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Leadless pacemaker: Performance andcomplications

Justin Z. Lee, MBBS, Siva K. Mulpuru, MD, and Win K. Shen, MD⁎

Division of Cardiovascular Diseases, Mayo Clinic, 5777 East Mayo, Boulevard, Phoenix, AZ

a b s t r a c t

Traditional transvenous cardiac pacemakers have pitfalls due to lead- and device pocket-related complications. Leadless pacemakers

were developed and introduced into clinical practice to overcome the shortcomings of traditional transvenous pacemakers. In this

review, we provide a description of leadless pacemaker devices, and summarize existing data on device performance. We also describe

associated complications during implantation procedure as well as during the follow-up period. Although current generation devices are

limited to single-chamber pacing, future generation devices are expected to progress to multi-chamber multi-component pacing

systems, and eventually to battery-less devices.

Key words: Leadless pacing, Cardiac pacing.

& 2018 Published by Elsevier Inc.

Background

An estimate of more than 200,000 pacemakers are implantedannually in the United States, and the numbers are expectedto increase as our population ages and patients are livinglonger with multiple comorbidities [1,2]. However, despiteadvances in technology, conventional pacemakers still havethe same structure since its early introduction in the 1960s,which consist of an extravascular pulse generator containingthe power source and the electronic circuitry connected tothe cardiac myocardium using transvenous leads. This sys-tem is associated with up to 9.5% rate of complications,which includes device-related complications such as hema-toma or pocket infection, as well as lead placement-relatedcomplications, such as pneumothorax, cardiac perforation,and lead dislodgement [3] (Fig. 1).The weakest link in the pacemaker system is the trans-

venous lead, which is present in a hostile environment whereit is subjected to repetitive mechanical stress with eachcardiac cycle and shoulder girdle movement, leading to lead

1016/j.tcm.2017.08.001blished by Elsevier Inc.

uthors have reported that they have no relationshthor. Tel.: þ1 480 342 0348.wshen@mayo.edu (W.K. Shen).

failure in a small proportion of patients. The transvenouslead can also impinge on leaflet motion of the tricuspid valveor subvalvular apparatus leading to significant tricuspid valvedysfunction. Furthermore, the extravascular nature of thepulse generator also serves as a potential source for infec-tions following device-related surgical procedures [4,5]. Theattached transvenous leads can serve as a conduit forbacterial entry into the blood stream. The presence of hard-ware in the blood steam creates a nidus for recurrentbacteremia after initial infection.As early as 1970, the concept of a completely self-contained

intracardiac pacemaker has been proposed, but the clinicalrealization of this concept was limited by lack of a practicallonger lasting power source [6]. Since then, advances intechnology have led to progression of miniaturized high-density energy sources, electronics, and communicationtechnology, which eventually led to the development of theleadless pacemaker.Leadless pacemakers can be categorized into two broad

groups: single component system and a multicomponent

ips relevant to the contents of this paper to disclose.

Fig. 1 – Transvenous pacemaker-related complications. Complications and associated rates from previous studies are listed inthe table.

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system. The single component system refers to the pace-maker containing all components of the pacemaker within asingle system, including battery, electronics, stimulatingelectrodes and rate adaptive sensors. The multicomponentsystem refers to the intra cardiac pacemaker device beingpart of a cohort of components. The pacemaker acts as anenergy transducer within the cardiac chamber, convertingexternal ultrasound or radio wave energy into pacing pulse.

Single component systems

Device characteristics

There are currently two main single component systemdevices that are available: (1) Nanostim leadless cardiacpacemaker (LCP) (Abbott Laboratories, Abbott Park, IL) and(2) Micra transcatheter pacing system (TPS) (Medtronic, Min-neapolis, MN) (Fig. 2). The Micra TPS received U.S. Food andDrug Administration (FDA) approval in April 2016, and theNanostim LCP is currently awaiting FDA approval.Table 1 displays the device characteristics of the Nanostim

LCP and Micra TPS. Comparing both devices, the Micra TPS issmaller and lighter, but has shorter estimated battery lon-gevity. The rate modulating mechanism in the Nanostim LCPis based on blood temperature, whereas the Micra TPS utilizes

Fig. 2 – Nanostim LCP and Micra TPS. The Nanostim LCP hasa longer profile with active fixation mechanism. The activehelix acts as a cathode while the body acts as anode in theNanostim LCP. Cathode is located centrally between thetimes in the Micra TPS while the ring electrode is on thebody.

a 3-axis accelerometer. Nanostim LCP utilizes conductivetelemetry for pacemaker communication which saves batterycharge, although it does require placement of skin patchesfor pacemaker communication [7]. The Micra TPS deviceuses radiofrequency telemetry, which permits daily passivefollow-up and daily alerts [8]. The Micra TPS device can befollowed remotely for device diagnostics while remote moni-toring capabilities are currently unavailable in the NanostimLCP. The Micra TPS has autocapture threshold algorithm thatcan potentially prolong battery life.

Device implantation

The anatomical challenges of leadless pacemaker implanta-tion are illustrated in Fig. 3. The ideal leadless pacemakershould be compact, lightweight, small enough to permitplacement of multiple devices in the future if or when it isneeded, and easily implanted and extracted. The deviceshould not be associated with significant thromboembolicevents or cause mechanical ectopy. The delivery systemshould not cause any associated damage to the valvular orsub-valvular apparatus. The incidence of myocardial perfo-ration should be similar to or lower than transvenous leads.The current leadless pacemakers meet most of the require-ments. Both systems are implanted via a sheath inserted in afemoral vein and are delivered to the right ventricle (Fig. 4).The introducer sheath for the Micra TPS device has a largerdiameter. The large sheath size may be prone to clot for-mation, and therefore, one of the procedural anticoagulationstrategies is to administer 5000 units of heparin bolusfollowing sheath deployment and maintaining continuousheparinized flush with infusion at 250 ml per hour. Thefixation mechanism is different for both devices, with theNanostim LCP using an active fixation helix (Fig. 5) that issecured into the RV apical septum via rotation of the deliverycatheter handle control knob, while the Micra TPS uses fourintegrated self-expanding electrically inert nitinol tines thatallow the device to be secured into the RV myocardiumwith only passive fixation (Fig. 6). Typically, device placementis facilitated only by fluoroscopic guidance. Although

Table 1 – Comparison of leadless single component pacemakers.

Nanostim (LCP) Micra (TPS)

Indications VVI(R) VVI(R)Size (h × w) 42 × 6 mm 26 × 6.7 mmVolume, cc 1.0 0.8Weight 2.0 g 2.0 gDelivery sheath diameter 18-F inner diameter and 21-Frouter diameter 23-F inner diameter and 27-F outer

diameterBattery technology Lithium carbon monofluoride Lithium silver vanadium oxide/carbon

monofluorideEstimated longevity, yearsa 9.8 (2.5 V @ 0.4 ms) 4.7 (2.5 V @ 0.4 ms)Longevity based on nominal

settings, years14.7 (1.5 V @ 0.24 ms) 9.6 (1.5 V @ 0.24 ms)

Autocapture thresholdalgorithm

Not available Available, optimizes pacing output to 0.5 Vabove pacing threshold

Fixation mechanism Active fixation with screw-in helix Passive fixation with electrically inertnitinol tines

Rate modulationmechanism

Blood temperature 3-Axis accelerometer

Pacemaker communication Conductive telemetry—requires placement ofskin patches for pacemaker communication

Radiofrequency telemetry

Remote monitoring Not available AvailableFDA approval Awaiting approval Approved in April 2016

FDA, Food and Drug Administration.a Longevity based on International Organization for Standardization (ISO) for reporting battery longevity: 2.5 V, 0.4 ms, 600 Ω, 60 beats/min,and 100% pacing.

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intracardiac echocardiography may facilitate localization ofdevice placement or assess procedurally related complica-tions, the role of intracardiac echocardiography needs to beformally evaluated due to the additional expense and theneed to obtain separate venous access. A “figure of 8” iscommonly placed near the femoral access site for hemostasiscontrol after the procedure. The current primary modality fortraining for leadless pacemaker implantation is by proctoring.However, as devices become more common in clinical prac-tice, it is anticipated that training will be more widelyavailable.

Post-implantation follow-up

The first follow-up session following device implantationshould occur within 24 h of implant to check for devicedislodgement, wound healing, and postoperative

Fig. 3 – Anatomical challenges in leadless pacemakerinsertion. (Anatomical Image courtesy of William EdwardsMD and Joseph J Maleszewski MD)

complications. During the first few months after implant,the patient may require close monitoring. After that, follow-up sessions should occur at least every 3 months to reviewbattery voltage, device status, device performance with sens-ing, impedance and threshold testing. For the Micra TPSdevice, patients may undergo activity vector test to deter-mine the vector that provides appropriate rate response,where patients simulate various postures from lying towalking, and the Micra TPS device is programmed based onthe most appropriate activity vector. Ventricular pacing fromthe Nanostim leadless pacemaker may produce high fre-quency pacing artifacts on surface electrocardiogram (Fig. 7).

Indications and contraindications

Table 2 displays the general indications and contraindica-tions of leadless pacemakers. In general, the Nanostim LCPand Micra TPS devices may be suitable for patients who meetindications for permanent single-chamber right ventricularpacing (VVIR). Patients that were selected for implantation inthe leadless pacemaker trials included patients with chronicatrial fibrillation with atrioventricular block, normal sinusrhythm with second or third degree AV block and with a lowlevel of physical activity or short expected lifespan, and sinusbradycardia with infrequent pauses or unexplained syncopewith abnormal electrophysiological findings such as pro-longed HV interval [9–11]. Major exclusion criteria in theleadless pacemaker trials included mechanical tricuspidvalve prosthesis, or preexisting endocardial pacing or defib-rillation leads [10,11]. Patients with contraindication forsingle dose of 1.0 mg of dexamethasone acetate were alsoexcluded as the device’s tip is coated with dexamethasoneacetate delivered via a controlled-release mechanism to

Fig. 4 – Insertion of Micra TPS introducer sheath. (A) 8-F sheath in femoral vein, with preparation of a series of dilators.(B) Stepwise upsizing of access site from 10-F, 12-F, and 14-F, followed by (C) 16-F, 18-F, 20-F, and 22-F dilators. (D) Insertion of24-F dilator. (E) Preparation of introducer and dilator which has a 23-F inner diameter and 27-F outer diameter. (F) Insertion ofintroducer sheath. (G) Micra TPS withdrawn into delivery cup with tines extended. (H) Micra TPS deployed from deliver cupwith tines released. (I) Transfemoral delivery catheter with Micra TPS at distal end and consist of a handle and a long shaftwith a fixed and articulating curve. (Images courtesy of Yong- Mei Cha MD.)

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minimize tissue reaction and facilitate low-threshold per-formance. Patients that were also excluded from the Nano-stim LCP trials were patients with pacemaker syndrome, pre-existing pulmonary arterial hypertension or significant lungdisease, and venous thrombosis in venous access site. TheMicra TPS trial also excluded patients with recent acutecoronary syndrome (o30 days), implantation of neurostimu-lator or any other chronically implanted device which useselectrical current, left ventricular assist device, morbidlyobese, femoral venous anatomy unable to accommodatea 23 Fr introducer, known intolerance to nickel–titanium(nitinol) Alloy, life expectancy of less than 12 months,and pregnant or breastfeeding women. Presence of inferiorvena cava (IVC) filter is considered a contraindication as well,however, feasibility of implantation of leadless pacemakerdevices with careful pre-, intra-, and post-procedural mon-itoring of the IVC filter has been demonstrated [12].Patients who may be reasonable candidates for leadless

pacemakers include those with end-stage renal diseasepatients due to the increased risk of developing device-related infections. This group of patients commonly hascentral venous catheters and tunneled hemodialysis cathe-ters, repeat microbial exposure during intravenous accessand uremia-associated immunosuppression, making themat-risk for infections [13,14]. Furthermore, preservation ofboth central and peripheral vessels for vascular access isimportant for patients on dialysis. Other patients who are

reasonable candidates for leadless pacemakers includepatients with severe or recurrent device infection, or venousocclusion due to previous pacemaker implantation.

Implantation safety and complications

Success rate of implantation of the Nanostim LCP device was97% (32 of 33) in the LEADLESS study and 96% (504 of 526) inthe LEADLESS II study [9,10] (Table 3). In LEADLESS II, majorcomplications occurred in 6.5% of patients, where 1.1% hadcardiac perforation requiring intervention. There was 1.1%rate of device dislodgement identified at a mean of 8 daysafter implantation, with four cases of device migration to thepulmonary artery and two cases of device migration to theright femoral vein. All dislodged devices were successfullyretrieved percutaneously. There was also delayed retrievalin 1.3% of patients (7 of 526) with a mean retrieval time of160 days, with all devices retrieved without complications.Reasons for retrieval included elevated pacing thresholds(4 patients), worsening heart failure (2 patients), and electiveexplantation (1 patient). There was a 1.2% vascular accesscomplication rate, which included bleeding, arteriovenousfistula, pseudoaneurysm, and failure of vascular closuredevice requiring intervention. There were no device-relateddeaths in the study cohort.In the Micra TPS study of 725 patients, the device was

successfully implanted in 99% of patients (719 of 725) [11].

Fig. 5 – Positioning of the Nanostim LCP in the right ventricular apex in the right anterior oblique (A) and left anterior oblique(B) view with contrast injection via delivery sheath. (C) Release of the device from the delivery sheath. (D) Final device position.Postoperative posteroanterior (E) and lateral (F) chest radiograph projections.

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Major complication occurred in 4% of patients, where 1.6%had traumatic cardiac injury requiring intervention, 0.7% hadvascular access complications including arteriovenous fistulaand pseudoaneurysm, and 0.3% of thromboembolism. Therewas no device dislodgement. One device was percutaneouslyretrieved 17 days after implantation due to intermittent lossof capture. Its performance in the real-world setting basedon a worldwide post-approval registry, which included 795patients also revealed a high rate of implant success (99.6%)and a low rate (1.5%) of major 30-day complications, with a0.13% of cardiac effusion or perforation and 0.13% of devicedislodgement. A potential cause for persistent high pacing

impedence values and lack of ventricular capture despitemultiple repositionings is thrombus formation at the tip ofthe leadless pacemaker [15]. Long-term data of patients withelevated pacing thresholds between 1.0 and 2.0 V followinginitial Micra TPS implantation revealed pacing thresholddecrease in a majority of patients after implant, which maysuggest that device positioning may not be necessary if thepacing threshold is ≤2.0 V [16].The reliability of the leadless pacemaker has also paved the

way to simultaneous atrioventricular node (AVN) ablationand leadless pacemaker implantation, which was success-fully performed in two reported cases [17]. Potential

Fig. 6 – Positioning of the Micra TPS in the right ventricular apex in the right anterior oblique (A) and left anterior oblique (B)view with contrast injection via delivery sheath. Final device position in the right anterior oblique (C) and left anterior obliqueview (D). Postoperative posteroanterior (E) and lateral (F) chest radiograph projections.

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challenges to consider include mechanical dislodgement andelectromagenetic inference. Although these case examplesdemonstrate the feasibility of leadless pacemaker implanta-tion and AVN ablation performed during the same procedure,an observation of 2 weeks following the pacemaker implan-tation before AVN ablation to ensure adequate pacemakerfunction is considered routine in clinical practice today.There may be concerns for device longevity in the real-world

setting, as highlighted by a recent issue with Nanostim LCPdevice battery malfunction, occurring in 1.97% of implanteddevices worldwide [18]. This led to a pause in Nanostim LCPimplants and for device replacement in pacemaker-dependent

patients. This issue underscores the importance of reviewing thelatest long-term data for leadless pacemaker devices, especiallywhen considering implantation of leadless pacemakers in pace-maker-dependent patients.

Device safety concerns: magnetic resonance imaging,radiation therapy, shock, and cremation

The Micra TPS device has been FDA approved for 1.5 T and 3 Tmagnetic resonance imaging (MRI) scans under specific con-ditions for use [8]. A published study of a patient with MicraTPS implanted who underwent a clinically indicated MRI scan

Fig. 7 – Ventricular pacing from a Nanostim leadless pacemaker. Note the high frequency artifact noted during the later part ofthe QRS. This is due to conductive communication between the device and the programmer. The programmer transmitssignals to an implanted leadless cardiac pacemaker with subliminal 250-kHz pulses applied to the skin electrodes. Data areencoded in 5 high-frequency pulses (per heart beat), sent by the leadless cardiac pacemaker during the absolute ventricularrefractory period. (Tracing courtesy of Paul A. Friedman MD.)

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revealed normal device function after the MRI scan [19]. TheNanostim LCP has also received CE Mark approval for MRIconditional labeling for 1.5 T scans in Europe.Safe delivery of radiotherapy in a patient with Micra TPS

device has been previously reported [20]. For the Micra TPSdevice, in order to avoid oversensing, device damage, anddevice operational errors, the following precautions wererecommended: (1) reprograming to asynchronous pacing ifthe average radiation dose rate at the device exceeds 1 cGy/min, (2) avoiding accumulated dose of 500 cGy by usingappropriate shielding, and (3) delivery of photon beam ener-gies less than or equal to 10 MV if possible, or interrogate thedevice after radiotherapy [21].

Table 2 – Major indications and contraindications of leadless p

Indications• Chronic atrial fibrillation with AV block or significant pauses• Sinus rhythm with high grade AV block with low level of physical ac• Sinus bradycardia with infrequent pauses• Unexplained syncope with abnormal electrophysiological findings su

Contraindications• Mechanical tricuspid valve• Pre-existing endocardial pacing or defibrillation leads• Inferior vena cava filter• Hypersensitivity to dexamethasone acetate• Unfavorable femoral venous anatomy• Morbid obesity preventing implanted device from obtaining telemetr• Pacemaker syndrome• Pre-existing severe pulmonary hypertension

Current data suggest no significant effect of defibrillationtherapy on functioning of leadless pacemaker [22,23].Recommended precautions include using the lowest clini-cally appropriate defibrillation energy as possible, and also toperform post-shock device interrogation [21].Cremation of the Micra TPS device has been tested in

human cadavers and performed in real-life situations, andwas found not to be associated with any noticeable explosionor damage to crematory chambers [24,25]. This may be due tothe small lithium carbon monofluoride battery volume, whencompared to the size of contemporary transvenous pace-makers. Cremation recommendations for Nanostim LCPdevice include cremation in an enclosed crematorium if

acemakers [10,11].

tivity

ch as prolonged HV interval

y communication

Table 3 – Overview of implantation outcomes and safety data.

LEADLESS,n

% LEADLESSII, n

% MicraTPS, n

% Micra postapprovalregistry, n

%

No. of patients 33 526 725 795Implantation success 32 97.0 504 95.8 719 99.2 792 99.6

Electrical performanceBaseline R-wave amplitude, mV 8.3 7.8 11.2 11.4Follow-up R-wave amplitude, mV 10.6 (3 months) 9.2 (12 months) 15.5 (24 months) NA

ComplicationsCardiac effusion or perforation

requiring intervention1 3.0 6 1.1 11 1.5 2 0.3

Deep vein thrombosis or pulmonaryembolism

0 0.0 1 0.2 2 0.3 1 0.1

Vascular complications NA 7 1.3 5 0.7 6 0.8Device dislodgement 0 0.0 6 1.1 0 0.0 1 0.1Pacing threshold elevation requiring

intervention0 0.0 4 0.8 2 0.3 0 0.0

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possible, and if open-air cremation is conducted, bystandersand inflammable materials must be kept back at least 10 m(33 ft) [26].

Comparison with transvenous pacemakers

Comparison of data from historical VVI pacemaker cohortsrevealed comparable absolute short-term (≤2 months) device-related complications rates in leadless pacemakers (4.8%) andconventional pacemakers (4.1%) [27]. However, there aredifferences in the nature of complications encounteredduring implantation of these two systems. In cohorts ofconventional pacemakers, the short-term complications weremostly due to pneumothorax (0.6–0.9%), lead dislodgement(0.4–1.7%), hematoma (0.2–0.7%), and cardiac perforation(0.1–0.3%) [3,27–30]. In leadless pacemaker trials, there wasa 4.8% risk of short-term device-related complication, whichincluded 1.5% risk of cardiac perforation, and 0.9% risk ofvascular complications, 0.5% risk of pacing threshold eleva-tion requiring re-intervention and 0.5% risk of acute devicedislocation [27].As for 12-month outcomes, the Micra TPS has been com-

pared to propensity matched historical controls with trans-venous systems, and has been found to have 48% lower riskof major complications, which was primarily driven by 47%reduction in hospitalizations and 82% reduction in pace-maker system revisions [31,32]. Comparison of 12-monthoutcomes from the LEADLESS II study to standard single-chamber pacemaker implantation revealed 71% reduction incomplications related to standard pacemakers [33].Overall, based on indirect comparisons with historical

cohorts, leadless pacemakers were associated with a reduc-tion in risk of pneumothorax, subclavian vein thrombosis orocclusion, lead-related complications such as dislodgementor fracture, pocket hematoma, but increased risk of femoralvein complications. Randomized trials comparing leadlesspacemakers and conventional pacemakers are needed tocompare short- and long-term outcomes and complicationrates. Other factors to consider when deciding the

appropriateness of leadless pacemaker implantation includeits limited battery longevity, which may be a barrier to its usein young patients. Furthermore, leadless pacemakers mayonly be appropriate in patients where atrial tracking is lessimportant and therefore only require VVIR pacing, such aspatients with chronic atrial fibrillation, or infrequent pausesor bradycardias. Other practical considerations would includethe more expensive cost of the leadless pacemaker comparedto the traditional transvenous pacemaker.

Deactivation and retrieval

Proposed options at the end of service (EOS), when the batterylife reaches its end, include programming the device off,which permanently deactivates pacing and sensing, andimplanting a new leadless pacemaker or transvenous pace-maker. Pre-clinical study on six human cadaver heartsrevealed that three Micra TPS devices could be accommo-dated in the right ventricle within the traditional pacinglocations [34]. The other option is to retrieve the device andto implant a new leadless pacemaker or transvenous pace-maker [8].Beyond EOS, other possible reasons for device retrieval

include elevated pacing threshold, need for biventricularpacing therapy or upgrade to a secondary prevention defib-rillator, and systemic infection with vegetation noted ondevice [8,35,36]. Both the Nanostim LCP and the Micra TPSincorporate a posterior docking button to facilitate late deviceretrieval. Retrieval of the Nanostim LCP is via the NanostimLCP retrieval system, which is a single or triple loop snarewith an integrated protective sleeve (Fig. 8) [35]. The techni-que for Micra TPS retrieval is almost similar, utilizing aretrieval feature at the proximal end, which can accommo-date a snare that can firmly hold the device for removal.Complete encapsulation of the device, which is thought to

theoretically reduce risk of infection leadless pacemakersthat are left in-situ at EOS, may also complicate the retrievalprocess [37]. Available data from Nanostim LCP trials revealedthat the success rate for pacemaker retrieval was 100% in

Fig. 8 – Fluoroscopic images in RAO 30° demonstrate extraction of a leadless pacemaker in patient with pacemaker relatedectopy. (A) Nanostim LCP retrieval system is positioned behind the docking system with the single loop snare. (B) Snareengages the docking feature. (C) Retrieval catheter engages the leadless pacemaker. (D) Protective sleeve facilitates coaxialalignment and device is rotated counter clockwise to unscrew the leadless pacemaker from the endocardium. The pacemakeris then fully covered by the protective sleeve and is then withdrawn from the body. (E) The retrieved Nanostim LCP device.(Images courtesy of Paul A. Friedman MD.)

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devices implanted within 6 weeks (5 of 5 patients), and 91%(10 of 11 patients) for those implanted for more than 6 weeks(with a mean retrieval time of 346 days, ranging from 88 daysto 1188 days) [11]. The case of the unsuccessful retrieval,

which was 103 days after implantation, was due to failure ofengagement of the docking feature due to the position of thedevice relative to the subvalvular apparatus. There were noprocedure-related adverse events in all the retrieval cases.

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There have also been preclinical studies in ovine models,demonstrating successful retrieval at a mean of 2.3 ± 0.1years [38].Data with Micra TPS revealed successful percutaneous

retrieval in 7 of 9 attempts, with all of the successful attemptsperformed within 6 months post-implant [8]. One of the failedattempts was 229 days after implantation. The Micra TPS wasthen turned to off mode and a transvenous pacing systemwas implanted. The other failed attempt was related tofluoroscopy malfunction and retrieval was abandoned. Pre-clinical study in sheep revealed successful percutaneousretrieval of Micra TPS at 28 months in 3 out of 4 devices.The one unsuccessful retrieval was due to complete encap-sulation of the Micra TPS discovered during necropsy analy-sis. Studies will be needed to look into the possibilities ofcurrent available imaging modalities to determine level ofencapsulation, which may help estimate risk of deviceretrieval.

Subcutaneous implantable cardioverter-defibrillator (s-icd)and leadless pacemaker

Currently, patients with a subcutaneous ICD who develop apacing indication will have to switch to a transvenous pace-maker. With leadless pacemaker, there is a potential forcombination of a leadless pacemaker in patients with sub-cutaneous ICD that may benefit patients with venous occlu-sion as well as those with recurrent lead or pocket infections.The interaction between S-ICD and leadless pacemaker wasstudied by Tjong et al. [22], which revealed no interference insensing and pacing during intrinsic and paced rhythm in twosheep models and one human subject. There was also noeffect of defibrillation therapy on leadless pacemaker func-tion based on follow-up of two patients with leadless pace-makers who received electrical cardioversion. However, moredata are required before broad adoption of this combinationtechnology, which may permit anti-bradycardia and anti-tachycardia pacing together with a subcutaneous ICD.

Multicomponent system

Wireless cardiac resynchronization system

The wireless cardiac resynchronization system (WiSE-CRT,EBR Systems, Sunnyvale, CA) utilizes a multicomponentstrategy to for leadless cardiac resynchronization. It is a9.1 × 2.7 mm receiver electrode composed of titanium coveredby polyester. It is delivered into the left ventricle utilizingpercutaneous aortic retrograde approach and implantedendocardially in the left ventricle via three self-expandingnitinol tines. A separate device, which is a pulse generator,is implanted subcutaneously in the left lateral thorax.This device generates ultrasound pulses that are convertedto electrical pacing stimuli by the endocardial receiverelectrode. There is no battery in the endocardial receiverelectrode. It has an added benefit of left ventricular endo-cardial pacing, which has been proposed to be superior toconventional epicardial pacing based on several pre-clinicaland human studies [39–41].

This system was investigated in the WiSE-CRT study andthe more recent SELECT-LV study, both of which wereprospective multicenter observational studies [42,43]. TheWiSE-CRT study enrolled 17 patients and the SELECT-LVstudy enrolled 35 patients. Both studies included patientswho failed conventional cardiac resynchronization therapy(CRT) such as those who failed coronary sinus lead cannula-tion or non-responders to conventional CRT implantation.The Wise-CRT study also included eight patients that wereenrolled as an upgrade from previously implanted pacemakeror ICD device. Unfortunately, the study was suspended earlydue to a high incidence of intra-procedural hemodynamicinstability related to severe pericardial effusion (n ¼ 3, 18%)due to delivery sheath manipulation or guide wire placement,with one death associated with one of these events. Follow-ing redesign of the delivery sheath to include a balloon,which permits atraumatic engagement with the LV endocar-dium, the more recent SELECT-LV study did not have anyincidences of cardiac tamponade. However, there were threeimmediate procedural complications (n ¼ 3, 8.6%), with oneventricular fibrillation due to catheter-induced ventricularectopy, one electrode embolization to the lower extremity,and one femoral artery fistula requiring surgical repair.Nonetheless, the study showed a high implant success rateof 97% with clinical and structural improvements comparableto conventional CRT trials [44,45]. Additional studies will beneeded to evaluate long-term outcomes.

Future perspectives

The future of leadless pacemaker lies in the advancement ofeffective communication between multiple wireless compo-nents. Improvement in inter-device communication will permitseamless coordination between multi-component leadlesspacemakers implanted in the right atrium, right ventricle, andleft ventricle, permitting optimal atrio-ventricular sensing,pacing, resynchronization therapy, and if needed, defibrillationtherapy via a subcutaneously placed device. Improvement ininter-device communication will permit coordination withdefibrillation therapy, anti-tachycardia pacing, as well as otherimplantable monitoring devices including pulmonary arterypressure sensors [46]. There is also the possibility of a futurewhere all the leadless components are batteryless motionharvesting pacemakers, led by advancement in technologypermitting high-efficiency conversion of mechanical to electricalenergy based on the natural contractile and relaxation motionsof the heart, lung, and diaphragm [47].

Conclusion

Leadless cardiac pacemakers may potentially revolutionizecardiac pacing, and early data from current generation ofleadless pacemaker devices shows promise. However, long-term data are still needed to verify device performance, safetyand extractability prior to wider adoption of this technology.Randomized trials are needed to determine if leadless pace-maker systems are superior to conventional pacemakers inlong-term safety and performance.

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Acknowledgments

The authors would like to thank Margaret McKinney for helpwith illustrations.

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