Atrial Torsades De Pointes Post Covid Myocarditis

Background: Among patients with COVID-19 infection, the risk of adverse cardiovascular outcome, particularly myocarditis and dysrhythmias remain elevated at least up to one year after infection. We present a case of atrial tachycardia and atrial Torsades de Pointes from COVID myocarditis, persisted 6 months after infection, which was successfully managed by ablation. Objective(s): A 25-year-old female presented with mild COVID-19 infection, Omicron variant, in May 2022. One month after, her Covid infection resolved;she presented with symptomatic atrial tachycardia, paroxysmal atrial fibrillation and flutter. ECG showed multiple blocked premature atrial contractions (PAC) (Figure 1A). Holter monitor showed PAC triggered atrial tachycardia degenerating to paroxysmal atrial fibrillation, atrial Torsades de Pointes. She has mild persistent troponin elevation. Echocardiography was normal. Cardiac MRI showed evidence of mild myocarditis with subepicardial late Gadolinium enhancement (LEG) along the lateral mid-apical left ventricular wall and edema. (Figure 1B). She was treated with Colchicine for 2 months. Repeat cardiac MRI 4 months after COVID infection showed resolution of edema and LGE. However, her symptomatic PAC and atrial tachycardia did not respond to betablocker and amiodarone. She underwent electrophysiology study. Activation mapping of PAC using CARTO revealed earliest activation at the right anterior atrial wall, with close proximity to tricuspid valve;unipolar signal showed QS pattern, bipolar signal showed 16 msec pre-PAC (Figure 1C and 1D). Mechanical pressure from ThermoCool SmartTouch ablation catheter (Biosense Webster Inc.) at this site suppressed the PAC. Radiofrequency ablation resulted with an initial acceleration and then disappearance of the PAC. We did not isolate pulmonary veins or ablate cavotricuspid isthmus. Post ablation, PAC and atrial fibrillation were not inducible on Isoproterenol. Method(s): N/A Results: Covid myocarditis can result in dysrhythmia that lingers long after Covid myocarditis has resolved. Covid myocarditis can be caused by direct viral invasion of myocytes or more commonly is inflammatory related to cytokine release and edema. Our case demonstrates that dysrhythmias can persist despite resolution of myocarditis. Catheter ablation can successfully to treat these arrhythmias. Conclusion(s): This case highlights the importance of recognizing cardiac dysrhythmia as possible the long-term cardiac complications of COVID-19, requiring specific treatment such as catheter ablation. [Formula presented]Copyright © 2023

Tocilizumab- a Treatment Option for Torsades De Pointes in Covid-19 Patients

Background The incidence of ventricular arrhythmias (VA) in Coronavirus disease 2019 (COVID-19) patients ranges from 1.6 to 5.9%. COVID-19 can trigger a systemic inflammatory response, which may unmask arrhythmias. Here we discuss a challenging case of COVID-19 that manifested as recurrent Torsades de Pointes (TdP). Case A 39-year-old female with no known past medical history presented with a complaint of multiple syncopal episodes in the last two days. Initial electrocardiograms (EKG) showed a heart rate of 62 with frequent premature ventricular contractions (PVCs) and a prolonged corrected QT(QTc) interval of 520ms. Frequent PVCs soon converted to TdP with loss of consciousness which was managed with successful direct current cardioversion (DCCV). However, the patient relapsed into TdP, warranting another successful DCCV. COVID-19 workup came back positive. Electrolytes were within normal limits;however, C-reactive protein (CRP) and troponin T levels were elevated. Decision-making The patient was started on intravenous (IV) magnesium for 24 hours. Following another episode of self-limiting TdP, IV isoproterenol was started, and tocilizumab was given. An echocardiogram showed no evidence of structural heart disease. During the hospital course, telemetry showed PVCs that decreased in frequency paralleled with a decrease in CRP and troponins. Repeat EKGs showed normalization of QTc interval. The patient declined implantable device placement or procedures and was eventually discharged with a heart monitor and a beta blocker. On follow-up, the patient denied any symptoms since the discharge, QTc remained normal, and the heart monitor did not show any VA. Conclusion Management of TdP generally involves magnesium, IV isoproterenol, and transvenous pacing. However, as described in this case, tocilizumab can cause QT interval shortening and a reduction in CRP and cytokine levels and may be beneficial for use in COVID-19 patients with QT prolongation and VA, including TdP. There are no strict guidelines for arrhythmias in COVID-19 patients. Accordingly, more studies need to be done to follow this patient population managed with tocilizumab for their eventual outcomes.Copyright © 2023 American College of Cardiology Foundation

Takotsubo cardiomyopathy presenting with QT prolongation and Torsade de pointes in the setting of coronavirus disease 2019.

Cardiovascular complications resulting from coronavirus disease 2019 (COVID-19) are occasionally observed; however, takotsubo cardiomyopathy (TCM) with QT prolongation and Torsade de pointes have rarely been reported. We herein present a case of TCM that occurred after QT prolongation and Torsade de pointes. A 58-year-old woman was admitted because of COVID-19 pneumonia. Seven days after admission, she had a sudden loss of consciousness without any precursor of cardiovascular disease. Monitoring electrocardiogram indicated Torsade de pointes and a prolonged QT interval. Emergency cardiac catheterization revealed the presence of TCM. She received favipiravir and steroids, followed by rehabilitation, which improved her condition. Routine electrocardiography screening is considered for patients with COVID-19 because asymptomatic TCM could be detected.

Whole blood drug levels do not correlate with QTc intervals in hydroxychloroquine treated systemic lupus erythematosus patients.

OBJECTIVES: Hydroxychloroquine is recommended for all patients with systemic lupus erythematous, but reports of cardiac toxicity in SARS CoV-2 patients raised concerns. We aimed to study the relationship between hydroxychloroquine blood levels and QTc intervals. METHODS: Cohort 1 is a retrospective review of 90 SLE patients with data collected regarding demographics, QTc interval and chronic kidney disease (CKD). Cohort 2 is a prospective study of 84 SLE patients with data collected regarding demographics, dose of HCQ, duration of HCQ treatment, presence of echocardiographic abnormalities, and CKD simultaneous with whole blood HCQ levels measured by high performance liquid chromatography. Statistical analysis utilized one way ANOVA, Pearson's correlation coefficient and t test. RESULTS: In the retrospective cohort there was no significant difference in mean QTc based on 75 HCQ-treated (437.91 +/- 20.02) as compared with 15 untreated (434.6 +/- 27.49) patients. In patients with CKD mean QTc in HCQ users (448 +/- 23.37) as compared with non-users (444.5 +/- 24.61) was also with no significant difference. In the prospective cohort HCQ levels did not correlate with QTc interval (r = 0.017) and this applied regardless of dose prescribed (r = 0.113 for 400 mg and r = 0.06 for 200 mg), duration of exposure (p= 0.36 for 0-5, 5-10, or > 10 years), CKD (r = 0.482) or underlying cardiac abnormalities (r = 0.430). CONCLUSION: This is the first study relying on measured blood levels demonstrating the absence of clinically consequential increase in QTc levels in HCQ treated SLE patients.

Takotsubo Syndrome and Sudden Cardiac Death.

Takotsubo syndrome (TTS), triggered by intense emotional or physical stress, occurring most commonly in post-menopausal women, presents as an ST-elevation myocardial infarction (MI). Cardiovascular complications occur in almost half the patients with TTS, and the inpatient mortality is comparable to MI (4-5%) owing to cardiogenic shock, myocardial rupture, or life-threatening arrhythmias. Thus, its prognosis is not as benign as previously thought, as it may cause mechanical complications (cardiac rupture) and potentially lethal arrhythmias and sudden cardiac death (SCD). Similar to MI, some patients may perish before reaching the hospital due to out-of-hospital cardiac arrest; this may lead to underestimation of the actual SCD risk. Furthermore, after discharge, some patients may develop late SCD and/or TTS recurrence that may result in SCD. There are risk factors for SCD in TTS patients, such as severe/persistent QT-interval prolongation inciting torsade-de-pointes, other ECG abnormalities (diffuse giant negative T-waves, widened QRS-complex), bradyarrhythmias, comorbidities, concurrent obstructive coronary artery disease or vasospasm, male gender, older age, severe left ventricular dysfunction, and use of sympathomimetic drugs. All these issues are herein reviewed, case reports/series and data from large cohort studies and meta-analyses are analyzed, risk factors are tabulated, and proarrhythmic effects and management strategies are discussed and pictorially illustrated.

ECG Abnormalities in Patients Affected with COVID-19: A Review

Cardiovascular inclusion has been accounted for in patients with serious intense respiratory condition Covid 2 contamination, which might be reflected by electrocardiographic changes. Cardiovascular injury is additionally connected with humanity, need for intensive care, and seriousness of illness in patients due to Coronavirus. Some case features cardiovascular contribution as an intricacy related with Coronavirus, even without indications and indications of interstitial pneumonia. Two Coronavirus incidents in our report displayed diverse ECG indications by means of the sickness caused decay. The main case introduced brief SI QIII TIII sound structure followed by changeable almost whole atrioventricular square, and the second exhibited ST-section height joined by choroidal ventricular tachycardiac. The hidden systems of these ECGs irregularities in the serious phase of Coronavirus might be ascribed to hypoxia and incendiary harm brought about by the infection. Since the scourge of Coronavirus pulled in the consideration, hearsays were encompassing ECG variations in the contaminated people. We pointed toward indicative dissimilar noticed ECG discoveries and talking about their experimental importance. This deliberate audit recommends that recognizing ECG designs that may be connected with Coronavirus is fundamental. Given that doctors don't perceive these examples, they may mistakenly hazard the existences of their patients. Moreover, significant medication instigated ECG changes give attention to the medical care laborers on the dangers of potential treatments. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Evaluation of QTc-Interval Prolongation and Arrhythmogenic Indices and Associated Factors in Patients With COVID-19

Background: Patients with a prolonged corrected QT (QTc) interval are at risk of arrhythmias, including Torsade de pointes (TdP). This interval could be affected by demographic characteristics, ischemia, and most importantly drugs. Furthermore, hospitalized patients tend to experience arrhythmias, accompanied by electrolyte abnormalities and the inflammatory status of diseases. Methods: The present retrospective study recruited 135 patients with COVID-19. We observed the QTc interval on the third post-administration day and laboratory findings for possible risk factors for QTc-interval prolongation. Results: Ischemic heart disease was markedly more common among patients with prolonged and severely prolonged QTc intervals. Laboratory findings showed a significantly higher neutrophil-to-lymphocyte ratio (NLR) in patients with prolonged or severely prolonged QTc intervals compared with those with normal QTc intervals and QTc intervals exceeding 500 milliseconds (P<0.001) on admission and the third day. Ribavirin caused the most elevation in the QTc interval after 3 days of hospitalization compared with other drugs. Forty percent of the patients who took ribavirin experienced a QTc interval exceeding 500 milliseconds, which was significant compared with other therapeutic regimens. Conclusions: In addition to the well-known predisposing factors for the prolongation of QTc interval, we suggest focusing on the history of ischemic heart disease and inflammatory status (eg, by NLR) in patients with COVID-19 before making decisions to commence drugs that greatly affect QTc intervals. Further studies are required to shed light on the cardiac side effects of medications applied for COVID-19, particularly ribavirin.

Torsade de pointes associated with chloroquine, hydroxychloroquine, and azithromycin: a retrospective analysis of individual case safety reports from VigiBase.

PURPOSE: To analyze the cases of torsade de pointes (TdP) and related symptoms reported in association with chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZT) to the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase) using qualitative and quantitative pharmacovigilance approaches. METHODS: The main characteristics of the ICSRs reporting TdP with CQ, HCQ, and AZT have been summarized. Co-reported drugs with risk to cause QT prolongation have been described. Reporting odds ratios (RORs) as a measure of disproportionality for reported TdP and individual drugs have been calculated. RESULTS: One hundred seventy ICSRs reporting TdP in association with the drugs of interest were identified (CQ: 11, HCQ: 31, CQ + HCQ: 1, HCQ + AZT: 27, AZT: 100). From these, 41 (24.3%) were received during the pandemic period (December 2019 to February 2021). The median age of the patients was 63, 53, and 63 years old for CQ, HCQ, and AZT, respectively. Reports included concomitant use of other QT-prolonging drugs (CQ 25.0%, HCQ 71.2%, AZT 64.6%). A proportion of the cases were fatal (CQ 25.0%, HCQ 8.6%, AZT 16.1%). Increased disproportionality has been found for the individual drugs and TdP: CQ (ROR: 7.41, 95% confidence interval (CI): 3.82, 12.96), HCQ (ROR: 8.49, 95% CI: 6.57, 10.98), azithromycin (ROR: 8.06, 95% CI: 6.76, 9.61). Disproportionality was also found for other related symptoms, Standardized MedDRA Query for torsade de pointes/QT prolongation (narrow): CQ (ROR: 11.95, 95% CI: 10.04-14.22); HCQ (ROR: 20.43, 95% CI: 19.13, 21.83), AZT (ROR: 7.78, 95% CI: 7.26, 8.34). CONCLUSIONS: The prescription of CQ, HCQ, and AZT should be restricted to therapeutic indications with established positive benefit/risk profile. Doctors and patients should be aware of this potential adverse reaction especially when several risk factors are present.

Antiviral and anti-inflammatory drugs to combat COVID-19: Effects on cardiac ion channels and risk of ventricular arrhythmias.

Introduction: Drugs with no indication for the treatment of cardiovascular diseases (e.g., drugs employed to treat COVID-19) can increase the risk of arrhythmias. Of interest, a six-fold increase in the number of arrhythmic events was reported in patients with severe COVID-19. In this study, we reviewed (i) the pro-arrhythmic action of drugs given to patients with COVID-19 infection, and (ii) the effects of inflammatory cytokines on cardiac ion channels and possible generation of arrhythmias. Methods: We conducted a literature search on the drugs with purported or demonstrated efficacy against COVID-19 disease, emphasizing the mechanisms by which anti-COVID-19 drugs and inflammatory cytokines interfere with cardiac ion channels. Results: Antibiotics (azithromycin), antimalarials (hydroxychloroquine, chloroquine), antivirals (ritonavir/lopinavir, atazanavir), and some of the tyrosine kinase inhibitors (vandetanib) could induce long QT and increase risk for ventricular arrhythmias. The pro-arrhythmic action results from drug-induced inhibition of Kv11.1 (hERG) channels interfering with the repolarizing potassium IKr currents, leading to long QT and increased risk of triggered arrhythmias. At higher concentrations, these drugs may interfere with IKs, IK1, and/or Ito potassium currents, and even inhibit sodium (INa) and calcium (ICa) currents, inducing additional cardiac toxicity. Ibrutinib, an inhibitor of Bruton's TK, increased the incidence of atrial fibrillation and ventricular tachycardia associated with a short QT interval. Inflammatory cytokines IL-6 and TNF-α inhibit IKr and Ito repolarizing potassium currents. High levels of inflammatory cytokines could contribute to the arrhythmic events. For remdesivir, favipiravir, dexamethasone, tocilizumab, anakinra, baricitinib, and monoclonal antibodies (bamlanivimab, etesevimab, and casirivimab), no evidence supports significant effects on cardiac ion channels, changes in the QT interval, and increased risk for ventricular arrhythmias. Conclusion: This study supports the concept of hERG channel promiscuity. Different drug classes given to COVID-19 patients might delay repolarization, and increase the risk of ventricular arrhythmias. The presence of comorbid pro-arrhythmic disease states, and elevated levels of pro-arrhythmic cytokines, could increase the risk of ventricular arrhythmias. Discontinuation of nonessential drugs and correction of electrolyte abnormalities could prevent severe ventricular arrhythmias. Altogether, the most effective therapies against COVID-19 (remdesivir, dexamethasone, monoclonal antibodies) lack pro-arrhythmic activity.

Arrhythmia in COVID-19.

The current outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) also known as coronavirus disease 2019 (COVID-19) has quickly progressed to a global pandemic. There are well-documented cardiac complications of COVID-19 in patients with and without prior cardiovascular disease. The cardiac complications include myocarditis, heart failure, and acute coronary syndrome resulting from coronary artery thrombosis or SARS-CoV-2-related plaque ruptures. There is growing evidence showing that arrhythmias are also one of the major complications. Myocardial inflammation caused by viral infection leads to electrophysiological and structural remodeling as a possible mechanism for arrhythmia. This could also be the mechanism through which SARS-CoV-2 leads to different arrhythmias. In this review article, we discuss arrhythmia manifestations in COVID-19.

In vitro ion channel profile and ex vivo cardiac electrophysiology properties of the R(-) and S(+) enantiomers of hydroxychloroquine.

Hydroxychloroquine (HCQ) is a derivative of the antimalaria drug chloroquine primarily prescribed for autoimmune diseases. Recent attempts to repurpose HCQ in the treatment of corona virus disease 2019 has raised concerns because of its propensity to prolong the QT-segment on the electrocardiogram, an effect associated with increased pro-arrhythmic risk. Since chirality can affect drug pharmacological properties, we have evaluated the functional effects of the R(-) and S(+) enantiomers of HCQ on six ion channels contributing to the cardiac action potential and on electrophysiological parameters of isolated Purkinje fibers. We found that R(-)HCQ and S(+)HCQ block human Kir2.1 and hERG potassium channels in the 1 µM-100 µM range with a 2-4 fold enantiomeric separation. NaV1.5 sodium currents and CaV1.2 calcium currents, as well as KV4.3 and KV7.1 potassium currents remained unaffected at up to 90 µM. In rabbit Purkinje fibers, R(-)HCQ prominently depolarized the membrane resting potential, inducing autogenic activity at 10 µM and 30 µM, while S(+)HCQ primarily increased the action potential duration, inducing occasional early afterdepolarization at these concentrations. These data suggest that both enantiomers of HCQ can alter cardiac tissue electrophysiology at concentrations above their plasmatic levels at therapeutic doses, and that chirality does not substantially influence their arrhythmogenic potential in vitro.

Effects of cardiac toxicity of combination therapy with hydroxychloroquine and azithromycin in COVID-19 patients.

Coronavirus disease 2019 (COVID-19), which began in China, caused a global pandemic. Few studies have shown the benefit of hydroxychloroquine (HY) ± azithromycin (AZ) for treating COVID-19. Concerns of QT prolongation and increased risks of torsade's de pointes (TdP) with this combination have been raised since each agent can individually prolong the QT interval. This retrospective, observational study included hospitalized patients treated with HY and AZ from March 2020 to May 2020 at a large community hospital. Serial assessments of the QT interval were performed. Our aim is to evaluate the safety and characterize the change in QTc interval and arrhythmic events in COVID-19 patients treated with HY/AZ. A total of 21 COVID patients who received at least four days of HY and AZ were included in this study. Mean baseline was QTc 403 ms, mean maximum QTc was 440 ms, mean change in QTc was 36 ms. Only one patient (4.8%) developed prolonged QTc > 500 ms. No patient had a change in QTc of 60 ms or more. No patient developed TdP. Fifteen patients (71.4%) had hypoxia on admission, with only two patients (9.5%) required oxygen of 1-2 L at discharge. 80.9% of patients have been discharged home or inpatient rehabilitation.

Drug-Induced QTc Prolongation: What We Know and Where We Are Going.

Drug-induced QTc prolongation is a concerning electrocardiogram (ECG) abnormality. This cardiac disturbance carries a 10% risk of sudden cardiac death due to the malignant arrhythmia, Torsades de Pointes. The Arizona Center for Education and Research on Therapeutics (AzCERT) has classified QTc prolonging therapeutic classes, such as antiarrhythmics, antipsychotics, anti-infectives, and others. AzCERT criteria categorize medications into three risk categories: "known," "possible," and "conditional risk" of QTc prolongation and Torsades de Pointes. The list of QTc prolonging medications continues to expand as new drug classes are approved and studied. Risk factors for QTc prolongation can be delineated into modifiable or non-modifiable. A validated risk scoring tool may be utilized to predict the likelihood of prolongation in patients receiving AzCERT classified medication. The resultant risk score may be applied to a clinical decision support system, which offers mitigation strategies. Mitigation strategies including discontinuation of possible offending agents with a selection of an alternative agent, assessment of potential drug interactions or dose adjustments through pharmacokinetic and pharmacodynamic monitoring, and initiation of both ECG and electrolyte monitoring are essential to prevent a drug-induced arrhythmia. The challenges presented by the COVID-19 pandemic have led to the development of innovative continuous monitoring technology, increasing protection for both patients and healthcare workers. Early intervention strategies may reduce adverse events and improve clinical outcomes in patients identified to be at risk of QTc prolongation.

Worldwide Survey of COVID-19-Associated Arrhythmias.

[Figure: see text].

Polymorphic Ventricular Tachycardia with a Normal QTc Interval in a Patient with COVID-19 and Fever: Case Report.

Arrhythmias or conduction system disease are not the most common manifestation of COVID-19 infection in patients requiring hospital admission. Torsade de pointes typically occurs in bursts of self-limiting episodes with symptoms of dizziness and syncope. However, it may occasionally progress to ventricular fibrillation and sudden death. In this article, we report a case of COVID-19 patient who developed polymorphic ventricular tachycardia with torsade de pointes morphology with normal QTc interval in the setting of fever. An 81-year-old woman was admitted with symptoms of COVID-19. She was treated with hydroxychloroquine, azithromycin, and doxycycline at an outside facility and finished the treatment 5 days prior to admission to our facility. Her course was complicated by atrial fibrillation with rapid ventricular response requiring cardioversion. Later, she developed two episodes of polymorphic ventricular tachycardia with TdP morphology with normal QTc. There was a correlation with fever triggering the ventricular tachycardia. We advocated aggressive fever control given the QTc was normal and stable. Following fever control, the patient remained stable and had no abnormal rhythm. COVID-19 patients are prone to different arrhythmias including life-threatening ventricular arrhythmias with normal left ventricular systolic function and normal QTc, and they should be monitored for fever and electrolyte abnormality during their hospital stay.

Safely Administering Potential QTc Prolonging Therapy Across a Large Health Care System in the COVID-19 Era.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) has resulted in a global pandemic. Hydroxychloroquine±azithromycin have been widely used to treat coronavirus disease 2019 (COVID-19) despite a paucity of evidence regarding efficacy. The incidence of torsade de pointes remains unknown. Widespread use of these medications forced overwhelmed health care systems to search for ways to effectively monitor these patients while simultaneously trying to minimize health care provider exposure and use of personal protective equipment. METHODS: Patients with COVID-19 positive who received hydroxychloroquine±azithromycin across 13 hospitals between March 1 and April 15 were included in this study. A comprehensive search of the electronic medical records was performed using a proprietary python script to identify any mention of QT prolongation, ventricular tachy-arrhythmias and cardiac arrest. RESULTS: The primary outcome of torsade de pointes was observed in 1 (0.015%) out of 6476 hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin. Sixty-seven (1.03%) had hydroxychloroquine±azithromycin held or discontinued due to an average QT prolongation of 60.5±40.5 ms from a baseline QTc of 473.7±35.9 ms to a peak QTc of 532.6±31.6 ms. Of these patients, hydroxychloroquine±azithromycin were discontinued in 58 patients (86.6%), while one or more doses of therapy were held in the remaining nine (13.4%). A simplified approach to monitoring for QT prolongation and arrythmia was implemented on April 5. There were no deaths related to the medications with the simplified monitoring approach and health care provider exposure was reduced. CONCLUSIONS: The risk of torsade de pointes is low in hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin therapy.

A pharmacovigilance study to quantify the strength of association between the combination of antimalarial drugs and azithromycin and cardiac arrhythmias: implications for the treatment of COVID-19.

Background: Hydroxychloroquine, an antimalarial drug, combined with azithromycin has been considered a potential treatment for COVID-19. However, these drugs may cause electrocardiogram QT prolongation (QTp) and torsade de Pointes (TdP). We examined potential safety signals for these cardiac arrhythmias. Methods: Using the OpenVigil 2.1 MedDRA platform, we mined data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) from December 2019 to June 2020. We extracted individual case safety reports based on exposures of seven antimalarial drugs, azithromycin, and combinations. All other drugs in FAERS served as controls. Events of interest included QTp and TdP, with associations between drug exposures and events expressed as adjusted Reporting-Odds-Ratios (aRORs) and confidence intervals. The lower end of aROR 95% confidence interval >1 was used as the statistically significant signal detection threshold. Results: QTp safety signals were found for hydroxychloroquine[aROR:11.70 (10.40-13.16)], chloroquine[aROR:18.97 (11.30-31.87)], quinine[aROR:16.66 (10.18-27.25)], atovaquone[aROR:6.91 (4.14-11.56)], azithromycin alone [aROR:28.02 (22.87-34.32)] and hydroxychloroquine + azithromycin [aROR:75.23 (51.15-110.66)]. TdP safety signals were found for hydroxychloroquine [aROR: 5.62 (4.94-6.38)], chloroquine[aROR:49.37 (30.63-79.58)], and hydroxychloroquine + azithromycin[aROR:33.09 (21.22-51.61)]. Conclusion: Hydroxychloroquine/chloroquine and/or azithromycin was associated with QTp/TdP safety signals and their use should be monitored carefully.

Prolonged QT Interval in a Patient With Coronavirus Disease-2019: Beyond Hydroxychloroquine and Azithromycin.

Recent reports have suggested an increased risk of QT prolongation and subsequent life-threatening ventricular arrhythmias, particularly torsade de pointes, in patients with coronavirus disease-2019 (COVID-19) treated with hydroxychloroquine and azithromycin. In this article, we report the case of a 75-year-old female with a baseline prolonged QT interval in whom the COVID-19 illness resulted in further remarkable QT prolongation (>700 ms), precipitating recurrent self-terminating episodes of torsade de pointes that necessitated temporary cardiac pacing. Despite the correction of hypoxemia and the absence of reversible factors, such as adverse medication effects, electrolyte derangements, and usage of hydroxychloroquine/azithromycin, the QT interval remained persistently prolonged compared with the baseline with subsequent degeneration into ventricular tachycardia and death. Thus, we highlight that COVID-19 illness itself can potentially lead to further prolongation of QT interval and unmask fatal ventricular arrhythmias in patients who have a prolonged QT and low repolarization reserve at baseline.

Drug-induced 'Torsade de Pointes' in a COVID-19 patient despite discontinuation of chloroquine. Importance of its long half-life: a case report.

BACKGROUND: Early studies have led to the repositioning of a subgroup of antimalarial agents (e.g. chloroquine and hydroxychloroquine) as antiviral treatment in coronavirus disease 2019 (COVID-19) patients. These drugs are now being prescribed based on small non-controlled studies, but larger controlled studies have yet to demonstrate the positive effect of these drugs. In addition, these drugs are also known for their QT interval-prolonging effect associated with significant morbidity and mortality. CASE SUMMARY: We present a case of a 66-year-old female admitted to the intensive care unit with respiratory failure due to COVID-19. She was treated with chloroquine (QTc interval at baseline was 429 ms). Despite cessation of chloroquine, but after the start of erythromycin, she developed severe QTc interval prolongation (QTc interval 550 ms) and 'Torsade de Pointes'. Two weeks after cessation of all QTc interval-prolonging drugs, the QTc interval was restored. DISCUSSION: The elimination half-life of chloroquine ranges from days up to weeks. Even after discontinuation of chloroquine, ECG monitoring in COVID-19 patients is warranted. We recommend observation of the QT interval after cessation of chloroquine in cases where other potentially QT interval-prolonging drugs are introduced.

Hazard of acquired long QT syndrome during coronavirus pandemic. Focus on hydroxychloroquine / [A szerzett hosszú-QT-szindróma veszélye a koronavírus-járvány idején. Fókuszban a hidroxiklorokin]

Hydroxychloroquine is an immunomodulatory drug that has been used to treat malaria and autoimmune diseases such as systemic lupus erythematosus and inflammatory arthritis. The authors conclude the proarrhytmic effects of hydroxychloroquine and the most important signs of drug-induced long QT syndrome. This article is especially relevant and timely due to the more frequent (currently not evidence-based) use of the drug during the 2019­2020 coronavirus pandemic. Orv Hetil. 2020; 161(17): 689­691.