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Background: Paroxysmal supraventricular tachycardia (PSVT) is a common episodic arrhythmia characterized by unpredictable onset and burdensome symptoms including palpitations, dizziness, chest pain, distress, and shortness of breath. Treatment of acute episodes of PSVT in the clinical setting consists of intravenous adenosine, beta-blockers, and calcium channel blockers (CCBs). Etripamil is an intranasally self-administered L-type CCB in development for acute treatment of AV-nodal dependent PSVT in a nonmedical supervised setting., Methods: This paper summarizes the rationale and study design of NODE-303 that will assess the efficacy and safety of etripamil. In the randomized, double-blinded, placebo-controlled, Phase 3 RAPID trial, etripamil was superior to placebo in the conversion of single PSVT episodes by 30 minutes post initial dose when administered in the nonhealthcare setting; this study required a mandatory and observed test dosing prior to randomization. The primary objective of NODE-303 is to evaluate the safety of symptom-prompted, self-administered etripamil for multiple PSVT episodes in real-world settings, without the need for test dosing prior to first use during PSVT. Secondary endpoints include efficacy and disease burden. Upon perceiving a PSVT episode, the patient applies an electrocardiographic monitor, performs a vagal maneuver, and, if the vagal maneuver is unsuccessful, self-administers etripamil 70 mg, with an optional repeat dose if symptoms do not resolve within 10 minutes after the first dose. A patient may treat up to four PSVT episodes during the study. Adverse events are recorded as treatment-emergent if they occur within 24 hours after the administration of etripamil., Results: Efficacy endpoints include time to conversion to sinus rhythm within 30 and 60 minutes after etripamil administration, and the proportion of patients who convert at 3, 5, 10, 20, 30, and 60 minutes. Patient-reported outcomes are captured by the Brief Illness Perception Questionnaire, the Cardiac Anxiety Questionnaire, the Short Form Health Survey 36, the Treatment Satisfaction Questionnaire for Medication and a PSVT survey., Conclusions: Overall, these data will support the development of a potentially paradigm-changing long-term management strategy for recurrent PSVT., Competing Interests: Conflicts of interest Sarah Omodele, Silvia Shardonofsky and David B. Bharucha are employees of Milestone Pharmaceuticals. Bruce S. Stambler received compensation as a consultant for Milestone Pharmaceuticals. Peter Noseworthy declares no conflict of interest. Hanh Bui declares no conflict of interest. A John Camm received compensation as a consultant for Milestone Pharmaceuticals; grants and personal fees from Boehringer Ingelheim, Bayer, Pfizer, Bristol-Myers Squibb, and Daiichi Sankyo; personal fees from Medtronic, Boston Scientific, Menarini, and Biotronik; and support from Anthos, Sanofi, Abbott, GlaxoSmithKline, and Johnson & Johnson. Benoit Coutu declares no conflict of interest. Maria Leonor Parody declares no conflict of interest. Samuel F Sears received compensation from Medtronic and Abbott as a consultant; he also received speaker compensation from Medtronic, Zoll, and Biotronik; serves as a quality-of-life consultant for Thyve, Tenaya, and Milestone Pharmaceutical. Narendra Singh declares no conflict of interest. Juan Agudelo Uribe declares no conflict of interest. John Vyselaar declares no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cardiac disease associated with cancer treatment is a common adverse effect that is well-treated with appropriate monitoring. However, some cardiac adverse effects with cancer treatment are not well-understood, in particular rituximab-associated ventricular tachycardia. We present the fourth case of rituximab-associated ventricular tachycardia in a patient who is rituximab-naive and who does not have known cardiac disease history. This patient developed non-sustained polymorphic ventricular tachycardia 14 hours after rituximab was started and 6 hours after it was stopped, and after extensive monitoring including a 30-day event monitor, did not develop further significant runs of ventricular tachycardia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We present the case of a 46-year-old man who received ephedrine for hypotension after surgery for a mandibular lesion under intravenous (IV) moderate sedation with dexmedetomidine (DEX) and experienced transient ventricular tachycardia (VT). The patient was scheduled to have cystectomy and multiple apicoectomies for the mandibular periapical infection and the simple bone cyst. Other than obesity, snoring, and a nonalcoholic fatty liver, he denied any other significant medical history, medications, or allergies. The surgery was successful; however, his blood pressure dropped after stopping the DEX infusion. Ephedrine was administered IV several times, which resulted in the onset of VT on the electrocardiogram (ECG). His blood pressure could not be measured at the time, but he was able to respond and breathe independently. A defibrillator was immediately made available. The ECG revealed a spontaneous transition from VT to atrial fibrillation with ST depression. Because he was unable to revert to a normal sinus rhythm, the patient was transferred to a general hospital, where he underwent additional testing. No abnormalities were observed in his heart or brain. After DEX administration, its long-lasting alpha-2 adrenoceptor agonist effects can cause vasodilation and inhibition of sympathetic activity, leading to hypotension in some patients. Should that occur, ephedrine can be used to increase blood pressure, but it may also provoke transient coronary artery spasms and lead to VT. Consequently, extreme caution should be exercised in patients who develop hypotension following DEX administration. We also recognize the significance of regular training sessions, such as advanced cardiac life support programs., (© 2023 by the American Dental Society of Anesthesiology.)

Aims: Conflicting results have been reported in the literature on the potential antiarrhythmic effect of sacubitril/valsartan in heart failure patients with reduced ejection fraction (HFrEF). The objectives of this study were: 1- to evaluate the long term effects of sacubitril/valsartan on arrhythmic burden in HFrEF patients; 2- to evaluate the correlation between the reduction of premature ventricular complexes during f-up and reverse remodelling., Methods: We identified 255 consecutive HFrEF patients treated with sacubitril/valsartan between March 2017 and May 2020 and followed by the Heart Failure and Cardiac Transplant Unit of IRCCS San Matteo Hospital in Pavia (Italy). Within this subgroup, 153 patients underwent 24 h-Holter-ECG or implantable cardioverter defibrillators (ICD) interrogation at baseline, at 12 months (t1) and at 24 months (t2) and transthoracic echocardiography at baseline and after 12 months after the beginning of sacubitril/valsartan. Cardiac-related hospitalizations were analyzed in the 12 months preceding and during 24 months following the drug starting date., Results: Global burden of 24-h premature ventricular complexes (PVC) was significantly reduced at 12 months (t1) and at 24 months (t2) as compared to the same period before treatment (1043 [304-3360] vs 768 [82-2784] at t1 vs 114 [9-333] at t2, P = 0.000). In the subgroup of patients implanted with biventricular ICD (n = 30), the percentage of biventricular pacing increased significantly (96% [94-99] vs 98% [96-99] at t1 vs 98%[97-100] at t2; P = 0.027). The burden of non-sustained ventricular tachycardia and sustained ventricular tachycardia did not change from baseline to t1 and t2, but a reduction of patients with at least one ICD appropriate shock was reported. The correlations between reduction in 24 h PVC and reduction in LV-ESVi or improvement in LVEF were not statistically significant (respectively R = 0.144, P = 0.197 and R = -0.190, P = 0.074). Heart failure related hospitalizations decreased during follow up (11.1% in the year before treatment vs 4.6% at t1 and 4.6% at t2; P = 0.040)., Conclusion: Sacubitril/valsartan reduced the number of premature ventricular complexes and increased the percentage of biventricular pacing in a cohort of HFrEF patients already on optimal medical therapy. PVC reduction did not correlate with reverse left ventricular remodelling. Whether sacubitril/valsartan has any direct antiarrhythmic effects is an issue to be better explored in future studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Importance: Although adenosine is the recommended first-line therapy for patients with paroxysmal supraventricular tachycardia (SVT), it may fail to restore normal sinus rhythm. The factors associated with this failure remain unclear., Objective: To assess the response rate to adenosine and identify the factors causing adenosine failure in the management of paroxysmal SVT., Design, Setting, and Participants: This retrospective study was conducted on adult patients diagnosed with paroxysmal SVT and treated with adenosine in the emergency departments of two large tertiary hospitals between June 2015 and June 2021., Outcome Measure and Analysis: The primary outcome of the study was the patient response to adenosine, defined as the restoration of sinus rhythm documented in the patients' files. Backward-stepwise multivariate logistic regression was used to examine the predictors of adenosine failure based on the overall response to adenosine therapy., Main Results: A total of 404 patients, with a mean age of 49 (SD 15) years and a BMI of 32 (SD 8) kg/m 2 , and treated with adenosine for paroxysmal SVT, were included. Sixty-nine percent of patients were women. The overall response rate to any adenosine dose was 86% (n = 347). The baseline heart rate did not significantly differ between adenosine responders and non-responders (179.6 ± 23.1 vs. 183.2 ± 23.4). An association was observed between the history of paroxysmal SVT and successful response to adenosine (odds ratio = 2.08; 95% confidence interval 1.05-4.11)., Conclusion: The findings of this retrospective study suggested that the use of adenosine restored normal sinus rhythm in 86% of patients with paroxysmal SVT. Furthermore, a history of paroxysmal SVT and older age were associated with an increased chance of adenosine success., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Despite various advantages of laparoscopic surgical procedures, artificial pneumoperitoneum might lead to hemodynamic fluctuations including severe bradycardia and cardiac arrest. Atropine is usually proposed to treat intraoperative severe bradycardia ( < 40 beats per minute). However, atropine could induce ventricular arrhythmias, which might be life-threatening in severe case., Patient Concerns: Here, we reported a 41-year-old female who was diagnosed with gallbladder polyps and was scheduled for laparoscopic cholecystectomy under general anesthesia., Diagnoses: Bradycardia occurred suddenly during the operation and atropine was injected intravenously. Eventually the patient developed ventricular tachycardia and acute heart failure., Interventions: We organized an urgent consultation and the patient was treated immediately., Outcomes: Fortunately, the patient experienced no complications after timely diagnosis and treatment. After 6 months of follow-up, her New York Heart Association classification was I with no complications., Lessons: This case highlighted that the administration of atropine to treat bradycardia may lead to ventricular tachycardia and acute heart failure, and anesthesiologists should remain vigilant to avoid potentially life-threatening consequences., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

17-year-old male presented with COVID-19 vaccine-associated myocarditis. Six months later, due to chest discomfort with exercise, the patient underwent an exercise stress test that revealed a 3-beat run of nonsustained ventricular tachycardia at 230 bpm at peak exercise. The long-term outcomes of COVID-19 vaccine-associated myocarditis are unclear. This patient had nonsustained ventricular tachycardia over 6 months after diagnosis., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Guidelines classify sacubitril/valsartan as a significant part of medical treatment of heart failure with reduced ejection fraction (HFrEF). Data have shown that the HbA1c levels in patients with diabetes mellitus could be impacted by sacubitril/valsartan. A possible positive effect in diabetes patients treated with sacubitril/valsartan on outcome and echocardiography parameters is not well studied yet., Aims: The aim of the present study was to compare the impact of sacubitril/valsartan on life-threatening arrhythmias, atrial fibrillation, different echocardiography parameters and congestion rate in patients suffering from HFrEF according to the diagnosis diabetes mellitus or no diabetes mellitus., Methods and Results: Consecutive 240 patients with HFrEF from 2016 to 2020 were treated with sacubitril/valsartan and separated to concomitant diabetes mellitus (n = 87, median age 68 years interquartile range (IQR) [32-87]) or no diabetes mellitus (n = 153, median age 66 year IQR [34-89]). Different comorbidities and outcome data were evaluated over a follow-up period of 24 months. Arterial hypertension (87% vs. 64%; P < 0.01) and coronary artery disease (74% vs. 60%; P = 0.03) were more often documented in patients with diabetes mellitus compared with patients without diabetes mellitus. Over the follow-up of 24 months several changes were noted in both subgroups: Median left ventricular ejection fraction (EF) increased significantly in non-diabetes (27% IQR [3-44] at baseline to 35% IQR [13-64]; P < 0.001), but not in diabetic patients (29% IQR [10-65] at baseline to 30% IQR [13-55]; P = 0.11). Accordingly, NT-proBNP and troponin-I levels decreased significantly in non-diabetes patients (NT-brain natriuretic peptide [NT-proBNP] from median 1445 pg/mL IQR [12.6-74 676] to 491 pg/mL IQR [13-4571]; P < 0.001, troponin-I levels from 0.099 ng/mL IQR [0.009-138.69] to 0.023 ng/mL IQR [0.006-0.635]; P < 0.001), but not in diabetic patients (NT-proBNP from 1395 pg/mL IQR [100-29 924] to 885 pg/mL IQR [159-4331]; P = 0.06, troponin-I levels from 0.05 ng/mL IQR [0.013-103.0] to 0.020 ng/mL IQR [0.015-0.514]; P = 0.27). No significant change of laboratory parameters e. g. glomerular filtration rate, potassium level and creatinine levels were found in diabetes or non-diabetes patients. Comparing further echocardiography data, left atrial surface area, right atrial surface area, E/A ratio did not show a significant change either in the diabetes or non-diabetes group. However, the tricuspid annular plane systolic excursion was significantly increased in non-diabetes mellitus patients (from 17 mm IQR [3-31] to 18 mm [2.5-31]; P = 0.04), and not in diabetic s patients (17.5 mm IQR [8-30] to 18 mm IQR [14-31]; P = 0.70); the systolic pulmonary artery pressure remained unchanged in both groups. During follow-up, a similar rate of ventricular tachyarrhythmias was observed in both groups. The congestion rate decreased significantly in both groups, in diabetes patients (44.4% before sacubitril/valsartan and 13.5% after 24 months treatment; P = 0.0009) and in non-diabetic patients (28.4% before sacubitril/valsartan and 8.4% after 24 months treatment; P = 0.0004). The all-cause mortality rate was higher in patients with diabetes mellitus as compared with those without diabetes (25% vs. 8.1%; P < 0.01)., Conclusions: Sacubitril/valsartan reverses cardiac remodelling in non-diabetes patients. However, it reduces the congestion rate in diabetes and non-diabetes patients. The rates of ventricular tachyarrhythmias were similar in DM compared with non-DM over follow-up. The mortality rate remained to be over follow-up higher in diabetes patients compared with non-diabetes; however, it was lower compared with published data on diabetes and concomitant HFrEF not treated with sacubitril/valsartan., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The natural history of chronic lymphocytic leukemia (CLL) was dramatically improved by the introduction of ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. In this review, we aimed to summarize and critically evaluate the association between first- and second-generation BTK inhibitors and the risk of atrial fibrillation (AF) and ventricular arrhythmias (VA)., Summary: Since the first clinical experience, the development of AF was observed as the result of off-target effects that likely combined with patient's predisposing risk factors and concomitant cardiac morbidities. More recently, both ibrutinib dose reduction and arrhythmia management allowed long-term treatment, with positive effects on progression-free survival and reduced all-cause mortality as well. Second-generation BTK inhibitors, acalabrutinib, and zanubrutinib have been tested and validated in CLL. A lower occurrence of AF as compared with ibrutinib has been found, although AF has always been a secondary endpoint of all studies that probed these agents., Key Messages: For this reason, caution should be exercised before concluding that second-generation BTK inhibitors are safer than ibrutinib. Recent data on the effectiveness of ibrutinib over a follow-up of 8 years show a remarkable benefit on all-cause mortality, which is of great value also for interpreting the clinical impact of the few cases of VA and sudden cardiac death (SCD) reported for ibrutinib, independently of QT lengthening. Since a risk of VA and SCD has been recently reported also during treatment with second-generation BTK inhibitors, it appears that this risk, usually reaching its maximum size effect at long-term follow-up, likely denotes a class effect of BTK inhibitors., (© 2022 S. Karger AG, Basel.)

Competing Interests: Funding Support and Author Disclosures Dr Cheung has received speaker/consulting fees from Abbott, Biotronik, Boston Scientific and Zoll Medical; has received fellowship grant support from Abbott, Biosense, Biotronik, Boston Scientific, and Medtronic; and has received research grant support from Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Programmed cell death protein 1 (PD-1) inhibitors open a new era of cancer immunotherapy, but they are associated with immune-related adverse events (irAEs) involving multiple endocrine organs of which thyroid dysfunction is the most common An uncommon condition of coronary artery spasm and ventricular tachycardia associated with thyrotoxicosis, induced by a PD-1 inhibitor, is discussed in this case. A 60-year-old male patient with a 1-week history of chest tightness and palpitation at rest was referred to us in July 2021. No obvious abnormalities were noted on physical examination and electrocardiography. He was being treated with a PD-1 inhibitor (camrelizumab, 200 mg) for lung metastasis of liver cancer; treatment stopped because he was found to have hyperthyroidism. Holter recorded intermittent STsegment arch back raised 0.5-14 mm upward lasting for 1-5 min, accompanied by ventricular tachycardia. He was treated with antivasospasm drugs (isosorbide mononitrate and diltiazem). Thyroid function was reexamined and revealed elevated FT3 and FT4 levels, decreased TSH levels, and negative thyroid-associated antibodies. After antivasospasm treatment and iodine taboo diet, his symptoms were relieved, and ST-segment elevation and ventricular tachycardia were disappeared. This case adds to our knowledge of the association between coronary artery spasms and thyrotoxicosis, which is an irAE induced by a PD-1 inhibitor. Patients treated with PD-1 inhibitors need regular follow-ups for cardiac complications, especially those with a history of heart disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as "Known Risk of TdP" but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the "Known Risk" substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500 ms was reported in 138 (18.2%) of the 760 cases. The most common "Known Risk" substances were citalopram, escitalopram and cocaine. Although not in the "Known Risk" category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500 ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2-55.8) and methadone (OR 7.1, 95% CI 2.1-23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of "Known Risk of TdP" QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A massive tricyclic overdose of 10 g of amitriptyline resulted in cardiovascular collapse with multiple episodes of ventricular tachycardia and ventricular fibrillation despite aggressive attention to current recommended therapy of sodium bicarbonate and hypertonic saline, and correction of electrolytes. Second-line antiarrhythmic therapies failed to reduce the recurrent deterioration to malignant ventricular rhythms. Progression to extracorporeal support was avoided by the use of a titrated esmolol infusion. We discuss the physiological rationale by which esmolol may prevent tachyarrhythmia and fibrillation in severe amitriptyline toxicity., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We report the case of a 50-year-old female patient with breast cancer who, during preoperative workup, presented repeated wide QRS complex tachycardias, recorded by Holter ECG. She was immediately referred to a hub center for electrophysiological study where she was diagnosed with right ventricular outflow tract ventricular tachycardia and underwent catheter ablation. The chemotherapy with paclitaxel that the patient was receiving combined with psychological stress may have triggered the arrhythmias.

Study Objective: The primary objective of this retrospective safety study was to determine the incidence of torsades de pointes (TdP) or death following perioperative administration of low-dose, 4 mg, ondansetron for postoperative nausea and vomiting., Design and Setting: This is a single-center retrospective clinical trial., Patients: The authors identified 32,737 patients who received 37,589 doses of ondansetron during a 2-year time frame between March 2009 and February 2011 for surgical nausea prophylaxis or treatment of nausea., Measurements and Main Results: Patients were cross-matched with an electrocardiogram and adverse outcome database; this identified 4759 patients with documentation of a QTc >450 milliseconds (ms), all ventricular tachycardias including TdP within 48 hours of receiving ondansetron, or death within 7 days of receiving ondansetron. No patients developed TdP or died as a direct result of ondansetron administration (n = 0; event rate = 0.0 per 10,000, 95% CI 0.0 to 1.1 per 10,000). Forty-six of 32,737 surgical patients had documented monomorphic ventricular tachycardia (VT) (n = 14; event rate = 4.3 per 10,000, 95% CI 2.3 to 7.2 per 10,000) or died (n = 32; event rate = 9.8 per 10,000, 95% CI 6.7 to 13.8 per 10,000) within 48 h of ondansetron administration. All monomorphic VT episodes were precipitated by existing cardiovascular disease; and 7 of 14 patients had documented monomorphic VT prior to receiving ondansetron. Of the 32 surgical patients who died, all deaths were precipitated by pre-existing disease., Conclusion: No episodes of TdP were identified in patients receiving ondansetron perioperatively. This suggests that low-dose ondansetron does not contribute to the development of TdP., (© 2022 Pharmacotherapy Publications, Inc.)

Atypical antipsychotics are used in cardiac intensive care units (CICU) to treat delirium despite limited data on safety in patients with acute cardiovascular conditions. Patients treated with these agents may be at higher risk for adverse events such as QTc prolongation and arrhythmias. We performed a retrospective cohort study of 144 adult patients who were not receiving antipsychotics before admission and received olanzapine (n = 50) or quetiapine (n = 94) in the Michigan Medicine CICU. Data on baseline characteristics, antipsychotic dose and duration, length of stay, and adverse events were collected. Adverse events included ventricular tachycardia (sustained ventricular tachycardia attributed to the medication), hypotension (systolic blood pressure <90 mm Hg attributed to the medication), and QTc prolongation (QTc increase by ≥60 ms or to an interval ≥500 ms). Twenty-six patients (18%) experienced an adverse event. Of those adverse events, 20 patients (14%) experienced QTc prolongation, 3 patients (2%) had ventricular tachycardia, and 3 patients (2%) had hypotension. Patients who received quetiapine had a higher rate of adverse events (25% vs 6%, p = 0.01) including QTc prolongation (18% vs 6%, p = 0.046). Intensive care unit length of stay was shorter in patients who received olanzapine (6.5 vs 9.5 days, p = 0.047). Eighteen patients (13%) had their antipsychotic continued at discharge from the hospital. In conclusion, QTc prolongation was more common in patients treated with quetiapine versus olanzapine although the number of events was relatively low with both agents in a CICU cohort., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Mutant cardiac ryanodine receptor channels (RyR2) are "leaky," and spontaneous Ca 2+ release through these channels causes delayed afterdepolarizations that can deteriorate into ventricular fibrillation. Some patients carrying RYR2 mutations in type 1 catecholaminergic polymorphic ventricular tachycardia exhibit QT prolongation and are initially diagnosed with long QT syndrome. However, none have been reported to cause drug-induced ventricular fibrillation in patients with RYR2 variants. We describe the first case of an elderly woman with drug-induced QT prolongation and ventricular fibrillation who carried a novel RYR2 variant but no other mutations related to long QT syndrome. Oral adrenergic agents might induce QT prolongation and subsequent ventricular fibrillation in patients carrying an RYR2 variant. Screening for RYR2 could be valuable in patients with suspected drug-induced long QT syndrome.

Lithium, a mood stabilizer used in the treatment of bipolar disorder is known for its anti-inflammatory properties with the discussion of its potential use in COVID-19 infection. The SARS-CoV-2 virus causing COVID-19 infection is known to enter the target cells through angiotensin converting enzyme-2 receptors present in abundance in the lung and renal tissue. Recent research supports the evidence for direct renal injury by viral proteins. Here we report two patients with bipolar disorder presenting with lithium toxicity in the presence of COVID-19 infection. Two patients with bipolar disorder, maintaining remission on lithium prophylaxis, presented to the psychiatric emergency with recent-onset fever and altered sensorium. Both the patient's investigations revealed lithium toxicity, elevated serum creatinine, urea and inflammatory markers. Hypernatremia, hyperkalaemia, and hyperchloremia were seen in one patient. Lithium and other psychotropic medications were stopped immediately, and COVID-19 treatment was initiated. Patient with clinical signs of lithium toxicity, hypernatremia, hyperkalaemia, and hyperchloremia developed ventricular tachycardia. He survived and regained consciousness after 2 weeks of aggressive conservative management. However, another patient died of acute respiratory failure on day 3. Possible direct infection of the kidney by SARS-CoV-2 viral proteins can manifest with acute kidney injury and lithium toxicity among patients on long-term lithium therapy. Health professionals treating COVID-19 infection among individuals on lithium therapy should be aware of the possibility of lithium toxicity in the background of renal injury., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Previous studies have raised serious concerns on cardiovascular safety of widely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, the aim of this study was to characterize the electrophysiological effects of certain NSAIDs in an established whole heart model of proarrhythmia., Methods and Results: Thirty-eight hearts of New Zealand White rabbits were harvested and retrogradely perfused employing a Langendorff setup, and electrophysiology studies were performed to investigate action potential duration at 90% of repolarization (APD 90 ), QT intervals, and effective refractory period (ERP). After generating baseline data, hearts were perfused with ibuprofen (Group 1, n = 12; 10 and 30 μM), indomethacin (Group 2, n = 13; 10 and 20 μM) and diclofenac (Group 3, n = 13; 10 and 20 μM), respectively, and the pacing protocols were repeated for each concentration. In all groups, perfusion with the NSAIDs resulted in a significant and reproducible shortening of APD 90 and QT interval. In all groups, the arrhythmia susceptibility was significantly raised as occurrence of monomorphic ventricular tachycardia under programmed ventricular stimulation was significantly increased under perfusion with ibuprofen, indomethacin and diclofenac in all concentrations., Conclusion: The perfusion with ibuprofen, indomethacin and diclofenac in commonly used doses raised the arrhythmia susceptibility in an established rabbit whole-heart model while APD shortening and shortened ERP seem to be crucial for arrhythmogenesis., (© 2021 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Objectives: To assess the risks of ventricular tachyarrhythmia/sudden cardiac death (VT/SCD) with domperidone use in Parkinson's disease (PD)., Study Designs and Settings: Using Bayesian methods, results from an observationalstudy were combined with prior beliefs to calculate posterior probabilities of increasedrelative risk (RR)) of VT/SCD with use of domperidone compared to non-use and ofharm, defined as risk exceeding 15%. The analyses were carried with normallydistributed priors (log (RR)): uninformative (N(0,10)) or informative (N(0.53,179)),derived from a meta-analysis (OR (95%CI):1.70 (1.47-1.97)). Sensitivity analyses used:different priors' strengths, different priors, and Bayesian meta-analysis RESULTS: The uninformative prior yielded a RR: 1.23 (95% credible interval (CrI):0.94-1.62), like the published frequentist RR: 1.22 (95% CI:0.99-1.50), with 69% probabilityof harm. With an informative prior weighted at 100%, 50% and 10%, the RR were 1.63(1.41-1.88), 1.57 (1.31-1.91) and 1.39 (1.10-1.93), respectively. The correspondingprobabilities of harm were 100%, 99%, and 94%, respectively., Conclusion: While both the frequentist and Bayesian approaches with anuninformative prior were unable to reach a definitive conclusion concerning thearrhythmic risk of domperidone in PD patients, the Bayesian analysis with informativepriors showed a high probability of increased risk that was robust to multiple priorsensitivity analyses., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Fractional flow reserve (FFR) is considered the standard for assessment of the physiological significance of coronary artery stenosis. Intracoronary papaverine (PAP) is the most potent vasodilator used for the achievement of maximal hyperemia. However, its use can provoke ventricular tachycardia (VT) due to excessive QT prolongation. We evaluated the clinical efficacy and safety of the administration of PAP after nicorandil (NIC), a potassium channel opener that prevents VT, for optimal FFR measurement.A total of 127 patients with 178 stenoses were enrolled. The FFR values were measured using NIC (NIC-FFR) and PAP (PAP-FFR). We administered PAP following NIC (NIC-PAP). Changes in the FFR and electrogram parameters (baseline versus NIC versus PAP) were assessed and the incidence of arrhythmias after PAP was evaluated. In addition, we analyzed another 41 patients with 51 stenoses by assessing the FFR using PAP before NIC (PAP-NIC). After propensity score matching, the electrogram parameters between 2 groups were compared.The mean PAP-FFR was significantly lower than the mean NIC-FFR (0.82 ± 0.11 versus 0.81 ± 0.11, P < 0.05). The mean baseline-QTc, NIC-QTc, and PAP-QTc values were 425 ± 37 ms 1/2 , 424 ± 41 ms 1/2 , and 483 ± 54 ms 1/2 , respectively. VT occurred in only 1 patient (0.6%). Although PAP induced QTc prolongation (P < 0.05), the PAP-QTc duration was significantly shorter in NIC-PAP compared to PAP-NIC (P < 0.05).The administration of PAP with NIC may induce sufficient hyperemia and prevent fatal arrhythmia through reductions in the PAP-induced QTc prolongation during FFR measurement.

Purpose of Review: The purpose of this review is to summarize the epidemiology, mechanisms, and management of cardiovascular complications of Bruton's Tyrosine Kinase inhibitors (BTKIs)., Recent Findings: Ibrutinib increases the risk of atrial fibrillation, bleeding, and hypertension compared with non-BTKI therapies. The evidence to support an association between ibrutinib and other cardiovascular complications including ventricular tachyarrhythmias or cardiomyopathy is limited. Ibrutinib metabolism can be inhibited by some medications used to treat cardiovascular complications. The cardiovascular effects of more selective BTKIs, such as acalabrutinib, remain to be determined. Future research should address the mechanisms underlying the cardiovascular complications of BTKIs and how best to manage them. The risks and benefits of more selective BTKIs as compared with ibrutinib require further evaluation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Prolongation of QTc interval, a common electrocardiographic (ECG) abnormality encountered in the toxicology patient, is reportedly associated with an increased risk of malignant ventricular dysrhythmias (MVD), such as ventricular tachycardia (VT, with and without a pulse), ventricular fibrillation (VF), and/or cardiac arrest. Quantifiable cardiac arrest risk in relation to specific QTc interval length is not known in this population., Methods: We conducted a retrospective, observational study to assess the rate of cardiac arrest and its association with degree of QTc prolongation in a cohort of patients requiring toxicology consultation., Results: 550 patients were included in our analysis (average age 36 years and 49% male). Average QTc was 453 milliseconds (ms). Overall incidence of cardiac arrest in the study cohort was 1.1% with 6 reported cases; when considering patients with QTc > 500 ms, incidence was 1.7%. Two patients with cardiac arrest experienced ventricular dysrhythmia with decompensation prior to cardiac arrest; four patients developed sudden cardiac arrest., Conclusions: The risk of malignant ventricular dysrhythmia, including cardiac arrest, is low in this poisoned patient population with an overall rate of 1.1%. Two-thirds of cardiac arrest cases occurred in patients with normal QTc intervals. When considering patients with prolonged QTc intervals, the rate of cardiac arrest remains very low at 0.8%. Considering QTc greater than 500 ms, the rate of cardiac arrest is 1.7%. Further prospective studies are required to quantify the risk of malignant ventricular dysrhythmias, including cardiac arrest, and its relation to the degree of QTc interval in poisoned patients., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We sought to review the effects of statins on the ryanodine receptor (RyR) and on RyR-associated diseases, with an emphasis on catecholaminergic polymorphic ventricular tachycardia (CPVT). Statins can affect skeletal muscle and produce statin-associated muscle symptoms (SAMS) but have no adverse effects on cardiac muscle. These contrasting effects may be due to differences in how statins affect the skeletal (RyR1) and cardiac (RyR2) RyR. We searched PubMed to identify English language articles reporting the pathophysiology of the RyR, the effect of statins on RyR function, and on RyR-associated genetic diseases. We selected 150 articles for abstract review, 96 of which provided sufficient information to be included and were reviewed in detail. Fifteen articles highlighted the interaction of statins with the RyR. Nine identified the interaction of statins with RyR1, six addressed the interaction of statins with RyR2, 13 suggested that statins reduce ventricular arrhythmias (VA), and seven suggested that statins increase the risk of malignant hyperthermia (MH). In general, statins increase RyR1 and decrease RyR2 activity. We identified no articles examining the effect of statins on CPVT, a condition often caused by defects in RyR2. Statins appear to increase the risk of MH and decrease the risk of ventricular arrhythmia. The effect of statins on CPVT has not been directly examined, but statins' reduction in RyR2 function and their apparent reduction in VA suggest that they may be beneficial in this condition.

Background: Trends in off-label postpartum use of domperidone and the impact of safety advisories on its use remain unknown. Our objectives were to describe postpartum use of domperidone in Canada, to evaluate the impact of Health Canada advisories on prescribing patterns, and to describe the association between domperidone use and a composite end point of sudden cardiac death or ventricular tachycardia (VT) among postpartum patients., Methods: We conducted a multidatabase cohort study involving pregnant patients with live births between 2004 and 2017 using administrative health databases from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario). We excluded patients with less than 1 year of prepregnancy database history and with approved indications for domperidone. We assessed domperidone use in the 6 months postpartum and the impact of the 2012 and 2015 Health Canada advisories on prescribing via interrupted time series analysis. We estimated crude rates of VT and sudden cardiac death., Results: We included 1 190 987 live births. Mean maternal age was 28.6 (standard error 0.6) years. Domperidone use increased over time, from 7% in 2003-2005 to 12% in 2009-2011, when it plateaued. The 2012 advisory was followed by a drop in use and a reduction in slope, and the 2015 advisory had a more modest impact. Crude analysis suggests that domperidone may be associated with increased VT or sudden cardiac death (0.74 v. 0.37 per 10 000 person-years; difference per 10 000 person-years: 0.37, 95% confidence interval -0.67 to 1.41)., Interpretation: Postpartum domperidone use increased between 2004 and 2017, with prescribing attenuated after Health Canada advisories and a very low absolute rate of VT or sudden cardiac death. These findings suggest that Health Canada advisories affected prescribing; any potential increase in VT or sudden cardiac death with use of domperidone is small and could not be confirmed in this large study STUDY REGISTRATION: ClinicalTrials.gov, no. NCT04024865., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

Purpose: Most psychiatric drugs, such as antidepressants (AD) and antipsychotics (AP), may cause cardiac adverse events (CAE). We used summaries of product characteristics (SmPC) for assessing the likelihood of AD and AP to cause CAE., Methods: We identified all original medicinal products (OMP) of AD and AP approved in Germany. We searched for their SmPCs using the online services of PharmaNet.Bund, Gelbe liste®, Rote Liste®, Fachinfo-Service®, and via manufacturer contact. We extracted frequencies of reported CAE (QT prolongation, Torsade de Pointes tachycardia, and ventricular arrhythmia) and performed a risk assessment., Results: We obtained the SmPCs of 24 AD and 26 AP identified as OMP. Comparably high reported frequencies regarding QT prolongation were found for Invega® (paliperidone), Serdolect® (sertindole) (≥ 1/100 and < 1/10), and Zoloft® (sertraline) (≥ 1/10.000 and < 1/1000); regarding Torsade de Pointes tachycardia were found for Serdolect® (≥ 1/1000 to < 1/100), Zoloft®, and Trevilor® (venlafaxine) (≥ 1/10.000 and < 1/1000); regarding ventricular tachycardia for Solian® (amisulpride), Xomolix® (droperidol), Zyprexa® (olanzapine), and Trevilor® (≥ 1/10.000 and < 1/1000)., Conclusion: The risk and frequency of CAE, as reported in the SmPCs, varied significantly among substances and between groups. There are more reports for AP than AD. The AP with the most frequently reported CAE (QT prolongation and Torsade de Pointes tachycardia) was Serdolect®; for AD, Zoloft® (QT prolongation, Torsade de Pointes tachycardia) and Trevilor® (Torsade de Pointes tachycardia and ventricular tachycardia) carried a higher cardiac risk.

Several case reports suggest QT prolongation leading to ventricular arrhythmias with fatal outcome after intoxication with the μ-opioid receptor agonist and anti-diarrheal agent loperamide. The number of cases of loperamide misuse are growing due to its potential stimulating effects. Loperamide intoxications can be treated by naloxone. However, previous reports described a further QT prolongation associated with naloxone administration. Therefore, the aim of this study was to investigate the effects of loperamide and naloxone on the cardiac electrophysiology in a sensitive whole-heart model. Twenty-six hearts of New Zealand White rabbits were retrogradely perfused in a modified Langendorff apparatus. Monophasic action potentials were recorded by endo- and epicardially positioned catheters. Hearts were stimulated at different cycle lengths, thereby obtaining action potential duration at 90% of repolarization (APD 90 ) and QT intervals. Programmed ventricular stimulation was used to assess ventricular vulnerability. Fourteen hearts were perfused with ascending concentrations of loperamide (0.2 μM, 0.35 μM, and 0.5 μM) after obtaining baseline data. Another 12 hearts were treated with naloxone (0.1 μM, 0.5 μM, 2 μM). Loperamide led to a significant increase in QT interval, APD 90 , and ventricular tachycardia (VT) episodes. In contrast, naloxone led to a decrease in QT interval and APD 90 . Accordingly, the number of VT episodes was unaltered. To the best of our knowledge, this is the first experimental study that investigated the effects of loperamide and naloxone in a whole-heart model. Loperamide led to a significant increase in action potential duration and QT interval. Simultaneously, the number of ventricular tachycardias was significantly increased. In contrast, naloxone led to a shortening of the action potential duration without altering arrhythmia susceptibility.

Takotsubo cardiomyopathy (TC) is a syndrome characterized by acute and transient regional systolic myocardial dysfunction. TC often mimics myocardial infarction without obstructive coronary disease. We present a case of a 48-year-old woman who developed TC following the onset of polymorphic ventricular tachycardia in the setting of methadone intoxication.

The usage of flavored electronic nicotine delivery systems (ENDS) is popular, specifically in the teen and young adult age-groups. The possible cardiac toxicity of the flavoring aspect of ENDS is largely unknown. Vaping, a form of electronic nicotine delivery, uses "e-liquid" to generate "e-vapor," an aerosolized mixture of nicotine and/or flavors. We report our investigation into the cardiotoxic effects of flavored e-liquids. E-vapors containing flavoring aldehydes such as vanillin and cinnamaldehyde, as indicated by mass spectrometry, were more toxic in HL-1 cardiomyocytes than fruit-flavored e-vapor. Exposure of human induced pluripotent stem cell-derived cardiomyocytes to cinnamaldehyde or vanillin-flavored e-vapor affected the beating frequency and prolonged the field potential duration of these cells more than fruit-flavored e-vapor. In addition, vanillin aldehyde-flavored e-vapor reduced the human ether-à-go-go-related gene (hERG)-encoded potassium current in transfected human embryonic kidney cells. In mice, inhalation exposure to vanillin aldehyde-flavored e-vapor for 10 wk caused increased sympathetic predominance in heart rate variability measurements. In vivo inducible ventricular tachycardia was significantly longer, and in optical mapping, the magnitude of ventricular action potential duration alternans was significantly larger in the vanillin aldehyde-flavored e-vapor-exposed mice than in controls. We conclude that the widely popular flavored ENDS are not harm free, and they have a potential for cardiac harm. More studies are needed to further assess their cardiac safety profile and long-term health effects. NEW & NOTEWORTHY The use of electronic nicotine delivery systems (ENDS) is not harm free. It is not known whether ENDS negatively affect cardiac electrophysiological function. Our study in cell lines and in mice shows that ENDS can compromise cardiac electrophysiology, leading to action potential instability and inducible ventricular arrhythmias. Further investigations are necessary to assess the long-term cardiac safety profile of ENDS products in humans and to better understand how individual components of ENDS affect cardiac toxicity.

A 63-year-old woman on flecainide, furosemide, and triamterene-hydrochlorothiazide presented with weakness and diarrhoea. She had profound hyponatraemia, hypokalaemia and a pre-renal acute kidney injury (AKI). Her ECG showed a regular wide complex tachycardia concerning for monomorphic ventricular tachycardia. She was haemodynamically stable and treated with aggressive electrolyte repletion and amiodarone. Flecainide toxicity can present as a variety of arrhythmias and early recognition is crucial. This case focuses on flecainide toxicity from multiple concomitant insults: diuretic use, diarrhoea, hypokalaemia, hyponatraemia and pre-renal AKI. We emphasise the importance of close outpatient monitoring of electrolytes in a patient on diuretics and flecainide to prevent life-threatening arrhythmias. We discourage use of multiple diuretics in patients taking flecainide., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

A 57-year-old man on maintenance hemodialysis was admitted to a hospital after suffering from cardiac arrest. He had collapsed soon after hemodialysis and was restored to sinus rhythm after receiving direct-current shocks. Further examination revealed old myocardial infarction with triple-vessel disease, and he was referred to our hospital for surgical treatment. Soon after performing coronary artery bypass grafting, we started the patient on intravenous amiodarone for frequent ventricular tachycardia. However, incessant ventricular tachycardia occurred frequently which necessitated several countershocks. Although ventricular tachycardia disappeared by replacing intravenous amiodarone with intravenous nifekalant, it reappeared when we initiated oral amiodarone instead of intravenous nifekalant. So therefore, we stopped using any anti-arrhythmic drug except bisoprolol fumarate, whereby ventricular tachycardia ceased once again. Amiodarone is known as relatively safe anti-arrhythmic drug that is often used after cardiovascular surgery. However, we should pay close attention to the possibility of amiodarone-induced arrhythmia.

We investigated the effect of the papaverine dose increment method to confirm maximal hyperemia for fractional flow reserve (FFR) measurements. We evaluated 115 consecutive patients involving 200 lesions. FFR was measured after intracoronary papaverine injection into the left (12 mg) and right (8 mg) coronary arteries as standard doses. Except for 2 patients who had ventricular tachyarrythmia (VTA), we administered a higher papaverine dose (2 mg added to the standard dose). We compared the FFR values after using different papaverine doses. VTA incidence and electrocardiogram parameters were compared according to the papaverine doses used. The QTU interval and corrected QTU were significantly prolonged after using a higher dose compared with a standard dose. VTA occurred in one patient (0.9%) at the higher dose. There was no significant difference with a strong correlation between the FFR values in the 2 doses (r = 0.963, P < 0.001). Maximal hyperemia was achieved in most patients at the standard papaverine dose. However, 19 lesions changed ischemic diagnosis at the higher dose (12 lesions changed from ischemia negative to positive, and 7 lesions changed from positive to negative). Therefore, to confirm the appropriate ischemia diagnosis for borderline FFR values, it may be favorable to perform another FFR measurement at an incremental papaverine dose.

Importance: Conflicting evidence exists on the association between azithromycin use and cardiac events., Objective: To compare the odds of cardiac events among new users of azithromycin relative to new users of amoxicillin using real-world data., Design, Setting, and Participants: This retrospective cohort study used data from Truven Health Analytics MarketScan database from January 1, 2009, to June 30, 2015. Patients receiving either amoxicillin or azithromycin and enrolled in a health care plan 365 days before (baseline period) the dispensing date (index date) were included in the study. Patients were matched 1:1 on high-dimensional propensity scores. Data were analyzed from October 1, 2018, to December 31, 2019., Exposures: New use of azithromycin compared with new use of amoxicillin., Main Outcomes and Measures: The primary outcome consisted of cardiac events, including syncope, palpitations, ventricular arrhythmias, cardiac arrest, or death as a primary diagnosis for hospitalization at 5, 10, and 30 days from the index date. Logistic regression models were used to estimate odds ratios (ORs) with 95% CIs., Results: After matching, the final cohort included 2 141 285 episodes of each index therapy (N = 4 282 570) (mean [SD] age of patients, 35.7 [22.3] years; 52.6% female). Within 5 days after therapy initiation, 1474 cardiac events (0.03%) occurred (708 in the amoxicillin cohort and 766 in the azithromycin cohort). The 2 most frequent events were syncope (1032 [70.0%]) and palpitations (331 [22.5%]). The odds of cardiac events with azithromycin compared with amoxicillin were not significantly higher at 5 days (OR, 1.08; 95% CI, 0.98-1.20), 10 days (OR, 1.05; 95% CI, 0.97-1.15), and 30 days (OR, 0.98; 95% CI, 0.92-1.04). Among patients receiving any concurrent QT-prolonging drug, the odds of cardiac events with azithromycin were 1.40 (95% CI, 1.04-1.87) greater compared with amoxicillin. Among patients 65 years or older and those with a history of cardiovascular disease and other risk factors, no increased risk of cardiac events with azithromycin was noted., Conclusions and Relevance: This study found no association of cardiac events with azithromycin compared with amoxicillin except among patients using other QT-prolonging drugs concurrently. Although azithromycin is a safe therapy, clinicians should carefully consider its use among patients concurrently using other QT-prolonging drugs.

A 26-year-old woman presented after an intentional ingestion of 20 g of caffeine. She suffered a profound respiratory alkalosis with metabolic acidosis, hypokalaemia and sustained polymorphic ventricular tachycardia. She was treated with intravenous intralipid and haemodialysis, and her arrhythmia was controlled using magnesium sulphate. Once invasively ventilated and unable to hyperventilate the patient became acidotic and required intravenous bicarbonate to correct her acid-base status. Two days following the overdose the patient was extubated, haemodialysis was stopped and norepinephrine was weaned off. The patient was discharged after a further 7 days. Serial caffeine levels were taken during this patient's care; the highest measured caffeine concentration 7 hours after ingestion was 147.1 mg/L. The known lethal dose of caffeine is 80 mg/L. Intralipid and haemodialysis represent a new and viable treatment in life-threatening caffeine overdose. Intravenous magnesium may terminate unstable arrhythmias in caffeine-poisoned patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Tiamulin is a semisynthetic pleuromutilin diterpene veterinary antibiotic, widely used in farms. We present a case of prolonged QT-interval and ventricular tachyarrhythmia after tiamulin inhalation. Case presentation: A 43-year-old veterinarian without previous medical history was dividing granulated powder of antibiotic gravimetrically without wearing personal protective equipment. Half an hour after exposure, nausea occurred; four hours later he started to vomit and soon after that he experienced syncope. He was unconscious three minutes; afterwards he became somnolent, dizzy and nauseated with sweating and salivation. On admission to hospital five hours after exposure, he was conscious and had heart rate 70 beats/min and blood pressure 140/80 mmHg. Initial laboratory results were normal. Electrocardiography showed a prolonged QTc-interval of 730 ms with numerous polymorphic ventricular extrasystoles and episodes of non-sustained polymorphic ventricular tachycardia that resolved after treatment with lidocaine and magnesium. Subsequent electrocardiography revealed gradual shortening of QTc-interval with QTc-interval normalization (430 ms) between 24 and 32 hours after tiamulin exposure. Laboratory tests, morphologic heart diagnostics and genetic testing excluded other potential causes of QTc-interval prolongation. Subsequent toxicology analysis by LC-MS/MS confirmed tiamulin in his serum samples on admittance (500 ng/mL). Conclusion: Tiamulin inhalation can be associated with prolonged QT-interval and ventricular tachyarrhythmia. QT-interval prolongation could be expected in overdoses of emerging human pleuromutilins.

This report presents the case of a young man of 24 years old with Asperger syndrome who ingest quantities of medication whose flecainide. Resume of his stay in intensive care unit, notably serious adverse effect which ventricular tachycardia with membrane stabilizing effect and lengthening of stay in intensive care unit. Study of literature of different take care already published, with notion of mid-term leaching of flecainide which were ingest days before, at different levels all over the world., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

A 65-year-old woman called paramedics for stridor and neck swelling following an insect bite with a possible anaphylactic reaction. On arrival paramedics administered intramuscular epinephrine without any observed improvement in stridor. Paramedics then prepared 5 mg of 1:1000 epinephrine for nebulised administration, which was inadvertently given intravenously. The patient developed tachycardia, anxiety and a severe headache, with biochemical evidence of cardiac necrosis without any haemodynamic compromise. The patient recovered over the next 24 hours and no long-term sequelae were identified on CT coronary angiogram, electrocardiography (ECG) echocardiography or invasive angiography. This case highlights the risk of cardiac ischaemia during epinephrine administration and the importance of protocols to ensure appropriate dosing. This case also raises questions regarding appropriate management of epinephrine overdose and shines a light on the absence of guidelines on the prevention of complications from epinephrine administration., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)