Clinical Heart and Vascular Center

Advances in Diagnostic and Therapeutic Options for Patients with Amyloid Heart Disease

By Elizabeth A. Hardin, M.D., Assistant Professor of Internal Medicine

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Transthyretin amyloid cardiomyopathy (ATTR-CM), a disease caused by misfolding of the transthyretin (TTR) protein, has historically been thought of as uncommon. However, studies have shown that cardiac amyloidosis might account for the etiology of cardiomyopathy in up to 10-15% of patients hospitalized for heart failure with preserved ejection fraction (HFpEF). During an AHA session titled “Amyloid Heart Disease: Emerging from the Shadows Into YOUR Practice,” a group of experts gathered to discuss advances in both diagnostic and therapeutic options for these patients as discussed below.

There is a significant delay in diagnosis of ATTR-CM, with 50% of diagnoses made >1 year from symptom onset and after visiting four or more physicians. Suspicion should be heightened in HFpEF patients with a history of bilateral carpal tunnel syndrome, tendon rupture, lumbar spinal stenosis, or peripheral neuropathy. Other clues include intolerance to nodal blockade and low voltage on EKG in the setting of left ventricular hypertrophy.

Imaging modalities with echocardiography and cardiac MRI with gadolinium can be suggestive, but not diagnostic, of ATTR-CM. The diagnosis can be made noninvasively with use of bone scintigraphy (technetium 99m pyrophosphate, PYP) in the absence of a monoclonal gammopathy. The sensitivity and specificity of the diagnosis approaches 100% when the PYP scan shows grade 2 or 3 uptake or the heart/contralateral lung ratio is >1.5 and there is no evidence of a monoclonal gammopathy as evidenced by a normal serum immunofixation electrophoresis study and a normal serum free light chain ratio.

“Suspicion should be heightened in HFpEF patients with a history of bilateral carpal tunnel syndrome, tendon rupture, lumbar spinal stenosis, or peripheral neuropathy.”

Elizabeth A. Hardin, M.D.
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Current treatments for ATTR-CM rely on either stabilization of the misfolded protein or silencing of the TTR gene with RNA interference (iRNA). In the ATTR-ACT study published in the New England Journal of Medicine in 2018, tafamidis versus placebo was shown to reduce all-cause mortality and cardiovascular hospitalizations. In patients with associated neuropathy, silencing agents such as patisiran and inotersen are additional options. Several clinical trials investigating additional therapeutic options are underway. For expert consensus recommendations, please refer to Circ Heart Fail. 2019;12:e006075.

Read more articles from our Physician Update AHA Edition.