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\begin{document}

\title{Paclitaxel Coated Balloon Fibroplasty: A more effective treatment of
chronic symptomatic lead-related venous obstruction?}



\author[1]{Omar Yacob}%
\author[1]{Vijaywant  Brar}%
\author[1]{Arooje Towheed}%
\author[1]{Cyrus Hadadi}%
\author[1]{Susan O'Donoghue}%
\author[1]{Seth Worley}%
\affil[1]{MedStar Washington Hospital Center}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\selectlanguage{english}
\begin{abstract}
Subclavian venous obstruction is a common complication after cardiac
device placement. Patients typically remain asymptomatic but at times
may present with acute symptoms due to thrombus formation immediately
after device placement or years later, due to chronic obstruction, with
pain and swelling. Various techniques have been attempted to resolve
symptoms in patients with chronic lead-related subclavian obstruction
but are associated with a high recurrence of restenosis. Drug coated
balloons (DCB) have been used subsequently after pre-dilation with
high-pressure balloons, of the stenosed region, in patients with
arteriovenous fistula obstruction, and have shown promising results. We
discuss the utilization of DCB in our patient with chronic subclavian
obstruction due to a permanent pacemaker lead.%
\end{abstract}%



\sloppy


\textbf{Title:} Paclitaxel Coated Balloon Fibroplasty: A more effective
treatment of chronic symptomatic lead related venous obstruction?

\textbf{Author:} Omar Yacob MD \textsuperscript{1a}, Vijaywant Brar
MD\textsuperscript{2a}, Arooge Towheed MD \textsuperscript{2}, Cyrus
Hadadi MD\textsuperscript{2}, Susan O'Donoghue MD \textsuperscript{2},
Seth Worley MD \textsuperscript{2}

\textbf{Affiliation:}

\textsuperscript{1} MedStar Washington Hospital Center -- Internal
Medicine

\textsuperscript{2} MedStar Washington Hospital Center -- Division of
Cardiac Electrophysiology

\textsuperscript{a} Both authors contributed equally to the manuscript

\textbf{Funding:} None

\textbf{Disclosure:} None

\textbf{Corresponding Author:}

Omar Yacob, MD

MedStar Washington Hospital Center

Electrophysiology suite, Floor 5, 110 Irving St NW, Washington DC,
20010(USA)

omaryacob07@gmail.com

omar.yacob@medstar.net

\textbf{Abbreviations:}

\begin{itemize}
\tightlist
\item
  Arteriovenous Fistula -- AVF
\item
  Biventricular Permanent Pacemaker -- BiV-PPM
\item
  Central Venous Catheter - CVC
\item
  End Stage Renal Disease -- ESRD
\item
  Drug Coated Balloon- DCB
\item
  Paclitaxel Coated Balloons- PCB
\item
  Superior Vena Cava -- SVC
\end{itemize}

\textbf{Key teaching points:}

\begin{itemize}
\tightlist
\item
  Lead related chronic fibrotic venous obstruction can occasionally be
  highly symptomatic
\item
  Fibroplasty is a safe option that provides immediate relief however
  symptoms frequently recur presumably due to restenosis
\item
  Drug coated balloons reduce restenosis in dialysis fistulas and may
  improve the long-term results in symptomatic patients with lead
  related chronic obstruction
\end{itemize}

\textbf{Introduction}

Upper extremity venous occlusion is a common complication encountered
after transvenous lead placement that presents either acutely or
chronically. Thrombus formation presents acutely with a painful, swollen
upper extremity. Treatment can include catheter directed thrombolytics
or anticoagulants/antiplatelet medications in an attempt to reduce
thrombus burden and allow time for collateral formation (1)(2). Patients
with acute symptoms that fail to resolve have undergone balloon dilation
or subsequent stenting even though both techniques are associated with
high rate of restenosis. Chronic lead related irritation of the venous
endothelium results in neointimal hyperplasia with fibrosis. In many
patients the lead related fibrosis eventually results in venous
obstruction. Patients typically remain asymptomatic, due to formation of
collateral circulation as fibrosis ensues (3) and the obstruction is
typically discovered at the time of lead addition or replacement. Those
who present with chronic symptoms presumably related to limited
collaterals are sometimes managed with balloon dilation although
symptoms quickly recur. The addition of stenting to balloon dilation has
similar results in jailing and potential damage to the leads. The
management of chronic lead related symptomatic venous obstruction is not
well established. Herein we discuss the addition a paclitaxel-coated
balloon (PCB) to high pressure balloon dilation as a potential way to
improve the results in chronic symptomatic lead related venous
obstruction

\textbf{Case repor} t

A 54-year-old woman with history of complete heart block status post
biventricular permanent pacemaker (BiV-PPM) implantation, three years
prior, presented with persistent left arm pain and swelling that
resulted in limitations of her daily activities. Physical examination
revealed edema above the clavicle, the arm and the hand. The remainder
of the physical examination was unremarkable. Subclavian venogram
revealed total occlusion of her left subclavian vein. Recognizing the
limitations of balloon dilation alone and the risk and uncertain results
of lead extraction followed by stenting an alternative strategy was
sought. Given the favorable results of adding a drug coated balloon to
high pressure balloon dilation in patients with stenotic dialysis
fistulas we decided to add the drug coted balloon to high pressure
balloon dilation.

\emph{Procedural Technique:}

The procedure was performed, under general anesthesia in the
electrophysiology lab. A left arm venogram was performed, which
demonstrated total occlusion of the left subclavian vein with collateral
formation (Figure: 1).

\begin{itemize}
\tightlist
\item
  The left axillary vein was cannulated using a 21-gauge micro puncture
  needle distal to the occlusion
\item
  A 0.018 - inch micro-puncture wire was advanced to the left subclavian
  vein. The micro-puncture wire was unsuccessful in crossing the
  occlusion so further advanced techniques (4) were applied to cross the
  lesion
\item
  After crossing the lesion, subclavian fibroplasty was performed using
  a 4-mm non-compliant balloon from the superior vena cava-right atrium
  junction to the device pocket
\item
  Multiple sites of severe stenosis of the left subclavian vein were
  noted
\item
  After pre-dilatation, a PCB (7 X 40 mm) was advanced to the site of
  initial total occlusion and the balloon was inflated for 30 seconds.
\item
  The balloon was withdrawn \& hemostasis achieved
\end{itemize}

\emph{Post-operative Course:}

The procedure was successfully performed in approximately 1 hour with no
associated complications. Post-operatively the patient reported
significant improvement in symptoms, with mild pain over the incision
site. There was no damage to the leads \& the patient was discharged the
following day after satisfactory pacing checks and chest X-ray.

\textbf{Discussion}

The current approach to chronic symptomatic lead related venous
obstruction is unsatisfactory. Balloon dilation, to relieve the
obstruction, results in symptom recurrence in a short duration and
reintervention is required. Stenting without prior lead extraction is
not considered to be an option. Even when leads are extracted, and
stents deployed the results are not well defined. Given the apparent
similarity between dilating a dialysis fistula and lead related venous
obstruction the addition of a drug coated balloon to high pressure
balloon dilation was considered a favorable option. Subclavian stenosis
has been observed in approximately 15\% of patients prior to device
placement and increases up to 50\% after transvenous manipulation (5).
Although many factors are involved in the development of vascular
occlusion the two primary processes involved are: thrombus formation and
neointimal hyperplasia with subsequent fibrosis. In the acute settings
thrombus formation around the lead can lead to acute symptoms for which
anticoagulative agents are often used to reduce the risk of embolic
complications while collaterals develop. Lead placement also irritates
the venous endothelium inducing an inflammatory cascade leading to
excessive proliferation of the connective tissue resulting in a fibrotic
occlusion (5).

Multiple strategies have been attempted for patients with chronic
symptomatic lead related venous obstruction. Surgical approaches
predominated in the 1990s until the advent of percutaneous techniques
and subsequent introduction of balloon dilation. Riley et al (6)
conducted the first retrospective pooled analysis of 104 patients with
symptomatic lead associated superior vena cava syndrome and reported
that the most common treatment approach superior with the lowest rate of
restenosis. However stenting results in compression of the lead between
the stent and the wall of the vein referred to as `jailing' of the lead.
`Jailing' can compromise lead integrity and/or result in fracture.
Jailing also complicates lead removal in the cases of infection. The
current Heart Rhythm Society expert consensus is to extract transvenous
leads before stenting, to avoid their entrapment (7).

In the Mayo clinic (8) six patients identified with lead associated
symptomatic superior vena syndrome had stent implantation performed
after successful lead removal followed by reimplantation of the leads
however some patients required reintervention. Anticoagulation and
antiplatelet therapy have also been utilized in chronic occlusions but
have produced conflicting results, with majority studies reporting that
anticoagulant or antiplatelet use was~not associated with a decreased
incidence of venous stenosis or thrombosis (2)(9) due to their
ineffectiveness on chronic fibrotic lesions, that often exist in these
patients, rather than atherosclerotic lesions (6). In a study done at
Cleveland Clinic (10) 861 device leads were histologically examined
after extraction, in patients with leads for \textgreater{} 1 year, and
examination of tissue demonstrated dense fibrous tissue with the
presence of calcification. From these histological findings the nature
of the tissue involved can help guide further treatment.

Worley et al (11) performed balloon fibroplasty in 371 asymptomatic
patients with significant subclavian stenosis to facilitate lead
revision or upgrade demonstrating the safety and practicality of
subclavian balloon fibroplasty, using non-complaint balloons. Balloon
dilation is the standard treatment in end stage renal disease (ESRD)
patients with stenosis of their arteriovenous fistulas (AVF). Compared
to standard non-compliant balloons (Rate Burst Pressure 20 ATM)
ultra-noncompliant high-pressure balloons (Rate Burst Pressure 30 ATM)
improve fistula patency. However even with high pressure balloons
(12)(13) durability was limited thus stenting was added in an attempt to
prolong patency. However even stents for AVF were associated with a high
risk of restenosis. Due to the meager long terms successes of balloon
angioplasty and vascular stents Kitrou et al (14) and Lookstein et al
(15) studied the effect of PCBs on dysfunctional AVF. Because of their
low rated burst pressure, PCBs, required pre-dilation with high pressure
balloons to dilate the hard stenotic and rigid lesions in the
vasculature. Adding PCB demonstrated superiority to both non-compliant
balloons and high-pressure balloons in maintaining target vessel patency
at 6 months with non-inferior primary safety end points. PCBs also
significantly extended the event-free period for the AVF circuit.
Presumably, deliverance of local drug-delivery device inhibits the
process of neointimal hyperplasia and enabled a longer intervention-free
period.

The stenosis observed in an AVF is due to endothelial irritation leading
to tissue proliferation and subsequent fibrosis. It is likely that the
fibrotic occlusion associated with chronic leads is similar to that
observed in patients with AVF. Our report describes the first addition
of DCB for subclavian fibroplasty in a symptomatic patient with chronic
transvenous leads. Because DCBs have been proven safe and effective in
maintaining patency of stenotic dialysis fistulas (16)(17) they may help
improve long term patency in symptomatic lead related obstruction. When
fibroplasty is performed for access in asymptomatic patients with
chronic leads the vein quickly reocclude. The addition of a PCB balloon
may be useful in maintaining patency.

To know for certain whether PCB improve patency in chronic symptomatic
patients with lead related obstruction requires a randomized trial.
However, given the limited alternatives it is important to consider the
addition of a PCB to balloon dilation as an option for patients with
symptomatic venous obstruction before resorting to extraction and
stenting. PCB may also prove useful in maintaining patency in
asymptomatic patients requiring fibroplasty for lead replacement or
upgrade.

\textbf{Acknowledgments}

Dr. Worley receives has in the past received compensation in various
forms from Medtronic. He currently receives compensation in various
forms including royalties from Merit Medical, Pressure Products,
Guidant, and St. Jude Medical. No financial support was provided for the
creation of this case report.

\textbf{Reference:}

1. Rooden CJV, Molhoek SG, Rosendaal FR, Schalij MJ, Meinders AE,
Huisman MV. Incidence and Risk Factors of Early Venous Thrombosis
Associated with Permanent Pacemaker Leads. J Cardiovasc Electrophysiol.
2004;15(11):1258--62.

2. Abu-El-Haija Basil, Bhave Prashant D., Campbell Dwayne N., Mazur
Alexander, Hodgson-Zingman Denice M., Cotarlan Vlad, et al. Venous
Stenosis After Transvenous Lead Placement: A Study of Outcomes and Risk
Factors in 212 Consecutive Patients. J Am Heart Assoc. 4(8):e001878.

3. Stoney WS, Addlestone RB, Alford WC, Burrus GR, Frist RA, Thomas CS.
The Incidence of Venous Thrombosis Following Long-Term Transvenous
Pacing. :5.

4. Zou F, Brar V, Worley SJ. Interventional device implantation, Part I:
Basic techniques to avoid complications: A hands-on approach. J
Cardiovasc Electrophysiol. 2020 Sep 18;

5. Spittell PC, Hayes DL. Venous Complications After Insertion of a
Transvenous Pacemaker. Mayo Clin Proc. 1992 Mar 1;67(3):258--65.

6. Riley RF, Petersen SE, Ferguson JD, Bashir Y. Managing superior vena
cava syndrome as a complication of pacemaker implantation: a pooled
analysis of clinical practice. Pacing Clin Electrophysiol PACE. 2010
Apr;33(4):420--5.

7. Bongiorni MG, Burri H, Deharo JC, Starck C, Kennergren C, Saghy L, et
al. 2018 EHRA expert consensus statement on lead extraction:
recommendations on definitions, endpoints, research trial design, and
data collection requirements for clinical scientific studies and
registries: endorsed by APHRS/HRS/LAHRS. EP Eur. 2018 Jul
1;20(7):1217--1217.

8. Fu H-X, Huang X-M, Zhong L, Osborn MJ, Bjarnason H, Mulpuru S, et al.
Outcome and Management of Pacemaker-Induced Superior Vena Cava Syndrome:
PACEMAKER-INDUCED SUPERIOR VENA CAVA SYNDROME. Pacing Clin
Electrophysiol. 2014 Nov;37(11):1470--6.

9. Goto Y, Abe T, Sekine S, Sakurada T. Long-Term Thrombosis after
Transvenous Permanent Pacemaker Implantation. Pacing Clin
Electrophysiol. 1998;21(6):1192--5.

10. Tarakji KG, Saliba W, Markabawi D, Rodriguez ER, Krauthammer Y,
Brunner MP, et al. Unrecognized venous injuries after cardiac
implantable electronic device transvenous lead extraction. Heart Rhythm.
2018 Mar;15(3):318--25.

11. Worley SJ, Gohn DC, Pulliam RW, Raifsnider MA, Ebersole BI, Tuzi J.
Subclavian venoplasty by the implanting physicians in 373 patients over
11 years. Heart Rhythm. 2011 Apr 1;8(4):526--33.

12. Beathard GA. The Treatment of Vascular Access Graft Dysfunction: A
Nephrologist's View And Experience. Adv Ren Replace Ther. 1994 Jul
1;1(2):131--47.

13. Buri\selectlanguage{ngerman}ánková E, Köcher M, Bachleda P, Utíkal P, Kojecký Z, \selectlanguage{polish}Č\selectlanguage{english}ern\selectlanguage{ngerman}á M, et
al. Endovascular treatment of central venous stenoses in patients with
dialysis shunts. Biomed Pap. 2003 Dec 1;147(2):203--6.

14. Kitrou PM, Papadimatos P, Spiliopoulos S, Katsanos K, Christeas N,
Brountzos E, et al. Paclitaxel-Coated Balloons for the Treatment of
Symptomatic Central Venous Stenosis in Dialysis Access: Results from a
Randomized Controlled Trial. J Vasc Interv Radiol. 2017
Jun;28(6):811--7.

15. Lookstein RA, Haruguchi H, Ouriel K, Weinberg I, Lei L, Cihlar S, et
al. Drug-Coated Balloons for Dysfunctional Dialysis Arteriovenous
Fistulas. N Engl J Med 2020 Aug 19 doi/10.1056/NEJMoa1914617

16. Massmann A, Fries P, Obst-Gleditsch K, Minko P, Shayesteh-Kheslat R,
Buecker A. Paclitaxel-Coated Balloon Angioplasty for Symptomatic Central
Vein Restenosis in Patients With Hemodialysis Fistulas. J Endovasc Ther.
2015 Feb 1;22(1):74--9.

17. Kennedy SA, Mafeld S, Baerlocher MO, Jaberi A, Rajan DK. Drug-Coated
Balloon Angioplasty in Hemodialysis Circuits: A Systematic Review and
Meta-Analysis. J Vasc Interv Radiol. 2019 Apr 1;30(4):483-494.e1.\selectlanguage{english}
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