PARIS — Two new studies provide insights but no easy answers regarding who should receive embolic protection during transcatheter aortic valve replacement (TAVR) to reduce major cerebrovascular events.
A new meta-analysis showed that use of embolic protection in TAVR did not reduce mortality but was associated with fewer strokes at 30 days, the latter driven largely by registry data and not confirmed by randomized controlled trials.
The rate of new silent ischemic cerebral lesions detected with diffusion-weighted (DWI) MRI reached 80%. However, no differences were seen in the number of new lesions detected in patients treated with and without embolic protection, study author Luca Testa, MD, IRCCS Policlinico San Donato, Milan, Italy, said during a hotline session at the Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2018.
"The available literature does not support the routine use of cerebral protection in patients undergoing TAVR," he concluded. Rather, "it should be considered in selected patients who are at high risk of embolization from the aortic valve, root, and arch."
A SENTINEL trial substudy that examined anatomy in great detail, however, found a consistent trend toward stroke reduction with embolic protection (Sentinel TCEP, Claret Medical) across all anatomic subsets, including arch type, root angulation, and calcium burden.
The data are from a small number of patients and are hypothesis-generating, but "I put to you that at least as we perform with carotid stenting routine cerebral embolic use, perhaps we need to consider the same with transcatheter aortic valve implantation," study author Hasan Jilaihawi, MD, New York University Langone Health, New York City, said during the same late-breaking, hotline session.
Jilaihawi pointed out that the average stroke rate is 4.4% among contemporary TAVR studies, with most being nonrandomized registries that may underestimate the true neurologic risk. Few predictors other than prior stroke and advanced age have been identified.
Prior results from SENTINEL showed that embolic debris is captured in 99% of patients and that 30-day stroke risk is reduced from 9.1% without the device to 5.6% with the device, although the study was not powered for clinical endpoints.
The anatomic substudy involved 347 of the trial"s 363 patients who had complete anatomic data at baseline, of whom 16 patients had a stroke 3 days after TAVR.
For patients with a type 1 aortic arch, who comprised more than 80% of patients in the analysis, "there was a clear and significant reduction in stroke events" with Sentinel vs without (7/196 vs 8/80; P = .042), Jilaihawi said. Type 2 arches were too few to reliably analyze.
Stroke rates trended lower with protection regardless of aortic root angulation severity or aortic arch calcium severity. The greatest benefit, however, appeared to be in patients with the lowest range of aortic calcium, whether graded semi-quantitatively as trivial or mild on the Rosenhek scale (1/66 vs 4/35; P = .033) or quantitatively with a cutoff of 73.5 mm3 or less (1/76 vs 4/37; P = .026). This paradox potentially could be explained by the friable nature of the tissue at high risk for embolization, he said.
Session co-chair Alain Cribier, MD, University of Rouen Charles Nicolle Hospital, France, questioned how many patients had predilatation or repositioning of the valve, which greatly increases stroke risk and sometimes is needed, for example, with the CoreValve (Medtronic) because of a lack of calcium. "It"s not clear to me whether the anatomical factors only play a role," he said.
"This is a very important point," Jilaihawi agreedhe said. "There is an interplay between procedural aspects and the anatomy that is not completely captured in this study because we don"t know the cases which were recaptured multiple times, which certainly could contribute."
Panelist Manesh Manoharan, MD, RoyalVictoriaHospital, Belfast, United Kingdom, commented that "In all the registries so far, there has been no real difference shown between repositional versus nonpositional in a clinical trial data sense." Nevertheless, it is important to remember that registries report only major strokes but that all strokes events are important to patients undergoing TAVR.
Co-chair Ran Kornowski, MD, RabinMedicalCenter, Petah Tikva, Israel, questioned who should be targeted for cerebral protection, noting that a lack of reimbursement in Europe currently limits its use to about 10% to 20% of TAVR cases.
"I hoped to find a strata that was truly high risk but there is no clear strata that is truly high risk, so it [stroke] remains an unpredictable event," Jilaihawi concluded. "So in the ideal world, we would use it in everyone."
Panelist Saibal Kar, MD, Cedars-Sinai Medical Center, Los Angeles, California, quipped, "So you would conclude, it is like a seat belt, you should wear it."
Benefit on MRI
Testa and his colleagues examined data from 1285 patients, half of whom were women, who participated in eight TAVR trials through December 2017. Their mean age was 81.7 years, 13% had a previous stroke, and atrial fibrillation was present at baseline in 30.6%.
Stroke was reported in 4.8% of patients treated with the embolic protection device (EPD) and 6.0% of those without EPD use.
At 30 days, mortality was similar between the two groups (odds ratio [OR], 0.43; P = .3), while stroke rates were significantly lower with embolic protection (OR, 0.55; 95% CI, 0.31 - 0.98; P =.04), with a number needed to treat of 33.
As previously noted, DW-MRI revealed no difference in the number of new lesions between patients treated with and without embolic protection (mean difference, –0.19) but its use was associated with smaller volume per lesion (mean difference, –0.52; P =.002) and smaller total volume of lesions (mean difference, –0.23; P = .02).
"So in a sense the use of EPD reduced the burden of the emboli," Testa said.
Embolic protection was also more beneficial in patients treated with a self-expanding vs a balloon-expandable valve.
Limitations of the study include the use of different devices, including the Sentinel, which covers only 9 of 28 brain regions, the TriGuard (Keystone Heart), and the Embrella (Edwards Lifescience), which is no longer available, Testa said. Also, the results may have been affected by the use of different MRI scanners and different MRI windows, which varied by up to 7 days after TAVR.
"The percentage of patients experiencing a brain damage assessed by diffusion-weighted MRI following TAVI is significantly higher than those having a clinically relevant cerebrovascular event," Testa concluded.
Panelist Corrado Tamburino, MD, PhD, University of Catania, Italy, said the finding that so many lesions exist in the brain with no clinical consequences is interesting but that stroke itself remains a rare event.
"Should this not be put into the balance when you have to spend time, money, and add some additional risk to use cerebral protection device?" he asked.
Tamburino went on to express concern about the routine use of embolic protection devices in all cases, "especially at a time when TAVR is moving toward a younger population."
Kar countered that given the inability to predict who is at high risk and that the safety of the devices has been demonstrated in randomized trials, "I think we should protect against stroke because the cost of a stroke is much more costly than the cost of the device."
Testa noted that the stroke rate dropped to 4.8% with embolic protection but that the absolute reduction was only about 1%. Kar quickly interjected, "4.8% is still high… I think a 1% reduction of stroke is very important, especially as we go into low-risk patients."
An audience member suggested, however, that the 6% stroke rate without embolic protection does not reflect current practice with newer-generation stents.
Testa said it"s only logical that the procedure and device manipulation would affect stroke rates, but to predict who would benefit from embolic protection in TAVR, future randomized trials need to be large, enroll younger patients, and be able to detect possible differences in a clinical endpoint of stroke rather than a surrogate endpoint based on MRI results. "Because this is what matters."
Jilaihawi reports receiving grants/research support from Abbott and Medtronic and honoraria or consultation fees from Edwards Lifesciences and Venus Medtech.