Evolving Evidence for Cerebral Protection Devices in Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of symptomatic aortic stenosis (AS). However, the benefits of TAVR are mitigated by the occurrence of stroke, which remains a major issue of this procedure, associated with increased mortality and early-reduced quality of life. Indeed, the PARTNER IIA trial reported a 30-day stroke rate of 5.5% after TAVR, confirming that procedure-related neurological events remain a significant concern even in lower-risk patients and with next-generation transcatheter heart valves.

The primary mechanism of peri-procedural stroke related to TAVR is embolic; hence, cerebral protection devices (CPD) have been developed to minimize the risk of peri-procedural ischemic strokes. Early experience with CPD have demonstrated a reduction in the volume and number of cerebral lesions using diffusion-weighted magnetic resonance imaging (DW-MRI). However, these studies have been hampered by the fact that they were underpowered to detect differences in clinical outcomes, primarily due to the relatively low rate of clinical neurological events at short-term follow-up and the high frequency of new DW-MRI lesions after TAVR. Furthermore, it has been proposed that DW-MRI endpoints may not be an ideal surrogate marker of cerebrovascular events or clinical outcomes, and that study endpoints should be tailored for clinical outcomes in TAVR patients. Individual studies have failed to demonstrate a clinical difference in the incidence of strokes in patients with and without CPD. However, limitations of individual studies may be overcome by combining data and performing a meta-analysis. This is particularly true in studies that may be underpowered and can be used to drive further studies in the field.

In this issue of Cardiovascular Revascularization Medicine , Mohananey et al. present a meta-analysis evaluating the safety and efficacy of CPDs based on clinical endpoints using numerous time intervals to elucidate the impact of CPD during TAVR. A total of 1,225 patients, of whom 570 received embolic protection using CPD, were included from 4 randomized controlled trials (RCTs) and 2 prospective observational studies. Their analysis showed borderline evidence of difference in peri-procedural strokes [RR 0.53 (95% CI 0.27-1.07), p=0.08] between patients with and without CPD. Interestingly, sensitivity analysis using the “one-study-removal” method revealed that removal of study by Haussig et al. moves the overall effect in favor of CPD [RR 0.37 (0.15-0.90)]. Moreover, overall strokes were significantly lower in the CPD group [0.56 (95% CI 0.33-0.96)] at 1-week follow-up. These findings are important, as the risk of stroke after TAVR is greatest in the first week after TAVR, validating the efficacy of CPD. Indeed, a sub-analysis of the PARTNER trial revealed that 64% and 85% of the strokes are diagnosed within 2 and 7 days after the procedure, respectively, thereby demonstrating that these events are overwhelmingly procedural in nature. In addition, the authors found no evidence of difference between patients with and without CPD for: stroke or all-cause mortality at 30 days; mortality at 30 days; and major bleeding, life-threatening bleeding, or major vascular events. This provides further weight to the safety and efficacy of CPD as adjunctive therapy to TAVR. In addition to the clinical endpoints outlined by Mohananey et al., several of the included studies have also shown improvement in short-term neuropsychiatric testing (Montreal Cognitive Assessment) with use of CPD; the long-term benefits of this have yet to be fully elucidated.

The evolving beneficial role of CPD in TAVR is becoming clearer. We are dealing with a potential benefit that cannot be ignored, with greater number of TAVR procedures being performed globally. Such considerations become more important as TAVR shifts to younger and lower-risk patients, where preventing procedure-related cerebral injury remains a significant unmet clinical need with potentially important long-term sequelae. There remain two resounding issues as we aim overcome this unmet need. Primarily, if we are to say CPD is important, then it is imperative that iterations of current devices provide complete neurological coverage. Secondly, as Mohananey et al. outline, the cost of CPDs forms an important part of decision-making for any new procedure. We can hypothesize that the impact of using a CPD that provides comprehensive cerebral protection will yield greater clinical benefit and that this will assist in illuminating the net financial benefit of CPDs for healthcare systems by avoiding short- and long-term sequalae of cerebral injury. Indeed, the recent acquisition of Claret Medical by Boston Scientific highlights the potential economic and clinical value of CPD and will help to drive penetration as well as future clinical studies of CPD in TAVR and other transcatheter interventions. However, for CPD to become routine in all TAVR procedures will require further device iteration, specific CPD reimbursement and, for the purists, a randomized trial that is adequately powered to detect a difference in clinical stroke.

CRM

Evolving Evidence for Cerebral Protection Devices in Transcatheter Aortic Valve Replacement

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