Discussion
The main findings of our retrospective analysis can be summarized as
follows: 1) MVCs were the most frequent among major complications of CA
for AF and occurred twice as often in females than in males, 2) Body
size, particularly low body height in females, was an important
determinant of MVCs, 3) US-guided venipuncture lowered MVCs only in
males, and 4) trend in reducing MVCs was observed during the study
period.
Risk of vascular complications
The above data on a higher frequency of vascular and bleeding
complications in females after catheter ablation for AF (including
hospital readmissions) were recently reported from the US nationwide
database, analyzing nearly 55 thousand patients.7However, no subgroup analysis was performed for anthropometric
parameters in this study. Another recent analysis of 21 thousand
patients with the previous ablation for AF confirmed that females have a
higher risk of virtually all complications and more frequent
readmissions.8 Both Shah et al.4 and
Spragg et al.9 identified female gender (odds ratio
(OR): 1.3, 95% CI: 1.1–1.7, P < 0.05 and OR: 3.0, 95% CI:
1.3–7.2, P = 0.014, respectively) as the independent predictors of
major complications of the AF ablation procedure. In the latter series,
the vascular injury was the most prevalent complication, occurring in
1.7% of the cases.9 In other similar studies, access
site hematoma was by far the most common vascular complication which was
more frequent in females vs. males (2.1 vs. 0.7% and 6.8 vs. 0.9%, P =
0.026, P = 0.027 respectively).10,11 All the above
data are very similar to our results, where groin hematoma accounted for
2.4 and 0.7% in females and males, respectively. In total, MVCs in our
trial reached 2.4% and included also groin hematomas prolonging
hospitalization and/or retroperitoneal bleeding. This rate may look
higher than in other studies, where vascular complications ranged from
1.1 to 1.9%.12,13 However, these trials mostly
addressed only arterio-venous fistula and pseudoaneurysm as vascular
complications. In a trial by Shah et al.4, in which
vascular complications were classified more broadly, the vascular
complication rate reached 2.6%, replicating our results.
Vascular complications are also the most common in patients undergoing
percutaneous coronary interventions with access site hematoma the most
frequent among them.14 Even in this setting of
arterial access and the use of antiplatelet drugs together with
unfractionated heparin, bleeding complications were more pronounced in
females vs. males (4.3 vs. 1.9% with OR: 2.3 (95% CI:
1.6–3.3)14 or 5.8 vs. 2.5%, (P =
0.02).15
Summarizing all the above data, both CA for AF and percutaneous coronary
intervention bear a similar rate of vascular complications, which are
higher in females compared to males.
Body size as a risk factor
Searching for predictors of MVCs after CA for AF, we revealed an
important role of body size. The body size can be characterized by body
weight or height or BSA. Of these, the body height was most tightly
associated with MVCs although BSA was a significant competitor that was
comparably strong in prediction models. In our previous study, low body
weight was identified as a single independent risk factor for major
complications with a 0.8% increase per 10 kg of body weight
reduction.6 This analysis covered the early period
when oral anticoagulants were interrupted before the procedure and low
molecular weight bridging was used. Such a strategy could contribute to
a higher risk of bleeding in subjects with lower body weight.
Underweight patients were also found to have higher exposure to oral
anticoagulants.16 The former study was considerably
smaller, utilized slightly different definition of complications, and
did not analyze MVCs separately. Nevertheless, it was not reported that
BSA was comparable to body weight in predicting complications already at
that time.
The current study identified low body height to be the most predictive
for MVCs, particularly in females. Females of low stature independently
of body weight are at higher risk of MVCs, which is in contrast to the
common belief and scarce data17 that obese patients
may have relatively lower levels of anticoagulants, causing less
frequent complications. Our high-risk female patients were of low
stature, not notably underweight. Of importance is the magnitude of the
effect. By every 5 cm of decrease of body height in females, MVCs rise
by 1.3%. On the contrary, in males body height failed to characterize
patients with MVCs, while BSA was univariately associated with MVCs. A
similar relationship of vascular complications to body size was observed
in a study by Piper et al. after the coronary
interventions.18 They found lower stature and BSA
< 1.6 m2 (OR: 4.4, 95% CI: 3.32–5.96, P =
0.001) as a predictor of vascular complications, however, no gender
differences were analyzed.
We may only speculate about higher MVC in females and relationship to
body size. Although female gender itself did not numerically play a role
in a rate of MVCs, this is not by far a proof of absent impact. First,
it has been shown that the pharmacokinetic profile of heparin is
different in females as compared to males with a higher preponderance of
women to increased values of ACT after administration of the same
loading dose of a drug.17 Body size and composition
likely influence the plasma level of heparin. Winkle et
al.19 showed that with the increased level of heparin
anticoagulation, vascular and hemorrhagic complications increased
linearly from 1.62 to 5.55%. Second, some studies described the
differences in femoral vascular anatomy between men and women, with a
smaller size of both artery and vein and the femoral artery and
circumflex branches running very close and often overlapping the femoral
vein in females.20,21 Sharma et al. demonstrated that
one of the predictors of the MVC was the use of more than 4 vascular
accesses in the groin.22 In UK prospective PCI
registry, the use of larger size femoral access sheaths was associated
with an increased risk of bleeding.
US-guided venipuncture
Among predictors of MVCs, US - guidance for venous access plays a
paramount role. Sharma et al. documented a significant decrease in MVCs
using US guidance.22 In another analysis on 499
elderly women, vascular complications occurred less often in the
US-guided group. 23 In our former randomized trial,
US-guided venipuncture did not demonstrate a significant benefit in
respect to MVCs, probably due to low event rate, however, all
intra-procedural measures were in favor of the US-guided
approach.24 In a meta-analysis by Sobolev et al., the
use of real-time US-guidance decreased access-related bleeding and
life-threatening vascular complications, thought the number needed to
treat was quite large.25 Another larger meta-analysis
demonstrated that the use of US-guidance for vascular access in EP
procedures reduces the risk of MVC by 71% compared with the standard
anatomical approach.26 Moreover US guidance
significantly reduced puncture time and inadvertent arterial
puncture.26 Our results confirmed favorable outcome in
respect to MVCs only in males, females do not seem to benefit from
US-guidance. This may support the hypothesis about gender-related
differences in the pharmacokinetic profile of heparin and dependence of
plasma heparin level on body size and composition or size of the sheaths
in relation to the vessel diameter rather than the arrangement of the
vessels.
Complication rate during the study period
In this study, we revealed a mean reduction of MVCs by 1.7% during the
study period embracing almost 13 years. Within this time frame, several
changes in procedural workflow occurred. These include the switch to
uninterrupted oral anticoagulation without bridging with low molecular
weight heparin, increasing use of direct oral anticoagulants,
US-guided venipuncture or the use
of “Z”-stitch for venous access site closure as examples. Only
US-guided venipuncture led to the reduction of MVCs in males, other
measures have not resulted in the tangible reduction of MVCs. In
contrast to the vast clinical knowledge of lower bleeding rate with the
use of uninterrupted oral anticoagulation in CA for
AF27, no MVC reduction was observed in our analysis.
Unfortunately, we do not have the data on the proportion of direct oral
anticoagulants and this may be one of the factors. Generally, low
complication rate may be another factor. Besides these changes,
individual and cumulative operator experience also played a role, but
this cannot be easily quantified and analyzed.
Implications
Our observations may have implications for clinical practice. First,
because a body size contributes to the level of intraprocedural
anticoagulation, we may reconsider a lower level of ACT target in
females, especially in those with lower stature. In this respect, it has
to be emphasized that current recommendations of intraprocedural ACT
between 300 to 350 s are largely based on intracardiac echocardiographic
observation of small thrombi with ACT values around 250 s in the era of
interrupted periprocedural oral anticoagulation and not on actual
clinical events. Some observations documented the safety of the AF
ablation procedure with lower ACT levels (even below 210
s).17 Second, given a higher rate of MVCs in smaller
women, we may speculate that using a smaller diameter of vascular
sheaths could decrease the risk of MVCs.
Limitations
The study has several limitations. First, it is a retrospective analysis
and during the study period, many changes occurred in the procedural
strategy and anticoagulation treatment. Consequently, some relevant
factors, e.g. bridging strategy, details on non-interruption schemes,
types of anticoagulants, experience of operators, fellows in training
engagement, were not collected systematically to be included in the
multivariate analysis. Second, the relatively low rate of MVCs in our
center results in a relatively low power of the study to identify the
effect of other procedural and anticoagulation factors. Third,
conclusions derived from multivariate analysis do not necessarily
reflect the causality, so that we cannot exclude the impact of gender
itself on a rate of MVCs. Finally, although quite large, it still
reflects single-center experience.