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

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

Detailed Description
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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.

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

Conditions
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Severe Symptomatic Aortic Stenosis

Intervention / Treatment
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* Device: coronary physiology


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Coronary physiology evaluation<br>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<br>* To evaluate the association between microvascular disfunction and myocardial fibrosis identified per computed tomography among subjects undergoing TAVI for severe, symptomatic aortic stenosis.<br>|

What is the study measuring?
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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 |