Cardiac Amyloidosis in Spinal Stenosis: the CASS-study

Study Overview
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Brief Summary
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Background: A significant portion of cardiac amyloidosis patients have a 5 to 10 years prior history of spinal canal stenosis, reflecting a diagnostic red flag that should raise suspicion for amyloidosis presence. Mild troponin release and NT-proBNP elevation, both serum cardiac biomarkers, often coincide with cardiac amyloidosis. Early cardiac amyloidosis treatment improves survival, warranting timely diagnosis. Study aim: to test a prospective screening strategy, based on serum cardiac biomarkers, to increase early detection of cardiac amyloidosis in patients with spinal canal stenosis. Design: Single-centre prospective observational non-interventional diagnostic study. Methods: Consecutive patients during a one-year period in AZ Sint-Jan Bruges, without known cardiac amyloidosis history and scheduled for spinal canal stenosis surgery, will have cardiac evaluation including serum cardiac biomarker (high-sensitive troponin T and NT-proBNP) assessment, electrocardiography and transthoracic echocardiography. During surgery, all patients will undergo ligamentum flavum biopsy to evaluate presence and burden of transthyretin amyloid deposition (Congo-red staining and immune histochemistry). All patients with suspicion for cardiac amyloidosis will undergo further diagnostic testing (including laboratory test and bone scintigraphy). A chronologic cascade screening process will be used starting with abnormal serum cardiac biomarkers (high-sensitive troponin T ≥ 14 ng/ml and/or NT-proBNP > 125 pg/ml), followed by electrocardiography, transthoracic echocardiography and finally ligamentum flavum biopsy results. The diagnostic performance of this biomarker-based strategy will be compared to electrocardiography, echocardiography and ligamentum flavum biopsy. Conclusion: It is hypothesised that serum cardiac biomarker testing in patients undergoing spinal canal stenosis surgery represents a simple and valuable prospective screening strategy for early detection of cardiac amyloid(osis).

Official Title
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Cardiac Amyloidosis in Spinal Stenosis: the CASS-study

Conditions
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Cardiac Amyloidosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cervical or lumbar spinal canal stenosis, scheduled for spinal surgery > 18 years old Exclusion Criteria: Prior diagnosis of cardiac amyloidosis and evident alternative explanations for troponin and/or NT-proBNP elevation are the main reasons for exclusion. known cardiac amyloidosis severe valvular regurgitation or stenosis Left ventricular ejection fraction (LVEF) < 40% Glomerular filtration rate (GFR) ≤ 25 ml/kg/min or dialysis recent heart failure admission ≤ 1 month recent myocarditis ≤ 3 months recent acute coronary syndrome ≤ 1 month recent percutaneous coronary intervention (PCI) ≤ 1 month recent cardiac surgery ≤ 3 months active or planned pregnancy unwilling to participate or provide signed informed consent

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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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic performance hs-Troponin T (ng/L) to early diagnose cardiac amyloidosis | Diagnostic performance of a prospective screening strategy, based on elevated hs-Troponin T (ng/L), in patients with spinal canal stenosis undergoing spinal surgery, to early diagnose cardiac amyloidosis | 12 months after spinal canal surgery | 
| Diagnostic performance of NT-proBNP (pg/ml) to early diagnose cardiac amyloidosis | Diagnostic performance of a prospective screening strategy, based on elevated NT-proBNP (pg/ml), in patients with spinal canal stenosis undergoing spinal surgery, to early diagnose cardiac amyloidosis | 12 months after spinal canal surgery | 
| Difference in diagnostic performance of NT-proBNP (pg/ml) and echocardiography, electrocardiography and ligamentum flavum biopsy | Difference in diagnostic performance of NT-proBNP (pg/ml) with CA suspicion based on echocardiography (left ventricular wall thickness), electrocardiography (QRS amplitude, presence of atrial fibrillation) and ligamentum flavum biopsy (presence of transthyretin-amyloid deposits) | 12 months after spinal canal surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in diagnostic performance of hs-Troponin T (ng/L) and electrocardiography parameters | Difference in diagnostic performance of hs-Troponin T (ng/L) with CA suspicion based on electrocardiography (QRS amplitude, presence of atrial fibrillation) | 12 months after spinal canal surgery | 
| Difference in diagnostic performance of hs-Troponin T (ng/L) and echocardiography parameters | Difference in diagnostic performance of hs-Troponin T (ng/L) with CA suspicion based on echocardiography (left ventricular wall thickness) | 12 months after spinal canal surgery | 
| Difference in diagnostic performance of hs-Troponin T (ng/L) and ligamentum flavum biopsy | Difference in diagnostic performance of hs-Troponin T (ng/L) with CA suspicion based on ligamentum flavum biopsy (presence of transthyretin-amyloid deposits) | 12 months after spinal canal surgery | 
| Difference in diagnostic performance of NT-proBNP (pg/ml) and echocardiography parameters | Difference in diagnostic performance of NT-proBNP (pg/ml) with CA suspicion based on echocardiography (left ventricular wall thickness) | 12 months after spinal canal surgery | 
| Difference in diagnostic performance of NT-proBNP (pg/ml) and electrocardiography parameters | Difference in diagnostic performance of NT-proBNP (pg/ml) with CA suspicion based on electrocardiography (QRS amplitude, presence of atrial fibrillation) | 12 months after spinal canal surgery | 
| Difference in diagnostic performance of NT-proBNP (pg/ml) and ligamentum flavum biopsy | Difference in diagnostic performance of NT-proBNP (pg/ml) with CA suspicion based on ligamentum flavum biopsy (presence of transthyretin-amyloid deposits) | 12 months after spinal canal surgery | 
| To determine the prevalence of TTR amyloid in both cervical and lumbar spinal canal stenosis patients as function of age and clinical presentation |  | 6 months after spinal canal surgery | 
| To correlate TTR amyloid burden on ligamentum flavum biopsy to echocardiographic (e.g. ventricular wall thickness) parameters |  | 12 months after spinal canal surgery | 
| To correlate TTR amyloid burden on ligamentum flavum biopsy to cardiac biomarker parameters (e.g. hs-Troponin T (ng/L)) |  | 12 months after spinal canal surgery |