Leadless Pacing - Clinical Tree

Implantable cardiac pacing was born in 1958 and has never stopped evolving since. The contribution of new advances has been dramatic in this development, especially over the last 25 years, because of the introduction of electronics and the progress in battery technology. However, the physical structure of the system remained the same: a can containing the battery and the electronic circuit is connected to the heart by one or more leads. The first implantations were surgical with epicardial leads, but the standard procedure fast became endovascular. Since the origins of the art, the implanters have become accustomed to complications related to this hardware, especially those due to the very presence of the case, placed mostly in an infraclavicular subcutaneous position, and those related to the endovenous electrodes. With longer life expectancy, many implanted patients suffer the pangs of chronic complications that are dangerous in themselves and can also affect the success of their treatmentl. Material infection is in the foreground and requires complete extraction of the hardware by trained operators in a safe environment. Finding new solutions was mandatory to eliminate these complications. This was the primary reason for seeking leadless pacing. Other justifications include the provision of the pacing technique to a larger number of patients. As the world population is growing, so is the number of pacing indications. Emerging countries have a very high birth rate and the need for pacemakers will be substantial in the future. In economically developed countries, the population is aging, and pacing indications are also increasing. However, medical demography does not increase proportionally with the population. The world is experiencing an economic downturn or even recession. Therefore solutions that are simpler, less expensive, and quick to set up are needed. This assertion means the development of minimally invasive and safe implant procedures, usable by nonexpert hands in clinics that do not necessarily have high performance equipment. The path chosen is the one of a miniature pacemaker implantation in the right ventricle (RV). The first step is to ensure safety.

In parallel, cardiac resynchronization therapy (CRT) added its own complications to those of traditional pacing. They are linked to the placement of the left ventricular (LV) lead into a vein of the coronary sinus network. In addition, the proportion of nonresponders to this procedure is far too important and forces us to seek other implantation techniques that are tailored to each patient. This objective must be achieved in light of the most recent studies, but the current procedure leaves no freedom of choice of the LV pacing site. Therefore we must move away from the coronary sinus veins and find other solutions for LV pacing. These two requirements lead us to leadless pacing. However, this line of research is somewhat in contrast with the one of conventional pacing, because the path is much more complex. We must search for and determine the optimal stimulation sites and adapt the implantation technique to each patient. Thus specific delivery systems must be developed. These requirements mean the continuation of intensive research to understand the mechanisms of resynchronization, a research that is far from complete more than 20 years after the first definition of this therapy and its first application. Therefore the objective is different and leads to complex and expensive systems, set up in sophisticated centers, in which we will observe that the energy supply is the most challenging aspect.

These two themes will be addressed in this chapter. The first topic will be illustrated by the first data of the validation protocols in progress with leadless pacemakers; the second will explain the principles of cardiac pacing by a capsule receiving its energy from an extrathoracic transmitter.

In a third section, we will detail research performed in our institution, which aims to develop noninvasive tools, based on high intensity focused ultrasound (HIFU) for pacing the heart. The goal is twofold: diagnostic, to test various pacing modalities before providing implantable cardiac pacing tailored to the individual, and therapeutic, to deliver noninvasive temporary cardiac pacing in emergency situations.

Leadless Pacemakers for Permanent Cardiac Pacing

Usually, each new pacemaker or defibrillator is constructed from a well-known base to which a portion of hardware or software is added or substituted in order to improve diagnostic or therapeutic features. This time, the entire system has been redesigned which represents an extraordinary technical and technologic challenge.

For a long time, alternative techniques have been sought in order to remove the leads that are at the origin of the most serious long-term complications. Thus as the leads disappear, we must implant the pacemaker directly in contact with the myocardium. Although the concept sounds simple, the device has to comply with certain requirements and meet the following conditions ( Fig. 20-1 ):

Small
Quick and easy to implant and follow-up
Safe in terms of fixation and operation
Offer the same functionality as conventional pacemakers
Long service life
Compatible with the modern environment (specifically with [magnetic resonance imaging [MRI])
Allow for remote monitoring

We are on the right track as two ventricular pacing, ventricular sensing, inhibition response and rate adaptability (VVIR) leadless pacing systems are being validated for approval by the relevant authorities.

Figure 20-1, General Concept of the Leadless Pacemakers.

The new devices are made of a small cylindrical capsule composed of electronics, a battery, the electrodes, and the fixation system. The miniaturization of the electronic circuit was mandatory and is available today. Space constraints within the capsule required the development of a different way to wind or fold the electronic support. Energy consumption of the hardware has been reduced. The same applies to communication with the outside, whether this is a programmer for telemetry or a transmitter for telemedicine. The onboard energy is high density, and requires a life at least as long as the one of the conventional pacemakers. Finally, many of the functions are devolved to the energy economy.

The development of those new pacing systems fully benefits from existing advanced techniques sometimes applied to other therapies, such as new materials and processes that allow us to conceive new shapes and fixations applicable to our devices. For instance, nitinol is flexible and regains its shape when it is released from mechanical stress, as well as surface treatments, which accelerate the endothelialization process or reduce platelet aggregation. To implant the prosthesis into the ventricle means the development of new delivery systems. Several transcutaneous therapies have already forced the development of similar systems such as the implantation of a left atrial appendage occluder for permanent foramen ovale or of percutaneous heart valves.

The concept is not new, since William Spickler in 1970 described what we have in hand today, including the method to implant the system. It took 45 years for the technology to make available this revolutionary concept, according to current specifications.

Description of the Existing Leadless Pacemakers and Implantation Methods

Every company is now developing this type of pacemaker, but only two devices have reached the validation phase:

NanoStim (St. Jude Medical, St. Paul, MN)
Micra (Medtronic, Minneapolis, MN) ( Fig. 20-2 )

Their characteristics and delivery methods are very similar, and both offer features similar to a conventional VVIR pacemaker. Both systems are self-contained, hermetically enclosed miniaturized rate-responsive single-chamber pacemakers and weigh approximately 2 g for 1 cm ³ . They are delivered percutaneously via a single-use transfemoral catheter and an introducer sheath (18 Fr, and 23 Fr, respectively) ( Fig. 20-3 ). The fixation mechanism for the Nanostim is a helix and four electrically inactive protractable nitinol tines for Micra. They include a docking button that allows attachment of the device to the catheter for delivery, repositioning, and retrieval.

Figure 20-3, The Delivery Tools for Implanting the Micra Device.

In Nanostim, a temperature sensor is devoted to rate-responsiveness. In Micra, the primary differences are a three-axis accelerometer sensor to allow the physician to select an alternative axis to sense activity, capture management with automatic hourly safety margin confirmation to ensure pacing outputs remain at safe levels, and an end-of-service (EOS) operation to allow subsequent implants without requiring a Micra explant. (The device can be permanently programmed “OFF to OOO mode.”) They are equipped with a lithium carbon monofluoride (Li-CFx) battery. Their battery life is close to 10 years at 100% pacing (2.5 V, 600 ohms, 60 bpm for Nanostim; 1.5 V, 0.24 msec pulse width, 600 ohms, 60 bpm for Micra), and more than 14 years at 50% pacing.

Both pacemakers have similar electrical equipment. The steroid eluting tip electrode is made of titanium nitride coated platinum-iridium and has a surface area of 2 to 2.5 mm ² . A large surface area anodal ring electrode is on the titanium pacemaker case.

A dedicated programmer communicates with Nanostim by wireless telemetry, for interrogation and programming. Signal transmission from the programmer to the implanted Nanostim is accomplished by applying subliminal 250-kHz pulses to the skin electrodes. Except for this special type of signal transmission, the programmer obeys the same operating principles as conventional pacemaker programmers. For Micra, the conventional programmer is used with communication through the programmer header.

The delivery systems include a steerable catheter with a protective sleeve designed to protect the fixation hardware. It is advanced from a percutaneous access site in the groin via the femoral vein to the apex of the RV. Delivery is accomplished by rotation of the Nanostim to secure the helix in the myocardium, and by a simple push of the Micra to engage the tines into the myocardium. Then both devices are undocked from the delivery catheter, but still maintaining a link to the device with a tether when thresholds are measured, without the catheter applying forces to the device. If thresholds are judged unacceptable or if fixation is not ensured, devices can be unfixed and retrieved into the sleeve of the delivery system in order to find another location until thresholds are acceptable. To release the device, the tether is disconnected (Nanostim), or cut (Micra), and removed. (Refer to Case Study 20-1 for a video-enhanced illustration of the successive steps for the implantation of a Micra pacemaker; also see Figs. 20-9 to 20-20 .) A retrieval catheter system, which uses either a single-loop or a triple-loop snare to engage the docking feature on the proximal end of the Nanostim, can be used to unscrew and to retrieve the leadless cardiac pacemaker (LCP). A lasso must be used to remove a Micra device from the heart.

Given the structure of these systems and their implementation mode, what can we expect from this new therapeutic modality?

Case Study 20-1

Implantation Procedure of a Leadless Pacemaker

The Case

50-year-old male
Permanent atrial fibrillation, no indication for RF ablation
- Atrial fibrillation started 9 years before
- Huge dilation of the left atrium
- Patient became highly symptomatic
Fast ventricular rate, failure of rate control with drugs
Left ventricular ejection fraction: 55%, no right ventricular (RV) dysfunction, no valvular disease
Ablate and pace strategy proposed to the patient
Included in the Micra study, signed informed consent

The Procedure

Placement of a 6-French sheath in the right femoral vein to introduce a multipurpose catheter over a 0.035-J wire up to the superior vena cava (SVC) ( ).
Exchange of the J wire for a superstiff J wire through the multipurpose catheter that is then removed as well as the 6-French introducer, leaving the stiff J wire up the SVC ( ). Over this latter wire, introduction of 23-French introducer plus dilator under fluoroscopic control. The system is pushed and rotated in order to facilitate its progression. Some back pain may be felt by the patient, especially females, when the tool is within the inferior part of the inferior vena cava (IVC), that disappears as soon as the dilator and stiff wire are removed from the introducer.
Dilator and stiff wire removed leaving the introducer in the lower right atrium. A marker ring can be seen at the tip of the introducer.
The delivery system is pushed through the introducer, up to the right atrium ( ). The Micra can be seen inside the distal tube of the delivery system (a marker ring is visible at the tip of the catheter). Tines are maintained straight inside the tube, ahead of the tip electrode.
The introducer is pulled back to the IVC, and the delivery catheter is curved toward the tricuspid valve (anteriorly and leftwards) ( ).
The catheter is pushed through the tricuspid valve into the right ventricle ( ). This maneuver must be slow and gentle because the catheter may trigger fast runs of premature ventricular contractions when it hits the ventricular walls. The tip of the catheter is blocked against the right ventricular wall. It should be pulled back, then rotated and then pushed again toward the apex.
A cautious dye injection shows that the catheter tip is far from the ventricular apex in the anteroposterior view (it was confirmed in the 50-degree left anterior oblique view) ( ). Just a small quantity of dye is needed (5 to 7 cm ³ ). Pressure imposed on the syringe should remain low in order to avoid any risk of intramyocardial dissection, or to favor perforation. The goal is to know where the catheter tip is relative to the myocardial wall. In this example, the inferior part of the tip ring is against the inferior wall of the right ventricle. If the catheter is pushed further on, it may create an injury of the right ventricular inferior wall. All maneuvers must be gentle and slow.
The catheter tip is closer to the apex, but still more oriented toward the inferior and apical wall ( ). The catheter tip should be directed higher, toward the septum.
shows a 50-degree left anterior oblique view. This time, the catheter tip is at the right spot.
shows confirmation of the correct positioning of the catheter in the anteroposterior view.
The tether that maintains the device inside the delivery catheter is freed. Pressure is maintained against the myocardium.
- The device is slowly pushed by the cup that is behind it, using a cursor of the handle at the proximal end of the delivery catheter ( ). Nitinol tines can be seen coming out from the distal end of the catheter. At that stage, tines are engaging into the myocardial wall. The catheter is pulled further back slowly, tines regain their original shape and are fully engaged into the myocardium.
- While the implanter continues to push the device, the catheter is slowly pulled back in order to maintain the alignment between the catheter and the device when the latter is completely outside the delivery catheter. This maneuver avoids kinking of the device that might disengage one or more tines from the myocardium and compromise fixation.
The device is deployed, still attached to the delivery catheter by a tether ( ). The delivery catheter is pulled back continuously, and no kinking occurred. Both devices are perfectly aligned. A curve of the delivery catheter should be maintained until the catheter is back to the introducer, to avoid excessive tension on the tether.
The programmer head faces the pacemaker over the anterior chest wall ( Fig. E20-1 ). Electrical tests were not satisfactory (R wave: 1.5 mV, impedance: 680 ohms, threshold: 2.75 V at 0.24 msec pulse width [PW]). The pacemaker has to be retrieved, simply by pushing the delivery catheter back to the pacemaker, and using the stretched tether as a guide.
New delivery attempt ( ). Another position must be found. A new dye injection in the 50-degree left anterior oblique view shows that the catheter tip is over the apex, along the anterior midseptal wall. Delivery of the pacemaker is performed at that spot as previously described. Control of electrical performance. R wave is 12 mV, impedance is 800 ohms, and capture threshold is 0.38 V at 0.24 msec PW.
Pull and hold test ( ). The device is pulled with the tether until heart beating can be felt. Then cine is recorded. The manufacturer recommends that at least two tines should be moving, proving their proper engagement into the myocardium and proper fixation of the device. Different views are frequently needed to perform this important check.
- During systole, the inferior tines are moving. The upper ones do not.
- Different sequences were recorded. Three tines were engaged. The pacemaker is ready to be released. A complete check of the device functioning is performed again with the programmer.
The tether has been cut and removed ( Fig. E20-2 ). The introducer was also removed. Compression of the femoral vein was performed. The pacemaker has been controlled.

After the Procedure

Patient was discharged the next day.
Atrioventricular node ablation will be performed in 3 weeks, after pacemaker check.
A programming session is planned right after ablation, including various exercises in order to optimize rate responsiveness.

Expected Benefits of Leadless Pacing

From the description of the material, it is possible to imagine the kind of classic complications that can be eliminated completely, and the new specific complications that can be encountered. Only the test of time will accurately determine the benefits and risks of this new method. Table 20-1 reports the most common complications that can be foreseen with leadless systems, in comparison with the conventional pacing therapy.

TABLE 20-1

Complications That Are Observed With Conventional VVI Pacing and Complications That Are Expected or Avoided With Leadless VVI Pacing

Complication	Conventional VVI	Leadless VVI
Pneumothorax	+ +	− −
Hemothorax	+	− −
Arrhythmias	+ +	+ +
Perforation	+ +	+ +
Tamponade	+	+
Dislodgement	+ +	+
Diaphragmatic stimulation	+	+
Lead/valve conflict	+	−
Venous thrombosis	+ + +	− −
Pocket hematoma	+ + +	− −
Wound pain	+ + +	− −
Pocket infection	+ + +	− −
Bloodstream infection	+ + +	− −
Device-related endocarditis	+ + +	+
Groin hematoma/atrioventricular fistula	− −	+ +
Impossible implantation	−	+ +

A simple implantation by a femoral venous access, the absence of surgery, a reduction of radiation exposure, and an obvious cosmetic benefit to the patient should significantly reduce the rate of complications. However, some may be dangerous. If the capsule migrates, it is necessary to grab and remove it completely from the femoral vein, a maneuver that can be quite difficult if the capsule has migrated to the pulmonary circulation.

However, the most feared complication of cardiac pacing is infection. It leads to the complete extraction of the material, a dangerous technique when performed years after implantation. During extraction, fibrotic tissue around the lead(s) favors injury to the vascularature and to the tricuspid valve leading to immediate surgical repair and sometimes to death. In the case of leadless pacing, the diagnosis of infection might be difficult in the absence of vegetation, for example. Complementary diagnostic methods should then be used, such as positron emission tomography (PET) scan that can show a hot spot at the site of the device implantation in the RV. Extraction is made difficult by the difficulty of gripping the capsule. The explant will likely be easy if done a few months or even years after implantation, but will certainly be complex after several years due to the gradual encapsulation of the system. Only surgery would then be effective and safe. This is the major difference with the traditional pacing therapy, where surgery is very rarely necessary. Probably the most common complications will be those of the femoral access. First, because of the possible difficulty of venipuncture in the elderly or obese, for example, and also the risk of accidental puncture of the femoral artery with subsequent arteriovenous fistula, and the risk of postprocedural hematoma due to the size of the introducer (18 and 23 Fr).

These observations will only be analyzed after years of experience.

Results

Ongoing studies are used for device approval, and the authors are not allowed to disclose interim results, because results have not yet been published. The results reported in this chapter are only partial because of the step back to the use of leadless pacemakers; they focus on animal studies and very low numbers in humans. These tests show similar results with the two systems.

In Animals

These new techniques have been widely tested in animal experiments. The results presented here are those of the chronic study of Micra. The purpose was twofold: to measure chronic electrical performance of a device small enough to be implanted in the RV and to start to learn the major issues regarding electrode leadless performance with the pacer concept. Sixteen adult sheep were implanted with a prototype of Micra via the jugular vein, connected to a standard pacemaker in order to perform weekly electrical measurements for 6 months. All devices were placed at the RV apex. No movement and no adverse event has occurred: tamponade, pericardial effusion, damage to valves or other cardiac structure, thromboembolism or infection. The determination of the strength-duration curve revealed a shorter chronaxy than that found with conventional electrodes. Thus a 0.24-msec nominal pulse width has been chosen. This is an important factor for energy consumption reduction, extending the life of the device accordingly. R-wave amplitudes are excellent, stimulation thresholds are very low, and impedances are high, also energy saving factors ( Figs. 20-4 through 20-6 ). These animal experimental data show the substantial encapsulation of the device and the weak development of fibrosis at the active electrode site compared with conventional screw-in leads ( Figs. 20-7 and 20-8 ).