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Review
. 2025 Apr;18(4):478-499.
doi: 10.1016/j.jcmg.2024.10.011. Epub 2025 Jan 8.

The Last Decade in Cardiac Amyloidosis: Advances in Understanding Pathophysiology, Diagnosis and Quantification, Prognosis, Treatment Strategies, and Monitoring Response

Marianna Fontana  1 , Adam Ioannou  2 , Sarah Cuddy  3 , Sharmila Dorbala  3 , Ahmad Masri  4 , James C Moon  5 , Vasvi Singh  3 , Olivier Clerc  3 , Mazen Hanna  6 , Fredrick Ruberg  7 , Martha Grogan  8 , Michele Emdin  9 , Julian Gillmore  2
Affiliations
Review

The Last Decade in Cardiac Amyloidosis: Advances in Understanding Pathophysiology, Diagnosis and Quantification, Prognosis, Treatment Strategies, and Monitoring Response

Marianna Fontana et al. JACC Cardiovasc Imaging. 2025 Apr.

Abstract

Cardiac amyloidosis represents a unique disease process characterized by amyloid fibril deposition within the myocardial extracellular space. Advances in multimodality cardiac imaging enable accurate diagnosis and facilitate prompt initiation of disease-modifying therapies. Furthermore, rapid advances in multimodality imaging have enriched understanding of the underlying pathogenesis, enhanced prognostication, and resulted in the development of imaging-based markers that reflect the amyloid burden, which is of increasing importance when assessing the response to treatment. Whereas conventional therapies have focused on reducing amyloid formation and subsequent stabilization of the cardiac disease process, novel agents are being developed to accelerate the immune-mediated removal of amyloid fibrils from the heart. In this context, the ability to track changes in the amyloid burden over time is of paramount importance. Although advanced imaging techniques have shown efficacy in tracking the treatment response, future research focused on improved precision through use of artificial intelligence may augment the detection of changes earlier in the course of treatment.

Keywords: Cardiac amyloidosis; systemic light-chain amyloidosis; transthyretin amyloidosis.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Fontana has received support from the British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/21/33447) and has received consulting fees from Intellia, Novo-Nordisk, Pfizer, Eidos, Prothena, Akcea, Alnylam, Caleum, Alexion, Janssen, Ionis, and AstraZeneca. Dr Cuddy has received grants from National Institutes of Health award National Institutes of Health 1K23HL166686-01 and the American Heart Association award 23CDA857664; and has served on advisory boards for Bridge Bio, Ionis, Alexion Pharmaceuticals, AstraZeneca, and Novo Nordisk. Dr Singh has received grants from the American Society of Nuclear Cardiology/Pfizer and is on the speakers bureau for Pfizer and AstraZeneca. Dr Hanna has served on advisory boards for Alnylam, Bridge Bio, Pfizer, Ionis, and Alexion Pharmaceuticals. Dr Ruberg has received grants from National Institutes of Health awards R01HL139671 and R01AG081582; has received research grants to his institution from Akcea, Anumana, and Pfizer; and has received consulting fees from AstraZeneca and Attralus. Dr Grogan has received grants and/or consulting fees paid to her institution from Anumana, Alnylam, AstraZeneca, Attralus, BridgeBio/Eidos, Pfizer, Janssen, and NovoNordisk. Dr Gilmore has received consulting fees from Ionis, Eidos, Intellia, Alnylam, and Pfizer.

Figures

FIGURE 1
FIGURE 1
Typical Echocardiographic Features of a Patient With Cardiac Transthyretin Amyloidosis
FIGURE 2
FIGURE 2. Serum Amyloid P Scintigraphy Images Showing Evidence of Organ Regression in Patients With Systemic Amyloid a Amyloidosis and Systemic Light Chain Amyloidosis
(A) Hepatic regression. (B) Splenic regression. (C) Renal regression.
FIGURE 3
FIGURE 3. CMR Images
Cardiac magnetic resonance (CMR) images showing an increasing transmurality of late gadolinium enhancement (LGE) and extracellular volume (ECV) as more amyloid fibrils accumulate in the myocardium.
FIGURE 4
FIGURE 4. Cardiac Scintigraphy Images
Cardiac scintigraphy images with 99mtechnetium-labelled pyrophosphate of a patient with varying degrees of myocardial radiotracer uptake. %ID = percentage injected dose; CAA = cardiac amyloid activity; SUV = standardized uptake value.
FIGURE 5
FIGURE 5. False Positive Cardiac Scintigraphy Due to Blood Pool Activity
(A) 99mTechnetium-labelled pyrophosphate scan showing positive heart-to-contralateral (HCL) lung ratio of 1.5 on planar images. There is significant blood pool activity as is shown on single-photon emission computed tomography (SPECT) images. The HCL lung ratio is a false positive due to residual blood pool activity. (B) The same patient underwent 99mtechnetium-labelled hydroxydiphosphonate scan that showed a negative HCL lung ratio of 0.95 at 2 hours, and axial SPECT images confirm absence of left ventricular myocardial activity and no significant residual blood pool radiotracer activity (HCL lung ratio also negative).
FIGURE 6
FIGURE 6. 18F-Florbetapir and 124I-Evuzamitide PET/CT Images for a Patient With Cardiac Light Chain Amyloidosis
CT = computed tomography; PET = positron emission tomography.
FIGURE 7
FIGURE 7. Changes on CMR Imaging in Response to Treatment in the Context of Cardiac Light Chain Amyloidosis
Abbreviations as in Figure 3.
CENTRAL ILLUSTRATION
CENTRAL ILLUSTRATION
Typical Imaging Features for a Patient With Cardiac Transthyretin Amyloidosis
See this image and copyright information in PMC

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