Diagnostic Accuracy of Intravascular Ultrasound-Derived Fractional Flow Reserve for Online Assessment of Functionally Significant Coronary Stenosis: A Multicenter Prospective Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 292
- 试验地点
- 1
- 主要终点
- Diagnostic Accuracy of IVUS-FFR in Identifying Hemodynamically Significant Coronary Stenosis
研究概览
简要总结
IVUS-FFR Online Accuracy for Coronary Stenosis What is this study testing? This study is testing a new technology called IVUS-FFR , which uses ultrasound imaging inside heart arteries (IVUS) to quickly measure whether a narrowed artery ( coronary stenosis ) is reducing blood flow. Unlike the current standard test (FFR), this new method doesn't require extra wires or medication to work.
Why is this important?
Many patients with heart artery narrowing need tests to decide if a stent is necessary.
Current FFR tests involve inserting a pressure wire and giving medication (like adenosine) that can cause discomfort.
IVUS-FFR could provide equally accurate results faster, cheaper, and more comfortably .
What happens in the study?
If you join:
Standard heart artery imaging (angiogram) will be performed. An ultrasound probe (IVUS) will be moved through the artery to create detailed images.
The new IVUS-FFR software will analyze these images immediately to estimate blood flow.
For comparison, a standard FFR test (with pressure wire and medication) will also be done.
All steps use existing approved devices and take <10 extra minutes. Who can participate?
Adults (≥18 years) with:
Suspected or known heart artery disease At least one artery narrowing (30%-90% blocked) Excluded: Recent heart attack (<72 hrs), severe kidney/heart failure, or pregnancy.
What are the risks and benefits?
Risks: Same as routine heart catheterization (bleeding, infection, artery injury). The IVUS and FFR steps add minimal extra risk.
Benefits: No direct benefit, but results may improve future care by reducing need for invasive tests.
Study goal:
To validate if IVUS-FFR is as accurate as the current FFR standard in 292 patients across multiple hospitals in China.
Who is running the study? Led by heart specialists at Fuwai Hospital (Beijing) - China's top cardiovascular center - with ethics committee oversight.
详细描述
- Introduction and Study Rationale This study focuses on developing and validating an innovative technology called IVUS-derived Fractional Flow Reserve (IVUS-FFR), which aims to address limitations in current methods for assessing coronary artery stenosis. Coronary artery disease often requires precise evaluation of blood flow restrictions to determine if interventions like stents are necessary. The gold standard, Fractional Flow Reserve (FFR), involves invasive pressure wires and vasodilator drugs (e.g., adenosine), leading to increased costs, procedural time, and potential complications such as allergic reactions or hemodynamic instability. By contrast, IVUS-FFR integrates intravascular ultrasound imaging with computational fluid dynamics to estimate functional significance without additional devices or medications. This approach could streamline clinical workflows, reduce patient discomfort, and lower healthcare expenses, making it a promising advancement in cardiovascular diagnostics.
- Primary Research Objectives The core goal is to evaluate the diagnostic accuracy of the IVUS-FFR system in identifying hemodynamically significant coronary stenosis, defined as a reduction in blood flow warranting intervention. Using a prospective, multicenter design, the study directly compares IVUS-FFR against FFR as the reference standard. Secondary objectives include assessing feasibility in real-time catheterization lab settings, establishing standardized operational protocols, and refining the technology for broader clinical adoption. Additionally, the study will contrast IVUS-FFR with quantitative coronary angiography (QCA), an anatomical assessment tool, to demonstrate superior diagnostic performance in detecting functionally relevant lesions.
- Study Design and Methodology Overview This research employs a prospective, multicenter, self-controlled clinical trial framework. It targets enrollment of 292 adult participants with suspected or confirmed coronary artery disease, specifically those exhibiting at least one visually estimated coronary stenosis between 30% and 90% diameter reduction. Participants undergo sequential assessments: first, standard coronary angiography and IVUS imaging to generate detailed vascular reconstructions; second, immediate online IVUS-FFR analysis using proprietary algorithms; and third, conventional FFR measurement for validation. Blinding protocols ensure objectivity-IVUS-FFR operators are unaware of FFR results during analysis, and an independent core lab processes QCA data. Statistical methods include receiver operating characteristic (ROC) curves to calculate area under the curve (AUC), sensitivity and specificity analyses, and Delong tests for comparing IVUS-FFR and QCA performance. The sample size provides 90% statistical power to detect a target diagnostic accuracy of 83% for IVUS-FFR.
- Technological Innovations and Workflow Integration The IVUS-FFR system represents a significant leap in computational physiology. It combines high-frequency intravascular ultrasound (40MHz probes) with artificial intelligence-driven segmentation. This involves deep neural networks to automatically delineate vessel structures, such as the lumen and external elastic lamina, enabling precise 3D vascular modeling. Blood flow simulations leverage Murray's law for adaptive hemodynamic calculations, ensuring accurate pressure drop estimations across stenoses. Key innovations include real-time processing capabilities-results are generated within 90 seconds of IVUS data acquisition-and compatibility with existing catheterization lab equipment. This integration minimizes workflow disruptions, adding less than 10 minutes to standard procedures while eliminating the need for pressure wires or vasodilators.
- Participant Eligibility and Ethical Safeguards Eligible participants are adults aged 18 years or older with coronary artery disease symptoms, such as stable or unstable angina, who are scheduled for diagnostic angiography. Exclusion criteria prioritize safety, excluding individuals with recent myocardial infarction (within 72 hours), severe heart failure, significant kidney impairment, pregnancy, or contraindications to iodinated contrast agents. All participants provide informed consent, and the study adheres to stringent ethical oversight through Fuwai Hospital's institutional review board. Rigorous risk mitigation strategies include protocolized management of potential complications like vessel injury during IVUS catheterization and on-site emergency resources for adenosine-related adverse events.
- Expected Outcomes and Broader Implications Upon completion, the study aims to validate IVUS-FFR as a non-inferior alternative to FFR, with anticipated diagnostic accuracy exceeding 83%. This could establish new clinical standards, reducing reliance on invasive FFR and cutting procedural costs by approximately $850 per case. Broader impacts include intellectual property development, such as 2-3 national patents for the core algorithms and 1-2 software copyrights. Dissemination will occur through high-impact publications in Q1-ranked journals and presentations at international conferences, potentially influencing future guidelines on coronary revascularization. If successful, IVUS-FFR could extend to peripheral vascular applications, enhancing patient outcomes globally by enabling faster, safer, and more accessible functional assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •General Requirements
- •18 years of age Diagnosed with stable/unstable angina or post-acute phase myocardial infarction (>72 hours after onset) Able to comprehend study design and provide written informed consent Angiographic & IVUS-Specific Requirements
- •1 epicardial coronary artery with 30%-90% visual diameter stenosis Reference vessel diameter ≥2.0 mm at target stenosis site
排除标准
- •General Exclusions Contraindications to invasive procedures/FFR per operator judgment Acute myocardial infarction within 72 hours Cardiogenic shock or severe heart failure (NYHA class ≥III or LVEF <30%) Severe renal dysfunction (Creatinine >150 μmol/L or eGFR <45 mL/min/1.73m²) Allergy to iodinated contrast media or adenosine Pregnancy/lactation Life expectancy <1 year Concurrent participation in other interventional trials Angiographic & IVUS-Specific Exclusions Myocardial bridging at target lesion Severely calcified or tortuous vessels precluding safe IVUS Isolated >90% stenosis with TIMI flow grade <3 in major epicardial artery Other conditions deemed unsuitable for IVUS/FFR by investigators
研究组 & 干预措施
IVUS-FFR Online Assessment
Intervention Protocol
Participants receive a real-time functional coronary evaluation using the integrated IVUS-FFR system during diagnostic angiography. The procedure consists of three sequential phases:
IVUS Image Acquisition A clinically approved IVUS catheter (40MHz frequency) is advanced to the target coronary segment Standardized automated pullback (0.5 mm/sec) captures cross-sectional vessel images Minimum imaging length: 30mm proximal-to-distal to stenosis Real-Time Computational Analysis DICOM data transfer to IVUS-FFR processing platform
AI-driven segmentation of:
Lumen boundaries External elastic lamina (EEL) Plaque morphology
Hemodynamic simulation using:
Adaptive blood flow models based on Murray's law Branching-specific flow distribution algorithms Processing time: ≤90 seconds Diagnostic Output Delivery Primary metric: Computed IVUS-FFR value (scale 0-1) Clinical threshold: IVUS-FFR ≤0.80 = hemodynamically significant stenosis Quality control: Auto
干预措施: Ultrasound-Derived Fractional Flow Reserve Computational System (Diagnostic Test)
结局指标
主要结局
Diagnostic Accuracy of IVUS-FFR in Identifying Hemodynamically Significant Coronary Stenosis
时间窗: Single time point assessment: immediately after IVUS-FFR computation during the index cardiac catheterization procedure.
Diagnostic accuracy of IVUS-FFR (online, HRU100) vs. invasive FFR (pressure wire, adenosine) for functionally significant stenosis (≤0.80). Primary metric: proportion of correct classifications (true positives + true negatives) among all lesions. Secondary metrics: sensitivity, specificity, PPV, NPV, AUC. Measurement: paired real-time assessment; IVUS-FFR computed during catheterization, then FFR measured. Blinding: IVUS-FFR operator blinded to FFR result until after recording. Quality assurance: core lab verification; analyses with segmentation confidence \<95% rejected.
Diagnostic Accuracy of IVUS-FFR in Identifying Hemodynamically Significant Coronary Stenosis
时间窗: Single assessment at time of index cardiac catheterization procedure.
This outcome measures the diagnostic performance of IVUS-FFR (computed online during catheterization using the HRU100 system) against the gold standard invasive FFR (measured with a pressure wire under adenosine-induced hyperemia). Functionally significant stenosis is defined as ≤0.80 for both methods. The primary metric is the proportion of correct classifications (true positives + true negatives) among all evaluated lesions. Secondary metrics derived from the same data include sensitivity, specificity, positive predictive value, negative predictive value, and area under the ROC curve. Measurement Method: Paired real-time assessment: IVUS-FFR computed first, immediately followed by invasive FFR measurement. Blinding: IVUS-FFR operator masked to FFR result until after recording. Quality Assurance: Core laboratory verification of all measurements; automatic rejection of analyses with segmentation confidence \<95%.
次要结局
未报告次要终点
研究者
Kefei Dou, MD
Kefei Dou, MD, Professor, China National Center for Cardiovascular Diseases
China National Center for Cardiovascular Diseases