SystematIc StudY of Patients with atHerosclerotic neUrovascular Stenoses (SISYPHUS): Study Protocol for a Prospective Observational Cohort Evaluating 3D Rotational Angiography and Final Implant Quality in Carotid Stenting
- 1Hospital de Clinicas de Porto Alegre
Abstract
Background and PurposeMinor periprocedural ischemic events remain an important limitation of carotid artery stenting (CAS) compared with endarterectomy. Adverse stent-vessel-plaque interactions and in-stent plaque protrusion are proposed as contributing mechanisms. Selective intra-arterial three-dimensional rotational angiography (3DRA) provides high-resolution volumetric imaging directly in the endovascular suite without additional device crossing. Its incremental value for characterizing final implant quality and informing prognosis remains incompletely established.
ObjectivesWe aim to determine whether adding 3DRA to conventional digital subtraction angiography (DSA): (1) improves expert characterization and reproducibility of Final Implant Quality (Imaging Domain); and (2) provides incremental prognostic information for 90-day Textbook Outcome failure beyond baseline clinical risk and conventional DSA (Prognostic Domain).
MethodsSISYPHUS is a prospective, multicenter observational cohort of 67 patients undergoing elective CAS across three tertiary centers. Three blinded neuroradiologists will evaluate standardized image packages sequentially under DSA-only and DSA+3DRA conditions. Final Implant Quality will be assessed with a structured 10-item instrument: Q1-Q8 characterize specific findings, Q9 evaluates global implant adequacy (primary imaging variable), and Q10 captures technical image quality. Concealed repeat assessments will be performed in a randomized 17-patient subset for intra-reader reliability. The primary imaging estimand is the within-reader ordinal shift in Q9 after 3DRA is added, modeled with cumulative-link mixed-effects regression. The primary clinical endpoint is 90-day Textbook Outcome failure, integrating early neurological deterioration, major bleeding/procedural complications, stroke, TIA, MI, death, unplanned revascularization, and unplanned readmission within prespecified ascertainment windows. Incremental prognostic performance will be evaluated using nested ridge-penalized logistic regression models (M2 vs M3) with 2,000-resample bootstrap internal validation.
Trial Status & Prospective LockRecruitment is complete (n=67), while protocol-defined follow-up remains ongoing. The Orthanc/OHIF reader study environment is being implemented; formal reader evaluations have not yet begun. The principal analytical architecture was prospectively locked in the Statistical Analysis Plan (SAP) Version 1.1.1 before formal inspection of reader results and before real-data prognostic model fitting.
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BibTeX
@misc{cabral2026systematic,
title = {{SystematIc StudY of Patients with atHerosclerotic neUrovascular Stenoses (SISYPHUS): Study Protocol for a Prospective Observational Cohort Evaluating 3D Rotational Angiography and Final Implant Quality in Carotid Stenting}},
author = {L. S. Cabral and M. V. Wainstein and S. O. Martins and R. Brondani and J. A. Duarte and A. G. De Almeida and A. Dal Pizzol and R. M. Castilhos and M. A. Stefani},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.20.26363509},
url = {https://www.medrxiv.org/content/10.64898/2026.09.20.26363509v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - SystematIc StudY of Patients with atHerosclerotic neUrovascular Stenoses (SISYPHUS): Study Protocol for a Prospective Observational Cohort Evaluating 3D Rotational Angiography and Final Implant Quality in Carotid Stenting
AU - L. S. Cabral
AU - M. V. Wainstein
AU - S. O. Martins
AU - R. Brondani
AU - J. A. Duarte
AU - A. G. De Almeida
AU - A. Dal Pizzol
AU - R. M. Castilhos
AU - M. A. Stefani
PY - 2026
DA - 2026/09/20
PB - medRxiv
DO - 10.64898/2026.09.20.26363509
UR - https://www.medrxiv.org/content/10.64898/2026.09.20.26363509v1
AB - Background and PurposeMinor periprocedural ischemic events remain an important limitation of carotid artery stenting (CAS) compared with endarterectomy. Adverse stent-vessel-plaque interactions and in-stent plaque protrusion are proposed as contributing mechanisms. Selective intra-arterial three-dimensional rotational angiography (3DRA) provides high-resolution volumetric imaging directly in the endovascular suite without additional device crossing. Its incremental value for characterizing final implant quality and informing prognosis remains incompletely established. ObjectivesWe aim to determine whether adding 3DRA to conventional digital subtraction angiography (DSA): (1) improves expert characterization and reproducibility of Final Implant Quality (Imaging Domain); and (2) provides incremental prognostic information for 90-day Textbook Outcome failure beyond baseline clinical risk and conventional DSA (Prognostic Domain). MethodsSISYPHUS is a prospective, multicenter observational cohort of 67 patients undergoing elective CAS across three tertiary centers. Three blinded neuroradiologists will evaluate standardized image packages sequentially under DSA-only and DSA+3DRA conditions. Final Implant Quality will be assessed with a structured 10-item instrument: Q1-Q8 characterize specific findings, Q9 evaluates global implant adequacy (primary imaging variable), and Q10 captures technical image quality. Concealed repeat assessments will be performed in a randomized 17-patient subset for intra-reader reliability. The primary imaging estimand is the within-reader ordinal shift in Q9 after 3DRA is added, modeled with cumulative-link mixed-effects regression. The primary clinical endpoint is 90-day Textbook Outcome failure, integrating early neurological deterioration, major bleeding/procedural complications, stroke, TIA, MI, death, unplanned revascularization, and unplanned readmission within prespecified ascertainment windows. Incremental prognostic performance will be evaluated using nested ridge-penalized logistic regression models (M2 vs M3) with 2,000-resample bootstrap internal validation. Trial Status & Prospective LockRecruitment is complete (n=67), while protocol-defined follow-up remains ongoing. The Orthanc/OHIF reader study environment is being implemented; formal reader evaluations have not yet begun. The principal analytical architecture was prospectively locked in the Statistical Analysis Plan (SAP) Version 1.1.1 before formal inspection of reader results and before real-data prognostic model fitting.
ER -