Author + information
- E. Kevin Heist, MD, PhD∗ ()
- ↵∗Address for correspondence:
Dr. E. Kevin Heist, Cardiac Arrhythmia Service, Massachusetts General Hospital, 55 Fruit Street, GRB-8, Boston, Massachusetts 02114.
Cardiac resynchronization therapy (CRT), using a left ventricular (LV) lead placed through a branch of the coronary sinus (CS), has become standard therapy for patients with systolic heart failure and a broad QRS complex or obligatory ventricular pacing. Although CRT does not completely normalize ventricular conduction, it improves inter- and intraventricular electrical and mechanical dyssynchrony and thereby leads to significant improvements in congestive heart failure (CHF) symptoms, and LV dimensions and function, and reduces overall mortality (1). Despite these important benefits of traditional CRT, it cannot be offered uniformly to all patients who may benefit, and some patients show little or no response to therapy. Difficulty in navigating an LV lead through the highly variable CS anatomy, lack of adequate CS branches overlying optimal LV segments, high pacing thresholds, phrenic nerve stimulation, and nonphysiological LV depolarization originating from the epicardial LV surface are all potential impediments to effective CRT delivery.
Some patients who may benefit from CRT do not receive the therapy at all due to failure to place an LV lead. This failure to place an LV lead has dropped from >10% in early CRT studies to approximately 5% in more modern series. Other patients receive CRT but do not derive maximal benefit from the therapy due to suboptimal LV lead position related to the constraints of CS lead placement mentioned previously. Multiple published studies have documented a greater response to CRT based on LV lead placement strategies based on the distance from the LV to the right ventricular (RV) lead electrodes (2), avoidance of the LV anterior wall or apex (targeting basal and midventricular sites in the posterior and lateral LV wall) (3,4), and targeting sites of LV electrical delay and of mechanical dyssynchrony and away from ventricular scar (5–9). Although most practitioners who implant CRT are aware of at least some of these LV lead-based predictors of CRT response, CS anatomic variation, variable pacing thresholds, and phrenic nerve location often prevent placement of an LV lead at a targeted site.
LV endocardial pacing potentially offers a way around the constraints of placing an LV lead through the CS. Acute studies have demonstrated greater potential resynchronization and acute hemodynamic response with LV endocardial pacing than with epicardial pacing, even with optimal LV lead positioning at each site (10). The CS with its variable anatomy and the phrenic nerve are removed completely from the equation, and one would expect good pacing thresholds throughout much of the LV endocardial surface, with the exception of LV scar (which should not be targeted for LV pacing anyway). Techniques for mapping the LV endocardium that were developed for ventricular tachycardia ablation allow a skilled operator relatively free access across the LV endocardial surface.
However, endocardial LV pacing also creates challenges compared with traditional CS pacing. A conventional pacing lead can be placed into the LV endocardial surface through a transseptal approach, but this presents its own procedural technical issues, and leaving a large segment of pacing lead permanently exposed to the left side of the heart also carries the risk of thromboembolism and stroke, even among patients who are taking anticoagulation therapy (11). Leadless RV pacing (with the battery and all electronics contained within the pacemaker) is now in routine clinical use for patients who require single-chamber ventricular pacing, but this system has not been approved for use in the LV and does not allow for atrioventricular or RV-LV synchrony as is typically required for conventional CRT (12).
The WiSE-CRT system (EBR Systems, Sunnyvale, California) has been developed as an alternative strategy for endocardial LV pacing, which allows for atrioventricular and RV-LV synchronization when paired with a conventional pacemaker or implantable cardioverter-defibrillator with RV pacing capability. In the WiSE-CRT system, a small passive electrode is implanted in the LV endocardial surface. The WiSE-CRT system uses a subcutaneous detector and transmitter to then detect the RV pacing spike and then transmit ultrasound energy to be picked up by the passive LV electrode and converted into an LV pacing stimulus that occurs just after the RV pacing stimulus. Initial publications have demonstrated implantation feasibility for the WiSE-CRT system as well as QRS narrowing and both echocardiographic and clinical response to this novel form of CRT in patients who were nonresponders or could not undergo implantation of conventional CRT with a CS LV lead (13). In addition, the very small size of the WiSE-CRT LV endocardial electrode does not require long-term anticoagulation and has not been associated with obvious thromboembolic risk in small series of patients studied to date.
Important questions that arise with LV endocardial pacing (including use of the WiSE-CRT system) are how the LV electrode should be targeted within the ventricle and whether the same strategies for LV electrode placement that have shown benefit for epicardial (CS) LV leads in multiple published studies can be extrapolated to LV endocardial pacing. In this issue of JACC: Clinical Electrophysiology, Sieniewicz et al. (14). provide data to begin to answer that question. They studied 3 different strategies for LV electrode placement in 26 patients in a nonrandomized fashion (the strategy for performing the implantations was center specific and based on those used in 3 other centers in the United Kingdom). The 3 strategies included: 1) targeting mechanically late LV regions with avoidance of scarred regions based on echocardiography; 2) targeting electrically late LV regions with avoidance of nonviable areas (based on high pacing thresholds); and 3) combining electroanatomic mapping to identify electrically late LV regions coupled, when feasible, with cardiac magnetic resonance imaging identification of mechanically delayed LV regions and avoidance of scar.
The main findings are that the overall LV targeting approach used in this study (grouping the 3 strategies together) produced a substantial rate of reverse remodeling (71%) and composite echocardiographic response (90%) (14) that was higher than that in a prior study of the WiSE-CRT system performed in a similar group of patients but without these more intensive strategies to optimize LV lead localization, in which the reverse remodeling rate was 52% (13). Indices of electrical delay at the LV electrode implantation site (QLV and QLV/QRS duration) (5,6), which have been previously demonstrated to predict acute hemodynamic response to conventional CRT, were similarly significantly predictive in this study of the WiSE-CRT system, and avoidance of scar was also found to be significantly beneficial. QRS narrowing with CRT demonstrated a nearly significant trend toward improvement in acute hemodynamic response. As with anatomic strategies for traditional CS LV lead placement, the basal-mid posterior and lateral LV walls were most often identified as the optimal sites for LV electrode placement with the WiSE-CRT system but with large variability between patients.
There are several important limitations to this current study. This was a small (26 patients) nonrandomized study, with 3 implant strategies deployed based entirely on which of the 3 centers was performing any given implantation. This study was far too small to determine which of the 3 strategies produced optimal outcomes, and there was not a control group in this study to determine definitively that any of the 3 LV electrode strategies was superior to a random or anatomic LV electrode placement strategy. It is notable, however, that well-accepted strategies for traditional epicardial CRT also showed apparent benefit with the WiSE-CRT system. These strategies (targeting electrically or mechanically delayed areas and avoidance of scar) have a solid physiologic basis, and it should therefore come as no surprise that they would demonstrate benefit in resynchronization from pacing either the LV endocardium or epicardium.
How should a practitioner synthesize the new WiSE-CRT system findings? To start, as with conventional CRT, it is now reasonable to believe that patient-specific targeting of the LV endocardial electrode with the WiSE-CRT system is likely to improve patient outcomes. Second, it is not yet clear which strategy of LV electrode targeting is “best” with the WiSE-CRT system; despite a huge amount of published work on the subject, there is still no consensus on the “best” strategy for traditional CRT LV lead placement (but it is clear that having a strategy is better than having no strategy). Very few practitioners of conventional CRT use all available targeting strategies to place CS leads; most target the lead based on the expertise (whether electrical delay, mechanical delay, scar avoidance, or a combination) available at their institution. In fact, that is what was done in this study with the WiSE-CRT system, with each of the 3 centers selecting an LV electrode targeting strategy that best fit its own particular institutional expertise. Until or unless definitive data demonstrate that a particular method of endocardial LV targeting is superior to the alternatives, targeting the WiSE-CRT LV electrode based on the particular expertise and equipment available to a given operator (and likely roughly the same strategies each operator is currently using for traditional CRT but freed from constraints of the CS anatomy and phrenic nerve) is a perfectly reasonable approach, and likely to result in better CRT outcomes than a blind, nontargeted approach.
↵∗ Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology.
Dr. Heist has served as a consultant for Boston Scientific, Biotronik, Medtronic, Pfizer, and St. Jude Medical; and has received research grants from Biotronik and St. Jude Medical.
The author attests he is in compliance with human studies committees and animal welfare regulations of the author’s institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- 2018 American College of Cardiology Foundation
- Gold M.R.,
- Yu Y.,
- Wold N.,
- Day J.D.
- Khan F.Z.,
- Virdee M.S.,
- Palmer C.R.,
- et al.
- Behar J.M.,
- Rajani R.,
- Pourmorteza A.,
- et al.
- Nguyên U.C.,
- Mafi-Rad M.,
- Aben J.P.,
- et al.
- Tjong F.V.,
- Reddy V.Y.
- Reddy V.Y.,
- Miller M.A.,
- Neuzil P.,
- et al.
- Sieniewicz B.J.,
- Behar J.M.,
- Gould J.,
- et al.