The effect of dofetilide on ventricular defibrillation thresholds

Area of Science:

• Cardiology
• Electrophysiology
• Pharmacology

Background:

• High defibrillation thresholds (DFTs) pose a challenge in defibrillator implantation.
• An inadequate safety margin for defibrillation can be a serious complication.
• Dofetilide, a Class III antiarrhythmic, has shown promise in reducing DFTs in preclinical models.

Purpose of the Study:

• To evaluate the efficacy of dofetilide in reducing DFTs in human patients.
• To determine if dofetilide can obviate the need for complex lead systems.
• To assess the impact of dofetilide on defibrillation safety margins.

Main Methods:

• Sixteen patients with high DFTs (> or =20 J) received dofetilide therapy.
• Follow-up DFT testing was performed acutely and/or chronically after drug administration.
• Amiodarone was discontinued in four patients prior to implantation.

Main Results:

• Dofetilide significantly reduced DFTs from 28 +/- 4 J to 19 +/- 7 J (P < 0.0001).
• This resulted in an improved safety margin of 15 +/- 8 J for implanted devices.
• Five patients successfully terminated spontaneous arrhythmias with shocks after dofetilide treatment.

Conclusions:

• Dofetilide is effective in reducing DFTs in patients with implantable cardioverter-defibrillators.
• This pharmacological approach can prevent the requirement for more complex lead systems.
• Dofetilide should be considered for patients with inadequate defibrillation safety margins.