Early Performance of a Miniaturized Leadless Cardiac Pacemaker

The Micra Transcatheter Pacing Study

Philippe Ritter; Gabor Z. Duray; Clemens Steinwender; Kyoko Soejima; Razali Omar; Lluís Mont; Lucas VA Boersma; Reinoud E. Knops; Larry Chinitz; Shu Zhang; Calambur Narasimhan; John Hummel; Michael Lloyd; Timothy Alexander Simmers; Andrew Voigt; Verla Laager; Kurt Stromberg; Matthew D. Bonner; Todd J. Sheldon; Dwight Reynolds

Disclosures

Eur Heart J. 2015;36(37):2510-2519. 

In This Article

Discussion

This is the largest data set reported for any transcatheter pacing technology to date. Early results of this pacemaker are encouraging. The TPS demonstrated safety and efficacy through the acute phase by passing both of its early performance assessment objectives. One hundred and forty (100%) successful implants were achieved in a wide variety of patient demographics, cardiac conditions, and indications for pacing. This was accomplished by 37 physicians in 23 study centres in 11 countries. In two procedures, a second device was used due to unacceptable electrical measurements and decision to change the device was motivated by uncertainty due to early experience of implanters. The majority of implants (81%) were successfully completed with one or two positionings.

Safety Performance

USADE is an ISO standard for assessing primary risks to patient health when implementing a new medical device. The endpoint is often used for safety evaluation,[11,12] but is uniquely different from the study's primary objective.[9] The trial had no USADEs after 266.4 months of follow-up, far exceeding its primary safety objective. Thirty adverse events related to the procedure or system were identified in the 140 implanted patients, none of which were due to device dislodgement or infections. There were no deaths related to the procedure or system and no re-operations were required. Telemetry contact remained feasible in all patients. Adverse events did not differ substantially across patient sub-groups.

One case of pericardial effusion occurred in the context of 18 positionings due to undesirable electrical performance. In light of this observation, persistent repositioning should be avoided in order to limit the possible injury to the myocardium and surrounding vessels. In case of undesirable thresholds immediately after deployment, some waiting time should be considered before measuring electricals again. As is frequently observed in tined and helix-based pacemaker leads,[13] thresholds may improve within minutes, thus allowing release of the device. In all cases, consideration of the potential benefit of multiple repositioning vs. risk is warranted.

Transient AV (in patients with LBBB or AV conduction abnormalities) or right bundle branch block during navigation of the delivery tool was reported in a few cases, suggesting a mechanical trauma by the delivery system which bears consideration in crossing the tricuspid valve. Prevention of ventricular arrhythmias warrants a similar consideration. However, these events can occur with any right-heart procedure. Temporary pacing is a preventive option and may be considered in patients with LBBB.

The management of pre- and peri-operative anticoagulants was left to the discretion of the physician because of lack of experience with the implantation of the TPS. No specific recommendation was given to investigators who were free to define their own protocol with the condition that all catheters were flushed with heparinized saline, and that a heparinized drip was placed on the introducer to reduce clotting. A variety of approaches were used and minimal haematomas or bleeding were observed, without correlation to approach (40% received heparin and 36% did not receive any anticoagulation; there were two haematomas and three events of minor groin bleeding). Therefore, no obvious advantages or disadvantages due to anticoagulation approach have become apparent, although a heparin bolus may reduce risk of clotting on the device and within the delivery tool. The risk of inadvertent arterial puncture (with possible subsequent complications such as pseudoaneurysms, AV fistulas, and haematomas) might be mitigated by using ultrasound techniques for venous access, although this has not been evaluated within this study. With regard to post-procedural closure/haemostasis, investigators have successfully used various techniques as a pre-specified closure method was not mandated. The majority (46%) of closure methods utilized manual pressure with a suture method (Figure of 8, purse string). A suture method without manual pressure was used in 39% of cases. A vascular closure device was used in 11% of cases (with or without pressure or a suture), and manual pressure alone was used in 4% of cases.

Efficacy Performance

Device functionality and efficacy was successfully demonstrated at 3 months with a mean pacing threshold of 0.51 V at 0.24 ms pulse width; exceeding the intended goal of <2.0 V. Further, ambulatory ECG monitoring in the first 25 patients at 1-month demonstrated the device was performing as expected. Pacing thresholds remained low and stable, with no measurements at or above 2.0 V at 3 months follow-up. This last observation is important because any programming requiring high energy levels may result in a significant reduction in the life expectancy of the device. One patient had a pacing threshold >2 V at implantation, though this decreased to <1 V at 3 months. Based on pacing conditions from the 60 patients followed to 3 months, mean device longevity was estimated at 12.6 years, with 95% of the patients over 10 years and shortest of 8.6 years. This longevity performance would be no worse than conventional pacing systems.[14,15] The TPS uses a new capture management approach with automatic hourly 0.5 V safety margin confirmations to ensure pacing outputs remain at safe levels and to optimize battery longevity.

Alternate Transcatheter Pacemakers

While other manufacturers are developing transcatheter pacemakers, it will be of importance to consider technical differences in the design and performance of the various technologies. In the LEADLESS Trial, the Nanostim™ leadless cardiac pacemaker (St Jude Medical, St Paul, MN, USA) was successfully implanted in 32 of 33 patients.[16] One patient experienced a RV perforation and cardiac tamponade during the procedure, and later died as a result of stroke. Two patients required device retrieval post-implantation, one for inadvertent left-ventricular placement and the other for developing an indication for an implantable cardioverter defibrillator. Compared with TPS, the Nanostim device is of similar size but longer (41.4 vs. 25.9 mm) and narrower in diameter (18 vs. 20 Fr). Rate response is controlled by RV blood temperature compared with an accelerometer in TPS. Although the implant approach is also transcatheter delivered via the femoral vein, endocardium fixation is different. The TPS uses four protractible nitinol tines vs. a fixed helical coil with Nanostim.

Technology Implications

Transvenous lead technology was developed in 1959 and with the introduction of implantable pacemakers in the 1960s, the implant technique has largely been unchanged. Today, it is estimated that ~600 000 pacemakers are implanted worldwide each year,[17] 358 000 of which are in the USA.[18] Compared with single-chamber atrial-based systems and the more costly dual-chamber systems, VVI pacemaker utilization varies regionally with rates reported from trials of 8% in the USA[19] and 25% in the Netherlands.[4] VVI pacemakers are guideline recommended for patients with permanent or persistent atrial arrhythmias and slow intrinsic heart rates.[20] Future developments of this technology may include AAI, VDD, DDD, or even biventricular pacing systems. However, in the meantime, mode selection may be influenced by the technological advantages of a miniaturized transcatheter pacemaker, advantages that include the absence of lead and pocket related risks and device implant cosmesis. Atrial and dual-chamber pacing modes have recently been preferred for bradyarrhythmia patients without permanent or persistent atrial tachyarrhythmia due to risks associated with AV dysynchrony, notably pacemaker syndrome.[19] Over one-third of the patients who received TPS in our trial were without history of permanent or persistent atrial tachyarrhythmia. Of these patients, the primary pacing indication was SND (45%) or AV block (39%). Physicians selected VVI pacing for reasons due to 'infrequent pacing expected' (69%), 'advanced age' (22%), and other reasons that included sedentary lifestyle, anatomical limitations, or co-morbidities increasing risk of complication.

Limitations

This study is non-randomized and so the evaluation of benefit of this new technique over contemporary single-chamber or dual-chamber systems is indirect. This is the first report of early performance of the TPS in a multi-stage assessment protocol and there was limited representation of pacemaker-dependent patients in this cohort. The patient cohort is too small to determine any recommendation regarding anticoagulation management and post-procedural closure/haemostasis. No devices have yet to be retrieved, thus retrievability remains uncertain. Also, performance with multiple or concomitant devices has not yet been observed. This is an ongoing study that may bring more precision regarding these issues.

Conclusion

Early performance assessment shows the TPS pacemaker can safely and effectively be applied. It is premature to draw definitive conclusions about the benefits of this system. Long-term safety and benefit associated with the absence of a subcutaneous pulse generator and transvenous lead will further be evaluated in the trial. However, these early results meet and exceed initial pre-specified expectations. The fact that such data were obtained in a multicentre study involving 37 investigators at 23 different centres around the world with a variety of patients is encouraging.

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