Study: NCT03029026

Intervention type: OTHER
Intervention: Baseline assessment
Description: Baseline assessment will include clinical history, Quality of Life Questionnaire (EQ-5D/SF-12), a 6-minute-walk test, blood sampling for haematocrit, renal function, biomarkers (NT-pro-BNP and troponin), and biobanking (also for AL exclusions if scanning positive), a urine sample for biobanking (also for AL exclusions if scanning positive), as well as tests performed as the routine pre-operative work-up (clinical electrocardiogram, blood pressure to estimate global LV afterload, valvulo-arterial impedance).

Intervention type: OTHER
Intervention: Baseline assessment
Description: Baseline assessment will include clinical history, Quality of Life Questionnaire (EQ-5D/SF-12), a 6-minute-walk test, blood sampling for haematocrit, renal function, biomarkers (NT-pro-BNP and troponin), and biobanking (also for AL exclusions if scanning positive), a urine sample for biobanking (also for AL exclusions if scanning positive), as well as tests performed as the routine pre-operative work-up (clinical electrocardiogram, blood pressure to estimate global LV afterload, valvulo-arterial impedance).

Intervention type: OTHER
Intervention: Baseline assessment
Description: Baseline assessment will include clinical history, Quality of Life Questionnaire (EQ-5D/SF-12), a 6-minute-walk test, blood sampling for haematocrit, renal function, biomarkers (NT-pro-BNP and troponin), and biobanking (also for AL exclusions if scanning positive), a urine sample for biobanking (also for AL exclusions if scanning positive), as well as tests performed as the routine pre-operative work-up (clinical electrocardiogram, blood pressure to estimate global LV afterload, valvulo-arterial impedance).

Intervention type: PROCEDURE
Intervention: Transthoracic echocardiography
Description: Patients will undergo a clinical transthoracic echocardiogram for the assessment of AS severity and diastolic function in line with the British Society of Echocardiography guidance. Simultaneous, optimised 2-chamber, 3-chamber and 4-chamber views will need to be recorded (over 3 cycles) for strain analysis.~Severe AS will be defined using standard echocardiography guidelines in conjunction with MDT consensus.

Intervention type: PROCEDURE
Intervention: Transthoracic echocardiography
Description: Patients will undergo a clinical transthoracic echocardiogram for the assessment of AS severity and diastolic function in line with the British Society of Echocardiography guidance. Simultaneous, optimised 2-chamber, 3-chamber and 4-chamber views will need to be recorded (over 3 cycles) for strain analysis.~Severe AS will be defined using standard echocardiography guidelines in conjunction with MDT consensus.

Intervention type: PROCEDURE
Intervention: Transthoracic echocardiography
Description: Patients will undergo a clinical transthoracic echocardiogram for the assessment of AS severity and diastolic function in line with the British Society of Echocardiography guidance. Simultaneous, optimised 2-chamber, 3-chamber and 4-chamber views will need to be recorded (over 3 cycles) for strain analysis.~Severe AS will be defined using standard echocardiography guidelines in conjunction with MDT consensus.

Intervention type: PROCEDURE
Intervention: 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy
Description: Scanning will use a hybrid SPECT-CT gamma camera after intravenous injection of 700 MBq of DPD (effective dose 4mSv). Acquisition technique: 5-minute (early) and then 3-hour (late) whole body planar scans, followed by SPECT-CT of the heart. Qualitative visual (Perugini) scoring of the cardiac uptake is performed from the 3-hour whole body planar images and the SPECT-CT images.

Intervention type: PROCEDURE
Intervention: 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy
Description: Scanning will use a hybrid SPECT-CT gamma camera after intravenous injection of 700 MBq of DPD (effective dose 4mSv). Acquisition technique: 5-minute (early) and then 3-hour (late) whole body planar scans, followed by SPECT-CT of the heart. Qualitative visual (Perugini) scoring of the cardiac uptake is performed from the 3-hour whole body planar images and the SPECT-CT images.

Intervention type: PROCEDURE
Intervention: 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy
Description: Scanning will use a hybrid SPECT-CT gamma camera after intravenous injection of 700 MBq of DPD (effective dose 4mSv). Acquisition technique: 5-minute (early) and then 3-hour (late) whole body planar scans, followed by SPECT-CT of the heart. Qualitative visual (Perugini) scoring of the cardiac uptake is performed from the 3-hour whole body planar images and the SPECT-CT images.

Intervention type: RADIATION
Intervention: CT 3-5-minute post-contrast research sequences
Description: Cardiac CT for ECV will use the dedicated cardiac CT scanner (Somatom FORCE; Siemens Medical Solutions, Germany). 3-5-minute post contrast research images will be taken at the end of the clinically indicated TAVR work-up CT.

Intervention type: PROCEDURE
Intervention: Cardiac Magnetic Resonance
Description: CMR will be performed using a 1.5-T Aera for standard late gadolinium enhancement, as well as T1 mapping and ECV.

Intervention type: PROCEDURE
Intervention: Endomyocardial biopsy
Description: Septal tissue specimens will be taken under direct vision by the surgical team using a 14-gauge coaxial needle system. Biopsies will be screened for amyloid by Congo red staining; if positive, tissue will be fully sub-typed (immunohistochemistry, mass spectrometry).

Intervention type: OTHER
Intervention: Follow-up assessment
Description: 1-year follow-up with clinical echocardiogram (for sAVR and TAVI patients) and/or telephone interview for all patients (if not carried out in person at the time of the echocardiogram). This will include a follow up Quality of Life Questionnaire as per baseline. If attending clinic or echocardiogram a 6-minute-walk test will also be performed.

Intervention type: OTHER
Intervention: Follow-up assessment
Description: 1-year follow-up with clinical echocardiogram (for sAVR and TAVI patients) and/or telephone interview for all patients (if not carried out in person at the time of the echocardiogram). This will include a follow up Quality of Life Questionnaire as per baseline. If attending clinic or echocardiogram a 6-minute-walk test will also be performed.

Intervention type: OTHER
Intervention: Follow-up assessment
Description: 1-year follow-up with clinical echocardiogram (for sAVR and TAVI patients) and/or telephone interview for all patients (if not carried out in person at the time of the echocardiogram). This will include a follow up Quality of Life Questionnaire as per baseline. If attending clinic or echocardiogram a 6-minute-walk test will also be performed.