Potentially modifiable factors of dofetilide-associated risk of torsades de pointes among hospitalized patients with atrial fibrillation.

Abstract

PURPOSE:

There is a significant variation in the clinical approach of initiation and dose adjustment of dofetilide in atrial fibrillation (AF). Excessive QT prolongation could predispose patients to torsades de pointes (TdP), which can be fatal.

METHODS:

We performed a retrospective case-control study at Mayo Clinic Rochester (January 1, 2003 to December 31, 2016). "TdP risk" cases were defined as patients on dofetilide therapy for AF with subsequent TdP or excessive QTc prolongation requiring dose reduction or discontinuation (N = 31). A control group was matched 1:1 with cases by age, gender, year of admission, and dofetilide dose (N = 31).

RESULTS:

Using multivariate regression analysis, independent predictors of TdP risk included baseline QTc exceeding recommendations (adjusted odd ratio [AOR] 4.57; P = 0.023); underlying AF with rapid ventricular rate (AOR 16.95; P = 0.004); and diuretic therapy for acute heart failure (AOR 8.42; P = 0.007). Poor inter-observer agreement was identified among QT interval measurement in patients with AF and rapid ventricular rate compared to those in rate controlled AF or sinus rhythm. TdP risk cases receiving diuretics for acute heart failure had a significant decline in creatinine clearance than controls, although serum electrolytes and replacement did not differ among the two groups.

CONCLUSIONS:

Excessive QTc prolongation and AF with rapid ventricular rate at time of dofetilide initiation (likely due to difficulty in measuring QT intervals), and diuretic therapy for acute heart failure were independent factors for dofetilide-related TdP risk. Based on these data, possible preventive strategies could be adapted for safety protocols among hospitalized patients.

• Authors: Niyada Naksuk, Alan M Sugrue, Deepak Padmanabhan, Danesh Kella, Christopher V DeSimone, Suraj Kapa, Samuel J Asirvatham, Hon-Chi Lee, Michael J Ackerman, Peter A Noseworthy
• Journal: Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing (J Interv Card Electrophysiol) Vol. 54 Issue 2 Pg. 189-196 (Mar 2019) ISSN: 1572-8595 [Electronic] Netherlands
• PMID: 30353374 (Publication Type: Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Phenethylamines
• Sulfonamides
• dofetilide

Topics

• Academic Medical Centers
• Aged
• Anti-Arrhythmia Agents (adverse effects, therapeutic use)
• Atrial Fibrillation (diagnostic imaging, drug therapy)
• Case-Control Studies
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Electrocardiography (methods)
• Female
• Heart Rate (drug effects)
• Hospitalization (statistics & numerical data)
• Humans
• Logistic Models
• Long QT Syndrome (diagnostic imaging, drug therapy)
• Male
• Middle Aged
• Multivariate Analysis
• Observer Variation
• Phenethylamines (adverse effects, therapeutic use)
• Prognosis
• Retrospective Studies
• Risk Assessment
• Sulfonamides (adverse effects, therapeutic use)
• Survival Rate
• Torsades de Pointes (chemically induced, diagnostic imaging)
• Treatment Outcome