Effectiveness and Safety Profiles of Vernakalant for Cardioversion of Acute-onset Atrial Fibrillation: A Systematic Review and Meta-analysis

PurposePharmacologic cardioversion is an effective clinical strategy for fibrillation. Vernakalant is a novel drug used to treat atrial fibrillation (AF). This study aimed to evaluate the efficacy- and tolerability-related data on vernakalant from clinical trials.MethodsLiterature from PubMed and the Cochrane Library was systematically reviewed, and 139 eligible studies were found after specific key words were identified. Twelve randomized clinical trials discussing vernakalant cardioversion in patients with AF were chosen for the meta-analysis after scrutiny. Ten of the 12 trials used placebo while two reported data on active and established drugs to compare the effects of vernakalant. Three of the 12 trials included relevant clinical states in addition to AF.FindingsIn this meta-analysis of data from 12 studies (2365 patients, 887 events), the rate of cardioversion from AF to sinus rhythm (SR) was significantly greater with vernakalant compared with placebo and active comparators (risk ratio = 5.60; 95% CI, 2.83–11.09; I² test for heterogeneity, 92%). Tolerability-related data revealed that dysgeusia, paresthesia, atrial flutter, and hypotension were major adverse events that occurred with vernakalant use, but the data were not clinically significant compared to placebo and active drug (risk ratio = 1.13; 95% CI, 0.86–1.47). Eleven deaths were reported in 4 trials, with vernakalant directly implicated in two deaths. Vernakalant was well tolerated and effective in patients with rapid-onset AF.ImplicationsVernakalant appears to be a good choice when AF is manifested postoperatively or exists with ischemic heart disease and valvular states. Tolerability-related data are promising, but a specific trial may be required to identify the causes of the deaths considered unrelated to vernakalant use.     

Efficacy of Biphasic Shock for Transthoracic Cardioversion of Persistent Atrial Fibrillation:

Although electrical cardioversion of atrial fibrillation (AF) is frequently performed, initial energy requirements for cardioversion of persistent AF is still a matter of debate. The aim of the study was to determine the efficacy of biphasic shocks for transthoracic cardioversion of persistent AF and to predict adequate initial energy. A prospective study enrolled 94 consecutive patients with persistent AF, who were referred for elective cardioversion with a biphasic waveform. The paddles were placed in the anterolateral position. A step-up protocol was used to estimate the cardioversion threshold. The initial shock energy was 50 J, with subsequent increments to 100, 200, and 300 J in the event of cardioversion failure. The mean age of the study group was of about 65 years (6 ± 11 years) and a median duration of AF was 65 days (3–324). Sixty-two out of 94 patients were men, 55% of the study population was classified as having well-controlled hypertension. The overall success rate of cardioversion was 89%, with a mean 2.2 ± 1.4 shocks, and effective J 217.8 ± 113 delivered during repeated cardioversions. The success rate of low energy shocks: 50 and 50 +100 J was 51%. By logistic regression analysis the only independent predictor of success at low energy shock was shorter duration of AF (r =−0.51; P = 0.02). Patients with shorter duration of AF have a higher probability for successful cardioversion with low energy. In patients with longer AF duration, a 200 J shock should be considered for cardioversion as the initial energy. (PACE 2004; 27[Pt. I]:764–768)     

Hot Off the Press: Chemical Versus Electrical Cardioversion for Atrial Fibrillation

Atrial fibrillation (AF) is a significant dysrhythmia that often requires treatment in the emergency department (ED). This can be performed with rhythm control using electrical or chemical cardioversion or with rate control. There is widespread variation in management of AF within Canada and worldwide. This study focuses on rhythm control techniques, comparing ED length of stay when using an electrical‐first strategy versus a chemical‐first strategy of cardioversion.     

口服普罗帕酮与胺碘酮联合电复律转复持续性房颤的随机对照试验

目的比较普罗帕酮与胺碘酮联合电复律转复持续性心房颤动及维持窦性心律的疗效与安全性。方法将60例基础疾病治疗良好的持续性房颤患者随机分为两组,每组各30例。普罗帕酮组:普罗帕酮600mg顿服后观察6h,未转复者予电复律,并以最低有效量口服维持窦律;胺碘酮组:胺碘酮600mg分3次口服,连服7天,未转复者电复律,以最低有效量维持窦律。结果单纯药物复律,普罗帕酮组4例,胺电酮组3例,联合电复律两组分别转复25例和22例,两组早期有效率分别为90.0%和80.0%,晚期有效率分别为73.3%和70.0%,两组比较差异无统计学意义。住院时间普罗帕酮组短于胺碘酮组(P<0.001)。普罗帕酮组1例服药后出现一过性低血压,放弃复律,经对症治疗后好转;胺碘酮组4例服药后恶心、呕吐,未能坚持负荷量连服7天;但两组副反应发生率差异无统计学意义。结论普罗帕酮与胺碘酮联合电复律治疗持续心房颤动安全而有效,但普罗帕酮起效快,可相对减少患者的住院时间。     

Ventricular Pauses during Atrial Fibrillation Predict Relapse after Electrical Cardioversion: A Prospective Study

Aims: To investigate the use of ambulatory electrocardiogram (ECG) monitoring in atrial fibrillation (AF) to predict recurrence after electrical cardioversion (ECV). Methods: RR interval variables were obtained from 24 hours ECGs recorded before ECV in 119 patients (85 men, age 66 ± 10 years) with persistent AF. Patients were followed for 1 month. Results: Of the 119 patients, 16 (13%) failed ECV and 65 (55%) were in AF at 1 week and 81 (68%) at 1 month after ECV. The maximum RR interval (RR‐max) and the minimum RR interval (RR‐min) during AF were found to be reproducible. The RR‐max was longer in those who had AF 1 week (2.55 ± 0.49 vs 2.01 ± 0.52 seconds, P = 0.005) and 1 month (2.56 ± 0.50 vs 1.89 ± 0.43 ms; P < 0.001) after ECV than in those who maintained sinus rhythm. Those in AF at 1 month included more patients with RR‐max ≥ 2.8 seconds (31% vs 11% P = 0.021). The average heart rate was lower in patients with RR‐max ≥ 2.8 seconds, but the average rate was not predictive of AF recurrence. Conclusion: Ventricular pauses during AF predict relapse after ECV. (PACE 2010; 934–938)     

Rounded Biphasic Waveform Reduces Energy Requirements for Transvenous Catheter Cardioversion of Atrial Fibrillation and Flutter

We postulated that reducing peak leading edge shock voltage and its rate of rise (waveform rounding) would reduce energy requirements for cardioversion of AF and AFI, and may therefore reduce patient discomfort. Transvenous defibrillating catheters (In-Control Inc.) were placed in the RAA (active fixation) and the CS of six anesthetized sheep. AF or AFI was induced by electrical stimulation (100 Hz, 2 V; Grass stimulator). A standard trapezoidal biphasic (S) waveform (3-ms duration each phase) was compared with a similar waveform that had the first phase rounded (R). Cardioversion was attempted after 30 seconds of arrhythmia, using a Ventritex HVS-O₂ defibrillator modified to allow waveform rounding. Each waveform was randomly tested several times at 100-, 150-, and 200-V leading edges, and percentage cardioversion success calculated. Shock energy was calculated from delivered current and voltage using Flukeview (Fluke, Inc.) software. At 100-V leading edge R (64% success) and S (59%), shocks were similarly efficacious (P = 0.37). However. R delivered less current, voltage, and energy than the comparable S shock (means 1.30 A, 65.0 V, 0.33 J R vs 1.92 A, 94.2 V, 0.47 J S; P = 0.0001). Both waveforms were equally successful at 150 V (88% vs 100%; P = NS) and 200 V(100% vs 100%), but again R delivered less current, voltage, and energy (2.05 A, 102.5 V, 0.82 J R vs 2.78 A, 142.3 V, 1.11 J S at 150 V; 2.76 A, 141.2 V, 1.58 J R vs 3.77 A, 189.4 V, 2.03 J S at 200 V; both P = 0.0001). No arrhythmic or other complications occurred in the 174 shocks delivered. Waveform rounding reduces delivered peak voltage, current, and energy without reducing defibrillation efficacy. To determine if these changes are associated with a reduction in discomfort, patients with AF are currently being cardioverted with these waveforms during electrophysiological studies.     

Ventricular Fibrillation Following Successful DC Cardioversion for Atrial Fibrillation

Cardioversion remains an important therapy in the management of atrial fibrillation. Here, we report a case where direct current cardioversion resulted in a sudden dramatic change of heart rate that was associated with multiple ventricular fibrillation arrests in a manner akin to that previously observed post-atrioventricular node ablation. (PACE 2012;35:e361-e364).     

Cardioversion for Atrial Fibrillation: Treatment Options and Advances

Atrial fibrillation (AF) is associated with significant morbidity and mortality. There are two basic approaches to managing AF: slowing the ventricular rate, while allowing the arrhythmia to continue (the rate-control approach), and restoring and maintaining sinus rhythm (the rhythm-control approach) with antiarrhythmic drugs (AADs) and/or ablation, electrical cardioversion (CV), if needed, or both. Strategy trials comparing rate and rhythm control have found no survival advantage of one approach over the other, but other considerations, such as symptom reduction, often necessitate pursuit of rhythm control. Electrical, or direct current, CV is a widely used and effective method for termination of nonparoxysmal AF, although its success can be affected by patient- and technique-related variables. Pharmacological CV options also exist and are preferable in specific circumstances. Both pharmacological and electrical CV are associated with the risk of proarrhythmia. Many AADs are under development for both CV and maintenance of sinus rhythm. Some are atrioselective, such as vernakalant, and target ion channels in the atria, with little or no effects in the ventricle. Vernakalant, currently under Food and Drug Administration review, appears to offer a safer profile than current CV agents and is likely to expand the role of pharmacological CV. Other new AADs that provide increased efficacy or safety while maintaining normal sinus rhythm may also be better than current drugs; if so, rate-rhythm comparisons will differ from those of previous studies. In conclusion, further trials should clarify the long-term safety profiles of new atrioselective agents and other investigational drugs and define their role in the treatment of AF.     

Multiple Shocks Affect Thoracic Electrical Impedance During External Cardioversion of Atrial Fibrillation

Background: Thoracic impedance (TI) influences the success of external cardioversion (ECV) or defibrillation because current intensity traversing the heart is inversely related to TI. Experimental data suggest that TI decreases after multiple shocks. We undertook a clinical study to determine changes of TI values in patients with atrial fibrillation or flutter requiring ECV. Methods: We enrolled 222 consecutive patients (age 73 ± 11 years; males 67%; body weight 75 ± 13 kg) who underwent ECV between January 2004 and February 2007. Biphasic shocks were delivered through adhesive pads placed in the anteroposterior position. The initial energy was set at 1 J/kg, with progressive increases up to a maximum of 180 J in case of failure. In the last 39 elective patients, plasma concentration of interleukin‐6 (IL‐6) and tumor necrosis factor (TNF)‐α were determined before and 6 hours after ECV. Results: Sinus rhythm was restored in 202 patients (91.0%). Of these, 155 (69.8%) required more than one shock (on average, 2.5 ± 1.5 shocks/patient). Final values of energy and peak current intensity were 136 ± 47 J and 50 ± 14 A, respectively. TI decreased significantly by 6.2% from baseline after ≥2 shocks (P < 0.001). The absolute reduction was correlated with baseline TI, number of delivered shocks, and hemoglobin oxygen saturation. IL‐6 and TNF‐α increased with ECV (P < 0.001 and P = 0.014, respectively). Conclusions: TI decreases significantly after multiple shocks, possibly by activation of acute inflammation.     

Outpatient Electrical Cardioversion of Atrial Fibrillation: 8 Years' Experience. Analysis of Shock-Related Arrhythmias

Background: Outpatient electrical cardioversion (EC) of atrial fibrillation is currently the standard of care. Shock-related arrhythmias may be particularly deleterious in this setting. Preoperative identification of high-risk patients may be very useful.
Methods: A retrospective analysis was made of 543 consecutive elective EC procedures in 457 outpatients over an 8-year period in a university cardiological institute. The protocol included adequate anticoagulation, intravenous anesthesia, direct current shock, and a direct observation after a shock to detect procedure-related complications. No patients were excluded due to severity of pathology or comorbidities. Clinical characteristics, energy delivered, medications, arrhythmic phenomena, and predictors of success and complications were analyzed.
Results: Of 543 ECs performed, 88.2% restored sinus rhythm, which persisted at discharge in 83.2%. No anesthesia-related complications were detected. No thromboembolic complications were detected. Use of a biphasic cardioverter was the only predictor of success (P = 0.0001). The bradyarrhythmic complication rate was 1.5%. No ventricular arrhythmic events were detected. Atrial flutter was present in five of eight patients who developed complications versus 44 of 535 patients who had no complications (P < 0.0005), and prosthetic heart valves in four of eight complicated versus 40 of 535 uncomplicated cases (P = 0.0044). The combination of atrial flutter and prosthetic heart valve was found in four of eight complicated versus 11 of 535 uncomplicated cases (P < 0.0005).
Conclusion: Shock-related arrhythmias are essentially bradyarrhythmias. Atrial flutter and previous cardiac surgery identify a subgroup of patients at high risk of postshock bradyarrhythmic complications.     

Safety of High Energy Internal Cardioversion for Atrial Fibrillation

High energy internal cardioversion has been proposed as an alternative method to cardiovert drug refractory or external cardioversion refractory atrial fibrillation. However, the safety of this technique has not been clearly evaluated. We reviewed findings in 53 patients who underwent 55 sessions of high energy internal cardioversion (2 patients underwent 2 sessions] for termination of longstanding atrial fibrillation. Shocks energy varied from 70–270 J. Three patients had 3 shocks during the same session, 5 had 2, and 47 only 1. Success rate was 89% (success was defined as immediate conversion to normal sinus rhythm).
Low cardiac output occurred in two patients, and resulted in the death of one of these individuals, a patient with significant hypertrophic cardiomyopathy and heart failure. The other patient recovered completely. In 11% of the cases, shock induced transient atrioventricular block, necessitating ventricular pacing until sinus rhythm was restored. In three patients, a moderate but asymptomatic and uncomplicated pericardial effusion was diagnosed on echocardiogram. Finally, four patients had side effects related to venous puncture, which resolved spontaneously. These results suggest that high energy internal cardioversion is effective for conversion of atrial fibrillation. However, the technique may not be optimal in patients with advanced hypertrophic cardiomyopathy and in such cases the technique should be used carefully and only in the case of failure of external cardioversion; no more than two shocks should be delivered during the same procedure. Temporary ventricular pacing should be provided in all patients and an echocardiogram should be performed before patients are being discharged.     

Efficacy of Dronedarone Versus Propafenone in the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation After Electrical Cardioversion

Purpose

Our objective was to compare the efficacy of dronedarone and propafenone in maintaining sinus rhythm in patients with atrial fibrillation (AF) after electrical cardioversion.

Methods

In this single-center, open-label, randomized trial, we randomly assigned patients with AF after electrical cardioversion to receive dronedarone 400 mg BID or propafenone 150 mg TID.Follow-up clinical evaluations were conducted at 1, 2, 3, and 6 months of treatment. The primary end point was the time to the first recurrence of AF.

Findings

A total of 98 patients were enrolled (79 men; mean age, 59.2 years; n = 49 per group). The median times to first recurrence of AF were 31 days in the dronedarone group and 32 days in the propafenone group (P = 0.715). The median (interquartile range) ventricular rates at first recurrence of AF were 76.5 (67.3–86.5) beats/min in the dronedarone group and 83.0 (71.0–96.0) beats/min in the propafenone group (P = 0.059).

Implications

Dronedarone and propafenone had similar efficacies in maintaining sinus rhythm in patients with AF after electrical cardioversion. The ventricular rate at the first recurrence of AF was numerically but not statistically significantly lower in the dronedarone group than in the propafenone group. ClinicalTrials.gov identifier: NCT01991119.     

Quadruple Pads Approach for External Cardioversion of Atrial Fibrillation

MARROUCHE, N.F., et al. : Quadruple Pads Approach for External Cardioversion of Atrial Fibrillation. This study examined the alternative of transthoracic quadruple pads shock delivery of two simultaneous 360-J shocks to convert refractory AF in patients failing standard external cardioversion. Forty-six patients (  mean age 58 ± 11 years, 23 men  ) with chronic AF (  duration 14 ± 17 months, range 1–60 months  ) were included. The left atrial diameter was  47 ± 7 mm  . The left ventricular ejection fraction was  59 ± 11%  . Antiarrhythmic drugs had failed to convert 44 (96%) of these patients. All patients underwent conventional external transthoracic cardioversion with pads applied in the antero-apical position using energy settings of 200 and 360 J, consecutively. In all patients who failed conventional cardioversion, quadruple pads were applied. Quadruple pads consisted of four pads, two in the antero-posterior position and two in a second apex-posterior position. Standard cardioversion to sinus rhythm was successful in 19 (41%) patients after use of a single 200-J shock and an additional 8 (17%) after a single 360-J shock. The total success rate was 58% after conventional cardioversion. The quadruple pads were successful in 14 (74%) of the remaining 19 patients. Four of the five patients who failed the quadruple pads approach subsequently also failed internal cardioversion. Thus, the cardioversion success rate was increased from 48% using the conventional approach to 89% using the quadruple pads approach. Quadruple pads external cardioversion is highly effective in converting chronic AF refractory to standard shock protocols to sinus rhythm. Moreover, the failure of the quadruple pads approach seems to predict poor response to internal cardioversion.     

The Induction of Atrial Flutter and Fibrillation and the Termination of Atrial Flutter by Esophageal Pacing

In patients with Wolff-Parkinson-White syndrome (WPW), it is important to assess the ventricular response during atrial flutter or fibrillation since conduction across the accessory pathway during these atrial rhythms may cause hemodynamic impairment or life-threatening ventricular arrhythmias. We have recently reported the effective use of an esophageal electrode in pacing the atrium. In this study we praspectively assessed the ability to induce atrial flutter and fibrillation by esophageal pacing in 23 patients with WPW or other electrophysiological abnormalities. An esophageal bipolar electrode with 29 mm interelectrode distance was positioned in the esophagus to record the most rapid and largest esophageal electrogram (mean distance of 36.6 ± 2.9 cm (SD) from the nares). Pacing was performed at cycle lengths of 40–340 ms (mean 166 ± 72), pulse durations of 7.0–9.9 ms, and currents of 10–25 mA. Atrial flutter alone was induced in 6 patients, fibrillation alone in 11 patients, and both arrhythmias in 5 patients, In one patient neither flutter nor fibrillation was induced by esophugeal pacing, and fibrillation was induced only with difficulty using intracavitary pacing. Of the 11 patients with flutter, the arrhythmia was terminated in 8 by esophageal pacing at cycle lengths of 160–220 ms fmean 176 ± 18 ms). All patients tolerated the procedure well with only mild to moderate discomfort. Therefore, esophageal pacing appears to offer an effective, well tolerated method of initiating atrial fibrillation and flutter and terminating atrial flutter and offers a potentially useful noninvasive method of following patients serially.