Otherwise Unexplained Transient QTc Prolongation in a Patient Admitted with COVID Disease

Background. Several cardiovascular manifestations of coronavirus disease 2019 (COVID-19) have been previously described. QT prolongation has been reported in COVID-19 infection in association with medications such as azithromycin, hydroxychloroquine, and chloroquine but has not previously been reported as a direct result of COVID-19 infection. Case summary. We report the case of a 65-year-old female who developed a prolonged corrected QT interval (QTc) during a hospital admission with COVID-19. This patient was not on any QT prolonging treatment, serum electrolytes were normal, and there was no identifiable reversible cause for the QTc lengthening. Daily serial ECGs during admission showed resolution of the ventricular repolarization abnormality in synchronization with resolution of her COVID-19 viral illness. Discussions. Although there have been reports of QTc prolongation in COVID-19 patients, previous reports of this are for patients receiving medication that causes QT prolongation. This case uniquely demonstrates the development and resolution of this temporary ventricular repolarization abnormality in a patient with a structurally normal heart with no evidence of myocardial fibrosis or edema on cardiac MRI, that is unexplained by other confounding factors, such as medication. This suggests there may be a direct association between COVID-19 and temporary QTc prolongation.

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What is the role of QTc prolongation assessment in new drugs development phase I oncology trials?

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.2006 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 2006-2006

Author(s):

G. Curigliano ◽

C. Cipolla ◽

C. Sessa ◽

C. Noberasco ◽

T. De Pas ◽

...

Keyword(s):

Phase I ◽

Qt Interval ◽

Phase I Study ◽

Qt Prolongation ◽

New Drugs ◽

Accurate Information ◽

Investigational Drug ◽

Qtc Interval ◽

Qtc Prolongation ◽

Qt Interval Prolongation

2006 Background: QT interval prolongation associated with “torsades de pointes” (TdP) has been a common cause of withdrawal from the market for several promising drugs. We determined the degree of QT prolongation in patients treated within a phase I study with a thioxanthone derivative known to have arrhythmogenic potential. Methods: Clinical data and serial ECGs from 31 patients with advanced tumors who received 86 courses of investigational drug were prospectively reviewed. The drug has been administered intravenously over 24 hours every 3 weeks. Patients have been on a 24 hour Holter monitor until 24 hours after infusion was complete. Three baseline ECGs were done and compared to those every 6 hours during therapy and once 6 hours after the infusion was complete. ECGs were read at a central lab according to a standard protocol. All QT measurements were then corrected for heart rate (QTc) using Bazett’s formula (QTc = QT interval divided by the square root of the R-R interval). Results: Overall,843 ECG tracings were obtained, all evaluable for analysis. No basal ECG showed significant abnormalities. Prolonged QT intervals developed in 2 patients without clinical symptoms (1 patient had intervals 500 milliseconds).In both cases it was associated with the maximum concentration of the drug. Compared with baseline, the QTc interval was prolonged by 30 to 60 milliseconds in 20% of total tracings, and by more than 60 milliseconds in 2% of ECGs. In patients receiving multiple courses, QTc intervals returned to pretreatment levels before the second course. Conclusions: The assessment of QTc prolongation was a major effort in this study but produced an accurate information about such event. In phase I study such an effort is justified when arrhythmogenicity is suspected. The timing of collection of ECGs should be guided by the available preclinical information about the pharmacokinetic profile of the drug. Nevertheless uncertainty remains regarding the specific relationship between the degree of QT prolongation and the risk of life-threatening arrhythmias. The decision to use the drug ultimately has to be based on an estimation of the perceived risk relative to expected benefits for patients. No significant financial relationships to disclose.

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Indexes for ventricular repolarization abnormality: Re-evaluation of QT interval.

Japanese Journal of Electrocardiology ◽

10.5105/jse.12.327 ◽

1992 ◽

Vol 12 (3) ◽

pp. 327-335

Author(s):

Takahisa Maruyama ◽

Tohru Ohe ◽

Yoshiaki Okano ◽

Takashi Kurita ◽

Naohiko Aihara ◽

...

Keyword(s):

Qt Interval ◽

Ventricular Repolarization ◽

Repolarization Abnormality

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PARP inhibitor-induced torsades de pointes in long QT syndrome: a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytz230 ◽

2019 ◽

Vol 4 (1) ◽

pp. 1-5

Author(s):

Louise Segan ◽

Ashley Beekman ◽

Shane Parfrey ◽

Mark Perrin

Keyword(s):

Qt Interval ◽

Parp Inhibitor ◽

Torsades De Pointes ◽

Parp Inhibitors ◽

Qt Prolongation ◽

Long Qt ◽

Brca Mutations ◽

Case Summary ◽

Dose Dependent Increase ◽

Dose Dependent

Abstract Background Poly ADP-ribose polymerase (PARP) inhibitors target pathogenic BRCA mutations in chemotherapy-resistant malignancies. PARP inhibitors cause modest dose-dependent QT prolongation in the setting of a normal baseline QT interval. Case summary We describe a case of PARP inhibitor-induced torsades de pointes (TdP) in an 86-year-old gentleman prescribed rucaparib due to chemotherapy-resistant, metastatic prostate cancer with pre-existing long QT, with an apparent dose-dependent increase in QT interval. The patient presented with syncope and recurrent TdP requiring direct cardioversion reversion (200 J biphasic) and an isoprenaline infusion (2 μg/min). There were no other QT prolonging agents and no electrolyte or metabolic disturbance to account for this arrhythmia. Improvement in QT interval was observed within 72 h of rucaparib cessation. Discussion PARP inhibitors cause a modest, dose-dependent increase in QT interval in patients with a normal baseline. The safety of PARP inhibitors in patients with pre-existing long QT has not been evaluated. This is the first reported case of rucaparib-associated TdP in a patient with pre-existing long QT, highlighting the amplified effect of this agent in individuals with pre-existing QT prolongation and the risk of fatal arrhythmias.

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QT Interval Prolongation and Torsade De Pointes in Patients with COVID-19 treated with Hydroxychloroquine/Azithromycin

10.1101/2020.04.27.20074583 ◽

2020 ◽

Cited By ~ 8

Author(s):

Ehud Chorin ◽

Lalit Wadhwani ◽

Silvia Magnani ◽

Matthew Dai ◽

Eric Shulman ◽

...

Keyword(s):

Retrospective Study ◽

Qt Interval ◽

Potential Benefit ◽

Drug Exposure ◽

Torsade De Pointes ◽

Careful Consideration ◽

Qt Prolongation ◽

Interval Prolongation ◽

Qtc Prolongation ◽

Qt Interval Prolongation

AbstractBackgroundThe emergence of the COVID-19 pandemic has resulted in over two million affected and over 150 thousand deaths to date. There is no known effective therapy for the disease. Initial reports suggesting the potential benefit of Hydroxychloroquine/Azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns regarding the potential risk of QT prolongation and induction of torsade de pointes (TdP).MethodsThis is a multicenter retrospective study of 251 patients with COVID-19 treated with HY/AZ. We reviewed ECG tracings from baseline and until 3 days after completion of therapy to determine the progression of QTc and incidence of arrhythmia and mortality.ResultsQTc prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc prolongation to > 500 ms, a known marker of high risk for TdP had developed in 15.9% of patients. One patient developed TdP requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc of patients exhibiting QTc prolongation of > 60 ms was normal.ConclusionThe combination of HY/AZ significantly prolongs the QTc in patients with COVID-19. This prolongation may be responsible for life threating arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in lights of its unproven efficacy. Strict QTc monitoring should be performed if the regimen is given.

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Torsade De Pointes Resulting from the Addition of Droperidol to an Existing Cytochrome P450 Drug Interaction

Annals of Pharmacotherapy ◽

10.1345/aph.17351 ◽

1998 ◽

Vol 32 (7-8) ◽

pp. 761-765 ◽

Cited By ~ 54

Author(s):

Elizabeth Landrum Michalets ◽

Laura K Smith ◽

Eric D Van Tassel

Keyword(s):

Cytochrome P450 ◽

Qt Interval ◽

Tricyclic Antidepressants ◽

Torsade De Pointes ◽

Tendon Repair ◽

Qt Prolongation ◽

Drug Induced ◽

Case Summary ◽

P450 Inhibitors

OBJECTIVE: To report a case of QT prolongation associated with concomitant cyclobenzaprine and fluoxetine administration followed by torsade de pointes potentiated by droperidol. CASE SUMMARY: A 59-year-old white woman who had been receiving long-term fluoxetine and cyclobenzaprine therapy was admitted for Achilles tendon repair. Baseline QTc was prolonged at 497 msec. Prior to surgery, the patient received droperidol, an agent known to prolong the QT interval. During surgery the patient developed torsade de pointes, which progressed into ventricular fibrillation. On postoperative day 1, after cyclobenzaprine discontinuation, the QTc decreased toward normal (440 msec). DISCUSSION: Cyclobenzaprine shares anticholinergic effects, tachycardia, and dysrhythmic potential with the tricyclic antidepressants (TCAs). Fluoxetine is a known inhibitor of the CYP2D6 isoenzyme (along with CYP3A4 and CYP2C) and has been shown to increase TCA serum concentrations. The combination of cyclobenzaprine and fluoxetine resulted in significant QT prolongation in our patient that progressed to torsade de pointes after preoperative droperidol administration. Resolution of QT abnormalities after cyclobenzaprine discontinuation provided further evidence of a drug-induced etiology. Other possible medical and drug-related causes of torsade de pointes are reviewed and ruled out. CONCLUSIONS: Clinicians should be aware of the dysrhythmic potential of cyclobenzaprine and fluoxetine, monitor for other cytochrome P450 inhibitors, and avoid concomitant drugs known to prolong the QT interval.

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A Rapid Method to Evaluate Cardiac Repolarization Changes: The Effect of Two Coffee Strengths on the QT Interval

Cardiology ◽

10.1159/000381177 ◽

2015 ◽

Vol 131 (3) ◽

pp. 203-208 ◽

Cited By ~ 1

Author(s):

Janos Molnar ◽

John C. Somberg

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Systolic Blood Pressure ◽

Healthy Volunteers ◽

Qt Interval ◽

Ventricular Repolarization ◽

Cardiac Repolarization ◽

Qtc Prolongation ◽

Time Points ◽

Time Point

Objectives: To assess the effect of coffee on ventricular repolarization as measured by an electrocardiogram. Methods: Fifty-four healthy volunteers (34 males and 20 females, age 23 ± 5 years) received 1 cup of coffee (caffeine content 120 mg) and 11 participants received 2 cups. Blood pressure and heart rate were measured prior to coffee and every hour thereafter for 5 h. A 12-lead digital Holter recorded continuously, and RR, QT, and QTc intervals were obtained every 30 min. Results: Following coffee, RR increased from 802 ± 102 to 873 ± 126 ms (p = 0.001), QT increased from 359 ± 26 to 367 ± 27 ms at 1.5 h (p = 0.047), and QTc decreased from 387 ± 21 to 381 ± 23 ms at 30 min (p = 0.001), with no changes noted at other time points. Caffeine users and caffeine-naive subjects did not differ in QTc effects (p = 0.971). Females had longer QTc at each time point than males (p = 0.037), but neither had QTc prolongation following coffee. The heart rate decreased from 73 ± 9 to 69 ± 11 bpm at 1 h (p = 0.018), and no significant changes in blood pressure were noted. The effects of 1 or 2 cups of coffee did not differ in terms of QTc (p = 0.663), heart rate (p = 0.161), diastolic (p = 0.250), or systolic blood pressure (p = 0.168). Conclusion: Neither 1 nor 2 cups of coffee increased ventricular repolarization.

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QT prolongation associated with azithromycin/hydroxychloroquine combination in treatment of COVID-19: a single centre study

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20210593 ◽

2021 ◽

Vol 8 (3) ◽

pp. 369

Author(s):

Sami M. Alrasheedi ◽

Bader Alothman ◽

Ayman Alharbi ◽

Ahmad Alkhdairi ◽

Mohammed Zeitouni ◽

...

Keyword(s):

Risk Score ◽

Qt Interval ◽

Retrospective Cohort ◽

Heart Association ◽

Torsades De Pointes ◽

Qt Prolongation ◽

Cardiac Complications ◽

Qtc Prolongation ◽

Qt Interval Prolongation ◽

Combined Drugs

Background: The long QT syndrome is characterized by prolongation of QT interval, which may lead to life-threatening cardiac arrhythmias. Objectives were to assess prevalence, quantity and severity of QTc prolongation with combined drugs (azithromycin and hydroxychloroquine) in adults COVID-19 patients treated on these agents at KFSHRC. And to characterize cardiac complications of QTc prolongation with combined drugs.Methods: A retrospective cohort study at KFSH&RC, in Riyadh, Saudi Arabia. Baseline and daily ECG was done until completion of duration as per KFSH&RC guidelines for management of Covid-19, QTc prolongation>500 or increase of at least 60 ms compared with the pre-drug baseline value, or presence of cardiac conductive complications (torsades de pointes). The QTc prolongation was defined as>470 for male and >480 for female as per American Heart Association. A risk score that has been validated by Tisdale et al, for prediction of QT prolongation drug-related in admitted patients in cardiac care unit. The study duration was specified as one month after study approval by Research Ethics committee.Results: A total of 74 patients were included in the study. The patients were distributed according to their risk score for prediction of QT prolongation as the following: low (67/74), medium (6/74), high (1/74). Two patients with medium risk were started on both azithromycin and hydroxychloroquine. one of them his baseline QT was 490, Azithromycin was stopped as QT reached 502. The second patient has QT baseline 471, after starting treatment; QT range was 472-475, hydroxychloroquine was stopped on day 4. None of them had torsades de pointes. Only one patient with low risk, no baseline QT was recorded, but QT was 499 on day three, so hydroxychloroquine was stopped. Repeated ECG showed: QT decreased to 478, no torsades de pointes. Conclusions: In this single centered-retrospective cohort, we noticed that a small percentage of patients developed QT prolongation with the use of this combination. With the increasing the risk of developing QT prolongation the number of the patient who developed the condition increased. We used Tisdale score which is a scoring system Identifying hospitalized patients at risk for QT interval prolongation could lead to interventions to reduce the risk of torsades de pointes validated in May 2013.5 None of our population developed significant cardiac complications of QTc prolongation with combined drugs.

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Empagliflozin significantly prevents QTc prolongation due to amitriptyline intoxication via intracellular calcium regulation

European Heart Journal ◽

10.1093/eurheartj/ehab724.3439 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

V Baris ◽

E Gedikli ◽

A B Dincsoy ◽

A Erdem

Keyword(s):

Intracellular Calcium ◽

Qt Interval ◽

Qt Prolongation ◽

Control Group ◽

Diabetic Patients ◽

Calcium Balance ◽

Qtc Prolongation ◽

Toxic Dose ◽

Positive Effects ◽

Normal Limits

Abstract Background Empagliflozin is a SGLT-2 inhibitor used in the treatment of Type 2 diabetes and has positive effects on cardiovascular outcomes. Amitriptyline can be used in many clinical indications but leads to cardiotoxicity by causing QT prolongation. Aim Our aim in the present study is to observe the effect of the concomitant use of amitriptyline and empagliflozin together, which have an effect on sodium and calcium balance in myocytes, on QTc by using ECG. Materials and methods Twenty-four male Wistar-Albino rats were randomized into four groups. The control group received only serum physiologic (1ml) via orogastric gavage (OG). The EMPA group received empagliflozin (10 mg/kg) via OG. The AMT group received amitriptyline (100 mg/kg) via OG. The AMT+EMPA group (n: 6) received amitriptyline and empagliflozin at same dose. Under anesthesia; QT and QTC intervals were measured at baseline, first, and second hours. Results The differences in QT and QTc values between the AMT group and control group were observed from the 1nd hour (Table 1, Figure 1). It was detected that the measurements of the control group were within normal limits. In the control group, QT was 77.33±9.02 ms at the basal, 73.50±2.26 ms at the 1st hour, 78.17±6.18 ms at the 2nd hour. QTc calculation was 165.42±18.34±10.5 ms at the basal, 166.63±17.92 msat the 1st hour, 184.65±12.86 ms at the 2nd hour. ECG findings of the EMPA group were within normal limits and similar to the control group (Table 1). The durations of QT interval and QTc calculations were found to be statistically longer in the AMT group than the control group at the 1st and 2nd hour (p≤0.001). Empagliflozin significantly ameliorated AMT-induced QT and QTc prolongation. The durations of QT interval were significantly lower at first (p<0,001) and 2nd hours (p<0.01) in the AMT+EMPA group compared to the AMT group. Moreover, QTc calculation was significantly lower in the AMT+EMP group than the AMT group at 1st and 2nd hour (P<0.01) (Table 1). Electrocardiographic comparisons of all groups for one second within the second hour can be seen in Figure 2. Conclusion In the present study, we have detected that empagliflozin significantly ameliorates amitriptyline induced QT prolongation. This effect is probably due to the opposite effects of these two agents in the intracellular calcium balance. It's known that; toxic dose of amitriptyline increases the amount of Sarcoplasmic Ca and the calcium permeability of Ryanodine channels, decreases SERCA-mediated Ca-reuptake by decreasing the calcium binding capacity of calsequestrin, and these leads QTc prolongation. It has been shown that empagliflozin increases Ca reuptake by causing a significant increase in SERCA activity, and decreases Ca sparks by causing inhibition of Ryanodine activity. With more clinical trials, the routine use of empagliflozin may be suggested to prevent QTc prolongation in the diabetic patients receiving amitriptyline. FUNDunding Acknowledgement Type of funding sources: None. Table 1. QT, QTc durations and HR for groups Figure 1. ECG traces – a: CON, b: EMPA, c: AMT, d: AMT+EMP

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Changes of QT interval in the acute phase after pulmonary vein isolation for paroxysmal atrial fibrillation

European Heart Journal ◽

10.1093/ehjci/ehaa946.0414 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Chikata ◽

T Kato ◽

K Ududa ◽

S Fujita ◽

K Otowa ◽

...

Keyword(s):

Atrial Fibrillation ◽

Pulmonary Vein ◽

Female Patient ◽

Pulmonary Vein Isolation ◽

Acute Phase ◽

Paroxysmal Atrial Fibrillation ◽

Qt Interval ◽

Qt Prolongation ◽

Qtc Interval ◽

The Impact

Abstract Introduction Pulmonary vein isolation (PVI) affects ganglionated plexi (GP) around the atrium, leading to a modification of the intrinsic cardiac autonomic system (ANS). In animal models, GP ablation has a potential risk of QT prolongation and ventricular arrhythmias. However, the impact of PVI on QT intervals in humans remains unclear. Purpose This study aims to evaluate the Impact of PVI on QT interval in patients with paroxysmal atrial fibrillation. Methods We analyzed consecutive 117 PAF patients for their first PVI procedures. 12-lead ECG was evaluated at baseline, 4 hr, day 1, 1 month, and 3 months after ablation. Only patients with sinus rhythm on 12-lead ECG at each evaluation point without antiarrhythmic drugs were included. Results Heart rate significantly increased at 4 hr, day 1, and 1 month. Raw QT interval prolonged at 4 hr (417.1±41.6 ms, P<0.001) but shortened at day 1 (376.4±34.1 ms, P<0.001), 1 month (382.2±31.5 ms, P<0.001), and 3 months (385.1±32.8 ms, P<0.001) compared to baseline (391.6±31.4 ms). Bazett- and Fridericia- corrected QTc intervals significantly prolonged at 4hr (Bazett: 430.8±27.9 ms, P<0.001; Fridericia: 425.8±27.4 ms, P<0.001), day1 (Bazett: 434.8±22.3 ms, P<0.001; Fridericia: 414.1±23.7 ms, P<0.001), 1M (Bazett: 434.8±22.3 ms, P<0.001; Fridericia: 408.2±21.0 ms, P<0.05), and 3M (Bazett: 420.1±21.8 ms, P<0.001; Fridericia: 407.8±21.1 ms, P<0.05) compared to baseline (Bazett: 404.9±25.2 ms; Fridericia: 400.0±22.6 ms). On the other hand, Framingham- and Hodges- corrected QTc interval significantly prolonged only at 4hr (Framingham: 424.1±26.6 ms, P<0.001; Hodges: 426.8±28.4 ms, P<0.001) and at day1 (Framingham: 412.3±29.3 ms, P<0.01; Hodges: 410.6±40.2 ms, P<0.05) compared to baseline (Framingham: 399.2±22.7 ms; Hodges: 400.7±22.8 ms). At 4 hr after ablation, raw QT and QTc of all formulas significantly prolonged than baseline. Raw QT and QTc prolongation at 4hr after ablation were more frequently observed in female patients. Multiple regression analysis revealed that female patient is a significant predictor of raw QT and QTc interval prolongation of all formulas 4hr after PVI. Conclusions Raw QT and QTc prolonged after PVI, especially in the acute phase. Female patient is a risk factor for QT prolongation in the acute phase after PVI. Funding Acknowledgement Type of funding source: None

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Empagliflozin significantly attenuates QTc prolongation in rats due to sotalol

European Heart Journal ◽

10.1093/ehjci/ehaa946.3348 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

V.O Baris ◽

B Dincsoy ◽

E Gedikli ◽

A Erdem

Keyword(s):

Qt Prolongation ◽

Control Group ◽

Diabetic Patients ◽

Protective Effects ◽

Qtc Prolongation ◽

Positive Effects ◽

T Wave ◽

Qt Intervals ◽

Electrocardiogram Ecg

Abstract Introduction Sotalol (SOT) is a Class 3 antiarrhythmic drug and commonly used for various arrhythmia treatments. However; it can prolong QT interval and lead to malignant arrhythmias. Empagliflozin is a selective SGLT-2 inhibitor used in the treatment of Type 2 diabetes and has been shown to have positive effects on cardiovascular outcomes. Since the effect of empagliflozin (EMPA) on potassium channel activation is not yet known, there is no recommendation for the concomitant use of these drugs. Purpose In this study, we aimed to evaluate possible protective effects of empagliflozin in sotalol induced QT prolongation. Materials and methods Twenty-four male Wistar Alba rats were randomized into four groups. The first (control) group (n: 6) received only serum physiologic (1ml) via orogastric gavage (OG). The second (EMPA) group (n: 6) received EMPA (10 mg/kg) via OG. The third (SOT) group (n: 6) received SOT (80 mg/kg) via OG. The fourth (EMPA+SOT) group (n: 6) received EMPA (10 mg/kg) and SOT (80 mg/kg) via OG. Under anesthesia; PR, QT intervals and heart rate (HR) were measured and QTc value was also calculated at second hour on lead II using electrocardiogram (ECG). Results In the SOT group; QT intervals, T wave durations and QTc values were found to be statistically longer than the control group, whereas HR was found to be lower than the control group (p<0.01). In the EMPA+SOT group; QT intervals, T wave durations and QTc values were significantly lower and HR was significantly higher compared to the SOT group (p<0.001, p<0.01, p<0.001, p<0.001 respectively) (Table) Conclusion In the present study, we detected that EMPA significantly ameliorates SOT induced QT prolongation. In addition to this, we have also shown that EMPA can be used safely with SOT in clinical practice. With more clinical trials, the routine use of EMPA may be suggested to prevent QTc prolongation in diabetic patients receiving SOT. Finally; our study indicates that EMPA can effect on potassium channels. Funding Acknowledgement Type of funding source: None

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