Packer, Douglas L.

Background— The long-term natural history of lone atrial fibrillation is unknown. Our objective was to determine the rate and predictors of progression from paroxysmal to permanent atrial fibrillation over 30 years and the long-term risk of heart failure, thromboembolism, and death compared with a control population. Methods and Results— A previously characterized Olmsted County, Minnesota, population with first episode of documented atrial fibrillation between 1950 and 1980 and no concomitant heart disease or hypertension was followed up long term. Of this unique cohort, 76 patients with paroxysmal (n=34), persistent (n=37), or permanent (n=5) lone atrial fibrillation at initial diagnosis met inclusion criteria (mean age at diagnosis, 44.2±11.7 years; male, 78%). Mean duration of follow-up was 25.2±9.5 years. Of 71 patients with paroxysmal or persistent atrial fibrillation, 22 had progression to permanent atrial fibrillation. Overall survival of the 76 patients with lone atrial fibrillation was 92% and 68% at 15 and 30 years, respectively, similar to 86% and 57% survival for the age- and sex-matched Minnesota population. Observed survival free of heart failure was slightly worse than expected ( P =0.051). Risk for stroke or transient ischemic attack was similar to the expected population risk during the initial 25 years of follow-up but increased thereafter ( P =0.004), although CIs were wide. All patients who had a cerebrovascular event had developed ≥1 risk factor for thromboembolism. Conclusions— Comorbidities significantly modulate progression and complications of atrial fibrillation. Age or development of hypertension increases thromboembolic risk.

Background Propofol infusion syndrome is first manifest by unexplained metabolic acidosis. Its incidence is unknown. Methods Charts of all patients undergoing nonsurgical, catheter radiofrequency ablation for atrial flutter or fibrillation from 1999 through 2001 at Mayo Clinic Rochester, who received propofol and had an arterial blood gas drawn during the procedure, were reviewed retrospectively for metabolic acidosis, prospectively defined as base excess -2 or less. Of 301 radiofrequency ablation cases, 55 had an arterial blood gas. Virtually all radiofrequency ablation patients received propofol, so they could not be used as nonpropofol controls. Instead, all carotid endarterectomy patients in 2000 who did not receive propofol and had an arterial blood gas drawn after anesthetic induction and before surgical incision were used as a comparator group. Results In propofol radiofrequency ablation patients with no apparent cause of metabolic acidosis besides propofol, 13 of 55 (24%) had base excess of -2 or less, versus 22 of 267 carotid patients (8.2%) (P<0.01). Maximal negative base excess was -4.2+/-1.7 in these propofol patients and was not correlated with propofol dose, age, or fluid dose, versus base excess of -3.2+/-1.5 in carotid patients (P>0.05). Propofol patients received prolonged anesthetics (7 h) and high-dose propofol (20 mg/kg). Conclusions This is the first incidence estimate of metabolic acidosis during prolonged propofol infusion and suggests that it is not rare. The study is limited by its retrospective nature and by the lack of baseline arterial blood gas data and will require confirmation by prospective study.

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— Although segmental or circumferential ablation is effective in eliminating pulmonary vein (PV)–mediated atrial fibrillation (AF), this procedure may be complicated by the occurrence of PV stenosis. Methods and Results— To establish the clinical presentation, diagnostic manifestations, and interventional management of PV stenosis, 23 patients with stenosis of 34 veins complicating ablation of AF were evaluated. Each patient became symptomatic 103±100 days after undergoing ablation. In 8 veins, the ablation producing the PV stenosis was a repeated procedure for continued AF. Nineteen patients presented with dyspnea on exertion, 7 with dyspnea at rest, 9 with cough, and 6 with chest pain. On multirow spiral computed tomography examination, the narrowest lumen of the affected PVs measured 3±2 mm compared with 13±3 mm at baseline ( P ≤0.001). The relative perfusion of affected lung segments on isotope scans was reduced to 4±3% of total perfusion compared with 22±10% in unaffected segments. At percutaneous intervention, these veins showed 80±13% stenosis, with a mean gradient of 12±5 mm Hg. This was significantly reduced to a residual stenosis of 9±8% ( P ≤0.001) and a residual gradient of 3±4 mm Hg ( P ≤0.001). Twenty veins were treated with balloon dilatation alone, whereas 14 veins were stented with standard 10-mm-diameter bare-metal stents. Although the symptomatic response was nearly immediate and impressive, 14 patients developed in-stent or in-segment restenosis, requiring repeated interventions in 13. Conclusions— Percutaneous intervention produces rapid and dramatic symptom relief in patients with highly symptomatic PV stenosis after radiofrequency ablation for AF. Nevertheless, alternative treatment methods will be required to decrease recurrent in-stent or in-segment restenosis.

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.

Background — The Multicenter Unsustained Tachycardia Trial (MUSTT) was designed to evaluate an antiarrhythmic treatment strategy, including drugs and implantable defibrillators (ICDs), guided by electrophysiological (EP) testing. We performed several statistical analyses to assess the contribution of defibrillators to the observed treatment benefit. Methods and Results — First, the effects of defibrillators were indirectly examined by comparing the randomized treatment arms (EP-guided therapy versus no antiarrhythmic therapy) within subgroups that varied according to ICD usage. Use of ICDs increased during the trial; hence, the randomized treatments were compared according to date of enrollment. There were also site-specific differences in ICD use; hence, the randomized arms were compared within groups of sites defined by level of ICD use. There was a distinct “dose response” in relation to ICD use. Where ICD use was high, EP-guided therapy produced significant reductions in arrhythmic death or cardiac arrest ( P <0.004). Where ICD use was low, there was no benefit of EP-guided therapy. Finally, outcomes of EP-guided therapy patients who received an ICD were directly compared with outcomes of other patients using the Cox proportional hazards model with receipt of an ICD as a time-dependent covariate. Adjusted for other prognostic factors, patients who received an ICD had risk reductions of >70% in arrhythmic death or cardiac arrest and >50% in total mortality ( P <0.001 for both end points). Conclusions — The benefit of EP-guided antiarrhythmic therapy observed in MUSTT was due to improved outcomes among patients who received an ICD but not among patients who received antiarrhythmic drugs.