Screening Algorithm for Early Detection of Occult Cardiac Amyloidosis

NCT05693376 | Completed

• 1 other identifier: 209268
• Study Type: observational
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiac Amyloidosis

Keywords

Cardiac amyloidosis; Aortic stenosis; AS-ATTR

Outcome Measures

Primary Outcomes (1)

• Diagnosis of occult cardiac amyloidosis

  Early diagnosis of occult cardiac amyloidosis, based on a proposed screening algorithm

  3 years

Study Arms (2)

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.

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects with severe aortic stenosis, that fulfill the inclusion criteria.

You may qualify if:

• 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:
• Carpal tunnel syndrom
• Non-traumatic rupture of the biceps tendon
• NT-proBNP \> 1000 pg/ml
• hs Troponin value above the 99th percentile without dynamic changes (≤ 20%)
• Minor criteria:
• Diastolic dysfunction (at least grade 2, E' \< 10 cm/s)
• Sinus bradycardia/AV block/pacemaker
• Atrial fibrillation

You may not qualify if:

• Known cardiac amyloidosis (ATTR or AL)
• Unable to provide written informed consent
• Refusal to provide written informed consent
• Contraindications for study investigations

Sponsors & Collaborators

• University Hospital, Essen: lead

Study Sites (1)

University Hospital Essen

Essen, North Rhine-Westphalia, 45122, Germany

Location

Related Publications (20)

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MeSH Terms

Conditions

Amyloid Neuropathies, Familial; Aortic Valve Stenosis

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; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Aiste Monika Jakstaite, MD

  University Hospital, Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Cardiologist

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: January 23, 2023
• Study Start: August 5, 2020
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: August 20, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)