Vikram S. Kashyap

Background/Objectives: Abdominal aortic aneurysm (AAA) surveillance is based largely on monitoring the maximum diameter, a single scalar metric that obscures regional remodeling and offers limited information on the location and time dependency of the growth rate. The present work addresses this limitation with a geometry-based patient-specific framework that learns local, linear evolution from longitudinal clinical imaging, yielding 3D forecasts of AAA geometry at arbitrary future times. Methods: Lumen and outer wall surfaces are represented on a centerline-anchored cylindrical grid, with subsequent implementation of individualized linear mixed-effects models. The model is explicitly interpretable as the fixed effects predict global trends and the random effects represent regional heterogeneity. In a multicenter cohort of 79 patients, we evaluated forecasts using spatial similarity (with the 95th percentile of the Hausdorff distance—HD95) and clinically relevant global geometric scalars such as maximum diameter and volume. Results: When forecasting a future AAA geometry, the model achieved sub-millimetric HD95 spatial errors and less than 6% error for the aforementioned global scalars. The model was deployed in an interactive application named the Aneurysm Forecasting Studio, which allows a user to visualize the AAA in an explorable forecast space. Conclusions: During typical clinical surveillance intervals, AAA geometric remodeling is reasonably approximated as locally linear in time, enabling transparent, fast forecasts that support surveillance optimization, threshold timing, and digital twin-based interventional planning.

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.

Improvements in medical therapy, carotid-artery stenting, and carotid endarterectomy call into question the preferred management of asymptomatic carotid stenosis. Whether adding revascularization to intensive medical management would provide greater benefit than intensive medical management alone is unclear. We conducted two parallel, observer-blinded clinical trials that enrolled patients with high-grade (≥70%) asymptomatic carotid stenosis across 155 centers in five countries. The stenting trial compared intensive medical management alone (medical-therapy group) with carotid-artery stenting plus intensive medical management (stenting group); the endarterectomy trial compared intensive medical management alone (medical-therapy group) with carotid endarterectomy plus intensive medical management (endarterectomy group). The primary outcome was a composite of any stroke or death, assessed from randomization to 44 days, or ipsilateral ischemic stroke, assessed during the remaining follow-up period up to 4 years. A total of 1245 patients underwent randomization in the stenting trial and 1240 in the endarterectomy trial. In the stenting trial, the 4-year incidence of primary-outcome events was 6.0% (95% confidence interval [CI], 3.8 to 8.3) in the medical-therapy group and 2.8% (95% CI, 1.5 to 4.3) in the stenting group (P = 0.02 for the absolute difference). In the endarterectomy trial, the 4-year incidence of primary-outcome events was 5.3% (95% CI, 3.3 to 7.4) in the medical-therapy group and 3.7% (95% CI, 2.1 to 5.5) in the endarterectomy group (P = 0.24 for the absolute difference). From day 0 to 44, in the stenting trial, no strokes or deaths occurred in the medical-therapy group and seven strokes and one death occurred in the stenting group; in the endarterectomy trial, three strokes occurred in the medical-therapy group and nine strokes occurred in the endarterectomy group. Among patients with high-grade stenosis without recent symptoms, the addition of stenting led to a lower risk of a composite of perioperative stroke or death or ipsilateral stroke within 4 years than intensive medical management alone. Carotid endarterectomy did not lead to a significant benefit. (Funded by the National Institute of Neurological Disorders and Stroke and others; CREST-2 ClinicalTrials.gov number, NCT02089217.).

BACKGROUND: The optimal strategy for lower extremity revascularization (surgical bypass versus endovascular intervention) in patients with chronic limb-threatening ischemia (CLTI) is unclear. We examined the effectiveness of open surgical bypass using single-segment great saphenous vein conduit (SSGSV), alternative conduits (AC), or endovascular interventions (ENDO) among patients with CLTI deemed acceptable for either open surgical bypass or ENDO treatment. METHODS: This was a planned as-treated analysis of the multicenter BEST-CLI (Best Endovascular Versus Best Surgical Therapy in Patients With Critical Limb Ischemia) randomized controlled trial comparing open surgical bypass and ENDO for CLTI due to infrainguinal peripheral artery disease. Outcomes were tabulated based on the initial revascularization received: SSGSV bypass, AC bypass, and ENDO. Analyses were performed for all treated patients and then excluding those who experienced early technical failure. Multivariable Cox regression models were used. End points included the primary trial outcome (major adverse limb event [MALE] or all-cause death), major amputation, MALE at any time or perioperative (30-day) death, reintervention-amputation-death, and all-cause mortality. RESULTS: Among 1780 patients with CLTI, treatments received included SSGSV bypass (n=621), AC bypass (n=236), and ENDO (n=923) procedures. There were no significant differences in 30-day mortality, major adverse cardiovascular events, or serious adverse events; subjects treated with ENDO experienced greater MALE within 30 days (13.1% versus 2.7%, 3% for SSGSV, AC; P P P =0.017), MALE or perioperative death (hazard ratio, 0.51 [0.41–0.62]; P P <0.001). AC bypass was associated with reduced MALE or perioperative death and reintervention-amputation-death compared with ENDO. Significant benefits of SSGSV over ENDO remained when excluding patients who experienced early technical failure. There were no significant differences in long-term mortality by initial treatment received. When analyzed by the level of disease treated, the improved outcomes of SSGSV were greatest among patients who underwent femoropopliteal revascularization. CONCLUSIONS: Analysis of as-treated outcomes from the BEST-CLI trial demonstrates the safety and clinical superiority of bypass with SSGSV among patients with CLTI who were deemed suitable for either open surgical bypass or ENDO revascularization. Assessment of great saphenous vein quality should be incorporated into the evaluation of patients with CLTI who are surgical candidates. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT02060630 and NCT02060630.