Class Ic Antiarrhythmic Agent Research Articles

A prospective analysis of the efficacy and safety of ethacizine during premature atrial contractions and premature ventricular contractions

Abstract Background Ethacizine, a class Ic antiarrhythmic agent, is prescribed for managing severe or refractory supraventricular and ventricular arrhythmias, including premature atrial (PACs) and ventricular contractions (PVCs). Despite its use, there is a lack of substantial research exploring the therapeutic effects of ethacizine at present. Purpose The study evaluated the efficacy and safety of ethacizine in addressing PACs and PVCs, in cases where other antiarrhythmic medications proved ineffective. Methods We performed a prospective analysis of ethacizine treatment (50 mg. b.i.d.) for early (30-45 days) and late periods (150-210 days), in male (n=58; 59.2%) and female (n=40; 40.8%) patients aged ≥ 18 years (18-72 y.o; mean age 45 years), with 46 cases of PACs and 52 cases of PVCs, who had previously been treated with another antiarrhythmic medication (bisoprolol, metoprolol, sotalol, verapamil, amiodarone, or propafenone) and had not achieved the target rate of extrasystoles (≤1000/24h). Results The findings reveal a substantial decrease in the mean parameters of PACs during both, the early period (initial 6877 ± 2432, following 761 ± 341); (88,9%); t([45]) = [13,336], p = [< .001) and the late period (initial 6877 ± 2432, following 574 ± 294); (91,7%); t([45]) = [15,124], p = [< .001). The quantitative reduction in PACs reached a maximum of 93.8% in the early period (19406 PACs □ 1211 PACs) and 94.3% in the late period (19406 PACs □ 1105 PACs). The mean parameters of PVCs in the early period experienced a significant reduction (initial 3205 ± 1145, following 550 ± 194); (82,8%); t([51]) = [8,284], p = [< .001). Similarly, the mean PVC values in the late period exhibited a noteworthy decrease (initial 3205 ± 1145, following 490 ± 181); (84,8%); t([51]) = [8,553], p = [< .001). For PVCs, the maximum effect observed in the early period was 94.8% (18929 PVCs □ 989 PVCs), and in the late period, it reached 95% (18929 PVCs □ 950 PVCs). The target rate in the late period (≤1000/24h.) for PACs reached 89%, and for PVCs - 86% (Figure 1). Adverse effects were noted in a mere four subjects (4%). These events manifested as 2nd-degree AV block (Mobitz 1), sustained ventricular tachycardia, asymptomatic nonsustained polytopic ventricular tachycardia, and asymptomatic transient ST-segment elevation observed through 24-hour ECG holter monitoring. Conclusion A prospective study on ethacizine treatment (50 mg. b.i.d.) confirmed its effectiveness and safety in reducing PACs and PVCs. It demonstrated a sustained reduction in extrasystole occurrences for an extended period, achieving the target rate with minimal side effects. Ethacizine merits consideration for addressing extrasystolic arrhythmia, particularly in cases where other antiarrhythmic medications prove ineffective.Results of the study

Encainide, a class Ic anti-arrhythmic agent, blocks voltage-dependent potassium channels in coronary artery smooth muscle cells.

Voltage-dependent K+ (Kv) channels are widely expressed on vascular smooth muscle cells and regulate vascular tone. Here, we explored the inhibitory effect of encainide, a class Ic anti-arrhythmic agent, on Kv channels of vascular smooth muscle from rabbit coronary arteries. Encainide inhibited Kv channels in a concentration-dependent manner with an IC50 value of 8.91 ± 1.75 μM and Hill coefficient of 0.72 ± 0.06. The application of encainide shifted the activation curve toward a more positive potential without modifying the inactivation curve, suggesting that encainide inhibited Kv channels by altering the gating property of channel activation. The inhibition by encainide was not significantly affected by train pulses (1 and 2 Hz), indicating that the inhibition is not use (state)-dependent. The inhibitory effect of encainide was reduced by pretreatment with the Kv1.5 subtype inhibitor. However, pretreatment with the Kv2.1 subtype inhibitor did not alter the inhibitory effects of encainide on Kv currents. Based on these results, encainide inhibits vascular Kv channels in a concentration-dependent and use (state)-independent manner by altering the voltage sensor of the channels. Furthermore, Kv1.5 is the main Kv subtype involved in the effect of encainide.

Evaluation of five algorithms in predicting the sublocalisation of right ventricular outflow tract arrhythmia (RVOTA) when compared to 3D electroanatomical mapping origin

Abstract Introduction The majority of idiopathic ventricular arrythmias arise from the right ventricular outflow tract (RVOT) and they represent nearly 10% of all ventricular tachycardia (VT) admissions. It is paramount to precisely predict the origin of RVOT arrhythmias to define the appropriate approach before the ablation procedure. Conventional 12-lead electrocardiogram (ECG) is a useful tool for analysing cardiac arrhythmias, and numerous ECG algorithms for predicting the origin of RVOT arrhythmias have been reported. Purpose To compare the predictive accuracy of five different algorithms as verified by successful ablation site using 3D electroanatomical non-contact mapping in patients with symptomatic and asymptomatic but high ventricular burden right ventricular outflow tract (RVOT) tachycardias. Methods 28 consecutive patients admitted for radiofrequency catheter ablation for symptomatic and asymptomatic, but high ventricular burden idiopathic premature ventricular contractions (PVC) were recruited for this study. All patients had previous failed or intolerant to beta-blocker and/or at least one class IC anti-arrhythmic agents, and they had normal left ventricular ejection fraction. All patients had documented monomorphic PVC with left bundle branch block morphology and an inferior axis. Concordance of the arrhythmia origin based on ECG algorithm and 3D mapping system site were further evaluated. Of the five algorithms, two algorithms with easy-applicability and having a memorable design (Dixit and Joshi) and three algorithms with more complex and detailed design (Ito, Zhang, Pytkowski) were selected for comparisons. Results Assessment of the diagnostic accuracy showed that each of the five algorithms had only moderate accuracy, and the greatest accuracy was observed in the algorithm proposed by Pytkowski algorithm when assessed by a general cardiologist and Dixit and Pytkowski algorithms when evaluated by the electrophysiologist. However, when the algorithms were compared for their accuracy, specificity, sensitivity, no significant differences were found (p=0.99). Conclusions All the five published 12-lead ECG algorithms for RVOT location were similar in terms of the diagnostic accuracy, specificity, and sensitivity. In our study, Pytkowski algorithm exhibits the best accuracy and sensitivity among the algorithms, while predicting a precise location and when evaluation is performed by electrophysiologists and/or cardiologists. Funding Acknowledgement Type of funding sources: None.

Evaluation of five algorithms in predicting the sublocalisation of right ventricular outflow tract arrhythmia (RVOTA) when compared to 3D electroanatomical mapping origin

PurposeTo compare the predictive accuracy of five different algorithms as verified by successful ablation site using 3D electroanatomical non-contact mapping in patients with symptomatic and asymptomatic but high ventricular burden RVOT tachycardias.Methods28 Consecutive patients admitted for radiofrequency catheter ablation for symptomatic and asymptomatic, but high ventricular burden idiopathic VPC were recruited for this study. All patients had previous failed or intolerant to beta-blocker and/or at least one class IC anti-arrhythmic agents, and they had normal left ventricular ejection fraction. All patients had documented monomorphic VPC with left bundle branch block morphology and an inferior axis. Concordance of the arrhythmia origin based on ECG algorithm and 3D mapping system site were further evaluated. Of the five algorithms, two algorithms with easy‐applicability and having a memorable design (Dixit and Joshi) and three algorithms with more complex and detailed design (Ito, Zhang, Pytkowski) were selected for comparisons.ResultsAssessment of the diagnostic accuracy showed that each of the five algorithms had only moderate accuracy, and the greatest accuracy was observed in the algorithm proposed by Pytkowski algorithm when assessed by a general cardiologist and Dixit algorithm when evaluated by the electrophysiologist. However, when the algorithms were compared for their accuracy, specificity, sensitivity, no significant differences were found (p = 0.99).ConclusionsThe ECG based algorithms for precise localising RVOTA origin simplify the mapping process, reduce the procedural and fluoroscopic time, and improve clinical outcomes, resulting in greater clinical utility. All the five published 12-lead ECG algorithms for ROTVA differentiation were similar in terms of the diagnostic accuracy, specificity, sensitivity and LRs.

Inhibition of voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic agent lorcainide

Voltage-dependent K+ (Kv) channels play the role of returning the membrane potential to the resting state, thereby maintaining the vascular tone. Here, we used native smooth-muscle cells from rabbit coronary arteries to investigate the inhibitory effect of lorcainide, a class Ic antiarrhythmic agent, on Kv channels. Lorcainide inhibited Kv channels in a concentration-dependent manner with an IC50 of 4.46 ± 0.15 μM and a Hill coefficient of 0.95 ± 0.01. Although application of lorcainide did not change the activation curve, it shifted the inactivation curve toward a more negative potential, implying that lorcainide inhibits Kv channels by changing the channels’ voltage sensors. The recovery time constant from channel inactivation increased in the presence of lorcainide. Furthermore, application of train steps (of 1 or 2 Hz) in the presence of lorcainide progressively augmented the inhibition of Kv currents, implying that lorcainide-induced inhibition of Kv channels is use (state)-dependent. Pretreatment with Kv1.5 or Kv2.1/2.2 inhibitors effectively reduced the amplitude of the Kv current but did not affect the inhibitory effect of lorcainide. Based on these results, we conclude that lorcainide inhibits vascular Kv channels in a concentration and use (state)-dependent manner by changing their inactivation gating properties. Considering the clinical efficacy of lorcainide, and the pathophysiological significance of vascular Kv channels, our findings should be considered when prescribing lorcainide to patients with arrhythmia and vascular disease.

Formulation and stability of an extemporaneously compounded propafenone hydrochloride oral suspension for children with arrhythmia

ObjectivesIn children, supraventricular tachycardia is the most common form of arrhythmia, and propafenone is an effective class Ic antiarrhythmic agent used in this population. No suitable paediatric-specific, dosing-flexible preparation is...

Abstract 16505: Sinus Node Sparing Surgical Hybrid Thoracoscopic Ablation for Inappropriate Sinus Tachycardia: Results of a Prospective Multicenter Registry (the Susruta Registry)

Background: Medical treatment for inappropriate sinus tachycardia (IST) remains suboptimal. Radiofrequency Sinus node Modification (RFSM) has been used for managing drug-refractory symptomatic IST. Although, acute success is reasonable, it is faced with high complications and recurrence rates. A novel Sinus Node sparing surgical thoracoscopic hybrid ablation (SUSRUTA) has been recently proposed. Objective: To report outcomes of SUSRUTA for IST patients from a prospective multicenter registry. Methods: This is a multicenter, prospective registry of patients who received SUSRUTA which is SN sparing hybrid ablation using surgical thoracoscopic video-assisted epicardial ablation comprised of a RF bipolar clamp which was used for sparing the SN region (identified by endocardial 3D mapping) and isolation of superior and inferior vena cava with creation of a lateral line across the crista terminalis during IST with isoproterenol challenge. Gaps in the epicardial lesion set are filled in by endocardial RFA. Patients were treated with post op Colchicine and were enrolled in cardiac rehabilitation program. Results: Of the 139 patients, mean age was 26±4 yrs, 91% women and mean duration of IST was 40±21.5 months. 90% were on ivabradine, 86% on beta-blocker, 77% on calcium channel blocker and 77% were on class IC antiarrhythmic agent. Heart rate post-procedure was significantly lower when compared with pre-procedure (110±10 vs. 64±11 bpm, p<0.0001). After a blanking period of 3 months, normal sinus rhythm was restored in 100% of patients in the hybrid group. Postop pericarditis was the most common complication in 80%(severe-4%), severe bradycardia (HR <35 bpm) in 5%, pneumothorax 3.5% and pleural effusion requiring drainage in 2.1% of cases. One patient required a permanent pacemaker. Hospital length of stay was 4.5±0.8 days. At 1041±541 days follow up 94.5% (131/139) were free of symptoms after a single procedure and the 8 patients required a redo-RF catheter ablation.95% patients are off all preprocedural rate controlling medications Conclusion: SUSRUTA appears to be efficacious and safe for the treatment of symptomatic drug resistant IST.

The Case of Flecainide Toxicity: What to Look For and How to Treat

Introduction: Flecainide is a class Ic antiarrhythmic agent used to prevent and treat both ventricular and supraventricular tachycardias including atrial fibrillation, AV nodal re-entrant tachycardia (AVNRT), and Wolff- Parkinson-White syndrome (WPW). Flecainide can cause serious side effects include cardiac arrest, arrhythmias, and heart failure. Despite its growing use, the presenting signs and symptoms of flecainide toxicity are not familiar to most clinicians. Case description: This was a 58 year-old female who presented from her skilled nursing facility due to hypoxia and altered mental status. Past medical history was notable for paroxysmal atrial fibrillation for which she was on flecainide. At the nursing facility the patient was noted to be obtunded, whereas at baseline she was reportedly alert and oriented. On presentation to the Emergency Department EKG demonstrated wide-complex tachycardia. Subsequent lab results were notable for hypokalemia and an acute kidney injury (AKI). A repeat EKG was concerning for ischemia in leads II, III, aVF and cardiology was emergently consulted. They noted the EKG changes were consistent with flecainide toxicity, specifically a prolonged PR interval and QRS. She was eventually admitted to the medical intensive care unit. Her wide complex tachycardia on admission was ultimately attributed to flecainide toxicity in setting of AKI. Six days after presentation, it was found that her flecainide level was in the toxic range at 2.02 ug/mL (normal range: 0.20-1.00 ug/mL, toxic>1.50 ug/mL). Discussion: Flecainide intoxication is rare but serious due to the potential for cardiogenic shock. Its diagnosis can be difficult as the flecainide serum level may take days to result and there are no pathognomonic clinical signs. This case demonstrates the necessity of keeping flecainide toxicity on the physician’s differential for patients who are taking the drug, as well as what ECG and laboratory findings can suggest it as the etiology. A heightened suspicion is warranted in the patient with new renal impairment. Treatment can be lifesaving if initiated promptly.

The Ubiquitous Premature Ventricular Complex.

Premature ventricular complexes (PVCs) are one of the most commonly encountered arrhythmias and are ubiquitous in clinical practice, both in the outpatient and inpatient settings. They are often discovered incidentally in asymptomatic patients, however, can cause myriad symptoms acutely and chronically. Long thought to be completely benign, PVCs have been historically disregarded without pursuing any further evaluation. Newer data have revealed that a high burden of PVCs with specific characteristics can significantly increase a patient's risk of developing PVC-induced cardiomyopathy. The aim of this literature review is to provide further clarification on the identification of high-risk PVCs, subsequent workup, and the currently available treatment options. PVCs arise from an ectopic focus within the ventricles. Patients with PVCs can be either asymptomatic or have severe disabling symptoms. The diagnostic workup for PVCs includes electrocardiogram (ECG) and 24-h Holter monitor to assess the QRS morphology and its frequency. A transthoracic echocardiogram (TTE) is done to look for structural heart disease and cardiomyopathy. Management of PVCs should be focused on identifying and treating the underlying causes, such as electrolyte abnormalities, substance use, and underlying structural heart disease. Beta-blockers are first-line therapy for symptomatic PVCs. Nondihydropyridine calcium channel blockers, classic antiarrhythmic agents, and amiodarone can be considered as second-line agents. Patients who are unable to tolerate medical therapy should undergo catheter ablation of the PVC focus to prevent PVC-induced cardiomyopathy. PVCs are common in clinical practice, and it is vital to identify patients at higher risk for PVC-induced cardiomyopathy to facilitate early intervention. Patients with no evidence of structural heart disease and infrequent PVCs should be monitored closely, while those who are symptomatic should be treated medically. For those who have failed medical therapy, catheter ablation of the PVCs focus is recommended. Catheter ablation has been shown to reduce PVCs burden and improve left ventricular ejection fraction (LVEF) in those with PVC-induced cardiomyopathy.

6082A prospective, multicenter, nationwide, observational study of flecainide controlled release on the quality of life of patients with atrial fibrillation in Greece, the REFLEC-CR study

Abstract Background/Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia with a considerable impact on patients' quality of life (QoL). Flecainide acetate, is a class Ic antiarrhythmic agent, recommended as first line treatment in AF patients without underlying structural heart disease. Purpose This prospective, multicenter, nationwide, observational study aimed to evaluate the effect of oral treatment with controlled-release (CR) flecainide administered once daily on AF patients' QoL and treatment compliance during a 12-week period. Methods A total of 70 cardiologists participated in the study enrolling consecutive adult patients with paroxysmal or persistent AF, treated with flecainide CR in the context of a rhythm control strategy. The effect on QoL was assessed by the Canadian Cardiovascular Society Severity of Atrial Fibrillation scale (CCS-SAF) measured at baseline and at 12 weeks of treatment. Results In total, 679 patients (53.2% females, mean age 65.9±11.7 years, 86.9% paroxysmal AF) were included in the analysis. At least one prior antiarrhythmic treatment was documented in 43.8% of patients. The initial daily dose of flecainide CR was 100mg in 71.7% of the patients, with a titration to 200mg by the end of study achieved in 67%. In 93.6% of patients an excellent compliance score (100%) to treatment was recorded at the end of the study period. Treatment with flecainide CR resulted in a significant improvement in QoL as presented in the table. Table 1 CCS-SAF score Baseline (Week 0) End of study visit (Week 12) N=679 N=634 Class 1 (minimal effect on QoL) 343 (50.5) 464 (73.2) Class 2 (minor effect on QoL) 253 (37.2) 140 (22.1) Class 3 (moderate effect on QoL) 73 (10.8) 28 (4.4) Class 4 (severely impairs QoL) 10 (1.5) 2 (0.3) CCS-SAF continuous score Mean ± SD 1.64±0.73 1.32±0.57 Change from baseline‡ Mean (95% CI) −0.325 (−0.379, −0.271) p-value <0.0001 ‡Paired t-test is used. Conclusions This prospective, multicenter, observational study demonstrated that treatment of AF patients with flecainide CR, was associated with a significant improvement of QoL and excellent compliance to treatment. Acknowledgement/Funding Sponsored by WinMedica S.A.

Inhibitory effects of class I antiarrhythmic agents on Na+ and Ca2+ currents of human iPS cell-derived cardiomyocytes.

IntroductionHuman induced pluripotent stem cells (hiPSCs) harboring cardiac myosin heavy chain 6 promoter can differentiate into functional cardiomyocytes called “iCell cardiomyocytes” under blasticidin treatment condition. While iCell cardiomyocytes are expected to be used for predicting cardiotoxicity of drugs, their responses to antiarrhythmic agents remain to be elucidated. We first examined electrophysiological properties of iCell cardiomyocytes and mRNA levels of ion channels and Ca handling proteins, and then evaluated effects of class I antiarrhythmic agents on their Na+ and Ca2+ currents.MethodsiCell cardiomyocytes were cultured for 8–14 days (38–44 days after inducing their differentiation), according to the manufacturer's protocol. We determined their action potentials (APs) and sarcolemmal ionic currents using whole-cell patch clamp techniques, and also mRNA levels of ion channels and Ca handling proteins by RT-PCR. Effects of three class I antiarrhythmic agents, pirmenol, pilsicainide and mexiletine, on Na+ channel current (INa) and L-type Ca2+ channel current (ICaL) were evaluated by the whole-cell patch clamp.ResultsiCell cardiomyocytes revealed sinoatrial node-type (18%), atrial-type (18%) and ventricular-type (64%) spontaneous APs. The maximum peak amplitudes of INa, ICaL, and rapidly-activating delayed-rectifier K+ channel current were −62.7 ± 13.7, −8.1 ± 0.7, and 3.0 ± 1.0 pA/pF, respectively. The hyperpolarization-activated cation channel and inward-rectifier K+ channel currents were observed, whereas the T-type Ca2+ channel or slowly-activating delayed-rectifier K+ channel current was not detectable. mRNAs of Nav1.5, Cav1.2, Kir2.1, HCN4, KvLQT1, hERG and SERCA2 were detected, while that of HCN1, minK or MiRP was not. The class Ia antiarrhythmic agent pirmenol and class Ic agent pilsicainide blocked INa in a concentration-dependent manner with IC50 of 0.87 ± 0.37 and 0.88 ± 0.16 μM, respectively; the class Ib agent mexiletine revealed weak INa block with a higher IC50 of 30.0 ± 3.0 μM. Pirmenol, pilsicainide and mexiletine blocked ICaL with IC50 of 2.00 ± 0.39, 7.7 ± 2.5 and 5.0 ± 0.1 μM, respectively.ConclusionsIn iCell cardiomyocytes, INa was blocked by the class Ia and Ic antiarrhythmic agents and ICaL was blocked by all the class I agents within the ranges of clinical concentrations, suggesting their cardiotoxicity.

30-Year-Old Man With Outside-of-Hospital Cardiac Arrest

30-Year-Old Man With Outside-of-Hospital Cardiac Arrest

Inhibition of voltage-dependent K+ current in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic drug propafenone.

In this study, we demonstrated the inhibitory effect of the Class Ic antiarrhythmic agent propafenone on voltage-dependent K+ (Kv) channels using freshly isolated coronary artery smooth muscle cells from rabbits. The Kv current amplitude was progressively inhibited by propafenone in a dose-dependent manner, with an apparent IC50 value of 5.04±1.05 µM and a Hill coefficient of 0.78±0.06. The application of propafenone had no significant effect on the steady-state activation and inactivation curves, indicating that propafenone did not affect the voltage-sensitivity of Kv channels. The application of train pulses at frequencies of 1 or 2 Hz progressively increased the propafenone-induced inhibition of the Kv current. Furthermore, the inactivation recovery time constant was increased after the application of propafenone, suggesting that the inhibitory action of propafenone on Kv current is partially use-dependent. Pretreatment with Kv1.5, Kv2.1 or Kv7 inhibitor did not change the inhibitory effect of propafenone on the Kv current. Together, these results suggest that propafenone inhibits the vascular Kv channels in a dose- and use-dependent manner, regardless of Na+ channel inhibition.

Simultaneous determination of serum propafenone and its metabolites using high-performance liquid chromatography.

Propafenone, a class Ic antiarrhythmic agent, is metabolized to 5-hydroxypropafeone (5-OHP) and N-depropylpropafenone (NDPP). Simultaneous determination of serum propafenone and its metabolites was performed using HPLC equipped with a conventional octadecylsilyl silica column and ultraviolet detector. The wavelength was set at 250 nm. Propafenone and its metabolites in the serum were extracted using diethyl ether. The mobile phase solution, comprising 1-pentanesulfonic acid sodium salt (0.1m), acetonitrile and acetic acid (280:185:2.5, v/v/v), was pumped at a flow rate of 1 mL/min. The recoveries of propafenone, 5-OHP and NDPP were greater than 85, 82 and 60%, respectively, with the coefficients of variation (CVs) less than 5.4, 1.9 and 2.9%, respectively. The calibration curves were linear for a concentration range of 12.5-1500 ng/mL for propafenone and 2-500 ng/mL for 5-OHP and NDPP (r > 0.999). CVs in the intraday assays were 1.0-3.8% for propafenone, 0.6-2.0% for 5-OHP and 0.6-1.7% for NDPP. CVs in interday assays were 1.3-7.7% for propafenone, 1.1-6.5% for 5-OHP and 5.4-8.0% for NDPP. The present HPLC method can be used to assess the disposition of propafenone and its metabolites for pharmacokinetic studies and therapeutic drug monitoring of propafenone.

Efficacy of Intravenous and Oral Sotalol in Pharmacologic Conversion of Atrial Fibrillation: A Systematic Review and Meta-Analysis

Objectives: The role of sotalol is well established for the maintenance of sinus rhythm after successful conversion of atrial fibrillation (AF). However, its role in pharmacologic conversion of AF is poorly defined. The purpose of this study is to compare the efficacy of sotalol to that of other antiarrhythmic agents for AF conversion. Methods: Standard methods of meta-analysis were employed. Full-text publications of clinical trials in English that compared the efficacy of sotalol to that of other antiarrhythmics or placebo/no treatment were eligible for inclusion. Results: A systematic review revealed 10 eligible publications. Sotalol was superior to placebo and/or no antiarrhythmic therapy in AF conversion, with a relative success of 24 (95% CI 4.7-119, p < 0.001). Sotalol was not significantly different from class IA antiarrhythmic drugs. Similarly, sotalol was not different from class IC antiarrhythmic drugs or amiodarone in terms of conversion efficacy. In one study, sotalol was less effective than high-dose ibutilide (2 mg), with a relative success of 0.248 (95% CI 0.128-0.481, p < 0.001). Ibutilide caused more proarrhythmia. Conclusions: Sotalol is as effective as class IA and class IC antiarrhythmic agents, and it is also as effective as amiodarone for pharmacologic conversion of AF. Only ibutilide at a high dose showed a greater conversion rate of AF.

Could Propafenone hydrochloride Cause Visual Hallucination?

Introduction: There may be some cardiac and non-cardiac side effects of propafenone hydrochloride, which is a class IC antiarrhythmic agent used for medical cardioversion in atrial fibrillation and atrial flutter. Case Report: Propafenone hydrochloride (600 mg) was orally administered to a 74-year-old patient with tachycardia due to new-onset atrial fibrillation with rapid ventricular response. After 30 min, sinus bradycardia in response to atropine, swelling and numbness in the tongue, slurred speech, blurred vision, diplopia, spasm and contradiction at the right arm and leg, drowsiness, and visual hallucinations lasting for 24 h developed. The patient recovered without any sequel and was discharged from the coronary intensive care unit. Conclusion: Although propafenone hydrochloride is known to be safe at therapeutic doses, various possible multiple side effects should be considered.

Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart

Objectives: Flecainide is class Ic antiarrhythmic agent that was found to increase the risk of sudden cardiac death. Arrhythmic responses to flecainide could be precipitated by exercise, suggesting a role played by inappropriate rate adaptation of ventricular repolarization. This study therefore examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length. Design: ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation. Results: Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged ventricular repolarization, delayed its rate adaptation, and decreased the amplitude of QT interval and APD shortening upon rapid cardiac pacing. During extrasystolic stimulation, flecainide attenuated APD shortening in premature ventricular beats, with effect being greater upon using a longer basic drive cycle length (S1-S1=550 ms versus S1-S1=300 ms). Conclusions: Flecainide-induced arrhythmia may be partly accounted for by attenuated adaptation of ventricular repolarization to sudden changes in cardiac cycle length provoked by transient tachycardia or ectopic beats.

Wide QRS Tachycardia in a Dual Chamber Pacemaker Patient: What is the Mechanism?

A 67-year-old man with a DDD pacemaker for complete atrioventricular block had dyspnea with cardiomegaly on a chest radiogram. Additionally, he had atrial fibrillation, which was well controlled with a class Ic antiarrhythmic agent. He had chronic kidney disease; therefore, uremic pericardial effusion was highly suspected, and pericardiostomy was performed. During surgery, the pacemaker mode was temporarily set to DOO to avoid electrical interference. After surgery, dyspnea was relieved, but it recurred 2 days later without aggravated pericardial effusion. An electrocardiogram showed wide QRS tachycardia at 150 beats per minute. What is the mechanism?

Propafenone shows class Ic and class II antiarrhythmic effects.

Propafenone is a well-known Class Ic antiarrhythmic agent. It has the typical chemical structure of a beta-blocker, but human studies on its beta-blocking effects revealed conflicting results. Twelve healthy males received single oral doses of 600 mg propafenone and placebo according to a randomized, double-blind, placebo-controlled, cross-over protocol. Four hours following drug intake, heart rate and blood pressure were measured, and plasma concentrations of propafenone were determined at rest, during exercise and after recovery. At exercise, propafenone significantly decreased heart rate (-6%, P < 0.05), systolic blood pressure (-6%, P < 0.05), and the rate-pressure product (-11%, P < 0.05). Plasma concentrations of propafenone increased during exercise (+23%, P < 0.05) and decreased during recovery (-33%, P < 0.05). Both effects on heart rate and blood pressure as well as the changes of plasma concentrations of propafenone during exercise represent two particular features of beta-blockers. Therefore, we conclude that propafenone is both a Class Ic and a Class II antiarrhythmic agent, and 600 mg propafenone, i.e. the dose recommended in current guidelines for cardioversion of paroxysmal atrial fibrillation, cause clinically significant beta-blockade. Thus, single oral doses of 600 mg propafenone appear also suitable for cardioversion of paroxysmal atrial fibrillation in patients with structural heart disease since beta-blockers are explicitly indicated in the treatment of both coronary artery disease and heart failure.

Utility of Routine Exercise Testing to Detect Rate-Related QRS Widening in Patients Without Structural Heart Disease on Class Ic Antiarrhythmic Agents (Flecainide and Propafenone)

Class Ic antiarrhythmic agents are effective in the treatment of various atrial tachyarrhythmias. They are known to cause rate-related QRS widening in the presence of structural heart disease, which can lead to life-threatening arrhythmias. The role of routine exercise electrocardiography in patients without structural heart disease is unknown. All patients initiated on class Ic antiarrhythmic agents and who had exercise electrocardiography performed from June 2009 to June 2013 were included. Symptom-limited treadmill electrocardiography was performed to detect significant QRS widening at peak exercise (defined as an increase of >25% of baseline QRS). Fifty-six patients were included in the study. All patients were screened for structural heart disease before initiation of the medication. Significant QRS widening and atrial tachycardia occurred in a single patient, which terminated with cessation of exercise. This patient had a history of tachycardia-mediated cardiomyopathy with normalization of ejection fraction 3 years before being placed on flecainide. In conclusion, routine exercise testing to detect QRS widening is not warranted in patients with no structural heart disease.