Article Figures & Data
Figures
- FIGURE 1.
Amyloid molecular mechanisms and imaging characteristics. Source protein, misfolding, fibril formation, and deposition are depicted for cardiac ATTR and cardiac AL. In both ATTRwt and ATTRv, transthyretin proteins are secreted by liver, fold abnormally, and form fibrils that are deposited in myocardium. In AL, immunoglobulin light-chain proteins misfold and form fibrils also deposited in myocardium (1). TTR = transthyretin; Wt = wild-type. (Adapted from (1).)
- FIGURE 2.
Systemic amyloidosis red flags. Pervasiveness and debilitating nature of amyloidosis compels early recognition of clinical manifestation red flags to ensure prompt initiation of disease-modifying therapies. Systemic amyloidosis can affect many organs and systems concurrently, triggering visual, central nervous, dermatologic, cardiac, renal, autonomic nervous, sensory-motor, and orthopedic signs and symptoms. ECG = electrocardiogram; HF = heart failure; LV = left ventricle.
- FIGURE 3.
Cardiac amyloidosis electrocardiographic findings. (A) Electrocardiogram demonstrating low QRS voltage of less than 5-mm QRS amplitude in limb leads and less than 10-mm in precordial leads in patient with cardiac ATTR. (B) Electrocardiogram demonstrating pseudoinfarct pattern with Q waves in limb leads (II, III, and AVF) and early precordial leads (V1–V4) in patient with cardiac ATTR and no prior myocardial infarction. (Courtesy of Dr. Saurabh Malhotra.)
- FIGURE 4.
Echocardiogram cardiac amyloidosis findings. (A) Parasternal long axis view demonstrating severely increased left ventricular wall thickness in patient with cardiac ATTR (arrows). (B) Apical sparing (bull’s-eye) pattern identified on longitudinal strain echocardiography from same patient. ANT = anterior; ANT_SEPT = anteroseptal; INF = inferior; LAT = lateral; POST = posterior; SEPT = septal. (Courtesy of Dr. Saurabh Malhotra.)
- FIGURE 5.
CMR amyloidosis late gadolinium enhancement. Images obtained after administration of gadolinium contrast material show accumulation in tissue with increased extracellular space. Short-axis orientation demonstrates diffuse transmural gadolinium enhancement of left ventricular myocardium. LV = left ventricle; RV = right ventricle.
- FIGURE 6.
Blood pool on 99mTc-pyrophosphate scintigraphy. (A) Anterior planar image with Perugini score of 2. (B) SPECT images demonstrating no evidence of myocardial uptake. ANT = anterior.
- FIGURE 7.
99mTc-pyrophosphate scan interpretation steps. 99mTc-pyrophosphate images should be interpreted in logical order. Step 1 is visual inspection of both planar and SPECT images to determine presence or absence of radiotracer uptake in heart area. SPECT images are scrutinized to ensure no blood-pool activity, focal or regional uptake, areas of absent tracer, or overlapping bone activity. Step 2 is semiquantitative grading of planar and SPECT images comparing myocardial uptake with rib uptake. Step 3 evaluates H/CL ratio when grading is equivocal.
- FIGURE 8.
Cardiac amyloidosis 99mTc-pyrophosphate semiquantitative and quantitative interpretation. (Top) Planar 3-h images demonstrating diffuse myocardial uptake and grade based on comparison of 99mTc-pyrophosphate myocardial uptake with rib. (Middle) H/CL ratio. (Bottom) Gray-scale and color SPECT images confirming myocardial uptake. PYP = pyrophosphate.
- FIGURE 9.
Cardiac amyloidosis differential diagnosis algorithm. First step in diagnosing cardiac amyloidosis is recognition of one or more clinical red flags in patients with HFpEF, along with one or more echocardiography or CMR red flags. Although diagram suggests that steps are sequential, serum light-chain evaluation and nuclear imaging usually occur simultaneously. If monoclonal proteins are present and nuclear imaging with bone-seeking tracer such as 99mTc-pyrophosphate is positive (grade 2 or 3), cardiac AL is likely. Patient should undergo hematologic evaluation. If monoclonal proteins are present and 99mTc results are equivocal (grade 1), additional histologic assessment is necessary for diagnosis. If monoclonal proteins are present and 99mTc-pyrophosphate scan is negative (no myocardial tracer uptake), findings are negative for cardiac amyloidosis. However, patient should be further assessed to confirm systemic AL. When monoclonal proteins are absent, and there is no 99mTc-pyrophosphate scan myocardial uptake, cardiac AL and cardiac ATTR are unlikely. However, if monoclonal proteins are absent and 99mTc-pyrophosphate scan demonstrates myocardial uptake, findings indicate cardiac ATTR, and patient should be referred for genetic testing to determine type of cardiac amyloidosis: ATTRwt or ATTRv. DPD = 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid; ECHO = echocardiography; HMDP = hydroxymethylene diphosphonate; LV = left ventricle; PYP = pyrophosphate.
- FIGURE 10.
Cardiac amyloidosis treatment. Treatment of cardiac amyloidosis follows 2 parallel pathways: managing cardiac symptoms (e.g., heart failure and arrhythmias) and treatment of underlying disease process. First, AL vs. cardiac ATTR must be confirmed before plan to treat underlying disease process can be formulated. Cardiac AL is treated with chemotherapy. Treatment of cardiac ATTR depends on whether it is ATTRwt or ATTRv. Appropriate ATTRv treatment depends on whether patient has clinical manifestations of cardiomyopathy, neuropathy, or cardiomyopathy with neuropathy. ATTRwt and ATTRv are treated with transthyretin silencers (patisiran, inotersen, or vutrisiran) or stabilizers (diflunisal or tafamidis).
Tables
Study category Reason False-positive Residual cardiac blood pool Rib activity (e.g., prior fracture or metastasis) Mitral valve and annular calcification Pericarditis Chemotherapy Myocardial toxic drugs (e.g., hydroxychloroquine) Recent myocardial infarction (<6 wk) False-negative Minimal myocardial uptake in early disease stages Amyloidosis variants that do not accumulate 99mTc-pyrophosphate (e.g., Phe64Leu or Val30Met) Large old myocardial infarction Parameter Red flag Clinical Biceps tendon rupture Carpal tunnel syndrome Elderly Intolerance to heart failure medications Low-flow, low-gradient aortic stenosis Lumbar stenosis Neuropathy Transthyretin gene positive Echocardiogram Left/right ventricular wall thickening Diastolic dysfunction Reduced global longitudinal strain Relative apical sparing Atrial enlargement Low-flow, low-gradient aortic stenosis CMR Left/right ventricular wall thickening Atrial enlargement Diffuse late gadolinium enhancement Expanded extracellular volume Blood-pool signal nulling before myocardial nulling
