Back to resultsMicrovascular Function in Patients Undergoing Transcatheter Aortic Valve Implant (TAVI) for Severe Symptomatic Aortic Stenosis: Association With Myocardial Fibrosis
Primary Purpose
Severe Symptomatic Aortic Stenosis
Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
coronary physiology
Sponsored by
About this trial
This is an interventional other trial for Severe Symptomatic Aortic Stenosis
Eligibility Criteria
Inclusion Criteria:
• All patients referred to IRCCS Ospedale San Raffaele who are candidates to receive a TAVI implant for severe, symptomatic aortic stenosis under current appropriateness criteria and clinical practice guidelines will be considered eligible to take part in the study
Exclusion Criteria:
- Age <18 years
- Inability to express informed consent to take part in the present study.
- Pregnancy or lactation
- Pre-existing known disease determining a prognosis quo ad vitam shorter than the follow up of the present study
- Significant chronic kidney disease (estimated glomerular filtration rate <30 ml/min)
- Known significant epicardial coronary artery stenosis
- Known contraindication to adenosine administration:
- Known allergic reactions
- Second or third degree atrioventricular block before the procedure (in absence of a functional permanent pacemaker)
- Long QT syndrome
- Unstable angina
- Severe hypotension
- Acutely decompensated heart failure
- Chronic obstructive pulmonary disease with bronchospasm
- Concomitant use of dypiridamole
Sites / Locations
- IRCCS San RaffaeleRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Coronary physiology evaluation
Arm Description
Patient will undergo TAVI and then Myocardial fibrosis will be evaluated on images acquired at the time of the cardiac CT obtained for TAVI planning. Briefly, an extra late post-contrast acquisition image will be acquired. The delayed post-contrast scan will be reconstructed with a soft convolution kernel and will be reformatted in the short- and long-axis planes (slice thickness 8 mm; gap 0 mm) in average mode.
Outcomes
Primary Outcome Measures
The burden of myocardial fibrosis
Myocardial fibrosis measured as the percentage of delay-enhanced myocardium over total myocardial volume
Index of microcirculatory resistance (IMR)
IMR a validated estimate of resistance in the coronary capillary, computed as the ratio between transit time of a 3 cc bolus of room temperature saline and distal coronary artery pressure.
Secondary Outcome Measures
Acute change in coronary flow reserve (CRF)
Ratio of maximal coronary blood flow obtained by hyperemia to baseline coronary blood flow
Acute change in index of microcirculatory resistance (IMR)
Estimate of microvascular resistance derived by pressure and an indirect estimate of flow
Computed tomography derived extracellular volume
The extracellular volume fraction (ECV) is the relative value of the volume of the extracellular space in the myocardium, therefore express as a percentage. It could be measured from computed tomography (CT) and Index of microcirculatory resistance (MRI) images, and was validated with histology. ECV-CT is calculated as follows:
ECVCT = (1-haematocrit) × (ΔHUmyo/ΔHUblood) where ΔHU is the change in Hounsfield unit attenuation pre- and post-contrast (i.e. HUpost-contrast - HUpre-contrast)
All-cause death
Death from any cause
Cardiovascular death
Death from any cardiac condition (e.g. myocardial infarction, acute pulmonary edema, low-output state, etc..) or vascular condition (including aortic dissection, stroke, etc…)
Any rehospitalization
Admission to an inpatients' service for any cause lasting >24h
Cardiovascular rehospitalization
Admission to an inpatients' service for cardiovascular conditions lasting >24h
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05326126
Brief Title
Microvascular Function in Patients Undergoing Transcatheter Aortic Valve Implant (TAVI) for Severe Symptomatic Aortic Stenosis: Association With Myocardial Fibrosis
Official Title
Microvascular Function in Patients Undergoing Transcatheter Aortic Valve Implant (TAVI) for Severe Symptomatic Aortic Stenosis: Association With Myocardial Fibrosis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 8, 2021 (Actual)
Primary Completion Date
October 30, 2023 (Anticipated)
Study Completion Date
October 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Matteo Montorfano
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Microvascular function in patients undergoing Transcatheter Aortic Valve Implant (TAVI) for severe symptomatic aortic stenosis: association with myocardial fibrosis
Detailed Description
Severe symptomatic aortic stenosis is commonly encountered in clinical practice, affecting close to 5% of individuals older than 65 years of age, and carries a dismal prognosis if left untreated.(1,2) Chronically increased left ventricular afterload triggers a compensatory myocardial response, ultimately leading to ventricular hypertrophy, aimed at reducing chronically increased wall tension an restore cardiac performance.(3) Hypertrophy ultimately results in maladaptive changes and ultimately leads to heart failure and eventually increased risk of cardiac mortality. Myocardial fibrosis and altered myocardial perfusion appear to play a role in progressive cardiac decompensation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Symptomatic Aortic Stenosis
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
TAVI's intervention will be performed as per current clinical indications and according to the hospital's clinical practice. To this will be added the evaluation of coronary physiology using Pressure Eire X and Coroventis software, which, although performed in accordance with the IFU of the aforementioned devices, is considered an experimental procedure. Adenosine will be required to complete the measurement of coronary physiology
Masking
None (Open Label)
Masking Description
Patients will be assigned a univocal identification code. Medical personnel in charge of baseline, in-hospital and follow-up data acquisition will be allowed to know each patient identity.
Allocation
N/A
Enrollment
75 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Coronary physiology evaluation
Arm Type
Experimental
Arm Description
Patient will undergo TAVI and then Myocardial fibrosis will be evaluated on images acquired at the time of the cardiac CT obtained for TAVI planning. Briefly, an extra late post-contrast acquisition image will be acquired. The delayed post-contrast scan will be reconstructed with a soft convolution kernel and will be reformatted in the short- and long-axis planes (slice thickness 8 mm; gap 0 mm) in average mode.
Intervention Type
Device
Intervention Name(s)
coronary physiology
Intervention Description
To evaluate the association between microvascular disfunction and myocardial fibrosis identified per computed tomography among subjects undergoing TAVI for severe, symptomatic aortic stenosis.
Primary Outcome Measure Information:
Title
The burden of myocardial fibrosis
Description
Myocardial fibrosis measured as the percentage of delay-enhanced myocardium over total myocardial volume
Time Frame
1 year
Title
Index of microcirculatory resistance (IMR)
Description
IMR a validated estimate of resistance in the coronary capillary, computed as the ratio between transit time of a 3 cc bolus of room temperature saline and distal coronary artery pressure.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Acute change in coronary flow reserve (CRF)
Description
Ratio of maximal coronary blood flow obtained by hyperemia to baseline coronary blood flow
Time Frame
1 year
Title
Acute change in index of microcirculatory resistance (IMR)
Description
Estimate of microvascular resistance derived by pressure and an indirect estimate of flow
Time Frame
1 year
Title
Computed tomography derived extracellular volume
Description
The extracellular volume fraction (ECV) is the relative value of the volume of the extracellular space in the myocardium, therefore express as a percentage. It could be measured from computed tomography (CT) and Index of microcirculatory resistance (MRI) images, and was validated with histology. ECV-CT is calculated as follows:
ECVCT = (1-haematocrit) × (ΔHUmyo/ΔHUblood) where ΔHU is the change in Hounsfield unit attenuation pre- and post-contrast (i.e. HUpost-contrast - HUpre-contrast)
Time Frame
1 year
Title
All-cause death
Description
Death from any cause
Time Frame
1 year
Title
Cardiovascular death
Description
Death from any cardiac condition (e.g. myocardial infarction, acute pulmonary edema, low-output state, etc..) or vascular condition (including aortic dissection, stroke, etc…)
Time Frame
1 year
Title
Any rehospitalization
Description
Admission to an inpatients' service for any cause lasting >24h
Time Frame
1 year
Title
Cardiovascular rehospitalization
Description
Admission to an inpatients' service for cardiovascular conditions lasting >24h
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
• All patients referred to IRCCS Ospedale San Raffaele who are candidates to receive a TAVI implant for severe, symptomatic aortic stenosis under current appropriateness criteria and clinical practice guidelines will be considered eligible to take part in the study
Exclusion Criteria:
Age <18 years
Inability to express informed consent to take part in the present study.
Pregnancy or lactation
Pre-existing known disease determining a prognosis quo ad vitam shorter than the follow up of the present study
Significant chronic kidney disease (estimated glomerular filtration rate <30 ml/min)
Known significant epicardial coronary artery stenosis
Known contraindication to adenosine administration:
Known allergic reactions
Second or third degree atrioventricular block before the procedure (in absence of a functional permanent pacemaker)
Long QT syndrome
Unstable angina
Severe hypotension
Acutely decompensated heart failure
Chronic obstructive pulmonary disease with bronchospasm
Concomitant use of dypiridamole
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marco Ancona, MD
Phone
+39/26437331
Ext
4840
Email
ancona.marco@hsr.it
First Name & Middle Initial & Last Name or Official Title & Degree
Vega Rusconi
Phone
+39 02/26437338
Ext
7338
Email
vega.rusconi@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matteo montorfano, MD
Organizational Affiliation
IRCCS San Raffaele
Official's Role
Principal Investigator
Facility Information:
Facility Name
IRCCS San Raffaele
City
Milan
ZIP/Postal Code
20132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ancona Marco, MD
Phone
+39/02/26437331
Ext
4840
Email
ancona.marco@hsr.it
First Name & Middle Initial & Last Name & Degree
Vega Rusconi, MS
Phone
+39/02/26437338
Ext
7338
Email
vega.rusconi@gmail.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Microvascular Function in Patients Undergoing Transcatheter Aortic Valve Implant (TAVI) for Severe Symptomatic Aortic Stenosis: Association With Myocardial Fibrosis
We'll reach out to this number within 24 hrs