azd-7009 and Arrhythmias--Cardiac

To describe the characteristics of patients presenting with morphological T wave changes that lead to measurement difficulties, and to identify possible predictors of such changes at baseline and early after start of treatment.. ECGs from 145 patients receiving a combined potassium and sodium channel blocking agent for conversion of atrial fibrillation (AF), underwent semiautomatic analysis in a digitalized high-precision analysis program. In 15 patients, one or more ECGs were identified as difficult to interpret due to morphological T wave changes. They were compared with the 130 patients without such changes.. A history of cardiac failure (p=0.027), a smaller left atrial area (p=0.010) and a longer QT(tang) minus QT(top) interval (p<0.001) at baseline was significantly more frequent as compared to the controls. Identified patients also had somewhat longer baseline QT interval duration (median QT(cB) 432 vs. 408 ms, N.S.) and a larger proportion of them were females (47% vs. 27%, N.S.). After start of infusion the QT(cB) became significantly longer in identified patients than in controls (p=0.012).. Independent predictors of subsequent morphological changes were found at baseline and shortly after start of treatment, and may be of use to identify individuals with a reduced repolarization reserve.

Topics: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Double-Blind Method; Electrocardiography; Female; Heart Conduction System; Humans; Infusions, Parenteral; Logistic Models; Male; Middle Aged; Organic Chemicals; Potassium Channel Blockers; Predictive Value of Tests; Risk Assessment; Risk Factors; Sodium Channel Blockers; Sweden; Time Factors; Treatment Outcome; Young Adult

To compare the electrophysiological and antiarrhythmic effects of AZD7009, azimilide, and AVE0118 in the acutely dilated rabbit atria in vitro.. In the isolated Langendorf-perfused rabbit heart, the atrial effective refractory period (AERP) and the inducibility of atrial fibrillation (AF) were measured at increasing concentrations of AZD7009 (0.1-3 microM), azimilide (0.1-3 microM), and AVE0118 (0.3-10 microM). In separate groups of atria, termination of sustained AF was assessed. In non-dilated atria, the AERP was 82+/-1.3 ms (mean+/-SEM) and AF could not be induced. Dilation significantly reduced the AERP to 49+/-1.0 ms (P<0.001) and 92% of the atria became inducible. Perfusion with AZD7009, azimilide, and AVE0118 concentration-dependently increased the AERP and reduced the AF inducibility. At the highest concentrations of AZD7009, azimilide, and AVE0118, AERP and AF inducibility changed from 50+/-4.5 to 136+/-6.6 ms and 80 to 0% (both P<0.001) from 51+/-3.0 to 105+/-9.9 ms (P<0.001) and 80 to 0% (P<0.01) and from 46+/-2.8 to 85+/-6.0 ms and 90 to 0% (both P<0.001). Restoration of sinus rhythm was seen in 6/6, 5/6, and 5/6 hearts perfused with AZD7009, azimilide, and AVE0118, respectively.. In the dilated rabbit atria, AZD7009, azimilide, and AVE0118 concentration-dependently increased AERP, effectively prevented AF induction, and rapidly restored sinus rhythm.

Topics: Analysis of Variance; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Biphenyl Compounds; Dilatation, Pathologic; Heart Atria; Hydantoins; Imidazolidines; In Vitro Techniques; Organic Chemicals; Piperazines; Rabbits