Native T1 CMR Imaging for Diagnosis of Cardiac Amyloidosis

Study Overview
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Brief Summary
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The study aims to test the diagnostic accuracy of native T1 mapping for the diagnosis of cardiac amyloidosis prospectively. The hypothesis is that native T1 mapping with a cut-off value of 1341ms (3 tesla CMR) in older patients with symptomatic heart failure, increased LV wall thickness and elevated cardiac biomarkers is non-inferior to the reference method to diagnose cardiac amyloidosis (CA). As secondary measure, a web-based ATTR probability estimator for the diagnosis of CA will be evaluated.

Detailed Description
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Cardiac amyloidosis (CA) is an important differential diagnosis in older patients with symptomatic heart failure with preserved or mid-range ejection fraction and increased left ventricular wall thickness. The prevalence of CA among patients with heart failure and left ventricular (LV) hypertrophy is approximately 13%. However, diagnosis of CA is challenging because specific clinical signs are often lacking. Amyloid fibrils deposit in the extracellular space of the myocardium increases myocardial T1 values on cardiac magnetic resonance (CMR). Therefore, native T1 imaging provides a promising non-invasive method to identify CA. A preliminary retrospective analysis of 128 patients with increased LV wall thickness identified an area under the curve of 0.9954 (p<0.0001) for native T1 to detect CA. The optimal cut-off value was 1341ms, with a sensitivity of 100% and a specificity of 97%. The investigators aim to test the diagnostic accuracy of native T1 mapping with the threshold of 1341ms for the diagnosis of CA compared to the reference method prospectively. Moreover, the web-based ATTR probability estimator for the diagnosis of CA will be evaluated.

Official Title
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Native T1 Cardiac Magnetic Resonance Imaging for Diagnosis of Cardiac Amyloidosis

Conditions
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Heart Failure NYHA Class III, Heart Failure NYHA Class IV, Heart Failure With Preserved Ejection Fraction, Hypertrophy, Left Ventricular, Heart Failure NYHA Class II, Heart Failure With Mid Range Ejection Fraction, Cardiac Amyloidosis

Intervention / Treatment
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* Diagnostic Test: Native T1 CMR
* Diagnostic Test: Web-based ATTR probability estimator (Pfizer, New York)
* Diagnostic Test: 99mTc-DPD scintigraphy
* Diagnostic Test: Laboratory screening for multiple myeloma / AL amyloidosis
* Procedure: Cardiac biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 60 years Symptomatic heart failure (NYHA II-IV) with LVEF ≥40% Increased LV wall thickness (≥12mm end-diastolic) NT-proBNP ≥1000pg/mL Elevated hs-troponin T ≥14ng/L Exclusion Criteria: Contraindications for CMR Acute myocarditis Acute myocardial infarction <1 month Severe aortic stenosis and RAISE score < 2 points

Ages Eligible for Study
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Minimum Age: 60 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Native T1 CMR<br>Diagnostic accuracy of native T1 CMR and ATTR probability estimator are tested against the reference methods (99mTc-DPD scintigraphy, laboratory screening for multiple myeloma / AL amyloidosis; or cardiac biopsy, if noninvasive evaluation is inconclusive) | Diagnostic Test: Native T1 CMR<br>* Observed method<br>Diagnostic Test: Web-based ATTR probability estimator (Pfizer, New York)<br>* Observed method<br>Diagnostic Test: 99mTc-DPD scintigraphy<br>* Reference method<br>Diagnostic Test: Laboratory screening for multiple myeloma / AL amyloidosis<br>* Reference method<br>Procedure: Cardiac biopsy<br>* If non-invasive tests for CA (99mTc-DPD scintigraphy, biochemistry) are inconclusive<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy of native T1 LV mapping for diagnosis of CA | Comparison native T1 CMR with the reference method for diagnosis of CA | up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy of ATTR probability estimator to predict CA | Comparison of a probability score to predict ATTR with the final diagnosis of ATTR | up to 7 days | 
| Association of native T1 values with cardiovascular outcome | All-cause death, cardiovascular death and heart failure hospitalizations | 1 years | 
| Association of ATTR probability estimator values with cardiovascular outcome | All-cause death, cardiovascular death and heart failure hospitalizations | 1 year |