ATTR Amyloidosis in Elderly Patients With Aortic Stenosis

NCT04061213 | Unknown DMC

• 1 other identifier: 4083 / KEK-Nr. 2019-00880
• Study Type: observational
• Target: 489
• Locations: 1 country
• Sites: 1

Brief Summary

Severe aortic stenosis is defined with a mean transvalvular pressure gradient (MTPG) \> 40mmHg and a calculated aortic valve area of \< 1cm2. However, a considerable proportion of patients do have a MTPG \< 40mmHg due to a reduced stroke volume (stroke volume indexed to body surface area ≤ 35ml/m2) despite a normal left ventricular ejection fraction (LVEF \> 50%). This entity is termed paradoxical low flow low gradient aortic stenosis (PLFLG AS) and is associated with a worse prognosis. ATTR amyloidosis is a disease of the elderly and might coexist in patients with severe aortic stenosis. Case reports and small observational studies suggest that senile ATTR amyloidosis could be frequent but underdiagnosed in patients with aortic stenosis. There is significant overlap between PLFLG AS and cardiac amyloidosis with regard to symptoms, increasing prevalence with age, concentric hypertrophy, impaired diastolic filling of the left ventricle (LV), as well as longitudinal LV dysfunction despite preserved ejection fraction - all features, which lead to a reduction in stroke volume, the underlying mechanism of the low flow condition as observed in PLFLG AS patients.

Conditions

Aortic Stenosis Symptomatic; Amyloidosis Cardiac

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with grade 2 or 3 cardiac uptake in scintigraphy and without pathological light chains in immunological assays

  Evaluation of incidence rate

  In-Hospital [7 days]

Secondary Outcomes (2)

• All-cause and cardiovascular mortality

  30 days, 12months

• CPET - maximal exercise capacity

  In-Hospital [7 days]

Study Arms (1)

Patients with symptomatic severe aortic stenosis

Elderly patients referred for TAVR evaluation

Diagnostic Test: Tc-99m-DPD scintigraphy

Interventions

Tc-99m-DPD scintigraphy DIAGNOSTIC_TEST

Myocardial scintigraphy

Patients with symptomatic severe aortic stenosis

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with symptomatic, severe aortic stenosis undergoing pre-evaluation for (transcatheter) aortic valve replacement

You may qualify if:

• Symptomatic, severe aortic stenosis

You may not qualify if:

• More than mild valvular disease of any other valve
• Other severe disease with a life expectancy \< 1 year
• Participating in trial interfering with routine clinical practice or use of a non-CE marked device

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

University Hospital Bern - Inselspital

Bern, Canton of Bern, 3010, Switzerland

Location

Related Publications (2)

• Bernhard B, Leib Z, Dobner S, Demirel C, Caobelli F, Rominger A, Schutze J, Grogg H, Alwan L, Spano G, Boscolo Berto M, Lanz J, Pilgrim T, Windecker S, Stortecky S, Grani C. Routine 4D Cardiac CT to Identify Concomitant Transthyretin Amyloid Cardiomyopathy in Older Adults with Severe Aortic Stenosis. Radiology. 2023 Dec;309(3):e230425. doi: 10.1148/radiol.230425.

  PMID: 38085082 DERIVED

• Dobner S, Pilgrim T, Hagemeyer D, Heg D, Lanz J, Reusser N, Grani C, Afshar-Oromieh A, Rominger A, Langhammer B, Reineke D, Windecker S, Stortecky S. Amyloid Transthyretin Cardiomyopathy in Elderly Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation. J Am Heart Assoc. 2023 Aug 15;12(16):e030271. doi: 10.1161/JAHA.123.030271. Epub 2023 Aug 10.

  PMID: 37581394 DERIVED

MeSH Terms

Conditions

Amyloid Neuropathies, Familial

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies

Study Officials

• Stefan Stortecky, MD

  Swiss Cardiovascular Center Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2019
• First Posted: August 19, 2019
• Study Start: August 26, 2019
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: December 15, 2022

Record last verified: 2022-12

Locations

CH (1)