Ventricular arrhythmias proarrhythmias

Proarrhythmia refers to development of a significant new arrhythmia (such as VT, ventricular fibrillation [VF], or TdP) or worsening of an existing arrhythmia. Proarrhythmia results from the same mechanisms that cause other arrhythmias or from an alteration in the underlying substrate due to the antiarrhythmic agent. TdP is a rapid form of polymorphic VT associated with evidence of delayed ventricular repolarization due to blockade of potassium conductance. TdP may be hereditary or acquired. Acquired forms are associated with many clinical conditions and drugs, especially type la and type III IKr blockers. 

Type Ic drugs profoundly slow conduction velocity while leaving refractoriness relatively unaltered. Although effective for both ventricular and supraventricular arrhythmias, their use for ventricular arrhythmias has been limited by the risk of proarrhythmia. 

Proarrhythmia Like other antiarrhythmic agents, sotalol can provoke new or worsened ventricular arrhythmias in some patients, including sustained ventricular tachycardia or ventricular fibrillation, with potentially fatal consequences. Because of its effect on cardiac repolarization, is the most common form of proarrhythmia associated with sotalol, occurring in approximately 4% of high-risk patients. 

Proarrhythmia Mexiletine can worsen arrhythmias it is uncommon in patients with less serious arrhythmias (freguent premature beats or nonsustained ventricular tachycardia) but is of greater concern in patients with life-threatening arrhythmias, such as sustained ventricular tachycardia. 

An initial increase in cardiac arrhythmias (proarrhythmic effect) may occur when class III drugs are instituted. The most important proarrhythmia is known as torsades de pointes, which is a form of ventricular tachycardia that can be fatal.11,40 Specific class III agents are associated with various other side effects. Amiodarone, for example, is associated with pulmonary toxicity and liver damage. Other class III drugs may have a more favorable side-effect profile but may not be as effective as amiodarone in controlling arrhythmias. Side effects of class HI drugs there-... 

The Cardiac Arrhythmia Suppression Trial (CAST) highlighted the importance and awareness of proarrhythmia. The main finding of CAST was that, despite elimination of complex ventricular ectopy after myocardial infarction, mortality was significantly higher in patients treated with encainide or flecainide. Others have reported that the overall risk of cardiac mortality is higher, presumably due to proarrhythmia, in patients treated with Type la antiarrhythmics for atrial fibrillation who have con-... 

The Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) trial was a randomized, double-blind, parallel-controlled trial of a high-risk population that included patients with left ventricular ejection fraction < 0.35, QRS duration > 130ms and New York Heart Association Functional Class III or IV despite optimal medical beatment. Patients received devices with combined CRT and ICD capabilities and were randomized to the ICD therapy on or off. At 6 months, patients assigned to CRT had a greater improvement in median quality of life score and functional class as compared to controls. No significant differences were observed in changes in left ventricular size or function, overall heart failure status, survival, and rates of hospitalization. No proarrhythmia was observed and arrhythmia termination capabilities were not impaired (82). 

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