Improving outcomes in AL amyloidosis

AL amyloidosis is a rare, underdiagnosed disease with a complex clinical presentation. In article highlights from the European Society of Cardiology Congress 2023, learn clinical strategies for increasing awareness of AL amyloidosis with cardiac dysfunction, targeted screening, earlier diagnosis using artificial intelligence, and risk stratification.

AL amyloidosis at ESC 2023

To determine the clinical features of amyloid light-chain (AL) amyloidosis, “you need to image the organs that are involved; you need a biochemical assessment of the severity of the disease; and you need a biopsy in order to type exactly what AL amyloidosis you are facing”. Watch the video to learn more from Professor Stefano Perlini (University of Pavia, Italy).

Screening, diagnosis and monitoring

By Eleanor McDermid

Research findings on cardiac amyloidosis presented at this year’s ESC congress included improved approaches to screening, diagnosis and monitoring, as well as data on common comorbidities.

To begin with screening, the results of a study from the Medical University of Innsbruck in Austria suggest that combining transoesophageal echocardiography (TEE) markers may improve the efficiency of screening for cardiac amyloidosis.

As reported by Gerhard Pölzl, the team sought to improve on the current left ventricular (LV) wall thickness cutoff of 12 mm or greater, noting that this may miss many people who have early-stage disease. When applied to 900 TEE reports, this standard cutoff was highly sensitive for cardiac amyloidosis, at 94%. However, it would have required 32.0% of the cohort to undergo further testing and specificity was only 19%, meaning much testing would be unnecessary.

But combining the 12 mm cutoff with a left atrial/LV end-diastolic diameter of at least 1.0 reduced the proportion of patients requiring further assessment to 4.2% without impacting the sensitivity or specificity. Moreover, this combination of markers identified a further 4.2% of patients who had LV wall thickness below 12 mm but nonetheless warranted further investigation.

The combination of these markers therefore preserves sensitivity but restricts further testing to “a manageable number” of patients, said Pölzl.

Professor Perlini observes: “The patient needs to be very aware that not several specialists, but a single team is taking care of her or him.” Watch this video to learn the benefits and limitations of multidisciplinary care for AL amyloidosis.

Smart monitoring

Artificial intelligence applied to electrocardiography could flag a high risk of amyloidosis in the absence of clear clinical suspicion

When further testing is required, artificial intelligence (AI) may be helpful in determining a diagnosis, as illustrated in a clinical cases session. Courtney Kenyon (Mayo Clinic Arizona, Phoenix, USA) detailed the case of a 69-year-old woman who presented with a 3-week history of fatigue and dyspnoea. She had new-onset atrial fibrillation, bilateral ankle oedema, jugular venous distension and bilateral crepitations.

The woman had no specific symptoms of amyloidosis; however, application of a previously published AI tool¹ to the patient’s electrocardiogram revealed a 93% probability of amyloidosis. Further testing confirmed the presence of AL amyloidosis with kappa predominance, and the patient was started on chemotherapy.

For monitoring of existing amyloidosis, early findings suggest a role for the novel radiotracer ¹²⁴I-evuzamitide. Researchers looked at baseline and repeat imaging examinations conducted approximately 3 years apart in 18 people with cardiac amyloidosis. This revealed decreased radiotracer binding in the liver, spleen and heart of several of the eight participants who had AL amyloidosis. Seven had reductions in cardiac amyloid – of around 20% in two cases. Just one person had an increase in cardiac amyloid load in this time, by about 100%.

Tracer uptake correlated with serum levels of N-terminal pro B-type natriuretic peptide, reported Emily Martin (University of Tennessee Graduate School of Medicine, Knoxville, USA). She noted that the study cohort had stable disease, on the whole, and that future research should include people with more severe symptoms.

Cardiac comorbidities

The advances in diagnostics that Professor Perlini observed at the ESC Congress 2023 were “positive results of bone scintigraphy that may hide the presence of AL amyloidosis and measuring extracellular tissue by magnetic resonance”. Watch to learn more.

Among research looking at comorbidities in people with diagnosed cardiac amyloidosis was a poster presentation from Carolina Donà and team at the Medical University of Vienna in Austria, which illustrated the potential for concomitant coronary artery disease. The researchers identified this in 34% of 205 people with cardiac amyloidosis, including 19% of those with AL amyloidosis.

The team also observed that the majority of study participants with known coronary artery disease had typical diffuse late gadolinium enhancement on cardiac magnetic resonance imaging, making it difficult to visualise post-ischaemic changes.

In an oral presentation, Robert Adam (Institute of Cardiovascular Diseases Prof. C.C. Iliescu, Bucharest, Romania) focused on the risk of atrial fibrillation in people with cardiac amyloidosis. His team’s research revealed that measuring left atrial peak longitudinal strain (PALS) may help identify those at increased risk of this complication, facilitating early intervention with anticoagulants.

The team studied 93 people with cardiac amyloidosis. None of these people had a history of atrial fibrillation at baseline, but 44 developed it during a median 11 months of follow-up. People with PALS at or below the optimal cutoff of 14.3% had a greater than fivefold increased risk of new-onset fibrillation, compared with those with higher PALS. At this threshold, PALS had a sensitivity of 71% and a specificity of 73% for predicting new-onset atrial fibrillation.

Reference

1. Grogan M, Lopez-Jimenez F, Cohen-Shelly M, Dispenzieri A, Attia ZI, Abou Ezzedine OF, et al. Artificial Intelligence-Enhanced Electrocardiogram for the Early Detection of Cardiac Amyloidosis. Mayo Clin Proc. 2021;96(11):2768-2778.