Leadless Pacemaker: Report of the First Experience in Hawai‘i

Abstract

We had the opportunity to implant the first leadless pacemakers in Hawai‘i. This device represents a major change in pacemaker technology. This is a report of the first five cases and a review of the literature. All these devices were implanted via femoral venous access (versus conventional upper chest axillary/subclavian/cephalic routes), with an unique fixation mechanism allowing direct attachment to the ventricular myocardium (dispensing the usage of long transvenous electrode leads). The miniature generator can is over an order of magnitude smaller and lighter than the currently available ones. This article provides an understanding of the device design, implantation technique, the advantages and limitations, and the potential of this new pacemaker.

Introduction

Pacemaker implantation in humans began in 1958 with Drs. Elmvist and Senning, needing thoracotomy and epicardial electrode placement. Transvenous pacing (with the electrode wire inserted through a vein on the chest wall thus sparing the thoracotomy) came in 1962, with Drs. Lagergren, Parsonnet, and Weltri.¹ Since the first implant over half a century ago, there were many innovations, and these included programmability (altering the set pacing and sensing parameters), dual chamber capability (pacing in the right atrium as well as the right ventricle), remote monitoring (allowing radiofrequency interrogation of the device at a distance, from a nearby console), rate adaptiveness (altering the pacing rate according to the patient's physiological needs), resynchronization therapy (involving pacing a third chamber typically the left ventricle, to allow both the left and right ventricles to contract in synchrony).² Yet despite all these advances, the basic device format remained unchanged: an electronic generator housed in a pectoral pocket with one or more electrical conducting leads inserted via an upper chest vein (subclavian, axillary, cephalic) and anchored or screwed into the atrial or ventricular myocardium.³

The pectoral pocket transvenous lead configuration is burdened by significant complications. Pocket complications include bleeding (hematoma), erosion, infection, and discomfort. Lead complications involve pneumothorax, dislodgement, perforation, phrenic nerve stimulation, erosion, venous thrombosis/occlusion, lead insulation defect and conductor failure, pericardial effusion (sometimes tamponade), tricuspid valve malfunction, and infection.⁴ It is estimated that for each implant, there is at least a 20% chance of a significant complication.⁴ Infection generally demands removal of the entire pacing system with its attendant morbidity. Infections often occur at a rate of 1%–2% at one year, 3% over the lifetime of the initial system, and over 10% after generator replacement.⁴ A leadless system that eliminates the generator pocket and the leads would avoid most of the above complications.

The concept of the leadless pacemaker started as early as 1970 with Dr. Spickler.⁵ A practical device that underwent successful human implantation and clinical testing came into fruition only recently. There are two devices in use: Micra (Medtronic Inc., Dublin, Ireland), and Nanostim (St. Jude Medical Inc., St. Paul, Minnesota). Both systems are available commercially in Europe (as of 2012 and 2013 respectively). In the United States, only the Micra was approved by the US Food and Drug Administration (since April 6, 2016). The current indication is for patients who have symptomatic bradycardia requiring single chamber ventricular pacing, typically with persistent atrial arrhythmia (fibrillation/flutter). It is also appropriate for patients with rare bradycardia (such as infrequent long pauses), when the lack of atrial sensing/pacing is not of major consequence. Symptomatic bradycardia with lack of upper chest venous access may prove to be an indication in selected patients.^4,6 This article is a report of the first 5 cases of leadless pacemaker implantation in Hawai‘i. This report also provides a review of the device design, implantation technique, and the advantages and limitations of the new technology.

Device and Implantation

The Medtronic Micra device is a small cylinder weighing 2 gm, with a size of 2.59 x 6.7 mm (height and width) and a total volume of 0.8 mL (Figure 1). It is a self-contained miniaturized titanium cased single chamber rate-responsive pacemaker. It is powered by a lithium carbon monofluoride (Li-CFx) battery, with an estimated battery life of 12 to 14 years (14 years at 50% pacing at 1.5 V at 0.24 msec pulse width at 600 ohms at 60 bpm). The rate-response mechanism is a three-axis accelerometer sensor. The steroid-eluting cathodal tip electrode is made of titanium nitride coated platinum iridium. There is an anodal ring electrode on the generator case. The fixation mechanism is composed of 4 electrically inactive protractible nitinol prongs.^4,6

Figure 1.

The size of a Micra generator as compared with the latest generation Medtronic dual chamber pacemaker and a quarter coin.

The device delivery is by femoral venous access. After access is achieved, the vein is progressively dilated to accept the 23 French (Fr) introducer sheath over a super-stiff guidewire. The sheath is advanced up the inferior vena cava to the floor of the right atrium. The deflectable delivery catheter is then introduced into the right atrium and then the right ventricle. With a clockwise rotation, the catheter is turned to face the septum. The catheter is then pushed against the endocardium firmly. The position is confirmed by fluoroscopy in the right anterior oblique and left anterior oblique projections and by small injections of contrast through the catheter tip. The pacemaker is housed in a well at the tip, with the tines in a straight configuration, and with the back end connected to the outside of the delivery tool via a tether or rope. The well is gradually retrieved, allowing the preformed prongs to resume their curved form and dig into the myocardium. The attachment is deemed acceptable when the measured parameters (sensitivity and capture threshold) meet criteria and when at least 2 out of the 4 prongs are attached (as evidenced by the prongs flaring out when the pacemaker is tugged via the tether). When the position is acceptable, one of the two tether ropes is cut and the tether can be pulled out, leaving the can in place (Figures 2 and 3). After the introducer sheath is removed, hemostasis can be achieved by a combination of Perclose Proglide closure device, purse-string (or figure-of-8) subcutaneous stitch, and manual pressure.⁶

Figure 2.

Implantation of the device, with the delivery catheter pushed up against the right ventricular septum. In left anterior oblique view.

Figure 3.

The generator is delivered, and the delivery sheath is pulled back. In right anterior oblique view.

While not the focus of this article, the Nanostim is quite similar in shape and size, being slightly longer (2 gm, 42.0 x 6.0 mm, 1.0 mL), with the fixation mechanism being a helix, which requires rotation of the delivery catheter for fixation. The introducer sheath is smaller at 18 Fr. The battery life is similar. The rate responsive mechanism is temperature based.^4,6

Case Series

Our series comprised of five consecutive patients, with mean age of 73.6 ± 11.0 years (range 64 to 86 years). They all had Micra devices. The implantations were performed between April 19, 2017 and July 31, 2017. They were four males and one female. The indications were atrial fibrillation with high grade AV block in two patients and sick sinus syndrome in three patients (two with lack of upper chest venous access).

The acute implant success rate was 100%. The average duration of the procedure was 47 ± 11 minutes. The duration progressively shortened from a peak of 65 minutes for our second case to 38 minutes for the last case. The mean capture threshold (the least amount of electrical current or energy needed to depolarize the ventricle) was 0.53 ± 0.27 volts (V) at 0.24 msec pulse width (range 0.25 V to 0.88 V). The mean sensitivity (the magnitude of the patient's own ventricular depolarization detected by the device) was 13 ± 5.8 mV (range 5.2 to 19.1 mV). Two of the five patients had a narrow paced QRS complex. Typically, with conventional right ventricular pacing, the paced complexes were wide, due to dispersion of electrical conduction from the pacing site through both ventricles. A narrow paced complex suggested a more orderly sequence of depolarization, resembling more the spontaneously conducted QRS complexes.

There was no acute dislodgement. There was no major bleeding at the access site. One patient had minor oozing which resolved with manual pressure. Four out of five patients ambulated after 3 hours. The patient with mild oozing ambulated the morning after the procedure. The acute complications common to conventional pacemaker implantation were not present (pneumothorax, pocket hematoma, lead perforation). All patients were alive, with no dislodgement or infection on follow up at 5 months.

Discussion

The commercial availability of leadless pacemakers is a true revolution, a major paradigm shift. For over half a century (since 1962), the format for pacemaker implantation was pectoral generator pocket and transvenous lead insertion. This device eliminated the lead and the need for a pocket.

From the available literature, it is appreciated that the procedure is simple and easy, with few acute and chronic complications.^7,8

The landmark Micra trial was published in 2016.⁷ This was a prospective, nonrandomized, multicenter, single-arm study enrolling 725 patients. The device was successfully implanted in 99% of patients. The primary safety endpoint was freedom from system-related or procedure-related major complications at 6 months. This was achieved in 96% of study patients compared to 83% of historical controls. The primary efficacy end point was the percentage of patients with low and stable capture thresholds at 6 months. This was attained in 98% of study patients versus 80% of historical controls. Both endpoints are significantly better among Micra patients than historical controls. The complications included perforation or pericardial effusion (1.6%), groin complication (0.7%), elevated threshold (0.3%), venous thromboembolism (0.3%), and others (1.7%). There was no dislodgement or infection. Compared with an unmatched historical control cohort of 2667 patients, the absolute risk reduction was 3.4% at 6 months, resulting in the need to treat 29 patients to benefit one. Compared with cohorts, there was a reduction in subsequent hospitalizations (2.3% vs 3.9%) and device revisions (0.4% vs 3.5%). Longer term follow-up data from the Nanostim study showed an absolute risk reduction of 11.7% at 2 years, suggesting a need to treat 8.5 patients to benefit one.⁸ With more prolonged follow-up, the relative risk reduction, and thus the advantage of leadless pacing, is expected to increase.

Compared with conventional pacemakers, there is a 1% to 2% groin complication rate which is unique to leadless devices.⁴ This is in large part related to the very large introducer sheath, which may be difficult to significantly improve on. The cardiac perforation rate may be improved with cautious sheath maneuvering and by always implanting the device on the septum.

There are other advantages with leadless pacing. The procedure time is shorter, and should average 37 minutes for the Micra.⁶ There was a learning curve, as our first 2 cases took 50 and 65 minutes respectively, and our last case took 38 minutes. For conventional single chamber pacemaker implantation, the authors typically take 50 to 60 minutes. The is also a cosmetic advantage. The immediate shoulder mobility may allow for earlier resumption of normal activities (our first patient had a great round of golf three weeks post implantation), thereby avoiding the “frozen shoulder” and worsening of preexistent arthritis. Both leadless systems were designed to be compatible with magnetic resonance imaging (MRI). The battery life is longer (the average transvenous pacemaker lasts 7 years compared to 12 to 14 years for Micra). Lead related tricuspid regurgitation is fairly common with 10% of patients experiencing new severe regurgitation.⁴ This should be minimized as the small leadless generator does not physically interact with the tricuspid valve. What has not been emphasized in the studies so far is that a high septal implant would allow for a fairly natural sequence of ventricular depolarization (as evidenced by a narrow paced QRS complex in two of our five patients). This may theoretically obviate the long-term ventricular desynchronization and heart failure seen in some patients with conventional right ventricular apical pacing.⁹ Without the constant reminder of the bulge in the upper chest, our patients report not being aware of the presence of a pacemaker. The persistent questions of ability to do pushups, lift weights, shoot a rifle, wear a seat-belt, and don a low cut dress have also ceased.

One question often raised is end-of-life of the battery and new generator replacements. The Micra does not have a dedicated retrieval system, unlike the Nanostim. Retrieval up to three years post implant has been done with the Nanostim system without event. About twelve to fifteen years post implant, the generator is likely to be well encapsulated and retrieval may be technically challenging. But retrieval of a used generator may not be necessary. A study using human cadaver hearts have shown feasibility of 3 simultaneous right ventricular Micra implants without physical interaction.¹⁰ Thus simply implanting a new device may be all that is needed.

Limitations of Current Study

The current case series only has 5 patients and no firm conclusion can be drawn from our results. Our cohort has expanded to ten patients at the time of the article review and the experience is unchanged. The statements made in the article mainly reflect the authors' experiences and the current literature.

Limitations of Micra Device

It is estimated the Micra costs about $10,000 per unit. A regular single chamber pacemaker costs $2,500 to $5,000 with another $800 for a single lead. The higher upfront cost may be balanced by the longer battery life (which is practically double that of a conventional pacemaker). The reduced complication rate should translate to cost savings on a population basis. A cost-efficacy study reported that one complication of a transvenous pacemaker was more expensive than the initial implant itself.¹¹ One should also take into account the reduction of morbidity and human suffering (for example, the discomfort of a chest tube for pneumothorax, and the risk of severe complications in lead extraction for infection).

Indications for single chamber pacing constitute about 20–30% of all pacemaker implants (which exceed 1 million per year worldwide).¹² Patients with intact sinus rhythm will generally benefit from a dual chamber pacemaker with atrial sensing and pacing capabilities, unless the need for pacing is highly infrequent and the pacing duration is short.

Future Directions

Right atrial implants and dual chamber pacing is the next logical step of leadless pacemaker evolution. Active research is underway in this regard and prototypes are being studied.

Further evolution may include an implantable cardioverter-defibrillator (ICD) itself being leadless and implantable endocardially. This is unlikely to happen in the near future, the limitations being that the defibrillator requires a large enough power source and a sizable capacitor to allow for rapid charge and discharge, and thus obliges a certain size which is difficult to miniaturize.

However, the leadless pacemaker may work well with the subcutaneous implantable cardioverter-defibrillator (SICD). This is a defibrillator by which the power source and the leads are all implanted subcutaneously on the chest. This setup provides only defibrillation. The leadless pacemaker may allow for anti-tachycardia as well as backup bradycardia pacing. The combination is currently being studied in a device by Boston Scientific.⁶

Conclusions

Leadless pacing is an effective and safe alternative to standard transvenous pacing, with significant reduction in acute and intermediate term complications. It is a dramatic step forward in the art and science of pacemaker therapy.

Conflict of Interest

None of the authors identify any conflict of interest.