\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Leadless pacing: also an option for the young?}



\author[1]{Karel Breeman}%
\author[1]{Reinoud E. Knops}%
\author[1]{Fleur Tjong}%
\affil[1]{Amsterdam UMC Locatie AMC}%


\vspace{-1em}



  
  \date{May 24, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


\emph{Editorial accompanying `Implantation of a leadless pacemaker in
young adults'}

\textbf{Leadless pacing: also an option for the young?}

Karel T.N. Breeman, MD MSc\textsuperscript{1,2}, Reinoud E. Knops, MD
PhD\textsuperscript{1,2}, Fleur V.Y. Tjong, MD PhD\textsuperscript{1,2}

\emph{\textsuperscript{1}Amsterdam UMC location AMC, Department of
Cardiology, Amsterdam, The Netherlands}

\emph{\textsuperscript{2}Amsterdam Cardiovascular Sciences, Heart
failure \& arrhythmias, Amsterdam, The Netherlands}

Leadless pacemakers (LPs) were designed to overcome lead- and
pocket-related complications. To date, no randomized clinical trials
have been performed, but observational trials in large patient groups
have demonstrated adequate safety and efficacy up to two years after
implantation(1-3). Hence, LPs are incorporated in the latest guidelines
on pacing therapy and should be considered for selected patients(4).
Young age is currently regarded as an argument against leadless pacing.
On the one hand, this is due to limited data on real-world long-term
battery longevity and replacement strategies. Retrievability of LPs with
a screw-in helix fixation mechanism was acceptable (long-term success
rate \textgreater{}80\%(5)), but reliable data on retrievability of LPs
with a tine-based fixation mechanism is expected in the next years.
Co-implantation is feasible with two LPs, but has not yet been
described\emph{in vivo} with three of more LPs. On the other hand, data
on safety and efficacy in the young is scarce. For instance, the
patients studied in trials were typical single-chamber ventricular
pacemaker recipients, i.e. well over 70 years old. To date, it is
unknown whether the results of those trials also apply to young
patients.

The young may, however, specifically benefit from certain advantages of
leadless pacing. There are less mobility and sports restrictions and the
lack of a pocket is a cosmetic advantage. Further, not only do young
patients have a higher yearly risk of lead fractures, they also have
more remaining years at risk of lead- and pocket-related
complications(6). Hence, the lifetime risk reduction of those
complications with LP therapy is expected to be greater in the young.
Besides, certain young patients may benefit from general LP advantages,
such as patients with an increased infection risk. The lack of
experience and limited data on potential disadvantages in the young
makes adequate weighing of risks and benefits hard. It is important to
unveil those unknowns.

To address this issue, Strick et al. describe an multicenter
observational cohort of 35 patients with a mean age of 34\selectlanguage{ngerman}±8 years (all
18-40 years old) who underwent Micra VR LP implantation between 2015 and
2021 at four university hospitals in France. Patients were included when
the advantages of LP therapy outweighed the current disadvantages
(single-chamber behaviour) and unknowns. The indications were mainly
sinus node dysfunction (23\%), and various degrees of AV block (52\%).
The implantation was successful in all. The endpoints were shown at 6
months and during complete follow-up. At 6 months, the safety endpoint
of no system- or procedure-related major complications was met in 100\%
and the efficacy endpoint (pacing capture threshold \selectlanguage{english}[?]2V and
\textless{}1.5V increase, similar to the Micra LP landmark trial(7)) was
met in 97\%, as one patient had a pacing threshold of 2.75V at
implantation. During complete follow-up of mean 26+-15 months, the safety
endpoint remained 100\% and the efficacy endpoint 94\% as one patient
had a gradual increase in pacing threshold of 1.87V in the year
post-implantation. Further, there was 1 case of pacemaker syndrome in a
patient with only 0.1\% pacing, but this was resolved by lowering the
lower rate. This should be seen as a disadvantage of single-chamber
ventricular pacing in patients without atrial fibrillation rather than a
specific LP problem.

This is one of the first studies regarding the safety and efficacy of LP
therapy in young adults. Because LP therapy in young patients is a rare
phenomenon, the authors have added relevant knowledge by bundling the
cases they treated. Leadless pacing is a vastly different method of
pacing than transvenous pacing, with a different fixation mechanism and
overall morphology. Hence, it is reassuring that no unexpected large
safety or efficacy concerns related to the LP were found.

This study, however, does have important limitations. Foremost, these
findings are observational and not randomized, which makes a direct
comparison of safety and efficacy between leadless and transvenous
pacemakers in the young difficult. However, this is also the case for
all other LP studies and this is the only and best data we have to date.
Further, the sample size was small with only 35 implantations and the
mean follow-up duration was a little over 2 years. Complications that
occur infrequently can be missed by the small sample size and, as the
authors mention, certain unexpected complications may reveal themselves
later than 2 years post-implantation, for example the Nanostim LP
battery problem(8). Lastly, this study does not inform us about the risk
of different replacement strategies, while in fact this is a very
important part of the safety of LPs in younger patients.

Nevertheless, the data presented is encouraging. Previous large LP
studies did not include the presented age group, as the mean age was
approximately 75-80 years with a distribution suggesting very few
patients younger than 50 years(1-3). From this study it seems that the
results of those trials can be extrapolated to younger adults. Compared
to those trials, the complication rate in this study was lower and the
efficacy was similar. The lower complication rate may be partly
explained by the operator learning curve and ongoing improvements in
knowledge, such as a preference for septal placement and the strive for
a minimum number of repositions(9). An observational study including 73
patients \textless{}50 years old with an LP reported results comparable
to the study of Strick et al(10). As mentioned, in the young, the
benefits of LP therapy compared to transvenous pacemakers will likely
manifest itself during long-term follow-up. The younger patients in this
study were not at increased risk of complications compared to older LP
recipients in previous trials. Studies comparing young and old
transvenous pacemaker recipients, though, show mixed results(11, 12).
However, there are fundamental differences in replacement strategies,
and more experience about this topic may change our perspective.

These results may help clinical decision-making by decreasing our lack
of experience. With these results, the risks and benefits of LP therapy
in young adults can be better estimated. Yet, until more data is
available on the real-world battery longevity and optimal replacement
strategy of LPs, in young adults, expected pacing burden should be
considered even more in choosing between leadless and transvenous
pacemakers.

In conclusion, these small-scale results demonstrate no unexpected
safety or efficacy concerns for using LPs in young adults, when
replacements are not considered. This study brings LP therapy closer to
certain younger patients that will specifically benefit from it.

\textbf{References}

1. El-Chami MF, Al-Samadi F, Clementy N, Garweg C, Martinez-Sande JL,
Piccini JP, et al. Updated performance of the Micra transcatheter
pacemaker in the real-world setting: A comparison to the investigational
study and a transvenous historical control. Heart Rhythm.
2018;15(12):1800-7.

2. Piccini JP, El-Chami M, Wherry K, Crossley GH, Kowal RC, Stromberg K,
et al. Contemporaneous Comparison of Outcomes Among Patients Implanted
With a Leadless vs Transvenous Single-Chamber Ventricular Pacemaker.
JAMA Cardiol. 2021.

3. El-Chami MF, Bockstedt L, Longacre C, Higuera L, Stromberg K,
Crossley G, et al. Leadless vs. transvenous single-chamber ventricular
pacing in the Micra CED study: 2-year follow-up. Eur Heart J.
2022;43(12):1207-15.

4. Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash
IM, et al. 2021 ESC Guidelines on cardiac pacing and cardiac
resynchronization therapy. Eur Heart J. 2021;42(35):3427-520.

5. Reddy VY, Knops R, Neuzil P, Exner DV, Beurskens N, Hutson CS, et al.
B-PO01-029 CHRONIC RETRIEVABILITY OF A LEADLESS PACEMAKER: WORLDWIDE
EXPERIENCE OUT TO 7 YEARS. Heart Rhythm. 2021;18(8, Supplement):S62-S3.

6. Shirwaiker A, William J, Mariani JA, Kistler PM, Patel HC,
Voskoboinik A. Long-Term Implications of Pacemaker Insertion in Younger
Adults: A\&\#xa0;Single Centre Experience. Heart, Lung and Circulation.
2022;31(7):993-8.

7. Reynolds D, Duray GZ, Omar R, Soejima K, Neuzil P, Zhang S, et al. A
Leadless Intracardiac Transcatheter Pacing System. N Engl J Med.
2016;374(6):533-41.

8. Lakkireddy D, Knops R, Atwater B, Neuzil P, Ip J, Gonzalez E, et al.
A worldwide experience of the management of battery failures and chronic
device retrieval of the Nanostim leadless pacemaker. Heart Rhythm.
2017;14(12):1756-63.

9. Tjong FVY, Beurskens NEG, Neuzil P, Defaye P, Delnoy PP, Ip J, et al.
The learning curve associated with the implantation of the Nanostim
leadless pacemaker. J Interv Card Electrophysiol. 2018;53(2):239-47.

10. Gulletta S, Schiavone M, Gasperetti A, Breitenstein A, Palmisano P,
Mitacchione G, et al. Peri-procedural and mid-term follow-up age-related
differences in leadless pacemaker implantation: Insights from a
multicenter European registry. International Journal of Cardiology.
2022.

11. Kirkfeldt RE, Johansen JB, Nohr EA, Jorgensen OD, Nielsen JC.
Complications after cardiac implantable electronic device implantations:
an analysis of a complete, nationwide cohort in Denmark. Eur Heart J.
2014;35(18):1186-94.

12. Armaganijan LV, Toff WD, Nielsen JC, Andersen HR, Connolly SJ,
Ellenbogen KA, et al. Are elderly patients at increased risk of
complications following pacemaker implantation? A meta-analysis of
randomized trials. Pacing Clin Electrophysiol. 2012;35(2):131-4.

\selectlanguage{english}
\FloatBarrier
\end{document}

