Screening for Amyloidosis Before Aortic Valve Elective Replacement (SAVER)

• ClinicalTrials.gov Identifier: NCT04869631
• Recruitment Status: Recruiting
• First Posted: May 3, 2021
• Last Update Posted: May 6, 2021
• Sponsor: Charite University, Berlin, Germany
• Collaborators: Deutsches Herzzentrum Berlin, Klinik für Innere Medizin - Kardiologie; Klinik für Neurologie mit Experimenteller Neurologie, Charité - Universitätsmedizin Berlin
• Information provided by (Responsible Party): Isabel Mattig, Charite University, Berlin, Germany

Study Description

Brief 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).

Condition or disease	Intervention/treatment
Amyloidosis; Aortic Valve Stenosis	Other: The outcome of an intervention is not evaluated, but aortic stenosis and additional amyloidosis are compared.

Detailed 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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 1000 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Screening for Amyloidosis Before Aortic Valve Elective Replacement (SAVER)
• Actual Study Start Date: February 1, 2021
• Estimated Primary Completion Date: February 28, 2023
• Estimated Study Completion Date: January 28, 2028

Groups and Cohorts

Group/Cohort	Intervention/treatment
Aortic valve stenosis undergoing aortic valve replacement; Aortic valve stenosis undergoing aortic valve replacement.	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.

Outcome Measures

Primary Outcome Measures :

1. Number/ proportion of ATTR cases identified by systematic screening [ Time Frame: Enrolment period: 18 months ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients >40 years with aortic valve stenosis who are scheduled to undergo interventional or surgical aortic valve replacement at Deutsches Herzzentrum Berlin or Charité - Universitätsmedizin Berlin during a recruiting period of 18 months; in total approximately 1500 patients.

Criteria

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

Contacts and Locations

Contacts

Contact: Isabel Mattig, MD; +49 30 450 513 142; isabel.mattig@charite.de

Contact: Daniel Messroghli, MD; +49 30 4593 2400; dmessroghli@DHZB.de

Locations

Germany

Charité - Universitätsmedizin Berlin; Recruiting

Berlin, Germany, 10117

Contact: Isabel Mattig, MD +49 30 450 513 142 isabel.mattig@charite.de

Principal Investigator: Daniel Messroghli, MD

Principal Investigator: Fabian Knebel, MD

Principal Investigator: Isabel Mattig, MD

Principal Investigator: Katrin Hahn, MD

Sub-Investigator: Wrede-Wihl Katrin

Sponsors and Collaborators

Charite University, Berlin, Germany

Deutsches Herzzentrum Berlin, Klinik für Innere Medizin - Kardiologie

Klinik für Neurologie mit Experimenteller Neurologie, Charité - Universitätsmedizin Berlin

More Information

Additional Information:

Amyloidosis center of the Charit&#233; 

Publications:

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.

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.

Castaño 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.

• Responsible Party: Isabel Mattig, Project lead, Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT04869631
• Other Study ID Numbers: EA4/235/20
• First Posted: May 3, 2021
• Last Update Posted: May 6, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Isabel Mattig, Charite University, Berlin, Germany:

Cardiac Amyloidosis; Transthyretin Amyloidosis; ATTR; Aortic Stenosis; Screening

Additional relevant MeSH terms:

Aortic Valve Stenosis; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction