Neurocognition and Cerebral Lesion Burden in High-Risk Patients Before Undergoing Transcatheter Aortic Valve Replacement: Insights From the SENTINEL Trial.

OBJECTIVES: The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. BACKGROUND: TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. METHODS: SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤-1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below -1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume. RESULTS: Among 234 patients tested, the mean composite z-score was -0.65 SD below the normative mean. Domain scores ranged from -0.15 SD for attention to -1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p < 0.001), verbal memory (p < 0.001), and visual memory (p < 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations. CONCLUSIONS: There was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.

Protection Against Cerebral Embolism During Transcatheter Aortic Valve Replacement.

BACKGROUND: Neurological complications after transcatheter aortic valve replacement (TAVR) may be reduced with transcatheter cerebral embolic protection (TCEP). OBJECTIVES: This study evaluated the safety and efficacy of TCEP during TAVR. METHODS: Nineteen centers randomized 363 patients undergoing TAVR to a safety arm (n = 123), device imaging (n = 121), and control imaging (n = 119). The primary safety endpoint consisted of major adverse cardiac and cerebrovascular events (MACCE) at 30 days, and the primary efficacy endpoint was reduction in new lesion volume in protected brain territories on magnetic resonance imaging scans at 2 to 7 days. Patients underwent neurocognitive assessments, and the debris captured was analyzed. RESULTS: The rate of MACCE (7.3%) was noninferior to the performance goal (18.3%, pnoninferior < 0.001) and not statistically different from that of the control group (9.9%; p = 0.41). New lesion volume was 178.0 mm3 in control subjects and 102.8 mm3 in the device arm (p = 0.33). A post hoc multivariable analysis identified pre-existing lesion volume and valve type as predictors of new lesion volume. Strokes at 30 days were 9.1% in control subjects and 5.6% in patients with devices (p = 0.25) Neurocognitive function was similar in control subjects and patients with devices, but there was a correlation between lesion volume and neurocognitive decline (p = 0.0022). Debris found within filters in 99% of patients included thrombus, calcification, valve tissue, artery wall, and foreign material. CONCLUSIONS: TCEP was safe, captured embolic debris in 99% of patients, and did not change neurocognitive function. Reduction in new lesion volume on magnetic resonance scans was not statistically significant. (Cerebral Protection in Transcatheter Aortic Valve Replacement [SENTINEL]; NCT02214277).

The Cobalt chromium STent with Antiproliferative for Restenosis II (COSTAR II) trial study design: advancing the active-control evaluation of second-generation drug-eluting stents.

BACKGROUND: Randomized clinical trials have demonstrated the superiority of drug-eluting stents (DESs) compared with bare-metal stents in reducing the need for revascularization and major adverse cardiac events (MACEs) in low-risk patients with single-vessel lesions. Rapid DES uptake has necessitated shifting the paradigm to active DES-controlled noninferiority study models with most studies using surrogate angiographic measurements to attain adequate statistical power. No previous prospective trial has specifically compared a new DES with an active-control DES in a high-risk patient population using primary clinical end points. OBJECTIVE: COSTAR II is designed to compare use of the investigational Costar stent (Conor MedSystems, Palo Alto, CA) with the Taxus (Boston Scientific, Maple Grove, MN) stent in single- and multivessel percutaneous coronary intervention. The primary end point is the clinical composite of MACE at 8 months supported by consistent results in the evaluation of 8-month MACE rates in the single- and multivessel cohorts and of in-segment late loss in a small angiographic substudy at 9 months. METHODS: A total of 1700 patients, 50% with single-vessel and 50% with multivessel disease, are randomized in a 3:2 ratio to receive either Costar or Taxus stent(s) in this prospective, multicenter, noninferiority study design. Because no prior data were available to determine control multivessel MACE rates, an imputed placebo statistical analysis plan incorporating a variable delta based on actually observed control DES MACE rates will be implemented. The results of COSTAR II will provide information about a novel coronary stent device as well as unique data regarding both control and test DES use in more complex "real-world" patients.