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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: A sTudy invesTigating the Role of Occult cArdiaC Amyloid in The Elderly With Aortic Stenosis

Brief 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 implantation (TAVI). 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

Detailed Summary:

INTRODUCTION

Calcific aortic stenosis (AS) is the most common valve disease in the West with a prevalence of 2.8% in patients over 75 years. Once symptomatic with severe AS, outcome is poor, unless the valve is replaced surgically (sAVR) or via transcatheter aortic valve replacement (TAVR), which is predominantly used in elderly patients for whom surgery is deemed too high risk.

Systemic amyloidosis is a multisystem disease characterised by extracellular deposition of abnormally folded protein, which over time results in progressive organ dysfunction. These protein deposits bind Congo red stain, producing the pathognomonic apple-green birefringence under polarised light. Cardiac involvement is the leading cause of morbidity and mortality in these patients. Amyloidosis due to transthyretin deposition (ATTR) can be due to wild-type transthyretin amyloid deposits, also known as senile systemic amyloidosis, which predominantly accumulates in the heart. Primary light chain (AL) amyloidosis and hereditary transthyretin amyloidosis can also affect the heart.

Wild-type ATTR (wtATTR) amyloid deposition is present in up to a 25% of individuals aged over 85 at autopsy. To date, this has been no more than an academic observation, but technology is changing this: cardiac imaging, particularly cardiovascular magnetic resonance (CMR) and 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy, can now detect the disease antemortem, which is generating a major increase in national awareness. There are also significant advances being made in the treatment of amyloidosis. There are several drugs in clinical trial including novel antisense and interfering RNA therapeutics that can reduce production of TTR by up to 80-90%. Also on the horizon are treatments to promote clearance o
Sponsor: Queen Mary University of London

Current Primary Outcome: Patient mortality [ Time Frame: 1-year ]

From patient notes, GP records or Office of National Statistics.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Major adverse cardiovascular events (MACE) [ Time Frame: 1-year ]
    From patient's medical records. Includes for example: cardiac death, myocardial infarction and emergency cardiac surgery or intervention.
  • Length of hospital stay [ Time Frame: 1-year ]
    From patient's medical records
  • Pacemaker implantation [ Time Frame: 1-year ]
    From patient's medical records
  • Outcome of the various cardiac imaging modalities [ Time Frame: 1-year ]


Original Secondary Outcome: Same as current

Information By: Queen Mary University of London

Dates:
Date Received: January 9, 2017
Date Started: September 2016
Date Completion: April 2019
Last Updated: January 19, 2017
Last Verified: November 2016