MICRA and the Future of Leadless Pacing

Danesh Kella, MBBS, FHRSStaff Clinical Cardiac Electrophysiologist

Piedmont Heart Institute2019 Atlanta Cardio Conference

Disclosures

• None

Objectives

• Understand the concept of leadless pacing - benefits and limitations compared to traditional pacemakers

• Identify ideal candidates for this therapy

• AV synchrony with leadless pacemakers

• Review future devices in this arena• LV pacing – CRT• Subcutaneous ICD (Anti-tachycardia pacing)

Pre-Question

• Which of the following leadless pacemaker is currently commercially available?

• MICRA

• Nanostim

• Bullet (Nutri-powered)

• WiSE-CRT

Pre-Question

• Manatee is a/an,• Mammal

• Reptile

• Amphibian

• Fish

Pacing brief history

Pacemaker brief history

Image from: https://www.medmuseum.siemens-healthineers.com/en/stories-from-the-museum/herzschrittmacher/Medtronic Website

1958 Pocket complicationsTransvenous lead complications

2015/2016

Deshmukh, Friedman et al: JAFIB 10:1, 2017

Leadless pacemaker deployment

Source: Medtronic; Youtube

Free WallApical Pouch

SeptalCurve

RAO LAO

Lucency of AV Groove

RVA LVA

Courtesy: Dr. Deshmukh Mayo Clinic

Leadless pacemakersNANOSTIM – LEADLESS II (NEJM 2015) Micra Transcatheter Pacing Study (NEJM 2016)

Leadless Pacemaker ImplantationEfficacy Outcomes

Nanostim (LCP) Micra (TPS)

Implant success (%) 95.8 99.2

Pacing capture threshold and sensing efficacy endpoint (%)

90.0 (≤2.0 V at pulse width of 0.24 msec and an increase of ≤1.5 V from time of implantation

98.3 (≤2.0 V at 0.4 msec and sensing amplitude ≥5.0 mV or a value ≥ value at implantation

Threshold at implant 0.82 V @ 0.4 0.63 V @ 0.24

Threshold at 6 mo 0.4 V @ 0.4 0.54 V @ 0.24

Deshmukh, Friedman et al: JAFIB 10:1, 2017

Leadless Pacemaker ImplantationSafety Outcomes

Nanostim (%)n=526

Micra (%)n=729

Total events (Leadless) 6.5 4.0Cardiac perforation 1.6 1.6

Vascular complication 1.2 0.7

Arrhythmia during device implantation 0.6 0.0

Cardiopulmonary arrest during implantation procedure

0.2 0.0

Device dislodgement 1.1 0.0

Device migration during implantation owing to inadequate fixation

0.4 0.0

Pacing threshold elevation with retrieval and implantation of new device

0.8 0.3

Pulmonary embolism 0.2 0.1

Deshmukh, Friedman et al: JAFIB 10:1, 2017

MICRA historical control

Reynolds: N Eng J Med; November 9, 2015.

Ideal Candidates for Leadless pacemaker

• Single chamber – ventricular pacing only. Patients who do

not need AV synchrony

• Chronic Atrial Fibrillation with slow ventricular rates

• Atrial Fibrillation with planned AVN ablation

• Infrequent pacing

• High risk for infection/recurrent infections (ESRD?)

Atrial Fibrillation and AVN ablation

Micra Major Complications

Reynolds: N Eng J Med; November 9, 2015.

Global Trial(n=726)no. (%)

US continued access study + EU post-approval study +

Commercial experience(n=1,420)

no. (%)

Perforation 11 (1.5) 10 (0.7)

Dislodgement 0 (0.0) 0 (0.0)

Groin (AV fistula,pseudoaneurysm, etc.) 5 (0.7) 3 (0.2)

Infection 0 (0.0) 1 (0.1)

0.63 0.58 0.57 0.55 0.54 0.54

0.00

0.50

1.00

1.50

2.00

Implant(n=710)

Discharge(n=640)

1-month(n=624)

3-month(n=498)

6-month(n=300)

12-month(n=57)

Battery Longevity EstimateBased on use conditions of the 300 patients with 6-month data, median battery longevity estimate is 12.5 years*

Micra Pacing Thresholds at 12-monthPacing Capture Threshold

Volt

s (a

t 0.

24 m

s)

Reynolds: N Eng J Med; November 9, 2015.

MICRA and AV node ablation

• 21 patients MICRA followed by AV node ablation

• 2 deaths – non cardiac

• 1 pacing induced cardiomyopathy

• 67% f/u at 1 year and stable thresholds

Leadless pacemaker implantation and concurrent atrioventricular junction ablation in patients with atrial fibrillation. PACE 2018

Comparison of Device Performance at a Median Follow-up of 12 Months- Nanostim

Yarlagadda et al: Heart Rhythm 15:994, 2018

0.0

0.2

0.4

0.6

0.8

1.0

Implant 2 wks 3 mos 6 mos 12 mos

Volta

ge in

V

Follow-up

0

246

81012

14

Implant 2 wks 3 mos 6 mos 12 mos

Volta

ge in

mv

Follow-up

0

100200

300400500

600700

Implant 2 wks 3 mos 6 mos 12 mos

Impe

danc

e in

Ohm

s

Follow-up

Capture Threshold at Follow-up R Wave amplitude at Follow-up

Impedance at Follow-upLeadlessSingle chamber

P=0.009P=0.446

P=0.003

1 MAE (loss of pacing and sensing) LP group 2 (lead dislodgement) in the CTP group

Mismatch between 27F Sheath and 8F ablation catheter• Serial sheaths to allow for

hemostatic seal

Ho HRJ 2017

14F8F

Figure of eight stich for hemostasis

IPEC. Volume 17, Issue 5, 2017

AV synchrony?

Courtesy: Ashish Bhimani, MD

Atrial Contraction Detection Via Accelerometer

Heart Rhythm. 2018 Sep;15(9):1363-1371

A1 – Isovolumic contraction and mitral/tricuspid valve closings

A2 – Aortic/pulmonic valve closing

A3 – Early passive ventricular fillingA4 – Atrial contraction generating active fillingMASS/MASS2 studies collected open-loop data

N=75 patientsMARVEL tested the closed loop performance

The Micra - FUTURE

Time

Bradyarrhythmia with AF

Micra VR•Approved•>36,000 pts.

Micra AV• Atrial synchronous

ventricular pacing• Mechanical sensing

accelerometer

Micra AR• Atrial pacing• Modified fixation

Micra DDD• Dual chamber pacing &

sensing

AV Block Sinus Node Dysfunction

AV Block + Sinus Node Dysfunction

HRS 2019 Lucas Boersma, MD

Deshmukh, Friedman et al: JAFIB 10:1, 2017

Heart Rhythm 2017:14:1756-63

Subcutaneous ICD

Markus Bettin et al. JACEP 2017;3:1499-1506

EFORTLESS REGISTRY 3 year f/u 1000 pts – 50% VT not VF

Tjong et al. Herzschr Elektrophys 2018

*mCRMTM Systems, EMBLEMTM S-ICD mCRMTM functionality, and EMPOWERTM Modular Pacing Systems are in development and not approved for sale in any geography.

Implantable Devices

EMPOWER™ Modular Pacing SystemEMBLEM™ Family of S-ICDs

ProgrammersModel 3200 S-ICD Programmer

Next GenerationBSC 3300 LATITUDEProgramming System

EMPOWER™ Delivery and Retrieval

Dedicated delivery and retrieval catheters

Dedicated retrieval system with single &

tri-loop snares

Preloaded delivery catheter with extendable inner catheter

EMPOWER™ Details32.1 mm x 6 mm0.8 cc

Active fixation talonsTether / Snare port

HRS 2019 Petr Neuzil, MD,PhD,FESC

Tjong et al, AMC Heart Center, JACC Letters, http://dx.doi.org/10.1016/j.jacc.2016.02.039Tjong et al, ACC2016,Moderated Poster Session,

Heart Failure and Cardiac dyssynchrony

JACC Volume 69, Issue 2, 17 January 2017, Pages 189-210

Cardiac Resynchronization

Cardiac Resynchronization• MUSTIC SR• MIRACLE

• MUSTIC AF• PATH CHF• MIRACLE-ICD• CONTAK-ICD• MIRACLE-ICD II• COMPANION

• CARE-HF• REVERSE

• MADIT-CRT• RAFT• DANISH

• Reduced mortality (24% to 36% benefit)

• Reduced hospitalizations (30% decrease)

• Improved 6 minute walk test (50 to 70 meter increase)

• Improved 105 -point Minnesota scale (greater than or equal to 10 point reduction of HF symptoms)

• Improved NYHA class• Increase in peak oxygen

consumption

Heart Rhythm, Vol 9, No 8S, August Supplement 2012

CRT – Benefit and pitfalls

• ~5% failure rate

• ~Up to 10% complication rate (including dislodgement and phrenic stimulation)

• ~ 1/3rd of patients are non-responders

• Upgrades – higher risk and high non-responder rate

How about we go inside the LV?

Europace, Volume 11, Issue suppl_5, November 2009

WiSE-CRT, EBR Systems, Sunnyvale, California

JACC 2017Br J Cardiol 2018;25(suppl 3):S30–S34

DETECT Co-implant RV pacing WiSE-CRT; EBR system

Locates and transmits WiSE-CRT; EBR system

Receive and Pace WiSE-CRT; EBR system

Alternate to Transvenous LV lead WiSE-CRT; EBR system

JACC 2017Br J Cardiol 2018;25(suppl 3):S30–S34

SELECT-LV ↑HF clinical composite score in 85% (n=35)

SELECT-LV results n=35

• 97% successful implantation (34 patients)

• 62.5% pts ≥ 5%increase in LVEF (N=32)

• 52% pts ≥ 15% improvement in LVESV (N=25)

• Mean QRS decrease of 36 ms(165 to 129 ms or 22% reduction. (N=20)

• 66.7% pts ≥ 1 class improvement in functional capacity (N=33)

Complications n=35

Next Step….

• SOLVE CRT clinical study. (Stimulation of the Left Ventricular Endocardium for Cardiac Resynchronization Therapy) • Prospective randomized, double blinded pivotal trial

• Safety and Efficacy – FDA Approval

• Randomize 350 heart failure patients in the United States, Europe, and Australia who have failed to respond to, or are otherwise unable to receive, conventional CRT

• Piedmont participation

Possibilities with Leadless TechnologyApplications of leadless technology

Dual ChamberNanostim

§ 2 Discrete devices: Right Atrium and Right Ventricle

§ Beat to Beat Communication§ Chronically retrievable

Leadless ICD/PM

§ Leadless ICD system with device-to-device communication to Nanostim

§ Nanostim device paces, senses, and delivers ATP therapy

Leadless CRT

§ Evaluate leadless options for CRT therapy delivery

§ Applicable to low and high voltage

PediatricLeadless

§ Miniaturize present leadless pacemaker§ Fully retrievable§ Reduce complications from venous

adhesions

(RAO)

HRS 2019 Lucas Boersma, MD; Abbott/ St Jude Medical

Future – the Swiss

Zurbuchen et al. Heart Rhythm 2017Haeberlin et al. Ann of Biomed Engineer 2017

ISC C ¼ q"Z

/AM1:5G kð ÞTk kð ÞEQE kð Þdk ð1Þ

Second, the same skin samples were put on the stan-dard reference solar cell (4.5 9 4.5 mm). On top of theskin samples, an optically opaque frame (10 9 10 mm)was stacked to prevent lateral irradiation. The setupwas irradiated by a solar simulator (LS0811, LOT-Quantum Design, Germany) simulating 1 sun(100 mW cm22, AM1.5G). The measured short circuitcurrent ISC M was determined with a sourcemeter withfour terminal sensing (Keithley 2400, Keithley Instru-ments, USA) during irradiation. The differencebetween ISC C and ISC M will be discussed in the Dis-cussion section.

Based on the obtained transmittance results, acombination of two optical filters that emulate thetransmittance profile TkðkÞ of 2.3 mm thick skin(Fig. 3) was determined: A 550 nm longpass(FGL550S, Thorlabs, Germany) and an absorptiveneutral density filter (NE205B, OD: 0.5, Thorlabs,Germany) were stacked on top of each other. Thesefilters are placed directly on top of the solar cells of themeasurement device (Fig. 2). The wavelength-depen-dent short-circuit current ISC kð Þ [A m22] was com-puted to determine the performance of the opticalfilters compared to real skin. For full sun irradiation(AM1.5G, 100 mW cm22), ISC kð Þ is obtained by thefollowing formula, whereas the transmittance spectraof either the optical filters or the 2.3 mm thick skin isused for Tk kð Þ.

ISC kð Þ ¼ /AM1:5G kð ÞTk kð ÞEQE kð Þq ð2Þ

Solar Cells

The employed solar cells are monocrystalline siliconcells (KXOB22-12X1L, IXYS Corporation, USA) with

an efficiency of 22%. Three cells are connected in seriesand the resulting total active area is 3.6 cm2. The threesolar cells are aligned in parallel which results in a totalouter dimension of 21 9 22 mm.

Measurement Circuit

The maximum power point tracker (BQ25570,Texas Instruments, USA) modulates its input im-pedance to regulate US at 80% of the solar cells’ open-circuit voltage (UOC). At US = 80% UOC, the solarcells exhibit maximum output power. The MPPT ob-tains the latest value for UOC every 16 s, which takes256 ms and during this time the solar cells’ outputcurrent IS is zero. IS is measured by a high-side current-sense circuitry featuring a 1 X sense resistor connectedin series between the solar cells and the MPPT. Thevoltage drop over the sense resistor is amplified(ADA4051, Analog Devices, USA) and digitized by atwo-channel 16-Bit ADC (ADS1118, Texas Instru-ments, USA). The system makes use of the ADC’sinternal programmable gain amplifier (PGA) to in-crease the resolution for currents in the lA-range. Thecircuit can measure currents up to 15 mA with a dy-namic resolution between 80 nA and 0.6 lA, theoret-ically. This range covers full sunlight irradiation(AM1.5G, 100 mW cm22) considering attenuation ofthe filters as described previously. The solar cell’soutput voltage US is buffered by a unity gain amplifierto minimize measurement induced error and thendigitized with a resolution of 0.6 lV by the same ADC,range US = 0–2 V. The microcontroller coordinatesthe measurement: IS and US are measured with asampling frequency of 1 Hz. Finally, the values (date,time (h:min:s), IS, US, PGA) are stored on a memorycard. The electronic components are assembled on aprinted circuit board (PCB). The device features arechargeable battery that enables a continuous mea-surement for more than two weeks.

FIGURE 2. (a) Cross-sectional view of the measurement device. The solar cells (1) are located directly below the optical filters (2).Furthermore, the PCB (3) and battery (5) are enclosed in the housing (4). (b) Measurement device fixated on the upper arm.

BEREUTER et al.1174

The aim of this study was to demonstrate the feasibility ofbattery- and leadless cardiac pacing using a custom-made pace-maker supplied by an energy harvestingmechanism derived froma reliable Swiss wristwatch. The device’s ability to harvest energyfrom heart motions was tested during experiments with a robotthat mimics human heart motions. Finally, the pacemakerprototype was tested during an acute animal trial to show thefeasibility of pacing a heart with its own energy.

MethodsMyocardial contractions provide continuous energy in theform of mechanical motion. An energy harvesting mecha-nism was introduced to convert the heart’s mechanicalenergy into electrical energy. A dedicated electronics wasdeveloped to process and store the converted energy and totreat the heart with minute pacing stimuli (cf Figure 1). Asthe results will show, during this process, only a smallportion (~80 μW) of the heart’s total energy (~1.4 W) isconverted and can be used to power the device electronics.The following subsections describe the energy harvestingmechanism and the pacemaker electronics, as well as thesetup for testing the device on the bench and in vivo.

Energy harvesting mechanismThe energy harvesting mechanism is based on an automaticclockwork (ETA 204, ETA SA, Grenchen, Switzerland). Thesystem was adapted to harvest energy from heart motion:time and date indicating parts were removed and a newoscillation weight was developed.28 The total weight of 9.2 gwas achieved by skeletonizing the clockwork’s framework.This reduced the energy harvesting system to 4 maincomponents (cf Figure 2) with the following functions:

1. The oscillation weight translates externally applied accel-erations into an oscillating rotational motion. To increaseits sensitivity to heart motions the oscillation weight wasoptimized and redesigned using a mathematical modelreported previously.24,28 The new oscillation weightfeatures a mass of 7.7 g and is made of a platinum alloy(Pt 950/CO).

2. The mechanical rectifier translates the previouslydescribed oscillation into a unidirectional rotation. Thisallows harvesting energy from rotations in bothdirections.

3. The unidirectional rotation spans a spiral spring thattemporarily stores the energy in mechanical form.

4. At last, an electrical micro generator (MG205, Kinetronbv, Tilburg, The Netherlands) converts a rotationalmotion into an electrical signal. When the torque of thespiral spring equals the holding torque of the generator,the spring unwinds and drives the electrical microgenerator. The resulting impulse comprises !80 µJ at aload resistance of 1 kΩ.

Pacemaker electronicsThe electronics of pacemakers typically includes differentfeatures such as sensing, pacing, or automatic rate adapta-tion. Each individual feature consumes energy from thebattery and determines the lifetime of the device. Therefore,in the development of the modern pacemaker electronics, it isimportant to reduce the power consumption of the electronicsto a minimum. But their lifetime is also determined byexternal factors: a small tissue impedance, a high pacingthreshold voltage, a wide pacing pulse, or a high pacingfrequency will increase the overall power consumption of apacemaker electronics.

The here presented pacemaker electronics inherits 2 mainfunctions that serve the purpose of demonstrating thefeasibility of battery- and leadless pacing (cf Figure 3):

1. An energy management circuit receives an alternatingcurrent impulse from the micro generator that needs to berectified. Each such impulse is temporarily stored in abuffer capacity (47 µF capacitor TM8T476K010UBA,Vishay, Shelton, CT). The voltage level in the buffercapacity can reach levels between 0.8 and 6 V, whichmainly depends on the actual energy conversion rate ofthe energy harvesting mechanism for the present myo-cardial motion.

Figure 1 Working principle: The mechanical heart motion is converted into electrical impulses by an energy harvesting mechanism. The pacemakerelectronics processes the electrical impulses, temporarily stores the energy, and generates electrical stimuli to pace the myocardium with 2 pacemaker electrodes.

G

A B C D

Figure 2 Energy harvesting mechanism: The schematics of the energyharvesting mechanism illustrating (A) an oscillation weight, (B) a mechan-ical rectifier, (C) a spiral spring, and (D) an electromagnetic micro generator.

295Zurbuchen et al Heartbeat-Driven Lead- and Batteryless Pacemaker

Future

Summary

• Single ventricular pacemaker available commercially• Retrieval - ?• Niche indications – needs further development for more widespread use• AV synchrony soon• Multi-chamber – in future

• LV pacing – trial in future

• Sub Q ICD – leadless pacemaker; work in progress

Post-Question

• Which of the following leadless pacemaker is currently commercially available?

• MICRA

• Nanostim

• Bullet (Nutri)

• WiSE-CRT

Post-Question

• Which of the following leadless pacemaker is currently commercially available?

• MICRA

• Nanostim

• Bullet (Nutri)

• WiSE-CRT

I'll be back

Pre-Question

• Manatee is a/an,• Mammal

• Reptile

• Amphibian

• Fish

Acknowledgements

• Dr. Abhishek Deshmukh – Mayo Clinic

• Sponsors

• Alliance of Cardiovascular Professionals

• Michael Cavness

Thank you for your attentionQuestions

danesh.kella@piedmont.org

Leadless pacing – MICRA Trial• N=725 patients• 719 with successful implantation• Complications n=25 (4%)

• Cardiac Injury=11 (1.6%)

NEJM Feb 2016

Other leading device companies

St. Jude Medical (Abbott)Nanostim Pacemaker.

Boston Scientific

Abbott formerly St. JudeJACC EP 2017