Acquired QT Interval Prolongation Research Articles

Transient Acquired QT Interval Prolongation After Administration of Intravenous Ondansetron

A 62-year-old man with a history of stable ischemic heart disease presented to the emergency room with nausea, vomiting, and chest pain at rest. The chest pain was atypical in nature; it did not respond to nitroglycerin and did not worsen with exertion. He took only aspirin, metoprolol, and ramipril at home. The patient was normotensive and normoxemic. Serial high-sensitivity troponin test results were normal, and other bloodwork (including calcium and magnesium levels) was unremarkable, with the exception of a serum potassium level of 2.4 mmol/L. His presenting electrocardiogram (ECG; Fig. 1A ) showed sinus rhythm with a right bundle branch block and a mildly prolonged QTc interval (450 msec using Bazett’s formula1Bazett H. An analysis of the time-relations of electrocardiograms.Heart. 1920; 7: 353-370Google Scholar). However, conduction delays prolong the QRS interval, which affects the length of the QT interval without significant impact on the repolarization duration. Bogossian’s formula can correct the QTc interval in the presence of bundle branch blocks, and this yielded a normal QTc interval of 302 msec.2Bogossian H. Linz D. Heijman J. et al.QTc evaluation in patients with bundle branch block.Int J Cardiol Heart Vasc. 2020; 30: 100636PubMed Google ScholarFigure 1Electrocardiogram showing (A) sinus rhythm with a right bundle branch block (bbb) and mildly prolonged QTc interval; (B) ST changes with profound QTc interval prolongation; and (C) partial resolution of the ST changes.View Large Image Figure ViewerDownload Hi-res image Download (PPT) During his time in the emergency room, he experienced nausea and was given 4 mg of ondansetron intravenously. He was also given 40 mmol of KCl orally for his hypokalemia. Fifteen minutes later, the patient had a mild recurrence of atypical chest discomfort at rest, and another ECG Fig. 1B) was performed. This showed nonspecific ST changes with profound QTc interval prolongation, using both Bogossian’s formula (562 msec) and Bazett’s formula (628 msec). In addition to QTc interval prolongation, there was a dramatic difference in T wave morphology, including prolongation of the Tpeak–Tend interval. Ten minutes later, an ECG (Fig. 1C) and blood work were repeated, which showed a serum potassium level of 3 mmol/L, and partial resolution of the ST changes. The patient was not given any further QT-prolonging medication, and he was subsequently diagnosed with noncardiac chest pain after undergoing normal stress myocardial perfusion imaging. Severe hypokalemia is a known cause of QT interval prolongation.3Yelamanchi V.P. Molnar J. Ranade V. Somberg J.C. Influence of electrolyte abnormalities on interlead variability of ventricular repolarization times in 12-lead electrocardiography.Am J Ther. 2001; 8: 117-122Crossref PubMed Scopus (35) Google Scholar However, this patient’s initial ECG demonstrates a normal (by Bogossian’s formula) or only modestly prolonged (by Bazett’s formula) QTc interval. Subsequent administration of IV ondansetron resulted in profound transient QTc interval prolongation relative to this patient’s baseline, and marked changes in T wave morphology. It has been previously described that intravenous ondansetron administration can lead to QT interval prolongation and T wave changes. Our patient had a history of ischemic heart disease; the presence of structural heart disease increases the risk for acquired QT interval prolongation. Such prolongations of the QTc and Tpeak–Tend intervals are associated with increased risk of Torsades de Pointes and sudden cardiac death, with the risk increasing proportionally to QTc interval duration.4Thomas S. Behr E. Pharmacologic treatment of acquired QT prolongation and torsades de pointe.Br J Clin Pharmacol. 2016; 81: 420-427Crossref PubMed Scopus (67) Google Scholar, 5Hafermann M. Namdar R. Seibold G. et al.Effect of intravenous ondansetron on QT interval prolongation in patients with cardiovascular disease and additional risk factors for torsades: a prospective, observational study.Drug Healthc Patient Saf. 2011; 3: 53-58PubMed Google Scholar, 6Tse G. Gong M. Meng L. et al.Predictive value of Tpeak-Tend indices for adverse outcomes on acquired QT prolongation: a meta-analysis.Front Physiol. 2018; 9: 1226Crossref PubMed Scopus (18) Google Scholar These images demonstrate the importance of cautious administration of QT interval–prolonging medications, particularly in the presence of other risk factors for QT interval prolongation such as hypokalemia and underlying structural heart disease, even if the baseline QTc interval is not markedly prolonged.Novel Teaching Points•Proper assessment of the QT interval is important in the setting of a bundle branch block, as widening of the QRS will cause subsequent QT interval prolongation without significant impact on the duration of repolarization.•Bogossian’s formula is an alternative method for calculating the QT interval in the setting of a bundle branch block. However, no single formula is perfect for QTc interval calculation in every situation.•Caution is needed when prescribing medications that prolong the QT interval, especially for patients with an underlying predilection for QT interval prolongation.

MACROVOLT TWAVE ALTERNANS: A FOREBODING SIGN FOR VENTRICULAR ARRHYTHMIA IN SEVERE SYSTEMIC ILLNESS

Microvolt t-wave alternans (TWA) is a risk factor for sudden cardiac death but is only discernible on stress ECG using signal processing techniques. This case represents an example of acquired QT interval prolongation and macrovolt TWA leading to torsades de pointes (TdP). 63 year old man with

Predictive Value of T peak - T end Indices for Adverse Outcomes in Acquired QT Prolongation: A Meta-Analysis.

Background: Acquired QT interval prolongation has been linked with malignant ventricular arrhythmias, such as torsade de pointes, in turn predisposing to sudden cardiac death. Increased dispersion of repolarization has been identified as a pro-arrhythmic factor and can be observed as longer Tpeak – Tend interval and higher Tpeak – Tend/QT ratio on the electrocardiogram. However, the values of these repolarization indices for predicting adverse outcomes in this context have not been systematically evaluated.Method: PubMed, Embase and Cochrane Library databases were searched until 14th February 2018, identifying 232 studies.Results: Five studies on acquired QT prolongation met the inclusion criteria and 308 subjects with drug-induced LQTS patients (mean age: 66 ± 18 years old; 46% male) were included in this meta-analysis. Tpeak – Tend intervals were longer [mean difference [MD]: 76 ms, standard error [SE]: 26 ms, P = 0.003; I2 = 98%] and Tpeak – Tend/QT ratios were higher (MD: 0.14, SE: 0.03, P = 0.000; I2 = 29%) in patients with torsade de pointes compared to those without these events.Conclusion: Tpeak – Tend interval and Tpeak – Tend/QT ratio were higher in patients with acquired QT prolongation suffering from torsade de pointes compared to those who did not. These repolarization indices may provide additional predictive value for identifying high-risk individuals.

Acquired QT interval prolongation and ventricular arythmias associated with brucellosis: A case report and review of literature

Brucellosis is a zoonosis caused by Brucella species and usually involves the lymphoreticular system. Cardiovascular involvement is rare but fatal. Endocarditis is the most common cardiovascular manifestation of brucellosis. Herein we report a case of brucellosis with a presentation of acquired QT prolongation and ventricular tachycardia without a clear clinical picture of endocarditis and myocarditis.

Acquired QT Interval Prolongation & Methadone: The Risk of Pharmacological Interaction

Methadone is known to be associated with acquired long QT (LQT) syndrome and the subsequent development of Torsades de Pointes (TdP). We describe a case of acquired LQT and TdP in a patient taking methadone maintenance therapy (MMT) in conjunction with medications known to prolong QT interval, and in the setting of hypokalemia and hypomagnesemia. We highlight the risk of QT interval prolongation when polypharmacy and electrolyte imbalances coexist, demonstrate the importance of early and effective therapy of LQT and suggest potential future alternatives to MMT that appear to have less QT prolonging properties in patients with multiple risks for LQT and TdP.

Abstract 638: A Novel Mutation In The KCR1 Gene May Influence Susceptibility To The Acquired Long QT Syndrome

Introduction : Acquired QT interval prolongation and torsade de pointes can be caused by exposure to certain drugs, electrolyte imbalance, and myocardial ischemia. Acquired LQTS is more prevalent than the congenital LQTS and represents a significant problem for public health. Previous reports showed that K + channel regulator 1 (KCR1), an α glucosyltransferase, diminishes HERG drug sensitivity , and that a KCR1 polymorphism, Ile447Val, is associated with protection against drug-induced LQTS in humans. However, few studies address the effects of genetic changes in KCR1 and we screened the coding region of KCR1 in Japanese patients with the acquired LQTS. Hypothesis : We hypothesized that mutations or polymorphisms in KCR1 may influence the development of acquired LQTS. Methods: The genomic DNA of 70 unrelated patients with congenital LQTS, 41 unrelated patients with acquired LQTS, and 130 unrelated control subjects was screened by PCR-SSCP, PCR-RFLP, and direct sequencing. Appropriate sequence changes were introduced into subcloned KCR1 cDNA using site-directed mutagenesis, and HERG plus WT or mutant KCR1 cDNA was transiently transfected into CHO-K1 cells. HERG current was recorded using whole cell patch-clamp techniques and drug block of HERG current was assessed. Results : We identified a novel mutation in KCR1 , Glu33Asp in a Japanese acquired LQTS patient. Similar to what we reported previously, WT KCR1 diminished the susceptibility of HERG current to dofetilide (50 nM). After 15 min of continuous pulsing, 74±7% current remained in the presence of WT KCR1 vs 54±5% in the absence of KCR1. In contrast, 48±6% of HERG current remained in the presence of Glu33Asp KCR1 which was comparable to that of HERG alone. Significantly, we found that unlike WT KCR1, Glu33Asp KCR1 is no longer able to complement the genetic defect in α glucosyltransferase activity in yeast strain YG649, suggesting that enzymatic function of Glu33Asp KCR1 is compromised. We found no evidence for the Ile447Val KCR1 in Japanese LQTS patients and control subjects, which is present at an allele frequency of 7% allele frequency in a control population of the United States. Conclusion: These data suggest that the Glu33Asp KCR1 genetic change may predispose to the development of acquired LQTS.

The effect of propofol dose on myocardial repolarization in children

Introduction: Acquired QT interval prolongation on the ECG is commonly drug-induced, and is traditionally associated with torsades de pointes (TdP). A better predictor of TdP is the time interval between the peak and the end of the T wave (Tp-e)(1). Sevoflurane prolongs the corrected QT interval (QTc), although the Tp-e remains unaffected(2). In contrast, target controlled infusion of propofol at 3 μg/mL has no effect on QTc or Tp-e. This plasma concentration of propofol is at the extreme lower end of the range for surgical anesthesia. The purpose of this randomised double-blind clinical study was to investigate the dose-response relationship between propofol, QTc and Tp-e in a range of doses clinically relevant for surgical anesthesia. Methods: Written ethics committee approval and consent was obtained. 60 healthy unpremedicated children, aged 3-10 years, were recruited. Subjects were randomised to receive target controlled infusions of propofol, to achieve one of three plasma concentrations: 3μg/mL, 4.5μg/mL and 6μg/mL. A pre-operative 12 lead ECG was performed and repeated 5 minutes post induction. Two investigators, blinded to the group allocation and to the timing of the ECG traces, independently measured QTc and Tp-e within and between each group. Paired t-tests were used to compare QTc and Tp-e within groups. One way analysis of variance was used for inter-group analysis. The primary outcome measure was a change of >25msec in Tp-e both within and between groups.

Genetic aspects in acquired long QT syndrome ? a piece in the puzzle

Torsade de pointes (TdP) is a serious complication which is induced by a large variety of cardiovascular and non-cardiovascular drugs. Many clinical conditions and risk factors for the occurrence of TdP during administration of drugs with a proarrhythmic potential have been identified. All such drugs have in common that they reversibly alter myocardial repolarization due to the prolongation of the action potential (acquired QT interval prolongation) which is per se not arrhythmogenic. TdP is initiated (acquired long QT (LQT) syndrome) only when a threshold level is reached leading to early after-depolarizations (EADs) and triggered beats together with a marked dispersion in recovery of excitability. The underlying mechanisms of TdP are not yet satisfactorily elucidated but, in general, alterations in cardiac ion currents which tune the normal action potential play a major role in arrhythmogenesis. Following recent advances in molecular biology and genetics, it has become clear that in some clinical instances (e.g. congestive heart failure or cardiac hypertrophy) ion channel genes become less expressed (down-regulated) and the consequent reduced ion currents (e.g. IKr) are likely to cause prolonged myocardial repolarization. In this setting, the use of drugs with action potential-prolonging properties could possibly be harmful and could not be compensated by the normal cardiac ‘repolarization reserve’. In congenital LQT syndrome some of the same ion channel components were found to be genetically altered, suggesting that either quantitative or qualitative changes of ion currents may be involved in ventricular arrhythmogenesis through similar mechanisms (‘final common pathway’). A variable clinical expressivity and, especially, an incomplete penetrance has been found in patients carrying the same LQT genotype, even when near-relatives, which raises the question on the frequency and importance of ‘silent’ (i.e. minor functional) ion channel gene mutations that may become functionally significant in presence of action potential prolonging drugs and other coexisting factors. The observation of adverse drug reactions in apparently healthy (‘normal heart’) individuals is suggestive of a genetic susceptibility for ‘acquired’ arrhythmias. This report reviews and summarizes the recent knowledge on unapparent ion channel gene mutations and preliminary concepts about ‘acquired’ arrhythmias.