Novel Echocardiographic and Invasive Haemodynamic Measurements in the Assessment of Patients Low Flow Low Gradient Aortic Stenosis Undergoing TAVI

Study Overview
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Brief Summary
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In this study the investigators will assess a variety of novel markers of heart strength (contractility) and assess whether they can give a clearer indication of how well patients with weak hearts respond to the TAVI procedure. The investigators will perform a stress echocardiogram prior to each TAVI procedure and measure the global longitudinal strain (GLS) in the left ventricle (LV) heart muscle, a detailed marker of muscle strength. The investigators will then proceed to the TAVI procedure and measure the contractility of the main pumping chamber in the heart before and after giving a very low dose of an adrenaline -like drug (dobutamine). The patient will already have received this short acting drug (at the same and higher doses) during their routine care planning stress echocardiogram.

Detailed Description
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In this study the investigators will assess a variety of novel markers of heart strength (contractility) and assess whether they can give a clearer indication of how well patients with weak hearts respond to the TAVI procedure. The investigators will perform a stress echocardiogram prior to each TAVI procedure and measure the global longitudinal strain (GLS) in the left ventricle (LV) heart muscle, a detailed marker of muscle strength. The investigators will then proceed to the TAVI procedure and measure the contractility of the main pumping chamber in the heart before and after giving a very low dose of an adrenaline -like drug (dobutamine). The patient will already have received this short acting drug (at the same and higher doses) during their routine care planning stress echocardiogram. The investigators will also measure the pressure across the aortic valve, known as the trans-aortic gradient, using the pressure wire (PW) and a standard (multipurpose) heart catheter. The investigators will repeat the resting measures (i.e. without pacing or dobutamine) at the end of the procedure to measure the early change in left ventricular contractility and then repeat the echocardiogram immediately and after 3 months to assess the outcome of the TAVI procedure in terms of left ventricular function volume and function

Official Title
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Utility of Novel Echocardiographic and Invasive Haemodynamic Measurements in the Assessment of Patients Low Flow Low Gradient Aortic Stenosis Undergoing TAVI

Conditions
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Cardiovascular Abnormalities

Intervention / Treatment
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* Other: Ultrasound
* Procedure: Catheters
* Procedure: Soft study wire
* Radiation: X-ray
* Drug: Dobutamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting symptomatic AS listed for TAVI Native aortic valve disease Ejection fraction </= 40% Mean trans aortic gradient (echo) of <35 mmHg AVA </= 1cm2 Able to give written informed consent prior to enrolment in the study No contraindication to study procedures CT scan confirmed severe AS *Able and willing to return to the implanting site for the follow-up visits* Exclusion Criteria: Unable to provide formal written consent Known pseudo-severe AS prior to TAVI Known allergy to agents required for stress echocardiography Known hypersensitivity or contraindication to aspirin, heparin, clopidogrel, Nitinol, or sensitivity to contrast media, which cannot be adequately premedicated. * Any clinical contraindication to TAVI procedure This pilot study will be restricted to English speaking subjects.
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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The Royal Wolverhampton NHS Trust- New Cross Hospital<br> | Other: Ultrasound<br>* Participants will have a routine ultrasound of the heart (echocardiogram) before the procedure. During this test we will take a few extra measurements, this will not add any significant time to the scan<br>Procedure: Catheters<br>* During the TAVI procedure 3 catheters (tubes) will be inserted into the blood vessels at the top of the participants legs as per normal standard care (there will be no extra skin punctures as part of the study).<br>Procedure: Soft study wire<br>* Participants will have a soft study wire inserted to measure the pressure in the left ventricle. This step is in addition to standard care.<br>Radiation: X-ray<br>* Participants will have chests x-ray when the soft study wire is inserted.<br>Drug: Dobutamine<br>* Participants will be given a low dose infusion of dobutamine, to make the heart pump quicker and more vigorously.. This will last for approximately 5 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LV ejection fraction at 3 months compared to pre procedural readings. | Change in LV ejection fraction as a percentage | 3 months | 
| Change in LV Volume at 3 months compared to pre procedural readings. | Change in LV Volume measured by BSA, mL/m2 | 3 months | 
| Change in global longitudinal strain at 3 months compared to pre procedural readings. | Change in global longitudinal strain measured by percentage | 3 months | 
| Change in fractional shortening by echocardiography at 3 months compared to pre procedural readings. | Change in fractional shortening measured by percentage | 3 months | 
| The change in contractility (dP/dT) with low dose dobutamine stress prior to TAVI, measured by invasive Pressure Wire | The change in contractility (dP/dT) with low dose dobutamine stress prior to TAVI, measured by invasive Pressure Wire | 3 months | 
| The change in aortic trans-valvular gradient with low dose dobutamine stress during TAVI prior to AV treatment. | The change in aortic trans-valvular gradient measured by mmHg | 3 months | 
| The change in contractility (dP/dT) from pre to post procedure at 3 months. | The change in derivative of pressure over time (dP/dT) is measured by the change in pressure per unit time. Measured ventricular pressure provides an indication of the contractility or relaxation of the ventricles of a heart. In this way, the derivative of pressure over time (dP/dt) provides a biphasic signal that can be used to evaluate acute directional changes of contractility | 3 months |