Clinical efficacy of dofetilide for the treatment of atrial tachyarrhythmias in adults with congenital heart disease.
BACKGROUND
Atrial tachyarrhythmias (AT) including atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia represent a clinical challenge in the adult with congenital heart disease (CHD). Dofetilide (D) is a rapidly activating delayed rectifier potassium channel (IKr) blocker effective in pharmacological conversion and maintenance of normal sinus rhythm in patients with AF and AFL. There is limited knowledge regarding the role of D in adults with CHD.


METHODS
Safety and efficacy of D was evaluated in a consecutive group of thirteen adult patients (age 40 ± 11; six women) with CHD and refractory AT.


RESULTS
Ten patients had persistent (four AFL, one AF, and five atrial tachycardia) and three paroxysmal (one AF and two atrial tachycardia) AT. All patients were symptomatic during tachycardia, 12 patients had previously failed 2 ± 1 antiarrhythmic drugs. Mean systemic ventricular ejection fraction was 55 ± 9%; baseline QRS complex duration was 129 ± 45 ms (>120 ms in six patients). Patients were followed on D for 33 ± 39 months (median 16). Among 10 patients with persistent AT, seven patients (70%) pharmacologically converted to sinus rhythm on D and three patients (30%) required direct current cardioversion. Two patients (15.4%) experienced complete arrhythmia suppression, and seven (53.8%) experienced significant clinical improvement with sporadic recurrences; average time to recurrence was 5.5 ± 3.5 months. One patient developed torsade de pointes during loading, and the drug was discontinued. D was discontinued in five (38.5%) other patients due to recurrence of AT (n = 4) and renal failure (n = 1). Corrected QT interval (QTc) increased from 452 ± 61 to 480 ± 49 ms (P = .04) and corrected JT interval (JTc) from 323 ± 39 to 341 ± 33 ms (P = .09).


CONCLUSIONS
D should be considered a pharmacologic alternative when adult patients with CHD develop AT. D does not depress conduction, sinus node, or ventricular function but needs close monitoring for potential ventricular pro-arrhythmia.
Penn State Hershey Heart & Vascular Institute, Penn State University, Hershey, Pa, USA.
Javier E
JE
Banchs
Giselle A
GA
Baquero
Michelle J
MJ
Nickolaus
Deborah L
DL
Wolbrette
John J
JJ
Kelleman
Soraya
S
Samii
Jennifer
J
Grando-Ting
Erica
E
Penny-Peterson
William R
WR
Davidson
Sallie K
SK
Young
Gerald V
GV
Naccarelli
Mario D
MD
Gonzalez
D000328:Adult; D000367:Age Factors; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001282:Atrial Flutter / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000009:adverse effects / Q000627:therapeutic use*; D026902:Potassium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013617:Tachycardia, Supraventricular / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D013449:Sulfonamides; C063533:dofetilide
Atrial Tachyarrhythmias; Congenital Heart Disease; Dofetilide