7.8 Cardiac Amyloidosis
7.8.1 Diagnosis of Cardiac Amyloidosis
| COR | LOE | Recommendations |
|---|---|---|
| 1 | B-NR | |
| 1 | B-NR |
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| 1 | B-NR |
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Synopsis
Cardiac amyloidosis is a restrictive cardiomyopathy with extracellular myocardial protein deposition, most commonly monoclonal immunoglobulin light chains (amyloid cardiomyopathy [AL-CM]) or transthyretin amyloidosis (ATTR-CM). ATTR can be caused by pathogenic variants in the transthyretin gene TTR (variant transthyretin amyloidosis, ATTRv) or wild-type transthyretin (wild-type transthyretin amyloidosis, ATTRwt). A diagnostic approach is outlined in Figure 13 (9).
Diagnostic and Treatment of Transthyretin Cardiac Amyloidosis Algorithm
Colors correspond to COR in Table 2. AF indicates atrial fibrillation; AL-CM, amyloid cardiomyopathy; ATTR-CM, transthyretin amyloid cardiomyopathy; ATTRv, variant transthyretin amyloidosis; ATTRwt, wild-type transthyretin amyloidosis; CHA2DS2-VASc, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack (TIA), vascular disease, age 65 to 74 years, sex category; ECG, electrocardiogram; H/CL, heart to contralateral chest; HFrEF, heart failure with reduced ejection fraction; IFE, immunofixation electrophoresis; MRI, magnetic resonance imaging; NYHA, New York Heart Association; PYP, pyrophosphate; Tc, technetium; and TTR, transthyretin.
Recommendation-Specific Supportive Text
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Diagnosis of ATTR-CM requires a high index of suspicion. LV thickening (wall thickness ≥14 mm) along with fatigue, dyspnea, or edema should trigger consideration of ATTR-CM, especially with discordance between wall thickness on echocardiogram and QRS voltage on ECG (10), or other findings such as apical sparing of LV longitudinal strain impairment on echocardiography and diffuse late-gadolinium enhancement on cardiac MRI. ATTR-CM is prevalent in severe aortic stenosis (1), HFpEF (2), carpal tunnel syndrome (3), lumbar spinal stenosis (4), and autonomic or sensory polyneuropathy (5). Practically, screening for the presence of a monoclonal light chain and technetium pyrophosphate (99mTc-PYP) scan can be ordered at the same time for convenience, but the results of the 99mTc-PYP scan are interpreted only on the context of a negative monoclonal light chain screen. 99mTc-PYP scans may be positive even in AL amyloidosis (7) and, thus, a bone scintigraphy scan alone, without concomitant testing for light chains, cannot distinguish ATTR-CM from AL-CM. Serum free light chain (FLC) concentration and serum and urine immunofixation electrophoresis (IFE) are assessed to rule out AL-CM. IFE is preferred because serum plasma electrophoresis and urine plasma electrophoresis are less sensitive. Together, measurement of serum IFE, urine IFE, and serum FLC is >99% sensitive for AL amyloidosis (6,11).
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The use of 99mTc bone-avid compounds for bone scintigraphy allows for noninvasive diagnosis of ATTR-CM (7). 99mTc compounds include PYP, 3,3-diphosphono-1,2-propanodicarboxylic acid, and hydromethylene diphosphonate, and PYP is used in the United States. In the absence of a light-chain abnormality, the 99mTc-PYP scan is diagnostic of ATTR-CM if there is grade 2/3 cardiac uptake or an H/CL ratio of >1.5. In fact, the presence of grade 2/3 cardiac uptake in the absence of a monoclonal protein in serum or urine has a very high specificity and positive predictive value for ATTR-CM (7). SPECT is assessed in all positive scans to confirm that uptake represents myocardial retention of the tracer and not blood pool or rib uptake signal (12).
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If ATTR-CM is identified, then genetic sequencing of the TTR gene will determine if the patient has a pathological variant (ATTRv) or wild-type (ATTRwt) disease (12). Differentiating ATTRv from ATTRwt is important because confirmation of ATTRv would trigger genetic counseling and potential screening of family members and therapies, inotersen and patisiran, which are presently approved only for ATTRv with polyneuropathy (13,14).