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.