Effect of digoxin on shocks in cardiac resynchronization therapy-defibrillator patients with coronary artery disease

Digoxin provides symptomatic relief in patients with systolic heart failure, yet it has potential proarrhythmic mechanisms and has not been formally studied in patients with cardiac resynchronization therapy-defibrillators (CRT-Ds). We evaluated the association between digoxin use and appropriate tachyarrhythmia therapy in patients with CRT-D with advanced heart failure, analyzing the incidence of appropriate device therapies and overall survival in 350 consecutive primary prevention recipients with CRT-D with baseline left ventricular ejection fraction (LVEF) ≤35%, non-right bundle-branch block native QRS complex ≥120 ms, New York Heart Association III to IV heart failure, and significant coronary artery disease. Digoxin was prescribed in 162 patients (46%) at discharge from CRT-D implant. Over 48 ± 32 months of follow-up, 59 patients (17%) received ≥1 appropriate shock. Digoxin therapy was associated with shorter time to first shock in intention-to-treat (corrected hazard ratio 2.18, 95% confidence interval 1.23 to 3.87, p = 0.007) and on-treatment analysis (corrected hazard ratio 2.27, 95% confidence interval 1.27 to 4.07, p = 0.006). Patients prescribed digoxin had a lower baseline LVEF, and digoxin therapy was associated with increased risk of shocks only in patients with LVEF <22% (median); there was no increased risk in patients with LVEF ≥22%. Overall survival and incidence of antitachycardia pacing were similar regardless of digoxin therapy. In conclusion, digoxin therapy is associated with increased likelihood of appropriate CRT-D shocks for rapid ventricular arrhythmias in primary prevention patients with coronary artery disease, and this risk appears to be most evident in patients with more severe baseline LV dysfunction. Digoxin use should be reexamined prospectively in patients with CRT-D.