Clinical trial NCT04653675: Cardiac Amyloidosis in Spinal Stenosis: the CASS-study
Official title: Cardiac Amyloidosis in Spinal Stenosis: the CASS-study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Cardiac Amyloidosis
Lead sponsor: AZ Sint-Jan AV
Sponsor class: OTHER
First posted: 2020-12-04
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with cervical or lumbar spinal canal stenosis scheduled for spinal surgery

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Diagnostic performance hs-Troponin T (ng/L) to early diagnose cardiac amyloidosis
timeFrame: 12 months after spinal canal surgery
measure: Diagnostic performance of NT-proBNP (pg/ml) to early diagnose cardiac amyloidosis
timeFrame: 12 months after spinal canal surgery
measure: Difference in diagnostic performance of NT-proBNP (pg/ml) and echocardiography, electrocardiography and ligamentum flavum biopsy
timeFrame: 12 months after spinal canal surgery
Secondary outcomes:
measure: Difference in diagnostic performance of hs-Troponin T (ng/L) and electrocardiography parameters
timeFrame: 12 months after spinal canal surgery
measure: Difference in diagnostic performance of hs-Troponin T (ng/L) and echocardiography parameters
timeFrame: 12 months after spinal canal surgery
measure: Difference in diagnostic performance of hs-Troponin T (ng/L) and ligamentum flavum biopsy
timeFrame: 12 months after spinal canal surgery
measure: Difference in diagnostic performance of NT-proBNP (pg/ml) and echocardiography parameters
timeFrame: 12 months after spinal canal surgery
measure: Difference in diagnostic performance of NT-proBNP (pg/ml) and electrocardiography parameters
timeFrame: 12 months after spinal canal surgery
measure: Difference in diagnostic performance of NT-proBNP (pg/ml) and ligamentum flavum biopsy
timeFrame: 12 months after spinal canal surgery
measure: To determine the prevalence of TTR amyloid in both cervical and lumbar spinal canal stenosis patients as function of age and clinical presentation
timeFrame: 6 months after spinal canal surgery
measure: To correlate TTR amyloid burden on ligamentum flavum biopsy to echocardiographic (e.g. ventricular wall thickness) parameters
timeFrame: 12 months after spinal canal surgery
measure: To correlate TTR amyloid burden on ligamentum flavum biopsy to cardiac biomarker parameters (e.g. hs-Troponin T (ng/L))
timeFrame: 12 months after spinal canal surgery
Other outcomes:
Locations:
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge-Oostende AV
Study officials:
affiliation: AZ Sint-Jan AV
name: Philippe Debonnaire, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: