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Notes: Hybrid Therapy for Atrial Fibrillation. Introduction: Maintenance of sinus rhythm in patients with recurrent atrial fibrillation is often difficult to achieve with pharmacologic therapy. Complex catheter ablative procedures are being developed, but efficacy and safety issues remain to be clarified. We hypothesized that combined pharmacologic and simple ablative therapies in a targeted subset of patients will improve success in the treatment of atrial fibrillation.Methods and Results: We identified 13 patients (mean age 61.5 ± 16.2 years) with atrial fibrillation who converted to electrocardiographic atrial flutter during antiarrhythmic drug treatment. Surface ECG suggested “typical” atrial flutter in 11 patients and “atypical” atrial flutter in 2. Intracardiac mapping and entrainment studies revealed 9 patients had counter-clockwise isthmus-dependent atrial flutter, and the remaining 4 had complex activation patterns, suggesting the presence of multiple wavefronts. All 9 patients with typical atrial flutter underwent successful ablation. None of the 4 patients with complex activation patterns had successful ablation. Patients were followed for recurrences of atrial arrhythmias via clinic visits, record review, and interviews. In patients who underwent successful ablation and continued on antiarrhythmic drugs, 88.9% remain in sinus rhythm after a mean follow-up of 14.3 ± 6.9 months (range 1 to 28).Conclusion: In patients who experience conversion of atrial fibrillation to atrial flutter during antiarrhythmic drug treatment, ablation and continuation of pharmacologic therapy is a safe and effective means of achieving and maintaining sinus rhythm.

Notes: Spatial Autocorrelation of APDs During Arrhythmogenic Insults. Introduction: Regional dispersions of repolarization (DOR) are arrhythmogenic perturbations that are closely associated with reentry. However, the characteristics of DOR have not been well defined or adequately analyzed because previous algorithms did not take into account spatial heterogeneities of action potential durations (APDs). Earlier simulations proposed that pathologic conditions enhance DOR by decreasing electrical coupling between cells, thereby unmasking differences in cellular repolarization between neighboring cells. Optical mapping indicated that gradients of APD and DOR are associated with fiber structure and are largely independent of activation. We developed an approach to quantitatively characterize APD gradients and DOR to determine how they are influenced by tissue anisotropy and cell coupling during diverse arrhythmogenic insults such as hypoxia and hypothermia. Methods and Results: Voltage-sensitive dyes were used to map APs from 124 sites on the epicardium of Langendorff-perfused guinea pig hearts during (1) cycles of hypoxia and reoxygenation and (2) after 30 minutes of hypothermia (32° to 25°C). We introduce an approach to quantitate DOR by analyzing two-dimensional spatial autocorrelation of APDs along directions perpendicular and parallel to the longitudinal axis of epicardial fibers. A spatial correlation length l was derived as a statistical measure of DOR. It corresponds to the distance over which APDs had comparable values, where l is inversely related to DOR. Hypoxia (30 min) caused a negligible decrease in longitudinal θL (from 0.530 ± 0.138 to 0.478 ± 0.052 m/sec) and transverse θT (from 0.225 ± 0.034 to 0.204 ± 0.021 m/sec) conduction velocities and did not alter θL/θT or activation patterns. In paced hearts (cycle length [CL] = 300 msec), hypoxia decreased APDs (123 ± 18.2 to 46 ± 0.6 msec; P 〈 0.001) within 10 to 15 minutes and enhanced DOR, as indicated by reductions of l from 1.8 ± 0.9 to 1.1 ± 0.5 mm (P 〈 0.005). Hypothermia caused marked reductions of θL, (0.53 ± 0.138 to 0.298 ± 0.104 m/sec) and θT (0.225 ± 0.034 to 0.138 ± 0.027 m/sec), increased APDs (128 ± 4.4 to 148 ± 14.5 msec), and reduced l from 2.0 ± 0.3 to 1.3 ± 0.6 mm (P 〈 0.05). l decreased with increased time of hypoxia and recovered upon reoxygenation. Hypoxia and hypothermia reduced l measured along the longitudinal (l1) and transverse (lT) axes of cardiac fibers while the ratio lL/lT remained constant.

Notes: Activation and Repolarization Patterns. Introduction: Substantial progress has been made in our understanding of transmural activation across ventricular muscle through studies of excitation patterns and potential distributions. In contrast, repolarization sequences are poorly understood because of experimental difficulties in mapping action potential durations (APDs) using extracellular electrodes. Methods and Results: Langendorff-perfused guinea pig hearts and isolated coronaryperfused left ventricular sheet preparations were stained with the voltage-sensitive dye RH-421 and optical APs were recorded with a photodiode array. Epicardial maps were constructed using a triangulation method applied to matrices of activation and repolarization times determined from (dF/dt)max and (d2F/dt2)max′ respectively. Numerical simulations were carried out based on: (1) a modified Luo-Rudy model; (2) the three-dimensional architecture of ventricular fibers; and (3) the intrinsic spatial distribution of APDs. In ventricular sheets, epicardial stimulation elicited elliptical activation patterns with the major axis aligned with the longitudinal axis of epicardial fibers. When the pacing electrode was progressively inserted from epicardium to endocardium, the major axes rotated gradually, clockwise by 45°, and the eccentricity decreased from 2 to 1.14. Repolarization showed a relatively uniform pattern, independent of pacing site, beginning at the apex and spreading to the base. Conclusion: In experiments and simulations, the helical rotation of epicardial excitation isochrones caused by pacing at increasing depth in the myocardium correlated with the helical three-dimensional architecture of ventricular fibers. In contrast, repolarization was independent of the activation sequence and was mainly guided by spatial differences in APDs between apex and base.

Notes: [Auszug] We have developed an application called HAPI (High-Density Array Pattern Interpreter), which facilitates the analysis of microarray data by selecting subsets of genes with specific characteristics and displaying them with dynamic links to web-based databases. This allows comparison of subsets of ...