Native T1 CMR Imaging for Diagnosis of Cardiac Amyloidosis

Active, not recruiting

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

• Registration Number: NCT04862273
• Lead Sponsor: University of Leipzig

Brief Summary

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

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.

Study Timeline

• Study Start: 2021-04-01
• Study First Submitted: 2021-04-20
• Study First Submitted QC: 2021-04-22
• Study First Posted: 2021-04-27
• Status Verified: 2023-11
• Primary Completion: 2023-11-01
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-11-29
• Study Completion: 2024-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 112

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Native T1 CMR	99mTc-DPD scintigraphy	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)
Native T1 CMR	Laboratory screening for multiple myeloma / AL amyloidosis	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)
Native T1 CMR	Native T1 CMR	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)
Native T1 CMR	Web-based ATTR probability estimator (Pfizer, New York)	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)
Native T1 CMR	Cardiac biopsy	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)

Primary Outcome Measures

Name	Time	Method
Diagnostic accuracy of native T1 LV mapping for diagnosis of CA	up to 7 days	Comparison native T1 CMR with the reference method for diagnosis of CA

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Leipzig; 🇩🇪 Leipzig, Saxony, Germany