Screening Algorithm for Early Detection of Occult Cardiac Amyloidosis

Study Overview
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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.

Official Title
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Evaluation of a Screening Algorithm for Early Detection of Occult Cardiac Amyloidosis in Subjects at Risk

Conditions
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Detection of Occult Cardiac Amyloidosis

Participation Criteria
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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: 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 Exclusion Criteria: Known cardiac amyloidosis (ATTR or AL) Unable to provide written informed consent Refusal to provide written informed consent Contraindications for study investigations

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Intervention group<br>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<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of occult cardiac amyloidosis | Early diagnosis of occult cardiac amyloidosis, based on a proposed screening algorithm | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac amyloidosis, aortic stenosis