1 DIPARTIMENTO DI RICERCA TRASLAZIONALE E DELLE NUOVE
TECNOLOGIE IN MEDICINA E CHIRURGIA
Corso di Laurea Magistrale in Medicina e Chirurgia
Tesi di Laurea Magistrale
“Risk scores to predict adverse events in cardiac lead extraction: literature
analysis and clinical application”
RELATORE: D.ssa Maria Grazia Bongiorni
CORRELATORE: Dr. Luca Segreti CANDIDATO Giulia Bernini Anno Accademico 2017/2018
2
Summary
Introducing cardiovascular implantable electronic devices (CIEDs) pag 4
Indications for CIEDs and lead extraction pag 8
TLE using a single sheath mechanical dilatation and multiple venous approaches:
an established, safe and effective mode of lead extraction pag 16
A new bidirectional mechanical lead extraction sheath pag 22
Hybrid minimally invasive lead extraction pag 24
The need of a risk score related to lead extraction pag 27
Predictors of adverse events in cardiac lead extraction pag 32
Clinical related risk factors pag 32
Device related risk factors pag 35
The ELECTRa Registry pag 38
Multiparametric risk score in literature pag 40
Brunner normogram risk score pag 40
Fu risk score pag 41
IKAR score pag 42
Bontempi risk score pag 42
Mazzone risk score pag 44
Advantages and limits of risk scores pag 50
Our experience in TLE risk scores: a retrospective study from 2009 to 2017 pag 53
Introduction to the study pag 53
Aim of the study pag 54
Methods pag 54
3
Results pag 56
Basal results pag 56
Fu risk score pag 68
Brunner risk score pag 70
IKAR score pag 74
LED index pag 77
Mazzone stepwise approach pag 79
Predictors for a new risk score pag 82
Discussion pag 87
Conclusion pag 90
Greetings pag 92
4
1. Introduction
1.1 Introducing cardiovascular implantable electronic devices (CIEDs)
In the past sixty years, CIEDs became an important therapeutic aid for patients
affected by cardiovascular diseases as bradycardia, tachycardia and heart failure,
which represents the first cause of hospitalization in population over 65-years.
Nowadays, we have two different kind of
CIEDs:
- Pacemakers (PM): is defined as an
electronic device implanted in the body
to regulate the heart beat. The PM is not
able to defibrillate the heart delivering
shocks. The PM delivers electrical
stimuli over leads with electrodes in
contact with the heart1.
Pace-makers can be single or double chamber; single chambers PM can be
classified as “ventricular asynchronous pacemaker” and “ventricular inhibited pacemaker”.
The ventricular asynchronous PM generates stimuli without relationship to the
spontaneous rhythm. The competitive stimuli will capture the ventricle only when
they fall outside the absolute refractory period of the ventricle that follows
spontaneous beats. This ventricular asynchronous pacemaker is now obsolete and
5
A ventricular inhibited (VVI) pacemaker senses the intracardiac ventricular
depolarization or electrogram which is recorded by measuring the potential
difference between the two electrodes (anode and cathode) used for pacing.
The sensing function is important in order to avoid the competition between the
PM and the intrinsic rhythm.
Dual chamber pacemakers can be classified as AV sequential (DVI) mode (now
no more used), DDI mode and VDD mode.
The DDI mode exhibits a constant ventricular rate; in the VDD mode, the atrial
output is turned off.
DDD pacemaker mode provide atrial and ventricular sensing and/or pacing,
depending on the programmed rate and on the spontaneous activity of atrial and
ventricular chamber.
The ability of the pacemaker to provide incremental rate pacing with physical
activity (accelerometer sensors) and or physiological requirements (sensors of
ventilation) of the patient is defined by the – R suffix.
- Implantable Cardioverter defibrillators (ICD): is defined as an electronic device
implanted in the body in order to protect against high ventricular rates. It is
designed to defibrillate the heart by delivering high voltage shocks or to stop
malignant tachycardias by antitachycardia pacing (short burst of rapid pacing
6
ICD transvenous leads contains either one or two shocking coils. Both these types
use a distal coil close to the lead tip for the right ventricle (RV) positioning.
The dual-coil lead, instead, has also a proximal coil located in the superior vena
cava (SVC) or in the subclavian vein.
Both single and dual coil defibrillation leads come with active or passive fixation.
ICDs leads use only a bipolar configuration for sensing: however, there are two
types of bipolar configuration: “integrated bipolar configuration” and “true bipolar configuration”.
In order to pace and sense, an integrated bipolar configurations connects the lead
tip and the distal defibrillation coil whereas a true bipolar configuration utilizes
the tip and an additional ring electrode.
True bipolar leads provide the best sensing and pacing performance and are less
7
The integrated configuration may be more favourable for defibrillating because of
the distal coil which can be mounted closer to the tip and hence closer to the RV
myocardium.
- ICD-CRT: this is a particular device implanted in patients who received the
cardiac resynchronization therapy. The CRT provides for the implantation of
biventricular pacing (left ventricular and right ventricular) and it is the established
therapy for patients with dilated cardiomyopathy (defined as a severe systolic LV
dysfunction on the basis of ischemic or not ischemic etiology) and congestive
heart failure (class III-IV NYHA) associated with major left-sided intraventricular
conduction delay such as a left side branch block.
The use of CRT without ICD should be consider in patients with a life expectation
survival less than 1 year and in health care logistical constrains and cost
considerations.
The US Guidelines for CRT includes medically refractory symptomatic NYHA
class III or IV heart failure, patients with idiopatic or post-ischemic dilated
cardiomyopathy, QRS > 130 ms, LV end-diastolic diameter > 55 mm and LVEF <
35%.
The European Guidelines are similar, except for the QRS > 120 ms instead of 130
ms.
The CRT therapy improves the cardiac efficiency by restoring the near-normal LV
contraction pattern. This translate into beneficial acute and long-term
hemodynamic effects by virtue of more coordinated and efficient LV contraction
8
1.2 Indications for CIEDs and leads extraction3
1.2.1 Leads’ failure
According to the 2017 Heart Rhythm Society Expert Consensus Statement on
Cardiovascular Implantable Electronic Device Lead Management and Extraction, over
1.2 – 1.4 million CIEDs are implanted annually worldwide: for that reason, questions
about lead management arise in several situations such as changes in patients’ clinical
conditions, non-functional leads, infections and in case of the presence of a lead
interfere with patients’ optimal treatment.
The integrity and reliability of CIEDs’ leads are important for the proper function of these devices and their capacity of delivering a life-sustaining treatment.
The leads must survive the hostile biological environment of the human host and
retain electrical integrity and chemical inertia while enduring repetitive mechanical
stress with million of cardiac cycle each year.
Although improving lead design and performance have been the target of
cardiovascular scientific research, CIEDs leads continue occasionally fail and the
failure can be related with adverse clinical outcome.
Lead failure can represent the breakdown of any of the lead components such as
insulation, conductors, connectors, terminal pins, electrodes and coils.
Clinical consequences depend on the failure mode and can lead to the system’s
inability to deliver appropriate therapy or to the delivery of inappropriate and
potentially harmful therapy.
Former studies have established a better overall survival rates of pacing leads
comparing with ICD leads. ICD leads, despite technological advances, continue to
9
The lead failure modes are pace-sense malfunction and shock component malfunction,
with the former accounting for the clear majority of diagnosed lead failures in clinical
practice.
In pace-sense circuits, conductor failure or insulation breach typically present as
oversensing of rapid, non-physiological signals, resulting in inappropriate shocks or
pacing inhibition.
Through past years, the common presentation of lead failure was inappropriate shocks
but, nowadays, due to device that can diagnose malfunction, detecting short intervals
and change of impedance, an increasing number of patients in recent years are
presenting with lead alerts, allowing early recognition of lead failure before the onset
of adverse clinical events.
Despite the progress in development of CIEDs, patients can still present with multiple
shocks because fracture might only become apparent after high-voltage therapy.
The malfunctions typically present with shock impedance change and, less commonly,
as failed defibrillation or in association with co-exsisting pace-sense failures.
The introduction of remote monitoring and enhanced lead diagnostics will likely
improve the early recognition of shock-component malfunction.
Diagnosis of leads’ failure is based on device electrogram (EGM) analysis: the most common observations in leads’ failure is oversensing.
It’s important to distinguish lead-failure related oversensing from other sources, such as electromagnetic interference, myopotentials, P or T-wave oversensing, R-wave
double counting and lead-lead interactions.
The typical characteristics of conductor-fracture EGMs are signals that are:
10
- High variable (amplitude, morphology, frequency);
- Not recorded on high voltage or shock channel.
The indication for lead extraction in patients with lead and/or CIED failure can be
challenging for the clinicians.
Rijal et al., found no difference in outcome between the group in which sterile
malfunctioning lead were extracted and the group with sterile and malfunctioning
abandoned pacemaker and defibrillator leads7.
A recent retrospective study compared efficacy and safety of TLE based on the
presence or the absence of abandoned leads. Rates of complete procedure success,
procedural complication and long-term survival are similar in the two groups, although
abandoned leads were associated with increased procedural complexity, including
higher rate of bailout femoral extraction8.
However, an early extraction could potentially decrease the risk of vascular disease
and infection and avoid a potential more challenging future extraction procedure.
In addition, higher number of leads is associated with increased adherences and
11 1.2.2 Infections
With the increase in CIED clinical applications for bradycardia, tachyarrhytmia and
heart failure, CIED’s infections has increased in cardiac disease management.
Former studies10 have established the increase of infections through years and the
higher incidence in patients ICD-carriers comparing with patients PM-carriers.
Relying on these studies, it’s important to develop effective means for preventing
device infection and early diagnosis are therefore important in reducing the mortality,
morbility and medical cost related to CIED infection.
A CIED infection is defined by the 2018 EHRA Consensus Document11 as:
- Isolated generator pocket infection: localized erythema, swelling, pain,
tenderness, warmth or drainage with negative blood cultures. This entity should be
differentiated from the superficial incisional infection, which involve only skin or
subcutaneous tissue without communication with the pocket and, for that reason, it
may not require the CIED extraction.
- Isolated pocket erosion: device and/or leads are through the skin, with exposure of
the generator or leads, with or without local signs of infection. Erosion is,
however, indicative of infection. Blood cultures are negative and the majority of
these patients have no symptoms.
- Bacteremia: positive blood cultures with or without systemic infection symptoms
and signs.
- Pocket site infection with bacteremia: local infection signs and positive blood
cultures.
12
- Pocket site infection with lead/valvular endocarditis: local signs and positive
blood cultures and lead or valvular vegetations
- CIED endocarditis without pocket infection: positive blood cultures and lead or
valvular vegetations. In order to define CIED endocarditis, it may be useful to
consider not only the modified Duke Criteria, but also additional criteria may be
considered.
These additional criteria are: positive culture on extracted lead in case of negative
blood culture, presence of the lead vegetations and abnormal metabolic activity
around the CIED generator and/or lead detected by the F-fluorodeoxyglucose PET
o PET/CT.
- Occult bacteraemia with probable CIED infection: absence of alternative source
resolves after CIED extraction.
- Situations in which CIED infection is not certain: impending exteriorization,
isolated left heart valvular endocarditis in a patient with CIED
- Superficial incisional infection: involves only skin and subcutaneous tissue of the
incision, not to the deep soft-tissue of the incision.
Clinical presentation of CIED or lead infection
The device pocket can be infected at the time of implantation, at replacement or
during the following surgical manipulation of the pocket.
A pocket infection manifests with local inflammatory changes like pocket erythema,
13
Patients might present with systemic symptoms as fever, chills, malaise, fatigue or
anorexia: these patients present with primary bloodstream infection. However, some
patients with CIED lead vegetation do not have systemic signs and symptoms.
The most common bacteria involved in CIED and lead infections are: staphylococcus
aureus, staphylococchi coagulase-negative, streptococcus pneumoniae, Klebsiella pneumoniae, Serratia Marcescens.
Diagnosis of CIED and lead infections
Diagnosis of CIED and lead infection is based on:
- Blood and device pocket culture: at least two sets of blood culture should be
obtained before starting an empirical antimicrobial therapy in patients with
suspected CIED infection. Blood cultures should include both aerobic and
anaerobic bacterial cultures.
Device pocket swabs are useful to identify the causative organism and support the
diagnosis of CIED infection. When a CIED infection is suspected, a percutaneous
pocket aspiration should be carefully considered because it has a low diagnostic
yield and there’s a potential risk in introducing microorganism into the pocket, causing an infection.
- Imaging diagnosis: Trans-esophageal echocardiography (TEE) is useful in order
to identify a CIED-related endocarditis and/or a lead infection. TEE is preferred
than transthoracic echocardiography because of his higher sensibility.
TEE can be considered for all patients who have documented or suspected
14
When the diagnosis of CIED pocket or lead infection is doubtful, a F-FDG
PET/TC can be considered to help the diagnosis.
In case of CIED infection, a complete device removal is recommended because it’s
associated with a better outcome12,13: an early diagnosed infection is associated with a
lower risk of in-hospital mortality.
Even if the presence of infection was not related directly with failed extraction and
major complications, it was associated with a poor long-term prognosis with 1-year
mortality of 13,2-20,2%141516.
On the other hand, it’s important to underline that a worse prognosis is associated with CIED infection relapse/recurrence after TLE. Diemberger et al., found three
factors correlating to death and/or CIED infection relapse/recurrence: a closed CIED
pocket, presence of ghost at post-TLE transesophageal echocardiography and renal
failure17.
15 1.2.3 Other indications for lead extraction
The 2018 EHRA Consensus Conference on Lead Extraction has listed other
indications for lead extraction, such as:
- Abandoned functional leads
- Lead related complications: leads may be functional but cause complications for
which extraction may be indicated. Situations that can occur are, for example,
thromboembolic events, superior vena cava syndrome, arrhythmias, perforation,
lead-lead interaction.
- Venous access issues: in particular, the development of stenosis that may hinder
additional lead implantation. There are a number of different management
strategies, like tunnelling a contra-lateral lead across the chest, venoplasty or lead
extraction to provide a channel through which new leads can be implanted.
- Access to magnetic resonance imaging: this topic is controversial because MRI
can be safely performed in patients implanted with non-conditional CIEDs but
abandoned or dysfunctional leads are considered contraindications. For that
reason, extraction of these leads can be performed after an accurate assessment of
risks and benefits.
- Chronic Pain: some patients have chronic pain in the site of lead implantation,
16 1.3 Transvenous removal of pacing and implantable cardiac defibrillating leads using a single sheath mechanical dilatation and multiple venous approaches: an
estabilished, safe and effective mode of lead-extraction18.
Recently, the use of implanted devices for cardiac pacing and defibrillation has
significantly increased: for that reason, also device-related complications have
increased and consequently, the need of removal too.
Over the past two decades, extraction techniques have evolved from simple traction
to extraction with dilators and powered sheats with a reported success rate over 95%.
By the way, percutaneous lead removal is still associated with a small but significant
percentage of complications, like procedural failure, morbidity and mortality.
As known, fibrotic tissue develops over time and cause the entrapment of the leads in
the veins and in the cardiac chambers: for that reason, conventional lead-extraction
techniques are sometimes not able to overcome these procedural difficulties causing
failure or/and complications.
According to these observations, Bongiorni and her group improved here in Pisa a
new approach of pacing and defibrillating leads extractions: this is based on a
modified percutaneous mechanical dilatation technique to improve the success rate
17
The procedure is performed in the cardiac electrophysiology laboratory, after have
obtained an informed consent by the patient, with cardiothoracic surgery standby
available. The patient must remain in a fasting state.
Before the extraction procedures, defibrillations pads are applied on the patient,
transvenous temporary pacing is placed and the patient is monitored by an invasive
arterial blood pressure measurement and pulse oximetry monitoring.
Once the patient was prepared, draped and sedated, the pulse generator pocket was
opened and the leads freed by electrocauthery from their adhesions down to the
venous insertion site or as far as possible.
The leads were cut 10-15 cm out of the venous entry site.
A stiff normal stylet, of appropriate length for the lead, was introduced into the lead
body with its tip as close as possible to the lead tip in order to stiffen it.
One or two, depending of the presence of unipolar or bipolar leads, ties of silk suture
18
Once the lead was freed and secured, gentle manual traction was performed in order
to remove the lead: when manual traction failed to remove the lead, Bongiorni
proposed to use a modified percutaneous dilatation technique.
If the leads were exposed through tributary veins of the superior vena cava system
(cephalic, subclavian, jugular vein), the venous entry site approach (VEA) was the
favourite technique.
Dilatation was started by using a single sheath with progressive wider inner diameter,
as close as possible to the lead body diameter.
Traction was maintained on the silk ties while the sheath was advanced under
fluoroscopy guide following the lead course and trying to avoid any angle. The
sheath is been advanced by rotating alternatively clockwise and counter-clockwise
with two or three turns.
While dilating, the operator perform a smooth traction in order to keep the lead in
tension but otherwise trying to avoid myocardial wall invagination or coil
lengthening and lead damage.
If the sheath’s advancement was difficult, it was taken back for a few millimetres and dilatation restarted. If unsuccessful, the dilator was changed to a new one of larger
diameter.
At the moment the tip was reached, while doing a mild traction and maintaining the
stylet inserted till the tip, dilatation was performed by continuous clock-wise and
counter-clockwise rotation of the sheath for dissect the distal binding site;
contemporary, the operator is checking by fluoroscopy that the sheath didn’t
19
Once the tip was freed, the sheaths and the leads can be removed through the
insertion vein.
When the lead is freed by traction and dilatation before the sheath reached the distal
part of the lead, but the retrieval was impossible because of unablated binding sites, a
transfemoral approach was used to grasp the lead tip and to remove it, trying to slip it
through the binding site.
If, despite the use of larger sheats, dilatation is stopped at any binding site for almost
five minutes, or if the dilatation was judged too risky, it’s preferable use an internal
transjugular approach (ITA).
In order to perform ITA, a transfemoral approach is necessary as a crossover step.
The transfemoral workstation, provided with a remote control tip deflecting wire,
was introduced through the right femoral vein and is advanced till the right atrium.
Firstly, the operator has to check the possibility of slipping the lead into the blood
flow: using the tip deflecting wire, the lead was grasped at the level of the right
atrium or superior vena cava below the point where dilatation stopped; then, using a
slight traction, the possibility of slipping the lead and make it free-floating was
valued.
If the lead cannot be slipped through, the operator have to check the possibility of
grasping the lead above the binding site and making it free floating.
At this point, the right internal jugular vein was cannulated and an introducer was
advanced through the jugular vein, the proximal end of the lead was taken back from
the jugular vein and exposed, after that, a percutaneous procedure for exposed leads
using dilating sheaths was performed.
20
- Case A: presence of free floating leads with free tips (for example: leads
migrated into the venous system, distal fixation site detached)
An intravascular tool was used to grasp the lead and, once the lead is grabbed, the
operator has to value the possibility of slipping the lead through the binding sites
in the upper course.
If the lead was free, it was taken back by traction into the workstation and
removed; while, in presence of adherences, dilatation was performed using the
workstation.
- Case B: presence of a free floating leads with anchored tips (for example: leads
migrated into the venous system, with the proximal end not accessible in the pacemaker pocket and tip fixed in the heart).
The ITA is the first choice approach. The possibility to move the lead was
checked by intravascular tools introduced using the TFA.
The lead was grasped by the tip deflecting wire and slipped, when possible,
through the adherences.
An intravascular tool was advanced via the jugular vein and the proximal end of
the lead was grasped and then exposed through the jugular vein; at this point, a
21 1.4 Complications of the new approach of lead extraction
It is important to distinguish two types of perioperative complications:
- Major complications are defined as complications that can imply the death or
severe morbility. Some major complications that occur in the patients enrolled in
the Bongiorni’s study about this new approach of lead extraction are: cardiac tamponade, pericardial drainage needed, surgical repair, hemothorax,
dislodgment of a functioning pacing lead or death.
- Minor complications are defined as complications that not require interventions.
Into this group are: pericardial effusion, thrombosis of the implant vein,
pulmonary embolism, arrhythmias requiring cardioversion, hematoma in the
22 1.5 A new bidirectional mechanical lead extraction sheath: safety and efficacy in
chronically implanted leads19
Figura 1: successfull extraction of an ICD lead using the mechanical rotation sheath.
As already mentioned, chronically implanted leads develop fibrous adhesions around
cardiac and vascular structures and for that reason, during TLE, is required the use of
mechanical sheaths, laser sheaths or electrosurgical dissection sheaths.
Recently, a rotational mechanical extraction device shows to be an effective and safe
tool for extracting implanted leads.
LE was performed following a stepwise approach: after an unsuccessful manual
traction, the new Evolution rotational sheath was used.
The rotation mechanism of the sheath allow movement along the lead body and cut
the fibrous attachments using a distal metal tip.
This device has a bi-directional rotational mechanism that prevents lead wrapping; it
has also a less aggressive tip that may reduce the risk of vascular and other leads
damage.
In Mazzone’s study, patients who underwent this new approach had no major complications and there were no deaths.
23
Some minor complications occur such as pericardial effusion not requiring
pericardiocentesis or surgical intervention, pneumothorax and hematoma at the pocket
requiring drainage.
This study demonstrate that this new rotational mechanical sheath is an effective tool
24 1.6 Hybrid Minimally invasive lead extraction: a new approach in high-risk
patients20
Despite TLE remains as gold standard in lead extraction, it is a procedure that can
present risks that require cardiac surgery in emergency in elective case.
For that reasons, Bontempi et al., elaborated a new hybrid, minimally invasive
approach for transvenous lead extraction, defined as a procedure performed by an
electrophysiologist with the support of a cardiac surgeon with a minithoracotomic or
thoracoscopic approach in the same operative session.
This approach was used in high-risk patients, selected with the LED score (previously
elaborated by Bontempi himself). Another criteria by which patients were enrolled for
this approach was the presence of extracardiac/extravascular lead presence, lead
attachment to critical cardiac structures and prior failed extraction with lead structural
compromise.
The hybrid procedure was performed in a hybrid operating room with all the
equipment of a cardiac surgery room.
The patient underwent general anesthesia, the skin is prepared and draping of patients’
chest was performed in order to be ready if a chest-opening will be required.
At this point, guide wires were introduced in femoral artery and vein.
Device pocket was opened using standard techniques, the leads were disconnected and
prepared for lead extraction by cutting the proximal portion.
Simultaneously, a minithoracotomy or a thoracoscopic approach was performed and
both these sets-up described, although with some technical differences, allowed a
continue monitoring of the critical area for potential vascular injury during the lead
25
So, a dilator sheat or a lase sheat were used to free the leads from adhesions within the
vascular tissue and/or the endocardium.
Figura 2: Hybrid passive-function right atrial lead extraction through video-assisted thoracoscopy. Bontempi performed 12 TLE with hybrid approach in high risk patients in order to
increase the overall safety of the procedure. Complete success was achieved in all
cases and this approach reveals to be more safety in high risk patients because it
allows monitoring of vascular and myocardial integrity and prompt treatment of
potential complications.
Another similar approach very recently elaborated by Migliore et al.,21 in order to be
used in high-risk patients instead of TLE.
The characteristics that Migliore indentify for describe a patient as high risk in TLE
are both clinical and device-related: age, systemic infection, dwell time, number of
extracted leads, use of ICD leads, use of dual-coil leads and the presence of passive
fixation are surely related with rate of complications and associated mortality.
The procedure described by Migliore is approximately the same as described by
26
complications in TLE and in order to avoid or, at least, promptly recognize the injury,
Migliore modified the minithoracotomy access, performing a small incision on the
right anterior portion of the 2nd intercostal space instead of 4th.
It seems that this minimal difference in the approach can allow a better direct
visualization of the critical area where potentially can occur a vascular injury during
TLE, such the SVC-right atrium junction.
The laceration of SVC is associated to high risk of mortality if not promptly
recognized and treated with hemostasis at most in 10 minutes.
As mentioned above, also a thoracoscopic approach was proposed but it seems to have
some limitations as the fact that not allow a complete direct visualization of the
critical area for potential vascular injury during TLE and it may not allow an
appropriate treatment for brachiocephalic vein injury, although it’s very rare comparing with SVC laceration.
27
2. The need of a risk score related to lead extraction
Transvenous lead extraction (TLE) is the gold standard in the treatment of
CIED-related infective complications and it’s often required in the management of lead malfunction.
Manual traction is often effective only to remove leads that were implanted a few
months prior, while leads implanted several years ago develop fibrous attachments and
require a more advanced extraction system9.
In the last 30 years, TLE has improved from the use of mechanical sheaths to powered
sheaths and laser-assisted methods to disrupt or dissect lead adherences.
As some studies reveal, transvenous lead removal is highly successful with few
serious procedural complications222324.
Efficacy and safety of the procedure can be in part predicted by some patient-related
and device-related factors25 26, but at the present, there isn’t a good validated multiparametric score that is able to establish a clear stratification of the efficacy and
safety of the procedure.
Some factors are reported to be correlated with a more difficult, challenging and
dangerous lead extraction procedure. These factor are listed in the table below.
Factor Criteria Comments and references
Body Mass Index < 25 Kg/m^2 Related more to size than gender
Sex Female gender Complications higher in woman
compared to men
Congenital Heart
Disease
28
Co-morbidities Age, poor LV function,
renal failure, coagulopathy,
large vegetations
Most of the risk are periprocedural
Venous State Occluded or severely
stenosed
Higher risk with greater lead
cross-sectional area in the young. Limited
access for additional procedures.
Number of leads Greater number of leads
present or extracted
More lead-lead and lead-tissue
interactions
Implantation time Greater than 1 year, rising
further thereafter
Time dependent tissue reaction to
leads.
Fixation mechanism Passive Active fixation safer to extract
Lead body-gemoetry Non isodiametric Catching on bridging tissue
ICD lead Coils/complexity Greater diameter. Uneven surface
unless coated
Special/Damaged lead
Designed/provoked
decifiencies
Notable examples: Riata, Starfix,
Accurfix, Encor
Volume’s centre < 30 extraction
procedures/years
Increased risk of complications
Operator Experience
< 300 extraction procedure
performed
Increased risk of complications
Tools, technique,
Approaches
Extraction outcomes and
complications
Femoral approach, powered sheaths
increased complications, internal
29
A procedure-correlated risk score could help clinicians in the difficult choice between
extracting or abandoning a lead.
2.1 Complications of lead extraction
Cardiac lead extraction is an effective and safe procedure but, obviously, it has more
potential complications than device implantation.
Complications are classified in 2018 EHRA Consensus document27 by their time in
relation with the procedure and their severity.
The timing classification includes:
- Intraprocedural complications: defined as any event related with the procedure
that happened while the patient is still in operating room;
- Early post-procedural complications: defined as any event related to the
procedure that occurs within 30 days following the procedure;
- Late post-procedural complications: defined as any event related with the
procedure that happened or become evident after 30 days following the procedure
and during the first year.
Complications are also classified relying on severity and reversibility in:
- Major complications are defined as any of the outcomes of the procedure that are
life-threatening or result in death, or any event that causes persistent disability or
any event that requires significant surgical intervention to prevent any outcome
listed above.
- Minor complications are defined as any event related with the procedure of LE
that required medical intervention, without limitation of patient’s function, life
30
The most frequently reported complications are cardiovascular lesions requiring
pericardial drainage, chest tube or surgical repair.
Less frequently are described major-complications as cardiac or vascular tear or
avulsion, respiratory arrest, cerebrovascular accident, arrhythmias, anesthesia related
complications.
Major non procedural related complications are frequently associated with heart
failure and sepsis.
Transvenous’ lead extraction complications, without an immediate treatment, could cause death.
In order to avoid that, prompt identification and correct management of the
complications appears crucial for reducing their impact on the outcome of the
extraction procedure.
The presence of cardiac and thoracic surgery physically on site permits the execution
of a sternotomy in case of necessity.
The rate of complication of TLE is associated either with the center’s volume, either with the operator’s experience.
ELECTRa study showed that the all-cause in-hospital major complications and deaths
were significantly lower in high volume centers (> 30 procedures/years) than in low
volume center (< 30 procedures/year). Moreover, high volume centers have more
procedural success rate comparing with low volume centers.
Complications’ rates are also related with operator’s experience: major and minor complications are reduced approximately about 50% relating with higher operator
31
These data show the need to avoid to perform more difficult and riskier procedure in
low-volume centers or during a learning curve: a correct preprocedural stratification
of the risk may help in the idenfitication of these procedures and could help in order to
32 2.2 Predictors of adverse events in cardiac lead extraction
The major difficulties to lead extraction are represented by the body response to the
foreign implanted material and by the development of fibrotic reaction between the
lead and the vascular system.
Within a year, fibrosis encapsulates the area where leads and the cardiovascular
structures are in direct contact.
The fibrotic binding sites can fuse and it may develop a dense adhesion area that can
calcify over time.
Calcified fibrotic lesions and dense adhensions significantly affect the ease of
extraction procedure. 339
Some clinical studies searched for the predictors of failure or major complication
during TLE procedures, in order to obtain a pre-procedural risk stratification scores.
We can distinguish two categories of risk factors: clinical related risk factors and
device related risk factor.
2.2.1 Clinical related risk factor
Several former studies indicate that women have an increased incidence of major
adverse events during TLE2425 26. In the initial experience of laser lead extraction
in USA reported by Birdy et al., female sex was the only multivariate predictor of
complications.
This observation was confirmed in the European Lead Extraction ConTRolled
(ELECTRa) Study24 and in the Acap Registry25.
Another clinical risk factor confirmed by a previous study is the lower BMI (< 25
33
success34. Smaller size of the veins could explain this risk but more studies are
needed about it.
Age’s role as risk factor remains controversial: some retrospective studies indicated age > 56 years old as a predictor of 30-days and one-year mortality in
patients undergoing TLE3435.
Maytin et al., reported that instantaneous mortality rate increases by 5% per each
year of patient age36. No correlations were found between age of patient and
efficacy, complexity and complications of TLE1523242631.
Although an in-vitro study showed higher risk of fibrosis in younger patients37,
age was not always a predictor of fibrous adherences in ICD lead extraction9.
Renal dysfunction, with or without dialysis, doesn’t seem to be correlated neither with lower clinical success rate in TLE, either with higher tax of major
complications.
However, renal impairment was associated with significantly higher mortality at 1
and 6 months.
Those data are confirmed by the LExICon Study, where creatinine > 2 mg/dl
increased mortality and by the retrospective study of Maytin et al., where a direct
correlation between mortality rate and serum creatinine was observed23.
The clinical status of patients undergoing LE is a predictor of major complications
during TLE.
Patients with infection are at higher risk of major complication during or soon
after the TLE: in particular, patients with sepsis, systemic infection and/or raised
34
Some studies correlated the presence of an infection with a greater ease of lead’s extraction: it may be possible by the fact that infection can inhibit the collagen
deposition and the fibrosis, leading to looser adhesion between the lead and the
cardiovascular tissue.
However, more studies reported a correlation between infections and venous
thrombosis: this connection makes the procedure of extraction more difficult3940.
Argwal et al., found a correlation between high white cell count and higher risk of
major complications, without differences about procedure difficulty41.It’s possible
that the risk can be better predicted by the presence of a systemic inflammation
instead of a local one.
Furthermore, modified Duke criteria provide reliable estimate of long term
outcomes in these patients, despite the criticism about the lack of sensitivity in the
diagnostic process16.
It’s right to point out that patients without manifest involvement of the CIED pocket at the admission for CIED extraction have a worse prognosis16.
This can be explained by an early diagnosis in the presence of pocket infection
leading to a better management these patients.
Severe ventricular dysfunction is also associated with the rate of major
complications and with 30-day-mortality42.
Diabetes mellitus and anemia are predictor for an increased risk of long term
mortality2342.
It’s essential to evaluate laboratory test before performing TLE because either low platelet count, either elevated INR are predictors for an increased risk of major
35
In addition, anticoagulant use give another risk in long term mortality in these
patients43.
Other interesting association is between hypertension and increased risk of failed
laser lead extraction: this association was described by Roux et al.44
Because of the activation of the RAA-system, hypertension is connected with
myocardial fibrosis: therefor it is possible that an enhanced fibrotic response to
intravascular leads occurs in this setting.
Similar conclusion are also described in patients affected by hypertrophic
cardiomiophaty.
A previous open-heart surgery seems to have a favourable effect against the
occurrence of major complications2441.
Fibrosis around the vessels and around the heart in the pericardial space in these
patients may reduce the risk associated with the development of a tear in the right
ventricle, right atrium or veins.
2.2.2 Device related risk factors
Lead characteristics consistently affects reactive fibrosis around them. In the last
20 years, designs were improved to ease implantation, decrease inflammation and
fibrosis, and finally, facilitating TLE.
Some recent innovations are active fixation mechanism45, tip steroid eluting
technologies46, new insulators47, isodiametric designs and single covered coil
technologies484950.
ICD lead extraction procedures are usually considered more challenging and
36
long-term mortality, increased incidence of major complications41 and need of a
laser assistance51 were reported.
Body’s reaction to foreign implanted material and the following development of fibrotic and calcific reaction between the CIED and the vascular system are the
most important obstacles to the lead extraction.
In the Pacing Lead Surveillance Study in Europe, transvenous ICD lead extraction
was associated with 12% risk of major complications, while the risk of major
complications in PM lead extraction was 1,7%52: we can explain this fact because
ICD leads, compared with standard pacing leads, show similar time-dependent
fibrous ingrowth but greater involvement of the lead course53.
Dual coil technology is a major predictor of adherence, in particular at level of
innominate vein and superior vena cava (SVC)9.
The presence of the dual-coil is correlated with a more complex procedure4854 and
it’s associated with a higher risk of SVC laceration and 30-days mortality55
.
Smaller lead diameter and greater proximal surface coil area were predictors of
major complications25.
Since the traction exerted during the LE and the technique used for the dissection
of binding sites are directly related to the tensile strength of the lead56, these
factors could explain this correlation.
Several studies demonstrated that longer dwell times resulted in increased
incidence of complications and more procedural difficulties.
In fact, dwell time is an independent predictor of fibrous adherences: this fact was
confirmed by the LExICon study that showed as procedural failure was higher in
37
The same results were found in our unit where a dwell time of 20 months was
independently associated with the need for mechanical dilatation and a value of 55
months predicted cross-over to the internal transjugular approach in ICD lead
extraction.
Longer lead duration was associated with major complications, procedure failure
and with the need for laser extraction.
Another important lead extraction lead factor is a high number of explanted lead23:
Argwal et al. reported a 3.5-fold increase in the risk of procedural complications
for every incremental lead extracted41. The risk is higher mostly if it’s planned to remove 3 or more leads2326.
Comparing pacing and ICD leads, leads in coronary sinus are often removed by
manual traction instead of dilatation.
In a multivariate analysis, unipolar design and non-infective indication were
independent predictors for mechanical dilatation57.
Unipolar leads were used at the beginning of the CRT-era, while new bipolar leads
with a more isodiametric design may reduce the risk of fibrous entrapment during
retrieval, allowing easier extraction with manual dilatation58.
Another association could be explained by a stronger adhesion promoted by a
dislodged lead and the malfunction could also be the consequence of a strong
tissue ingrowth.
The sites of fibrous adherence have been studied in our center: only 10% of
patients had evidence of fibrous adhesions within the CS or its branches,
suggesting that the sites generic to other intra-cardiac leads are likely to present
38 2.3 International Data Registry and ELECTRa Registry
The relatively low number of patients enrolled in each study, some referral bias and
highly experienced operators limit the generalizability of single report data: for that
reason, a real-world data registry of TLE was recently elaborated.
First of all, a total of 91.890 procedures were identified in the period 2006-2012 by
the NIS (United States Nationwide Inpatient Sample), in order to examinate utilization
patterns, frequency of adverse events and influence of hospitals’ volume on complications’ rate59
.
The study describes complications and deaths that occurred during the hospitalization
in which patients underwent transvenous lead extraction procedure: the reported
overall complications was 8.3% with an in-hospital mortality of 2.2%.
The most common complications included: bleeding requiring transfusion (2.6%),
respiratory compromise requiring mechanical ventilation (2.3%), vascular injury
(2.0%), pneumothorax/hemothorax (1.5%) and pericardial complications (1.4%).
The needing of open-heart surgery was only 0.2%.
It’s important to underline the fact that the higher rate of complications was recorded in teaching hospitals and was associated with infection as indication for lead removal.
Recently the National Cardiovascular Data Registry Implantable
Cardioverter-Defibrillator was analysed25: predictors of perioperative complications were studied
either in all extraction procedures, either in high-voltage lead.
From this study, some risk factors were extrapolated: female sex, admission other
from electivity for procedure, more than 3 lead extracted, longer implant duration,
39
correlated with a higher peri-operative risk and with an increased risk of
complications.
2.3.1 A focus on ELECTRa23 Study
The ELECTRa Study was conducted in order to identify the safety and the efficacy
of the current practice of TLE.
There are two important end-points in ELECTRa: the first one was TLE safety
defined as forecast the major procedure-related complications including death; the
second end-point included clinical and radiological success and overall
complication rates.
ELECTRa Study demonstrated that TLE procedures performed in high volume
centers compared with low volume centers, were associated with a lower
complications’ rate.
Major complications and death were common in: female patients, leads with a
dwell time > 10 years, use of powered sheaths, femoral approach.
Predictors of clinical failure were: low volume centers, female gender, 3 or more
lead planning for extraction, a lead dwell tme > 10 years, use of powered sheaths
and femoral approach.
Predictors of increased all-cause mortality during hospitalization were: extraction
in a low volume center, age >68 years, NYHA III/IV and systemic infection.
It’s important to underline as major complications can be solved if recognised and treated promptly.
40 2.4 Multiparametric risk score in literature
Risk stratifications scores have been proposed in literature in order to stratify patients
is low, moderate and high risk.
These scores can be useful in order to choose the best allocation for the single patient:
in fact, patient categorized as low risk can be operated in electrophysiological lab
while patients with higher risk maybe will be operated in operating room.
As we can noticed below, significant differences are present between enrolling
centers, enrolled population, tools and approaches used (mechanical vs laser sheaths)
and results.
2.4.1 Brunner risk score
Brunner and colleagues analysed retrospectively patients who underwent TLE of
41
They created a nomogram for predicting 30-days-mortality rate after TLE.
They enrolled 2999 procedures, totalizing 5521 leads extracted (74,9% PM, 25,1%
ICD). Lead implant duration was 4.7 years and 2.0 leads were extracted per
procedure.
Sixty-seven patients died by 30 days after TLE.
The nomogram (picture above) predicting 30-days mortality was elaborated using
baseline clinical variables and multivariable logistic regression modelling.
The elements included in the score are: age, haemoglobin, BMI, ESDR, ejection
fraction, NYHA functional class, lead extraction for infection, prior lead extraction
procedures performed by operator and dual-coil ICD lead extracted.
This nomogram has a good predictive ability and uses only clinical data readily
available to any clinicians.
The strength of the nomogram rely on the big population heterogeneity and size
from which it was derived.
2.4.2 Fu risk score
Fu and colleagues elaborated a risk stratification score based on 1378 pacing and
ICD lead removed in 652 patients (age 64+/- 17 years, M 68%) underwent to 702
procedures.
In total, 44% of leads requires laser assisted extraction.
The main characteristics associated to the need of laser extraction and procedural
failure were overall lead duration and implantable ICD lead.
The major complication rate was higher in the high-risk patients group (with a 10
42
5.3% of procedures versus 0% in low risk patients group (characterized by any
lead < = 1-year-old); moderate risk patients (with pacing lead 1-10 years old or
ICD lead 1-5 years old) experienced 1.2% of events.
2.4.3 Oszczygiel risk score - IKAR
Oszczygiel’s workgroup proposed IKAR score in order to predict one-year-mortality of patients undergoing TLE procedure.
The involved population included 130 patients (82 males, mean age 64 y)
implanted with PM (74%), ICD (15%), CRT-D (11%).
Total radiological success rate was 90% while clinical success rate was 93.5%.
One-year mortality was 28%.
The variables considerated in this study was: infective indications, kidney
disfunction, age > 56 y/o, removal of high voltage lead.
The patients with the IKAR score = 0 had a rate of 0% of mortality in 1-year,
while patients with IKAR 4 have 94% probability of death in one-year.
2.4.4 Bontempi risk score
Bontempi and his workgroup studied a total of 889 permanent leads that were
extracted from 469 patients in order to elaborate a score aimed to predict the
difficulty of lead extraction and able to discriminate which patients should be sent
to a referral site.
98.2% of the leads were completely removed and major complications were
43
Bontempi considered the fluoroscopy time of the procedure as index of difficulty:
a procedure is defined difficult if the fluoroscopy time was more than 31.2 min [90
th percentile].
The Lead Extraction Difficulty (LED) Score was defined as: number of leads
extracted + lead age (years from implant) + 1 if dual coil -1 if vegetation.
The LED score independently predicted complex procedure (with fluoroscopy
time > 90th percentile) both at univariate and multivariate analysis31.
A following study was designed to validate the estimation model based on the
LED index: a LED score greater than 10 could predict complex cases with a
sensitivity of 86.9% and a specificity of 70% and a negative predictive value of
98%. The multivariable logistic regression analysis confirmed a 12% increased
risk of high fluoroscopy for each additional point of LED.
The validation of the estimation model based on LED index < 10 confirmed its
high efficacy predicting simple TLE procedures.
Identifying patients who are at low risk could allow more appropriate allocation
for high-risk-patients and even recognize patients who could have a safe extraction
even in low-volume centers.
From an organizational point of view, this could mean better resources
management and cost optimization, without a reduction in the procedural safety.
Further studies are needed to determine and validate the utility of this scoring
44
2.4.5 Mazzone risk score
As the population that requires leads’ extraction is getting older, with more complex devices, comorbidities and prior procedures of extraction, nowadays LE
techniques is getting more complex60.
For these reasons, Mazzone and his workgroup implemented a stepwise
approach61, using most available standard and advanced tools since a single
technique cannot be the most appropriate for that single patient; in order to achieve
the best treatment for the single patient, Mazzone’s group have token into account the variety of the treated patients and leads characteristics.
By the way, the implementation of advanced techniques has considerable
implications regarding cost and appropriate expertise to avoid complications.
Furthermore, not all the centers can perform advanced lead extractions.
For all these reasons, awareness of factors related to the need for advanced tools
before extraction may facilitate procedure planning including patient transfer.
On the basis of these stepwise approach, Mazzone aim to identify those clinical
and techniques characteristics that can predict the need for advanced LE
45
Mazzone and his group identify four steps of lead extractions:
Step 1 - The leads were dissected free from the scar tissue in the pocket, the
anchors were removed.
- The active fixation mechanism was retracted (if present) - Manual traction
Step 2 - Insertion of a locking stylet with insulation bound suture
- Manual traction
Step 3 In case of excessive calcification:
- Advancement of dilators sheat set (in case of mild fibrosis) - Counterpressure
Step 4 Use of powered mechanical or laser sheat.
Counterpressure – countertraction.
All patients were monitored for complications related of the procedure at the time of
extraction, during the hospitalization and a one-month-follow up were scheduled with
their cardiologist.
Mazzone has defined:
- Complete success of the procedure as the removal of all target leads ad all the lead materials from the vascular space without disabling complications or
procedure-related death.
- Clinical success as the removal of all target leads and lead materials from the vascular space or the retention of a small part of the lead when the residual part doesn’t
46
- Failure of the procedure as inability to achieve either the complete procedure of extraction or clinical success.
- Major complications as outcomes that were life-threatening resulting significant or permanent disability or death or required surgical intervention.
- Minor complications as events related to the procedure that requires medical interventions or minor procedural intervention.
Mazzone considered 208 patients and step 4 lead extraction were performed in 122 of
208 patients; comparing these patients to those where extraction was performed
conventionally (86 of 208) were:
- Younger;
- Had greater number of leads exsisting before the procedure; - Exhibited a greater implant duration
- Underwent more frequently an extraction of a right ventricular defibrillator lead
In addition, the presence of infection (systemic or local) as the indication for
extraction was more prevalent in patients who underwent advanced LE.
In conclusion, in univariate logistic regression analysis Mazzone showed that younger
patient age, longer duration of initial implantation, the performance of more than one
implantation, the number of the leads exsisting prior the procedure, the leads extracted
and the presence of right ventricular defibrillator leads were significantly associated
47
In particular, Mazzone identify also the cut-off of these values that best predict the
step-4 LE:
- Age < 71 years old: younger patients form more vigorous scar which has higher tensile strength than older patients. This may be the mechanism by which leads are
more difficult to remove in younger patients.
- Extraction of at least 2 leads; - Implant duration > 37 months;
- One of the leads being a defibrillator lead
According to Mazzone’s analysis, these are the optimal values predicting the requirement of using step 4.
Specifically, the absence of all the four characteristics was accompanied by 0%
positive predictive value for requirement of step 4 for LE.
The existence of any one of the above variables increased the probability for using
advanced LE techniques only to 8.3% while the presence of two risk factors increase
the need of advanced LE-extraction techniques to 46,8% of the cases.
Positivity to three risk factors raises the possibility for using step-4 at 66,7% while the
coexistence of all above mentioned four risk factors is characterized by 86,7%
requirement of laser or mechanical sheath extraction.
From a clinical point of view, Mazzone’s group provided a simple prediction model developed based on the risk factors that were independently associated with the need
for proceeding into step-4 LE.
Mazzone’s results could also help the decision making process about proceeding or not to the removal of abandoned leads at the time of device upgrade.
48
In conclusion, patients’ and leads’ characteristics that Mazzone’s workgroup identify may help the operator plan of extraction.
Score Parameters End point
Fu et al.15,
< 1 year old lead
10 years pacing leads or
1-5 years ICD leads
>10 years pacing leads or >5
years ICD leads
Major complication rate 0%
1.2%
5.3%
Brunner et al.35, Variables: age, BMI,
haemoglobin, ESDR,
ejection fraction, NYHA
functional class, lead
extraction for infection, prior
lead extraction procedure
performed by operator, dual
coil ICD lead.
30-day all cause mortality The nomogram is based on a
total point ranging from 0 to
250. Concordance index 0.867 Oszczygiel et al.34, IKAR score I = infective indication (1) K = Kidney dysfunction (2) A = Age > 56 (1)
R = removal of high voltage
lead (1) 1-year mortality 0 = 0% 1-2 = 16% >= 3 = 79% >= 4 = 94%
49
LED index within the procedure
+ lead age
+1 If dual coil
-1 if vegetation
LED score >=10
ROC = 0.81
Mazzone et al.61, Age < 71 years old
Implanted more than 37
months ago;
Extraction of at least two
leads;
One of the leads being an
ICD-lead;
Step-4 lead extraction if all of these parameters are
50 2.5 Advantages and limits of risk scores
As we can deduce from the parameters and the results of the former presented scores,
there is a great variability in these scores, ranging from a very low risk of short term
mortality (30-days) to high risk of complex procedure.
In order to demonstrate that, we can present two different case from our center in
which we have tried to apply the scores previously described.
Predictors of procedural outcomes depends on tools, techniques and approaches used,
while long term mortality is more dependent on clinical characteristic of the patients.
First case
Woman, 63 years old with dual chamber pace-maker and a pocket related infection
was referred in our Unit for TLE.
The device was implanted eight years before for a complete BAV and a third
ventricular lead was subsequently implanted for malfunction of the previous one.
The echocardiogram was normal and the blood tests revealed a mild anemia and a
PCR slightly increased.
The atrial lead was easily removed by traction, while the ventricular one required the
use of 11.5 F sheath.
After the removal, a cardiac tamponade occurred: it was promptly treated with
pericardiocentesis.
The extraction of the ventricular lead was performed two days later with the
concomitant implantation of a contralateral dual-chamber pacemaker after the result
of two negative hemocolture.
51
Second case
Men, 44 years, carrier of a dual-chamber ICD and a dual coil ICD lead malfunction
was referred for TLE.
The leads were implanted 12 years before for an arrythmogenic right ventricular
dysplasia.
The patient had no comorbidities and blood tests were normal. During the procedure,
the ICD lead was not removed because of a tight binding sites at the tricuspid level
and a new single coil ICD lead was implanted without complications, obtaining a
clinical success procedure.
The follow-up after 1,6 and 12 months was uneventful.
The LED index classified both our cases as complex procedures, while Fu attributed a
higher risk of major complication to the second case, while we had the major
complication in the first one.
In the second case, using mechanical sheaths, we could appreciate a very tight binding
site and, according to clinical indication, we decided to abandon the lead and stop the
procedure.
By the fact that the score was developed on laser extraction, maybe this score is less
appropriate for mechanical sheaths: probably a laser sheath extraction in the same
patient would have been complicated.
The calculated rate of mortality using Brunner and Oszcygiel risk score was very
similar, even if the two patients are very different for sex, age, clinical conditions and
52
Due these considerations, although useful in risk stratifications, clinical decision
making through indiscriminate use of these scores appear still premature and risky.
Risk stratification and knowledge of procedure’s complexity is useful to discriminate patients who should be sent to a referral center.
Furthermore, using risk scores, we can identify which patients can be safety extracted
in electrophysiology laboratory and which ones are to be sent in operating room.
While in infection indications we have necessarily to remove the CIED, in case of
non-infective indications for removing, a pre-procedural stratification of the
peri-operative risk, 30-days and 1-year mortality can be very useful to decide either to
