Table 2.

Cardiac Modalities for Assessing Progression in ATTR Cardiomyopathy

Testing Modality	Strengths	Weaknesses	Comments
Serum biomarkers	•Readily available •Low cost	•Not specific	•Baseline assessment of NT-proBNP, cardiac troponin, and estimated glomerular filtration rate have been validated in risk prediction models (55,110) •Changes in NT-proBNP may be helpful to monitor disease progression, but data remain limited (8) •Lower baseline serum TTR concentration is associated with mortality in ATTRwt; over time, decreasing serum TTR levels correspond to worsening cardiac function (111)
Electrocardiography (ECG)	•Readily available •Low cost	•Not sensitive or specific for screening (17)	•Unclear role of serial ECG monitoring for disease progression
Holter monitoring	•Readily available		•Consider repeating with disease progression owing to high rates of conduction system disease, atrial and ventricular tachyarrhythmias •Prevalence of atrial fibrillation is high: 5%-28% for ATTRv and 27%-71% for ATTRwt (24,25,27, 28, 29,112,113)
Echocardiography	•Readily available	•Findings are not specific for CA •Cannot differentiate between ATTR and AL	•Appropriate to repeat in ATTR-CA with worsening cardiac symptoms (7) •Parameters associated with worse prognosis include low global longitudinal strain, abnormal early mitral inflow, low myocardial performance index, low myocardial contraction fraction, and low stroke volume index; however, there is no formal staging system that uses echocardiographic parameters (8)
Nuclear pyrophosphate (PYP) scan	•Technically straightforward acquisition •Allows for noninvasive diagnosis of ATTR-CA	•False positives/negatives if performed incorrectly (9) •Radiation exposure	•Appropriate to repeat in ATTR-CA with worsening cardiac symptoms (7) •Degree of uptake correlates with LV wall thickness and mass, troponin T, NT-proBNP, and ECG, and negatively with LVEF (8) •H/CL ratio of 1.6 is associated with higher mortality (114) •Serial PYP scanning may not correlate with clinical progression; more data are needed on serial PYP (115)
Cardiac magnetic resonance imaging	•Reference standard for LVEF and mass assessment •Good signal-to-noise ratio •No shape assumptions •Tissue characterization	•High cost •Not widely available •Cannot differentiate between ATTR and AL	•Appropriate to repeat in ATTR-CA with worsening cardiac symptoms (7) •Late gadolinium enhancement (LGE) pattern classic for CA has sensitivity ∼85% and specificity ∼90% •LGE pattern progressing from normal to subendocardial to transmural may indicate progressive disease (8) •Native T1 mapping and extracellular volume may track amyloid burden over time (8), although extracellular volume may be more predictive than T1 in ATTR-CA •T2 mapping may also emerge as a predictor of prognosis, but data in ATTR-CA are lacking
Cardiac positron-emission tomography	•Potential to image amyloid in other organs and quantify load in body	•High cost •Not widely available •Radiation exposure •Cannot differentiate between ATTR and AL	•11C-PIB, 18F-florbetapir, and 18F-florbetaben have been tested in pilot studies for CA, although more data are needed (8) and current utility in the clinical setting is not well defined

AL = light-chain amyloid; ATTR = transthyretin amyloid; ATTRv = variant transthyretin cardiac amyloidosis; ATTRwt = wild-type transthyretin cardiac amyloidosis; CA = cardiac amyloidosis; H/CL = heart/contralateral; LVEF = left ventricular ejection fraction; NT-proBNP = N-terminal pro–B-type natriuretic peptide; TTR = transthyretin.