Table 1.

Diagnostic Clues to ATTR-CM

History/examination clues

• Evidence of right-sided heart failure (eg, hepatomegaly, ascites, and lower extremity edema)  • HFpEF, particularly in men  • Intolerance to ACE inhibitors or beta blockers  • Bilateral carpal tunnel syndrome  • Lumbar spinal stenosis  • Biceps tendon rupture  • Unexplained peripheral neuropathy (eg, loss of warm/cold discrimination), particularly if associated with autonomic dysfunction (eg, postural hypotension, alternating bowel pattern)  • Unexplained atrial arrhythmias or conduction system disease/need for a pacemaker

Imaging clues

• Myocardial uptake on PYP/DPD or HMDP imaging  • “Infiltrative phenotype” (eg, biventricular hypertrophy pericardial effusion, valve thickening, interatrial septal thickening)  • Diffuse subendocardial or transmural LGE or increased ECV fraction on cardiac MRI  • Apical sparing on longitudinal strain imaging  • Low myocardial contraction fraction  • Restrictive LV filling with RV wall thickening

Combined clues

• HF with unexplained increased LV wall thickening and nondilated LV  • Concentric LV wall thickening, possibly with an abnormal QRS voltage-to-LV thickness ratio  • Depressed longitudinal LV function despite normal EF  • Aortic stenosis with RV thickening, particularly if paradoxical low flow/low gradient

ACE, angiotensin-converting enzyme; ATTR-CM, transthyretin amyloidosis with predominant cardiomyopathy; DPD, diphosphono-1,2-propanodicarboxylic acid; ECV, extracellular volume; EF, ejection fraction; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HMDP, hydroxymethylene diphosphonate; LGE, late gadolinium enhancement; LV, left ventricular; MRI, magnetic resonance imaging; PYP, pyrophosphate; RV, right ventricular.

The sensitivity and specificity of these “clues” has not been delineated in population-based samples with heart failure.