Long-term cerebral thromboembolic complications of transapical endocardial resynchronization therapy
Long-term cerebral thromboembolic complications of transapical endocardial resynchronization therapy
Zsuzsanna Kis 0 1 2
Andrea Arany 0 1 2
Gabriella Gyori 0 1 2
Attila Mihalcz 0 1 2
Attila Kardos 0 1 2
Csaba Foldesi 0 1 2
Imre Kassai 0 1 2
Tamas Szili-Torok 0 1 2
0 United St Istvan and St Laszlo Hospital , Nagyvarad ter 1., 1097 Budapest , Hungary
1 Gottsegen György National Institute of Cardiology , Haller utca 29, 1094 Budapest , Hungary
2 Thoraxcenter, Department of Clinical Electrophysiology, Erasmus MC , 's Gravendijkwal 230, Kamer BD416, Postbus 2040, 3000 CA Rotterdam , The Netherlands
Purpose Cardiac resynchronization therapy (CRT) is an established therapeutic option in selected heart failure patients (pts). However, the transvenous left ventricular (LV) lead implantation remains ineffectual in a considerable number of pts. Transapical LV (TALV) lead implantation is an alternative minimally invasive, surgical, endocardial implantation technique. The aim of the present prospective study is to determine the long-term outcome, including the cerebral thromboembolic complications, of pts who underwent TALV lead placement. Methods Twenty-six CRT candidates (19 men (78 %); mean age 61 ± 10 years) with a previously failed transvenous approach underwent TALV lead placement as a last resort therapy. The following data was collected: mortality rate, reoperation rate, and cerebrovascular event rate. Patients underwent a cerebral CT scan to determine any possible cerebrovascular event related to the presence of the TALV lead. Results Eleven out of 26 (47 %) patients survived after a median follow-up of 40 ± 24.5 months. Major acute ischemic stroke occurred in two cases, while in one case transient ischemic stroke was observed. Cerebral CT scan examination performed in asymptomatic patients revealed chronic ischemic lesions with minimal extension in two patients. Reoperation occurred in one case due to TALV lead fracture. Conclusions This is the first study reporting the long-term outcome, mortality, and thromboembolic event rate exclusively after TALV lead implantation. Patients who underwent TALV lead implantation have a comparable long-term mortality rate to conventional CRT, although a major ischemic cerebrovascular event after TALV lead implantation is worrisome and has an impact on the outcome.
Transapical left ventricle pacing; Resynchronization therapy; End-stage heart failure; Thromboembolic complication
Cardiac resynchronization therapy (CRT) is an established
therapeutic option in a subgroup of heart failure patients,
which improves heart function and functional clinical
status and decreases mortality [1–3]. Despite significant
technological improvements, the transvenous left ventricular
(LV) pacing lead implantation into one of the branches
of the coronary sinus (CS) can remain ineffectual in
certain cases [4, 5]. Epicardial pacing lead implantation is the
most frequently used alternative, although this requires
open heart surgery . Furthermore, reaching and pacing
the most delayed LV segment can be challenging due to
LV dilatation. In addition, the location of the epicardial
coronaries may be obscured due to pericardial adhesions.
Consequently, the prevention of any damage to important
vessels while inserting the epicardial LV lead can be
difficult. Nevertheless, epicardial pacing seems to be less
effective compared to endocardial LV pacing .
Endocardial stimulation is associated with a greater aortic
and mitral time velocity integral, and increased left
ventricular fractional shortening in comparison with epicardial
stimulation . Endocardial left ventricular pacing can be
achieved by different techniques such as transseptal and
transapical left ventricular pacing approaches. Transseptal
cardiac resynchronization therapy carries a high risk of
device-related infective endocarditis. This condition can
only be treated by hazardous surgical lead extraction and
repair or replacement of the mitral valve when affected [8,
9]. The transapical left ventricular (TALV) lead
implantation technique can eliminate most of the aforementioned
problems. The main advantages of the transapical
technique are the following: a minimally invasive, surgical
technique ensuring endocardial LV stimulation, avoiding
damage caused by contact with the mitral valve, which
provides an alternative last resort therapy for severely affected
patients [8, 9].
Despite promising mid-term transapical CRT outcome
data, recent evidence raised concerns about the long-term
thromboembolic complications of endocardial LV pacing
techniques . The aim of the present single-center prospective
study was to assess the long-term outcome and the incidence
of thromboembolic complications in patients who underwent
transapical endocardial LV lead placement.
2.1 Patient population
This study was approved by the Regional Medical
Ethical Committee conform the Medical Research Council-Scientific and Ethical Committee guidelines of
the 1975 Declaration of Helsinki. Informed consent was
obtained from all patients before the procedure.
Between October 2007 and September 2013, 26
consecutive patients (mean age 61 ± 10; seven women) with
ischemic (12 pts) and dilated (14 pts) cardiomyopathy
after failed transvenous LV lead implantation underwent
TALV lead placement as a last resort therapy. All
patients were eligible for CRT according to the ACC/
AHA/ESC guidelines [11, 12]. The main demographic
data and the medical therapy of patients are summarized
in Table 1. Since lifelong anticoagulation therapy is
mandatory after left ventricle lead implantation, patients
with any contraindication to anticoagulation therapy
were excluded from the study. Further exclusion criteria
were the following: presence of intracavital thrombus,
preoperative pericardial effusion, and/ or large coronary
artery branches around the apex [13–15].
2.2 Surgical procedures
The method of TALV lead implantation has been previously
reported [8, 9]. The procedures were performed under general
anesthesia. The patients were positioned for a limited left
thoracotomy via an infraclavicular incision. Initially,
transthoracic echocardiography was used to locate the LV apex. By
means of the mini-thoracotomy, a pericardiotomy was
executed above the LV apex to ensure free navigation of the LV lead.
Any type of active fixation pacing lead was allowed for
insertion through the apex into the LV cavity. We preferred the use
of the thinnest bipolar electrodes to decrease the traumatic
effect during insertion. A standard Seldinger-technique with
a peel-away sheath was used for insertion. Firstly, the apex
was punctured with a needle and a guidewire inserted through
the needle. After removal of the needle the apex puncture was
dilated with a peel-away sheath and dilator placed over the
guide wire. The guidewire and dilator were removed and the
pacing electrode inserted into the LV cavity. Once the lead was
in position, the peel-away sheath was removed. A
monofilament purse-string suture was applied around the insertion site
to control hemorrhage from the LV cavity (Fig. 1). Navigation
and endocardial fixation of the LV lead was performed under
fluoroscopic guidance (Fig. 2). After appropriate endocardial
LV lead-fixation, pacing and sensing measurements were
performed. The acceptable pacing threshold was less than 1 Vand
R-wave amplitude for sensing in this electrode was more than
5 mV. Purse-string sutures were used employed at the apex to
minimize the electrode movement through the apex and they
also were attached to the body of the electrode to achieve a
stable position . Afterwards, the proximal portion of the
electrode was subcutaneously tunneled to the infraclavicular
area and connected to the CRT-device . The right atrial
and ventricular leads were implanted through the cephalic or
Table 1 Baseline clinical and
Mean ± SD or %
SD standard deviation, ACE angiotensin convertase enzyme, ARB angiotensin receptor Blocker
subclavian vein using traditional percutaneous technique [8,
Finally, a pleural drain was inserted followed by standard
wound closure. The perioperative anticoagulation protocol
was identical to patients who underwent mitral valve
replacement with mechanical valve prosthesis . Intravenous
heparin was started 3 h postoperatively in the absence of bleeding
from pleural drain. Oral anticoagulation therapy was designed
to reach the targeted INR level (2.5–3.5) bridging with
heparin. Procedural data are summarized in Table 2.
2.3 Device implantation and pacing mode
Before surgical LV lead implantation, to identify the optimal
LV pacing site, the most delayed LV segment was determined
by tissue Doppler imaging and/or by electrical activation with
electroanatomical mapping . Twenty-six patients received
CRT devices, and the pacing algorithm was biventricular
DDD mode. Twelve patients underwent CRT-PM
implantation while in fourteen patients CRT-D device implantation was
performed. The majority of the patients were in sinus rhythm
Fig. 1 Intraoperative photo of the
transapical left ventricle lead
insertion and fixation. a Puncture
and dilatation of the left ventricle
apex using Seldinger-technique. b
Fixation of the transapical left
ventricular lead using purse-string
suture around the puncture site
Fig. 2 Positioning and fixation of transapical left ventricular lead under
at the time of implantation. The interventricular (VV) time
was empirically defined as minus 20 ms (LV first) . The
type of CRT devices and the type of TALV leads are described
in Table 1.
2.4 Follow-up and cerebral CT scan
All patients were scheduled for regular visits at 1, 3, 6 months
and every 6 months after that. Additional visits or
hospitalizations were registered. The INR level was checked and
corrected to be in the range between 2.5 and 3.5 generally
monthly but if required daily. During the median follow-up
period of 40 ± 24.5 months, we collected data on mortality
rate, reoperation rate, and cerebrovascular event rate.
Emergency CT scan was performed in patients with
symptomatic and/or suspected ischemic thromboembolic event.
Type of CRT devices and TALV leads
CRT cardiac resynchronization therapy, TALV transapical left ventricular
Asymptomatic patients underwent an elective,
noncontrast enhanced cerebral CT scan examination at median
follow-up of 40 ± 24.5 months in order to determine any silent
thromboembolic event possibly related to the presence of the
LV endocardial lead.
Scans were performed using a Siemens Somatom
Sensation 40 CT scanner. The scanning parameters were
140 kV and 230 mA. Estimated effective radiation dose was
2.2 mSv (average DLP 1092 mGy cm). The CT scan enabled
the acquisition of 40 slices per rotation with a 2-mm slice
2.5 Statistical analysis
Descriptive statistics were performed. Continuous variables
were presented as mean ± standard deviation (SD) and
compared with Student’s t test. Categorical data were expressed in
3.1 Mortality rate
During the median follow-up period of 40 ± 24.5 months, 3
out of 26 patients with transapical CRT were crossed over to
epicardial LV lead implantation; consequently, 23 pts could be
followed-up as pts with TALV lead implantation. The
mortality rate was determined utilizing the National Registry Office
database. Eleven out of 23 (47 %) patients with transapical
CRT survived after a median follow-up of 40 ± 24.5 months.
One patient was lost to follow-up. Ten patients died due to
exacerbated heart failure while one patient suffered sudden
3.2 Morbidity rate
Two out of the three patients crossed over to an epicardial
CRT system underwent right-sided infective endocarditis. In
the first case, the infection occurred 3 months after the TALV
lead implantation procedure. The second case materialized
3 years after the necessity of TALV lead repositioning and
reoperation, CRT generator decubitus was diagnosed. In these
cases, a new epicardial CRT-system was implanted via medial
sternotomy accompanied by the administration of
antibiotictherapy. A third patient was admitted to our hospital 1 month
after the transapical CRT implantation with symptoms of
pericardial tamponade, caused by the dislocation of the TALV
lead. During an emergency reoperation, the transapical LV
lead was removed and a new epicardial LV lead placed.
Furthermore, two cases of CRT-pocket infection were
observed and two cases CRT-pocket hematoma.
3.3 Procedural data
Reimplantation was necessary in one patient, after
interruption of anticoagulation therapy, due to TALV lead fracture
causing the deterioration of heart failure, 5 years after the
Repositioning of the TALV lead was necessary in three
cases. In two patients, lead dislocation was detected before
discharge from hospital. In one of the cases, it occurred during
closure of the pericardium, while in the other case, it was
observed on the second postoperative day . Repositioning
of these electrodes was performed without re-opening the
pleural cavity . In one case, TALV lead repositioning had
to be performed due to lack of capture at maximal output
(7.5 V /1.5 ms) despite repeated programming attempts.
In another patient, 1 week after the transapical CRT
implantation, dislocation of the right atrial electrode was
observed. In one other case, deterioration of heart failure was
detected, caused by right ventricular lead dislocation. Both
cases were resolved by repositioning of the dislocated
electrodes. In yet another patient, a local pocket infection was
detected, 2 years after the TALV lead implantation, requiring
CRT-P generator repositioning. Procedural complications are
summarized in Table 3. Dislocation of the TALV leads can
possibly be explained by different mechanisms. One of the
suspected mechanisms of TALV lead dislocation is
incomplete screw-in and subsequent tip release from the
endocardium . The other possible mechanism of TALV lead
dislocation may derive from the favorable changes in LV function
after CRT. Since better LV function and the more effective
contraction are achieved with CRT, this may increase the
chance of the LV lead pulling out . To avoid this
complication, as we previously reported, the lead should be securely
fixed at the apex and its position checked by chest X-ray 3–
5 weeks after the implantation . Despite all the procedures
Reoperation needed n = 4
-1 reoperation due to TALV lead fracture
-2 reoperations due to right-sided infective endocarditis
-1 reoperation due to TALV lead dislocation
Reposition needed n = 6
-2 repositioning due to TALV lead dislocation
-1 repositioning due to TALV lead capture problem
-1 repositioning due to right atrial lead dislocation
-1 repositioning due to right ventricle lead dislocation
-1 device generator repositioning due to pocket infection
Hematoma n = 2
Pocket infection n = 2
TALV transapical left ventricle
were performed by a highly experienced operator, the lack of a
dedicated device such as the learning curve of this novel
implantation technique might explain the slightly high
3.4 Thromboembolic complications and cerebral CT scan
The coexisting atrial fibrillation may increase the risk of
thromboembolic events. Atrial fibrillation was observed
in three patients at the time of device implantation.
However, during the follow-up period, atrial fibrillation
was detected in ten out of 26 patients. We chose CT
scan instead of magnetic resonance imaging (MRI)
modality to detect evidence of an ischemic event as neither
the CRT devices nor the attached leads were MRI
compatible. During the follow-up period, one case of
rightsided hemiplegia was observed 2 months after the
TALV lead implantation. An urgent non-contrast
enhanced cerebral CT scan identified an acute ischemic
occlusion in the middle cerebral artery. Systemic
thrombolytic therapy could not be applied as the patient was
receiving effective anticoagulation therapy. This was the
second ischemic stroke, with signs of right-sided
hemiplegia, that the patient had suffered.
There was an earlier occurrence 6 years before TALV
implantation. Both of these ischemic events healed without any
clinical symptoms. This patient died 3 years after the TALV
implantation due to heart failure deterioration. In the patient
who underwent reoperation due to TALV lead fracture,
requiring interruption of the anticoagulation therapy, left-sided
hemiparesis occurred 3 days after the procedure. The urgent
CT scan examination revealed acute major right-sided middle
cerebral artery occlusion with fronto-temporo-parietale
extension (Fig. 3d). Thrombolytic therapy was contraindicated
because of the history of anticoagulation therapy and the
CRTdevice reoperation within 1 week of this occurrence. The
patient received conservative therapy and neurological
rehabilitation with good success. In one case, facio-brachial
predominant hemiparesis occurred 4 months after TALV lead
placement. The CT scan revealed bilateral chronic ischemic stroke;
however, an acute lesion could not be detected. Thrombolytic
therapy was not instituted because of the absence of an acute
ischemic lesion and the presence of continuing effective
anticoagulation therapy. The patient’s symptoms resolved
after the administration of high dose parenteral vasoactive
medication. Nine months after TALV lead implantation, successful
LVAD implantation was performed.
In asymptomatic patients, the CT scan examination,
performed at the median follow-up of 40 ± 24.5 months, revealed
minimal extension chronic ischemic lesions in two cases
(6 mm lacuna in the right-sided nucleus caudatus, 4 mm
hypodensity in the left-sided centrum semiovale) (Fig. 3b, c).
Fig. 3 Non-contrast enhanced cerebral CT scan of patients after TALV
lead implantation: a no abnormality; b 6 mm lacuna in the right-sided
nucleus caudatus, c 4 mm hypodensity in left-sided centrum semiovale, d
middle cerebral artery occlusion with right-sided
The major finding of this study is that, although transapical
CRT can be used as an alternative method for CRT in selected
heart failure patients, it represents a worrisome
thromboembolic complication rate compared to traditional transvenous
CRT. As we previously reported, patients after TALV lead
implantation with 18-months follow-up period presented
promising outcomes with potential advantages such as shorter
procedure time and decreased postoperative burden compared
to epicardial left ventricle lead implantation techniques. 
However, only a few reports dealt with the thromboembolic
complications of LV endocardial pacing. Jais et al. and
Pasquie et al. with a clinical follow-up of 15 ± 12 and 85
± 5 months, both reported transient ischemic attack (TIA), 1
out of 11 and 1 out of 6 patients [17, 18]. Rademakers et al.
investigated the thromboembolic complication of endocardial
LV lead pacing (45 transseptal, 6 transapical) with mid-term
follow-up . The incidence of thromboembolic events per
100 patient-years was 6.1. Five patients had an ischemic
stroke (one had both stroke and TIA) and two patients suffered
from TIA . In these cases, the thromboembolic events
happened after interruption of anticoagulation therapy .
In our study, two major stroke and one transient ischemic
attack occurred during median follow-up of 40 ± 24.5 months.
One out of two thromboembolic events happened early after
the interruption of anticoagulation therapy due to the necessity
of TALV lead reoperation. Consequently, the major
cerebrovascular events were probably associated with insufficient
anticoagulation levels as stated in the reports of Jais et al.
and Pasquie et al. [17, 18]. The short-term cerebral
thromboembolic complications might be lowered if anticoagulation
therapy would not be interrupted with INR kept at >2.
Subtherapeutic INR levels frequently appear in everyday
practice . According to previous studies, only two thirds
of patients are within the target INR level. The duration of
decreased anticoagulation control is associated with increased
risk of stroke . Despite the fact that the efficacy of the
novel oral anticoagulants is more predictable, no experience
with its use is available in the endocardial LV pacing patient
population. Chronic heart failure and left ventricular dilatation
represents a higher risk of thromboembolism . The
severity of decreased ejection fraction appears to be an independent
risk factor for thromboembolic events in women . In the
SAVE trial, the risk of stroke was nearly twice as high among
patients with LVEF under 28 % than in the control group
(LVEF > 29 %) after myocardial infarction . Lead
compon e n t s m a y a l s o i n f l u e n c e t h e r i s k o f s t r o k e . T h e
thrombogenicity of polyurethane leads may be lower than
those of silicone . The report of Rademakers et al.
investigating cerebral thromboembolic complications after
endocardial lead placement (45 atrial transseptal, 6 transapical)
showed that all events happened with smaller diameter select
secure leads which had the same polyurethane outer insulation
. This result makes unlikely that the outer insulation of
endocardial LV lead is a critical factor in stroke occurrence
. The presence of an intraventricular anodal electrode may
represent an unknown factor as the source of intracavital
thrombus formation. The movement of the TALV electrode
may generate increased turbulent blood flow in the left
ventricle generating thrombus formation. Nowadays, novel
therapeutic options should be involved widely in the therapeutic
regime of end-stage heart failure patients. The application of
left ventricular or biventricular assist devices could be used as
destination therapy in end-stage heart failure patients;
however, one of their major complications is the occurrence of
Baroreflex activation therapy with centrally mediated
reduction of sympathetic outflow and increased
parasympathetic activity results in improvement of functional status, quality
of life, and exercise capacity. The technique can also be
advised for heart failure patients; however, its long-term
outcome is still unknown .
4.1 Limitations of the study
The lack of a control group does not make it possible
to determine the contribution of left ventricular
endocardial lead implantation to the occurrence of
thromboembolic events. A larger patient population is needed to be
able to compare the thromboembolic complications of
t r a n s a p i c a l LV l e a d i m p l a n t a t i o n t o t r a d i t i o n a l
t r a n s v e n o u s o r e p i c a r d i a l LV l e a d p o s i t i o n i n g
approaches. A further limitation of the study is the
relatively small number of implantations, which can be
attributed to the very strict inclusion criteria. In the case
of device or TALV lead endocarditis, in the absence of
special extraction techniques, the only solution to
remove the CRT-system is reoperation via sternotomy,
which is a high-risk maneuver in this severely diseased
patient population. Additionally, the absence of utilizing
brain MRI scan to detect evidence of a cerebral
ischemic event is a definite limitation of this study. As
neither MRI-compatible leads nor CRT devices were
available during the enrollment period, brain MRI scan was
not the method of choice to be executed during the
follow-up period. Consequently, it is possible that the
presence of silent cerebral thromboembolic lesions
likely related to TALV lead implantation is underestimated.
In conclusion, this study reports on long-term outcome
and mortality rate after implantation of a transapical
l e f t v e n t r i c u l a r e n d o c a r d i a l l e a d . P a t i e n t s w h o
underwent TALV lead implantation have a reasonable
long-term mortality rate, although occurrence of major
ischemic cerebrovascular event after transapical LV
lead implantation is worrisome and has an impact on
the outcome. Based on the aforementioned findings,
which are in accordance with other reported results,
the value of endocardial left ventricular pacing is
questionable and consequently cannot be promoted as an
alternative technique for CRT. It can only be
considered in selected cases. Theoretically, an improved
anticoagulation strategy, either using novel
anticoagulants or ensuring a higher target-INR level with
standard anticoagulants, might lower the occurrence of
thromboembolic events. This should obviously be
tested in prospective trials.
Compliance with ethical standards
Ethical approval All procedures performed in studies involving
human participants were in accordance with the ethical standards of the
institutional and/or national research committee and with the 1964
Helsinki declaration and its later amendments or comparable ethical
Informed consent Informed consent was obtained from all individual
participants included in the study.
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