This study revealed that patients who received Impella® RP devices were less likely to develop avWS during their treatment, relative to patients who received Impella® 5.0/CP devices. Furthermore, the development of avWS was associated with bleeding complications in our cohort. Moreover, we did not identify any cases of thrombotic complications or access site bleeding in the Impella® RP group. The combination of ECMO and Impella® therpy was not associated with a higher incidence of bleeding complications nor with the development of avWS.
Cases of avWS are relatively common after MCS therapy, with reported incidences of 30–100% depending on the type of support, device, and measurement method.8, 9, 14, 15 Furthermore, avWS is associated with an increased risk of bleeding among patients who require MCS.8, 9, 13, 18, 19, 26 In patients with left ventricular assist devices, avWS is associated with increased risks of early and long-term bleeding complications.8, 14 In patients who require temporary MSC, such as ECMO, avWS is also very common and is associated with an increased risk of major bleeding complications.11, 12, 15 The severity of the bleeding complications depends on comorbidities, the duration of MCS, and anticoagulation or platelet inhibition during MCS.27
This study revealed that the patients had elevated baseline values for vWF:Ag and vWF:Ac, with a normal activity-to-antigen ratio. Although none of the patients fulfilled the diagnostic criteria for possible avWS preoperatively, many exhibited reduced vWF function that was reflected in a reduced activity-to-antigen ratio. In this context, avWS is caused by the loss of large vWF multimers via increased vWF clearance, increased binding to cell surfaces, and/or proteolytic loss. During MCS, avWS is predominantly related to increased proteolytic cleavage of vWF by ADAMTS13, which is promoted by shear stress-dependent conformational changes in these multimers. This cleavage increases the risk of bleeding among patients who require MCS. In our cohort, despite similar pump power and support, avWS was less common in the group that received right ventricular support (vs. left ventricular support), which might be related to lower pressures and less shear stress at the right ventricular site. Another possible explanation is that the group that received left ventricular support was more likely to receive both ECMO and an Impella® device, which would suggest that two MCS strategies could increase the risk of avWS. However, we failed to detect a significant difference in avWS or major bleeding complications according to the use or non-use of ECMO.
Bleeding complications after Impella® CP/5.0 device implantation may compromise the outcomes in patients with cardiogenic shock.6, 21 In particular, access site complications have been discussed as potential causes of major bleeding. Unfortunately, previous studies have provided limited information regarding anticoagulation strategies, bleeding locations, and temporal relationships with Impella® device implantation. Therefore, further studies are needed to address these issues.
The Impella® RP device is a novel mechanical right ventricular support system. However, given the relatively uncommon nature of isolated acute right ventricular failure, there is limited experience with Impella® RP devices and most centers have performed < 10 implantations. Thus, given their early locations on the learning curve, most centers have been unable to provide useful data regarding access site bleeding and major bleeding complications in cases with Impella® RP usage. To the best of our knowledge, our experience with 20 patients who received Impella® RP devices is the largest single-center cohort at this time. We did not detect any right ventricular support cases with access site complications, which may be related to venous access being safe, based on the lower pressure and less calcification. Given the short learning curve, safe implantation for right and left ventricular support seems possible. Thus, while access site management might contribute to bleeding complications, it did not play a major role in our cohort.
We still observed a significant number of major and fatal bleeding events in our cohort (32 patients, 53%). This may be related to the use of these devices as a last resort in patients who were failing previous treatment, especially early in our learning curve, which might suggests that the patients had severe cardiogenic shock with or without right ventricular failure. Furthermore, after the first implantations, we used PTT and activated clotting time to control anticoagulation, while laboratory testing for other coagulation factors, such as vWF, was only performed for patients with bleeding complications. However, after clinical observation of bleeding complications, we established a standard operating procedure that included testing for coagulation factors and avWS screening. We suggest that anticoagulant management during Impella® treatment should be differentiated beyond simple testing for activated clotting time or PTT.
The present study has various limitations that should be considered. First, the retrospective analysis of data regarding avWS and bleeding events inherently selects for patients who underwent related testing, although this was not routinely performed during the first few months after this novel treatment was established. Thus, the results might be influenced by selection bias and a prospective study is needed to confirm the incidence of avWS during Impella® treatment and its association with bleeding complications. Second, the analysis of vWF parameters was limited to vWF:Ag and vWF:Ac, which precludes a commentary regarding vWF multimers and the potential influences of ADAMTS13 on vWF parameters. Furthermore, it can be difficult to evaluate the vWF activity-to-antigen ratio in a situation with highly elevated vWF parameters, although certain patients with avWS-associated disorders may only exhibit reduced concentrations of high molecular weight vWF multimers during laboratory testing. Third, a large subgroup of patients was receiving preprocedural antiplatelet and anticoagulation therapy, which suggests that alternative causes of bleeding complications are possible. Fourth, the shear stress induced by centrifugal pumps depends on the rotational speed, and pump designs with different flow patterns may have different effects on coagulation parameters. Further studies of these differences are needed to guide optimal anticoagulation management in this setting.
Based on the association between aVWS and bleeding complication observes in this study, we updated our diagnostic strategy for all patients who require axial flow pump support to routinely include testing for factors II, V, VII, VIII, X, and XIII, as well as antithrombin III, thrombin clotting time, aPTT, international normalized ratio, and vWF:Ac. Furthermore, all patients who require MCS are screened for avWS before implantation, as well as factor deficiencies and avWS on days 1, 3, and 5. In cases with major bleeding and avWS, we administer factor VIII and vWF (Haemate®) to achieve a platelet count of > 100,000/mL and normalize the aPTT. In cases with avWS but no bleeding, we aim for lower PTT values (35–40 s) and a platelet count of > 70,000/mL. We plan to evaluate the possible benefits of this more differentiated anticoagulation strategy in a prospective study.