Background-Catheter ablation of ventricular tachycardia (VT) is effective and particularly useful in patients with frequent defibrillator interventions. Various substrate modification techniques have been described for unmappable or hemodynamically intolerable VT. Noninducibility is the most frequently used end point but is associated with significant limitations, so the optimal end point remains unclear. We hypothesized that elimination of local abnormal ventricular activities (LAVAs) during sinus rhythm or ventricular pacing would be a useful and effective end point for substrate-based VT ablation. As an adjunct to this strategy, we used a new high-density mapping catheter and frequently used epicardial mapping. Methods and Results-Seventy patients (age, 67Ϯ11 years; 7 female) with VT and structurally abnormal ventricle(s) were prospectively enrolled. Conventional mapping was performed in sinus rhythm in all, and a high-density Pentaray mapping catheter was used in the endocardium (nϭ35)

Atrial fibrosis as defined by DE MRI is associated with slower and more organized electrical activity but with lower voltage than healthy atrial areas. Ninety percent of continuous CFAE sites occur at non-DE and patchy DE LA sites. These findings are important when choosing the ablation strategy in persistent AF.

Genes encoding polyadenylated mRNAs depend on their poly(A) signals for termination of transcription. Typically, transcription downstream of the poly(A) signal gradually declines to zero, but often there is a transient increase in polymerase density immediately preceding the decline. Special elements called pause sites are traditionally invoked to account for this increase. Using run-on transcription from the nuclei of transfected cells, we show that both the pause and the gradual decline that follow a poly(A) site are generated entirely by the poly(A) signal itself in a series of model constructs. We found no other elements to be involved and argue that the elements called pause sites do not function through pausing. Both the poly(A)-dependent pause and the subsequent decline occurred earlier for a stronger poly(A) signal than for a weaker one. Because the gradual decline resembles the abortive elongation that occurs downstream of many promoters, one model has proposed that the poly(A) signal flips the polymerase from the elongation mode to the abortive mode like a binary switch. We compared abortive elongators with poly(A) terminators and found a 4-fold difference in processivity. We conclude that poly(A) terminating polymerases do not merely revert to their prior state of low processivity but rather convert to a new terminationprone condition.

Background Complex fractionated electrograms (CFAE) are targets of atrial fibrillation (AF) ablation. Serial high density maps were evaluated to understand the impact of activation direction and rate on electrogram (EGM) fractionation. Methods and Results 18 patients (9 persistent) underwent high density, 3D, left atrial mapping (>400 points/map) during AF, Sinus (SR) and CS-paced (CSp) rhythms. In SR and CSp, fractionation was defined as EGM with ≥4 deflections, while in AF CFEmean <80ms was considered as continuous CFAE. The anatomic distribution of CFAE sites was assessed, quantified and correlated between rhythms. Mechanisms underlying fractionation were investigated by analysis of voltage, activation and propagation maps. A minority of continuous CFAE sites displayed EGM fractionation in SR (15+/−4%) and CSp (12+/(12+/−8%). EGM fractionation did not match between SR and CSp at 70+/−10% sites. Activation maps in SR and CSp showed that wave collision (71%) and regional slow conduction (24%) caused EGM fractionation. EGM voltage during AF (0.59+/−0.58mV) was lower than during SR and CSp (>1.0mV) at all sites. During AF, the EGM voltage was higher at continuous CFAE sites than at non-CFAE sites (0.53mV (Q1, Q3: 0.33–0.83) vs. 0.30 mV (Q1, Q3: 0.18–0.515), p<0.00001). Global LA voltage in AF was lower in persistent vs. paroxysmal AF patients (0.6+/−0.59mV vs. 1.12+/−1.32mV, p<0.01). Conclusions The distribution of fractionated EGMs is highly variable, depending on direction and rate of activation (SR vs. CSp vs. AF). Fractionation in sinus and CSp rhythms mostly resulted from wave collision. All sites with continuous fractionation in AF displayed normal voltage in SR suggesting absence of structural scar. Thus, many fractionated EGMs are functional in nature and their sites dynamic.

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