【別添】
Micra 経カテーテルペーシングシステム（Micra AV）に関する費用対効果評価 [第 1.0 版]
9. 補足資料
補足資料として、以下をまとめた。


同定した臨床研究(論文)の一覧表



システマティックレビューに組み込んだ臨床研究(論文)の詳細表



植込み後 30 日間に合併症が発生することによる追加的な死亡率

SF-36 で計測された HRQoL 値の変換

同定した臨床研究(論文)の一覧表
Name ofclinicalstudyInterventionComparator

Samplesize

Unpaired t-test,

pacemaker

Arai et al,2022

n withpostproceduralcomputedGrouped byplacementof leadless
pacemaker– septal or
non-septal

tomography

N=67;
N=28
Septalgroup
N=39
NonSeptal
group

without
persistent

N/A(retrospecti
N=50ve
analysis)

AF

Barletta etal, 2020

Micra TPSin subjects<79 years

test, Fisher exact
test,
Pearson’s
product-moment
correlation,

Arai H, Mizukami A, Hanyu Y, Kawakami T,
Shimizu Y, Hiroki J, Yoshioka K, Ohtani H, Ono
M, Yamashita S, Iwatsuka R, Ueshima D,
Matsumura A, Goya M, Sasano T. Leadless
pacemaker implantation sites confirmed bycomputed tomography and their parametersand complication rates. Pacing Clin
Electrophysiol 2022; 45: 196-203.

R software

Micra TPS
Arps et al,2021

Mann-Whitney U

EZR version 1.36,(CT)in subjects

Reference

Mean±SD,

Leadless
implantatio

Statistics

Micra TPSin subjects
>=80
years

Mean +/- SD, ttest, Wilcoxon
rank sum test,
McNemar test
Mean ±SD, t-

N = 109(46 above
80 years)

tests, MannWhitney U test,
Fisher’s exact test

Arps K, Piccini JP, Yapejian R, et al. Optimizing
mechanically sensed atrial tracking in patientswith atrioventricular-synchronous leadless
pacemakers: A single-center experience. Heart
Rhythm O2. 2021;2(5):455-462.
Barletta V, Zucchelli G, Parollo M, et al.
Leadless pacing in the elderly: never too old
for something new. Monaldi Arch Chest Dis.
2020;90(4). doi:10.4081/monaldi.2020.1255

Name ofclinicalstudyInterventionComparator

Samplesize

Micra TPS

Bhatia et al, extraction
2021
orabandoned
Micra

Reference

Mean ±SD,

implantatio
n withStatistics

Micra TPS
implantatio
n with no
extraction

All Micra
N=302
Abandoned N=12Extraction
N=11

Median andcategoricalvariables as %,Fisher’s exact
test, SAS version

Bhatia NK, Kiani S, Merchant FM, Delurgio DB,
Patel AM, Leon AR, Lloyd MS, Westerman SB,
Shah AD, El-Chami MF. Life cycle managementof Micra transcatheter pacing system: Data
from a high-volume center. J Cardiovasc
Electrophysiol 2021; 32: 484-490.

9.4

devicenumbers andleadless

percentages forpacemaker

categoricalimplantatio

variables, meansnBicong etal, 2022

withprevious
CIED

N/A(retrospecti
N=39ve
analysis)± SDs fornormally
distributed
continuous

infection

variables, andand lead

medians withextraction

25th–75th

Bicong, L., Allen, J. C., Arps, K., Al‐Khatib, S.
M., Bahnson, T. D., Daubert, J. P., FrazierMills, C., Hegland, D. D., Jackson, K. P.,
Jackson Il, L. R., Lewis, R. K., Pokorney, S. D.,
Sun, A. Y., Thomas, K. L. & Piccini, J. P.
Leadless pacemaker implantation after leadextraction for cardiac implanted electronic
device infection. Journal of cardiovascularelectrophysiology 2022, 33(3), 464-470.

percentile for3

Name ofclinicalstudyInterventionComparator

Samplesize

Statistics

Reference

nonnormally
distributed
continuous
variables
JMP 9.0 software,

Clementy et
al, 2021

Micra TPSin criticallyill patients

Conventionaltransvenous pacing in
critically illpatients

N=99
consecutiv
e patients
implanted
with Micra
TPS LPM

Mean ±SD, χ2 orFisher’s exact
test, Student’s ttest, MannWhitney-Wilcoxon
test, Kaplan-Meier

Clementy N, Coelho R, Veltmann C, Marijon E,
Tolosana J, Galand V, Ploux S, Eschalier R,
Simeon E, Blessberger H, Mueller-Leisse J,
Pujol-Lopez M, Martins R, Ritter P, Steinwender
C, Babuty D. Leadless pacemakers in criticallyill patients requiring prolonged cardiac pacing:
A multicenter international study. J Cardiovasc
Electrophysiol 2021; 32: 2522-2527.

methodT-tests, Chi-

Leadless
pacemaker
El-Chami etal, 2022

implantatio
n inMedicarebeneficiariesTransvenous VVI,
contemporaneouscontrolgroup

N=6,219de novo
Leadless
VVI;
N=10,212
de novo
Transveno
us VVI

squared tests,
Propensity scoreoverlap weights,
logistic regression
model, Fine-Graycompeting risk

El-Chami MF, Bockstedt L, Longacre C, Higuera
L, Stromberg K, Crossley G, Kowal RC, Piccini
JP. Leadless vs. transvenous single-chamber
ventricular pacing in the Micra CED study: 2year follow-up. Eur Heart J 2022; 43: 12071215.

models, Cox
4

Name ofclinicalstudyInterventionComparator

Samplesize

Statistics

Reference

proportional
hazards model,
SAS version 9.4
Student t tests,
Wilcoxon rank

El-Chami etal, 2022a

Micrasystempatients
withanticoagulat
ion therapy(AC)Interrupted
anticoagulation or no
anticoagulation

N=5,585
Group 1
(no AC),
N=5,795
Group 2(interrupted AC),
N=5,415
Group 3
(continuous AC)

sum test, Fisher
exact test, Firthpenalized
likelihood, Logistic
regression models
SAS Version 9.4
or R Version
4.0.2, PSweight

El-Chami MF, Garweg C, Iacopino S, Al-Samadi
F, Martinez-Sande JL, Tondo C, Johansen JB,
Prat XV, Piccini JP, Cha YM, Grubman E,
Bordachar P, Roberts PR, Soejima K,
Stromberg K, Fagan DH, Clementy N. Leadless
pacemaker implant, anticoagulation status, andoutcomes: Results from the Micra
Transcatheter Pacing System Post-Approval
Registry. Heart Rhythm 2022; 19: 228-234.

package in R
Version 1.1.4

El-Chami etal, 2021

Micra
implant
withconcomitant
AVNA.

Micra
implant
with noconcomitantatrioventricular node

N=192
Patients
undergoing AVNA,
N=2,616
Patients
notWilcoxon Rank
sum test, Fisher’s
exact test, logistic
regression model,
Cox proportional
hazards,
Standardized

El-Chami MF, Shinn T, Bansal S, MartinezSande JL, Clementy N, Augostini R, RavindranB, Sagi V, Ramanna H, Garweg C, Roberts PR,
Soejima K, Stromberg K, Fagan DH, Zuniga N,
Piccini JP. Leadless pacemaker implant withconcomitant atrioventricular node ablation:
Experience with the Micra transcatheter
5

Name ofclinicalstudy

Garweg etal, 2020

Garweg etal, 2021

InterventionComparator

Samplesize

ablation(AVNAsundergoing AVNAClass I or
II
indication
for Micra,
without
previous
valveinterventionN=170(54 with
previous
valvularintervention, 116
without)

Micra
implantation using
No use of
MARVEL 2
MARVEL 2
algorithm toalgorithm
provide AV
synchronous pacing

N=75
patients
implanted
with Micra
LPM andreceived
MARVEL 2
algorithm
AV Block
N=42, 1:1

Class I or II
indication
for Micra,
withprevious
valveintervention

Statistics

Referencemean differences,
SAS v9.4 or R
v4.0.2
Mean ±SD, MannWhitney U test,
Mann-Whitney U
test, KolmogorovSmirnov test, Chisquared test,
Wilcoxon signedrank test,
Pearson’s
correlation
coefficient,
ANOVA with
Bonferroni
correction

pacemaker. J Cardiovasc Electrophysiol 2021;
32: 832-841.

Mean ± SD or
Median andinterquartile
range, Paired ttests, Wilcoxon
signed rank test,
SAS v9.4

Garweg C, Vandenberk B, Foulon S, et al.
Leadless pacemaker for patients following
cardiac valve intervention. Arch CardiovascDis. 2020;113(12):772-779.

Garweg C, Khelae SK, Chan JYS, Chinitz L,
Ritter P, Johansen JB, Sagi V, Epstein LM,
Piccini JP, Pascual M, Mont L, Willems R, Splett
V, Stromberg K, Sheldon T, Kristiansen N,
Steinwender C. Behavior of AV synchrony
pacing mode in a leadless pacemaker during
variable AV conduction and arrhythmias. J
Cardiovasc Electrophysiol 2021; 32: 19471957.
6

Name ofclinicalstudyInterventionComparator

Samplesize

Statistics

Reference

Haddadin, F., Majmundar, M., Jabri, A., Pecha,
L., Scott, C., Daher, M., Kumar, A., Kalra, A.,
Fram, R., Haddadin, F., Almahameed, S.,
DeSimone C. V., Cha, Y.-M., Mulpuru, S. K.,
Ellenbogen, K. A., Saeed, M., Chelu, M. G. &Deshmukh, A. J. Clinical outcomes andpredictors of complications in patients
undergoing leadless pacemaker implantation.
Heart Rhythm 2022. Article in Press.

AVC
N=18,
Other
rhythms
N=13

Haddadin etal, 2022

Hauser etal, 2021

Hauser etal, 2022

leadless
pacemaker
implantationMACE
associatedwith Micra
LICP(leadlessintracardiac
pacemaker)
implantationDatabasesearch forconsequenc
es of Micra

N/A
Retrospective
databasestudy

N = 7,821

Means, median,SD, percentages,
multiplehierarchicallogistic
regression,

CapSureFix
lead usage
during first
30 daysafter
implant

Micra LICP
N=363,
CapSureFi
x N=960

Pearson χ2 orFisher’s exact
test, R version
3.6.0 in R Studio
Version 1.1.463

Hauser RG, Gornick CC, Abdelhadi RH, Tang
CY, Casey SA, Sengupta JD. Major adverse
clinical events associated with implantation of aleadless intracardiac pacemaker. Heart Rhythm
2021; 18: 1132-1139.

NA

N=563,
Perforatio
ns thatmanifeste

Pearson's chi‐square or Fisher's
exact tests, R
version 4.0.1

Hauser RG, Gornick CC, Abdelhadi RH, Tang
CY, Kapphahn-Bergs M, Casey SA, Okeson BK,
Steele EA, Sengupta JD. Leadless pacemakerperforations: Clinical consequences and related7

Name ofclinicalstudyInterventionComparator

LPM
perforations
and related
device andoperatoruse
problems.
Micra TPS
implanted
subjects,
increasedpacingthreshold

Samplesize
d clinicallyduringMicra
implantati
on within
30 days of
implant
N=60 (9in stable
thresholdgroup, 51
inincreasedpacingthreshold)

Statistics

Reference
device and user problems. J Cardiovasc
Electrophysiol 2022; 33: 154-159.

Shapiro-Wilk test,
Mann-Whitney U
test, Student’s ttest, Welch t-test,
Fisher’s exact
probability test,
ROC curve

Higuchi M, Shinoda Y, Hasegawa T, et al.
Predictors of increase in pacing threshold after
transcatheter pacing system implantation due
to micro-dislodgement. Pacing Clin
Electrophysiol. 2020;43(11):1351-1357.

Higuchi etal, 2020

Micra TPS
implanted
subjects,
stablepacingthresholdHoumsse etal, 2020

Micra TPS
implanted
subjectswith an IVC
filterNA

N=23

Mean (SD),Median (IQR)

Houmsse M, Karki R, Gabriels J, et al.
Implantation of leadless pacemakers via
inferior vena cava filters is feasible and safe:
Insights from a multicenter experience. J
Cardiovasc Electrophysiol. 2020;31(12):32773285.

Micra TPS
Implantation accessfrom left
femoralarteryMicra TPS
Implantation accessfrom rightfemoralarteryN=143;
N=18 left
femoralaccess;
N=125
Right

Jamovi project
version 1.2,
Shapiro-Wilk test,
Mean ± SD,
Student t-test,
Mann-Whitney U-

Jelisejevas J, Breitenstein A, Hofer D, Winnik S,
Steffel J, Saguner AM. Left femoral venous
access for leadless pacemaker implantation:
patient characteristics and outcomes. Europace
2021; 23: 1456-1461.

Jelisejevas
et al, 2021

8

Name ofclinicalstudyInterventionComparator

Samplesize
femoralaccessMicra TPSin subjects
withchronic/per
manent AF
associatedwith CHB,
SSS

Statistics

Reference

test Pearson χ2 orFisher’s exact test

N=443
(198 forTransvenou
Micra, 245sforpacemaker
transveno
us)

Mean +/- SD

Kumar V, Agarwal R, Singh Yadav M, Dhir S,
Kumar V. Implantation of the Micratranscatheter pacing system: A single centerNorth India experience. Indian Pacing
Electrophysiol J. 2021;21(1):19-24.

MartinezSande et al,2021

Micra TPS
implantation from left
femoralarteryN=443
Transvenou (198 forMicra, 245spacemaker fortransvenosus)

Mean +/- SD,
Propensity scorematching, Cox
regression
analysis, multiple
hypothesis testingwith BenjaminiHochberg
procedure,
Bayesian cohort
analysis (posterior
calculated using
MetropolisHastings
algorithm)

Martinez-Sande JL, Garcia-Seara J, GonzalezMelchor L, et al. Conventional single-chamber
pacemakers versus transcatheter pacing
systems in a “real world” cohort of patients: A
comparative prospective single-center study.
Indian Pacing and Electrophysiology Journal.
2021;21(2):89-94.
doi:10.1016/j.ipej.2020.12.004

Nicosia etal, 2022

leadlesssingle-N/Ameans and SD;

Nicosia, A., Iacopino, S., Nigro, G., Zucchelli,G., Tomasi, L., D’Agostino, C., Ziacchi, M.,

Kumar etal, 2021

N = 577

9

Name ofclinicalstudyInterventionComparator

Samplesizechamberpacemaker
Micra TPS
implants

Ngo et al,
2021

Systematic
review ofreportedoutcomesfrom Micra
implantation.

Systematic
review ofreportedoutcomesfrom
Nanostim
implantation.

36Studies,
N=4335

Oliviera etal, 2021

Micraleadless
pacemaker

N/A(Systematic Review)

58 papers
covering
4,739
subjects

Palmisanoet al, 2021

Micraleadless
pacemaker
withfemoralvein access

N = 243
Transvenou (leadless91,s
pacemaker transveno
us 152)

Statistics

Referenceminimum,
maximum, andmedian with
IQR, counts andpercentages,
Kruskal–Wallis
test, chi-square
test, Fisher`sexact test
Freedman-Tukey
double arcsine
transformation,
Stata version
16.0, Stata userwritten command
Metaprop, I2
statistic

Piacenti, M., De Filippo, P., Sgarito, G.,
Campisi, G., Nicolis, D., Foti, R. & Palmisano,
P. Performance of transcatheter pacing systemuse in relation to patients’ age. Journal ofInterventional Cardiac Electrophysiology, 2022,
1-8.

Mean +/- SD
Mean +/- SD,
Student’s t-test,
Mann-Whitney U
test, analysis ofvariance, Fisher’s
exact test, binary

Ngo L, Nour D, Denman RA, Walters TE,
Haqqani HM, Woodman RJ, Ranasinghe I.
Safety and Efficacy of Leadless Pacemakers: A
Systematic Review and Meta-Analysis. J Am
Heart Assoc 2021; 10: e019212.
Oliveira SF, Carvalho MM, Adão L, Nunes JP.
Clinical outcomes of leadless pacemaker: asystematic review. Minerva Cardiol Angiol.
2021;69(3):346-357.
Palmisano P, Guido A, Panico V, et al. Leadless
pacemaker versus transvenous single-chamber
pacemaker therapy: peri-procedural aspects,
utilization of medical resources and patient
acceptance. Expert Rev Med Devices.
2021;18(5):483-491
10

Name ofclinicalstudyInterventionPiccini et al,
2021

Micra
leadless
pacemaker
in Medicare
beneficiaries

Piccini et al,
2022

Micra
leadless
pacemaker
in previous
trialsRusso et al,
2022

Micra
leadless
pacemaker
in subjects
with AF

Comparator

Samplesize

Statistics

logistic regression
for propensity
scoresMean +/- SD, ttests, Chi-squared
N=5746
test, univariate
Transvenou (leadless), logistic
N=9662sregression, Finepacemaker (transveno Gray competingus)risk modules, Cox
proportional
hazards models
Mean +/- SD,
N=32
binomial(effusion), confidence
N/A
N=2785(pooledintervals,(noanalysis)
multivariable risk
effusion)
production model,
Lasso regression
Mean +/- SD,
median +/- IQR,
Micra
KolmogorovleadlessSmirnov test,
pacemaker N=140
Shapiro-Wilk test,in subjects
chi-squared tests
without AF
with Yatescorrection where

Reference

Piccini JP, El-Chami M, Wherry K, et al.
Contemporaneous Comparison of Outcomes
Among Patients Implanted With a Leadless vsTransvenous Single-Chamber Ventricular
Pacemaker. JAMA Cardiol. 2021;6(10):11871195.
Piccini JP, Cunnane R, Steffel J, et al.
Development and validation of a risk score forpredicting pericardial effusion in patients
undergoing leadless pacemaker implantation:
experience with the Micra transcatheter
pacemaker. Europace. Published online January
13, 2022. doi:10.1093/europace/euab315
Russo V, D’Andrea A, De Vivo S, et al. SingleChamber Leadless Cardiac Pacemaker inPatients Without Atrial Fibrillation: Findings
From Campania Leadless Registry. Front
Cardiovasc Med. 2022;8:781335.

11

Name ofclinicalstudyInterventionComparator

Samplesize

Statistics

Reference

appropriate,
Student’s t-test,
Mann-Whitney U
test, Wilcoxon
signed-rank test,
Kaplan-Meieranalysis

Sanchez etal, 2021

Sasaki etal, 2022

Micraleadless
pacemaker
in subjects
with normal
LVEF(>=50%)

N=198
Transvenou (131 fortransvenospacemaker us, 67 forleadless)

Mean +/- SD,
Student’s t-test,
Chi-squared test,
multivariate
analysisMicraleadless
pacemaker
for subjects
withbradyarrhyt
hmia (ClassI and II)

N=193
(leadless
110,
transveno
us 83),
Transvenou
N=116
s
with
pacemaker
propensity
score
matching(leadless
58,

Mean +/- SD,
median, IQR,
Student’s t-test,
Wilcoxon ranksum test, Fisher’s
exact test,
Kaplan-Meiermethod and logrank test, logistic
regression model

Sanchez R, Nadkarni A, Buck B, et al.
Incidence of pacing-induced cardiomyopathy inpacemaker-dependent patients is lower withleadless pacemakers compared to transvenous
pacemakers. J Cardiovasc Electrophysiol.
2021;32(2):477-483.

Sasaki K, Togashi D, Nakajima I, et al. Clinical
Outcomes of Non-Atrial Fibrillation
Bradyarrhythmias Treated With a Ventricular
Demand Leadless Pacemaker Compared Withan Atrioventricular Synchronous Transvenous
Pacemaker ― A Propensity Score-Matched
Analysis ―. Circulation Journal. Published
online 2022. doi:10.1253/circj.cj-21-088

12

Name ofclinicalstudyInterventionComparator

Samplesize

Statistics

ReferenceFriedman’s test,
Wilcoxon signedrank

毛利 崇人, 佐藤 俊明, 冨樫 郁子, 上田 明子, 三輪
陽介, 星田 京子, 野々口 紀子, 田代 身佳, 百瀬 裕
一, 勝目 有美, 副島 京子, リードレスペースメーカ植込み後の急性期および長期成績, 杏林医学会雑誌,
2020, 51 巻, 4 号, p. 257-263, 公開日
2020/12/25

Pearson X2 test, ttest, 1-way
analysis ofvariance,
numbers andpercentages

Vincent, L., Grant, J., Peñalver, J., Ebner, B.,
Maning, J., Olorunfemi, O., Goldberger, J. J. &Mitrani, R. D. Early trends in leadless
pacemaker implantation: Evaluating nationwide
in-hospital outcomes. Heart rhythm, 2022.
Article in press

Mean +/- SD,
median,percentages,
unpaired andpaired t-tests,
Mann-Whitney U

Zucchelli G, Tolve S, Barletta V, et al.
Comparison between leadless and transvenous
single-chamber pacemaker therapy in areferral centre for lead extraction. Journal ofInterventional Cardiac Electrophysiology.

transveno
us 58)

Takato etal, 2020

Class I andIIa
recommend
ations forMicraleadless
implant
withbradyarrhyt
hmia

Vincent etal, 2022

Micraleadless
pacemaker

Zucchelli etal, 2021

Micraleadless
pacemaker(Class I
indication)

NA

N=51

Micra:
n=
16,825

Transvenou
Transvenospacemaker us:n=565,845
N = 200(100 inTransvenou
leadless,s
100 inpacemaker
transvenous)

13Name ofclinicalstudyInterventionComparator

Samplesize

Statistics
test, Fisher’s
exact test

Reference
2021;61(2):395-404. doi:10.1007/s10840020-00832-9

14

システマティックレビューに組み込んだ臨床研究(論文)の詳細表
Arai et al, 2022
Study site
Participant recruitment
periodKameda Medical Center, Japan
September 2017 to November 2020

Details of comparator

All patients who underwent CT after recommended
ventricular demand pacing (VVI) pacemakers due to atrial
fibrillation, age, comorbidities, or low pacemakerdependency.
Patient did not have CT scan after leadless pacemaker
implantation
Micra transcatheter pacing system guided by vascularultrasound through right femoral vein. Using contrast
injection, the position of the delivery catheter was
confirmed.
Non-septal placement of the pacemaker

Study design

Retrospective single-center study

Blinding method
Primary endpoint
Key secondary
endpoints

NA
Cardiac injury related to implantation site

Target population

Key exclusion criteria
Details of intervention
methodStatistical analysis
methods

Sample size
Follow-up period
Main backgroundfactors of subjects
Results of primary
endpoints

Pacing failure
Mean±SD
Unpaired t-test
Mann-Whitney U test
Fisher exact test
Pearson’s product-moment correlation
EZR version 1.36
R software
N=67; N=28 Septal implantation group N=39 Non-septal
implantation group
Immediately, 1 week and 2 months after procedure
All must have had CT scan after leadless pacemaker
implantation
Cardiac injury 4 out of 39 all in non-septal group

Results of key
secondary endpoints

Pacing failure 4 out of 28 all in septal group

Limitations of the study

Retrospective single-center study
Limited patient number
Only patients who underwent CT for medical reasons after
leadless pacemaker implantation were enrolled
Procedural characteristics decided by operators
Differences in timing of CT scan

Arai et al, 2022
Conclusions

Arps, 2021
Study site
Participant recruitment
periodEven though there are inferior results from Septal
implantation, this is still recommended because of the
reduced risk of postprocedural complications.

Duke University, USA
Feb 2020 – Jan 2021

Details of comparator

Patients who received an AV synchronous leadless
pacemaker (Micra) without persistent AF
Persistent AF at implantation
Using the standard technique as detailed by El Chami etal. 2016. Devices were interrogated prior to discharge,
with manual atrial mechanical (MAM) test used to optimize
atrial sensing features and maximize atrial tracking insinus rhythm.
None

Study design

Retrospective single-center cohort study

Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods

NA
Pacing burden

Sample size

N = 50

Follow-up period
Main backgroundfactors of subjects

1-2 follow-ups

Target population
Key exclusion criteria
Details of intervention
methodResults of primary
endpoints

Results of key
secondary endpoints

Tracking index, total AVS, >70% AVS
Mean +/- SD, t-test, Wilcoxon rank sum test, McNemar
test

Mean age was 69 +/- 16.8 years, 48% female
The median pacing burden was 10% [0%, 92%], and 33
patients (67%) had <50% total RV pacing (median 1.2%
[0%, 9%]).
The mean tracking index (AM-VP divided by total VP) was
37% ± 33% in those with <50% pacing and 47% ± 35%
in patients with ≥50% pacing. In 13 patients with historyof paroxysmal AF, the mean tracking index was 26% ±
27%. The median total AV synchrony was 83% [49%,98%] overall and 59% [0%, 74%] in those requiring≥50% pacing. In patients with complete heart block, themean tracking index was 41% ± 31%, and median total
AV synchrony was 69% [16%, 96%]. A majority ofpatients (35/50, 70%) had device programming changes
at their first postimplant follow-up visit.
16

Arps, 2021

Limitations of the study

Conclusions

Barletta et al, 2020
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodDetails of comparator
Study design
Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods
Sample size
Follow-up period
Main backgroundfactors of subjects
Results of primary
endpoints

Single center study with limited sample size.
Quantification of AV synchrony was extrapolated fromdevice interrogated data and could not be validated with
continuous ambulatory telemetry.
No structured mechanism to report symptom burden or
quality of life.
Patient selection for leadless TPS was based on clinician
judgement.
Mode changes and adjustment in pacing parameters were
performed at each clinician’s discretion using MAM testingfor guidance.
In patients with AV-synchronous leadless pacemakers,
programming changes are frequent and are associatedwith increased atrial tracking and increased AV synchrony
in patients with complete heart block.

Azienda Ospedaliero-Universitaria Pisania, Italy
May 2014 – July 2019
All subjects eligible for Micra leadless pacemaker, <79years<18 years, hemodynamic instability, mechanical tricuspid
valve prosthesis, IVC filter, morbid obesity, femoral
venous occlusion
Standard technique, femoral vein access, non-apical sitewhere possible
All subjects eligible for leadless pacemaker, >=80 years
Prospective observational cohort study
NoneElectrical parameters during follow-up
Clinical follow-up
Mean ±SD, t-tests, Mann-Whitney U test, Fisher’s exact
test
N=109 (46 elderly)
18.05 months
77.7 years overall (85.85 for elderly cohort, 71.57 foryoung cohort), 76.15% male
No differences were observed between groups at 12
month F-U in pacing threshold, impedance or R wave
amplitude.

17

Barletta et al, 2020
Results of key
secondary endpoints
Limitations of the study
Conclusions

Bhatia et al, 2021
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodDetails of comparator
Study design
Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods
Sample size
Follow-up period
Main backgroundfactors of subjects

No acute complications were observed, including venous
access issues, fever or acute signs of infection. No device
related events were registered.
Small, single-center study
The implant is an effective and safe procedure in elderly
patients, with similar electrical performance and outcome
compared with younger patients at mid-term follow-up.

Emory Healthcare, Atlanta GA, USA
April 1, 2014 – October 31, 2019
Patients implanted with Micra TPS during long-term
follow-up
No Micra TPS implanted
Retrospectively identified patients who underwent Micra
TPS implantation using medical history, indications,
imaging, procedural characteristics, follow‐up electricalmeasurements, and outcomes.
All successful Micra implantations via femoral access.
Observational retrospective cohort study
None
Rate and reasons for Micra extraction/abandonment
Low revision rate, safety and efficiency
Mean ±SD, Median and categorical variables as %,Fisher’s exact test, SAS version 9.4
All Micra N=302, Abandoned N=12, Extraction N=111105.5 ± 529.3 days
72.7 ± 15.4 median age, Male 54.6%, HTN 83.4%,
Diabetes 35.8%, Coronary Heart disease 40.1%
Median time for extraction was 78 days
Reasons:•

Results of primary
endpoints

upgrade for pacing induced cardiomyopathy (n =3),•increased thresholds or failure to capture on
previous Micra TPS (n = 3),•

bridging from extraction to implantation of anotherdevice (n = 3),18

Bhatia et al, 2021•

tricuspid valve endocarditis secondary to
intravenous drug use (n = 1),•

aortic valve endocarditis (n = 1).

Median time of abandonment was 398.5 days
Reasons:• upgrade for pacing‐induced cardiomyopathy (n = 6)•

an increase in thresholds/failure to capture (n = 3),•

battery depletion due to elevated thresholds (n =2)•Results of key
secondary endpoints

Limitations of the study

Conclusions

Bicong et al, 2022
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodpacemaker syndrome (n=1)

Devices implanted after abandonment included CRT (n =5, 41.7%), Micra TPS (n = 2, 16.7%), transvenous pacing
system (n = 4, 33.3%),
Mean fluoroscopy time was 5.14 ± 3.6 min.
Revisions required for Micra TPS 6% (primarily pacing
cardiomyopathy)
Determined that RV can accommodate several Micra TPS
Retrospective study
Study only at one center with inherent patient selection
and procedural outcomes
Small number of patients
Not able to rule out device problems in patient not in
follow-up
Adverse events may occur after follow-up period
In this large single‐center study, 6% of patients implantedwith a Micrarequired a system modification during long‐term follow‐up,
most commonly due to the requirement for CRT pacing.
These patients were managed successfully with extraction
or abandonment.

Duke University Medical Center
November 11, 2014 to November 18, 2019.
Patients (1) who had a previous CIED infection (2)followed by lead extraction, and (3) underwent device
reimplantation with a Micra VR leadless pacemaker
Patients without follow-up information after hospitaldischarge
Modified Seldinger technique was used to access the
femoral vein with direct ultrasound guidance. The delivery
19Bicong et al, 2022

Details of comparator
Study design
Blinding method

Primary endpoint

tool with the Micra Transcatheter Pacing System(Medtronic) was used.
N/A
Single arm retrospective review of electronic medical
records
N/A
Not specified. Endpoints include: Patient demographics,
indication for Micra implantation, past medical history,
previous CIED infection, implant characteristics, device
electrical performance, adverse events in follow‐up,
including implant procedural complications, pacemakersyndrome, new‐onset heart failure, recurrent infection,and death.

Key secondary
endpoints

See above

Statistical analysis
methods

Patient characteristics are summarized as numbers andpercentages for categorical variables, means ± SDs fornormally distributed continuous variables, and medianswith 25th–75th percentile for non-normally
distributed continuous variables. Adverse outcomes wereassessed through post-implantation follow-up, andsummarized with numbers and percentages.

Sample size

N=39

Follow-up period

Main backgroundfactors of subjects
Results of primary
endpoints

Mean (± SD) = 24.8 (± 14.7)
Median = 24.6
Minimum—Maximum = 0.5 - 47.5
25th percentile—75th percentile = 12.2 ‐ 38.3
Patients with CIED infection with subsequent leadextraction and who underwent leadless pacemaker
implantation
three major complications in three patients related todevice implantation.

Results of key
secondary endpoints

Not specified

Limitations of the study

retrospective cohort study in a single quaternary carecenter, small cohort

Conclusions

Leadless pacemaker implantation is associated with a low
reinfection rate in patients with previous CIED infection
and lead extraction. Leadless pacing may be a safer
alternative to transvenous devices in patients with
bradycardia
indications who undergo CIED removal for infection.
20

Clementy et al, 2021
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodDetails of comparator

9 major tertiary European LPM implanting centers
September 2015 – August 2019
Consecutive patients implanted with a Micra LPM
during the
hospitalization in an intensive care unit
Previous implantation of a pacemaker
Implantation of Micra TPS in critically ill patients.
Conventional transvenous pacing

Study design

Retrospective observational study

Blinding method

None
Safety and efficacy of LPM implantation in the high‐risk
population of patients

Primary endpoint
Key secondary
endpoints
Statistical analysis
methods
Sample size
Follow-up period
Main backgroundfactors of subjects
Results of primary
endpoints
Results of key
secondary endpoints

Limitations of the study

Conclusions

Follow-up
JMP 9.0 software, Mean ±SD, χ2 or Fisher’s exact test,
Student’s t-test, Mann-Whitney-Wilcoxon test, KaplanMeier method
N=99 consecutive patients implanted with Micra TPS
LPMMedian follow-up 19 months
Mean age 75 years, Male 52%, AFib 53%, Charlson
Comorbidity index 7±3, Diabetes 28%
Successful implantation 98%, Implantation failure 2%,
Death 1%, Tamponade 3%, Pericardial effusion w/odrainage 1%, elevated threshold 1%
In‐hospital and 30‐day mortality rates were 6% and
7%, 91 patients discharged after median of 5 days
Study may not reflect the general population requiring
permanent pacing in ICU
Overall procedure costs with LPM not removed
Decrease in ICU stay may decrease some costs
LPMs implanted were one chamber devices
LPM appears as an acceptable alternative toconventional temporarytransvenous pacing in selected critically ill patientsrequiring prolonged cardiac pacing, especiallyregarding the risk of infection.

21

El-Chami et al, 2022
Study site
Participant recruitment
periodUnited States
March 9, 2017 to December 31, 2018

Details of comparator

Leadless VVI pacemakers in the US Medicare fee-forservice population.
Medicare beneficiaries
The study used administrative claims data to enroll
patients, ascertain patient characteristics, identify
comorbidities, and measure outcomes.
Transvenous VVI, contemporaneous control group

Study design

Continuously enrolling, observational, cohort study

Blinding method

NA
Device reinterventions, chronic complications, andmortality at 2 years between leadless VVI andtransvenous VVI patients

Target population
Key exclusion criteria
Details of intervention
methodPrimary endpoint
Key secondary
endpoints
Statistical analysis
methods
Sample size
Follow-up period

Main backgroundfactors of subjects

Results of primary
endpoints

Results of key
secondary endpoints

NA
T-tests, Chi-squared tests, Propensity score overlap
weights, logistic regression model, Fine-Gray competingrisk models, Cox proportional hazards model, SAS version
9.4
N=6,219 de novo Leadless VVI; N=10,212 de novo
Transvenous VVI
2 years
Medicare claims and enrollment data was used to identify
beneficiaries implanted with Micra leadless pacemaker.
Identified patients implanted with a transvenous VVI
pacemaker using the International Classification of
Diseases, limited transvenous VVI patients to hospitals
that implanted leadless VVI pacemakers during the study
period.
Reintervention rates were significantly lower in leadless
VVI patients.
System revisions, removals, and upgrades to CRT weresignificantly lower inthe leadless VVI patients.
Overall chronic complication rate was significantly lower inthe leadless VVI patients.
30-day all-cause mortality rate was not significantly
different between leadless VVI and transvenous VVI
patients
NA

22

El-Chami et al, 2022

Limitations of the study

Conclusions

El-Chami et al, 2022a
Study site
Participant recruitment
periodTarget population
Key exclusion criteria

Medicare administrative claims data are a secondary
database used primarily for billing purposes.
Not able to obtain device interrogation data to accessprogrammed lower rates, pacing thresholds and battery
longevity.
Possibility of residual confounding or selection bias cannot
be completely eliminated.
Analysis does not include patients implanted beyond
December 2018 and outcomes beyond December 2019In a real-world study of US Medicare patients, the Micra
leadless VVI pacemaker was associated with a 38% lower
adjusted rate of reinterventions and a 31% lower adjusted
rate of chronic complications compared with transvenous
VVI pacing. There was no difference in adjusted all-cause
mortality at 2 years.

United States
NA
Micra system patients with anticoagulation therapy (AC)No Micra system implanted
Patients undergoing Micra VR implant attempt who were

Details of intervention
methodenrolled in the Micra Post-Approval Registry (PAR).
Implanting Micra requires large-bore venous access andnavigation of the delivery system in the right ventricle toimplant the device.

Details of comparator

Interrupted anticoagulation or no anticoagulation

Study design

Prospective, nonrandomized, registry study

Blinding method
Primary endpoint
Key secondary
endpoints

NA
Safety and performance

Statistical analysis
methods
Sample size
Follow-up period

NA
Student t tests, Wilcoxon rank sum test, Fisher exact test,
Firth penalized likelihood, Logistic regression models
SAS Version 9.4 or R Version 4.0.2, PSweight package in
RVersion 1.1.4
N=5,585 Group 1 (no AC), N=5,795 Group 2 (interruptedAC), N=5,415 Group 3 (continuous AC)
NA

23

El-Chami et al, 2022a
Main backgroundfactors of subjects

Patients undergoing Micra VR implant attempt who wereenrolled in the Micra Post-Approval Registry (PAR) were
included in this analysis.
Rate of acute complications by AC strategy was 3.1%,
2.6%, and 1.5% for group 1, 2, and 3, respectively
Most major complication in all groups was pacing issues

Results of primary
endpoints

Combined rate of vascular and pericardial effusion events
regardless of severity was 6.5%, 4.8%, and 3.6% forgroups 1, 2, and 3, respectively,
Rate of pericardial effusion regardless of severity was
1.2%, 0.8%, and 0.5% in groups 1,2 3 respectively.

Results of key
secondary endpoints

Limitations of the study

Conclusions

El_Chami et al, 2021
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodDetails of comparator

NA
Study not randomized
Data on type of AC (DOAC vs warfarin) was not collected
Patients on AC are older

The overall incidence of vascular and pericardial effusion
complications after Micra implant is low. Implantation of
Micra using a strategy of uninterrupted AC seems to besafe, with no increased risk of vascular or pericardial
effusion events compared to a strategy that relies oninterruption of AC.

United States
NA
Patients enrolled in the Micra Transcatheter Pacing (IDE)
Study, Continued Access (CA) study, and Post‐Approval
Registry (PAR)Not included in the above studies
Enrolled patients with Class I or II pacing indications withno co‐morbidity
restrictions.
Patients not undergoing concomitant atrioventricular node
ablation (AVNA)

Study design

Observational cohort study

Blinding method

NA24

El_Chami et al, 2021
Primary endpoint

Safety and performance of Micra when AVNA is performed
at time of device implantation

Key secondary
endpoints

NA

Statistical analysis
methods
Sample size
Follow-up period
Main backgroundfactors of subjects

Wilcoxon Rank sum test, Fisher’s exact test, logistic
regression model, Cox proportional hazards, Standardized
mean differences, SAS v9.4 or R
v4.0.2
N=192 Patients undergoing AVNA, N=2,616 Patients notundergoing AVNA
20.4 ± 15.6 months
Mean age 77.4 ± 8.9 years, 72% female

Results of primary
endpoints

Pacing capture threshold (PCT) at implant was 0.58 ± 0.35
V at a pulse duration of 0.24 ms among patients with
AVNA compared to
0.65 ± 0.49 in patients without AVNA (p = .12).

Results of key
secondary endpoints

NA

Limitations of the study

Conclusions

Garweg et al, 2020
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodDetails of comparator
Study design
Blinding method

Residual confounding due to unmeasured factors cannot
be ruled out in an observational study
Sample size small leading to wider confidence intervals
The study does not have a comparison group of patients
undergoing AVNA weeks to months post LP implant.
No comparator group of patients undergoing concomitant
AVNA with TV‐PPM implant.
Concomitant AVN ablation and leadless pacemaker
implant is feasible. Pacing thresholds are stable over time.
However, patient comorbidities and the risk of majorcomplications are higher in patients undergoing AVNA.

University Hospital of Leuven, Belgium
July 2015 – Nov 2019
Class I or II indication for Micra, with previous valve
intervention
Standard exclusion criteria for Micra
Standard techniqueClass I or II indication for Micra, without previous valve
intervention
Prospective observational cohort study
None25

Garweg et al, 2020
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods
Sample size
Follow-up period
Main backgroundfactors of subjects
Results of primary
endpoints

Results of key
secondary endpoints

Limitations of the study

Conclusions

Successful implantation, electrical performance
Complications
Mean ±SD, Mann-Whitney U test, Mann-Whitney U test,
Kolmogorov-Smirnov test, Chi-squared test, Wilcoxon
signed-rank test, Pearson’s correlation coefficient, ANOVA
with Bonferroni correction
N=170 (54 with previous valvular intervention, 116
without)
12 months
82.0 years mean (82.5 years in valvular, 82.0 years in
non-valvular), 61.8% male (43.7% in valvular, 65.6% in
non-valvular)
Micra TPS was successfully implanted in all patients. Overtime, electrical performances were similar in both groups.
Complete AV block in one subject in valvular group andhad a loss of function at 6 month follow-up. Implantationof second device was successful. Flash pulmonary oedema
occurred in a patient previously treated by TAVI> Loss ofdevice function occurred in one subject in non-valvulargroup. No deaths related to Micra or procedure wereobserved.
Small number of subjects
All procedures were performed by the same operator
Absence of a direct comparison
No reporting on right ventricular and tricuspid valvefunction
The Micra™ leadless pacemaker is a safe and efficientpacing option in patients after valve intervention. The
absence of pacing lead through the tricuspid valve as well
as a reduction in device infections during follow-up are
significant advantages for this population.

26

Garweg et al, 2021
Study site
Participant recruitment
periodTarget population

Key exclusion criteria

Details of intervention
methodDetails of comparator
Study design
Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods
Sample size

Follow-up period

Main backgroundfactors of subjects
Results of primary
endpoints

Results of key
secondary endpoints

USA, Europe, Malaysia, Hong Kong
NA
Test MARVEL 2 in patients with AVC status who
have Micra LPM implanted
Patients who have persistent 30 AV block withnormal sinus rhythm and in the presence of sinus
arrhythmia, sinus bradycardia (<40 bpm), or
atrial/ventricular premature beats and atrial
arrhythmias.
To confirm the ability of a downloaded algorithm(hereafter referred to as the MARVEL 2 algorithm)
to provide AV synchronous pacing by mechanicallysensing atrial contraction via the accelerometersignal
No MARVEL 2 algorithm used
Prospective, non‐randomized multicenter clinical
trial
None
Demonstrate the superiority of the MARVEL 2
algorithm
SafetyMean ± SD or Median and interquartile range,
Paired t-tests, Wilcoxon signed rank test, SAS v9.4
N=75; AV Block N=42, 1:1 AVC N=18, Otherrhythms N=13
The performance of the AV synchronous pacing
mode and associated mode switches wascharacterized over the entire study duration which
averaged 153 ± 29 min.
Mean age 77.5±11.8, Male 60%, HTN 69.3%,
Diabetes 17.3%, AFib 18.7%, Coronary arterydisease 30.7%
The mode switching algorithm reduced VP inpatients with 1:1 AVC and appropriately switched to
VDD during AV block. No pacing safety issues wereobserved during arrhythmias.
The safety of the AVC mode switch was confirmedin patients with persistent third‐degree AV block as
it did not induce ventricular pauses greater than
1500ms, arrhythmias, or symptoms.

27Garweg et al, 2021

Limitations of the study

Conclusions

Small patient number
No ventricular using a leadless pacing system wasevaluated at rest in a limited patient sample for ashort duration
Behavior of the MARVEL 2 algorithm during thedifferent rhythms and varying AVC was assessedat rest and its performance during activities need
to be studied.
The mode switching algorithm reduced VP inpatients with 1:1 AVC andappropriately switched to VDD during AV block. No
pacing safety issues were observed duringarrhythmias.

Haddadin et al, 2022

Study site

Data were extracted from the National Readmission
Database(NRD), a nationally representative database
comprising discharge records from 28 states, withapproximately 35 million weighted discharges
annually (excluding rehabilitation and long-term
acute-care facilities). NRD represents
approximately 58.2% of all hospitalizations in the
United States.

Participant recruitment
period2016 – 2018

Details of intervention
methodDetails of comparator

all adults (≥ 18 years) who underwent leadless
pacemaker implantation
Patients discharged in December were excluded toensure 30-day follow-up
Patients with a leadless pacemaker implantationaccording to ICD10 code 02HK3NZ
N/A

Study design

Single arm retrospective database study

Blinding method

N/A
Clinical outcomes included in-hospital all-cause
death, stroke, venous thromboembolism, any
bleeding, and the need for blood transfusion.
Immediate procedure-related complications
included vascular complications, pericardial effusion
with and without the need for pericardiocentesis,
and device dislodgment.
Continuous variables: mean ± SD or median(interquartile range).

Target population
Key exclusion criteria

Primary endpoint

Key secondary
endpoints
Statistical analysis
methods28

Haddadin et al, 2022

Categorical variables: frequency (percentage). After
adjusting for covariates, multiple hierarchicallogistic regression analyses were used to measure
the predictors of immediate procedural
complications during the index admission.
Covariates included age, gender, primary payer,
median household income, hospital bed size,
hospital procedure volume, elective vs urgent
admission, Elixhauser comorbidity index, andbaseline comorbid conditions.

Sample size

N = 7,821

Follow-up period
Main backgroundfactors of subjects

30 daysResults of primary
endpoints

Results of key
secondary endpoints

Limitations of the study

N/AAll-cause death, n (%) = 513 (6.6)
Acute venous thromboembolism, n (%) = 443 (5.7)
Acute stroke, n (%) = 285 (3.6)
Any bleeding, n (%) = 1179 (15.1)
Blood transfusion, n (%) = 693 (8.9)
Total procedure-related complication rates, n (%) =588 (7.5)
All vascular complications, n (%) = 181 (2.31)
Vascular complications requiring repair, n (%) = 26
(0.33)
Procedure-related bleeding, n (%) = 194 (2.48)
Pericardial effusion without pericardiocentesis, n(%) = 146 (1.9)
Pericardial effusion requiring pericardiocentesis, n(%) = 82 (1.0)
Thoracotomy among patients with effusion, n (%) =26 (11.5)
Device dislodgment, n (%) = 40 (0.51)
Removal or repositioning of leadless pacemaker, n(%) = 253 (3.25)
Postprocedure length of stay (d) = 2 days (1–6)
Cost (US$) = $34,483 (23,602–57,040)
Risk of errors and inaccuracies in coding for
diseases and procedures.
NRD does not capture readmissions to nonparticipating hospitals, out-of-hospital death, or
postmortem diagnosis for the cause of death.
No comparison group.

29Haddadin et al, 2022
No information on post-discharge medications,medications adherence, and post-discharge
outpatient follow-up.
No information on device interrogation, capture
threshold, device sensitivity, number of deployment
attempts, deployment location in the right ventricle,
and echocardiographic, laboratory, and imaging
data.

Conclusions

Hauser et al, 2021
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodDetails of comparator

Overall complications related to leadless pacemakerplacement was slightly higher than in post-approval
registry studies.
Rate of serious complications remained relatively
low and comparable to prior studies in a high-risk
population with multiple comorbidities.

USA, FDA MAUDE database2016 – 2020
Micra LPM implanted patients who had major
adverse events (MACE) as well as using CapSureFix
leads
No MACE, did not use Micra LICP (leadless intra
cardiac pacemaker) or use of CapSureFix leads
To describe Micra implantation MACE and comparethem to implant procedure MACE for Medtronic
CapSureFix active-fixation transvenous pacing
leads.
CapSureFix lead usage during first 30 days after
implant

Study design

5-year Retrospective study

Blinding method

None
Describe MACE in Micra compared to CapSureFix
transvenous active-fixation ventricular pacing leads

Primary endpoint
Key secondary
endpoints
Statistical analysis
methods

NA
Pearson χ2 or Fisher’s exact test, R version 3.6.0 in
R Studio Version 1.1.463

Sample size

Micra LICP N=363, CapSureFix N=960

Follow-up period
Main backgroundfactors of subjects

NA
NA
30

Hauser et al, 2021

Results of primary
endpoints

MACE for Micra LICP is <1%Less MACE for implantation of CapSureFix leads
There were 11.0 times more deaths and 3.4 times
more cases of acute cardiac tamponade for Micra
implants compared to CapSureFix ventricular leadplacements
MACE: Deaths Micra 26.4%, CapSureFix 2.4%;
Tamponade Micra 79.1%, CapSureFix 23.4%; CPR
Micra 21.8%, CapSureFix 1.1%

Results of key
secondary endpoints

NA

Limitations of the study

Conclusions

Hauser et al, 2022
Study site
Participant recruitment
periodTrue numbers of MACE are not known, due tononreporting.
Underreporting in CapSureFix is more likely because
it is an older productSearch terms may have missed MACE
Possible that MAUDE reports contain erroneous
narrative information
Because of possibility of catastrophic myocardial
and vascular tears and perforation, Micra
implants should be performed in hospital withemergency cardiothoracic surgery capabilities.

USA, FDA MAUDE database
June 9, 2016 – July 31, 2021

Details of comparator

Micra VR and Micra AV MAUDE reports submitted by
Medtronic, Inc
Not available data in MAUDE database
Database search for consequences of Micra LPM
perforations and related device and operator use
problems.
NA

Study design

Retrospective study

Blinding method

None
Deaths, major adverse clinical events (MACEs), anddevice and/or operator use problems

Target population
Key exclusion criteria
Details of intervention
methodPrimary endpoint
Key secondary
endpoints
Statistical analysis
methods

NA
Pearson's chi‐square or Fisher's exact tests, R
version 4.0.1

31

Hauser et al, 2022
Sample size
Follow-up period
Main backgroundfactors of subjects

N=563, Perforations that manifested clinicallyduring Micra implantation within 30 days of implant
NA
NA

Results of primary
endpoints

27% Deaths, Cardiac tamponade 89%, Pericardial
effusions 11%, Emergency surgery 26%.
Perforations caused by: Device problems 25%,
Operator use problems 14%, combined device andoperator problems 11%

Results of key
secondary endpoints

NA

Limitations of the study

Conclusions

Incidences of MACE in MAUDE are unknown.
Because of long-term longitudinal surveillance
study, Micra MAUDE reports could be higher
Possible for some MACE were not reported to the
manufacturer or to the FDA and are not in the
MAUDE database.
High percentage of MACE in USA could be due tounderreporting in other countries
Do not know the qualifications, experience, orcaseload of the implanting physicians or
hospitals.
Micra perforations reported in MAUDE are often
associated with death and major complications
requiring emergency intervention. Device anduse problems account for at least half of
perforations. Studies are needed to identify who
is at risk for a perforation and how MACE can be
avoided or mitigated.

32

Higuchi et al, 2020
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodMito Saiseikai General Hospital, Japan
October 2017 – April 2020
Micra TPS implanted subjects, stable pacing
threshold
Missing data from attrition
Pull and hold method

Details of comparator

Micra TPS implanted subjects, increased pacing
threshold

Study design

Retrospective study

Blinding method
Primary endpoint
Key secondary
endpoints

None
Procedural data, transition of pacing threshold

Statistical analysis
methods
Sample size
Follow-up period
Main backgroundfactors of subjects

Results of primary
endpoints

Results of key
secondary endpoints

Complications
Shapiro-Wilk test, Mann-Whitney U test, Student’s
t-test, Welch t-test, Fisher’s exact probability test,
ROC curve
N=60 (9 in stable threshold group, 51 in increased
pacing threshold)7 months
89.1 years in stable pacing, 85.9 years in increased
pacing, 56% female in stable pacing, 53% inincreased pacing
No difference sin number of deployments, tines orindwelling site. Longer implantation time, lower
impedance and higher pacing threshold in increased
pacing group. 44% in increased pacing did not have
improved pacing thresholds after 3 months.
Improved pacing thresholds for most in stablegroup.
No cases of CV mortality or rehospitalization. Twocases of pacing failure in increased pacing group
without reimplantation. One lymph leakage atpuncture site in increased pacing group and one
pericardial effusion not requiring intervention instable pacing.

Limitations of the study

Limit in accurately determining number of tines
stably anchored to the myocardium by pull and hold
Follow-up was short – 7 months

Conclusions

An IPT was noted shortly after Micra-TPS
implantation owing to microdislodgement because of insufficient anchoring of
33

Higuchi et al, 2020
the device to the myocardium. Impedance >660 Ω
and threshold <1.0 V/0.24 ms may predict anincrease in pacing threshold.

Houmsse et al, 2020

Study site

Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodDetails of comparator

Nine centers in the USA/Canada (Wexner Medical
Center, Mayo Clinic, NY/Long Island Jewish Medical
Center, Fairfield Medical Center, Trihealth, Penn
State Health Milton S Hershey Center, Emory
University, Texas Cardiac Arrhythmia, McGill
University)
February 2014 to May 2020
Micra TPS implanted subjects with an IVC filter
None
NA
None

Study design

Multicenter, retrospective study

Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods

None
Procedural outcome

Sample size

N=23

Follow-up period
Main backgroundfactors of subjects

7 months

Long-term complications
Mean (SD), Median (IQR)

73.8 years mean age, 52.2% male gender

Results of primary
endpoints

Successful in 21 out of 22 subjects (one subject had
IVC filter removed before the procedure). No device
related complications or MACE. 3 patients had inhospital mortality – septic shock, complications of
prosthetic valve endocarditis and refractory heart
failureResults of key
secondary endpoints

No delayed complications observed

Limitations of the study

Retrospective study with experienced operators
Small sample size
Unclear whether the IVC filters were renderedineffective34

Houmsse et al, 2020
Conclusions

Safety and feasibility of Micra implantation via an
IVC filter

Jelisejevas et al,
2021
Study site
Participant recruitment
periodSwitzerland

Target population
Key exclusion criteria
Details of intervention
methodDetails of comparator

June 2015 – May 2020
Clinical indication for a single-chamber pacemakerand provided written
informed consent to the procedure
Not needing implantation of Micra TPS
Implantation access from left femoral artery
Implantation access from right femoral artery

Study design

Retrospective, non-randomized single center study

Blinding method
Primary endpoint
Key secondary
endpoints

NA
Safety of left access

Statistical analysis
methods
Sample size
Follow-up period
Main backgroundfactors of subjects

Results of primary
endpoints

Results of key
secondary endpoints

NA
Jamovi project version 1.2, Shapiro-Wilk test, Mean
± SD, Student t-test, Mann-Whitney U-test Pearson
χ2 or Fisher’s exact test
N=143 consecutive patients undergoing Micra TPS
implantation; N=18 (13%) Left femoral access;
N=125 (87%) Right femoral access
30 days interventional period
Mean age 79.8±7.5 yrs, Male 65%, Coronary arterydisease 32%, Diabetes 20%, Chronic renal failure
64%
Implantation rate 99.2% for Right femoral, 100%left femoral access
14 deaths (11%) in median 257 days,
Fluoroscopy and procedure times were notsignificantly different
Reason for left femoral access is previoustransfemoral TAVI causing poorer right access.
NA

35

Limitations of the study

Small study
RCT should be conducted with comparison of two
femoral venous approaches

Conclusions

A left femoral venous access for Micra TPS
implantation is safe and effective with anexcellent implantation success rate similar to aconventional right femoral venous access without
longer implantation and fluoroscopy times.

Kowlgi et al, 2022
Study site
Participant recruitment
periodTarget population
Key exclusion criteria

Details of intervention
methodDetails of comparator

three Mayo Clinic (Rochester, MN; Jacksonville, FL;
and Phoenix, AZ) sites
March 1 to September 1, 2020
All patients undergoing MicraTM‐AV implants
Patients with less than 3 months follow‐up (n = 6)
Patients with persistent atrial arrhythmia (n = 7)
indication for MicraTM AV implant was complete
heart block in 23 (53%) patients, symptomatic
bradycardia in 13 (30%) patients, and AF with rapid
ventricular rates planned for AV node ablation in 7
(16%) patients
Endpoints were compared between patients withand without atrial synchronous ventricular pacing(AsVP) ≥ 70%.

Study design

Retrospective database analysis

Blinding method

N/A
demographics, clinical presentation, medications,
relevant comorbidities, and implant‐related
complications

Primary endpoint
Key secondary
endpoints

N/A

Statistical analysis
methods

median (interquartile range [IQR]), mean ±standard deviation, percentages, Fisher exact test,
paired samples t‐test, Wilcoxon rank‐sum test

Sample size

N = 43

Follow-up period
Main backgroundfactors of subjects
Results of primary
endpoints

3 months, median follow‐up duration of the wholecohort was 138 (103−190.5) days.
Twenty‐eight patients (65%) achieved AsVP ≥ 70%,
and 15 (35%) had inadequate AsVP
65% of patients achieved AsVP ≥ 70%

36

Patients with adequate AsVP had smaller body massindices, a lower proportion of congestive heart
failure, and prior cardiac surgery.
Results of key
secondary endpoints

Limitations of the study

Conclusions

Kumar, 2021
Study site
Participant recruitment
periodN/ARetrospective review that has the inherent pitfalls
with potential confounding factors in the analysis of
AV synchrony.
Modest sample size, follow‐up durations are nonuniform.
In comparison to the original study, a significantly
lower proportion of AV synchrony was noted, mostly
attributable to physiological reasons combined witha learning curve that exists for any new technology.

Max Superspeciality Hospital, India
Unspecified

Details of intervention
methodDetails of comparator

Subjects with chronic/permanent AF associated withcomplete heart block, or SSS
Pacemaker syndrome, retrograde VA conduction,
drop in arterial blood pressure with onset ofventricular pacing, pre-existing endocardial
defibrillation, IVC filter, previous implanted leadlesscardiac pacemaker
Steerable catheter through femoral vein, advanced
into right ventricle and affixed to myocardium
Transvenous pacemaker

Study design

Prospective, observational, single center study

Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods

NA
Adverse events or complications

Sample size

N = 443 (TPS 198, VVI-PM 245)

Follow-up period
Main backgroundfactors of subjects
Results of primary
endpoints

3 years
Mean age of 71.71 +/- 8.44 years, male gender
71%
There was no adverse event or complications
reported for any of the subjects.

Target population

Key exclusion criteria

Mean time from hospitalization to discharge
Mean +/- SD

37

Results of key
secondary endpoints

Mean time from hospitalization to discharge was 1.5
days

Limitations of the study

Small sample size
No control group

Conclusions

Leadless cardiac pacemaker was capable ofproviding effective and safe pacemaker function in avaried group of patients who had indications forlong-term pacing therapy

Martinez-Sande,
2021
Study site

University Clinical Hospital of Santiago deCompostela, Spain

Participant recruitment
periodJun 2015 – Dec 2019

Details of comparator

Subjects with an indication for a single-chamber
pacemaker implant
None
Femoral access for TPS, Cephalic dissection or
subclavian puncture for VVI-PM (operator
preference)
Transvenous pacemakers (VVI-PM)

Study design

Prospective, observational, single center study

Blinding method
Primary endpoint
Key secondary
endpoints

NA
Complication rate

Target population
Key exclusion criteria
Details of intervention
methodMortality rate

Statistical analysis
methods

Mean +/- SD, Propensity score matching, Cox
regression analysis, multiple hypothesis testing with
Benjamini-Hochberg procedure, Bayesian cohort
analysis (posterior calculated using MetropolisHastings algorithm)

Sample size

N = 443 (TPS 198, VVI-PM 245)

Follow-up period

22.3 +/- 15.9 months
Mean age was 81.5 years (TPS 79.2 +/- 6.6 years,
VVI-PM 83.5 +/- 8.9 years), gender (TPS 62.1%
male, VVI-PM 27.3% male)
The TPS group reported significantly lower total
complications than the VVI-PM group (7, 3.5% vs.
21, 8.6% respectively, p = 0.0303). However, there
were no differences in major complications between

Main backgroundfactors of subjects
Results of primary
endpoints

38

Results of key
secondary endpoints

Limitations of the study

Conclusions

the groups (6, 3% vs. 14, 5.6% respectively,
p = 0.1761). In a multivariable analysis of data
matched by age, LVEF, chronic heart failure,
anticoagulation status, and chronic kidney disease,
the TPS group presented fewer complications thanthe VVI-PM group (Hazard ratio (HR) = 0.39,
confidence interval (CI) 95%: 0.15–0.98;
p = 0.013). The most frequent complications inpatients with TPS were vascular (4, 2%), andassociated with heart effusion (2, 1%). In patientswith VVI-PM, the most frequent complications were
pocket generator-related (12, 4.9%),
pneumothorax (3, 1.2%), and electrodedislodgement (3, 1.2%)
During the follow-up, 62 patients died (14%),
including 18 in the TPS group (9.1%) and 44 in the
VVI-PM group (17.9%) with significant difference
between the groups
Not a randomized trial
Choice of each pacemaker was based on clinicalconditions
Number of patients included and follow-up likely
underestimates infections in VVI-PM group
Pocket-related complications in mid and long-term
were not well represented
TPS patients had a lower overall complication rate
than VVI-PM patients including matched-pairsamples using a Bayesian analysis. These results
confirm the good safety profile of TPS in dailyclinical practice.

Nicosia et al, 2022
Study site

15 Italian centers participating to the One Hospital
ClinicalService project

Participant recruitment
periodMay 2016 to July 2019

Key exclusion criteria
Details of intervention
methodDetails of comparator

Patients indicated for permanent cardiac pacing who
underwent a TPS
implant (TPS Micra Medtronic, Inc.)
N/A
Each center utilized their own standard-of-carepractices and approaches during the implant.
N/A

Study design

Single arm

Target population

39

Blinding method

Primary endpoint

N/A
All reported procedural, peri-procedural, and postprocedural complications were collected. Procedural
Times of the total population of patients andstatistical comparisons between the groups ofpatients according to age

Key secondary
endpoints

N/A

Statistical analysis
methods

means and SD; minimum, maximum, and medianwith IQR, counts and percentages, Kruskal–Wallis
test, chi-square test, Fisher`s exact test

Sample size

N = 577

Follow-up period

median follow-up was 12.0 months (IQR: 5.9–23.8).

Main backgroundfactors of subjects
Results of primary
endpoints

Procedure-related complication occurrence was low(0.5%)
Procedural duration and fluoroscopy time exposure
were comparable among the four cohorts with nostatistical difference between age groups.

Results of key
secondary endpoints

N/A

Limitations of the study

Not reported

Conclusions

This multicenter real-world prospective data showed
high safety levels for TPS implant at different ages.
Procedural performance indicators were similar atthe different ages, and complication rates were low
and not related to the patient’s age. Even
procedural efficacy did not seem to be influenced byage.

Ngo et al, 2021
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodNA, systematic review
Studies published before June 6, 2020
Patients from observational studies of Nanostim andMicra leadless pacemaker implantation
No Micra or Nanostim LPM implanted
Systematic review of reported outcomes from Micra
implantation.
40

Details of comparator
Study design
Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods

Systematic review of reported outcomes from
Nanostim implantation.
Systematic review and meta-analysis (22Prospective, 10 Retrospective, 4 not reported)
None
Safety, efficacy with acceptable pacing threshold
Implantation success, specific complications up to
90 daysFreedman-Tukey double arcsine transformation,
Stata version 16.0, Stata user-written command
Metaprop, I2 statistic

Sample size

36 Studies, N=4335

Follow-up period
Main backgroundfactors of subjects

90 days, 1 year
83.3 yrs old, Male 61%, HTN 69.7%, Diabetes
23.3%, Coronary artery disease 28.5%, AFib 66.7%
Micra pool incidence of complications at 90 days
0.46%, 1 year 1.77%. Nanostim 90 days 6.06% 23.54% and 1 year 5.33% - 6.67%.
Micra lower odds of complications as compared toconventional transvenous pacemaker implant (3.0%versus 7.43%) OR 0.49

Results of primary
endpoints

Results of key
secondary endpoints

Limitations of the study

Conclusions

Oliviera, 2021
Study site
Study period
Inclusion Criteria

At 1 year, 98.96% implanted with Micra had goodpacing capture thresholds, Nanostim 90% - 100%good pacing capture thresholds
Data is entirely observational
Small sample size and short follow-up time for moststudies
Meta analysis for Micra and Nanostim were
performed separately
Low number of studies using Nanostim
Inconsistency in which complications were reported
Efficacy and primary endpoints were different witheach study
Most studies report outcomes for the Micra, which is
associated with a low risk of complications andgood electrical performance up to 1-year after
implantation.

NA2015 to 2019
Studies which used leadless pacemakers in humans
with heart disease41

Exclusion criteria
Details of intervention
methodDetails of comparator

Non-English/French/Spanish articles, animalstudies, case reports, guidelines
NA
NA

Study design

Systematic Review

Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods

None
Procedural success and failure
Complications during follow-up, Pacemakerindications

Sample size

58 papers covering 4,739 subjects

Follow-up period
Main backgroundfactors of subjects
Results of primary
endpoints

NA

Results of key
secondary endpoints

Limitations of the study

Conclusions

Mean +/- SDNA
4,670 out of 4,739 implantations were successful
5.23% complication rate, most common were
pacing issues (68), femoral access issues (64),procedure related cardiac injuries (47)
16 studies with complication rate below 10%, 21
studies with complication rate below 15%, 5 studies
with complication rate between 15-20%
360 deaths were described during follow-up (117from a cardiac cause, 11 from procedure/device)
Main indication was chronic AF with slow ventricularrate, other indications included low level of physicalactivity or short expended lifespan, sinus-node
dysfunction, second or third-degree AV block orbifascicular/trifascicular block
All studies were observational with a short follow-up
periodNo RCTs which compared leadless pacemakers toconventional pacemakers
Large heterogeneity between studies
Leadless pacemakers have a relatively low
complication rate. They may be a good option in
subjects with an indication for single-chamber
pacing and in subjects with conditions precludingtransvenous pacemaker implants.

42

Palmisano, 2021
Study site
Participant recruitment
periodGiovanni Panico Hospital, Italy
Feb 2016 – May 2020

Details of comparator

Subjects undergoing single-chamber PM
implantation for any cause
Leadless PM implantation after extraction of
conventional PM or transvenous PM implantation
after failed leadless PM attempt
Femoral vein catheter for implantation in septoapical region of RV or other position if notaccessible for leadless PM. Subclavian vein accesspositioned in right ventricular apical septum or rightventricular apex for transvenous PM.
Transvenous pacemaker

Study design

Prospective, cohort-matched, single center study

Blinding method
Primary endpoint
Key secondary
endpoints

None
Intra and post-procedural findings

Target population
Key exclusion criteria

Details of intervention
methodQuality of life, patient acceptance, complications

Statistical analysis
methods

Mean +/- SD, Student’s t-test, Mann-Whitney U
test, analysis of variance, Fisher’s exact test, binary
logistic regression for propensity scores

Sample size

N = 243 (leadless 91, transvenous 152)

Follow-up period

Baseline, 1 week, 3 months, 6 months
Mean age was 75.3 years for leadless and 80.6
years for transvenous. Gender was 72% male forleadless and 86% for transvenous.
Leadless implantation of Micra was significantly
longer than transvenous, required more fluoroscopy
and involved more team members. No significant
differences in electrical parameters on implantation.
Lower pain intensity for leadless compared totransvenous (persisted at 1 hour, no difference at 6hours). Leadless had a lower rate of patientsrequiring analgesics in postoperative period.
Mobilization was earlier for transvenous. Leadless
had a shorter duration of hospitalization.
Leadless had a significantly higher quality of life asmeasured by SF-36 compared to transvenous at 1
week, 3 weeks and 6 months. FPAS was higher inleadless than transvenous (patient acceptance).
Two transvenous developed pocket hematoma
within 24 hours, with one requiring surgical

Main backgroundfactors of subjects

Results of primary
endpoints

Results of key
secondary endpoints

43

Limitations of the study

Conclusions

Piccini, 2021
Study site
Participant recruitment
periodTarget population

Key exclusion criteria
Details of intervention
methodDetails of comparator

drainage. No device related complications wereobserved for leadless. One leadless and one
transvenous died in the follow-up.
Observational and non-random
Total population was relatively small
Duration was too short to assess long-term qualityof life
L-PM implantation procedure is longer and requires
more team members andlonger postoperative immobilization than T-PM
implantation. Patients who undergo L-PM
implantation have less intra- and post-proceduralpain and can be discharged earlier than those who
undergo T-PM implantation. On medium-term
follow-up, L-PM is associated with better QoL, on
both physical and mental health scales, and greater
patient acceptance than T-PM.

Medicare population, USA
March 2017 – Dec 2018
Medicare beneficiaries implanted with MedtronicMicra<12 months of continuous enrollment in Medicare
prior to pacemaker implantation and with evidenceof a prior cardiovascular implantable electronic
deviceUnspecified
Transvenous pacemaker

Study design

Continuously enrolling observational cohort study

Blinding method
Primary endpoint
Key secondary
endpoints

None
Acute complications
6-month complications, survival

Statistical analysis
methods

Mean +/- SD, t-tests, Chi-squared test, univariate
logistic regression, Fine-Gray competing risk
modules, Cox proportional hazards models

Sample size

N=5746 (leadless), N=9662 (transvenous)

Follow-up period
Main backgroundfactors of subjects

Mean follow-up of 606.5 +/- 265.9 days
Mean age was 81.0 (8.7) years and 43.5% werefemale44

Results of primary
endpoints

Results of key
secondary endpoints

Limitations of the study

Conclusions

Unadjusted overall acute complication rate washigher in patients with leadless (8.4% vs. 7.3%),
no significant difference in adjusted overall
complications (7.7% vs 7.4%), cardiac
effusion/perforation within 30 days was significantly
higher in leadless (0.8% vs. 0.4%), device related
complications such as dislodgement, infection andpocket complications were lower with leadless(1.4% vs. 2.5%)
Leadless had a reduction in 6-month complications
compared to transvenous (0.77 hazard ratio).
Leadless had a lower rate of device revisioncompared to transvenous (0.63 hazard ratio). No
difference in 6-month all-cause mortality (1.00
hazard ratio).
Non-randomized observational studies
Complications may be missed or inadequately
documented in administrative claims
Residual confounding cannot be completed
eliminatedPatients in whom a leadless pacemaker was
implanted were observed to have higher rates ofcardiac effusion or perforation within 30 days but
lower device-related complication rates andrequirements for device revision at 6 months

Piccini, 2022
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodDetails of comparator
Study design
Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods

Micra IDE, Micra CA and Micra PAR studies (pooled
cohort)December 2013 – March 2018
Subjects enrolled in previous Micra studies
Subjects missing >10 candidate variables, existing
pacemaker or ICD
Unspecified
None
Pooled analysis of prospective, non-randomized
studies
None
Risk of pericardial effusion
Prediction of pericardial effusion risk
Mean +/- SD, binomial confidence intervals,
multivariable risk production model, Lasso
regression
45

Sample size

N=32 (effusion), N=2785 (no effusion)

Follow-up period
Main backgroundfactors of subjects
Results of primary
endpoints

Study commencement to 2021

Results of key
secondary endpoints

C-index median was 0.73 for lasso logistic model,
0.73 for the scoring system

Limitations of the study

Conclusions

NA
32 subjects with symptomatic pericardial effusion(1.1%, 95% CI 0.8-1.6%)

Modelling may be subject to confounding
Unable to evaluate the location of attempted
deployments and risk of perforation
Echocardiograms were at the discretion of thephysician and not protocol-driven or systematic
Inability to divide into training or validation set
The overall rate of pericardial effusion following
Micra implantation attempt is 1.1% and has
decreased over time. The risk of pericardial effusion
after Micra implant attempt can be predicted using
pre-procedural clinical characteristics withreasonable discrimination.

Russo, 2022
Study siteCampania Leadless Registry, Italy (Monaldi Hospitalof Naples, University of Campania of Naples,
Umberto I Hospital of Nocera Inferiore)

Participant recruitment
periodJuly 2017 – Dec 2020

Target population
Key exclusion criteria

Inclusion in leadless pacemaker registry with Micra,
subjects with AF
Subjects who did not consent to inclusion in theregistry

Details of intervention
methodStandard technique

Details of comparator

Inclusion in leadless pacemaker registry with Micra,
subjects without AF

Study design

Retrospective review of multicenter registry

Blinding method

None
LLPM intraoperative data, perioperativecomplications
Syncope, cardiac hospitalization, pacemakersyndrome, all-cause death
Mean +/- SD, median +/- IQR, KolmogorovSmirnov test, Shapiro-Wilk test, chi-squared tests

Primary endpoint
Key secondary
endpoints
Statistical analysis
methods46

with Yates correction where appropriate, Student’s
t-test, Mann-Whitney U test, Wilcoxon signed-rank
test, Kaplan-Meier analysis
Sample size

N=140

Follow-up period
Main backgroundfactors of subjects

Mean follow-up of 606.5 +/- 265.9 days

Results of primary
endpoints

Results of key
secondary endpoints

Mean age was 76.7 +/-11.24 years, men 64.3%
5% of subjects experienced perioperativecomplications (no difference between groups), no
procedure-related death
Non-AF group showed higher percentage ofventricular pacing (52% vs 40%), LLPM electricalparameters remained stable and did not differ
between two groups, no significant difference inoutcome of interest between groups, no differenceon Kaplan-Meier on combined endpoints, 10
subjects died, 7 subjects reported cardiac
hospitalization and 5 reported syncope. None
reported pacemaker syndrome.

Limitations of the study

Retrospective and non-randomised study design
Small cohort size, differences in baselinecharacteristics, limited follow-up

Conclusions

LLPM may be considered a safe and reasonable
treatment in patients without AF in need of pacing

Sanchez, 2021
Study site
Participant recruitment
periodTarget population
Key exclusion criteria

Details of intervention
methodDetails of comparator

Ohio State University, USA
Feb 2014 – June 2019
Normal LVEF (>=50% at baseline)
History of CRT and recovered LVEF who underwent
extraction followed by single ventricle pacing,
individuals who were not 100% pacemakerdependent
Standard technique in addition to AV node ablation(concurrently or during follow-up). TV group
underwent ipsilateral venogram before axillary or
subclavian access. RV lead implantation based on
discretion of operator. Femoral venous approach
used for leadless.
Transvenous pacemaker47

Key secondary
endpoints
Statistical analysis
methods

Retrospective review of prospectively maintained
database
None
Incidence of pacing-induced cardiomyopathy (10%decrease in LVEF)
Acute and long-term procedure-related
complications
Mean +/- SD, Student’s t-test, Chi-squared test,
multivariate analysis

Sample size

N=198 (131 for transvenous, 67 for leadless)

Study design
Blinding method
Primary endpoint

Follow-up period
Main backgroundfactors of subjects

Results of primary
endpoints

Results of key
secondary endpoints

Mean of 592 +/549 days for transvenous and 817+/- 600 days for leadless
Mean age was 74 in transvenous and 73 forleadless. Female % was 95% in transvenous and
31% in leadless. LVEF was 59% for transvenous
and 57 for leadless.
Overall, 18 (13.7%) patients in TVP and 2 (3%) in
LP developed PICM after a median duration of 254(interquartile range [IQR]: 470) days after
implantation. The two patients in the LP groupdeveloped PICM after 180 and 350 days. The
median duration before PICM in TVP group was 194(IQR: 429). The incidence of PICM was significantly
higher with TVP compared with LP (p = .02).
Incidence of acute periprocedural and follow-up
complications (>30 days) was similar in bothgroups.

Limitations of the study

Retrospective single-center study
Non-randomized study and device selection basedon operator discretion

Conclusions

Pacemaker-induced cardiomyopathy is significantly
lower in leadless compared to transvenous
pacemakers.

Sasaki, 2022
Study site
Participant recruitment
periodTarget population
Key exclusion criteria

St Marianna University Hospital, Japan
Sept 2017 – Sept 2020
Bradyarrhythmias based on Class I and II guideline
recommendations
Reimplantation from lead failures, device upgrade
or device infection, complete removal of priordevice system
48

Details of intervention
methodDetails of comparator
Study design
Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods

Sample size

Follow-up period

Main backgroundfactors of subjects
Results of primary
endpoints
Results of key
secondary endpoints

Limitations of the study

Conclusions

Manufacturer’s protocol with target of RV midseptal region (apical or high RV septum as backup)
Transvenous pacemaker
Prospective, propensity score-matched, single
center study
NoneAll-cause mortality
Cardiovascular mortality, late device-related
adverse events, HF related hospitalization
Mean +/- SD, median, IQR, Student’s t-test,
Wilcoxon rank-sum test, Fisher’s exact test, KaplanMeier method and log-rank test, logistic regression
model
N=193 (leadless 110, transvenous 83), N=116 withpropensity score matching (leadless 58,
transvenous 58)
Median of 801 days (IQR 447-1,124 days) for
leadless group and 649 days (IQR 375-808) intransvenous group
Mean age was 81 years in leadless and 82 years intransvenous. Female % was 62% in leadless and
35% in transvenous. LVEF was 63% in both
leadless and transvenous cohorts.
Higher overall mortality in the leadless group over 4
year follow-up (28% vs. 4%, p = 0.059, nonsignificant)Higher HF readmission rate in leadless groupcompared to transvenous (29% vs. 2%). No
significant difference between leadless andtransvenous for device-related AEs (0% vs 4%).
Retrospective observational investigation with loss
to follow-up
Based on a single-center experience
Small sample size, reducing statistical power
Risk of overlooking clinically important predictors
from propensity score matching
Operators were experienced for leadless, which may
underestimate complications
Data on medications unavailable
The implantation of a VVI-LPM for non-AF
bradyarrhythmias increased the incidence of HFrelated rehospitalization at the mid-term follow up
compared to the use of a DDD-TPM

49

Takato, 2020
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodDetails of comparator

Kyorin University, Japan
March 2014 – Dec 2019
Class I and IIa recommendations for Micra leadless
implant with bradyarrhythmia
Not specified
Femoral venous access
None

Study design

Prospective cohort study

Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods

None
Electrical indicators

Sample size

N=51

Follow-up period
Main backgroundfactors of subjects

22 months

Results of primary
endpoints

Results of key
secondary endpoints

Limitations of the study

Conclusions

Complications
Friedman’s test, Wilcoxon signed rank

Mean age was 79 years, 64% maleResistance value decreased after 1 month comparedto implantation, no significant change to rightventricular capture thresholdNo reimplantation cases from pacing failure(increase in right ventricular capture threshold,inadequate sensing from decrease in rightventricular wave height or premature battery
voltage consumption)
No major acute complications, except for one caseof intracardiac leakage of intraoperative contrast
medium, 1 cardiovascular death up to 60 months,
no major chronic complications, one case withpacemaker syndrome, one case with CRT for
suspected herat failure from pacing induced
cardiomyopathy
Retrospective single-center observational studies
Small sample size with limited follow-up

No major acute complications, measured values
were stable even up to 5 years

50Vincent et al, 2022
Study site
Participant recruitment
periodTarget population
Key exclusion criteria
Details of intervention
methodDetails of comparator

Study design

National Inpatient Sample (NIS) database2017 – 2019
Patients who underwent Micra® (Medtronic) LICP
implantation (n = 16,825) or transvenous
permanent pacemaker (n = 564,100) implantation,
specified by ICD-10 procedure codes.
Age < 18, missing mortality data
Single-chamber leadless intracardiac pacemakerTransvenous pacemaker
Subsequent 1:1 case-control matching of patients
undergoing LICP (n = 3,084) or transvenous
pacemaker (n = 3,084) implantation by matchingfor patient age, gender, race, and significant
comorbidities was performed.

Blinding method
Primary endpoint
Key secondary
endpoints
Statistical analysis
methods
Sample size
Follow-up period
Main backgroundfactors of subjects

Results of primary
endpoints

Results of key
secondary endpoints

in-hospital all-cause mortality, pooled complication
rate, and total duration of hospitalization
in-hospital complications (vascular, infectious,
pericardial, requirement of pericardiocentesis, anddevice retrieval or replacement)
Pearson X2 test, t-test, 1-way analysis of variance,
numbers and percentages
Micra leadless pacemaker: n = 16,825
Transvenous pacemaker: n = 565,845
Single-chamber pacemaker: n = 1,255
Index hospitalization only
Average patient age was 75.4 ± 12.8 years.
majority of patients (55.2%) were male and selfidentified as White/non-Hispanic (75.6%),
compared to Black/African American (10.9%) or
Hispanic (7.5%).
In-hospital all-cause mortality was 5.2% amongleadless pacemaker implantations, with mortality
rates decreasing between 2017 and 2019 (8.2% vs4.2%). Average length of stay and total hospitalcharges increased. Pooled complication rates
decreased
Postoperative infection and device retrieval rates
decreased.

51

Limitations of the study

Conclusions

Zucchelli, 2021
Study site
Participant recruitment
periodTarget population

Key exclusion criteria

Details of intervention
methodDetails of comparator
Study design
Blinding method
Primary endpoint
Key secondary
endpoints

Patient data obtained is dependent on coded
diagnoses that were not adjudicated and may besubject to error or omission.
Outcomes are only reported during index
hospitalization and do not capture readmission or
out-of-hospital major adverse events or death overtime.
LICP implantations were performed in patients ofadvancing age, increasing comorbidities, andheightened acuity of illness in comparison to theinitial pivotal trials.
Postprocedural complication rates and in-hospital
all-cause mortality were higher in real worldpractice than previously reported.
Between 2017 and 2019, pooled procedural
complication rates decreased significantly, likely
because of improving operator skill.
Compared to transvenous pacemaker, leadless
pacemaker implantation was associated with lower
procedural complication rates but higher in-hospitalmortality.

University Hospital of Pisa, Italy
May 2014 – April 2019
Subjects who met Class I indication for pacing andwere suitable for single-chamber ventricular
stimulation<18 years, hemodynamic instability, mechanicaltricuspid valve prosthesis or inferior vena cava
filter, morbid obesity that could impair remote Micracontrol, femoral venous occlusion, allergy to Micra
TPS components, < 12 months life expectancy andrisk of interference with any other electronic device
Femoral vein catheter for implant in right ventricle(non-apical position where feasible)
Transvenous pacemaker
Prospective, comparison matched, single center
study
None
Intra and post-procedural findings
Quality of life, patient acceptance, complications

52

Statistical analysis
methods

Mean +/- SD, median, percentages, unpaired andpaired t-tests, Mann-Whitney U test, Fisher’s exact
test

Sample size

N = 200 (100 in leadless, 100 in transvenous)

Follow-up period

12 months
77.5 years for leadless and 78.8 years fortransvenous, 77% male for leadless and 67% fortransvenous, LVEF 56% for leadless vs. 54.8% fortransvenous
The implant procedure was successful in all
patients. In group 1, the procedure duration was
lower than in group 2 (43.86 ± 22.38 vs 58.38 ±17.85 min, p < 0.001), while the fluoroscopy time
was longer (12.25 ± 6.84 vs 5.32 ± 4.42 min, p <0.001). There was no difference about the rate of
septal implant at the right ventricle (76% vs 86%,
p = 0.10). Patients were followed-up for a medianof 12 months. No acute and chronic procedurerelated complication was observed in group 1, while
we reported acute complications in seven patients(7%, p = 0.02).
All electrical parameters remained stable during theentire follow-up in both groups. Mortality duringfollow-up was higher in TV-VVI PM vs Micra group(23 vs 7 deaths, p = 0.003). Ten patients
experienced a complication in group 2 (p = 0.004),
leading to system revision in six cases (p = 0.038).
Non-randomized observational study with small
population
Propensity score matched analysis was not used
due to limited number of transvenous PMs,
introducing a potential bias in the selection ofcontrol cases
Single center experience
Device longevity was only an estimate based on
pacing threshold and impedance, without ameasure of battery status
Micra implant is a safer procedure than TV-VVI PM
implant even in real-life setting including patients athigh risk of complications. It reduces acutecomplications and system revisions and minimize
the risk of infective issue in patients needing
ventricular pacing. Electrical measurements in suchleadless pacemaker are stable and very low at long-

Main backgroundfactors of subjects

Results of primary
endpoints

Results of key
secondary endpoints

Limitations of the study

Conclusions

53

term follow-up, with a longer estimated battery life
than TV-VVI PM.

54

55

Battery Survival, by Pacemaker Type100.0%
90.0%
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
10.0%
0.0%

0

12

24

36

48

60

72

84

96

Micra AV108 120 132 144 156 168 180 192 204 216 228 240
DDD TV-PM

56

植込み後 30 日間に合併症が発生することによる追加的な死亡率
An excess mortality of 9.5% observed during the first year in patients with earlycomplication vs. no early complication was estimated from the POINTED registry .
This percentage was multiplied by the absolute difference in complication events
observed between the TC-PM and TV-PM cohorts at one month to obtain anominal estimate for survival benefit associated with any reduced TC-PM earlycomplication rate.
The estimation of 9.5% mortality during the first year is obtained from Palmisano
et al. Figure 1.B: Excess mortality of approximately 9.5% is observed at 12
months (as evidenced by the difference in survival curves between patients withearly complications as compared to patients without complications). Beyond 12
months, the survival curves do not show substantial difference in shape. We
hence assumed no additional excess mortality beyond the 9.5% in the first year.
The 9.5% survival difference was incorporated by multiplying it by the absolutedifference in early complication rates between the TC-PM and TV-PM strategies.
For example, if the early complication rate for TC-PM patients was 5%, then TCPM patients were assumed to have a one-year mortality that was an absolute
9.5% x 5% = 0.475% lower than the TV-PM strategy’s mortality.

57

SF-36 で計測された HRQoL 値の変換
To obtain utility estimates for TC-PM and TV-PM, the identified SF-36 component
data at baseline, one month, and six months were converted to a mean EQ-5D
estimate using an established mapping algorithm (11,18). See Table S.4.1 for
the SF-36 component score reported in the underlying study. See Table S.4.2 forthe resulting mapped EQ-5D values.
Leadless Pacemaker (TC-PM)
SF-36 Component data per Cabanas-Grandio et al.

BL

1M

6M

Physical Functioning (PF)

44

61

63

Role Physical (RP)

23

59

64

Body Pain (BP)

51

66

69

Vitality (VT)

40

55

52

Role Emotional (RE)

61

74

75

Mental Health (MH)

61

73

75

Social Functioning (SF)

75

88

85

General Health (GH)

43

53

48

Transvenous Pacemaker (TV-PM)
SF-36 Component data per Cabanas-Grandio et al.

BL

1M

6M

Physical Functioning (PF)

41

45

42

Role Physical (RP)

22

18

36

Body Pain (BP)

52

64

60

Vitality (VT)

39

47

44

Role Emotional (RE)

62

61

68

Mental Health (MH)

61

70

65

Social Functioning (SF)

73

79

78

General Health (GH)

44

48

48

Table S.4.1: SF-36 component scores reported for Leadless pacemakers andTransvenous pacemakers at Baseline (BL), 1 month (1M), and 6 months (6M)
post implant, as reported by Cabanas-Grandio et al.

Leadless Pacemaker (TC-PM)

Computed

Absolute

Relative

EQ5-D Scorechangechange(based on Ara

to

to

58

et al., 2008

baselinebaselinealgorithm)

BL

0.586

1M

0.727

0.141

24.1%

6M

0.743

0.157

26.8%

EQ5-D Score

Absolute

Relative(based on Ara

changechangeet al., 2008

totoalgorithm)

baselinebaseline

ComputedTransvenous Pacemaker (TV-PM)

BL

0.577

1M

0.654

0.077

13.1%

6M

0.617

0.039

6.7%

Table S.4.2: EQ-5D index scores derived by mapping SF-36 component scoresshown in Figure S.4.1 using the algorithm by Ara et al, 2008.
At one year and for the remainder of the lifetime, we assumed the long-term EQ5D estimate reported for TV-PM patients at five years (Lopez-Liria et al.) applied
to both strategies, i.e., quality of life was assumed to be identical. For the periods
1 to 6 and 6 to 12 months, utility was modeled assuming a linear relationshipbetween the values reported at respective follow-up points.
In the absence of other utility data that might help to estimate the temporary
disutility associated with an endovascular intracardiac intervention, we looked atrecent data of the UK TAVI trial as a proxy for TC-PM placement. As the data by
Rombach et al. (Analysis of costs and quality of life at one year in the United
Kingdom Transcatheter Aortic Valve Implantation (UK TAVI) Trial, presented at
PCR Valves e-course, 2020) show, transcatheter aortic valve implantation (TAVI)
patients reached their long-term utility as early as two weeks post procedure (theutility at two weeks was approximately the same as the utility observed at 12
months post index treatment). As such, it is safe to assume that the temporary
disutility surrounding the procedure is at most 2 weeks. If we assume adecrement of 0.05 (patient remaining at baseline value) for one week, this59amounts to a QALY decrement of 0.05 * (1/52) =0.001. For TV-PM, we assumed
temporary disutility to be twice as high (a decrement of 0.05 in utility for two
weeks).
For any long-term complications in either TC-PM or TV-PM-treated patients, ouranalysis assumed a temporary reduction of 0.05 in utility for a period of one
month.
The effect of all of these assumptions was tested in sensitivity analyses and, per
results shown in the main paper, had minimal to negligible impact onto the costeffectiveness findings.

60