Aortic Stenosis and Cardiac Amyloidosis

NCT ID: NCT06129331

Last Updated: 2023-11-13

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-03-01
• Study Completion Date: 2024-12-31

Brief Summary

The dual pathology of aortic stenosis (AS) and cardiac amyloidosis (CA) is increasingly recognized. Even tough efforts have been undertaken to bring cohorts together, the largest cohort of AS-ATTR to date is <50 patients. It is the aim of the present international, multi-center registry to collect ~300 patients with AS-CA creating a big enough cohort to allow

1. thorough characterization of this condition

2. assessment of log-term clinical outcomes of AS-CA

3. assessment of effectiveness of amyloid-specific treatment on top of valve replacement

Detailed Description

Calcific aortic stenosis (AS) and transthyretin (ATTR) cardiac amyloidosis are both conditions commonly affecting the elderly. Bone scintigraphy using amyloid-avid tracers (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, DPD; 99mTc-pyrophosphate; or 99mTc-hydroxymethylene diphosphonate) represents the key imaging modality for non-invasive ATTR diagnosis. Recent studies have used this technology to screen AS patients and demonstrated that AS and ATTR may coexist in 8 to 16%. This is substantially higher than in non-cardiac referrals for bone scintigraphy (range 1-3% in individuals >80 years), which is considered the most accurate approach to estimate the ATTR prevalence in the general population. While the dual burden of AS and ATTR might suggest adverse prognostic implications, it has been shown that AS-ATTR and lone AS patients benefit equally from transcatheter aortic valve replacement (TAVR) with comparable 1- and 2-year survival rates. Yet, data on long-term outcomes are still missing.

With increased recognition and valvular treatment of AS-ATTR, the disease course after TAVR becomes a key issue. Our data suggest significantly different remodeling between lone AS and AS-ATTR, with the latter being transformed into a "lone-ATTR" cardiomyopathy phenotype at one-year post-TAVR. Novel ATTR-specific treatments are now available, with the potential to further improve prognosis in AS-ATTR on top of valvular replacement. However, patients with significant AS were not included in the ATTR-ACT trial, and treatment effectiveness in this patient population therefore remains unclear. Also, despite increased ATTR screening globally, the case numbers for dual AS-ATTR of individual centers are still low.

The present international multi-center study is therefore designed to provide detailed characterization of dual AS-ATTR, inform about long-term clinical outcomes and assess the effect of ATTR specific treatment.

Conditions

Cardiac Amyloidosis; Aortic Stenosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

AS-CA without amyloid-specific treatment

Patients with no amyloid-specific treatment

No amyloid-specific treatment

Intervention Type: OTHER

No amyloid-specific treatment

AS-CA with amyloid-specific treatment

Patients receiving newly available amyloid-specific drugs

Amyloid-specific treatment

Intervention Type: DRUG

Amyloid-specific treatment

Interventions

Amyloid-specific treatment

Amyloid-specific treatment

Intervention Type: DRUG

No amyloid-specific treatment

No amyloid-specific treatment

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients with significant AS and a concomitant diagnosis of cardiac amyloidosis who are eligible for inclusion as per local permissions

Exclusion Criteria

• Patients without significant AS (less than moderate AS)
• Patients with other subtypes of cardiac amyloidosis (e.g., light chain)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Allina Health System

OTHER

Sponsor Role: collaborator

Royal Free Hospital NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: collaborator

Laval University

OTHER

Sponsor Role: collaborator

Vilnius University Hospital Santaros Klinikos

OTHER

Sponsor Role: collaborator

Université Catholique de Louvain

OTHER

Sponsor Role: collaborator

Wolfson Medical Center

OTHER_GOV

Sponsor Role: collaborator

IRCCS Azienda Ospedaliero-Universitaria di Bologna

OTHER

Sponsor Role: collaborator

University of Trieste

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Christian Nitsche

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Medical University of Vienna

Vienna, , Austria

Site Status: RECRUITING

University College London

London, , United Kingdom

Site Status: RECRUITING

Countries

Austria; United Kingdom

Facility Contacts

Christian Nitsche, MD, PhD

Role: primary

christian.nitsche@meduniwien.ac.at

01 40400 46142

Thomas Treibel, MD, PhD

Role: primary

thomas.treibel.12@ucl.ac.uk

020 3386 9000

References

Nitsche C, Scully PR, Patel KP, Kammerlander AA, Koschutnik M, Dona C, Wollenweber T, Ahmed N, Thornton GD, Kelion AD, Sabharwal N, Newton JD, Ozkor M, Kennon S, Mullen M, Lloyd G, Fontana M, Hawkins PN, Pugliese F, Menezes LJ, Moon JC, Mascherbauer J, Treibel TA. Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis. J Am Coll Cardiol. 2021 Jan 19;77(2):128-139. doi: 10.1016/j.jacc.2020.11.006. Epub 2020 Nov 9.

Reference Type: RESULT

PMID: 33181246 (View on PubMed)

Nitsche C, Aschauer S, Kammerlander AA, Schneider M, Poschner T, Duca F, Binder C, Koschutnik M, Stiftinger J, Goliasch G, Siller-Matula J, Winter MP, Anvari-Pirsch A, Andreas M, Geppert A, Beitzke D, Loewe C, Hacker M, Agis H, Kain R, Lang I, Bonderman D, Hengstenberg C, Mascherbauer J. Light-chain and transthyretin cardiac amyloidosis in severe aortic stenosis: prevalence, screening possibilities, and outcome. Eur J Heart Fail. 2020 Oct;22(10):1852-1862. doi: 10.1002/ejhf.1756. Epub 2020 Feb 20.

Reference Type: RESULT

PMID: 32078212 (View on PubMed)

Nitsche C, Koschutnik M, Dona C, Radun R, Mascherbauer K, Kammerlander A, Heitzinger G, Dannenberg V, Spinka G, Halavina K, Winter MP, Calabretta R, Hacker M, Agis H, Rosenhek R, Bartko P, Hengstenberg C, Treibel T, Mascherbauer J, Goliasch G. Reverse Remodeling Following Valve Replacement in Coexisting Aortic Stenosis and Transthyretin Cardiac Amyloidosis. Circ Cardiovasc Imaging. 2022 Jul;15(7):e014115. doi: 10.1161/CIRCIMAGING.122.014115. Epub 2022 Jul 8.

Reference Type: RESULT

PMID: 35861981 (View on PubMed)

Patel KP, Scully PR, Nitsche C, Kammerlander AA, Joy G, Thornton G, Hughes R, Williams S, Tillin T, Captur G, Chacko L, Kelion A, Sabharwal N, Newton JD, Kennon S, Ozkor M, Mullen M, Hawkins PN, Gillmore JD, Menezes L, Pugliese F, Hughes AD, Fontana M, Lloyd G, Treibel TA, Mascherbauer J, Moon JC. Impact of afterload and infiltration on coexisting aortic stenosis and transthyretin amyloidosis. Heart. 2022 Jan;108(1):67-72. doi: 10.1136/heartjnl-2021-319922. Epub 2021 Sep 8.

Reference Type: RESULT

PMID: 34497140 (View on PubMed)

Scully PR, Patel KP, Saberwal B, Klotz E, Augusto JB, Thornton GD, Hughes RK, Manisty C, Lloyd G, Newton JD, Sabharwal N, Kelion A, Kennon S, Ozkor M, Mullen M, Hartman N, Cavalcante JL, Menezes LJ, Hawkins PN, Treibel TA, Moon JC, Pugliese F. Identifying Cardiac Amyloid in Aortic Stenosis: ECV Quantification by CT in TAVR Patients. JACC Cardiovasc Imaging. 2020 Oct;13(10):2177-2189. doi: 10.1016/j.jcmg.2020.05.029. Epub 2020 Aug 5.

Reference Type: RESULT

PMID: 32771574 (View on PubMed)

Scully PR, Patel KP, Treibel TA, Thornton GD, Hughes RK, Chadalavada S, Katsoulis M, Hartman N, Fontana M, Pugliese F, Sabharwal N, Newton JD, Kelion A, Ozkor M, Kennon S, Mullen M, Lloyd G, Menezes LJ, Hawkins PN, Moon JC. Prevalence and outcome of dual aortic stenosis and cardiac amyloid pathology in patients referred for transcatheter aortic valve implantation. Eur Heart J. 2020 Aug 1;41(29):2759-2767. doi: 10.1093/eurheartj/ehaa170.

Reference Type: RESULT

PMID: 32267922 (View on PubMed)

Treibel TA, Fontana M, Gilbertson JA, Castelletti S, White SK, Scully PR, Roberts N, Hutt DF, Rowczenio DM, Whelan CJ, Ashworth MA, Gillmore JD, Hawkins PN, Moon JC. Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis: Prevalence and Prognosis in Patients Undergoing Surgical Aortic Valve Replacement. Circ Cardiovasc Imaging. 2016 Aug;9(8):e005066. doi: 10.1161/CIRCIMAGING.116.005066.

Reference Type: RESULT

PMID: 27511979 (View on PubMed)

Nitsche C, Dobner S, Rosenblum HR, Patel KP, Longhi S, Yilmaz A, Merlo M, Papathanasiou M, Griffin J, Oerlemans MIFJ, Gama F, Hamdan A, Kelion AD, Schuster A, Glaveckaite S, Akyol N, Porcari A, Schlender L, Capovilla T, Autherith M, Hauptmann L, Halavina K, Cavalcante JL, Fontana M, Scully PR, Moon JC, Mascherbauer J, Ristl R, Biagini E, Stortecky S, Maurer MS, Treibel TA; AS-Amyloidosis Consortium. Cardiac transthyretin amyloidosis treatment improves outcomes after aortic valve replacement for severe stenosis. Eur Heart J. 2025 Jun 2:ehaf362. doi: 10.1093/eurheartj/ehaf362. Online ahead of print.

Reference Type: DERIVED

PMID: 40452225 (View on PubMed)

Other Identifiers

2218_2016

Identifier Type: -

Identifier Source: org_study_id