13 Clinical Value of Noninducibility by High-Dose Isoproterenol Versus Rapid Atrial Pacing After Catheter Ablation of Paroxysmal Atrial Fibrillation THOMAS CRAWFORD, M.D., AMAN CHUGH, M.D., ERIC GOOD, D.O., KENTARO YOSHIDA, M.D., KRIT JONGNARANGSIN, M.D., MATTHEW EBINGER, D.O., FRANK PELOSI Jr., M.D., FRANK BOGUN, M.D., FRED MORADY, M.D., and HAKAN ORAL, M.D. From the Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA Noninducibility by High-Dose Isoproterenol. Objective: To determine the relative clinical value of noninducibility of atrial fibrillation (AF) by isoproterenol (ISO) and by rapid atrial pacing (RAP) in patients with paroxysmal AF (PAF). Background: AF can be induced by RAP or ISO in >85% of patients with PAF. Methods: ISO was administered in escalating doses of 5, 10, 15, and 20 μg/min in 112 patients (age = 56 ± 13 years) with PAF before radiofrequency catheter ablation. AF was inducible in 97 of 112 patients (87%) at a mean dose of 15 ± 5 μg/min. RAP induced AF in the remaining 14 of 15 patients. Antral pulmonary vein (PV) isolation (APVI) was followed by ablation of complex fractionated atrial electrograms (CFAEs) as necessary to terminate AF and render AF noninducible in response to ISO. Results: AF terminated during APVI in 72 of 111 patients (65%) and after APVI plus ablation of CFAEs in 11 of 111 patients (10%). In the remaining 28 patients (25%), sinus rhythm was restored by transthoracic cardioversion. RAP was performed in the last 61 consecutive patients who were rendered noninducible by ISO. RAP initiated AF in 20 of 61 patients (33%) and atrial flutter in 6 patients (10%). No additional ablation was performed if AF was induced with RAP; however, atrial flutter was targeted. At 12 ± 5 months, 63/75 patients (84%) who were noninducible by ISO and 2 of 8 (25%) who still were reinducible by ISO were free from recurrent AF after a single ablation procedure without antiarrhythmic drugs (P = 0.001). AF recurred in 20 of 36 patients (56%) who required cardioversion for persistent AF after ablation (P < 0.001). Among the 61 patients who also underwent RAP, 12 of 20 (60%) who were, and 31 of 41 (76%) who were not inducible by RAP were free from recurrent AF (P = 0.21). The accuracy of noninducibility as a predictor of clinical outcome was 83% with ISO and 64% by RAP (P = 0.03). Conclusions: The response to isoproterenol after catheter ablation of PAF more accurately predicts clinical outcome than the response to RAP. (JCardiovasc Electrophysiol, Vol. 21, pp. 13-20, January 2010) atrial fibrillation, catheter ablation, isoproterenol, atrial pacing, pulmonary vein isolation In patients with paroxysmal atrial fibrillation (AF), the noninducibility of AF by rapid atrial pacing after catheter ablation identifies patients who are less likely to have recur- rent AF during follow-up than those who remain in AF or still have inducible AF. 1-3 However, even when AF is still inducible by rapid pacing at the end of an ablation procedure, >50% of patients remain free of AF during follow-up, indi- cating that the AF that is induced by rapid pacing sometimes is a nonspecific response. A recent study demonstrated that isoproterenol has high sensitivity and specificity for the induction of AF in pa- Drs. Oral and Morady are founders of Ablation Frontiers, Inc., and have consulted to Ablation Frontiers, Inc. No other conflicts of interest were declared. Address for correspondence: Hakan Oral, M.D., Cardiovascular Center, SPC 5853, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5853, USA. Fax: +1-734-936-7026; E-mail: oralh@umich.edu Manuscript received 15 March 2009; Revised manuscript received 30 June 2009; Accepted for publication 7 July 2009. doi: 10.1111/j.1540-8167.2009.01571.x tients with paroxysmal AF. 4 Therefore, it is possible that isoproterenol is a more accurate predictor than rapid pacing of clinical outcomes after ablation. However, no prior stud- ies have compared the clinical value of isoproterenol versus rapid atrial pacing as predictors of outcomes after catheter ablation of paroxysmal AF. The purpose of this study was to prospectively deter- mine whether the noninducibility of AF in response to iso- proterenol is predictive of freedom from recurrent AF af- ter catheter ablation and whether the predictive value of isoproterenol is higher or lower than that of rapid atrial pacing. Methods Study Subjects The subjects of this prospective study were 112 consecu- tive patients who presented to the electrophysiology labora- tory in sinus rhythm for catheter ablation of paroxysmal AF (PAF). There were 75 men and 37 women. The mean age of the patients was 56 ± 13 years. AF was first diagnosed 7 ± 6 years before presentation. The mean left ventricular ejection