Microvascular Function in Patients Undergoing Transcatheter Aortic Valve Implant (TAVI) for Severe Symptomatic Aortic Stenosis: Association With Myocardial Fibrosis

Microvascular function in patients undergoing Transcatheter Aortic Valve Implant (TAVI) for severe symptomatic aortic stenosis: association with myocardial fibrosis

Study Overview

• Status: Completed
• Conditions: Severe Symptomatic Aortic Stenosis
• Intervention / Treatment: Device: coronary physiology

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • IRCCS San Raffaele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Coronary physiology evaluation; 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.

Device: coronary physiology; To evaluate the association between microvascular disfunction and myocardial fibrosis identified per computed tomography among subjects undergoing TAVI for severe, symptomatic aortic stenosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The burden of myocardial fibrosis	Myocardial fibrosis measured as the percentage of delay-enhanced myocardium over total myocardial volume	1 year
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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute change in coronary flow reserve (CRF)	Ratio of maximal coronary blood flow obtained by hyperemia to baseline coronary blood flow	1 year
Acute change in index of microcirculatory resistance (IMR)	Estimate of microvascular resistance derived by pressure and an indirect estimate of flow	1 year
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)	1 year
All-cause death	Death from any cause	1 year
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…)	1 year
Any rehospitalization	Admission to an inpatients' service for any cause lasting >24h	1 year
Cardiovascular rehospitalization	Admission to an inpatients' service for cardiovascular conditions lasting >24h	1 year

Collaborators and Investigators

• Sponsor: Matteo Montorfano
• Investigators: Principal Investigator: Matteo montorfano, MD, IRCCS San Raffaele

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2021
• Primary Completion (Actual): June 30, 2025
• Study Completion (Actual): July 30, 2025

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 13, 2022

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: TAVI IMR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No