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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).
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
Prior diagnosis of cardiac amyloidosis and evident alternative explanations for troponin and/or NT-proBNP elevation are the main reasons for exclusion.
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Patients with cervical or lumbar spinal canal stenosis scheduled for spinal surgery
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| Name | Affiliation | Role |
|---|---|---|
| Philippe Debonnaire, MD, PhD | AZ Sint-Jan AV | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AZ Sint-Jan Brugge-Oostende AV | Bruges | Belgium |
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| ID | Term |
|---|---|
| D028227 | Amyloid Neuropathies, Familial |
| ID | Term |
|---|---|
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D009422 | Nervous System Diseases |
| D017772 | Amyloid Neuropathies |
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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 |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D028226 | Amyloidosis, Familial |
| D008661 | Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000686 | Amyloidosis |
| D057165 | Proteostasis Deficiencies |