Aronow, Herbert D.

Importance Cerebral hemodynamic impairment in patients with asymptomatic internal carotid artery (ICA) stenosis is associated with reduced cognition. It is uncertain whether revascularization might be an effective treatment for cognitive impairment in these patients. Objective To test whether any cognitive benefit from revascularization of high-grade, asymptomatic ICA stenosis varies based on the degree of baseline cerebral hemodynamic impairment. Design, Setting, and Participants This substudy was conducted within a multicenter phase 3 randomized clinical trial. Adults (aged 35-86 years) without dementia with eighth-grade education or higher and unilateral asymptomatic ICA stenosis greater than or equal to 70% were enrolled from January 2018 to July 2024 at 61 sites in North America (last follow-up in July 2025). Of 607 participants screened from 2485 in CREST-2, 392 were enrolled. Magnetic resonance or computed tomographic perfusion imaging tested for baseline hemodynamic impairment defined by delayed time-to-peak (TTP) arrival of intravenous contrast in the hemisphere ipsilateral minus contralateral to the stenotic artery. Intervention Carotid revascularization (endarterectomy or stenting) plus intensive medical management (IMM) vs IMM alone. Main Outcomes and Measures The primary outcome was the difference in composite cognitive z score over 1 year based on 5 cognitive tests. The primary analysis tested for an interaction between treatment group (revascularization vs IMM alone) and degree of baseline hemodynamic impairment among those with reduced baseline cognition (cognitive z score ≤−1.0 SD). Results Of 392 participants enrolled (mean age, 71 years; 125 [32%] females), 61 were excluded for missing baseline imaging and 40 for missing cognitive examinations or other covariates, leaving 291 with complete data. Fifty-one had reduced cognition at baseline (25 in the revascularization group and 26 in the IMM alone group). TTP ranged from no interhemispheric TTP delay to a more-than-2-second delay. Mean (SD) cognitive z scores were −1.36 (0.51) at baseline and −1.17 (0.47) at 1 year in the revascularization group and −1.34 (0.83) at baseline and −1.01 (0.97) at 1 year in the IMM alone group. The primary analysis showed no difference in cognition by treatment group over 1 year, adjusting for treatment group × hemodynamic status interaction and other covariates (adjusted difference in cognitive z score, −0.15 SD [95% CI, −0.54 to 0.24]). The interaction was not significant (β estimate = 0.018 [95% CI, −0.025 to 0.061]; P = .40). Conclusions and Relevance In this substudy of a randomized clinical trial, there was no differential effect of revascularization vs IMM alone on cognition over 1 year by cerebral hemodynamic status among those with baseline reduced cognition, suggesting that revascularization does not improve cognitive dysfunction by restoring flow to the brain in chronic asymptomatic carotid stenosis. Trial Registration ClinicalTrials.gov Identifier: NCT03121209

Objectives: Cerebral hemodynamic impairment in patients with asymptomatic high-grade internal carotid artery (ICA) stenosis confers a risk of stroke and cognitive decline, but correlations between degree of stenosis and hemodynamic impairment are derived from small case series only. Using baseline data from 282 participants in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis – Hemodynamics (CREST-H) study, we hypothesized that degree of stenosis, measured by peak systolic velocity (PSV) and end diastolic velocity (EDV) in the ipsilateral ICA, would correlate with time-to-peak (TTP) delay using MR (n=275) or CT (n=7) perfusion scans, adjusting for demographic and cardiovascular risk variables. Methods: Using a 7-10MHz Doppler probe, ICA PSV and EDV were assessed. Doppler results were adjudicated centrally. Dynamic contrast perfusion imaging was standardized across 61 CREST-H sites, using sequential T2*-weighted time-sequence scanning (e.g. TR=1500, TE=25ms, flip angle=60deg, phase=128, slice thickness=5mm for GE 3T magnet). CTP was acquired with standard clinical protocols. TTP delay was calculated in the ipsilateral versus contralateral MCA/ACA territories using OLEA software. Linear regression used TTP delay as the outcome variable and PSV and EDV as predictor variables, adjusting for covariates.The 282 with complete data for all variables were included in the analysis. Results: Among 392 CREST-H participants, 63% were men, 7% Black, 3% Hispanic, 33% with less than college education. Tables 1a/b show the regression results for PSV and EDV as main predictor variables. PSV and EDV on the index side significantly correlated with TTP delay (p=0.004, p=0.002 respectively). Neither PSV nor EDV on the non-index side correlated with TTP delay (p=0.49, p=0.82). Compared with moderate exercise, vigorous exercise correlated with lower TTP delay in both models (p=0.05. p=0.04). Compared with college graduates, those with HS education had longer TTP delays in both models (p=0.03. p=0.02). Conclusions: In this large cohort of patients with high-grade asymptomatic carotid stenosis, higher flow velocities correlated with greater TTP delays, suggesting an increasing hemodynamic impairment with greater degree of stenosis above 70%. Our findings have implications for management of asymptomatic carotid stenosis which are being tested in the CREST-H and CREST-2 studies. Exercise and education may independently impact cerebral hemodynamics.

BACKGROUND: Cerebral hemodynamic impairment in patients with asymptomatic high-grade (>70%) internal carotid artery (ICA) stenosis is associated with risk of stroke and cognitive decline, but correlations between the degree of stenosis and hemodynamic impairment are derived from small case series. Using baseline data from 242 participants in the CREST-H study (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis–Hemodynamics), we hypothesized that the degree of stenosis in the ICA would correlate with time-to-peak (TTP) delay in ipsilateral cerebral blood flow using MR/CT perfusion scans, adjusting for demographic and cardiovascular risk variables. METHODS: From all participants, ICAs were insonated using a 7 to 10 MHz probe for peak systolic velocity (PSV) and end diastolic velocity. Dynamic contrast perfusion imaging was standardized across 61 CREST-H sites, using standard sequential T2*-weighted perfusion imaging. CT perfusion used standard clinical protocols. TTP delay was calculated in the ipsilateral versus contralateral hemispheres. In cross-sectional analysis, linear regression was used to model TTP delay as the outcome variable and PSV, end diastolic velocity, and PSV ICA/common carotid artery ratio on the index and nonindex side as primary predictor variables in 6 separate models, adjusting for covariates, followed by automated backward elimination model reduction. RESULTS: Among 392 CREST-H participants, the 242 with complete data for all variables were included in the regression analysis (age, 70±7.6; 62% M). End diastolic velocity on the index side correlated with TTP delay (β=0.003, P =0.005). PSV had a similar correlation but did not reach significance (β=0.001, P =0.099), nor did ICA/common carotid artery ratio (β=0.003, P =0.126). Nonindex side PSV, end diastolic velocity, and ICA/common carotid artery ratio showed no correlation with TTP delay ( P =0.268, P =0.495, P =0.380, respectively). Circle of Willis completeness did not correlate with TTP. CONCLUSIONS: In this large cohort of patients with high-grade asymptomatic carotid stenosis, higher end-diastolic flow velocities correlated with greater TTP delays, supporting a definition of hemodynamically significant stenosis. Our findings have implications for the management of asymptomatic carotid stenosis, which will be tested in the CREST-H study. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03121209.

Abstract Context Patients with adrenal insufficiency (AI) have both increased risk of cardiovascular disease and adverse outcomes with many medical emergencies. However, limited data exist specifically regarding ST-segment elevation myocardial infarction (STEMI) in the context of AI. Objective To evaluate associations between AI and in-hospital outcomes of patients with STEMI. Methods Admissions for STEMI were identified in the 2016-2019 National Inpatient Sample. In-hospital outcomes were compared between patients with and without AI. The primary outcome was in-hospital mortality. Secondary outcomes included percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), intervention, acute kidney injury (AKI), vasopressor use, mechanical circulatory support (MCS), mechanical ventilation, ventricular tachycardia (VT), hospital length of stay (LOS), and total charges. Multivariable regression models were used to adjust for potential confounders. Results Among 690 430 STEMI hospitalizations, 1382 (0.2%) had a diagnosis of AI. AI was associated with higher odds of in-hospital mortality (adjusted OR [aOR] 1.51, 95% CI 1.03-2.2), lower odds of PCI (aOR 0.73, 95% CI 0.55-0.98), higher odds of CABG (aOR 2.8, 95% CI 1.89-4.2) and, AKI (aOR 2.38, 95% CI 1.72-3.3), VT (aOR 1.55, 95% CI 1.1-2.2), need for vasopressors (aOR 2.34, 95% CI 1.33-4.1), mechanical ventilation (aOR 2.11, 95% CI 1.54-2.89), and MCS (aOR 2.18, 95% CI 1.57-3.03). Patients with AI also had a longer LOS (10 days vs 4.2 days, P < .001) and higher charges ($258 475 vs $115 505, P < .001). Conclusion Patients with AI admitted for STEMI had higher in-hospital mortality, nonfatal adverse outcomes, and resource utilization than patients without AI.

BACKGROUND: Following regulatory approval, medical devices may be used “off-label.” Patent foramen ovale (PFO) closure is indicated to reduce recurrent stroke but has been proposed for other indications, including migraine, transient ischemic attack, and diving decompression illness. We sought to evaluate PFO closure rates and indications relative to the timing of regulatory approval and publication of key randomized trials. METHODS: We performed a retrospective cohort study using the OptumLabs Data Warehouse of US commercial insurance enrollees from 2006 to 2019. We quantified PFO closure among individuals with ≥2 years of preprocedure coverage to establish indications, classified hierarchically as stroke/systemic embolism, migraine, transient ischemia attack, or other. RESULTS: We identified 5315 patients undergoing PFO closure (51.8% female, 29.2%≥60 years old), which increased from 4.75 per 100 000 person-years in 2006 to 6.60 per 100 000 person-years in 2019. Patients aged ≥60 years accounted for 29.2% of closures. Procedure volumes corresponded weakly with supportive clinical publications and device approval. Among patients with PFO closure, 58.6% underwent closure for stroke/systemic embolism, 10.2% for transient ischemia attack, 8.8% for migraine, and 22.4% for other indications; 17.6% of patients had atrial fibrillation at baseline; and 11.9% developed atrial fibrillation postprocedure. Those aged ≥60 years and male were less likely to undergo closure for migraine than stroke/systemic embolism. CONCLUSIONS: From 2006 to 2019, PFO closure use was consistently low and corresponded weakly with clinical trial publications and regulatory status. Nearly half of patients underwent PFO closure for indications unapproved by the Food and Drug Administration. Regulators and payers should coordinate mechanisms to promote utilization for approved indications to ensure patient safety and should facilitate clinical trials for other possible indications.

AbstractThe Society for Cardiovascular Angiography and Interventions (SCAI) Think Tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community annually for high‐level field‐wide discussions. The 2021 Think Tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease. Each session was moderated by a senior content expert and co‐moderated by a member of SCAI's Emerging Leader Mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialog from a broader base, and thereby aid SCAI, the industry community and external stakeholders in developing specific action items to move these areas forward.

Introduction: The relative performance of carotid artery stenting (CAS) and carotid endarterectomy (CEA) among Medicare beneficiaries in routine clinical practice has not been established. Objective: To compare the performance of CAS relative to CEA among Medicare beneficiaries. Methods: We linked Medicare data (2000-2009) to the Society for Vascular Surgery’s Vascular Registry (SVS-VR; 2005-2008) and to the NCDR® Carotid Artery Revascularization and Endarterectomy Registry (CARE; 2006-2008/9). Medicare patients aged ≥66 years undergoing CAS or CEA were followed from the procedure date for the outcomes of death, stroke/transient ischemic attack (TIA), peri-procedural myocardial infarction (MI) or a composite endpoint for these outcomes. We derived high-dimensional propensity scores using registry and Medicare data to control for patient-level factors and adjusted for provider-level factors including past-year CAS/CEA physician and hospital volume, hospital ownership, teaching affiliation, and hospital size in a Cox regression model comparing CAS to CEA. Results: Among 5,254 SVS-VR (1,999 CAS and 3,255 CEA) and 4,055 CARE (2,824 CAS and 1,231 CEA) patients, CAS patients were more often at higher surgical risk (SVS-VR: 96.7% vs. 44.5%; CARE: 71.3% vs. 44.7%) and had a higher comorbidity burden. Crude outcome risks for death and stroke/TIA were lower for CEA. Adjusting for patient-level factors drove estimates downwards for CAS relative to CEA but only after further adjustment for provider-level factors did the performance of CAS and CEA become comparable on all outcomes (figure 1). Conclusion: Performance of CAS and CEA among Medicare beneficiaries was comparable after accounting for patient- and provider-level factors, which is consistent with landmark trials. Further studies are needed to understand the role of heterogeneity in provider-level characteristics.

Background and Purpose: Despite a higher incidence of stroke and a more adverse cardiovascular risk factor profile in Blacks and Hispanics compared with Whites, carotid artery revascularization is performed less frequently among these subpopulations. We assessed racial differences in high-grade (≥70% diameter-reducing) carotid stenosis. Methods: Consecutive clients in a Nationwide Life Line for-Profit Service to screen for vascular disease, 2005 to 2019 were evaluated in a cross-sectional study. The prevalence of high-grade stenosis, defined by a carotid ultrasound peak systolic velocity of ≥230 cm/s, was assessed. Participants self-identified as White, Black, Hispanic, Asian, Native American, or other. Race/ethnic differences were assessed using Poisson regression. The number of individuals in the United States with high-grade stenosis was estimated by applying prevalence estimates to 2015 US Census population estimates. Results: The prevalence of high-grade carotid stenosis was estimated in 6 130 481 individuals. The prevalence of high-grade stenosis was higher with increasing age in all race-sex strata. Generally, Blacks and Hispanics had a lower prevalence of high-grade stenosis compared with Whites, while Native Americans had a higher prevalence. For example, for men aged 55 to 65, the relative risk of stenosis compared with Whites was 0.40 (95% CI, 0.29–0.55) and 0.61 (95% CI, 0.46–0.81) for Blacks and Hispanics, respectively; and 1.53 (95% CI, 1.12–2.10) for Native Americans. When these prevalence estimates were applied to the Census estimates of the US population, an estimated 327 721 individuals have high-grade stenosis, of whom 7% are Black, 7% Hispanic, and 43% women. Conclusions: Despite their having a more adverse cardiovascular risk profile, there was a lower prevalence of high-grade carotid artery stenosis for both the Black and Hispanic relative to the White clients. This lower prevalence of high-grade stenosis is a potential contributor to the lower use of carotid revascularization procedures in these minority populations.