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Background: Termination of atrial fibrillation (AF), the most common arrhythmia in the United States, during catheter ablation is an attractive procedural endpoint, which has been associated with improved long-term outcome in some studies. It is not clear, however, whether it is possible to predict termination using clinical data. We developed and applied three quantitative indices in global multielectrode recordings of AF prior to ablation: average dominant frequency (ADF), spectral power index (SPI), and electrogram quality index (EQI). Methods: In N = 42 persistent AF patients (65 ± 9 years, 14% female) we collected unipolar electrograms from 64-pole baskets (Abbott, CA). We studied N = 17 patients in whom AF terminated during ablation ("Term") and N = 25 in whom it did not ("Non-term"). For each index, we determined its ability to predict ablation by computing receiver operating characteristic (ROC) and calculated the area under the curve (AUC). Results: The ADF did not differ for Term and Non-term patients at 5.28 ± 0.82 Hz and 5.51 ± 0.81 Hz, respectively (p = 0.34). Conversely, the SPI for these two groups was. 0.85 (0.80-0.92) and 0.97 (0.93-0.98) and the EQI was 0.61 (0.58-0.64) and 0.56 (0.55-0.59) (p < 0.0001). The AUC for predicting AF termination for the SPI was 0.85 ([0.68, 0.95] 95% CI), and for the EQI, 0.86 ([0.72, 0.95] 95% CI). Conclusion: Both the EQI and the SPI may provide a useful clinical tool to predict procedural ablation outcome in persistent AF patients. Future studies are required to identify which physiological features of AF are revealed by these indices and hence linked to AF termination or non-termination.

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Background and purposePharmacotherapy of atrial fibrillation (AF), the most common cardiac arrhythmia, remains unsatisfactory due to low efficacy and safety concerns. New therapeutic strategies target atrial-predominant ion-channels and involve multichannel block (poly)therapy. As AF is characterized by rapid and irregular atrial activations, compounds displaying potent antiarrhythmic effects at fast and minimal effects at slow rates are desirable. We present a novel systems pharmacology framework to quantitatively evaluate synergistic anti-AF effects of combined block of multiple atrial-predominant K+ currents (ultra-rapid delayed rectifier K+ current, IKur , small conductance Ca2+ -activated K+ current, IKCa , K2P 3.1 2-pore-domain K+ current, IK2P ) in AF.Experimental approachWe constructed experimentally calibrated populations of virtual atrial myocyte models in normal sinus rhythm and AF-remodelled conditions using two distinct, well-established atrial models. Sensitivity analyses on our atrial populations was used to investigate the rate dependence of action potential duration (APD) changes due to blocking IKur , IK2P or IKCa and interactions caused by blocking of these currents in modulating APD. Block was simulated in both single myocytes and one-dimensional tissue strands to confirm insights from the sensitivity analyses and examine anti-arrhythmic effects of multi-atrial-predominant K+ current block in single cells and coupled tissue.Key resultsIn both virtual atrial myocytes and tissues, multiple atrial-predominant K+ -current block promoted favourable positive rate-dependent APD prolongation and displayed positive rate-dependent synergy, that is, increasing synergistic antiarrhythmic effects at fast pacing versus slow rates.Conclusion and implicationsSimultaneous block of multiple atrial-predominant K+ currents may be a valuable antiarrhythmic pharmacotherapeutic strategy for AF.

AimsPersistent atrial fibrillation (AF) has been explained by multiple mechanisms which, while they conflict, all agree that more disorganized AF is more difficult to treat than organized AF. We hypothesized that persistent AF consists of interacting organized areas which may enlarge, shrink or coalesce, and that patients whose AF areas enlarge by ablation are more likely to respond to therapy.Methods and resultsWe mapped vectorial propagation in persistent AF using wavefront fields (WFF), constructed from raw unipolar electrograms at 64-pole basket catheters, during ablation until termination (Group 1, N = 20 patients) or cardioversion (Group 2, N = 20 patients). Wavefront field mapping of patients (age 61.1 ± 13.2 years, left atrium 47.1 ± 6.9 mm) at baseline showed 4.6 ± 1.0 organized areas, each separated by disorganization. Ablation of sites that led to termination controlled larger organized area than competing sites (44.1 ± 11.1% vs. 22.4 ± 7.0%, P

In patients with dyssynchronous heart failure (DHF), cardiac conduction abnormalities cause the regional distribution of myocardial work to be non-homogeneous. Cardiac resynchronization therapy (CRT) using an implantable, programmed biventricular pacemaker/defibrillator, can improve the synchrony of contraction between the right and left ventricles in DHF, resulting in reduced morbidity and mortality and increased quality of life. Since regional work depends on wall stress, which cannot be measured in patients, we used computational methods to investigate regional work distributions and their changes after CRT. We used three-dimensional multi-scale patient-specific computational models parameterized by anatomic, functional, hemodynamic, and electrophysiological measurements in eight patients with heart failure and left bundle branch block (LBBB) who received CRT. To increase clinical translatability, we also explored whether streamlined computational methods provide accurate estimates of regional myocardial work. We found that CRT increased global myocardial work efficiency with significant improvements in non-responders. Reverse ventricular remodeling after CRT was greatest in patients with the highest heterogeneity of regional work at baseline, however the efficacy of CRT was not related to the decrease in overall work heterogeneity or to the reduction in late-activated regions of high myocardial work. Rather, decreases in early-activated regions of myocardium performing negative myocardial work following CRT best explained patient variations in reverse remodeling. These findings were also observed when regional myocardial work was estimated using ventricular pressure as a surrogate for myocardial stress and changes in endocardial surface area as a surrogate for strain. These new findings suggest that CRT promotes reverse ventricular remodeling in human dyssynchronous heart failure by increasing regional myocardial work in early-activated regions of the ventricles, where dyssynchrony is specifically associated with hypoperfusion, late systolic stretch, and altered metabolic activity and that measurement of these changes can be performed using streamlined approaches. Author summary: Cardiac resynchronization therapy (CRT) can improve the synchrony of contraction between the right and left ventricles in DHF and reduce morbidity and mortality and increase quality of life. However, regional work before CRT and changes with CRT are not well understood. We used three-dimensional multi-scale patient-specific computational models parameterized by anatomic, functional, hemodynamic, and electrophysiological measurements to assess changes in eight patients with heart failure and left bundle branch block (LBBB) who received CRT. To increase clinical translatability, we also explored the utility of streamlined methods to estimate regional myocardial work. We found that CRT increased global myocardial work efficiency with significant improvements in non-responders. Reverse ventricular remodeling after CRT was greatest in patients with the highest heterogeneity of regional work at baseline. Decreases in early-activated regions of myocardium performing negative myocardial work with CRT best explained patient variations in reverse remodeling. These findings were also observed when regional myocardial work was estimated using ventricular pressure as a surrogate for myocardial stress and changes in endocardial surface area as a surrogate for strain. These findings suggest that CRT promotes reverse ventricular remodeling in human dyssynchronous heart failure by increasing regional myocardial work in early-activated regions of the ventricles and that measurement of these changes can be performed using streamlined approaches. [ABSTRACT FROM AUTHOR]