Screening Algorithm for Early Detection of Occult Cardiac Amyloidosis

NCT ID: NCT05693376

Last Updated: 2024-08-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

85 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-08-05

Study Completion Date

2023-05-01

Brief Summary

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Early diagnosis of cardiac amyloidosis (CA) is crucial because of the poor overall survival, high mortality and the need for early therapy including new treatment possibilities for transthyretin amyloidosis. Previously considered a rare condition, CA is being demonstrated to account for up to 17 % of heart failure with preserved ejection fraction cases as well as up to 16 % of Patients with severe aortic stenosis, undergoing surgical of transcatheter aortic valve replacement. It seems that CA is being underdiagnosed as the data of post-mortem studies demonstrate that at least 25% of elderly individuals have histologic evidence of amyloid deposits. Other common conditions with increased afterload such as hypertensive or hypertrophic heart disease that mimic echocardiographic features or clinical symptoms may be the reason of postponed recognition of CA. Furthermore, the lack of definitive biomarkers makes the diagnosis even more challenging. However, it has been shown that some clinical, laboratory and echocardiographic findings, so called "red flags", may indicate occult CA. A deeper and constructive analysis of the findings and establishment of prediction criteria could possibly lead to improvement of early CA recognition and survival in subjects at risk. We aim to prospectively perform a systematic screening for CA in individuals at risk based on predefined selection criteria. Our aim is to evaluate if specific criteria would lead to increased detection of CA and in this case, to define major and minor diagnostic criteria.

Detailed Description

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The study aims to perform a prospective screening and detect occult CA in subjects at risk with aortic valve stenosis, undergoing either transcatheter or surgical aortic valve replacement. The study has two main objectives. Firstly, we aim to determine the real prevalence of CA according to the targeted "red flags" analysis and secondly, we aim to establish an algorithm for early detection of CA.

Conditions

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Cardiac Amyloidosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Intervention group

Subjects who meet the following inclusion criteria: 1) Severe aortic stenosis. 2) Age \> 65 years for male and \>70 years for female. 3) Increased left ventricular wall thickness ≥14 mm. 4) Blood pressure ≤ 140/90 mmHg and at least 1 major or ≥ 2 minor criteria. Major criteria: a) Carpal tunnel syndrom; b) Non-traumatic rupture of the biceps tendon; c) NT-proBNP \> 1000 pg/ml; d) hs Troponin value above the 99th percentile without dynamic changes (≤ 20%). Minor criteria: a) Diastolic dysfunction (at least grade 2, E' \< 10 cm/s); b) Sinus bradycardia/AV block/pacemaker; c) Atrial fibrillation.

No interventions assigned to this group

Control group

Subjects who meet the following inclusion criteria: 1) Severe aortic stenosis. 2) Age \> 65 years for male and \>70 years for female. 3) Increased left ventricular wall thickness ≥14 mm. 4) Blood pressure ≤ 140/90 mmHg.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Fulfillment of following four criteria: 1) Severe aortic stenosis. 2) Age \> 65 years for male and \>70 years for female. 3) Increased left ventricular wall thickness ≥14 mm. 4) Blood pressure ≤ 140/90 mmHg and at least 1 major or ≥ 2 minor criteria.

Major criteria:

1. Carpal tunnel syndrom
2. Non-traumatic rupture of the biceps tendon
3. NT-proBNP \> 1000 pg/ml
4. hs Troponin value above the 99th percentile without dynamic changes (≤ 20%)

Minor criteria:

1. Diastolic dysfunction (at least grade 2, E' \< 10 cm/s)
2. Sinus bradycardia/AV block/pacemaker
3. Atrial fibrillation

Exclusion Criteria

* Known cardiac amyloidosis (ATTR or AL)
* Unable to provide written informed consent
* Refusal to provide written informed consent
* Contraindications for study investigations
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Essen

OTHER

Sponsor Role lead

Responsible Party

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Maria Papathanasiou

Principal Investigator, Cardiologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Aiste Monika Jakstaite, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Essen

Locations

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University Hospital Essen

Essen, North Rhine-Westphalia, Germany

Site Status

Countries

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Germany

References

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Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing Common Questions Encountered in the Diagnosis and Management of Cardiac Amyloidosis. Circulation. 2017 Apr 4;135(14):1357-1377. doi: 10.1161/CIRCULATIONAHA.116.024438.

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Damy T, Costes B, Hagege AA, Donal E, Eicher JC, Slama M, Guellich A, Rappeneau S, Gueffet JP, Logeart D, Plante-Bordeneuve V, Bouvaist H, Huttin O, Mulak G, Dubois-Rande JL, Goossens M, Canoui-Poitrine F, Buxbaum JN. Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness. Eur Heart J. 2016 Jun 14;37(23):1826-34. doi: 10.1093/eurheartj/ehv583. Epub 2015 Nov 3.

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Reference Type BACKGROUND
PMID: 27143678 (View on PubMed)

Other Identifiers

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209268

Identifier Type: -

Identifier Source: org_study_id

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