Relationship Between Fractional Flow Reserve/ Instantaneous Wave Free Ratio and Endothelial Wall Shear Stress (RELATE)

August 6, 2019 updated by: Fabrizio D'Ascenzo, Azienda Ospedaliera Città della Salute e della Scienza di Torino

RELATionship bEtween Lesion-level Invasive Fractional Flow Reserve AND Endothelial Wall Shear Stress the RELATE FFR and WSS Study

This study, designed as a retrospective registry, aims to investigate the relationship and potential interplay between fractional flow reserve (FFR) or instantaneous waves free ratio (iFR) with wall shear stress (WSS) in the context of intermediate coronary stenosis.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND AND RATIONALE Despite great advances in atherothrombosis science, the complex interplay of factors leading to plaque progression remains elusive. Specifically, the dynamics leading a stable plaque towards rupture and over imposed thrombosis are largely speculative. Wall shear stress (WSS), the mechanical force elicited by blood flow on the vessel walls, is emerging as a potent trigger of bio-humoral processes eventually leading to endothelial damage, plaque progression and destabilization.

Fractional flow reserve (FFR), assessing the aggregate hemodynamical significance of a stenosis on the subtended myocardium, stratifies the risk of major adverse cardiovascular events and reduces their occurrence when used to guide revascularization. While this event reduction is mainly driven by ischemia-caused urgent revascularization, it is emerging that FFR-guided revascularization may also reduce myocardial infarction.

While the physiological relationship between a lesion's FFR and resulting ischemia in the subtended myocardium is intuitive, the mechanisms linking FFR to atherothrombosis are less clearly defined.

Lesions with lower FFR are associated with adverse atherosclerotic plaque characteristics (APCs), however, the causative nexus of this relationship is not well established. It has been proposed both that the physiological base for this relation underlies in disturbed lesion hemodynamics, occurring at a greater extent as the degree of functional obstruction increases (i.e. FFR reduction drives APCs), and that APCs directly impair the vessel's vasodilatory reserve resulting in detrimental hyperemic perfusion (i.e. APCs drive FFR reduction).

WSS measures the regional tangential hemodynamic forces produced by viscous blood flow on the endothelium, which is established drivers of plaque progression and transformation toward an adverse plaque phenotype. Intriguingly, WSS may thus represent the missing link between FFR and atherothrombosis.

Few studies have focused on the interplay of FFR and WSS and the provided results are inconclusive (9, 10). This relation remains thus to be fully characterized.

This study will investigate the association of aggregate with regional hemodynamic forces as defined by the lesion-level relation of FFR or instantaneous wave-free ratio (iFR) and regional WSS across the lesion.

STUDY DESIGN This is a retrospective observational multi-center study, including consecutive patients who underwent coronary angiography at for symptom/ischemia-driven, suspected stable coronary artery disease or for acute coronary syndromes (ACS) with evidence of at least one lesion with 30-90% diameter-stenosis, that underwent subsequent iFR/FFR assessment.

Coronary angiography of the screened patients will be retrospectively evaluated by an experienced Interventional cardiologist and, if deemed suitable for baseline angiographic reconstruction will be included in this registry.

3-dimensional (3D) geometric reconstructions of each patient's target vessel will be created by using end-diastolic angiographic projections at least 25° apart. Computational fluid dynamics models will be applied to derive regional WSS values across the stenosis.

Clinical baseline characteristics and angiographic features obtained by visual and functional assessment, and 3-D reconstruction and computation, along with major adverse cardiovascular events, will be collected in a dedicated electronic form.

The analysts performing angiographic 3-D reconstruction and WSS computations will be blinded to FFR/iFR values and clinical data.

STUDY ENDPOINTS This study will investigate the association of aggregate and regional hemodynamic forces as established by the lesion-level relation of FFR/iFR with regional WSS across the lesion.

The association of regional WSS with major cardiovascular adverse events at available follow-up will be further evaluated to assess if lesion-level WSS might predict overall patient-level outcomes (in case of more than one lesion for a single patient, the lesion with the highest WSS will be considered for this analysis).

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Rivoli, Italy, 10098
        • Enrolling by invitation
        • Ospedale di Rivoli
      • Torino, Italy, 10126
        • Recruiting
        • AOU Città della Salute e della Scienza di Torino
      • Torino, Italy, 10144
        • Enrolling by invitation
        • Ospedale San Giovanni Bosco

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

- The study will include any patient referred for coronary angiography at each involved center and with a subsequent invasive physiological assessment performed with FFR or iFR (or both) at operating physician's discretion on intermediate coronary stenosis (diameter of stenosis ranging from 30-90% at visual angiographic estimation).

Description

Inclusion Criteria:

  • Angiography performed for suspected symptom/ischemia-driven stable coronary artery disease or for acute coronary syndromes
  • At least one lesion with 30-90% diameter stenosis at invasive angiography with FFR/iFR assessed (for patients with acute coronary syndromes, the invasive assessment will be performed on non-culprit stenosis
  • Patient informed consent for data collection and publication in anonymous studies

Exclusion Criteria:

  • Quality of angiographic frames not sufficient for 3D-reconstruction and/or computations
  • Patients denying informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Wall shear stress (WSS) / Fractional flow reserve (FFR) or instantaneous wave free ratio (iFR)correlation
Time Frame: WSS will be calculated after 3D coronary reconstruction, within one year after the completion of retrospective enrollement
After 3-dimensional coronary reconstruction through dedicated software (Qangio XA 3D (MEDIS), WSS will be calculated through fluydodinamic equations across the entire coronary vessel and across coronary stenosis. WSS values predicting positive invasive FFR and iFR (according to their dichothomic established values of positivity, namely FFR < 0.8 and iFR < 0.89) measurements will be searched, along with any possible relationship between WSS and FFR/iFR as continuos values.
WSS will be calculated after 3D coronary reconstruction, within one year after the completion of retrospective enrollement
MACE (major adverse cardiovascular events)
Time Frame: MACE will be evaluated for each patients through study completion, an average of 1 year
The association of regional WSS with major cardiovascular adverse events at available follow-up will be further evaluated to assess if lesion-level WSS might predict overall patient-level outcomes
MACE will be evaluated for each patients through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Collaborators

Politecnico di Torino

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2017

Primary Completion (Anticipated)

December 31, 2019

Study Completion (Anticipated)

December 31, 2020

Study Registration Dates

First Submitted

August 4, 2019

First Submitted That Met QC Criteria

August 6, 2019

First Posted (Actual)

August 7, 2019

Study Record Updates

Last Update Posted (Actual)

August 7, 2019

Last Update Submitted That Met QC Criteria

August 6, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RELATE FFR and WSS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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