The Role of Occult Cardiac Amyloid in the Elderly With Aortic Stenosis.

Summary

Aortic stenosis (AS) is the most common valvular heart disease. Once symptomatic with severe AS, outcome is poor unless the valve is replaced surgically or via transcatheter aortic valve replacement (TAVR). Transthyretin amyloid (ATTR) deposits are common in the heart muscle in up to 25% of octogenarians, and after an asymptomatic period of unknown duration, cause overt heart failure and arrhythmias in a proportion of cases. The prevalence and impact of covert ATTR amyloidosis in elderly individuals with AS are unknown. Detection would avoid misdiagnosis, guide treatment and, potentially, improve outcomes. Recent data have shown that echocardiography, cardiovascular magnetic resonance (CMR), computed tomography (CT), and DPD scintigraphy, can identify ATTR amyloid deposits, but the clinical performance of these various tests is unknown.

This study will investigate elderly patients with symptomatic severe AS using imaging to explore ATTR amyloid in AS and determine its prevalence and impact on outcome.

The investigators aim to recruit a total of 250 patients aged 75 or older being considered for intervention for severe AS. The prevalence of cardiac amyloid will be assessed in three arms (sAVR, TAVI and medical therapy, with a likely patient ratio of 50:150:50), using five investigation modalities - all cohorts (echocardiography and DPD scintigraphy); sAVR cohort (biopsy and CMR); TAVI cohort (EqCT); medical therapy only cohort (as per work-up/trial prior to no intervention decision).

The primary outcome measure is patient mortality. Secondary outcomes measures are major adverse cardiovascular events, length of stay, pacemaker implantation, ECV measured by EqCT and CMR.

Follow up will be at 1-year 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).

Conditions

• Cardiac Amyloidosis
• Aortic Stenosis

Interventions

OTHER

Baseline assessment

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).

PROCEDURE

Transthoracic echocardiography

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.

PROCEDURE

99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy

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.

RADIATION

CT 3-5-minute post-contrast research sequences

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.

PROCEDURE

Cardiac Magnetic Resonance

CMR will be performed using a 1.5-T Aera for standard late gadolinium enhancement, as well as T1 mapping and ECV.

PROCEDURE

Endomyocardial biopsy

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).

OTHER

Follow-up assessment

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.

Sponsors & Collaborators

• Queen Mary University of London

  lead OTHER

Eligibility

Min Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-02-22

Primary Completion

2021-03-01

Completion

2021-03-01

Countries

• United Kingdom

Study Locations