recent advances in lead less pacemaker

1. Leadless pacemakers and
biological pacemakers
Dr. Siva subramaniyan
PGIMER
Dr RML HOSPITAL
New Delhi.

2. HISTORY

3. • Advances in battery and circuit technology have led to programmable
multichamber pacemakers with a lifespan of 7–10 years.
• Conventional subcutaneous pacemaker implantation and transvenous lead
placement requires a surgical procedure.

4. • It is estimated that more than 700,000 pacemakers are inserted annually
worldwide .
• The number of permanent pacemaker implants is rising due to an increase in
mean age of populations and other medical co-morbidities.
• Despite the fact that conventional lead pacemakers improve patients’ clinical
status, the pacing leads have long been considered their Achilles’ heel .

5. • Despite these developments, this life-improving therapy is still associated with
significant complications, mostly related to the transvenous lead and the
subcutaneous generator pocket.
• Short-term complication rates as high as 8% to 12% have been reported.

6. • include
- pneumothorax,
- cardiac tamponade,
- pocket hematoma,and
- lead dislodgement.
• Transvenous leads can cause complications such as venous obstruction, tricuspid
regurgitation, and endocarditis.

7. • Transvenous lead– related endocarditis has been reported associated with a
mortality risk as high as 12% to 31%.
• In the long term, these leads are also prone to insulation breaks and conductor
fracture, requiring reintervention that puts the patient at risk for significant
morbidity.
• 0.7% to 2.4% of patients encounter serious complications related to the
subcutaneously placed pulse generator: skin erosion, pocket infection, and
septicemia

8. • To address these lead- and device pocket–related issues, leadless pacemaker
systems were conceptualized in the 1970s and have been gradually developed. In
2012, a new single-chamber right ventricular leadless cardiac pacemaker was
introduced.

9. LEADLESS CARDIAC PACEMAKER
• The leadless cardiac pacemaker (LCP) is an innovative concept involving
placement of a completely self-contained intra-cardiac device. Usage of LCPs in
humans became a realistic target when they were successfully studied in animal
models

10. • Leadless pacemakers (LCP) can overcome these issues due to absence of leads
and no requirement for a surgical pocket.
• Spickler et al. in 1970 were the first to introduce the concept of LCP

12. TYPES
• MULTI COMPONENT (NOT SELF-CONTAINED) LEADLESS PACING
- ultrasound-mediated energy transfer
- induction technology
• SINGLE-COMPONENT (FULLY SELF-CONTAINED) LEADLESS PACING
- VVIR

13. • Currently, there are three major LCPs being made and tested.
- the Nanostim leadless cardiac pacemaker (LCP)
- the Micra transcatheter pacing system (TPS)
- WiCS (Wireless Cardiac Stimulation; EBR Systems)

14. NANOSTIM
• The first is the Nanostim device made by St. Jude Medical (St Paul, MN, USA). It is
smaller than an AAA battery and can be completely placed within the heart .
• Most of the LCP consists of a battery.
• This 4-cm long, 6-mm wide, and just 2 g in weight LCP

18. IMPLANT PROCEDURE
• The introducer sheaths are dedicated for the procedure and measure 18F (inner
diameter)/21F (outer diameter) for the LCP, and 23F (inner diameter)/27F (outer
diameter) for the TPS.

19. PROCEDURE

22. • The pacemaker is deployed by using either a screw-in helix (LCP) or nitinol tines
(TPS) to actively fix the device to the myocardium.
• After electric measurements are obtained, the stability of the fixated pacemaker
is assessed by performing a gentle tug test.
• Subsequently, the pacemaker is released from the delivery catheter by
removing/unlocking the tether

27. • The implant success rate was 97% (n= 32)
• the majority of patients (n = 23, 70%) did not require any repositioning of the LCP
after its initial deployment.
• Five patients (15%) required the use of >1 LCP during the procedure due to either
- inadvertent placement of the device in the left ventricle (n=1),
- a malfunction of the release knob (n=1),
- delivery catheter damage related to tortuosity of the venous vasculature (n=1),
- damage to the LCP helix during insertion (n=1) and
- difficulty with the wire deflection mechanism of the delivery catheter (n = 1)

30. Safety
• The overall complication- free rate was 94% (31/33)
- tamponade
- LV placement

40. MIRCA

41. • Comparatively, the TPS (25.9 x 6.7 mm) is shorter but wider than the LCP (42 x
5.99 mm).
• the outer diameter of the delivery sheath for the TPS is larger (24-F) than that for
the LCP (18-F)
• the TPS uses 4 self-expanding nitinol tines to affix to the myocardium

45. • Major device-related complications occurred in 25 (3.4%) of the 725 patients,
including
- cardiac perforations in 1.5%,
- vascular complications in 0.7%,
- venous thromboembolism in 0.3%, and
- increased pacing thresholds in 0.3% of patients.
No device dislodgements were observed

46. • The electric performance of the TPS during 6 months of follow-up showed stable
measurements between implant and 6 months:
- mean R-wave amplitude of 11.2 mV and 15.3 mV,
- mean pacing capture threshold (at 0.24 ms) of 0.63 V and 0.54 V, and
- mean pacing impedance of 724Ω and 627Ω, respectively

48. Retrievability versus Abandonment
• Both leadless pacemaker systems are designed to be retrieved if necessary, and
recent publications support acute and midterm retrievability.
• The LCP has a dedicated retrieval catheter available with either a single-loop or
triloop snare, and has a screw-in fixation mechanism that may facilitate
atraumatic removal .
• The largest retrieval experience with the LCP includes 16 patients (77±13 years,
75% male) who required device removal for either elevated pacing thresholds (8
patients), worsening heart failure (5 patients), failure to pace (1 patient), upgrade
to defibrillator (1 patient), or elective explantation (1 patient)

49. • Catheter-based retrieval was successful in 15 of 16 patients (94%) without the
occurrence of retrieval-related Serious Device Adverse Effects (no pericardial
effusions occurred).
• The mean time from implant to retrieval was 240 days.
• Although this experience includes only a small number of patients followed for a
mean implant-to-retrieval timeof less than a year, there is some preclinical
evidence that retrieval of this device may be possible more long term.
• In an ovine study, LCP retrieval was 100% successful in 8 sheep in which devices
had been implanted for a mean of 2.3±0.1 years.

51. RETRIEVAL
Miller et al. Leadless Cardiac Pacing. J A C C V O L . 6 6 , NO. 1 0 , 2 0 1 5

52. Circulation. 2017;135:1458–1470.

53. • Considering the uncertainty of long-term retrieval attributable to device
encapsulation, the optimal end-of-life replacement strategy is yet to be defined.
• One strategy, which already has been exercised with the TPS, is to abandon and
turned-off leadless pacemaker in the RV.
• The small volume of these leadless devices (0.8–1.0 cc) accounts for <2% the
volume of a normal-sized RV and is quite unlikely to cause hemodynamic
compromise.

55. Leadless system for left ventricle pacing
• The leadless ultrasound-based technology used by the WiCS (Wireless Cardiac
Stimulation; EBR Systems) system is designed to achieve LV endocardial pacing.
•
• Leadless ultrasound pacing is accomplished by transmitting ultrasound energy
from a subcutaneous transmitter unit to an endocardial receiver unit.
• Fixation to the endocardium is achieved by three self-expanding nitinol tines
mounted at the distal end of the device.

56. • The whole CRT system comprises
(i) the LV endocardial unit, which receives ultrasound energyand converts it to
electrical energy for LV pacing,
(ii) the subcutaneously implanted pulse generator and
(iii) a conventional pacing device.
The subcutaneously implanted pulse generator comprises the battery and the
transmitter, connected by a cable. The transmitter includes an ultrasound
transducer array, the energy of which can be focused for effective transmission to
the LV endocardial unit.

58. BIOLOGICAL PACEMAKER

59. BIOLOGICAL PACEMAKER
• biological pacemaker is one or more types of cellular components that, when
"implanted or injected into certain regions of the heart," produce specific
electrical stimuli that mimic that of the body's natural pacemaker cells.

60. Why is a biological pacemaker needed?
• Electronic pacemakers “per se” have no physiological autonomic responsiveness
• There is a need for regular pacemaker unit testing and replacement.
• Potentially lethal complications can occur during both the perioperative period
and after long time also
• Electromagnetic interferences with pacemakers in medical and non-medical
environment have been reported.
• There is no ideal pacemaker for children.
Chauveau et al. Cytotherapy. 2014 July ; 16(7): 873–880.

61. Strategies for building a biological pacemaker
Three strategies reported till now to create biological pacemaker activity:
1. Up-regulation of adrenergic neurohumoral actions on heart rate (Edelberg1998,
2001).
2. Reduction of repolarizing current (Miake et al 2002).
3. Increasing inward current during diastole (Qu et al 2003).
Chauveau et al. Cytotherapy. 2014 July ; 16(7): 873–880.

62. Vectors and methods of gene delivery
• vector may be RNA or DNA viruses or non viral in nature.
• Viruses which have the capacity to incorporate themselves in the host genome
are used as vectors for gene therapy.
• The commonly used viral vectors are genetically modified retroviruses,
adenoviruses, adeno associated viruses and lentiviruses
Chauveau et al. Cytotherapy. 2014 July ; 16(7): 873–880.

63. Chauveau et al. Cytotherapy. 2014 July ; 16(7): 873–880.

64. Cell therapy
• embryonic stem cells (ESCs) can self-renew indefinitely in vitro and differentiate
into derivatives of the 3 different germ layers while human mesenchymal stem
cells (hMSCs) have only limited differentiation and regeneration capacities.
• To date two strategies have prevailed to construct a stem cell based biological
pacemaker:
(a) the injection of a cluster of inexcitable cells expressing an inward current that
will depolarize the contiguous cells to their action potential threshold or
(b) the injection of a cluster of excitable cells with the ability of generating
spontaneous action potentials.
Chauveau et al. Cytotherapy. 2014 July ; 16(7): 873–880.

65. MSC and the 2 cells pacing unit theory
• In 2004 Potapova et al. demonstrated that hMSCs can be transfected with one of
the pacemaker genes (mHCN2).
• By expressing mHCN2 in the hMSC, it was expected that an inward If-like current
would be expressed. This current would flow into the ventricular cells electrically
coupled to the transfected hMSCs
Chauveau et al. Cytotherapy. 2014 July ; 16(7): 873–880.

66. Recreating a SAN function with pluripotent
cells
• research efforts have focused on the possibility of creating an homology to the
SAN by inducing pluripotent stem cells to differentiate into spontaneously
beating cardiomyocytes.
Chauveau et al. Cytotherapy. 2014 July ; 16(7): 873–880.

68. BENEFITS OF LEADLESS CARDIAC PACING
• As its name implies, the most obvious potential benefit of leadless cardiac pacing
is the absence of a transvenous lead.
• Because the majority of acute and chronic complications of conventional
pacemakers are attributable to the transvenous lead, a system that eliminates
this component is desirable.
• The single-component systems do not require a surgical incision/subcutaneous
pocket, which mitigates the risk of surgical complications

69. • may provide a more favorable cosmetic profile.
• LCPs have projected battery longevity that is comparable to that of standard
single-chamber transvenous pacemakers.

70. • The LCP and TPS are also believed to be safe for use with magnetic resonance
imaging (conditionally), because of their lack of ferrous material; however,
additional pre-clinical and clinical testing is necessary to confirm this.
• Finally, because of the greater distance between the radiograph source and the
operator (located at the femoral insertion site) during LCP implantation, there is
potentially less radiation exposure for the implanting physician.

71. LIMITATIONS OF LEADLESS CARDIAC PACING
• For the current generation of single-unit LCPs, the most important limitation is
their ability to perform only single-chamber pacing.
• Therefore, these devices would not be appropriate for most patients with sinus
node dysfunction, who derive significant clinical benefit from dual-chamber
sensing/pacing

72. • there have not been any chronic device embolizations with singlecomponent
systems, but this remains a potential source of concern.
• accuracy of rate-responsive features, now that the sensor has been relocated
from the subcutaneous pulse generator to the intraventricular space, is not yet
known
• They are significantly smaller than conventional cardiac pacemakers, the portion
of the device that interacts with the endocardium has a wider diameter, which
has raised the possibility of proarrhythmia.

73. • Both require larger sheath (24-F for the TPS and 18-F for the LCP) and delivery
catheter.
• The larger caliber of the delivery units has the potential to increase complications
related to either the femoral access site or catheter manipulation within the right
ventricle.
• Indeed, in the LEADLESS study, the one and only major procedural complication
(cardiac perforation and subsequent death) was related to the delivery catheter.

74. FUTURE PERSPECTIVES
• To expand the benefits of leadless pacing to more patients, efforts are being
made to develop multicomponent, communicating leadless systems capable of
performing dual-chamber pacing and cardiac resynchronization therapy

75. • in the future, a patient with congestive heart failure might receive a
communicative device system consisting of:
(1) right atrial, right ventricular, and left ventricular leadless pacers for cardiac
resynchronization,
(2) a subcutaneous defibrillator for sudden death prophylaxis, and
(3) a pulmonary artery pressure monitor for heart failure monitoring.

77. CONCLUSION
• The first 2 leadless pacemaker systems have demonstrated similar performance
and initial promise of efficacy and safety.
• A significant implanter learning curve has been appreciated. No long-term
performance data of the leadless systems are yet available to determine
technological robustness.
• As leadless pacing matures, both in device technology and physician experience,
procedure-related complications are likely to decrease.
• Randomized controlled trials comparing leadless and conventional devices are
necessary to fully appreciate any differences between these technologies in
clinical practice

78. • Research is currently underway for harvesting kinetic energy from cardiac motion
to fuel pacemaker function (similarly to automatic watches).
• Intracardiac pacemakers may one day profit from such technology, thereby
dispensing with the need for device replacement.
• Intravascular defibrillators are another next step, and initial results of an
investigational device have recently been published.
• Currently, the devices are limited to patients with an indication for single-
chamber ventricular pacing.