Top Things to Know: Cardiac Amyloidosis: Evolving Diagnosis and Management
Published: June 01, 2020
Prepared by Paul St Laurent, DNP, RN, Sr. Science & Medicine Advisor, Lead, Office of Science, Medicine and Health, American Heart Association
- Transthyretin cardiac amyloidosis (ATTR-CM), a restrictive cardiomyopathy, results from the extracellular myocardial deposition of amyloid fibrils composed of the protein transthyretin (TTR) due to either a pathologic variant in transthyretin gene TTR (ATTRv), inherited in an autosomal dominant fashion or wild-type transthyretin protein (ATTRwt).
- The diagnosis and therapy for ATTR-CM is rapidly evolving with readily accessible, accurate, noninvasive diagnostic tests and therapies to slow the progression of symptoms and improve survival.
- This scientific statement is intended to inform clinical practice and facilitate management by covering current diagnostic and treatment strategies as well as unmet needs and areas of active investigation in ATTR-CM.
- ATTR-CM has historically been considered rare, but the true prevalence is challenging to estimate as it is under-recognized; cardiac amyloid deposition is evident in a significant proportion of patients with severe aortic stenosis, and heart failure with preserved ejection fraction (HFpEF), and is more common with advancing age.
- Because symptoms of ATTR-CM are non-specific, the key to diagnosis is a high index of suspicion. Suspect ATTR-CM in older patients presenting with HFpEF and increased wall thickness, especially in those with carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, or autonomic or sensory polyneuropathy.
- While echocardiography and cardiac magnetic resonance imaging (CMR) offer diagnostic clues, the use of bone scintigraphy with 99mtechnetium (99mTc) bone-avid compounds represents a paradigm shift, allowing for non-invasive diagnosis of ATTR-CM.
- While bone scintigraphy has emerged as a cornerstone of ATTR-CM diagnosis, scans may be positive even in AL amyloidosis, so ATTR-CM can only be diagnosed in the presence of a positive bone scintigraphy scan with concomitant negative testing for light chains (serum free light chain concentration and serum and urine immunofixation electrophoresis).
- TTR silencers target TTR hepatic synthesis. In randomized trials in patients with ATTRv amyloidosis and polyneuropathy, both patisiran and inotersen slow progression of amyloidosis-related polyneuropathy but their role in ATTR-CM without neuropathy is currently under investigation.
- Tafamidis, a TTR stabilizer, is FDA-approved for use in ATTR-CM. In the ATTR-ACT randomized trial of patients with ATTRwt-CM or ATTRv-CM, tafamidis reduced all-cause mortality (29.5% vs 42.9%) and cardiovascular-related hospitalization (0.48 per year vs. 0.70 per year) after 30 months.
- Despite advances in the management of ATTR-CM, areas of uncertainty remain in screening, disease progression, the role of TTR silencers and combination therapy in patients with ATTR-CM, timing of therapy initiation, and the financial burden of new therapies.
Citation
Kittleson MM, Maurer MS, Ambardekar AV, Bullock-Palmer RP, Chang PP, Eisen HJ, Nair AP, Nativi-Nicolau J, Ruberg FL; on behalf of the American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology. Cardiac amyloidosis: evolving diagnosis and management: a scientific statement from the American Heart Association [published online ahead of print June 1, 2020]. Circulation. doi: 10.1161/CIR.0000000000000792.