J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 11, Number 5, May 2019, pages 345-352

High Prevalence of Proarrhythmic Events in Patients With History of Atrial Fibrillation Undergoing a Rhythm Control Strategy: A Retrospective Study

Figure 1. The respective percentages of events of proarrhythmia, depending on the type of drug antiarrhythmic treatment for prophylaxis of AF relapses, are depicted (purple bars). AF: atrial fibrillation; IC: antiarrhythmics belonging to class IC of Vaughan Williams classification; BB: beta-blockers; amio: amiodarone; quin: hydroquinidine; dig: digoxin.

Figure 2. The respective percentages of events of atrial proarrhythmia, depending on the type of drug antiarrhythmic treatment for prophylaxis of AF relapses, are reported (purple bars). The histograms refer to two atrial proarrhythmia events with important clinical correlates, namely the second- or third-degree sino-atrial block (left panel) and the atrial flutter with AV 1:1 conduction (right panel). AF: atrial fibrillation; AFL: atrial flutter; AV: atrioventricular; IC: antiarrhythmics belonging to class IC of Vaughan Williams classification; BB: beta-blockers; amio: amiodarone; quin: hydroquinidine; dig: digoxin.

Figure 3. The respective percentages of torsades de pointes and type 2 second-degree AV block, depending on the type of drug antiarrhythmic treatment for prophylaxis of AF relapses, are represented (purple bars). All of the cases of type 2 second-degree AV block (n. 14) are attributable to IC + BB therapy. As regards the torsades de pointes the risk appears to be more pronounced when using hydroquinidine plus digoxin (33.3%) or sotalol (23.57%). AV: atrioventricular; IC: antiarrhythmics belonging to class IC of Vaughan Williams classification; BB: beta-blockers; amio: amiodarone; quin: hydroquinidine; dig: digoxin.

Figure 4. The respective percentages of sustained monomorphic ventricular tachicardia, depending on the type of drug antiarrhythmic treatment for prophylaxis of AF recurrences, are highlighted (purple bars). This very dangerous arrhythmia has been found in IC + BB group (1.19% of the treated patients) and sotalol group (2.14%). For further considerations, please see the text.

**Table 1.** Vaughan Williams Classification, Comprising the Main Antiarrhythmic Medications
Class	Known as	Examples	Medical uses
IA	Fast-channel blockers	Quinidine, ajmaline, procainamide, disopyramide	Ventricular arrhythmias, prevention of paroxysmal recurrent atrial fibrillation (triggered by vagaloveractivity), procainamide in Wolff-Parkinson-White syndrome, all these drugs increase QT interval
IB		Lidocaine, mexiletine, tocainide	Treatment and prevention during and immediately after myocardial infarction, though this practice is now discouraged given the increased risk of asystole; ventricular tachycardia
IC		Encainide, flecainide, propafenone, moricizine	Prevention of paroxysmal atrial fibrillation, treatment of recurrent tachyarrhythmias of abnormal conduction system; these drugs are contraindicated immediately after myocardial infarction
II	Beta-blockers	Carvedilol, propranolol, esmolol, timolol, metoprolol, atenolol, bisoprolol, nebivolol	Reduction in myocardial infarction mortality, prevention of tachyarrythmia's recurrences, propranolol has sodium channel-blocking effects
III		Amiodarone, sotalol, ibutilide, dofetilide, dronedarone	Sotalol: ventricular tachycardias and atrial fibrillation; Ibutilide: atrial flutter and atrial fibrillation, amiodarone: prevention of paroxysmal atrial fibrillation, and hemodynamically stable ventricular tachycardia
IV	Calcium channel blockers	Verapamil, diltiazem	Prevention of recurrences of paroxysmal supraventricular tachycardia, slowing-down of ventricular rate in patients with atrial fibrillation
V		Adenosine, digoxin, magnesium sulfate	Used in supraventricular arrhythmias, especially in heart failure with atrial fibrillation, contraindicated in ventricular arrhythmias; or in the case of magnesium sulfate, used in torsades de pointes

Table 1. Vaughan Williams Classification, Comprising the Main Antiarrhythmic Medications

Class

Known as

Examples

Medical uses

Fast-channel blockers

Quinidine, ajmaline, procainamide, disopyramide

Ventricular arrhythmias, prevention of paroxysmal recurrent atrial fibrillation (triggered by vagaloveractivity), procainamide in Wolff-Parkinson-White syndrome, all these drugs increase QT interval

Lidocaine, mexiletine, tocainide

Treatment and prevention during and immediately after myocardial infarction, though this practice is now discouraged given the increased risk of asystole; ventricular tachycardia

Encainide, flecainide, propafenone, moricizine

Prevention of paroxysmal atrial fibrillation, treatment of recurrent tachyarrhythmias of abnormal conduction system; these drugs are contraindicated immediately after myocardial infarction

Beta-blockers

Carvedilol, propranolol, esmolol, timolol, metoprolol, atenolol, bisoprolol, nebivolol

Reduction in myocardial infarction mortality, prevention of tachyarrythmia's recurrences, propranolol has sodium channel-blocking effects

III

Amiodarone, sotalol, ibutilide, dofetilide, dronedarone

Sotalol: ventricular tachycardias and atrial fibrillation; Ibutilide: atrial flutter and atrial fibrillation, amiodarone: prevention of paroxysmal atrial fibrillation, and hemodynamically stable ventricular tachycardia

Calcium channel blockers

Verapamil, diltiazem

Prevention of recurrences of paroxysmal supraventricular tachycardia, slowing-down of ventricular rate in patients with atrial fibrillation

Adenosine, digoxin, magnesium sulfate

Used in supraventricular arrhythmias, especially in heart failure with atrial fibrillation, contraindicated in ventricular arrhythmias; or in the case of magnesium sulfate, used in torsades de pointes

**Table 2.** The Absolute Number of Cases for Each Paradoxical Arrhythmia Variety
On the whole, there are 182 cases of paradoxical arrhythmia (proarrhythmic events) plus 36 cases of iatrogenic intraventricular conduction delay, namely 23 cases of left bundle branch block and 13 cases of right bundle branch block caused by antiarrhythmic drugs, especially flecainide and quinidine.
Torsades de pointes: 56 cases
Slow atrial flutter with 1:1 AV conduction: 24 cases
Intermittent high grade AV block in patients with asymptomatic chronic bifascicular block: one case
Left bundle branch block: 23 cases
Right bundle branch block: 13 cases
Second-degree sino-atrial block type 1: five cases
Second-degree sino-atrial block type 2: 45 cases
Third-degree sino-atrial block: 31 cases
Type 2 (Mobitz II) second-degree AV block: 14 cases
Sustained monomorphic ventricular tachycardia: six cases

Table 2. The Absolute Number of Cases for Each Paradoxical Arrhythmia Variety

On the whole, there are 182 cases of paradoxical arrhythmia (proarrhythmic events) plus 36 cases of iatrogenic intraventricular conduction delay, namely 23 cases of left bundle branch block and 13 cases of right bundle branch block caused by antiarrhythmic drugs, especially flecainide and quinidine.

Torsades de pointes: 56 cases

Slow atrial flutter with 1:1 AV conduction: 24 cases

Intermittent high grade AV block in patients with asymptomatic chronic bifascicular block: one case

Left bundle branch block: 23 cases

Right bundle branch block: 13 cases

Second-degree sino-atrial block type 1: five cases

Second-degree sino-atrial block type 2: 45 cases

Third-degree sino-atrial block: 31 cases

Type 2 (Mobitz II) second-degree AV block: 14 cases

Sustained monomorphic ventricular tachycardia: six cases