State-independent inhibition of the oncogenic Kv10.1 channel by desethylamiodarone, a comparison with amiodarone.

Kv10.1 is a voltage-dependent K channel whose ectopic expression is associated with several human cancers. Additionally, Kv10.1 has structure-function properties which are not yet well understood. We are using drugs of clinical importance in an attempt to gain insight on the relationship between pharmacology and characteristic functional properties of this channel. Herein, we report the interaction of desethylamiodarone (desAd), the active metabolic product of the antiarrhythmic amiodarone with Kv10.1: desAd binds to both closed and open channels, with most inhibition taking place from the open state, with affinity ~ 5 times smaller than that of amiodarone. Current inhibition by desAd and amiodarone is not synergistic. Upon repolarization desAd becomes trapped in Kv10.1 and thereafter dissociates slowly from closed-and-blocked channels. The addition of the Cole-Moore shift plus desAd open-pore-block time courses yields an increasing phase on the steady-state inhibition curve (H∞) at hyperpolarized holding potentials. In contrast to amiodarone, desAd does not inhibit the Kv10.1 Cole-Moore shift, suggesting that a relevant hydrophobic interaction between amiodarone and Kv10.1 participates in the inhibition of the Cole-Moore shift, which is lost with desAd.

Novel pyridyl-substituted nitronyl nitroxides as potential antiarrhythmic and hypotensive agents with low toxicity and enhanced stability in aqueous solutions.

This study explores the antiarrhythmic and hypotensive potential of pyridyl-substituted nitronyl nitroxides derivatives, uncovering the crucial role of a single carbon moiety of the pyridine cycle alongside radical and charged oxygen centers of the imidazoline fragment. Notably, the introduction of fluorine atoms diminished the antiarrhythmic effect, while the most potent derivatives featured the nitronyl nitroxide pattern positioned at the third site of the pyridine cycle. Gender-dependent responses were observed in lead compounds LCF3 and LMe, with LMe inducing temporary bradycardia and hypotension specifically in female rats, and LCF3 causing significant blood pressure reduction followed by rebound in females compared to milder effects in males. Mechanistic insights point towards ß1 adrenoceptor blockade as an underlying mechanism, supported by experiments on isolated rat atria. This research underscores the interplay between structure, cardiovascular effects and gender-specific responses, offering insights for therapeutic strategies for treating free radical-associated cardiovascular disorders.

Amiodarone and Dronedarone Causes Liver Injury with Distinctly Different Clinical Presentations.

OBJECTIVE: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database. METHODS: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020. RESULTS: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes. CONCLUSION: Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity.

Blocking channels to metastasis: targeting sodium transport in breast cancer.

The development of therapies that can suppress invasion and prevent metastasis, 'anti-metastatic drugs', is an important area of unmet therapeutic need. The new results of a recent open-label, multicentre randomised trial published in J Clin Oncol showed a significant disease-free survival (DFS) benefit for breast cancer patients receiving presurgical, peritumoral injection of lidocaine, an amide local anaesthetic, which blocks voltage-gated sodium channels (VGSCs). VGSCs are expressed on electrically excitable cells, including neurons and cardiomyocytes, where they sustain rapid membrane depolarisation during action potential firing. As a result of this key biophysical function, VGSCs are important drug targets for excitability-related disorders, including epilepsy, neuropathic pain, affective disorders and cardiac arrhythmia. A growing body of preclinical evidence highlights VGSCs as key protagonists in regulating altered sodium influx in breast cancer cells, thus driving invasion and metastasis. Furthermore, prescription of certain VGSC-inhibiting medications has been associated with reduced cancer incidence and improved survival in several observational studies. Thus, VGSC-inhibiting drugs already in clinical use may be ideal candidates for repurposing as possible anti-metastatic therapies. While these results are promising, further work is required to establish whether other VGSC inhibitors may afford superior metastasis suppression. Finally, increasing preclinical evidence suggests that several other ion channels are also key drivers of cancer hallmarks; thus, there are undoubtedly further opportunities to harness ion transport inhibition that should also be explored.

Keeping It "Current": A Review of Treatment Options for the Management of Supraventricular Tachycardia.

OBJECTIVE: To review treatment options and updates that exist for the management of paroxysmal supraventricular tachycardia (PSVT). DATA SOURCES: A literature search of PubMed was performed including articles from 1974 to June 2023 using the terms: arrhythmias, adenosine, verapamil, diltiazem, esmolol, propranolol, metoprolol, beta-blockers, amiodarone, PSVT, synchronized cardioversion, methylxanthines, dipyridamole, pediatrics, heart transplant, and pregnancy. Primary literature and guidelines were reviewed. STUDY SELECTION AND DATA EXTRACTION: Studies were considered if they were available in English and conducted in humans. DATA SYNTHESIS: PSVT is a subset of supraventricular tachycardia (SVT) that presents as a rapid, regular tachycardia with an abrupt onset and termination. Due to frequent emergency department (ED) visits annually with symptoms of PSVT, appropriate and efficient management of these patients is vital. This review provides an overview of the pathophysiology of PSVT, while also describing the literature behind nonpharmacologic and pharmacologic management of PSVT. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review describes new literature regarding the improved success of the modified Valsalva maneuver as a nonpharmacologic therapy in PSVT. In addition, it describes a new technique in administration of adenosine that has improved outcomes, defines dose adjustments needed for drug interactions with adenosine, compares the utilization of nondihydropyridine calcium channel blockers with adenosine, and provides management recommendations for patients in special populations. CONCLUSIONS: With high annual rates of ED visits for SVT, providers should be aware of the data behind management and modifications of therapy based on patient-specific factors (ie, patient preference, pharmacokinetics/pharmacodynamics, drug interactions, and special populations).

Intravenous Metoprolol Versus Diltiazem for Rate Control in Atrial Fibrillation.

BACKGROUND: Currently, it remains unclear whether ß-blockers or nondihydropyridine calcium channel blockers are preferred for the acute management of atrial fibrillation (AF). OBJECTIVE: The objective of this study was to compare the efficacy and safety of intravenous (IV) metoprolol and diltiazem for rate control. METHODS: This was a single-center, retrospective cohort study of patients who presented to the emergency department between 2015 and 2019 with AF with rapid ventricular rate (RVR) and received IV metoprolol or diltiazem. The primary outcome was the percentage of patients who achieved rate control (defined as heart rate < 100 beats per minute). Secondary outcomes included time to rate control, percentage of patients requiring additional agents for rate control, and incidence of cardioversion, bradycardia, and hypotension. RESULTS: A total of 200 patients were included in this study. Rate control was achieved in 35% and 41% of the metoprolol and diltiazem groups, respectively (P = 0.38). Mean time to rate control was not significantly different between the metoprolol and diltiazem groups (35 vs 21 minutes, P = 0.23). One patient developed hypotension, no patient developed bradycardia, and 4 patients required electric cardioversion. No adverse events were observed in patients with ejection fraction ≤40%. CONCLUSION AND RELEVANCE: There was no difference in the achievement of rate control between IV metoprolol and diltiazem. This is the largest study to date comparing the two classes of agents for acute rate control in AF. No patient-specific factors were identified that would influence the preferential use of one medication over the other.

Reappraising the role of class Ic antiarrhythmics in atrial fibrillation.

PURPOSE: The objective of the present systematic review was to compare the effectiveness and safety of class Ic agents for cardioversion of paroxysmal atrial fibrillation (AF), in patients with and without structural heart disease (SHD). METHODS: We focused on RCTs enrolling at least 50 adult patients with electrocardiogram-documented paroxysmal AF that compared either two pharmacological class Ic cardioversion agents (flecainide, propafenone), regardless of study design (parallel or crossover). We searched MEDLINE and the Cochrane Central Register of Controlled Trials. Initial search was performed from inception to 15 July 2021 with no language restrictions. RESULTS: Intravenous flecainide is the most effective option for pharmacologic cardioversion of AF since only 2 patients need to be treated in order to cardiovert one more within 4 h. Most importantly, class Ic agents appear to be safe in the context of pharmacologic cardioversion of AF irrespective of the presence of SHD, pointing towards a possible reappraisal of the role in this setting. CONCLUSION: We suggest that class Ic agents (with flecainide appearing to be more effective) should be used for pharmacologic cardioversion in stable AF patients presenting in emergency department with unknown medical history, after excluding severe cardiac disease through a bedside examination. REGISTRATION NUMBER (DOI): Available in https://osf.io/apwt7/ , https://doi.org/10.17605/OSF.IO/APWT7.

Linked biaromatic compounds as cardioprotective agents.

Cardiovascular diseases (CVDs) are widespread in the modern world, and their number is constantly growing. For a long time, CVDs have been the leading cause of morbidity and mortality worldwide. Drugs for the treatment of CVD have been developed almost since the beginning of the 20th century, and a large number of effective cardioprotective agents of various classes have been created. Nevertheless, the need for the design and development of new safe drugs for the treatment of CVD remains. Literature data indicate that a huge number of cardioprotective agents of various generations and mechanisms correspond to a single generalized pharmacophore model containing two aromatic nuclei linked by a linear linker. In this regard, we put forward a concept for the design of a new generation of cardioprotective agents with a multitarget mechanism of action within the indicated pharmacophore model. This review is devoted to a generalization of the currently known compounds with cardioprotective properties and corresponding to the pharmacophore model of biaromatic compounds linked by a linear linker. Particular attention is paid to the history of the creation of these drugs, approaches to their design, and analysis of the structure-action relationship within each class.

Cardioversion of recent-onset atrial fibrillation using intravenous antiarrhythmics: A European perspective.

Pharmacological cardioversion using intravenous antiarrhythmic agents is commonly indicated in symptomatic patients with recent-onset atrial fibrillation (AF). Except in hemodynamically unstable patients who require emergency direct current electrical cardioversion, for the majority of hemodynamically stable patients, pharmacological cardioversion represents a valid option and requires the clinician to be familiar with the properties and use of antiarrhythmic agents. The main characteristics of selected intravenous antiarrhythmic agents for conversion of recent-onset AF, the reported success rates, and possible adverse events are discussed. Among intravenous antiarrhythmics, flecainide, propafenone, amiodarone, sotalol, dofetilide, ibutilide, and vernakalant are commonly used. Antazoline, an old antihistaminic agent with antiarrhythmic properties was also reported to give encouraging results in Poland. Intravenous flecainide and propafenone are the only Class I agents still recommended by recent guidelines. Intravenous new Class III agents as dofetilide and ibutilide have high and rapid efficacy in converting AF to sinus rhythm but require strict surveillance with electrocardiogram (ECG) monitoring during and after intravenous administration because of the potential risk of QT prolongation and Torsades de Pointes, which can be prevented and properly managed. Vernakalant, a partial atrial selective was shown to have a high success rate and to be safe in real-life use.

Sepsis With Preexisting Heart Failure: Management of Confounding Clinical Features.

Preexisting heart failure (HF) in patients with sepsis is associated with worse clinical outcomes. Core sepsis management includes aggressive volume resuscitation followed by vasopressors (and potentially inotropes) if fluid is inadequate to restore perfusion; however, large fluid boluses and vasoactive agents are concerning amid the cardiac dysfunction of HF. This review summarizes evidence regarding the influence of HF on sepsis clinical outcomes, pathophysiologic concerns, resuscitation targets, hemodynamic interventions, and adjunct management (ie, antiarrhythmics, positive pressure ventilatory support, and renal replacement therapy) in patients with sepsis and preexisting HF. Patients with sepsis and preexisting HF receive less fluid during resuscitation; however, evidence suggests traditional fluid resuscitation targets do not increase the risk of adverse events in HF patients with sepsis and likely improve outcomes. Norepinephrine remains the most well-supported vasopressor for patients with sepsis with preexisting HF, while dopamine may induce more cardiac adverse events. Dobutamine should be used cautiously given its generally detrimental effects but may have an application when combined with norepinephrine in patients with low cardiac output. Management of chronic HF medications warrants careful consideration for continuation or discontinuation upon development of sepsis, and ß-blockers may be appropriate to continue in the absence of acute hemodynamic decompensation. Optimal management of atrial fibrillation may include ß-blockers after acute hemodynamic stabilization as they have also shown independent benefits in sepsis. Positive pressure ventilatory support and renal replacement must be carefully monitored for effects on cardiac function when HF is present.

Measurement and Management of QT Interval Prolongation for General Physicians.

One of the more challenging aspects of ECG interpretation is measurement and interpretation of the QT interval. This interval represents the time taken for the ventricles to completely repolarise after activation. Abnormal prolongation of the QT interval can lead to torsades de pointes, a form of potentially life-threatening polymorphic ventricular tachycardia (VT). Detection of a prolonged QT interval is essential as this can be a reversible problem, particularly in the context of the use of a variety of commonly prescribed medications in the hospital setting. Automated ECG printouts cannot be relied upon to diagnose QT interval prolongation; thus, the onus is on the clinician to identify it. This is a difficult task, as the normal QT interval is typically measured relative to the heart rate. Therefore, the QT interval often requires "correction" for the current heart rate, in order to correctly stratify the risk of torsades de pointes. A wealth of correctional formulae have been derived, but none has proven superior. We present an approach to the ECG in this context, and a step-by-step guide to manually measuring and correcting the QT interval, and an approach to management in common hospital-based clinical scenarios.

Differential effects of class I antiarrhythmic drugs on the guinea pig pulmonary vein myocardium: Inhibition of automatic activity correlates with blockade of a diastolic sodium current component.

The effects of class I antiarrhythmic drugs on the automaticity of isolated guinea pig pulmonary vein myocardia were investigated using microelectrode and voltage clamp methods. All of the drugs examined reduced the maximum rate of rise of automatic action potentials. The firing frequency and rate of diastolic depolarization were decreased by aprindine, flecainide and propafenone, but not by cibenzoline, disopyramide and pilsicainide, which correlated with blockade of the sodium current component induced by ramp depolarization mimicking the diastolic depolarization. In conclusion, class I antiarrhythmic drugs which block the diastolic sodium current component inhibit the automaticity of the pulmonary vein myocardium.

Botulinum Toxin-Chitosan Nanoparticles Prevent Arrhythmia in Experimental Rat Models.

Several experimental studies have recently demonstrated that temporary autonomic block using botulinum toxin (BoNT/A1) might be a novel option for the treatment of atrial fibrillation. However, the assessment of antiarrhythmic properties of BoNT has so far been limited, relying exclusively on vagal stimulation and rapid atrial pacing models. The present study examined the antiarrhythmic effect of specially formulated BoNT/A1-chitosan nanoparticles (BTN) in calcium chloride-, barium chloride- and electrically induced arrhythmia rat models. BTN enhanced the effect of BoNT/A1. Subepicardial injection of BTN resulted in a significant antiarrhythmic effect in investigated rat models. BTN formulation antagonizes arrhythmia induced by the activation of Ca, K and Na channels.

Effects of ajmaline on contraction patterns of isolated rat gastric antrum and portal vein smooth muscle strips and on neurogenic relaxations of gastric fundus.

Class-I-antiarrhythmics like ajmaline are known to alter smooth muscle function, which may cause alterations in gastrointestinal motility. The effects of ajmaline on isolated gastric and portal vein smooth muscle and the underlying mechanisms are unknown. We studied the effects of ajmaline on the contractile patterns of isolated preparations of gastric antrum and portal vein from Wistar rats. The organ bath technique was used to measure spontaneous or pharmacologically induced isometric contractions. Changes in force observed after application of ajmaline or under control conditions are reported as % of the amplitude of an initial K+-induced contraction. Electric field stimulation was used to study neurogenic relaxations of gastric fundus smooth muscle. Ajmaline increased the amplitude of spontaneous contractions of muscle strips (portal vein: control 31.1 ± 15.2%, with 100 µM ajmaline 76.6 ± 32.3%, n = 9, p < 0.01; gastric antrum: control 9.5 ± 1.6%, with 100 µM ajmaline 63.9 ± 9.96%, n = 14, p < 0.01). The frequency of spontaneous activity was reduced in portal vein, but not in gastric antrum strips. The effects of ajmaline were not blocked by tetrodotoxin, L-nitroarginine methyl ester, or atropine. Ajmaline abolished coordinated neurogenic relaxations triggered by electric field stimulation and partly reversed the inhibition of GA spontaneous activity caused by the gap junction blocker carbenoxolone. Ajmaline enhances the amplitude of spontaneous contractions in rat gastric and portal vein smooth muscle. This effect may be accompanied, but not caused by an inhibition of enteric neurotransmission. Enhanced syncytial coupling as indicated by its ability to antagonize the effects of carbenoxolone is likely to underlie the enhancement of contractility.

Comorbidity between epilepsy and cardiac arrhythmias: Implication for treatment.

Epilepsy is often comorbid with either neurological or nonneurological diseases. The association between epilepsy and cardiac arrhythmias is not infrequent, mostly in patients with severe forms of epilepsy or critically ill. Remarkably, these medical conditions share many similarities. Vascular and genetic disorders may predispose to both seizures and abnormalities of cardiac electrophysiology. Repeated and uncontrolled seizures may favor potentially life-threatening arrhythmias. Antiepileptic drugs (AEDs) may facilitate the occurrence of cardiac arrhythmias by acting on ionic channels at heart level. Antiarrhythmic drugs (AADs) can have effects on ionic channels expressed in the brain, as suggested by their efficacy in treating patients with rare forms of epilepsy; AADs may also be proconvulsant, mainly during their overdosage. In clinical practice, the AEDs with the lowest risk to influence cardiac electrophysiology are to be preferred in patients presenting with either seizures or arrhythmias. Traditional AEDs should be avoided because of their arrhythmogenic properties and enzyme-inducing effects, which may make ineffective the concomitant treatment with AADs. Some of the newer AEDs can rarely affect cardiac rhythm, and electrocardiogram (ECG) monitoring should be warranted.

Usefulness of Routine Transtelephonic Monitoring for Supraventricular Tachycardia in Infants.

OBJECTIVE: We hypothesize that routine daily transtelephonic monitoring (TTM) transmissions can accurately detect supraventricular tachycardia (SVT) in asymptomatic infants and/or assuage parental concerns rather than being used solely to diagnose arrhythmias. STUDY DESIGN: Single center, retrospective chart review of 60 patients with fetal or infant SVT prescribed TTM for at least 30 days, January 2010-September 2016. Patients were excluded if initial SVT was not documented, was perioperative, was atrial flutter/fibrillation, or chaotic atrial tachycardia. Categorical variables expressed as mean ± SD. Mann-Whitney, Spearman correlation, and Fisher exact tests were used for continuous and categorical variables respectively. RESULTS: Sixty patients were included. There were 2688 TTM transmissions received from 55 of 60 patients over 61.1 ± 66.7 days (0.73 ± 0.65 TTM/patient/days). Routine asymptomatic TTM transmissions revealed actionable findings in 5 of 2801 TTM transmissions sent by 5 patients (8.3%). No patient presented in shock or died. Forty-five of 2688 TTM transmissions were sent for parental concerns/symptoms in 16 patients (25.8%) with findings of normal sinus rhythm in 37 of 45 TTM transmissions and SVT in 8 of 45 TTM transmissions. Symptomatic actionable findings were more likely sent by patients discharged on class I or III antiarrhythmics (95% CI = 11.5%-68.3%, P = .004) and patients with prolonged initial hospitalizations (95% CI = 6.98%-59.7%, P = .01). Flecainide was discontinued in 1 patient after widened QRS was noted on routine TTM. CONCLUSIONS: TTM accurately diagnose asymptomatic recurrent SVT in neonates and infants before they develop signs of congestive heart failure or shock and is helpful for recurrent SVT management.

Evaluating class III antiarrhythmic agents as novel MYC targeting drugs in ovarian cancer.

OBJECTIVE: To evaluate the utility of amiodarone and its derivative dronedarone as novel drug repositioning candidates in EOC and to determine the potential pathways targeted by these drugs. METHODS: Drug-predict bioinformatics platform was used to assess the utility of amiodarone as a novel drug-repurposing candidate in EOC. EOC cells were treated with amiodarone and dronedarone. Cell death was assessed by Annexin V staining. Cell viability and cell survival were assessed by MTT and clonogenics assays respectively. c-MYC and mTOR/Akt axis were evaluated as potential targets. Effect on autophagy was determined by autophagy flux flow cytometry. RESULTS: "DrugPredict" bioinformatics platform ranked Class III antiarrhythmic drug amiodarone within the top 3.9% of potential EOC drug repositioning candidates which was comparable to carboplatin ranking in the top 3.7%. Amiodarone and dronedarone were the only Class III antiarrhythmic drugs that decreased the cellular survival of both cisplatin-sensitive and cisplatin-resistant primary EOC cells. Interestingly, both drugs induced degradation of c-MYC protein and decreased the expression of known transcriptional targets of c-MYC. Furthermore, stable overexpression of non-degradable c-MYC partially rescued the effects of amiodarone and dronedarone induced cell death. Dronedarone induced higher autophagy flux in EOC cells as compared to amiodarone with decreased phospho-AKT and phospho-4EBP1 protein expression, suggesting autophagy induction due to inhibition of AKT/mTOR axis with these drugs. Lastly, both drugs also inhibited the survival of EOC tumor-initiating cells (TICs). CONCLUSIONS: We provide the first evidence of class III antiarrhythmic agents as novel c-MYC targeting drugs and autophagy inducers in EOC. Since c-MYC is amplified in >40% ovarian tumors, our results provide the basis for repositioning amiodarone and dronedarone as novel c-MYC targeting drugs in EOC with potential extension to other cancers.

Structural Models of Ligand-Bound Sodium Channels.

X-ray and cryo-EM structures of tetrameric and pseudo-tetrameric P-loop channels are used to elaborate homology models of mammalian voltage-gated sodium channels with drugs and neurotoxins. Such models integrate experimental data, assist in planning new experiments, and may facilitate drug design. This chapter outlines sodium channel models with local anesthetics, anticonvulsants, and antiarrhythmics, which are used to manage pain and treat sodium channelopathies. Further summarized are sodium channel models with tetrodotoxin, mu-conotoxins, batrachotoxin, scorpion toxins, and insecticides. Possible involvement of sodium ions in the action of some ligands is discussed.

Antiarrhythmics in Cardiac Arrest: A Systematic Review and Meta-Analysis.

INTRODUCTION: It is widely accepted that antiarrhythmics play a role in cardiopulmonary resuscitation (CPR) universally, but the absolute benefit of antiarrhythmic use and the drug of choice in advanced life support remains controversial. AIM: To perform a thorough, in-depth review and analysis of current literature to assess the efficacy of antiarrhythmics in advanced life support. MATERIAL AND METHODS: Two authors systematically searched through multiple bibliographic databases including CINAHL, SCOPUS, PubMed, Web of Science, Medline(Ovid) and the Cochrane Clinical Trials Registry. To be included studies had to compare an antiarrhythmic to either a control group, placebo or another antiarrhythmic in adult cardiac arrests. These studies were independently screened for outcomes in cardiac arrest assessing the effect of antiarrhythmics on return of spontaneous circulation (ROSC), survival and neurological outcomes. Data was extracted independently, compared for homogeneity and level of evidence was evaluated using the Cochrane Collaboration's tool for assessing the risk of bias. The Mantel-Haenszel (M-H) random effects model was used and heterogeneity was assessed using the I2 statistic. RESULTS AND DISCUSSION: The search of the literature yielded 30 studies, including 39,914 patients. Eight antiarrhythmic agents were identified. Amiodarone and lidocaine, the two most commonly used agents, showed no significant effect on any outcome either against placebo or each other. Small low quality studies showed benefits in isolated outcomes with esmolol and bretylium against placebo. The only significant benefit of one antiarrhythmic over another was demonstrated with nifekalant over lidocaine for survival to admission (p=0.003). On sensitivity analysis of a small number of high quality level one RCTs, both amiodarone and lidocaine had a significant increase in survival to admission, with no effect on survival to discharge. CONCLUSIONS: This systematic review and meta-analysis suggests that, based on current literature and data, there has been no conclusive evidence that any antiarrhythmic agents improve rates of ROSC, survival to admission, survival to discharge or neurological outcomes. Given the side effects of some of these agents, we recommend further research into their utility in current cardiopulmonary resuscitation guidelines.

Impact of a Pharmacy-Cardiology Collaborative Practice on Dofetilide Safety Monitoring.

BACKGROUND: Limited studies have been published examining dofetilide's postmarketing use and its recommended monitoring. OBJECTIVE: To evaluate the impact of a collaborative pharmacy-cardiology antiarrhythmic drug (AAD) monitoring program on dofetilide monitoring. METHODS: This retrospective cohort study was performed to assess if a novel monitoring program improved compliance with dofetilide-specific monitoring parameters based on the Food and Drug Administration's Risk Evaluation and Mitigation Strategy. RESULTS: A total of 30 patients were included in the analysis. The monitoring parameters evaluated included electrocardiogram, serum potassium, serum magnesium, and kidney function. The primary outcome evaluated was the composite of these dofetilide monitoring parameters obtained in each cohort. In the standard cohort, 245 of 352 (69.6%) monitoring parameters were completed versus 134 of 136 (98.5%) in the intervention group ( P < 0.05). CONCLUSION: A collaborative pharmacy-cardiology AAD monitoring program was associated with a significant improvement in dofetilide monitoring. This improvement could potentially translate into enhanced patient safety outcomes, such as prevention of adverse drug reactions and decreased hospitalizations.