead ECG was not represented on telemetry. In patients with abnormal repolarization on 12-lead ECG, we recommend serial 12-lead ECGs while on QT-prolonging drugs. Telemetry may suffice as a surrogate for 12-lead ECG to follow QT intervals in most patients.

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Managing drug-induced QT prolongation in clinical practice

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2020-138661 ◽

2020 ◽

pp. postgradmedj-2020-138661

Author(s):

Rani Khatib ◽

Fatima R N Sabir ◽

Caroline Omari ◽

Chris Pepper ◽

Muzahir Hassan Tayebjee

Keyword(s):

Qt Interval ◽

Simple Algorithm ◽

Torsades De Pointes ◽

Daily Practice ◽

Qt Prolongation ◽

Key Factors ◽

Drug Induced ◽

Electrolyte Disturbances ◽

Related Risk ◽

Life Threatening

Many drug therapies are associated with prolongation of the QT interval. This may increase the risk of Torsades de Pointes (TdP), a potentially life-threatening cardiac arrhythmia. As the QT interval varies with a change in heart rate, various formulae can adjust for this, producing a ‘corrected QT’ (QTc) value. Normal QTc intervals are typically <450 ms for men and <460 ms for women. For every 10 ms increase, there is a ~5% increase in the risk of arrhythmic events. When prescribing drugs associated with QT prolongation, three key factors should be considered: patient-related risk factors (eg, female sex, age >65 years, uncorrected electrolyte disturbances); the potential risk and degree of QT prolongation associated with the proposed drug; and co-prescribed medicines that could increase the risk of QT prolongation. To support clinicians, who are likely to prescribe such medicines in their daily practice, we developed a simple algorithm to help guide clinical management in patients who are at risk of QT prolongation/TdP, those exposed to QT-prolonging medication or have QT prolongation.

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Optimal location of the QT interval evaluation in patients with drug‐induced QT prolongation and torsades de pointes: Limb leads, chest leads, or both?

Journal of Cardiovascular Electrophysiology ◽

10.1111/jce.14682 ◽

2020 ◽

Vol 31 (10) ◽

pp. 2702-2703

Author(s):

Bachir Lakkis ◽

Marwan M. Refaat

Keyword(s):

Qt Interval ◽

Torsades De Pointes ◽

Qt Prolongation ◽

Optimal Location ◽

Drug Induced ◽

Interval Evaluation

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Use of QT Prolonging Medications by Hemodialysis Patients and Individuals Without End‐Stage Kidney Disease

Journal of the American Heart Association ◽

10.1161/jaha.120.015969 ◽

2020 ◽

Vol 9 (13) ◽

Author(s):

Magdalene M. Assimon ◽

Lily Wang ◽

Patrick H. Pun ◽

Wolfgang C. Winkelmayer ◽

Jennifer E. Flythe

Keyword(s):

Risk Factors ◽

Kidney Disease ◽

Cardiac Death ◽

Medication Use ◽

Torsades De Pointes ◽

Hemodialysis Patients ◽

Qt Prolongation ◽

End Stage Kidney Disease ◽

Drug Induced ◽

End Stage

Background The rate of sudden cardiac death in the hemodialysis population exceeds that of the general population by >20‐fold. Hemodialysis patients may be particularly susceptible to sudden cardiac death provoked by drug‐induced QT prolongation because of their substantial cardiovascular disease burden, exposure to electrolyte shifts during dialysis, and extensive polypharmacy. However, population‐specific data regarding the frequency and patterns of QT prolonging medication use are limited. Methods and Results We conducted a descriptive drug utilization study using 3 administrative databases, the United States Renal Data System, MarketScan, and Medicare claims. We characterized the extent and patterns of QT prolonging medication use by adult hemodialysis patients and individuals without end‐stage kidney disease annually from 2012 to 2016. We also identified instances of high‐risk QT prolonging medication use among hemodialysis patients. In total, 338 515 hemodialysis patients and 40.7 million individuals without end‐stage kidney disease were studied. Annual utilization rates of QT prolonging medications with known torsades de pointes risk in hemodialysis patients were ~1.4 to ~2.5 times higher than utilization rates in individuals without end‐stage kidney disease. Hemodialysis patients with demographic and clinical risk factors for drug‐induced QT prolongation were exposed to medications with known torsades de pointes risk more often than patients without risk factors. Conclusions Hemodialysis patients use QT prolonging medications with known torsades de pointes risk more extensively than individuals without end‐stage kidney disease. Given the widespread use and instances of high‐risk prescribing, future studies evaluating the cardiac safety of these drugs in the hemodialysis population are needed.

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Successful treatment of bepridil-induced intraoperative torsades de pointes by isoproterenol infusion

JA Clinical Reports ◽

10.1186/s40981-021-00475-3 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Ken Shimano ◽

Kyungho Chang ◽

Yoshiki Hara ◽

Atsushi Yasuda ◽

Shigehito Sawamura

Keyword(s):

Heart Rate ◽

Antiarrhythmic Drugs ◽

Torsades De Pointes ◽

Qt Prolongation ◽

Residual Cancer ◽

Premature Ventricular Contractions ◽

Case Presentation ◽

Prolonged Qt Interval ◽

Prolonged Qt ◽

Isoproterenol Infusion

Abstract Background Several types of antiarrhythmic drugs are known to induce QT prolongation and torsades de pointes. Case presentation An 84-year-old man was scheduled for open gastrectomy for residual cancer. He had been prescribed bepridil for atrial fibrillation that converted to sinus rhythm with prolonged QT interval in the operating room. After the surgery was initiated under general and epidural anesthesia, the patient’s heart rate decreased to 50/min and multifocal premature ventricular contractions appeared, followed by several episodes of torsades de pointes, each lasting for 5 to 15 s. Infusion of isoproterenol was started (0.01 μg/kg/min), and the heart rate was maintained at around 80/min. Premature ventricular contractions disappeared, and torsades de pointes did not recur during the surgery. The operation was completed uneventfully. The serum bepridil concentration was found to be extremely high postoperatively. Conclusions Bepridil-induced intraoperative episodes of torsades de pointes were successfully treated by increasing the heart rate with isoproterenol.

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