Screening for Amyloidosis Before Aortic Valve Elective Replacement

Aortic Valve Stenosis Clinical Trial

— SAVER  

Official title:

Screening for Amyloidosis Before Aortic Valve Elective Replacement (SAVER)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04869631
• Other study ID #: EA4/235/20
• Status: Active, not recruiting
• Start date: February 1, 2021
• Est. completion date: March 31, 2028

Study information

• Verified date: September 2023
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Previous studies detected that up to 15% of patients undergoing aortic valve replacement (AVR) for degenerative aortic stenosis have concomitant transthyretin amyloidosis (ATTR) cardiomyopathy (Castano, 2017). The aim of this study is to investigate the effectivity and practicability of a systematic ATTR-Screening in patients undergoing planned AVR. Moreover, we plan to develop a screening algorithm to detect ATTR in aortic stenosis (AS).

Description:

Untreated cardiac amyloidosis is accompanied with an impaired prognosis. Amyloidosis is often associated with ventricular hypertrophy which leads to severe heart failure and occurs frequently in conjunction with bradycardic or tachycardic malignant arrhythmia. Patients with degenerative aortic valve stenosis suffer more frequently from cardiac ATTR. However, it remains unclear whether the development of aortic stenosis is promoted by ATTR. Due to very similar symptoms (shortness of breath during physical exertion, reduced walking distance) diagnosis of aortic valve stenosis is more often diagnosed in a typical cohort of patients aged between 70-80 years but, in contrast, leads to underdiagnosis of patients with additional cardiac amyloidosis. Six to fifteen percent of patients with aortic valve replacement due to degenerative aortic valve stenosis exhibit a cardiac amyloidosis. Since cardiac amyloidosis without therapeutic intervention is associated with significantly reduced life expectancy, it can be assumed that these patients will not benefit to the same extent from the AVR alone as patients without ATTR. New therapeutic approaches for patients exhibiting ATTR lead to a reduction of mortality and hospitalizations. The primary aim of this study is to establish a simple ATTR screening tool in patients with planned AVR in the clinical routine and, furthermore, to compare the clinical course following AVR between patients with and without ATTR.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1000
• Est. completion date: March 31, 2028
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 99 Years

Eligibility

Inclusion Criteria:

• age =40 years

• written informed consent from the patient or of his/her legal guardian

• hospitalization for AVR due to degenerative aortic valve stenosis

Exclusion Criteria:

• hemodynamically unstable patient

• severe co-morbidities with an estimated life expectancy of <1 year

Related Conditions & MeSH terms

• Amyloidosis
• Aortic Valve Stenosis

Intervention

Other:
• The outcome of an intervention is not evaluated, but aortic stenosis and additional amyloidosis are compared.
We aim to compare patients with aortic valve stenosis with and without cardiac amyloidosis.

Locations

Country	Name	City	State
Germany	Charité - Universitätsmedizin Berlin	Berlin

Sponsors (3)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Deutsches Herzzentrum Berlin, Klinik für Innere Medizin - Kardiologie, Klinik für Neurologie mit Experimenteller Neurologie, Charité - Universitätsmedizin Berlin

Country where clinical trial is conducted

Germany, 

References & Publications (3)

Castano A, Narotsky DL, Hamid N, Khalique OK, Morgenstern R, DeLuca A, Rubin J, Chiuzan C, Nazif T, Vahl T, George I, Kodali S, Leon MB, Hahn R, Bokhari S, Maurer MS. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J. 2017 Oct 7;38(38):2879-2887. doi: 10.1093/eurheartj/ehx350. — View Citation

Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM, Shah SJ, Hanna M, Judge DP, Barsdorf AI, Huber P, Patterson TA, Riley S, Schumacher J, Stewart M, Sultan MB, Rapezzi C; ATTR-ACT Study Investigators. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018 Sep 13;379(11):1007-1016. doi: 10.1056/NEJMoa1805689. Epub 2018 Aug 27. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number/ proportion of ATTR cases identified by systematic screening		Enrolment period: 18 months

External Links

•   Amyloidosis center of the Charité