Thromboembolic and Bleeding Complications in Transcatheter Aortic Valve Implantation: Insights on Mechanisms, Prophylaxis and Therapy

Abstract

Transcatheter aortic valve implantation (TAVI) has emerged as an important alternative to surgical aortic valve repair (SAVR) for patients with severe aortic stenosis. This rapidly advancing field has produced new-generation devices being delivered with small delivery sheaths, embolic protection devices and improved retrieval features. Despite efforts to reduce the rate of thrombotic complications associated with TAVI, valve thrombosis and cerebral ischaemic events post-TAVI continue to be a significant issue. However, the antithrombotic treatments utilised to prevent these dreaded complications are based on weak evidence and are associated with high rates of bleeding, which in itself is associated with adverse clinical outcomes. Recently, experimental data has shed light on the unique mechanisms, particularly the complex haemodynamic changes at sites of TAVI, that underpin the development of post-TAVI thrombosis. These new insights regarding the drivers of TAVI-associated thrombosis, coupled with the ongoing development of novel antithrombotics which do not cause bleeding, hold the potential to deliver newer, safer therapeutic paradigms to prevent post-TAVI thrombotic and bleeding complications. This review highlights the major challenge of post-TAVI thrombosis and bleeding, and the significant issues surrounding current antithrombotic approaches. Moreover, a detailed discussion regarding the mechanisms of post-TAVI thrombosis is provided, in addition to an appraisal of current antithrombotic guidelines, past and ongoing clinical trials, and how novel therapeutics offer the hope of optimizing antithrombotic strategies and ultimately improving patient outcomes.

Impact of Antithrombotic Regimen and Platelet Inhibition Extent on Leaflet Thrombosis Detected by Cardiac MDCT after Transcatheter Aortic Valve Replacement

“…Transcatheter aortic valve replacement (TAVR) has become the standard of care in patients with severe symptomatic aortic valve stenosis and who are at intermediate or high surgical risk [1,2]. Despite recent advances, a wide range of ischemic and bleeding complications might mitigate the beneficial effect of TAVR procedures [3]. Although early stent valve thrombosis after TAVR remains a rare complication, recent reports have emphasized that subclinical leaflet thrombosis (SLT) is detected in a sizeable proportion of patients (7–15%) with normal echocardiographic parameters.…”

Anticoagulation after Transcatheter Aortic Valve Implantation: Current Status

“…It includes valve-related flow turbulence, vessel wall disruption, metallic frame exposure (which in turn induces platelet activation) and patientrelated prothrombotic factors, irrespective of the valve type (balloonor self-expandable) or procedural approach (transfemoral or transapical). 34 Other patient-related factors, such as AF, periprocedural hypotension or hypoperfusion, should be considered determinants of CVEs. 35 The acute events seem to be slightly different: thrombi derive from the interaction between the device and the calcified aortic valve, with debris dislodgment due to the placement of wires and catheters, pre-and post-dilatation.…”

Antithrombotic Therapy After Transcatheter Aortic Valve Implantation

“…Indeed, TAVI interventions are associated with the occurrence of thrombotic and haemorrhagic events, which can occur periprocedurally or during the short-or longterm follow up after the index procedure. 7,8 Given the observed important rise in the number of interventions, it is of utmost relevance to determine the optimal antithrombotic strategy after TAVI. In this scenario, an accurate assessment of the balance between thrombotic and bleeding risk, which can be augmented if an unnecessarily potent antithrombotic regimen is chosen, is critical.…”

“…and inflammation (unlike normal valves, stenotic valve leaflets are rich in tissue factor and thrombin); changes in the flow patterns that may predispose to thrombus formation; and other mechanisms occurring during positioning and implantation (aortic wall injury, air embolism, rapid pacing or haemodynamic instability that may lead to cerebral hypoperfusion, etc.). [7][8][9][10] CVEs are undoubtedly among the most feared complications of TAVI, since they have a considerable impact on morbidity and mortality. [11][12][13] The greatest risk of suffering a clinically apparent stroke is within hours after TAVI, but remains high for up to 2-3 months.…”