Cerebral Protection Devices in Transcatheter Aortic-Valve Replacement

Abstract

Transcatheter aortic valve replacement (TAVR) is a common procedure used in the treatment of severe aortic stenosis and other cardiac valve diseases. Although this procedure has been shown to be effective and safe in improving cardiac function and life expectancy in this population, there is an inherent risk of neurological complications such as stroke and cognitive impairment. In the last years, there has been a breakthrough in the development of brain protection devices that minimize the risk of brain embolism during the procedure. These devices are designed to capture clots and calcium debris that could become dislodged during the valve implant, therefore keeping the embolus from entering the nervous system via the supra-aortic vessels. Some studies indicate that using brain protection devices during an aortic valve replacement could substantially decrease the burden of stroke and other associated neurological complications. However, despite the promising expected results, further studies are required to sustain the benefit of using these devices, besides with the ongoing development in this area it would be fundamental a face-to-face interaction between the devices in the current development. Furthermore, although the experience with these devices is limited and the recent experience indicates they are safe, it would be fundamental to identify and take in consideration possible risks and complications related to these devices.

1. Introduction

Aortic stenosis is the most prevalent valve disease in the developed countries. Its prevalence increases in the elderly; in this population, transcatheter aortic valve replacement (TAVR) is a viable option for subjects with intermediate or high risk of cardiac surgery. Despite the development of new generations of TAVR, cerebrovascular events are one of the most severe and scary complications because of the increase in morbidity and mortality, the risk of stroke at 30 days ranges from 2.7 to 10% [1, 2]. Apart from clinical strokes, subclinical strokes, defined by the appearance of new ischemic cerebral lesions by MRI, appear in 90% of patients undergoing TAVR [3]; however, their clinical significance is still unknown.

TAVR implantation-related strokes are divided into acute or periprocedural and late. For prevention, various methods have been identified. In the first group (acute), the main factors to take into consideration include optimization of the TAVR technique with reduction of embolization of calcified fragments and atheroma, and adequate anticoagulation during the procedure. For late strokes, the main factor is the use of an optimal antithrombotic regimen after implantation.

The greatest risk of embolization to the brain occurs during the procedure, during the positioning or implantation phase of the valve, as a result of manipulation of highly calcified structures or atheromatous embolization of thrombi or material [4]. Up to 70% of patients experience a stroke in the first 24 hours [5, 6, 7] with a considerable deterioration in quality of life and a 3–5-fold increase in mortality [8]. Cerebral protection devices (CPDs) have the potential to reduce stroke and ischemic brain injury associated with percutaneous aortic valve replacement. The results of a recent study that analyzed a database with 36,220 patients (525 of them with CPD systems and 35,695 without them) found that the use of a CPD was associated with a lower incidence of ischemic stroke (1.0% vs. 3.8%, p < 0.002) and lower in-hospital mortality. Importantly, silent strokes account for a significant proportion of these complications and are associated with a threefold increased risk of having a stroke, a further decline in cognitive function, and a twofold increased risk of developing dementia after follow-up for 4 years [9].

Until March 2023, only two authorized devices were identified as DPC, the Sentinel device, which is designed to capture emboli or debris detached during TAVI. It consists of a dual filter into the left common carotid and brachycephalic artery; inside a 6Fr catheter that is accessed through the radial artery, the proximal filter is placed in the brachiocephalic artery and the distal filter in the common carotid artery (available in United States and Europe) [1] and the TriGUARD 3 (available in Europe) is the only device that covers all the arteries of the aortic arch. Being a deflector device, it rejects emboli during TAVR placement. This device is advanced via femoral contralateral access to TAVI placement and is deployed to protect the supra-aortic vessels [10].

2. Risk factors for cerebrovascular events

The risk factors for post-TAVR stroke are divided into early (acute and subacute) and late (Table 1).

Multiple dilations of the aortic annulus or post-dilatation of the valve.

Pacing stimulation in multiple times.

Higher acceleration speed of the native aortic valve (greater calcification).

Non-femoral vascular access (axillary, transaortic, carotid, transapical).

Chronic kidney disease.

Female gender.

Decreased ejection fraction of the left ventricle.

Atrial fibrillation.

Table 1.

Risk factors for stroke in TAVR implantation.

Indicators of an early stroke encompass features of the patient and the procedure itself. Procedure features associated with early stroke risk include a greater number of dilations of the aortic valve annulus, a greater degree of valve acceleration velocity before implantation (reflecting more severe plaques with more calcium deposits, or the need for additional instrumentation to cross the aortic valve and complete the procedure), and a greater number of pacing events [11].

In a study carried out in more than 20,000 patients from Europe and Canada, the predictors of post-TAVR stroke were evaluated. Age, previous stroke and peripheral arterial disease, chronic kidney disease, atrial fibrillation, and diabetes were identified as risk factors [9].

In a recent analysis of the Transcatheter Valve Therapy (TVT) registry by Thourani et al., which included 97,600 patients, the approach with an alternative access for TAVR (i.e., use of an access other than transfemoral or direct aortic access) was identified to had the highest relative risk for TAVR intrahospital stroke [12].

In the CoreValve studies, factors such as reduced body surface area, severe aortic calcification, and frequent falls in the past 6 months were found to be indicators of increased risk of subsequent stroke [13].

3. Current evidence on the use of cerebral protection devices (CPD) in TAVR

An analysis of 108,315 patients undergoing TAVR examined the use of CPD in 4380 patients (4.0%). The results revealed that adjusted mortality was lower in those patients who underwent TAVR with CPD compared with those without CPD (0.5% vs. 1.3%, p < 0.01).

In addition, neurological complications, including hemorrhagic stroke and ischemic stroke, were also lower in the CPD group compared with the non-CPD group (1.4% vs. 2.2%, p < 0.01). Likewise, patients who experienced a stroke after TAVR and used CPD were found to have a significantly lower in-hospital mortality rate compared with those without CPD (6.3% vs. 11.8%; p = 0.023). These findings suggest the possibility that CPDs may prevent more severe and debilitating strokes, which in turn could reduce stroke-related morbidity and mortality [14].

A recent meta-analysis demonstrated that the use of CPD was associated with a lower risk of mortality related to stroke (odds ratio 0.47; 95% CI, 0.28–0.80), lower risk of stroke (odds ratio 0.54; 95% CI, 0.39–0.75), transient ischemic attack (odds ratio 0.47; 95% CI, 0.31–0.71), and adverse cardiovascular and cerebrovascular events (odds ratio 0.70; 95% CI, 0.56–0.87). These data suggest that CPD should be considered during TAVR procedures to reduce the risk of stroke-related mortality and other complications [15].

An observational study was conducted in 2023 using the TriGUARD 3 ™ (Figure 1) device to assess the incidence of stroke and transient ischemic attacks (TIA) within 72 hours or at discharge after TAVR implantation. The results revealed stroke incidence of 0.8%, suggesting that the use of this device is associated with a low frequency of clinically detectable strokes and device-related adverse events [11].

Figure 1.

TriGUARD ™ device.

The PROTECTED TAVR study evaluated the effectiveness of cerebral embolic protection (CEP) during TAVR in reducing the risk of stroke. The study involved 3000 patients, the primary endpoint being the identification of clinical stroke within 72 hours of TAVR or before discharge. The study found that the use of CEP did not have a significant effect on the incidence of periprocedural stroke; however, it reduced the incidence of disabling stroke. The study concluded that among patients with aortic stenosis undergoing transfemoral TAVR, the use of CEP had no significant effect on the incidence of periprocedural stroke [14] using Sentinel ™ (Figure 2).

Figure 2.

Sentinel ™ device.

4. Conclusions

Stroke related to TAVR represents one of the most common and scary complications and is an independent risk factor that predicts morbidity and mortality; therefore, new strategies have been implemented to reduce its appearance. CPDs represent a novel strategy in stroke protection in patients undergoing TAVR. This evidence suggests that the use of CPD reduces the number and size of ischemic lesions identified on magnetic resonance; however, they are not yet established as a protective measure in the appearance of embolic phenomena and the reduction of ischemic lesions in TAVR patients. None of the devices we mainly studied managed to reduce the appearance of stroke; however, there was a reduction in the number of disabling strokes, which has an impact ultimately in a possible better quality of life.