Cardiac Amyloidosis in Spinal Stenosis: the CASS-study

Cardiac Amyloidosis Clinical Trial

— CASS  

Official title:

Cardiac Amyloidosis in Spinal Stenosis: the CASS-study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04653675
• Other study ID #: 2741
• Status: Active, not recruiting
• Start date: January 1, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2023
• Source: AZ Sint-Jan AV
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 105
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyloidosis
• Cardiac Amyloidosis
• Spinal Stenosis

Locations

Country	Name	City	State
Belgium	AZ Sint-Jan Brugge-Oostende AV	Brugge

Sponsors (1)

Lead Sponsor	Collaborator
AZ Sint-Jan AV

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	To correlate TTR amyloid burden on ligamentum flavum biopsy to echocardiographic (e.g. ventricular wall thickness) parameters		12 months after spinal canal surgery
Secondary	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