Álvaro Lozano

Ivabradine as an Alternative to AV Node Ablation in a Patient With Permanent Atrial Fibrillation

For patients with atrial fibrillation (AF) to respond adequately to cardiac resynchronization therapy, ventricular rate should be strictly controlled to ensure the biventricular pacing rate is as close to 100% as possible. For this control, drugs are used that block atrioventricular (AV) conduction. When these fail, atrial node ablation is indicated, although this makes the patient pacemaker dependent. We present the case of a patient with AF with an implanted cardiac resynchronization device, in whom ivabradine was used as an alternative to AV node ablation for heart rate control. The 60-year old male patient had received a prosthetic mitral valve replacement as treatment for rheumatic mitral stenosis. He was in permanent AF with left bundle branch block. During followup, he showed severe systolic left ventricular dysfunction and heart failure in the absence of coronary lesions. A cardiac resynchronization therapy defibrillator was required. During postimplantation follow-up, 74% biventricular pacing was observed despite bisoprolol escalation to the maximum tolerated dose (5 mg/12 h) and device programming in VVIR mode with a minimum rate of 70 bpm. Digoxin was not administered due to a history of digitalis toxicity and renal failure. Before considering AV node ablation, we decided to try ivabradine (5 mg/12 h). Eleven days later, the device showed a biventricular pacing rate of 95% (Figure). In subsequent follow-up 1 month after Ivabradine initiation, pacing was maintained at 96% and therefore ablation was not required. Ivabradine is an inhibitor of If current, which is the main determinant of sinus node discharge rate. The beneficial effect as a drug that slows heart rate in patients with sinus rhythm has been clearly demonstrated, both in coronary artery disease and in heart failure. However, the sodium channel that controls If current is not located exclusively in the sinus node but is also present in high concentrations both in the compact AV node and in the posterior nodal extension. In addition to determining the automaticity of the subsidiary sinus node pacemaker, If current also seems to be directly related to the conduction properties of the AV node (impulse conductivity). In a clinical trial administering either an If current inhibitor (zatabradine) or placebo to patients without structural heart disease, active treatment induced a significant increase in the electrophysiological parameters of node conduction (AH interval, AV nodal effective refractory period, and Wenckebach cycle length). More recently, ivabradine has also been found to exercise this depressor effect on node conduction. In an animal model published by Verrier et al., ivabradine administration during paced atrial rhythm led to a lengthening of the PR and AH intervals. This was more marked at rapid atrial pacing rates (use dependence) without affecting His-Purkinje system conduction or QT interval. When the drug was administered during AF, decreased ventricular response was observed without affecting the dominant atrial rates. There is less extensive experience with ivabradine as a drug for controlling ventricular response during AF in humans. In a small case series, oral administration of ivabradine improved control of ventricular response and functional capacity in 4 of the 6 patients with rapid AF, despite treatment with beta blockers. More recently, a clinical trial with 32 patients with AF showed that ivabradine significantly decreased average and maximum heart rates compared with placebo, with no relevant changes in minimum heart rate after 1 month of treatment. Very few drugs are available to control heart rate for patients with ventricular dysfunction and therefore AV node ablation is often indicated. The safety of ivabradine, demonstrated in large clinical trials in patients at risk (coronary artery disease and heart failure), in conjunction with the lack of vasodilatory effects or myocardial contractility depression, make it a promising option for control of ventricular response in patients with AF. The inclusion of

ECG de septiembre de 2016

A 24-year-old man was referred for study. He had experienced syncope twice after getting up at night, during voiding. He had no medical history of interest. His mother had been diagnosed with vasovagal syncope, but there was no history of sudden death in the family. The physical examination and transthoracic echocardiography findings were normal. A baseline electrocardiogram was recorded (Figure 1). The abnormalities observed prompted an intravenous drug challenge with flecainide (Figure 2). What would your diagnosis be?

Ivabradine as an Atrioventricular Node Modulator. Promise or Reality? Response

First, we would like thank Dr Álvarez-Acosta et al. for their comments, which we will try to address here. In accordance with the relevant guidelines, we routinely implant cardiac resynchronization devices to treat heart failure in optimally treated and nondecompensated patients. Our patient was stable at the time of implantation and his heart rate, although controlled, was insufficient to guarantee an adequate pacing percentage. Nevertheless, simply implanting a resynchronization device in a patient with heart failure rarely confers a clinical improvement in subsequent weeks if the biventricular pacing percentage is only about 70%. It would be as incredible as a drug left untouched by a patient in a bedside drawer exerting a clinically relevant effect. Because we can rule out an ‘‘inherent improvement’’ from a resynchronization device unable to achieve adequate pacing and there were no changes in any other treatment between the 2 consecutive revisions, we must delve into the eventual role of ivabradine in our patient’s heart rate control. The criteria of causation include temporality, biological plausibility (there is a high-density If current in the atrioventricular node), analogy (ivabradine reduces heart rate during atrial fibrillation in animals), and experiment (ivabradine decreased heart rate in atrial fibrillation vs placebo in a human trial). If the pacing percentage were to decrease after ivabradine withdrawal, our hypothesis would be strengthened but such an approach would be ethically questionable. The possible effects of ivabradine on heart rate are in no way ruled out by the publications on ivabradine, which make no mention of this mechanism of action. However, it is not necessary to turn to rare genetic mutations to explain the inhibitory effect of ivabradine on node conduction because the United States prescribing information for this drug states that first-degree atrioventricular block is a frequent adverse reaction. We would also like to take this opportunity to report that the same effect on percentage of pacing was seen in another patient administered ivabradine in the same clinical setting. Promises can become reality if we are proactive in the search for therapeutic options by not only researching new molecules, but also by exploring new indications for existing ones.

The Usefulness of Vernakalant in Maintaining Sinus Rhythm During Ablation Procedures

The onset of atrial fibrillation (AF) when ablation is performed during an electrophysiology study (EPS) hinders and prolongs the procedure. The incidence of AF varies according to the underlying disease and the aggressiveness of the stimulation protocol, but rates of up to 10% have been described. Since persistent AF makes it impossible to perform an ablation during an EPS in some substrates, cardioversion (CV) is required to restore sinus rhythm. Pharmacological CV is less effective than electrical CV and also modifies the electrophysiologic properties of tissues, which can cause unsuccessful induction of clinical arrhythmia. As a result, electrical CV has become the method of choice. Vernakalant is an antiarrhythmic agent indicated in the conversion of recent-onset AF to sinus rhythm. Its antiarrhythmic effect stems from the selective inhibition of potassium channels IKur and IKAch that are specific to the atrial myocardium. Vernakalant causes a frequencyand voltage-dependent block of the sodium channels, also predominantly in the atrium. Its rapid conversion of recent-onset AF to sinus rhythm and selective action on the atrial myocardium makes it a good candidate for use in the electrophysiology laboratory. We present our experience of using vernakalant for conversion of AF induced during an EPS. To our knowledge, this is the first prospective series describing the use of vernakalant in this context. Since November 2011, we have administered vernakalant to 19 consecutive patients with AF induced during an EPS. At the start of the EPS, all patients were in sinus rhythm and AF appeared during catheter manipulation or during the atrial stimulation protocol. After 10 minutes of persistent arrhythmia, we administered vernakalant as the first option in 15 patients (78.9%) and on AF recurrence after effective electrical CV in the other 4 patients (21.1%). We administered the drug by intravenous infusion as recommended in the Summary of Product Characteristics. Conversion to sinus rhythm was achieved within 35 minutes of the start of the infusion in 10 patients (52.6%). Mean time to conversion was 9.9 min 4.0 minutes. Of the 9 remaining patients, 6 (31.6%) remained in AF and underwent electrical CV, which was successful in all patients. The AF organized into sustained typical atrial flutter in 1 patient (5.3%) and into left atrial flutter in 2 (10.5%). Since these arrhythmias matched the patients’ clinical symptoms, we decided to continue the study. As a result, we avoided performing electrical CV in 13 of the 19 patients (68.4%). Atrial fibrillation did not recur in any patients after the administration of vernakalant and the EPS and ablation were successfully completed. Patient response to vernakalant is summarized in the Figure. At the start of the study, clinical arrhythmia was induced in 11 patients (57.9%): 3 typical nodal reentrant tachycardias, 2 focal atrial tachycardias arising from the right atrium, 2 left atrial flutters, and 4 typical atrial flutters. In all patients, tachycardia could still be induced after administering vernakalant. Ablation was completed successfully in 10 patients and failed in 1 patient with left atrial flutter. The 8 patients (42.1%) with predocumented typical atrial flutter directly received ablation across the cavotricuspid isthmus and we achieved bidirectional conduction block in all patients. After a mean follow-up of 9.6 months 11.3 months, clinical arrhythmia recurred only in the 1 patient in whom ablation had failed. Patient baseline characteristics are shown in the Table, grouped by response to vernakalant. A clinical history of AF (36.4% vs 75%; P = .170) was associated with a lower rate of pharmacological conversion, without attaining statistical significance. Our multivariable analysis found no predictors of lack of response. Previous publications have reported that ventricular dysfunction (left ventricular ejection fraction < 55%) and structural heart disease are predictors of lack of response. Our series found no association between these factors and a lower conversion rate. Our results may be explained by the small sample size and low prevalence of these particular factors.

Change in the Grade of Preexcitation and Progressive Prolongation of S-Delta Interval: What Is the Mechanism?

A 37-year-old female basketball player without structural heart disease was referred to our center for electrophysiological evaluation, due to a history of palpitations and preexcitation. Three tetrapolar catheters were placed in the coronary sinus (CS), His bundle region and right ventricular apex (RVA). This article is protected by copyright. All rights reserved.

Change in the Grade of Preexcitation and Progressive Prolongation of S‐Delta Interval

A 37-year-old female basketball player without structural heart disease was referred to our center for electrophysiological evaluation, due to a history of palpitations and preexcitation. Three tetrapolar catheters were placed in the coronary sinus (CS), His bundle region and right ventricular apex (RVA). This article is protected by copyright. All rights reserved.

Response to ECG, September 2014

Flecainide administration produced a lengthening of the PR interval and disappearance of the abnormal Q waves observed in V1-V3. This occurred because the drug interrupted conduction through a right free wall accessory pathway that was causing the pre-excitation seen on the baseline electrocardiogram, leaving a right bundle branch block pattern. Nonetheless, the finding of this accessory pathway likely does not explain the mechanism causing the syncopes, which appear to be situational. Rev Esp Cardiol. 2014;67(10):853