Efficacy and safety of dofetilide, a new class III antiarrhythmic agent, in acute termination of atrial fibrillation or flutter after coronary artery bypass surgery

Chandy²,

et al. 2006

Cardiology

Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery. Despite the prevalence of AF occurring after cardiac surgery, its pathophysiology is incompletely understood. Our previous study demonstrated that age and left atrial enlargement were independent predictors of postoperative AF. Accordingly, the purpose of this study was to determine whether cellular changes such as fibrosis and/or hypertrophy occurred in the atrium in patients who subsequently developed postoperative AF. Right atrial appendage tissue was obtained during atriotomy in patients undergoing elective CABG surgery. Quantitative assessment of atrial fibrosis was performed with Sirius red stain, and atrial cell diameter was measured with the HE stain. Linear regression, t test, χ² test or Fisher exact test were used for statistical analysis. Sixty-one patients (mean age 71 ± 8 years) were studied. Increasing age was significantly associated with fibrosis (beta 0.3, 95% CI: 0.06–0.55, p = 0.017). The amount of right atrial fibrosis tended to correlate with the incidence of postoperative AF (p = 0.08). Cell diameter was not significantly different between patients with versus without postoperative AF (p = 0.85). These results suggest that the age-related atrial fibrosis rather than cellular hypertrophy may be important in the pathogenesis of AF after CABG surgery and should be further investigated.

Section: Discussionmentioning

confidence: 99%

Histologic Assessment of Right Atrial Appendage Myocardium in Patients with Atrial Fibrillation after Coronary Artery Bypass Graft Surgery

Chandy²,

et al. 2006

Cardiology

“…Dofetilide has a higher safety profile than most other class III agents. In 10 randomised trials for treatment of supraventricular arrhythmias, the hazard ratio for death of dofetilide was 1.1 (95% confidence interval 0.3-4.3), indicating no evidence of a side effect for dofetilide on mortality rates [28,29] . Two separate Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) studies performed in high-risk patients also demonstrated the safety of dofetilide [29] .…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effects of DC031050, a class III antiarrhythmic agent, on hERG channel and three neuronal potassium channels

Sun

Zhou

et al. 2012

Acta Pharmacol Sin

Aim: This study was conducted to test the selectivity of DC031050 on cardiac and neuronal potassium channels. Methods: Human ether-à-go-go related gene (hERG), KCNQ and Kv1.2 channels were expressed in CHO cells. The delayed rectifier potassium current (I K ) was recorded from dissociated hippocampal pyramidal neurons of neonatal rats. Whole-cell voltage patch clamp was used to record the voltage-activated potassium currents. Drug-containing solution was delivered using a RSC-100 Rapid Solution Changer. Results: Both DC031050 and dofetilide potently inhibited hERG currents with IC 50 values of 2.3±1.0 and 17.9±1.2 nmol/L, respectively. DC031050 inhibited the I K current with an IC 50 value of 2.7±1.5 μmol/L, which was >1000 times the concentration required to inhibit hERG current. DC031050 at 3 μmol/L did not significantly affect the voltage-dependence of the steady activation, steady inactivation of I K , or the rate of I K from inactivation. Intracellular application of DC031050 (5 μmol/L) was insufficient to inhibit I K . DC031050 up to 10 μmol/L had no effects on KCNQ2 and Kv1.2 channel currents. Conclusion: DC031050 is a highly selective hERG potassium channel blocker with a substantial safety margin of activity over neuronal potassium channels, thus holds significant potential for therapeutic application as a class III antiarrhythmic agent.

Semin Cardiothorac Vasc Anesth

“…41 The treatment of AF after cardiac surgery has certain differences to that used for AF in the nonsurgical setting. Since as many as 15% to 24% of patients with postoperative AF spontaneously convert to sinus rhythm in the first 2 hours 42,43 it is important that clinical trials include a placebo arm. Further, the high spontaneous conversion rates for AF are important when the relative benefits versus the adverse effect of any treatment are considered.…”

Section: Treatmentmentioning

confidence: 99%

Atrial Fibrillation After Cardiac Surgery: Pathophysiology and Treatment

Palin¹,

Rajagopal

Hogue

2004

Atrial fibrillation (AF) occurs in 25% to 60% of patients after cardiac surgery. It is most consistently associated with advanced age and valvular heart operations. Despite improving knowledge of the pathophysiology of chronic AF, postoperative AF remains an obstinate clinical problem. It is associated with an increased risk of stroke, longer hospital stay, and higher hospital expenditure. Consequently, there has been great interest in strategies to prevent and treat this arrhythmia. Treatment for postoperative AF may require immediate electrical cardioversion for hemodynamically unstable patients. Heart rate control is useful in most patients, with anticoagulation considered after 48 hours. Antiarrhythmic therapy is often effective in restoring sinus rhythm but its use needs to be balanced against the patient's risk of proarrhythmic side effects such as torsade de pointes.