Bruce, G. Keith

Background— Atrioventricular (AV) nodal ablation for management of atrial fibrillation (AF) is irreversible and requires permanent pacemaker implantation. We hypothesized that as an alternative, implantation of autologous fibroblasts in the perinodal region would focally modify AV nodal conduction and that this modulation would be enhanced by pretreatment with transforming growth factor-β1 (TGF-β1), a stimulant of fibroblasts. Methods and Results— Skin biopsies were taken from 12 mongrel dogs, and derived fibroblasts were dissociated and grown in culture for 2 weeks. Multiple injections (0.25 mL) were made through an 8F NOGA catheter along the fast/slow AV nodal pathways as guided by an electroanatomic mapping system. Seven dogs received fibroblasts alone (1×10 6 cells/mL), 7 dogs received TGF-β1 (5 μg), 4 dogs received fibroblasts and TGF-β1 (1×10 6 cells/mL+5 μg), and 4 dogs received saline only. AV node function was assessed at baseline and after 4 weeks. Saline (80 mL) with assigned therapy (0.25 mL per injection) was injected into the peri-AV nodal region in each dog. At baseline, the AH interval (66±3 ms) and the average RR interval (331±17 ms) in pacing-induced AF were similar in each cohort. The increase in AH interval in normal sinus rhythm was longer after fibroblast (23±4 versus 5±5 ms; P =0.05) and fibroblast plus TGF-β1 (50±5 versus 5±5 ms; P <0.001) injections than with saline alone, with similar findings during high right atrium and distal coronary sinus pacing. The AH interval was not significantly increased after TGF-β1 injections. The AH interval was significantly longer after fibroblast plus TGF-β1 injections than with either therapy (TGF-β1 or fibroblasts) alone. The RR interval during AF was increased in dogs that received fibroblasts alone (110±36 versus −41±34 ms) and to a greater extent with the addition of TGF-β1 (294±108 versus −41±34 ms). No AV block was seen in any cohort at 4 weeks. Labeled fibroblasts that expressed vimentin were identified in all dogs that received cell injections at 4 weeks. Conclusions— AV nodal modification can be achieved with injected fibroblasts without the creation of AV block. The effect on AV node conduction is substantially enhanced by pretreatment of fibroblasts with TGF-β1. These data have therapeutic potential for the management of rapid ventricular rate during AF without pacemaker implantation.

Background— It is not known whether catheter tip temperatures with a cooled-tip ablation can be reliably extrapolated to estimate actual tissue temperatures. The relationship between catheter tip temperatures, tissue temperatures, power, and microbubble formation is not known. Methods and Results— Nine dogs underwent 111 radiofrequency energy deliveries at the pulmonary vein ostia with a cooled-tip catheter. Catheter tip and tissue temperatures were markedly discrepant. Catheter tip temperature plateaus at 36°C to 39°C with increasing power, whereas tissue temperature increases to a mean of 75±3°C at 45 W (maximum temperature >100°C). Seventy-two energy deliveries were performed, titrating power to microbubble formation guided by intracardiac echocardiography. Type I and II microbubble formation occurred in 45 (63%) and 19 (26%) ablations, respectively. Type I microbubble emergence occurred at lower powers (21±8 versus 26±4 W; P =0.05), catheter tip temperatures (38±5°C versus 48±10°C; P =0.02), and tissue temperatures (65±19°C versus 81±9°C; P <0.001) than type II microbubble formation. Maximum impedance decreases during ablation before microbubble formation were less with type I microbubble (20±9 versus 37±11 Ω; P <0.001) compared with type II microbubbles. One quarter of type I microbubbles abruptly transitioned to type II microbubbles with significant changes in power or catheter tip temperature. No microbubbles were seen in 19 ablations (26%) despite powers up to 26±9 W and tissue temperatures up to 81±17°C. Conclusions— Catheter tip and tissue temperatures are markedly discrepant during cooled-tip ablation. Type I and II microbubble formation occurs at overlapping power and catheter tip and tissue temperature ranges. Neither the absence of microbubbles nor the presence of type I microbubble formation ensures against excessive tissue heating. The appearance of microbubbles may indicate possible tissue overheating and signal a need to decrease energy.

Background— Many ablative approaches in or near the orifice of the pulmonary vein (PV) have demonstrated success in eliminating atrial fibrillation. Despite current practice, there are no data regarding the in vivo efficacy and safety of an 8-mm catheter tip for ablation at the PV orifice. Methods and Results— Ten mongrel dogs were studied. Thermocouples were implanted in the atrial muscle of the PV orifice. Intracardiac echocardiography monitored catheter position, tip/tissue orientation, and microbubble formation. Ninety-four ablations were performed for 120 seconds. A temperature discrepancy >10°C between the catheter tip and tissue occurred during 47 (50%) of the ablations. Despite termination of energy delivery, the average tissue temperature remained within 1°C of the achieved steady state for 9 seconds. A temperature discrepancy >10°C was more common in the right superior PV, with oblique catheter positioning, when tissue temperatures were >60°C or 80°C, and with type 1 or type 2 microbubble formation. However, microbubbles were not present in 7 (13%, type 1) and 10 (40%, type 2) ablations with tissue temperatures >80°C. The maximum tissue temperature achieved with non–full-thickness lesions was 47.3±7.4°C vs 75.9±11.7°C ( P <0.0001) for full-thickness lesions. Conclusions— Marked discrepancies between catheter-tip and tissue temperatures occurred with higher temperatures, prolonged ablation times, and unfavorable catheter thermistor–tissue contact. Also, these data suggest a conservative approach to atrial ablation, because full-thickness lesions were obtained when tissue temperatures reached 50°C to 60°C and the tissue retained high heat levels despite termination of radiofrequency energy. Finally, microbubbles are inconsistent markers of tissue overheating.