815 C ardiac resynchronization therapy (CRT) is an established treatment of heart failure because of left ventricular (LV) systolic dysfunction, with evidence of electric and mechanical dyssynchrony. 1,2 The mechanism of improvement with CRT is based on the stimulation of the mostly delayed LV sites. 3–5 Phrenic nerve stimulation (PNS) is a major complication that may result in withdrawal of CRT. PNS is observed in 33% to 37% of patients, 6–8 and although it is actively addressed in different ways during implantation, 6 it may be difficult to overcome in the long-term management of CRT patients. 9–11 Indeed, ≈15% of patients need to be reevaluated after hospi- tal discharge because of PNS occurrence at follow-up, 9–11 and ≈6.6% eventually report PNS symptoms at long-term follow- up, despite multiple attempts to avoid PNS. 10 Clinical Perspective on p 820 Device manufacturers have developed approaches to man- age PNS, such as electronic repositioning, multiple pacing vectors, and modification of the pacing output, but no definite solution has fully addressed this demanding challenge. 12 We sought to investigate the physiological principles of PNS occurrence in an animal model to develop a comprehensive strategy aimed at PNS avoidance in the clinical practice. Methods This was an acute open-chest study on 6 anesthetized adult dogs. The dogs were premedicated with morphine (1 mg/kg IM), and anesthe- sia was induced with propofol (120 mg IV) and isoflurane to effect. ECG limb leads were placed and connected to an electrophysiology (EP) recording station (Prucka; GE Medical Systems) for monitoring. A jugular access was obtained, and a standard Attain catheter (model 6216A; Medtronic Inc, Minneapolis, MN) was introduced in the coronary sinus to perform a venogram (Figure 1A). An implantable cardioverter-defibrillator lead (model 6935; Medtronic Inc) was implanted in the right ventricle via jugular access to provide an anodal electrode for unipolar measurements and to guarantee backup pacing, if necessary. Decapolar EP catheter with standard (2 mm-5 mm-2 mm) interelec- trode spacing (model 041590CS, Torqr; Medtronic Inc) and modified (1 mm-5 mm-1 mm) interelectrode spacing was placed into a posterior/ © 2012 American Heart Association, Inc. Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org DOI: 10.1161/CIRCEP.112.971317 Received February 6, 2012; accepted June 29, 2012. From the Institute of Cardiology, University of Bologna, Bologna, Italy (B.M.); Medtronic Inc, Minneapolis, MN (F.L., E.B., E.M., G.N., S.J., H.T., Y.P.); and Medtronic Italia S.p.A, Rome, Italy (D.S.T., V.A.). Correspondence to Mauro Biffi, MD, Institute of Cardiology, University of Bologna Via Massarenti 940138 Bologna, Italy. E-mail mauro.biffi@aosp.bo.it Background—Phrenic nerve stimulation (PNS) is a common complication of cardiac resynchronization therapy when left ventricular (LV) pacing occurs via a coronary vein. The purpose of this study was to evaluate the effects of bipolar electrode spacing on PNS and LV pacing thresholds. Methods and Results—Electrophysiology catheters with standard (2 mm-5 mm-2 mm) or modified (1 mm-5 mm-1 mm) interelectrode spacing was, respectively, inserted in a posterior/lateral cardiac vein in a randomized order in 6 anesthetized dogs via jugular access. The phrenic nerve was dissected via a left minithoracotomy and repositioned over the vein as close as possible to one of the electrodes. The presence of PNS was verified (ie, PNS threshold <2 V at 0.5 ms in unipolar configuration). Bipolar pacing was delivered using the electrode closest to the phrenic nerve as the cathode, and multiple bipolar electrode spacing configurations were tested. During bipolar pacing, PNS threshold increased as bipolar electrode spacing was reduced (P<0.05), whereas LV pacing thresholds did not change significantly (P>0.05). Compared with a standard bipolar electrode spacing of 20 mm for LV leads, 1 and 2 mm bipolar electrode spacing resulted in a PNS threshold increase of 5.5±2.2 V (P=0.003) and 2.8±1.7 V (P<0.001), respectively. Similarly, PNS threshold increased by 6.5±3.7 V with 1 mm and by 3.8±1.9 V with 2 mm bipolar pacing (both P<0.001), compared with unipolar pacing. Conclusions—This study suggests that reducing LV bipolar electrode spacing from the standard 20 mm to 1 or 2 mm may significantly increase the PNS threshold without compromising LV pacing thresholds. (Circ Arrhythm Electrophysiol. 2012;5:815-820.) Key Words: interelectrode spacing ◼ cardiac resynchronization therapy ◼ phrenic nerve stimulation Effect of Bipolar Electrode Spacing on Phrenic Nerve Stimulation and Left Ventricular Pacing Thresholds An Acute Canine Study Mauro Biffi, MD; Laurie Foerster, BS; William Eastman, BS; Michael Eggen, PhD; Nathan A. Grenz, BS; John Sommer, BS; Tiziana De Santo, MSc; Tarek Haddad, MSc; Annamaria Varbaro, MS; Zhongping Yang, PhD by guest on November 29, 2016 http://circep.ahajournals.org/ Downloaded from