Additional electrodes on the Quartet TM LV leadprovidemoreprogrammablepacing options than bipolar and tripolar equivalents

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1 Europace (2017) 19, doi: /europace/euw039 CLINICAL RESEARCH Leads and lead extraction Additional electrodes on the Quartet TM LV leadprovidemoreprogrammablepacing options than bipolar and tripolar equivalents David O Donnell 1 *, Johannes Sperzel 2, Bernard Thibault 3, Christopher A. Rinaldi 4, Carlo Pappone 5, Klaus-Jürgen Gutleben 6, Christopher Leclercq 7, Hedi Razavi 8, Kyungmoo Ryu 8, Luke C. Mcspadden 8, Avi Fischer 8, and Gery Tomassoni 9 1 Electrophysiology Unit, Department of Cardiology, Austin Health, Studley Road, Heidleberg 3084, Melbourne, Australia; 2 Kerckhoff Klinik GmbH, Bad Nauheim, Germany; 3 Montreal Heart Institute, Montreal, Québec, Canada; 4 Guy s and St Thomas Hospitals, London, UK; 5 Department of Arrhythmology, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy; 6 Herz- und Diabeteszentrum NRW, Bad Oeynhausen, Germany; 7 CHU Pontchaillou, Rennes, France; 8 St Jude Medical, Inc., Sylmar, CA, USA; and 9 Baptist Health, Lexington, KY, USA Received 2 November 2015; accepted after revision 2 February 2016; online publish-ahead-of-print 19 March 2016 Aims The aim of this study was to evaluate any benefits to the number of viable pacing vectors and maximal spatial coverage with quadripolar left ventricular (LV) leads when compared with tripolar and bipolar equivalents in patients receiving cardiac resynchronization therapy (CRT).... Methods A meta-analysis of five previously published clinical trials involving the Quartet TM LV lead (St Jude Medical, St Paul, MN, and results USA) was performed to evaluate the number of viable pacing vectors defined as capture thresholds 2.5 V and no phrenic nerve stimulation and maximal spatial coverage of viable vectors in CRT patients at pre-discharge (n ¼ 370) and first follow-up (n ¼ 355). Bipolar and tripolar lead configurations were modelled by systematic elimination of two and one electrode(s), respectively, from the Quartet lead. The Quartet lead with its four pacing electrodes exhibited the greatest number of pacing vectors per patient when compared with the best bipolar and the best tripolar modelled equivalents. Similarly, the Quartet lead provided the highest spatial coverage in terms of the distance between two furthest viable pacing cathodes when compared with the best bipolar and the best tripolar configurations (P, 0.05). Among the three modelled bipolar configurations, the lead configuration with the two most distal electrodes resulted in the highest number of viable pacing vectors. Among the four modelled tripolar configurations, elimination of the second proximal electrode (M3) resulted in the highest number of viable pacing options per patient. There were no significant differences observed between pre-discharge and first follow-up analyses.... Conclusion The Quartet lead with its four electrodes and the capability to pace from four anatomical locations provided the highest number of viable pacing vectors at pre-discharge and first follow-up visits, providing more flexibility in device programming and enabling continuation of CRT in more patients when compared with bipolar and tripolar equivalents Keywords Cardiac resynchronization therapy (CRT) Quadripolar Left ventricular leads Device programming Introduction Cardiac resynchronization therapy (CRT) has been shown to reduce all-cause mortality and heart failure hospitalizations. 1,2 Conventional CRT has utilized implanted left ventricular (LV) leads that are bipolar with two pacing electrodes. This allows at most three different pacing vectors (one bipolar and two extended bipolar vectors). With the recent development of quadripolar LV leads, a larger number of pacing vectors are possible, providing added flexibility in CRT programming. These leads have three ring electrodes in addition to the distal tip electrode and can enable pacing and sensing capabilities from each of the four electrodes. * Corresponding author. Tel: ; fax: address: odonnell_research@hotmail.com Published on behalf of the European Society of Cardiology. All rights reserved. & The Author For permissions please journals.permissions@oup.com.

2 Better programmability with Quartet than bi- and tripolar equivalents 589 What s new? We compared the availability of viable pacing vectors for different modelled left ventricular (LV) lead configurations using two, three, or four electrodes of a quadripolar LV lead (Quartet TM ). Quartet lead with its four pacing electrodes and four unique anatomical pacing locations provided the greatest number of viable pacing vectors with capture thresholds 2.5 V and no phrenic nerve stimulation (PNS), when compared with modelled bipolar and tripolar equivalents. Available quadripolar pacing configurations in Quartet lead provided more options for resolving PNS by reprogramming than modelled bipolar and tripolar configurations. Available quadripolar pacing configurations in Quartet lead also provided the largest spatial coverage in terms of the distance along the lead between two furthest viable pacing cathodes when compared with the bipolar and tripolar equivalents. The first commercially available quadripolar LV lead, Quartet TM lead (St Jude Medical, Sylmar, CA, USA), has been extensively compared with conventional bipolar leads and has been shown to mitigate pacing complications both at implant and post-implant follow-up. With increased implant success and with reduced LV lead deactivation and/or replacement, more patients receive ongoingcrt,whichultimatelyresultsinlowermortalitywiththe Quartet lead compared with bipolar leads. 3 The Quartet lead also facilitates optimal LV basal pacing which improves haemodynamics, synchrony, and mortality compared with apical lead positioning Currently available quadripolar LV leads provide a variety of shapes with different electrode spacings. Given that the relative spacing of the electrodes on the lead defines the number of unique anatomical locations that can be paced, it is understood that the current designs allow a maximum of three or four unique options. The aim of this study was to evaluate any additional benefits of Quartet lead with its four unique anatomical locations when compared with bipolar and tripolar equivalents. These benefits were evaluated in terms of the number of viable pacing options and the maximal spatial coverage offered per patient. Methods A meta-analysis of five trials involving the Quartet LV lead was performed to study the number of viable pacing vectors and maximal spatial coverage per patient with Quartet when compared with modelled bipolar and tripolar equivalents at two different time points of pre-discharge and first follow-up. Included trials We included data from five previously published clinical studies involving the Quartet LV lead Characteristics of these studies are listed in Table 1. These included two single-centre and three multi-centre studies in Europe (n ¼ 4) and the USA (n ¼ 1). First follow-up ranged from 1 month + 7 days to 3 months + 14 days. Patient population Patients with a standard indication for CRT system implantation who fulfilled the inclusion and exclusion criteria of each respective trial were included. Each patient received a CRT device with a Quartet LV lead. The number of enrolments and complete data sets at pre-discharge and first follow-up are included in Table 1. Intotal,datafrom370 CRT recipients at pre-discharge and 355 at first follow-up were included in this analysis. Pacing vectors Quartet lead is a quadripolar lead with four pacing electrodes, labelled as D1, M2, M3, and P4 located distal to proximal along the lead body. The inter-electrode spacings along the lead are as follows: D1 to M2: 20 mm, M2 to M3: 10 mm, and M3 to P4: 17 mm. Using the four pacing electrodes, a total of 10 different pacing vectors are available for programming. The available pacing vectors included six bipolar vectors (D1 M2, M3 M2, M3 P4, D1 P4, M2 P4, and P4 M2) and four extended bipolar vectors (D1 RVcoil, M2 RVcoil, M3 RVcoil, and P4 RVcoil). Data collection Capture threshold and the presence of phrenic nerve stimulation (PNS) were tested for all 10 pacing vectors in patients included in this analysis at two time points of pre-discharge and first follow-up. A pulse width of 0.5 ms was used in all cases. Presence of PNS was tested at twice the capture threshold in most included studies. In the Promote Q NTA study, PNS was tested at the maximal amplitude of 7.5 V at predischarge. At first follow-up, if PNS was documented at maximal amplitude, PNS threshold was then measured and recorded. In the Promote Q IDE study, PNS was tested at capture threshold. Viable pacing vectors Viable pacing vectors were defined as those with capture threshold 2.5 V and without recorded PNS. Lead configurations To evaluate potential benefits of additional pacing electrodes on the LV lead, capture threshold and PNS data from the 10 pacing vectors available with Quartet LV lead were used to model three different electrode configurations as follows: (i) Quartet with all four electrodes as a quadripolar LV lead; (ii) Quartet with only three out of the four pacing electrodes, modelling equivalent tripolar LV leads; and (iii) Quartet with pairs of two adjacent pacing electrodes, representing equivalent bipolar LV leads (Figure 1). Within each modelled configuration, both the cathode and the anode of a given pacing vector had to be available to evaluate the viability of the pacing vector in terms of capture threshold and presence of PNS (Table 2). The modelled configurations included four tripolar configurations and three bipolar configurations and were compared in terms of the number of viable pacing vectors and maximum spatial coverage of pacing vectors. The best lead configuration was the one with the highest median number of viable pacing vectors. Multi- Point pacing was considered available if viable pacing vectors with at least two different cathodes existed for a given configuration. Resolving phrenic nerve stimulation by reprogramming The ability to resolve PNS by reprogramming to an alternate vector was compared among the quadripolar configuration, the best tripolar configuration, and the best bipolar configuration. An occurrence of PNS on an otherwise viable vector was considered resolvable by

3 590 D. O Donnell et al. Table 1 Characteristics of included studies Complete data set at first follow-up Complete data set at pre-discharge PNS testing First follow-up Number of enrolments Study name Year Region (no. of centres)... Promote Q NTA Europe V 1 month + 7 days MSLV NTA Europe capture threshold 1 month Promote Q IDE USA threshold 1 month MPP PV Loop Europe capture threshold 3 months + 7 days MPP Programming Europe capture threshold 3 months + 14 days Total reprogramming if another viable vector was available for that patient in the given configuration. Spatial coverage To determine maximal spatial coverage of each modelled LV lead configuration, known inter-electrode distances along Quartet lead body were used to calculate a total distance along the lead body between the two furthest viable pacing cathodes. In case of a single viable pacing option, a distance of 1 mm was used instead. Statistical analysis Non-normally distributed data are summarized as median and the interquartile range (IQR), with lower quartile Q1 at 25% and upper quartile Q3 at 75%. Comparisons were performed with the Wilcoxon signed rank test. A P-value less than 0.05 was considered statistically significant. Results Electrical data at pre-discharge Median capture threshold for each of the 10 available pacing vectors for the 370 included patients at pre-discharge is shown in Table 3. The D1 RVcoil extended bipolar vector exhibited the lowest median capture threshold of 0.75 V (IQR ), followed by the D1 M2 and D1 P4 vectors with a median capture threshold of 1.0 V (IQR ). Vectors with the most proximal electrode (P4) as cathode exhibited the highest capture threshold, with the P4 RVcoil vector having a median of 3.75 V (IQR ) and the P4 M2 vector having a median of 3.75 V (IQR ) (Table 3). The percentage of patients exhibiting PNS for each of the 10 available pacing vectors of Quartet LV lead for the 370 included patients at pre-discharge is also shown in Table 3. The presence of PNS was lowest for the P4 RVcoil vector at 9.5% and highest for the M2 RVcoil extended bipolar vector at 16.0%. Electrical data at first follow-up Median capture threshold for each of the 10 available pacing vectors for the 355 included patients at first follow-up is shown in Table 3. Similar to pre-discharge, the D1 RVcoil extended bipolar vector exhibited the lowest median capture threshold of 0.75 V (IQR ), followed by the D1 M2 and D1 P4 vectors with a median capture threshold of 1.0 V (IQR and , respectively). Vectors with the most proximal electrode (P4) as their cathode exhibited the highest capture threshold at first followup, with the P4 M2 vector having the highest median of 4.25 V (IQR ) (Table 3). The percentage of patients exhibiting PNS for each of the 10 available pacing vectors of Quartet LV lead for the 355 included patients at first follow-up is also shown in Table 3. The presence of PNS was lowest for the P4 RVcoil vector at 8.7% and highest for the M2 RVcoil and M3 RVcoil extended bipolar vectors at 15.5%. Viability of pacing options at pre-discharge and first follow-up Among the modelled bipolar configurations, the most distal pair of pacing electrodes (D1 and M2) provided the greatest number of viable pacing options per patient with a median of 3 vectors

4 Better programmability with Quartet than bi- and tripolar equivalents 591 A Quadripolar B Tripolar C Bipolar D1 M2 M3 P4 D1 M2 M3 D1 M2 20 mm 10 mm 17 mm 20 mm 10 mm D1 M2 P4 20 mm M2 M3 20 mm 27 mm D1 M3 P4 10 mm M3 P4 30 mm 17 mm M2 M3 P4 17 mm 10 mm17 mm Figure 1 Modelled lead configurations: (A) Quartet with all four electrodes as a quadripolar lead, (B) Quartet with only three electrodes as a tripolar equivalent lead, and (C) Quartet with only two adjacent electrodes as a bipolar equivalent lead. Table 2 List of included pacing vectors in each configuration Quartet... Tripolar configurations... Bipolar configurations... D1, M2, M3, P4 M2, M3, P4 D1, M3, P4 D1, M2, P4 D1, M2, M3 D1, M2 M2, M3 M3, P4... D1 D1 M2 D1 M2 D1 M2 D1 M2 D1 P4 D1 P4 D1 P4 D1 RVcoil D1 RVcoil D1 RVcoil D1 RVcoil D1 RVcoil M2 M2 P4 M2 P4 M2 P4 M2 RVcoil M2 RVcoil M2 RVcoil M2 RVcoil M2 RVcoil M2 RVcoil M3 M3 M2 M3 M2 M3 M2 M3 M2 M3 P4 M3 P4 M3 P4 M3 P4 M3 RVcoil M3 RVcoil M3 RVcoil M3 RVcoil M3 RVcoil M3 RVcoil P4 P4 M2 P4 M2 P4 M2 P4 RVcoil P4 RVcoil P4 RVcoil P4 RVcoil P4 RVcoil (IQR 2 3) and was classified as the best bipolar configuration at pre-discharge. The other pairs of electrodes showed fewer numbers of viable pacing options per patient with a median of 2 (IQR 1 3) for the M3 and M2 pair and a median of 1 (IQR 0 2) for the M3 and P4 pair. The same trends were observed at first follow-up with the same median and IQR values for all three modelled bipolar configurations. Among the modelled tripolar configurations, elimination of the M3 electrode resulted in the greatest number of viable pacing options per patient with a median of 4 (IQR 3 5) and was classified as the best tripolar configuration at pre-discharge. The other three tripolar configurations showed a lower median of 3 viable pacing options per patient, with an IQR of 2 5 for the D1, M2, and M3 configuration, IQR of 2 4 for the D1, M3, and P4 configuration, and IQR of 1 6 for the M2, M3, and P4 configuration. At first follow-up, elimination of the M3 electrode continued to provide the greatest median number of viable pacing vectors per patient at 4 (IQR 3 6). Elimination of the D1 electrode at first follow-up resulted in a median of 3 (IQR 1 5), with a lower 75th percentile when compared with pre-discharge. Median and IQR values remained the same from pre-discharge to first follow-up with modelled tripolar configurations eliminating the M2 and P4 electrodes. At pre-discharge, the Quartet LV lead provided the greatest number of viable pacing vectors compared to the best bipolar and tripolar configurations with a median of 6 (IQR 3 8), when compared with a median of 3 vectors (IQR 2 3) for the best bipolar configuration (P, 0.001) and a median of 4 vectors (IQR 3 5) for the best tripolar configuration (P, 0.001, Figure 2). At first follow-up, Quartet still provided the greatest number of viable vectors with a median of 5 (IQR 3 8), when compared with a median of 3 vectors (IQR 2 3) for the best bipolar configuration (P, 0.001) and a median of 4 vectors (IQR 3 6) for the best tripolar configuration (P ¼ 0.008). The additional electrodes on Quartet resulted in 95% of the patients (n ¼ 351) at pre-discharge or 96% of the patients (n ¼ 340) at first follow-up having at least one viable pacing vector, when compared with 93% (n ¼ 344) at pre-discharge or 95% (n ¼ 337) at first follow-up with the best tripolar configuration and 90% (n ¼ 333) at pre-discharge or 91% (n ¼ 324) at first follow-up with the best bipolar configuration. Furthermore, basal pacing was more often

5 592 D. O Donnell et al. Table 3 Summary of electrical data at pre-discharge and first follow-up Vector D1 RVcoil M2 RVcoil M3 RVcoil P4 RVcoil D1 M2 D1 P4 M2 P4 M3 M2 M3 P4 P4 M2... Pre-discharge (n ¼ 370) Median Capture 0.75 ( ) 1.25 ( ) 1.75 ( ) 3.75 ( ) 1.0 ( ) 1.0 ( ) 1.75 ( ) 2.5 ( ) 2.5 ( ) 3.75 ( ) threshold (V) (IQR) Presence of PNS (%) First follow-up (n ¼ 355) Median Capture 0.75 ( ) 1.25 ( ) 1.75 ( ) 3.75 ( ) 1.0 ( ) 1.0 ( ) 2.0 ( ) 2.75 ( ) 3.0 ( ) 4.25 ( ) threshold (V) (IQR) Presence of PNS (%) PNS, phrenic nerve stimulation. available with the Quartet lead with 54% (n ¼ 198) of the patients at pre-discharge and 51% (n ¼ 181) at first follow-up having at least one viable pacing vector with M3 or P4 as cathode when compared with the best tripolar configuration with 24% (n ¼ 89) at predischarge and 17% (n ¼ 62) at first follow-up. All four LV electrodes were available for pacing in 27% of the patients at pre-discharge (n ¼ 99) and 26% of the patients at first follow-up (n ¼ 93). Resolving phrenic nerve stimulation by reprogramming at pre-discharge and first follow-up Using the Quartet lead, 94% of vector unavailability due to PNS at pre-discharge could be resolved by reprogramming to an alternate vector when compared with 89% with the best tripolar and 68% with the best bipolar configurations. At first follow-up, 92, 87, and 60% of unavailability due to PNS could be resolved by reprogramming with the Quartet, best tripolar, and best bipolar configurations, respectively. Availability of MultiPoint pacing at pre-discharge and first follow-up With the Quartet lead, MultiPoint pacing was available in 284/370 (77%) patients at pre-discharge and 279/355 (79%) at first followup. With the best tripolar and bipolar configurations, respectively, MultiPoint pacing was available in 263/370 (71%) and 223/370 (60%) patients at pre-discharge and 257/355 (72%) and 216/355 (61%) patients at first follow-up. Spatial coverage With four unique anatomical pacing locations, Quartet provided significantly wider spatial coverage [median 30 mm (IQR 20 47)] when compared with the best bipolar and tripolar configurations [median 20 mm (IQR 1 20), P ¼ and median 20 mm (IQR 20 47), P, 0.001, respectively] (Figure 3). Median and IQR values for maximal spatial coverage remained the same between predischarge and first follow-up. Discussion The major finding of this study was that the Quartet quadripolar LV lead resulted in significantly increased numbers of viable electrodes compared with modelled bipolar or tripolar configurations. In addition, the spatial coverage of the Quartet lead was significantly greater than that of the bipolar or tripolar modelled configurations. This study used a modelled bipolar and tripolar lead, which gave every opportunity for the non-quadripolar leads to have their best results. The investigation looked at multiple configurations and chose the best modelled lead and, despite this, the best bipolar and tripolar leads were inferior to the quadripolar lead. In practice, when using non-quadripolar leads, there is not an option to electrically choose the two or three best suited poles. The more clinically relevant analysis compared the quadripolar lead with just the distal bipolar or tripolar leads, as this would represent the likely final lead position if a quadripolar lead was not chosen. The best modelled bipolar configuration in our study included the D1 and M2 electrodes. The spacing between these two electrodes is 20 mm, which is

6 Better programmability with Quartet than bi- and tripolar equivalents 593 Number of viable vectors per patient Median Mean 25% 75% 9% 91% Quartet Best tripolar Best bipolar Figure 2 Number of viable vectors with capture threshold 2.5 V and no PNS for Quartet vs. best tripolar and best bipolar modelled configurations at pre-discharge (n ¼ 370). The Quartet LV lead provided the greatest number of viable vectors per patient when compared with the best tripolar and best bipolar modelled configurations. Distance between two furthest viable cathodes (mm) Median Mean 25% 75% 9% 91% Quartet Best tripolar Best bipolar Figure 3 Spatial coverage of Quartet vs. best tripolar and best bipolar modelled configurations at pre-discharge (n ¼ 370) in terms of the distance between the two furthest viable cathodes. The Quartet LV lead provided the greatest spatial coverage when compared with the best tripolar and best bipolar modelled configurations. similar to the typical spacing on commercially available bipolar leads (St Jude Medical QuickFlex m 1258: 20 mm, Medtronic Attain Ability 4196: 21 mm). The analysis of quadripolar leads vs. the distal bipolar or tripolar leads further emphasized the increased value of the quadripolar lead. Quadripolar LV pacing leads have been available for delivery of resynchronization therapy since 2010 when Quartet was first implanted in humans. 16 The Quartet LV lead has been extensively evaluated in single-centre and multi-centre studies to demonstrate safety and efficacy in increasing implant success rates by providing additional programming options. 4,17 In particular, Shetty et al. 17 used Quartet LV leads in patients with previous failed attempts at LV lead implantation and demonstrated successful implants with satisfactory short-term lead parameters to mitigate implant challenges. During follow-up, electronic repositioning with Quartet has become an important non-invasive option for the management of PNS. 4,6,14,18 In particular, Vado et al. 18 successfully resolved 100% of all PNS issues by the non-invasive reprogramming of the Quartet stimulation vector in a single-centre study with 18.9 months of follow-up. In addition to increased implant success rates and reduced rates of necessary invasive interventions during follow-up, the Quartet lead has also been shown to result in improved haemodynamics. The increased spatial coverage of the Quartet lead increases the options to improve cardiac output (CO) and ultimately patient response. In the current study, we found that the Quartet lead resulted in greater availability of pacing vectors using proximal electrodes as the cathode than the best tripolar equivalent. Calò et al. 19 evaluated the haemodynamic effects of non-traditional pacing vectors on Quartet that make use of the P4 and M3 proximal electrodes and determined that these vectors were generally associated with improved velocity time integral, myocardial performance index, and mitral regurgitation measurements using 2D echocardiography. Optimizing the programming of the LV lead using these echocardiography-based parameters resulted in significant improvements in functional class and haemodynamics after 6 months. Cabrera Bueno et al. 20 evaluated CO in CRT patients receiving Quartet LV leads and showed that the best CO from a nontraditional pacing vector on Quartet lead was better than CO from the best conventional bipolar vector. The major finding of this study was that Quartet with its four electrodes provides a higher number of viable pacing options to patients and more options for resolving PNS when compared with modelled tripolar and bipolar configurations. As a result of the higher number of viable pacing options, the Quartet enables a wider maximal spacing between available pacing sites, allowing greater anatomical coverage of the LV. This study used fairly restrictive definitions of a viable vector in terms of threshold and PNS. These definitions were chosen as optimal in terms of battery longevity and patient tolerance. The analysis demonstrated improvement in patients with a least one viable vector from 90% with a distal bipolar configuration to 95% with a Quartet lead. In the patients without a viable vector, there may have been a usable vector with a higher threshold that may have limited battery longevity or a lower PNS safety margin resulting in occasional PNS. The choice to accept a suboptimal vector rather than reposition or deactivate the LV lead was not analysed in this article. The Quartet lead enables pacing of four distinct anatomical locations with a mm electrode spacing. Other currently available quadripolar LV leads have a variety of lead designs with different lead body shapes and electrode spacings, 21 some of which provide only three distinct anatomical locations to be paced. 22 Although different designs from different manufacturers offer choices according to individual patient s venous anatomy, the electrical characteristics of the lead remain as an important consideration. One well-known advantage of the Quartet lead is the ability to wedge the lead distally to maximize stability while still being able to pace

7 594 D. O Donnell et al. from a mid-ventricular or basal position with the proximal electrodes. Because configurations using the most proximal electrode as cathode tend to have higher pacing threshold, 14,23 a tripolar lead may frequently become essentially a bipolar lead due to the unavailability of the proximal pole and thus provide no option for basal pacing. As shown in this study, the quadripolar lead allowed for a proximal pacing configuration (M3 or P4) more than twice as often as the best tripolar configuration. We can only speculate about the reason for the higher threshold observed with more proximal electrodes, but it is likely related to larger vessel diameter closer to branch takeoff, resulting in poorer tissue electrode contact. Limitations This study had a number of potential limitations. Data were combined from five different studies and analysed retrospectively using data from the Quartet lead to model tripolar and bipolar configurations. One of the studies used slightly different methodology from the other studies to record the presence of PNS, which could alter the number of available configurations. However, we do not believe that this difference in methodology affects any of our conclusions. Vector availability in this study was defined on the basis of low capture threshold and absence of PNS, but selection based on these criteria does not ensure effective resynchronization. The most effective pacing vector varies from patient to patient and depends on many factors including the lead position and the nature of the underlying conduction disorder. The study included data from a single quadripolar lead design as the Quartet was the only commercially available quadripolar lead at the time data were collected. As a result, our analysis was limited to the pacing vectors available with the Quartet lead, which uses only M2, P4, and the RVcoil as anode. The results of this study may not be applicable to other quadripolar lead designs now on the market. The spatial coverage of different configurations was calculated using the distance along the lead body, which may differ from the three-dimensional interelectrode distance. Finally, although the proximal vectors of the Quartet lead may be the best for avoiding PNS and achieving optimal haemodynamic output, they have relatively higher capture threshold, which could limit their use due to battery longevity impact. Conclusions This study examined the viability of pacing options in terms of capture threshold and PNS at pre-discharge and first follow-up in a large cohort of patients when four, three, or two pacing electrodes are available. These results demonstrate that the Quartet LV lead with its design of four pacing electrodes at four distinct anatomical locations provides a larger number of pacing options and increased spatial coverage available for pacing when compared with conventional bipolar or tripolar lead designs. Conflict of interest: D.O. received research grants and speaker honoraria from Medtronic Inc. and St Jude Medical. B.T. has received research grants and speaker honoraria from Medtronic Inc. and St Jude Medical. C.R. receives consultancy fees from St Jude Medical. C.P. has received consultancy fees from St Jude Medical and B.C.L. receives consultancy fees and speaking honoraria from St Jude Medical. H.R., K.R., L.M., and A.F. are employees of St Jude Medical. G.T. reports modest consulting fees/honoraria from Topera, Stereotaxis, Biosense Webster, St Jude Medical, Boston Scientific, and Pfizer and advisory board membership from Topera, Stereotaxis, Biosense Webster, St Jude Medical, Biotronik, and Medtronic. References 1. Cleland JGF, Daubert J-C, Erdmann E, Freemantle N, Gras D, Kappenberger L et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352: Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009;361: Behar JM, Bostock J, Zhu Li AP, Chin HMS, Jubb S, Lent E et al. Cardiac resynchronization therapy delivered via a multipolar left ventricular lead is associated with reduced mortality and elimination of phrenic nerve stimulation: longterm follow-up from a multicenter registry. J Cardiovasc Electrophysiol 2015;26: Mehta PA, Shetty AK, Squirrel M, Bostock J, Rinaldi CA. 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8 Better programmability with Quartet than bi- and tripolar equivalents 595 response using a quadripolar LV lead. Pacing Clin Electrophysiol 2013;36: Rinaldi CA, Burri H, Thibault B, Curnis A, Rao A, Gras D et al. A review of multisite pacing to achieve cardiac resynchronization therapy. Europace 2015;17: Biffi M, Foerster L, Eastman W, Eggen M, Grenz NA, Sommer J et al. Effect of bipolar electrode spacing on phrenic nerve stimulation and left ventricular pacing thresholds an acute canine study. Circ Arrhythmia Electrophysiol 2012;5: Crossley GH, Biffi M, Johnson B, Lin A, Gras D, Hussin A et al. Performance of a novel left ventricular lead with short bipolar spacing for cardiac resynchronization therapy: primary results of the Attain Performa Quadripolar Left Ventricular Lead Study. Heart Rhythm 2015;12: EP CASE EXPRESS doi: /europace/euw203 Online publish-ahead-of-print 17 October Abrupt disruption of remote monitoring transmission as an indicator of safe backup mode Yoichi Ajiro*, Fumiaki Mori, and Kazunori Iwade Department of Cardiology, National Hospital Organization Yokohama Medical Center, Harajuku Totsuka-ku Yokohama-shi, Kanagawa , Japan * Corresponding author. Tel: ; fax: address: aziro-youichi@yokohamamc.jp A 78-year-old man with sick sinus syndrome and accompanying persistent atrial tachyarrhythmia had undergone dual-chamber pacemaker (Evia DR-T TM Biotronik Inc., Germany) implantation with bipolar screw-in atrial and ventricular leads (Siello JT53 TM and Siello S60 TM, Biotronik Inc.). Measured pacemaker and lead function values were within acceptable limits. Remote monitoring (Home Monitoring TM Biotronik Inc.) was used in addition to regular check-up visits for his out-of-hospital management. Data transmission via remote monitoring was favourable, with all parameters showing normal results. Twenty-two months after implantation, data transmission became disrupted. A 12-lead electrocardiography at an emergency pacemaker clinic indicated unipolar ventricular pacing (Figure). On interrogation, the pacemaker was found to be in the safe backup mode; the remote monitoring setting had been switched from ON to OFF, and pacemaker memories had been erased completely. Thorough inspection of the patient s surroundings did not identify the cause of the in-circuit excess current that resulted in the pacemaker setting changing to the safe backup mode. Pacemaker settings were reprogrammed to the former settings. The patient s clinical course was stable for 12 months thereafter. To our knowledge, this is the first case of abrupt disruption of remote monitoring transmission indicating a change to the safe backup mode. The full-length version of this report can be viewed at: escardio.org/guidelines-&-education/e-learning/clinical-cases/ Electrophysiology/EP-Case-Reports. & The Author Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com