A Prospective Study Comparing the Sensed R Wave in Bipolar and Extended Bipolar Configurations: The PropR Study

Transcription

1 A Prospective Study Comparing the Sensed R Wave in Bipolar and Extended Bipolar Configurations: The PropR Study ANEESH V. TOLAT, M.D.,* MELISSA WOICIECHOWSKI, M.S.N.,* ROSEMARIE KAHR, R.C.I.S.,* JOSEPH DELL ORFANO, M.D.,* ELLISON BERNS, M.D.,* BRUCE BERNSTEIN, PH.D., and NEAL LIPPMAN, M.D.* From the *Saint Francis Hospital and Medical Center, Section of Electrophysiology, University of Connecticut School of Medicine, Hartford, Connecticut; and St. Christopher s Hospital for Children, Section of General Pediatrics, Drexel University College of Medicine, Philadelphia, Pennsylvania Background: Progress in implantable cardiac defibrillator (ICD) technology has allowed for switching the sensing polarity for the detection of ventricular fibrillation (VF). However, whether one sensing polarity confers additional advantage over the other is not known. Objectives: To determine whether one sensing polarity is superior to the other for the detection of VF. Methods: Patients were enrolled into a prospective randomized study of sensing of VF and R waves in normal rhythm. Sensing of VF was determined by number of under sensed beats (USB), and time to detection of VF (TDVF). Each patient underwent ICD implantation followed by testing of the ICD. At each induction, patients were randomized to sensing in extended bipolar (EBP) or true bipolar (TBP) configuration. Additionally, R waves were compared at implant and at 1-month follow-up. Results: A total of 50 patients were enrolled into the study. When evaluating the primary endpoint, no difference was found between USB in EBP or TBP configuration; 1.1 ± 1.2 beats versus 1.3 ± 1.3 beats; P = NS. Also, no difference was found between TDVF in EBP or TBP configurations; 5.9 ± 0.6 seconds versus 5.9 ± 0.6 seconds; P = NS. With regard to the secondary endpoints, there was no difference between R waves in EBP or TBP configurations at the time of implant 10.9 ± 4.8 mv versus 10.9 ± 4.8 mv P = NS; or at 1-month follow-up 12.4 ± 4.7 mv versus 12.0 ± 5.4 mv P = NS. Conclusions: There is no difference in the detection of VF between EBP or TBP configurations in patients undergoing ICD implantation. (PACE 2013; 36: ) defibrillation ICD, clinical trials Introduction Since the introduction of the implantable cardiac defibrillator (ICD), technology has evolved rapidly to allow additional features to be added. More recent efforts have focused on avoiding inappropriate therapy using supraventricular tachycardia discriminators 1 and other algorithms. 2 Recently, Medtronic (Minneapolis, MN, USA) has provided the option of changing the sensing configuration using either true bipolar sensing (Vtip-Vring) or extended bipolar sensing (Vtip- RVcoil) on their defibrillator platform. This has Dr. Lippman has reported being a speaker for Medtronic. None of the other authors have reported any disclosures relevant to this study. This study was supported in part by an investigator initiated grant from Medtronic. Address for reprints: Aneesh V. Tolat, M.D., F.A.C.C., F.H.R.S., 1000 Asylum Ave., Suite 3206, Hartford, CT Fax: ; atolat@ctheartbeat.com Received September 12, 2012; revised November 10, 2012; accepted December 10, doi: /pace the potential for changing the way defibrillator implants and testing are performed. In addition, it may provide an opportunity to avoid oversensing of T waves and noise by changing polarity, while still maintaining sensitivity. Until recently, sensing in ventricular fibrillation (VF) could only be evaluated in one configuration. It is not clear whether sensing in VF in one configuration is necessarily the same, better, or worse than in another configuration. It is also not known whether the practice of using a longer detection interval to reduce inappropriate shocks may favor one sensing configuration over another. Finally, whether the amplitude of the R wave in sinus rhythm is more likely to change in one configuration versus the other over time is also not known. We performed a prospective randomized study comparing the true bipolar (TBP) and extended bipolar (EBP) sensing configurations for the detection of VF in each patient, and also compared the amplitude of R waves in normal sinus rhythm at implant and at 1-month followup. 2013, The Authors. Journal compilation 2013 Wiley Periodicals, Inc. PACE, Vol. 36 May

2 TOLAT, ET AL. Table I. Baseline Characteristics Demographic and Clinical Data N = 50 Patients Age-mean ± SD 63 ± 13 Male 35 (70%) History of CHF 45 (90%) History of MI 24 (48%) Cardiomyopathy Ischemic 29 (58%) Nonischemic 21 (42%) Primary prevention 41(82%) CHF = congestive heart failure; MI = myocardial infarction; SD = standard deviation. Methods Patient Population Our study enrolled 50 consecutive patients who were referred to the electrophysiology lab for implantation of a Medtronic ICD (Medtronic Inc., Minneapolis, MN, USA). All patients provided informed consent and participated in an institutional review board-approved protocol. Demographic and key clinical data are shown in Table I. Patients underwent implant of Medtronic ICD generator models Virtuoso (VR or DR) or Concerto (cardiac resynchronization therapydefibrillator), with lead model 6947 (Sprint Quattro, quadripolar, true bipolar, dual coil). All leads were placed at the right ventricular (RV) apical septum as prespecified in the protocol. Inclusion criteria included: age >18 with ability to give informed consent, subjects expected to live more than 1 year, with indication for defibrillator implant, and who were not pacemaker dependent. Patients were required to have either ischemic or nonischemic cardiomyopathy. Exclusion criteria included: the presence of preexisting leads, any condition which would preclude ICD testing at the end of the implant, and patients with inherited arrhythmias or ion channel-related arrhythmias. Study Protocol Patients who were enrolled into the study underwent standard ICD implantation followed by ICD testing at the time of implant. Testing was required in all patients with two tests performed for each patient unless in the opinion of the operator testing was not deemed to be safe for the patient. If only one test was performed, data for comparison between sensing in EBP and TBP configurations was not available and excluded from analysis. Patients were randomized to testing in one of two ways: (1) sensing of first induced VF episode in TBP followed by second induced VF in EBP, or (2) sensing of first induced VF episode in EBP, followed by second induced VF in TBP. VF was induced by either T wave shock or 50-Hz burst pacing, or both. Sensitivity on the RV ICD lead was set to 1.2 mv during testing, and the number of intervals to detect (NID) was programmed to 24/32 for all patients and both induction sequences. Final ICD programming for sensing vector (EBP or TBP) was required by protocol to be set the same as the first induction configuration unless the operator deemed the other configuration necessary for patient safety reasons. The number of beats undersensed by the device was counted from the first sensed beat to the declaration of VF detection by the device (Fig. 1). The number of undersensed beats was counted by two independent readers blinded to the sensing polarity. When disagreement existed about the number of undersensed beats, a third (blinded) experienced electrophysiologist then served to adjudicate the final number. R wave amplitudes were measured as reported by the device in both configurations at the time of implant prior to ICD testing, and at 1-month follow-up through the device reported sensing test. The primary endpoints of the study were prespecified as number of undersensed beats in VF, and time to detection of VF. Secondary endpoints of the study were sensed R wave amplitude in normal sinus rhythm or atrial fibrillation at the time of implant and at 1-month follow-up. Statistical Methods Data were evaluated and analyzed using SPSS software (IBM Corp., Armonk, NY, USA). Values of P < 0.05 were considered statistically significant. The paired T test was used to evaluate variables such as number of undersensed beats, time to VF detection, and R wave amplitudes while Pearson correlation was used to assess the relationship between decreasing ejection fraction (EF), and increased numbers of undersensed beats. Results Fifty patients were enrolled into the study, while 48 patients completed intraoperative testing, and 42 patients completed 1-month followup. Devices implanted by type included 26 single chamber, seven dual chamber, and 17 biventricular ICDs. Baseline characteristics of the study population can be found in Table I. With regard to the primary endpoints of the study, no significant difference was found between sensing of VF as measured by number of undersensed beats or time to detection of VF (Table II). During testing 542 May 2013 PACE, Vol. 36

3 THE PROPR STUDY Figure 1. Examples of differences in sensing of VF in true bipolar and extended bipolar configurations. In panel A, study patient #13 is shown undergoing defibrillation threshold (DFT) testing with undersensing seen in the true bipolar configuration (TBP). The same patient is seen in panel B undergoing a separate DFT test in extended bipolar configuration (EBP) with no undersensing. Panel C shows DFT testing in patient #27 showing fewer undersensed beats in the TBP configuration, as compared to a greater number of undersensed beats in the EBP configuration during a separate DFT test in the same patient. of VF detection at a ventricular sensitivity of 1.2 mv, the number of undersensed beats in EBP was Table II. Results of Testing of R Wave Sensing in VF and Sinus Rhythm Number of drop outs (beats) Time to VF detection (second) Mean R wave implant Mean R wave follow-up TBP EBP 1.3 ± ± 1.2 P = NS 5.9 ± ± 0.6 P = NS 10.9 ± ± 4.8 P = NS 12.0 ± ± 4.7 P = NS EBP = extended bipolar; TBP = true bipolar; VF = ventricular fibrillation. 1.1 ± 1.2 beats, while in TBP was 1.3 ± 1.3 beats; P = NS. The time to detection of VF in EBP configuration was 5.9 ± 0.6 second, and in TBP configuration was 5.9 ± 0.6 second; P = NS. With regard to secondary endpoints, no significant difference was found between the mean sensed R wave amplitude in TBP 10.9 ± 4.8 mv as compared to EBP 10.9 ± 4.8 mv configurations at the time of implant, or at 1-month follow-up; 12.0 ± 5.4 mv and 12.4 ± 4.7 mv, respectively (P = NS). There was a significant increase in mean R wave amplitude between EBP implant 10.5 mv and EBP follow-up 12.4 mv (P = 0.004) and between TBP implant 10.6 mv and TBP follow-up 12.0 mv (P = 0.033). We also evaluated the association between time to detection of VF and EF, and found a significant correlation between decreasing EF and increased time to detection of VF in TBP configuration; P = (Fig. 2). This trend was also seen in EBP configuration but did not reach statistical significance; P = PACE,Vol.36 May

4 TOLAT, ET AL. Figure 2. Shown above is the time to detection of VF as a function of EF. A significant (P=0.014) increase in time to detection is observed as EF decreases in the TBP configuration. Finally, we evaluated patients with a drop in R waves between implant and 1-month follow-up in TBP or EBP configurations to assess whether the alternative configuration had a similar effect. Of those patients who had a drop in R wave at followup, 26.2% (11 patients) occurred in the TBP configuration, while 26.8% (10 patients) occurred in the EBP configuration. A strong correlation of (P = 0.001) shown in Fig. 3, was observed between change in R waves (implant to follow-up) in TBP and EBP configurations. Discussion In our study of EBP versus TBP sensing of VF at the time of implant, we did not find a significant difference between either configuration as measured by the endpoints of mean number of undersensed beats or time to detection of VF (Table II). This finding has several important clinical implications. First, ICD testing can be performed in either configuration with an equal probability that the device will detect VF without undersensing or increased time to detection of VF. One recent smaller study of 28 patients reported a similar evaluation of EBP and TBP sensing in VF. 3 In the study, the investigators did not find a significant difference between EBP and TBP for the sensing of VF. However, the authors only measured time to detection of VF, and used an NID of 12/16. In contrast, our study used time to detection of VF and number of undersensed beats with an increased NID of 24/32, which still did not favor one configuration over another. We believe our results can be applied to patients with Figure 3. Relationship between change in R waves from implant to follow-up and sensing configuration. EBP FU initial indicates the extended bipolar R wave in follow-up minus implanted R wave; and TBP FU initial indicates true bipolar R wave in follow-up minus implanted R wave. A significant correlation of (P = 0.001) was found between change in R waves (implant to follow-up) and the two configurations. 544 May 2013 PACE, Vol. 36

5 THE PROPR STUDY a shorter NID because any difference in sensing of VF is less likely to be seen with a shorter NID. One important caveat however is that our testing was performed at 1.2 mv sensitivity favoring undersensing, while final programming is usually performed at 0.3 mv. Finally, while the PREPARE study 1 did show a reduction in arrhythmia-related shock therapy with an NID of 30/40 in primary prevention patients we chose to use a NID of 24/32 in our study because of the involvement of both primary and secondary prevention patients. At 1-month follow-up, we also did not see any oversensing occurring in either TBP or EBP sensing polarity. While the EBP sensing polarity may theoretically allow for more sensing of diaphragmatic myopotentials or T waves because of an increased electrode distance, this was not seen clinically. This may have been related to the small sample size and infrequent nature of this type of event. Other older studies with older leads and pulse generators have also shown a lack of difference between sensing of VF in TBP and EBP configurations. In a study by Goldberger et al., 4 the investigators compared simultaneous sensing in VF of both configurations at the time of ICD implant using a Transvene 6936 lead and found no significant difference between time to detection of VF or the number of undersensed beats, consistent with our findings. Interestingly, another older study did appear to find a difference between TBP and EBP sensing during redetection, after a failed first shock, favoring TBP sensing. 5 We were not able to confirm this observation in our study because we did not record simultaneously both TBP and EBP configurations, and the majority of our shocks were successful on first attempt. Another clinical implication of our study is that implanting physicians should not expect to see a difference in R waves between the two configurations in normal rhythm at the time of implant or at 1-month follow-up. This is in keeping with previous studies which also have not seen a difference in R waves. 3,5 There was, however, a significant increase in R waves between the time of implant and at follow-up, which is consistent with the generally accepted observation that the sensed electrogram usually becomes larger in follow-up. Time to Detection and EF There was a significant correlation between increased time to detection of VF, and reduced EF in the TBP configuration (Fig. 2). A similar trend was seen in the EBP configuration but was not statistically significant. To our knowledge, this observation has not been reported previously and deserves further investigation. There may be several explanations for this including that patients with lower EFs may have finer lower amplitude VF, making it more difficult for the ICD to detect; however, this would need to be evaluated in future studies. Recommendations for ICD Programming Given the results of our study, and more recent trends in ICD implantation, including the foregoing of ICD testing in primary prevention implantations, it would seem reasonable to program patients to either configuration if R waves were within acceptable range (>5 mv) in both configurations. In addition, if a patient experiences a drop in R waves in follow-up in one configuration, it may seem reasonable to reprogram to the other configuration, if the other configuration shows more robust R waves. Followup testing of the ICD may or may not need to be performed depending on the discretion of the operator, and clinical history of the patient, including whether the patient requires the ICD for primary or secondary prevention. In the future, ICD algorithms will continue to evolve which have the ability to switch sensing polarity automatically depending on the size of the R waves, presence of noise, T wave oversensing, and other factors. Our study would suggest that this could be performed since there was no significant difference overall between sensing in VF in either configuration. However, individual cases may vary and further studies would be required to confirm this. Finally, for those implanters who prefer to test defibrillators at the time of implant, testing both configurations may be a novel way of leaving the option of switching polarity without having to return to the EP lab. Limitations There are several limitations to our study that should be noted. First, our study was relatively small. In addition, the study only included patients without previous implants, and with either an ischemic or nonischemic cardiomyopathy. We did not record both TBP and EBP configurations simultaneously, but rather sequentially after testing in the opposite configuration. To reduce the chance of bias, however, we did randomize the sensing configuration tested during VF induction. Conclusions In conclusion, there was no difference in the detection of VF between EBP or TBP configurations as measured by undersensed beats, and time to detection of VF in patients with cardiomyopathy undergoing primary or secondary prevention ICD implantation. PACE,Vol.36 May

6 TOLAT, ET AL. References 1. Wilkoff BL, Williamson BD, Stern RS, Moore SL, Lu F, Lee SW, Birgersdotter-Green UM, et al. PREPARE Study Investigators. Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients: Results from the PREPARE (Primary Prevention Parameters Evaluation) study. J Am Coll Cardiol 2008; 52: Cao J, Gillberg JM, Swerdlow CD. A fully automatic, implantable cardioverter-defibrillator algorithm to prevent inappropriate detection of ventricular tachycardia or fibrillation due to T-wave oversensing in spontaneous rhythm. Heart Rhythm 2012; 9: Verga TA, Gillberg JM, Greenberg RM, Deger FT. True bipolar and integrated bipolar sensing and detection by implantable defibrillators. Pacing Clin Electrophysiol 2011; 34: Goldberger J, Horvath G, Donovan D, Johnson D, Challapalli R, Kadish AH. Detection of ventricular fibrillation by transvenous defibrillating leads: Integrated versus dedicated bipolar Ssensing. J Cardiovasc Electrophysiol 1998; 9: Frain B, Ellison K, Michaud G Koo CH, Buxton AE, Kirk MM. True bipolar defibrillator leads have increased sensing latency and threshold compared with the integrated bipolar configuration. J Cardiovasc Electrophysiol 2007; 18: May 2013 PACE, Vol. 36