Author + information
- Rasmus Borgquist, MD, PhD∗ ()
- Department of Clinical Sciences, Skane University Hospital, Cardiac Arrhythmia section, Lund University, Lund, Sweden
- ↵∗Address for correspondence:
Dr. Rasmus Borgquist, Cardiac Arrhythmia Section, Lund University, Skane University Hospital, Getingevagen, Lund, Skane 22185, Sweden.
- acute hemodynamic response
- cardiac resynchronization therapy
- multipoint pacing
- pressure-volume loops
- quadripolar lead
Despite the well-validated positive effects on morbidity and mortality for cardiac resynchronization therapy (CRT), the “nonresponder” rate of 20% to 40% continues to be an intriguing clinical challenge. In view of this situation, a growing number of publications over the last 5 years have examined the role of simultaneously pacing several spots on the left ventricular (LV) free wall, using either multisite pacing (MSP) or multipoint pacing (MPP), to improve the percentage of positive responders to CRT. MSP requires at least 2 different LV electrodes, whereas MPP has the advantage that it can be delivered by using a single multipolar LV electrode, and this method has therefore emerged as the preferred option. All the major manufacturers of CRT devices now have multipolar leads in their portfolio, and several commercially available devices are capable of delivering MPP with the use of quadripolar leads.
Initial in vivo experiences showed promising short-term hemodynamic results for MPP (1,2). The Thibault group used peak increase of left ventricular pressure (dP/dT) measurements and found that MPP improved acute hemodynamic parameters more than conventional biventricular (BiV) pacing. Rinaldi et al. (2) used surrogate echocardiographic parameters of dyssynchrony and LV function (peak radial strain and LV outflow velocity time integral) and found significant improvement in cardiac contractility for MPP compared with standard BiV pacing. In another study, Pappone et al. (3,4) used pressure volume loops and found similar short-term hemodynamic benefits of MPP, which also seemed to translate into midterm benefits at 1-year follow-up in which MPP-treated patients had sustained greater LV reverse remodeling. Zanon et al. (5) reported on 23 patients; >3 different MPP configurations were tested, on average, in each patient, and MPP offered a small but consistent numerical benefit (measured as increase in dP/dT) over conventional BiV pacing. Of note, a higher increase in dP/dT with MPP correlated positively to “classic” predictors of response such as longer Q-LV interval and greater reduction in QRS duration.
Most of the studies published thus far have been too small for any reliable subgroup analysis, although there are indications that initial nonresponders have greater benefit, as do men and patients with non–left bundle branch block (LBBB) and those with myocardial scarring (2,3,6,7). Intuitively, this outcome makes sense, because there is more to gain when you start from a lower point (i.e., nonresponders), and critically positioned LV scarring (e.g., ischemic cardiomyopathy with atypical bundle branch block) could hypothetically be overcome by simultaneously pacing on both sides of the scar (8).
In this issue of JACC: Clinical Electrophysiology, van Everdingen et al. (9) report on 43 patients with standard indications for CRT and a strict LBBB according to the Strauss criteria. These patients were extensively examined using hemodynamic measurements in the perioperative setting, comparing conventional BiV pacing and hemodynamically optimal biventricular pacing (BiV-OPT) versus MPP. Contrary to many of the previous studies, care was taken to use the optimal atrioventricular interval for each tested pacing configuration, and interlead LV conduction velocities were also measured. Pressure volume loops were used to calculate stroke work (SW), and comparisons were then made relative to baseline AAI pacing (Δ%SW). The main findings were as follows: 1) there was considerable individual variation in which electrode configuration produced the highest Δ%SW; and 2) overall, there was no significant change in Δ%SW between BiV-OPT and MPP (–5 ± 24%; p = 0.19), even though in 40% of individual cases, the MPP setting was numerically better than BiV-OPT. In multivariate analysis, male sex and low ejection fraction were the only independent predictors of favorable hemodynamic response to MPP compared with BiV-OPT. Overall, the added value of MPP was less than in some of the aforementioned studies but in line with the results of Sterliński et al. (10), who also used optimal atrioventricular delays for their comparisons between MPP and BiV-OPT. An important limitation of the present study is that only patients with strict LBBB were included, whereas previous research suggests that the patients most likely to benefit from MPP may indeed be those with a non-LBBB configuration.
Van Everdingen et al. (9) have added important data to support that patient-specific individualization of CRT is key. On a group level, the benefits are modest at best, but on an individual level, in the right patient, MPP can be a game-changer converting nonresponse to positive CRT response. However, it is still unclear whether MPP activation translates into clinically significant long-term benefits, as there are no prospective randomized trials with mid-term or long-term results yet published. However, the relatively large, prospective Italian IRON-MPP registry (Italian Registry on Multipoint Left Ventricular Pacing) (11) has published some promising data suggesting that patients with MPP function turned on were more likely than those with conventional CRT to exhibit an absolute increase in LV ejection fraction ≥5% (odds ratio: 2.5; p = 0.001) at 6 months.
Although electrophysiologists are generally technology oriented and early adopters of new “high-tech” gadgets in the laboratory, in the case of MPP, we may need to first ask ourselves if we really are making the most of existing BiV pacing options, before we jump at MPP as the holy grail. Available evidence shows that an optimized conventional BiV pacing can rarely be improved by MPP, and no pacing sequence will fully compensate for poor LV lead placement or incorrect atrioventricular intervals resulting in pseudofusion and low percentage of true BiV pacing. Pacing on >1 LV electrode will inevitably result in faster battery drain than standard bipolar CRT pacing and, in the long run, more frequent generator changes, thereby increasing the risk of infections and other complications.
Prospective randomized trials on MPP are ongoing, but results are a few years ahead, and we should use the waiting time to make sure that we deliver optimal individualized care to our patients with CRT. This approach includes the use of quadripolar leads and assessment of which vector is the most favorable to use, including trying MPP in cases of nonresponse. For now, the best-validated vector selection method is probably maximal Q-LV electrical delay for BIV pacing, and maximal intra-LV delay for MPP electrodes, in combination with QRS duration shortening on surface electrocardiogram. Device-simulated data regarding battery drain suggest that MPP thresholds <4 V are acceptable from a longevity perspective (<10% reduction of battery lifetime), compared with optimal BiV pacing, and that this goal can be achieved in the majority of cases (12). Being forced to accept a suboptimal MPP vector based on pacing thresholds is unfortunate, because the highest short-term hemodynamic benefit has consistently been seen with the longest LV1-LV2 delay. Although further hemodynamic optimization would be desirable, invasive hemodynamic assessment is not feasible in routine clinical practice, and echocardiography evaluation is inherently hampered by high variability. A promising modality could be radial tonometry as a surrogate of cardiac output; this technique has been used in the MPP setting with good preliminary results (13) but needs further validation.
Currently, numerous registered MPP studies are ongoing, several of them prospective randomized controlled trials addressing both hemodynamic and echocardiographic outcome measures, as well as hard clinical endpoints. We look forward to the results of these studies, which will help us further optimize care for our CRT recipients.
↵∗ 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. Borgquist has served on the Speakers Bureau for Medtronic and Abbott; and as an advisory board member for Pfizer.
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
- Umar F.,
- Taylor R.J.,
- Stegemann B.,
- et al.
- Sohal M.,
- Shetty A.,
- Niederer S.,
- et al.
- van Everdingen W.M.,
- Zweerink A.,
- Salden O.A.E.,
- et al.
- Sterliński M.,
- Sokal A.,
- Lenarczyk R.,
- et al.
- Forleo G.B.,
- Santini L.,
- Giammaria M.,
- et al.
- Akerström F.,
- Narváez I.,
- Puchol A.,
- et al.
- Ciconte G.,
- Ćalović Ž.,
- Vicedomini G.,
- et al.