Prevalencia de medicamentos que prolongan el intervalo QT en salas de cardiología de un hospital de alta complejidad / Drug induced prolongation of Q-T interval in cardiology wards

Resumen: Antecedentes: La prevalencia del síndrome del QT largo (SQTL) producido por medicamentos es una de las reacciones adversas que en el último tiempo ha aumentado en prevalencia y mortalidad. No solamente ocurre con el uso de medicamentos para el tratamiento de cardiopatías, sino también en medicamentos con otra acción terapéutica. Objetivo: Evaluar la prevalencia del síndrome del SQTL inducido por medicamentos en salas de cardiología de un hospital de alta complejidad. Métodos: Estudio prospectivo, de tipo descriptivo y de corte transversal en 36 pacientes cardiópatas, que consistió en evaluar la frecuencia del uso de medicamentos que son capaces de producir un SQTL y la prevalencia de este efecto adverso. Los datos clínicos se recolectaron de la ficha clínica y de entrevistas con los pacientes. Se efectuó un seguimiento para detectar la aparición de prolongación del intervalo QT. Los resultados obtenidos fueron presentados por medio de estadística descriptiva (programa estadístico Statgraphics Centurion, versión XVI). No hubo estadística inferencial dada la ausencia de un grupo control. Resultados: 41,7%, de los 36 pacientes presentaron SQTL que en 86,7% de ellos fue asociado a un medicamento. Los medicamentos más frecuentemente asociados a este efecto adverso fueron Amiodarona (38,5%) y Ondansetrón (23,1%), y el factor de riesgo mayormente involucrado fue el sexo femenino (61,5%). Conclusión: Existió una alta prevalencia del uso de medicamentos que producen un SQTL, destacándose que existen medicamentos utilizados para otras patologías que también pueden producirlo.

Abstract: Background: The prevalence of the Long QT interval syndrome (LQTS) associated to drugs has increased en the last decades along with an increased mortality due to this condition. It occurs not only with drugs used to treat cardiac disease but also to other drugs. Aim: To evaluate the prevalence of drug induced LQTS in cardiology wards of a high complexity hospital. Method: This is a prospective, descriptive and cross sectional study in 36 patients with heart disease. The use of drugs known to affect the QT interval along with the frequency of LGTS were evaluated. Clincal data was obtained from clinical records and personal interviews. Patients were followed for the appearance of LQTS. Descriptive were used to present the results. No inferential statistics were used as no control group was involved (Statgraphics Centurion, version XVI). Results: 41.7% of the 36 patients developed LQTS and the association with drugs was present in 86.7% of them. The drugs most commonly identified were amiodarone (38.5%) and ondansetron (23.1%) of patients. Female geneder was the most common associated condition (61.5%). Conclusion: There was a frequent use of drugs known to produce LQTS, but other drugs may also be associated int this group of patients with heart disease admitted to intensive or intermediate care facilities.

Polypharmacy Is Associated With Amiodarone-Induced Hypothyroidism.

Background: Amiodarone is rich in iodine, so in clinical practice amiodarone-induced hypothyroidism (AIH) is a major side effect. This drug is used in patients with arrhythmias, especially atrial fibrillation, the most common sustained arrhythmia. Polypharmacy, which can result in complex drug-drug interactions, occurs in more than 70% of the patients with atrial fibrillation. Therefore, polypharmacy may be involved in the expression of AIH. In this study, we investigated the association between polypharmacy and AIH. Methods: We conducted a retrospective study using data from January 2006 to May 2020 collected from a large, organized database of prescriptions constructed by the Japan Medical Information Research Institute, Inc. (Tokyo, Japan). To investigate the association between number of prescribed drugs with amiodarone and AIH, we divided patients into two groups: polypharmacy (≥ 5 prescribed drugs) and non-polypharmacy (< 5 prescribed drugs). We then performed a sequence symmetry analysis on the two groups: incident thyroxine after incident amiodarone and incident thyroxine before incident amiodarone. Finally, we conducted a case-control study on two further groups: those prescribed thyroxine after incident amiodarone (AIH group; n=555) and those not prescribed thyroxine after incident amiodarone (non-AIH group; n=6,192). Results: Sequence symmetry analysis revealed a significant association between amiodarone and thyroxine in both the polypharmacy and non-polypharmacy groups. The ranges for the adjusted sequence ratio in the two groups were 12.0-16.7 and 7.3-9.0, respectively. The case-control study showed that ≥5 prescribed drugs at the first prescription of amiodarone were found to significantly increase the odds of AIH (odds ratio: 1.48, 95% confidence interval: 1.18-1.84). Conclusion: Polypharmacy was suggested as an independent risk factor for AIH. Careful assessment of the appropriateness of prescription is warranted.

Appraisal of amiodarone-loaded PLGA nanoparticles for prospective safety and toxicity in a rat model.

AIMS: Amiodarone (AM) is a highly efficient drug for arrhythmias treatment, but its extra-cardiac adverse effects offset its therapeutic efficacy. Nanoparticles (NPs)-based delivery system could provide a strategy to allow sustained delivery of AM to the myocardium and reduction of adverse effects. The primary purpose was to develop AM-loaded NPs and explore their ameliorative effects versus off-target toxicities. MATERIALS AND METHODS: Polymeric NPs were prepared using poly lactic-co-glycolic acid and their physicochemical properties were characterized. Animal studies were conducted using a rat model to compare exposure to AM versus that of the AM-loaded NPs. Biochemical evaluation of liver enzymes, lipid profile, and thyroid hormones was achieved. Besides, histopathological changes in liver and lung were studied. KEY FINDINGS: Under optimal experimental conditions, the AM-loaded NPs had a size of 186.90 nm and a negative zeta potential (-14.67 mV). Biochemical evaluation of AM-treated animal group showed a significant increase in cholesterol, TG, LDL, T4, and TSH levels (ρ < 0.05). Remarkably, the AM-treated group exhibited a significant increase of liver enzymes (ρ < 0.05) coupled with an obvious change in liver architecture. The AM-loaded NPs displayed a reduction of liver damage and enzyme levels. Lung sections of the AM-treated group demonstrated thickening of interalveolar septa, mononuclear cellular infiltration with congested blood vessels, and heavy collagenous fibers deposition. Conversely, less cellular infiltration and septal thickening were observed in the animal lungs treated with the AM-loaded NPs-treated. SIGNIFICANCE: Our findings demonstrate the competence of the AM-loaded NPs to open several exciting avenues for evading the AM-induced off-target toxicities.

Patterns of Care for Atrial Fibrillation Before, During, and at Discharge From Hospitalization: From the Get With The Guidelines-Atrial Fibrillation Registry.

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Successful defibrillation using double sequence defibrillation: Case reports.

INTRODUCTION: Defibrillation is effective and the most common treatment for ventricular fibrillation (VF) and pulseless ventricular tachycardia in patients with cardiac arrest. PATIENT CONCERNS: Recently we experienced 3 cases refractory ventricular fibrillation (RVF) which was successfully terminated with double sequence defibrillation (DSD) in our emergency department, so we'd like to report and discuss it. DIAGNOSIS: Cardiac arrest. INTERVENTIONS: A single defibrillation 200J was performed twice for patients with ventricular fibrillation in the initial rhythm of the emergency room. At the same time, intubation and intravenous access were achieved and epinephrine and amiodarone were administered. The 400J DSD was performed on RVF patients with sustained VFs, despite several trials of 150-200J defibrillation and adherence to advanced cardiac life support. OUTCOMES: All three RVF patients recovered spontaneous circulation after DSD. CONCLUSION: The three cases we have shown are small, but DSD improves the chance of spontaneous circulation. Therefore it is suggested that attempts of DSD to patients with RVF, especially in the prehospital stages as a way to improve the return of spontaneous circulation.

Prediction of the dose range for adverse neurological effects of amiodarone in patients from an in vitro toxicity test by in vitro-in vivo extrapolation.

Amiodarone is an antiarrhythmic agent inducing adverse effects on the nervous system, among others. We applied physiologically based pharmacokinetic (PBPK) modeling combined with benchmark dose modeling to predict, based on published in vitro data, the in vivo dose of amiodarone which may lead to adverse neurological effects in patients. We performed in vitro-in vivo extrapolation (IVIVE) from concentrations measured in the cell lysate of a rat brain 3D cell model using a validated human PBPK model. Among the observed in vitro effects, inhibition of choline acetyl transferase (ChAT) was selected as a marker for neurotoxicity. By reverse dosimetry, we transformed the in vitro concentration-effect relationship into in vivo effective human doses, using the calculated in vitro area under the curve (AUC) of amiodarone as the pharmacokinetic metric. The upper benchmark dose (BMDU) was calculated and compared with clinical doses eliciting neurological adverse effects in patients. The AUCs in the in vitro brain cell culture after 14-day repeated dosing of nominal concentration equal to 1.25 and 2.5 µM amiodarone were 1.00 and 1.99 µg*h/mL, respectively. The BMDU was 385.4 mg for intravenous converted to 593 mg for oral application using the bioavailability factor of 0.65 as reported in the literature. The predicted dose compares well with neurotoxic doses in patients supporting the hypothesis that impaired ChAT activity may be related to the molecular/cellular mechanisms of amiodarone neurotoxicity. Our study shows that predicting effects from in vitro data together with IVIVE can be used at the initial stage for the evaluation of potential adverse drug reactions and safety assessment in humans.

Incidental finding of cornea verticillata or lamellar inclusions in kidney biopsy: measurement of lyso-Gb3 in plasma defines between Fabry disease and drug-induced phospholipidosis.

INTRODUCTION: Therapy with cationic amphiphilic drugs (Amiodarone or hydroxychloroquine) may result in biochemically and ultrastructurally similar lipid inclusions in many cells also affected by Fabry disease (FD). In addition, it often results in similar clinical manifestations such as cornea verticillata. This may lead to a FD misdiagnosis, especially when a complete medical history is not available to the ophthalmologist confronted with cornea verticillata or to the pathologist examining a kidney biopsy. When enzymatic/genetic test or pathological studies are not conclusive, a specific biomarker may help clarify this dilemma. The plasma globotriaosylsphingosine (lyso-Gb3) assay has high sensitivity and specificity and is elevated above normal levels in FD. MATERIALS AND METHODS: We measured plasma lyso-Gb3 levels in male patients receiving Amiodarone or hydroxychloroquine and compared it with male patients with classic and late onset variant of FD. RESULTS: In all Fabry patients (classic and late onset variant) α-GalA activity was deficient in dried blood spot and plasma lyso-Gb3 was above normal levels. Patients on treatment with Amiodarone or hydroxychloroquine had normal values for α-GalA activity and lyso-Gb3 in plasma. CONCLUSIONS: Even when Amiodarone or hydroxychloroquine may decrease α-GalA activity in vitro or in cell culture, our results showed that in all patients lyso-Gb3 plasma levels remain normal with no evidence of reduction in α-GalA activity, confirming the specificity of this biomarker for the diagnosis of FD.

Amiodarone Use Prior to Cardiac Transplant Impacts Early Post-Transplant Survival.

PURPOSE: It remains unclear if use of amiodarone pre-cardiac transplantation impacts early post-transplant survival. METHODS: We selected all patients undergoing heart transplant from 2004 to 2006 with available information using the United Network for Organ Sharing database (n = 4057). Multivariable Cox models compared the risk of death within 30 days post-transplant in patients who were taking amiodarone at the time of transplant listing (n = 1227) to those who were not (n = 2830). RESULTS: Mean age was 52 (± 12) years, and 23% were women. Patients who died within 30 days (n = 168) were older; had higher panel reactive antibody levels, higher bilirubin levels, and higher prevalence of prior cardiac surgery; were often at status 1B; and had higher use of amiodarone at listing compared to those who survived (5.3% versus 3.6%; p = 0.02). Cause of death was unknown in 49% and was reported as graft failure in 43% of cases. In multivariable Cox models, patients on amiodarone at the time of listing had 1.56-fold higher risk of post-transplant death within 30 days (95% confidence intervals 1.08-2.27) compared to patients who were not on amiodarone at listing (C-statistic 0.70). CONCLUSION: In conclusion, patients who reported taking amiodarone at the time of listing for transplant had a higher risk of death within 30 days post-transplant.

The use of intravenous amiodarone in patients with atrial fibrillation and Wolff-Parkinson-White syndrome.

BACKGROUND: It was reported that intravenous amiodarone might induce ventricular fibrillation for acute treatment in patients with atrial fibrillation (AF) and Wolff-Parkinson-White (WPW) syndrome. No study was done to assess its application comprehensively in this population. METHODS: This study was a retrospective analysis and undertaken by reviewing medical records and electronic databases to search for patients admitted with tachycardia resulting from WPW syndrome and AF, who have intravenously administrated amiodarone at the emergency department from January 2008 to June 2018. RESULTS: Thirty patients were involved in this study, of which 27 were males. The mean age of the patients was 47.8 ± 17.0 years. The mean systolic blood pressure and diastolic blood pressure were 111.9 ± 18.3 mmHg and 76.1 ± 14.6 mmHg, respectively. The mean heart rate was 171 (150-189) beats per minute. Half of the patients (53.3%) had no comorbidities, and only one had prior syncope. Nearly 17 patients (56.7%) started with a loading dose of 150 mg. No ventricular acceleration or VF developed. The incidence of hypotension was 3.3% (1/30). Eighteen patients (60.0%) restored to sinus rhythm by amiodarone with the conversion time of 486.0 (229.0-1278.0) minutes. CONCLUSIONS: Intravenous amiodarone might be an alternative for acute treatment of AF and WPW syndrome in patients characterized by stable hemodynamics, relatively low admission heart rate, few comorbidities, elder age, and no prior syncope. The loading dosage of 150 mg appeared to be preferred, and the maintenance period was better to less than 12 hours. Monitoring and electrolyte correction were also necessary. It is essential to keep a defibrillator nearby during pharmacologic cardioversion.

Frontal plane QRS-T angle in the monitoring of intravenous amiodarone infusion for pharmacological cardioversion of acute atrial fibrillation.

WHAT IS KNOWN AND OBJECTIVE: Intravenous amiodarone infusion is effective and widely used treatment for pharmacological cardioversion of recent-onset atrial fibrillation (Af). Although amiodarone may trigger various alterations in cardiac electrophysiology and electrocardiography (ECG), the impact of amiodarone treatment on frontal plane QRS-T angle remains unclear. Frontal plane QRS-T angle is the angle between the depolarization and repolarization axes and indicates instability in the cardiac cellular electrophysiology. Therefore, the present study aimed to investigate whether intravenous amiodarone infusion has effect on frontal plane QRS-T angle in patients with acute Af. METHODS: A total of 179 patients with acute-onset Af who underwent pharmacological cardioversion with intravenous amiodarone infusion were included into the study. Patients with successful and failed pharmacological cardioversion were compared regarding pre- and post-treatment frontal plane QRS-T angle. RESULTS AND DISCUSSION: At the end of the amiodarone infusion, sinus rhythm was restored in 112 (62.6%) patients, whereas Af was persisted in 67 (37.4%) patients. Despite the similar frontal plane QRS-T angle at baseline (59.6°±21.73°vs.60.4°±25.67°, p = 0.822), patients with failed pharmacological cardioversion had significantly higher post-treatment frontal plane QRS-T angle compared to patients with successful pharmacological cardioversion (68.8°±21.71°vs.58.6°±25.15° p < 0.001). Furthermore, multivariate analysis demonstrated that post-treatment increased frontal plane QRS-T angle was found to be an independent predictor of failure of pharmacological cardioversion with amiodarone infusion (OR:1.233, 95% CI:1.147-1.919, p = 0.024). WHAT IS NEW AND CONCLUSION: Amiodarone may significantly affect the frontal plane QRS-T angle. As a parameter that can be easily calculated from automated ECG recordings, frontal plane QRS-T angle may be useful in the monitoring of intravenous amiodarone treatment.

Comparable risk of recurrent ventricular tachyarrhythmias in implantable cardioverter-defibrillator recipients treated with single beta-blocker or combined amiodarone.

This study sought to assess the prognostic impact of treatment with single beta-blocker (BB) compared to combined therapy with BB plus amiodarone (BB-AMIO) on recurrences of ventricular tachyarrhythmias in implantable cardioverter-defibrillator (ICD) recipients. A large retrospective registry was used including consecutive ICD recipients with index episodes of ventricular tachyarrhythmias from 2002 to 2016. Patients treated with BB were compared to patients treated with BB-AMIO. Kaplan-Meier and Cox regression analyses were applied for the evaluation of the primary end-point defined as first recurrences of ventricular tachyarrhythmias at five years. Secondary end-points comprised first appropriate ICD therapies, first cardiac rehospitalization and all-cause mortality at five years. Among 512 ICD recipients, 81% were treated with BB and 19% with BB-AMIO. BB and BB-AMIO were associated with comparable risk of first recurrences of ventricular tachyarrhythmias (46% vs. 43%; log rank P = .941; HR = 1.013; 95% CI 0.725-1.415; P = .941) and appropriate ICD therapies (35% vs. 37%; log rank P = .389; HR = 0.852; 95% CI 0.591-1.228; P = .390). BB was associated with decreased long-term all-cause mortality within an univariable analysis only (20% vs. 28%; log rank p = 0.023). In conclusion, BB and BB-AMIO were associated with comparable risks regarding recurrences of ventricular tachyarrhythmias at five years.

Cardiomiopatia arritmogênica do ventrículo direito em maratonista: relato de caso / Arrhythmogenic right ventricular cardiomyopathy in marathon runners: case report

A cardiomiopatia arritmogênica do ventrículo direito é uma desordem hereditária caracterizada pela substituição fibrogordurosa do músculo cardíaco. O manejo clínico busca reduzir os riscos de morte súbita e melhorar a qualidade de vida, aliviando os sintomas arrítmicos e de insuficiência cardíaca. O ecocardiograma é o exame inicial para a investigação da cardiomiopatia arritmogênica do ventrículo direito, podendo apresentar dilatação das câmaras direitas e disfunção sistólica do ventrículo direito. Este relato chama atenção por envolver o diagnóstico de cardiomiopatia arritmogênica do ventrículo direito em paciente atleta. Mulher, 47 anos, maratonista, sem história familiar de morte súbita cardíaca, deu entrada na emergência com palpitação associada à pré-síncope. O eletrocardiograma da admissão mostrava taquicardia ventricular. O ecocardiograma revelou aumento de câmaras cardíacas direitas e disfunção sistólica do ventrículo direito. O cateterismo cardíaco não evidenciou doença coronária obstrutiva. A paciente foi orientada acerca da necessidade de suspensão de atividades físicas, porém, 3 meses depois, foi readmitida com instabilidade hemodinâmica por nova taquicardia ventricular, tendo sido cardiovertida. Realizou ressonância cardíaca, que evidenciou áreas de discinesia e formação de microaneurismas em ventrículo direito. Foi diagnosticada com cardiomiopatia arritmogênica do ventrículo direito, tendo sido com cardioversor desfibrilador implantável, amiodarona e betabloqueador. A diferenciação entre a cardiomiopatia arritmogênica do ventrículo direito e o coração do atleta representa um desafio, devido à sobreposição de alterações estruturais que coexistem nessas entidades, daí a importância da análise integrada de fatores clínicos, eletrocardiográficos e morfofuncionais.(AU)

Amiodarone inhibits arrhythmias in hypertensive rats by improving myocardial biomechanical properties.

The prevalence of arrhythmia in patients with hypertension has gradually attracted widespread attention. However, the relationship between hypertension and arrhythmia still lacks more attention. Herein, we explore the biomechanical mechanism of arrhythmia in hypertensive rats and the effect of amiodarone on biomechanical properties. We applied micro-mechanics and amiodarone to stimulate single ventricular myocytes to compare changes of mechanical parameters and the mechanism was investigated in biomechanics. Then we verified the expression changes of genes and long non-coding RNAs (lncRNAs) related to myocardial mechanics to explore the effect of amiodarone on biomechanical properties. The results found that the stiffness of ventricular myocytes and calcium ion levels in hypertensive rats were significantly increased and amiodarone could alleviate the intracellular calcium response and biomechanical stimulation. In addition, experiments showed spontaneously hypertensive rats were more likely to induce arrhythmia and preoperative amiodarone intervention significantly reduced the occurrence of arrhythmias. Meanwhile, high-throughput sequencing showed the genes and lncRNAs related to myocardial mechanics changed significantly in the spontaneously hypertensive rats that amiodarone was injected. These results strengthen the evidence that hypertension rats are prone to arrhythmia with abnormal myocardial biomechanical properties. Amiodarone effectively inhibit arrhythmia by improving the myocardial biomechanical properties and weakening the sensitivity of mechanical stretch stimulation.

Treatment of out-of-hospital cardiac arrest in the COVID-19 era: A 100 days experience from the Lombardy region.

INTRODUCTION: An increase in the incidence of OHCA during the COVID-19 pandemic has been recently demonstrated. However, there are no data about how the COVID-19 epidemic influenced the treatment of OHCA victims. METHODS: We performed an analysis of the Lombardia Cardiac Arrest Registry comparing all the OHCAs occurred in the Provinces of Lodi, Cremona, Pavia and Mantua (northern Italy) in the first 100 days of the epidemic with those occurred in the same period in 2019. RESULTS: The OHCAs occurred were 694 in 2020 and 520 in 2019. Bystander cardiopulmonary resuscitation (CPR) rate was lower in 2020 (20% vs 31%, p<0.001), whilst the rate of bystander automated external defibrillator (AED) use was similar (2% vs 4%, p = 0.11). Resuscitation was attempted by EMS in 64.5% of patients in 2020 and in 72% in 2019, whereof 45% in 2020 and 64% in 2019 received ALS. At univariable analysis, the presence of suspected/confirmed COVID-19 was not a predictor of resuscitation attempt. Age, unwitnessed status, non-shockable presenting rhythm, absence of bystander CPR and EMS arrival time were independent predictors of ALS attempt. No difference regarding resuscitation duration, epinephrine and amiodarone administration, and mechanical compression device use were highlighted. The return of spontaneous circulation (ROSC) rate at hospital admission was lower in the general population in 2020 [11% vs 20%, p = 0.001], but was similar in patients with ALS initiated [19% vs 26%, p = 0.15]. Suspected/confirmed COVID-19 was not a predictor of ROSC at hospital admission. CONCLUSION: Compared to 2019, during the 2020 COVID-19 outbreak we observed a lower attitude of laypeople to start CPR, while resuscitation attempts by BLS and ALS staff were not influenced by suspected/confirmed infection, even at univariable analysis.

Reducing the Incidence of Amiodarone-related Phlebitis Through Utilization of Evidence-based Practice.

BACKGROUND: Intravenous (IV) amiodarone has multiple indications including treatment of hemodynamically unstable patients and the prevention of atrial or ventricular arrhythmias after thoracic surgery. Inflammation of the vein, or phlebitis, is the most common adverse event associated with peripherally administered amiodarone. In 2017, a rise in reported phlebitis incidents was occurring at one large academic medical center. AIM: This evidence-based quality improvement initiative aimed to decrease and enhance early detection of phlebitis in patients receiving amiodarone. METHODS: Due to the variation in assessment and management standards, evidence-based practice (EBP) methodology was utilized to establish a process for quality improvement. A thorough literature search was completed, identifying evidence-based interventions to decrease phlebitis and enhance early detection. Thorough critiques of the literature and synthesis of the evidence were completed. Multidisciplinary guidelines based on the literature were created. The guidelines included interventions such as an increase in IV assessment frequency, vein selection criteria, and the utilization of a standardized grading tool for assessment. RESULTS: Phlebitis was reduced by 30%-88%. In the first 6 months post-intervention, there was a 48% reduction in phlebitis cases. In addition, the severity of phlebitis and the quality of reporting also improved dramatically. LINKING EVIDENCE TO ACTION: This evidence-based quality improvement process led to identifying relevant knowledge gaps in care that could be streamlined into everyday nursing practice to decrease patient harm. This paper describes an in-depth process of how EBP helped to quickly take a clinical inquiry and adapt change based on findings from the evidence. Other organizations can utilize EBP to solve patient safety concerns using similar processes.