Management of antithrombotic therapy in patients undergoing
electrophysiological device surgery
Valerio Zacà1, Rossella Marcucci2, Guido Parodi3, Ugo Limbruno4, Pasquale Notarstefano5, Paolo
Pieragnoli6, Andrea Di Cori7, Maria Grazia Bongiorni7, Giancarlo Casolo8
1
U.O.C. Cardiologia Ospedaliera, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera
Universitaria, Siena
2
Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze
3
Cardiologia Invasiva, Azienda Ospedaliero-Universitaria, Careggi, Firenze
4
U.O. Cardiologia, Ospedale Misericordia, Grosseto
5
Dipartimento Cardiovascolare e Neurologico, Ospedale San Donato, Arezzo
6
Dipartimento del Cuore e dei Vasi, Azienda Ospedaliera Universitaria, Careggi, Firenze
7
Second Division of Cardiovascular Diseases, New Santa Chiara Hospital, University of Pisa
8
Struttura Complessa di Cardiologia, Ospedale Versilia, Lido di Camaiore (LU)
Correspondence to:
Dr. Valerio Zacà
U.O.C. Cardiologia Ospedaliera,
Dipartimento Cardio-Toraco-Vascolare,
AOU Senese
Viale Bracci 16, 53100 Siena
e-mail: v.zaca@ao-siena.toscana.it
Supplementary data
Factors Associated with Enhanced Risk of Hemorrhagic Complications
Independently of the use of antithrombotic therapy, which remains the main predictor (1, 2),
numerous demographic, clinical and technical variables are potentially associated with a higher risk
of hemorrhagic complications from CIED implantation procedures. Adequate knowledge and
recognition of these factors may favor early identification of potentially high risk patients for whom
preventive or additional measures need to be put in place to prevent the risk from becoming
excessive. While aiming at defining the profile of the highest risk patients, we should nonetheless
acknowledge a substantial methodological limit attributable to the nature of the data, which are
mostly based on general conviction and, to a lesser extent, on scanty evidence. With the aim of
overcoming this limit, we have chosen to extrapolate only the data and information obtained from
studies performed on sufficiently numerous samples, excluding from this section of the document,
those works that investigate different periprocedural antithrombotic therapy strategies.
Advanced age (>65-70 years) involves a greater, albeit modest risk of periprocedural
complications from PM and ICD implantation, including hemorrhagic events, in part secondary to
the presence of comorbidity. In a retrospective study on 115,683 patients aged over 70 years
undergoing PM implantation, there was a comparable frequency of pocket hematomas (1.18 vs 1.29
vs 1.29%, p=0.22), but a higher incidence of perforation and cardiac tamponade with increasing age
in the 70-79, 80-89 and >90 tertiles (0.45 vs 0.5 vs 0.61%, respectively, p=0.03) (3). Data from an
extensive US registry on 150,264 patients (91,863 of whom >65 years of age) undergoing ICD
implantation for primary prevention indicate a substantial, albeit globally modest, increase in risk of
pocket hematoma requiring repeat surgery or transfusion, and of perforation and tamponade in
subjects aged ≥75 years (4).
The female sex was associated with a higher risk of pocket hematoma in a German study on
PM implantations (5). Such association was not confirmed in an extensive US registry on 161,470
patients undergoing ICD implantation, which however exhibited a significant increase in the
incidence of cardiac perforation and tamponade in female subjects compared with male subjects
(0.18 vs 0.05%, p<0.001 and 0.19 vs 0.06%, p<0.001, respectively) (6).
Various studies have instead reported a protective effect of overweight and obesity (7);
conversely, the presence of comorbidity, such as a history of heart failure, chronic kidney disease,
or individual bleeding diathesis is associated with an increased risk of pocket hematoma formation
(7, 8).
Technical variables related to the procedure may predispose to hemorrhagic complications,
although this is apparently in contrast with what is commonly perceived by the operators. There is a
general increased risk of pocket hematoma formation in non-elective procedures (9) enhanced by a
greater incidence of perforation if the procedure is preceded by an emergency placement of a
temporary transvenous pacing lead (10). There appears instead to be no difference in the occurrence
of hematomas based on the type of device and the number and specifications of the implanted leads
(11). On the contrary, the use of defibrillation or active fixation leads has been suggested to involve
an increased risk of clinically manifest cardiac perforation (10, 12), whereas implantation of atrial
leads, especially of the passive fixation type, raises the risk of silent, incidentally diagnosed
perforation almost threefold compared with ventricular leads, being more frequent with the latter in
case of defibrillation leads (13). The role of vascular access remains a controversial issue, with no
conclusive data to demonstrate the hypothetical advantage of open access via the cephalic vein
rather than subclavian or axillary venous puncture or cannulation in reducing the risk of bleeding. In
fact both approaches are associated with comparable rates of intraprocedural hemorrhage and
pocket hematoma formation (11, 14).
A variable that undoubtedly influences hemorrhagic risk is the so-called human factor,
responsible for a higher overall rate of complications, including bleeding, observed in trainee
operators or low-volume centers versus expert operators in high-volume centers (15). A recent
Scandinavia study has reported a 5% incidence of pocket hematoma formation in implants
performed by trainees (who had already performed at least 10 implantations as first operator) under
supervision, almost threefold higher than the 1.8% observed in implantations performed by
operators with 5-10 year experience (p=0.037) (16).
Technical Measures for Reducing the Risk of Developing Hemorrhagic Complications
CIED implantation technique does not differ in high hemorrhagic risk subjects and low-risk
patients, even if further measures can be adopted in the former. In fact, it is essential to maintain an
even higher level of attention to hemostasis throughout the procedure, with early identification and
control of active bleeding sources that may cause postprocedural hemorrhagic complications.
Generally, it is advisable to: 1. refer higher risk cases to expert operators, better if at high-volume
centers; 2. compatibly with the respective indications, where possible perform CIED implantation
before elective or deferrable interventional percutaneous procedures; and 3. adopt additional
measures to control bleeding, generally empirical and not validated in controlled studies, in higher
risk patients, based on the preference and/or personal experience of the operator. Some of the most
frequently reported technical measures are reported below.
Some operators prefer to prepare the CIED pocket before proceeding with vascular access
and positioning of the leads, with the theoretical advantage of better controlling intrapocket
bleeding sites even just by mechanical compression with gauze pads introduced into the pocket
(17). The position of the pocket may affect hemorrhagic risk with a possible protective effect of the
prepectoral subfascial position, which minimizes trauma to muscle tissues compared to the
subpectoral position (14).
The use of cephalic vein access excludes the risks of subclavian vein puncture
(pneumothorax, arterial puncture, hemothorax), however there are no data favoring this approach
rather than subclavian or axillary access in reducing the complication of pocket hematoma
formation. Nonetheless, specific technical measures such as subclavian or axillary venography,
permitting direct visualization during venous cannulation, or micropuncture, involving the use of
small-gauge needles to minimize potential bleeding from accidental arterial puncture, may also
reduce hemorrhagic risks caused by the puncture (11). In case of placement of several leads via the
subclavian vein, using a single puncture may reduce the risk of bleeding complications but is
associated with reduced maneuverability (resulting in longer procedure time) and potential damage
to lead insulation.
Although extensively reported in the literature (11) and widely used in clinical practice as a
method to improve intraoperative hemostasis, electrocautery does not appear to be associated with
reduced risk of pocket hematoma formation (1).
Based on other types of surgery, the use of fibrin, thrombin or collagen adhesives injected in
the pocket to favor better local hemostasis has been proposed in patients undergoing concomitant
anticoagulant or DAPT (18, 19). The evidence available is contrasting and only partly comparable,
given the use of different agents in heterogeneous patient populations. In a first study conducted on
82 patients treated with dicumarolic agents or sodium heparin in bridging therapy, injection of a
fibrin adhesive in the pocket before connecting the leads to the generator and placing the latter
prevented the formation of hematoma in all of the 41 patients treated, whereas the complication
occurred in 24.4% of controls (p<0.05) (18). More recently, in a prospective case-control study on
163 patients treated with oral anticoagulant or DAPT, injection inside the pocket of a thrombin and
collagen solution was associated with an increased incidence of the primary composite endpoint of
hematoma requiring evacuation, and infection of the pocket (14.6 vs 3.7% in controls, p=0.03) (19).
The latter data, in line with other observations, are consistent with a lack of efficacy in the
prevention of local hemorrhagic complications and a potentially increased risk of infection,
complemented by the risk of potential sensitization/allergic reactions, even of a severe nature, and a
questionable cost-effectiveness.
Placement of a passive or active surgical wound drain should be limited to selected cases of
excessive intraoperative bleeding (14), although the literature reports good results also for less
restrictive use (20), albeit a general increased risk of contamination and infection of the pocket.
Finally, it is common practice to apply a sterile compressive dressing on the wound, although the
real efficacy and the optimal application time are not known. The application of ice on the wound is
virtually universal, repeated also in the hours following the procedure for pain relief, although the
use of ice for post-surgery pain control is not supported by scientific evidence. Ice may also
potentially limit bleeding due to induced vasoconstriction.
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