The leadless pacemaker: A new era in cardiac pacing
On 8 October 1958 in Stockholm, Sweden, a 43-year-old man, Arne Larsson, became the first patient to undergo implantation of a permanent pacemaker. Physician turned engineer, Rune Elmqvist, and cardiac surgeon, Åke Senning, had been developing a battery powered implantable system for electrical cardiac stimulation, when Larsson’s wife appealed to Senning, asking him to help her husband who had been hospitalised with increasingly frequent Stokes Adams attacks. Forty-three years after that first pacemaker implantation, Arne Larsson died at the age of 86 years from melanoma, having outlived both Elmqvist and Senning. Over the course of his lifetime, Larsson received a total of 22 pacemaker generators and five lead systems.1
In the years since Elmqvist and Senning began their pioneering work, implant techniques have evolved. That first implantation involved a left sided thoracotomy, and the placement of epicardial leads which were tunnelled to the pacemaker pulse generator, situated in the abdominal wall.1 Today the leads are almost always placed endocardially via the venous system of the upper limb – cephalic, axillary or subclavian – and the pulse generator sits in a subcutaneous pocket in the infra-clavicular region, on top of,
or occasionally beneath, the pectoral muscle.
Pacemaker technology has also developed significantly over the years. Early batteries used nickel cadmium or zinc mercury, and had limited durability. Today’s lithium-iodine-polyvinylpyridine batteries allow for smaller devices with much greater longevity. Lead design has improved to provide greater stability at the interface with the myocardium, and less susceptibility to flexion damage. Where Arne Larsson’s first device provided only one pacing mode – asynchronous VOO pacing – modern microprocessor-driven devices are increasingly sophisticated and can employ various algorithms to optimise the pacing mode, depending on the patient’s needs.2
Today, permanent pacemaker implantation has become routine for bradyarrhythmia management. Worldwide, more than 700,000 pacemakers are implanted annually, with around 35,000 implanted in the UK.3,4
Although it has become a routine procedure and is very safe for most patients, problems relating to the leads, venous access or the pocket may occur. In the immediate- to short-term, the most significant potential complications include haematoma, pneumothorax, lead displacement or, rarely, cardiac perforation and tamponade.5 Device infection, which in turn may lead to septicaemia and endocarditis, carries a mortality of up to 35% and normally warrants device extraction, with its own inherent risk of myocardial or vascular injury.6 Other, longer-term complications, such as chronic lead failure from insulation damage or lead fracture, warrant a repeat procedure to replace the faulty lead. The risk of complications increases with the number of procedures required during a patient’s lifetime. A pacemaker recipient in his/her early 50s, for example, might expect to have a further three of four battery change procedures on top of the initial implantation, and with each opening of the pocket, the risk of infection rises.
Although there have been continuous developments in pacemaker technology over the last 60 years, a standard transvenous pacemaker today consists, in essence, of the same components it ever has: a pulse generator, including battery and circuitry, and at least one lead to deliver an electrical stimulus to the myocardium and to transmit any signals of intrinsic myocardial electrical activity back to the generator.
The leadless pacemaker was developed to avoid many of the potential complications encountered with traditional transvenous pacemakers.
In December 2012, the world’s first leadless pacemaker was implanted in a series of 11 patients at Homolka Hospital in Prague, Czech Republic, heralding the start of a new era in cardiac pacing.7 These small, capsule-shaped, self-contained devices are implanted directly into the right ventricle, and are entirely intracardiac, eliminating the need for a lead or subcutaneous pocket, and thereby avoiding many of the attendant complications.
Their major limitation is the restriction to single-chamber ventricular pacing, and thus to a comparatively small subgroup of patients who require pacing – predominantly those with concomitant atrial arrhythmia, those in whom there is an expectation of only infrequent pacing, or the elderly.
There are two kinds of leadless pacing system: the Nanostim™ Leadless Cardiac Pacemaker (LCP) by St Jude Medical (now Abbott), and the Micra™ Transcatheter Pacing System (TPS) by Medtronic. Currently only the Micra™ has Food and Drug Administration (FDA) approval for use in the United States. Some of their characteristics are summarised in Table 1, along with those of a standard transvenous single chamber pacemaker.8,9
Micra™ Transcatheter Pacing System (TPS)
The Micra™ TPS is a 25.9mm x 6.7mm device weighing 2g, with a volume of 0.8 cm3. Figure 2 illustrates the difference in size between it and a standard single chamber pacemaker. At the distal end of the device, four flexible nitinol (nickel titanium) tines affix the Micra™ to the myocardium. At the proximal end is a docking button by which it attaches to the delivery catheter during the implantation procedure, and from which it can later be snared for retrieval if required.
Implantation of the Micra™ takes place via the femoral vein through a large introducer sheath. The steerable delivery catheter enables the device to be positioned in the right ventricle (RV). As the device is deployed, the fixation tines emerge from the delivery system and engage with the myocardium (see Figure 3). Device stability and electrical parameters are then tested, and, if needed, the Micra™ can be retrieved and positioned in a different location, multiple times if necessary. When a satisfactory position is found with good electrical parameters, a tether is cut, the delivery catheter and sheath are withdrawn, and haemostasis achieved at the access site.10
The largest study of the Micra™ TPS, an international, multi-centre, single arm study, included 725 patients who underwent attempted implantation. Of these, 719 (99.2%) were successfully carried out. At six months, 96.0% of patients remained free from major complications.11 The remaining 4.0% included 11 cardiac injuries, five puncture site complications, two cases of thromboembolism, two pacing issues and eight other events. One death from metabolic acidosis in a dialysis-dependent patient was felt
to have been contributed to by a prolonged procedure. There was no incidence of radiologically apparent device dislodgement, no systemic infections and no failures in telemetry.
Comparison was made in this study with a historical control cohort of 2667 patients who had undergone transvenous pacemaker implantation. The 4.0% major complication rate in the Micra™ group compares with 7.4% in the transvenous pacemaker group (hazard ratio 0.49; 95% CI 0.33–0.75, p=0.001). The rates of hospitalisation (2.3% vs 3.9%) and system revision due to complications were also lower in the Micra™ group (0.4% vs 3.5%). There was no significant difference between the two cohorts in rates of cardiac injury, access site issues or problems with pacing.11
In 98.3% of patients capture thresholds were low and stable, and paired electrical data from implantation and six-month follow up indicate a tendency toward improvement over time. Electrical parameters are shown in Table 2.11
Real-world data from a worldwide registry corroborate the findings of the investigational study. Of 795 patients who underwent an attempted implantation, the Micra™ was successfully implanted in 792 (99.6%). The 30-day major complication rate was low at 1.51%, including six (0.75%) puncture site complications, one (0.13%) cardiac perforation with effusion requiring pericardiocentesis, and one (0.13%) device dislodgement without embolisation. One patient, a 96-year-old man with severe aortic valve disease, died from pulmonary oedema the day after the procedure. The device was functioning normally at the time, had not migrated and there was no evidence of pericardial tamponade.12 There were four (0.50%) other cardiac perforation events that fell outside the criteria for a major complication, because they did not result in death, system revision or prolonged hospitalisation. In three cases no action was required, and in one pericardiocentesis was undertaken.
Electrical parameters at the time of implantation and at six months closely approximated those seen in the investigational study.12
Nanostim™ Leadless Cardiac Pacemaker (LCP)
At 42mm in length, the Nanostim™ LCP is longer than the Micra™, but with a smaller diameter at 5.99mm requires a smaller introducer sheath at implantation.
The principles of the implantation procedure are broadly the same as with the Micra™, with the most notable difference being that the Nanostim™ is affixed to the myocardium by means of a screw-in helix at its tip. Figure 4 shows two chest X rays with a transvenous single chamber pacemaker and the Nanostim™ respectively.
The LEADLESS trial, the first study to assess safety and efficacy of the Nanostim™, was a small single-arm, multi-centre study involving 33 patients. Successful device implantation occurred in 32 (97%) patients, and 31 (94%) remained free from complications at 90 days. Of the remaining two patients, one had a patent foramen ovale through which the Nanostim™ had inadvertently been passed before implantation in the left ventricle. This was subsequently recognised and the device successfully retrieved. The other patient sustained cardiac perforation and tamponade at implantation, requiring pericardial draynage and later median sternotomy and surgical repair of the apical perforation. He later suffered a stroke and subsequently died.13
The much larger LEADLESS II trial included analysis of 526 patients, of whom successful implantation occurred in 504 (95.8%). The rate of freedom from complications up to six months post-implantation was 93.3%. There were 22 device related complications in 20 patients (6.7%), including device dislodgement (1.7%), cardiac perforation (1.3%), vascular complications (1.3%) and high capture thresholds requiring device retrieval and reimplantation (1.3%). Device migration occurred in six patients, either to the femoral vein or pulmonary artery, and in all cases the device was successfully retrieved percutaneously. There were two deaths (0.4%) adjudged to be procedure-related. Initial and follow up electrical parameters were again found to be very good in this larger cohort, also with a tendency toward improvement over time (see Table 2).14
Despite a promising beginning, St Jude Medical voluntarily halted further implantations of the Nanostim™ in October 2016 due to reports of premature battery failure leading to lost pacing output. There were 34 such failures reported, out of 1423 Nanostim™ implantations worldwide (2.4%). These occurred at a mean of 2.9 ± 0.4 years after implantation. There were no reports of any patients having come to harm as a result.15
Where retrieval of the device was attempted, it was successful in 90.4% of cases. In the remaining 9.6%, the docking button proved inaccessible, and in one case became detached and migrated to the pulmonary artery. A total of 115 patients were given an additional pacemaker without an attempt at retrieving the Nanostim™, and there were no reports of adverse interactions subsequently between the coexistent systems.15
End of service considerations
The issues affecting a small number of Nanostim™ LCP devices serve as a reminder that there are certain unknowns surrounding leadless pacemaker technology. This is particularly true with reference to the best strategy when they reach the end of service. These devices have not been in use long enough for any meaningful data to be available on actual battery longevity or long-term complications. Successful retrieval has been demonstrated after a comparatively short duration of implantation, but success rates diminish the longer the device has been in.16–18
Encapsulation over time can lead to greater difficulty retrieving the device. If the proximal retrieval button has been reached by the fibrous capsule, it may not be accessible, and the device may therefore have to remain in situ.19
If retrieval is not possible, having a new leadless system alongside an old one has been shown to be feasible. The human RV can accommodate at least three Micra™ TPS devices simultaneously, seemingly without mechanical interaction between them in a reanimated cadaver heart, although the long-term implications of having that amount of hardware left permanently in the heart are unknown.20
The restriction of leadless pacemakers to single-chamber ventricular pacing limits their use to a comparatively small subgroup of patients who require a pacemaker. Device companies will therefore be looking for ways to broaden the technology to enable dual chamber pacing, although this may yet be a long way off. In theory it should be possible to implant a separate device in the RA, perhaps with Bluetooth® as a means of communication between it and the ventricular device, though fixation of the device in the thin-walled RA poses a greater challenge, and perhaps a higher risk of complications. Remote monitoring of atrial activity from the ventricular device to enable atrial tracking is also under investigation.
If dual chamber leadless pacing becomes possible, then so might biventricular pacing, another natural progression for the application of this technology. As with an atrial device, however, the challenge beyond reliable continuous remote communication between the components, includes securing a device to a thin-walled cardiac vein without an undue risk of complications.
Another area of interest is the use of a leadless RV pacemaker in conjunction with a sub-cutaneous implantable cardioverter defibrillator (S-ICD). The S-ICD, another system without intravascular leads, can defibrillate malignant ventricular arrhythmias, but is unable to deliver anti-tachycardia pacing (ATP) which the conventional transvenous ICD systems can employ to treat ventricular tachycardia (VT), avoiding the need for a shock where possible. Combining an S-ICD with a leadless pacemaker could enable the delivery of ATP to treat VT, and then only deliver a shock should those therapies fail to restore a normal rhythm. The feasibility of combining the two devices has been proven, but much more work needs to be done.21
The arrival of leadless pacemaker technology represents an exciting development in cardiac pacing, with the potential to reduce complications by eliminating the need for leads and a pocket. After appropriate training the rate of successful implantations is very high, and the overall major complication rate is lower than that of conventional pacemakers.
However, wholesale use of leadless devices for all patients requiring a pacemaker is not likely to happen in the near future, in part due to the lack of dual chamber pacing capability, and in part due the considerable cost difference between leadless and conventional systems, at least in the acute phase. The current price to the National Health Service for a Micra™ is £6000, many times that of a single chamber transvenous system, which ranges between approximately £700 and £1000.
Questions remain on how best to manage these devices after battery depletion. The first leadless devices were only implanted at the end of 2012, so data on long-term complications and on outcomes with late retrieval versus leaving them in situ alongside a new device, are currently unavailable.
Time and further research are needed to improve our understanding of these issues. In the meantime, the early data give cause for cautious optimism that this new technology, in selected patients, may significantly reduce complication rates and improve outcomes.
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19 Tjong F et al. Postmortem histopathological examination of a leadless pacemaker shows partial encapsulation after 19 months. Circ Arrhythm Electrophysiol 2015; 8:1293–5.
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21 Tjong F et al. Combined leadless pacemaker and subcutaneous implantable defibrillator therapy: feasibility, safety, and performance. Europace 2016; 18(11):1740–7.