AHA Guidance for the Diagnosis and Management of Transthyretin Amyloid Cardiomyopathy

The American Heart Association (AHA) released a scientific statement published in Circulation providing up-to-date information and recommendations for the diagnosis and management of transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM).

The diagnosis and management of ATTR-CM have undergone a transformation in the past several years and experts with the AHA have summarized important developments. This statement updates the clinician in 3 main areas: diagnostic testing with important caveats in testing characteristics; enhanced awareness of the improved recognition and underdiagnosis of this condition; and important updates on the new therapies that have proven effective in treating this disease. 

Key points from this AHA scientific statement on cardiac amyloidosis include:

• Symptoms that should prompt investigation of ATTR-CM include sensorimotor peripheral neuropathy (paresthesias and weakness), autonomic dysfunction (orthostatic hypotension, postprandial diarrhea/alternating with constipation, gastroparesis, urinary retention, and incontinence), orthopedic manifestations (carpal tunnel syndrome, lumbar spinal stenosis, unprovoked biceps tendon rupture, hip and knee arthroplasty), black race, familial history of polyneuropathy, intolerance to antihypertensive or heart failure medications because of hypotension or orthostasis, persistent low elevation in serum troponin, discordance between QRS voltage and wall thickness, unexplained left ventricular (LV) or right ventricular (RV) or atrial thickening, or family history of cardiomyopathy.
• Echocardiography and cardiac magnetic resonance imaging are not diagnostic for ATTR cardiomyopathy but can suggest the diagnosis and may be useful when infiltrative cardiomyopathy, constrictive pericarditis, or myocarditis are suspected. The presence of moderate to severe LV thickening (wall thickness ≥14 mm) should trigger consideration of ATTR-CM, especially if there is discordance between wall thickness on echocardiogram and QRS voltage on electrocardiogram.

• The use of ^99mtechnetium (^99mTc) bone-avid compounds represents a paradigm shift because these scans allow for a noninvasive diagnosis of ATTR-CM, although the basis for binding to amyloid deposits remains unknown. Results of ^99mtechnetium-pyrophosphate (^99mTc-PYP) scans should be interpreted only in the context of a negative monoclonal light chain screen. Single-photon emission computed tomography imaging is required if there is grade 1 or higher ^99mTc-PYP to distinguish blood pool from myocardial retention. Mild elevations in the serum free light chain kappa/lambda ratio frequently occur in patients with renal disease, and in the setting of normal immunofixation, a kappa/lambda ratio of up to 3.0 can be normal. Consultation with a hematologist can be considered in such instances.

• Therapy for cardiac amyloidosis focuses on 3 areas: management of heart failure, management of arrhythmias, and initiation of disease-modifying agents. As a result of atrial dysfunction in ATTR-CM, anticoagulation is indicated for atrial fibrillation/flutter regardless of CHA₂DS₂-VASc score; amiodarone is the agent of choice for both rhythm and rate control.

• Targets for disease-modifying therapies in cardiac amyloidosis include TTR silencing (patisiran/inotersen), TTR stabilization (tafamidis, diflunisal, green tea, AG10), and TTR disruption/resorption (doxycycline/tauroursodeoxycholic acid), and monoclonal antibodies. TTR stabilizers bind to the TTR tetramer and prevent misfolding and thus, the deposition of amyloid fibrils. TTR silencers target TTR hepatic synthesis. Although not explicitly tested, there is evidence that TTR silencers may have beneficial cardiac effects. TTR disruptors target the clearance of amyloid fibrils from tissues.

• Despite advances in the management of ATTR-CM, areas of uncertainty remain in screening, disease progression, role of TTR silencers in patients with ATTR-CM, timing of therapy initiation, and financial burden of new treatments.

The authors conclude that “current and future studies will assess these unanswered knowledge gaps, and advocacy from clinicians at every level may aid in closing the gap between the best medical therapies for ATTR-CM and the ability of patients to afford them.”

Reference

Kittleson MM, Maurer MS, Ambardekar AV, Bullock-Palmer RP, Chnag PP, Eisen PP, et al. Cardiac amyloidosis: Evolving diagnosis and management: A scientific statement from the American Heart Association (published online June 1, 2020). Circulation. doi.org/10.1161/CIR.0000000000000792