Leadless pacing: Technical challenges and concerns Panos Vardas President Elect of the ESC, Prof. of Cardiology, Heraklion University Hospital
Modest consultancy fees/honoraria from Bayer Boehringer Ingelheim Bristol Myers Squibb Medtronic Menarini Servier
1957: First External Pacemaker
1958: First implanted pacemaker Elmquist Senning Larsson First implantable (Engineer) (Cardiologist) (Patient) pacemaker
Pacemakers (1957-2010) 5800 5858 Activitrax MicroMinix Thera EnPulse EnRhythm MRI First External Pacemaker Pediatric Asynchronous Pulse Generator Rate response Radically smaller size First Microprocessor-based, Mode switching Full automaticity MRI safe 1957 1970 1986 1990 1995 2004 2008 1960 1979 1989 1991 1998 2006 2010 First Implantable MDT Pacemaker Chardack-Greatbatch Byrel Dual chamber rate response Synergist Elite Rate response via activity & minute ventilation Kappa MVP, Full automaticity Adapta MVP, Full automaticity, MRI safe Advisa MRI
54 years after cardiac pacing is the only effective treatment for syncope due to symptomatic bradycardia
Milestones in Pacing 1960 s Durable permanent implants VVI and VAT modes Lithium-iodine battery cell 1970 s VDD and DDD pacing modes Rate-responsiveness 1980 s Microprocessors introduced Improved reliability of IPGs Steroid elution First ICD implant 1990 s-2000 s IS-1 connector standard Stored electrograms Biventricular pacing Transvenous ICD implants
Conventional sites of pacing leads Pacing from RA appendage Pacing from RV apex easy feasibility chronically stable mechanical positions stable stimulation thresholds
System proposed by Spickler in 1970
Questions that arise
Problems accompanying endocardial pacing
Leadless Pacemaker: Potential Advantages Less Invasive No surgery Fewer complications (no lead or subq device) Less radiation exposure for implanter More cosmetic for patient ( invisible ) Improved Efficiency No surgery; less infection risk Femoral venous access No system connections More readily MRI conditional (no antenna) More Cost-Effective Reduced length of hospital stay (same-day) Fewer acute and chronic complications (infection, erosion)
Leadless Pacemaker: Potential Disadvantages Multiple chamber pacing more complex Wireless communication from external / internal source External communication interference Memory capacity and down-loading limitations for multi chamber devices Implant risk Large diameter sheaths Embolization / retrieval Repositioning difficulty for high threshold Epicardial access issues (LV leads, pediatric apps) Removal / replacement Longevity limitations Abandon vs explant
Technical Challenges : Integration of Multiple Elements Physician training / comfort with new implant procedure Novel Delivery systems Unproven Fixation technology holding force, with repositioning/retrieval capability low, stable pacing thresholds Novel power sources and ultra-low power circuitry Increased electronic packaging density Communication systems: External (telemetry; wireless) Inter-device (intrabody) Biocompatible device packaging Lifetime hermeticity
Leadless pacing technologies EBR technology Energy transfer from an ultrasound transmitter to a receiver electrode to achieve cardiac stimulation Induction technology Magnetic field generated from a transmitter unit to the receiver coil in the heart and converted directly into voltage pulses for stimulation Wireless electrical stimulation An implantable RF rechargeable bion microstimulator transmits command signals to the coil that generates direct electrical stimulation
Induction technology The stimulation system consists basically of two components a transmitter unit (primary coil) implanted under the skin or the major pectoralmuscle just above the heart a small receiver unit (secondary coil) implanted in the right or left chamber of the heart The subcutaneous coil generates an alternating magnetic field and the receiver coil in the heart converts some fraction of the energy of this magnetic field directly into voltage pulses for stimulation Induction technology represents an energy transmission with an outstanding characteristic: very low energy loss Screw-equipped receiver unit without external connection Wieneke H et al, PACE 2009
Induction technology The complete control of the electrical pulse is in the transmitter unit The device can be programmed like a conventional pacemaker by telemetry pulse amplitude pulse duration frequency number of pulses Receiver unit mounted on an EP catheter positioned in the RV Receiver unit without external connection in the RV. The transmitter unit is placed on the outer thoracic wall directly beyond the receiver unit. Bottom: ECG tracing during wireless pacing
Leadless Pacemaker: Intracardiac Intracardiac VVIR pacemaker ~20F, ~24 mm length, 7-10 yr longevity Steerable Catheter +
Leadless Pacemaker: Intracardiac
Leadless Pacemaker: Communication This animation illustrates the potential connectivity between a totally self-contained intracardiac (and leadless) pacemaker and a smart phone. The information streamed to the phone would give the patient or the physician the ability to act upon as needed
Leadless pacing Comments Advantages Percutaneous catheter-based endovascular implant Precise placement in many locations True multisite ventricular stimulation Epicardial placement Possible endocardial left heart placement Reduced infection Reduced vascular occlusion Disadvantages Recharging energy source Compliance Travel Stability/embolization Complexity of follow up and programming
Novel technologies Biological pacemakers An approach to create a pacemaker in a cell that previously had little or no pacemaker function These approaches modify the electric signals generated by cardiac myocytes and/or specialized conducting cells to transform them into dominant pacemakers
Strategies to generate biological pacemakers Gene therapy overexpress a gene that will increase pacemaker rate in cardiac myocytes (by increasing inward current) knock out the function of a gene that would otherwise decrease pacemaker rate (and decrease outward current) Stem cell therapy Human embryonic stem cells-hescs Human mesenchymal stem cells-hmscs
Limitations for development of biological pacemaker Gene therapy-viral vectors Adenoviruses lead to only transient improvement in pacemaker function potential inflammatory responses Retroviruses risk of carcinogenicity and infectivity Stem cell therapy immunogenicity of cell potential for neoplasia proper engineering of pure cardiac lineages spatial non uniformity of implants need for an optimal cell mass and optimal cell-cell coupling for long term normal function