Wild-Type Transthyretin Amyloid Depositions in the Subcutaneous Fat and Skeletal Muscles of a Nonagenarian Who Had Heart Failure With Preserved Ejection Fraction and No Myocardial Technetium-99m-Labeled Pyrophosphate Uptake

Misfolded amyloid fibrils composed of transthyretin (ATTR) cause ATTR amyloidosis, which is a systemic disease. ATTR amyloidosis can be divided into hereditary and wild-type forms according to the presence or absence of transthyretin <i>(TTR</i>) gene mutations. Wild-type ATTR (ATTRwt) amyloidosis, a disease of the elderly, is more prevalent in men. ATTRwt is deposited in many organs and tissues, mainly the heart, lungs, ligaments, and tenosynovium. Orthopedic diseases caused by the deposition of ATTRwt in the ligaments and tenosynovium, such as carpal tunnel syndrome, biceps tendon rupture, spinal canal stenosis, and rotator cuff tears, are known to precede cardiac involvement by several years, leading to ATTRwt cardiomyopathy (ATTR-CM). ATTR-CM can coexist with common heart diseases in patients of heart failure with preserved ejection fraction (HFpEF) and aortic stenosis. Heart failure and rhythm disturbance resulting from ATTR-CM is the leading cause of mortality in patients with ATTRwt. The median life expectancy after the diagnosis of ATTR-CM is low without the administration of disease-modifying drugs. The presence or absence of cardiac involvement is defined by a left ventricular (LV) wall thickness of ≥12 mm on echocardiography, regardless of body size or sex differences. Scintigraphy with bone-avid radiotracers, including technetium-99m-labeled pyrophosphate (Tc-99m-PYP), provides sensitive imaging of myocardial ATTRwt depositions that lead to ATTR-CM. However, there are few reports of histopathologic confirmation of extracardiac ATTRwt deposition prior to myocardial deposition demonstrated by Tc-99m-PYP scintigraphy. We report the case of a 92-year-old woman with acute HFpEF and aortic valve stenosis. Tc-99m-PYP scintigraphy revealed tracer uptake in the subcutaneous fat and skeletal muscles but not in the myocardium. We suspected the patient had ATTR. Biopsy of the subcutaneous abdominal fat with tracer uptake confirmed ATTR deposition. <i>TTR</i> gene sequencing revealed no variants, and the results of Tc-99m-PYP scintigraphy led to the diagnosis of ATTRwt with no obvious ATTRwt deposition in the myocardium. Extracardiac Tc-99m-PYP uptake in this case, as in orthopedic diseases due to ATTRwt depositions, reflects a condition prior to myocardial ATTRwt deposition and is considered suspicious for ATTRwt. The clinical significance of reporting this patient is to prompt future studies to test whether ATTRwt is deposited in the hearts of similar patients and whether early detection and treatment of ATTRwt will improve prognosis, which will require the accumulation of similar cases.