Takahashi Koji, Yoshida Satoshi, Ueda Mitsuharu, Uemura Shigeki, Inoue Katsuji
Department of Community Emergency Medicine, Ehime University Graduate School of Medicine, Matsuyama, JPN.
Department of Dermatology, Ehime University Graduate School of Medicine, Matsuyama, JPN.
Cureus. 2025 May 24;17(5):e84759. doi: 10.7759/cureus.84759. eCollection 2025 May.
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 ) 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. 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.
由转甲状腺素蛋白（ATTR）组成的错误折叠淀粉样纤维会导致ATTR淀粉样变性，这是一种全身性疾病。根据转甲状腺素蛋白（TTR）基因突变的有无，ATTR淀粉样变性可分为遗传性和野生型。野生型ATTR（ATTRwt）淀粉样变性是一种老年疾病，在男性中更为普遍。ATTRwt沉积于许多器官和组织，主要是心脏、肺、韧带和腱鞘。已知ATTRwt在韧带和腱鞘中沉积引起的骨科疾病，如腕管综合征、肱二头肌肌腱断裂、椎管狭窄和肩袖撕裂，比心脏受累早数年出现，进而导致ATTRwt心肌病（ATTR-CM）。ATTR-CM可与射血分数保留的心力衰竭（HFpEF）和主动脉瓣狭窄患者的常见心脏病共存。ATTR-CM导致的心力衰竭和心律失常是ATTRwt患者死亡的主要原因。在不使用疾病修饰药物的情况下，ATTR-CM诊断后的中位预期寿命较低。无论体型或性别差异如何，超声心动图显示左心室（LV）壁厚度≥12mm可定义有无心脏受累。使用包括锝-99m标记焦磷酸盐（Tc-99m-PYP）在内的亲骨放射性示踪剂进行闪烁扫描，可对导致ATTR-CM的心肌ATTRwt沉积进行敏感成像。然而，在Tc-99m-PYP闪烁扫描显示心肌沉积之前，关于心外ATTRwt沉积的组织病理学证实的报道很少。我们报告了一例92岁患有急性HFpEF和主动脉瓣狭窄的女性病例。Tc-99m-PYP闪烁扫描显示皮下脂肪和骨骼肌有示踪剂摄取，但心肌无摄取。我们怀疑该患者患有ATTR。对有示踪剂摄取的腹部皮下脂肪进行活检证实有ATTR沉积。基因测序未发现变异，Tc-99m-PYP闪烁扫描结果诊断为心肌无明显ATTRwt沉积的ATTRwt。本例的心外Tc-99m-PYP摄取，与ATTRwt沉积引起的骨科疾病一样，反映了心肌ATTRwt沉积之前的情况，被认为是ATTRwt可疑表现。报告该患者的临床意义在于促使未来的研究去测试ATTRwt是否沉积于类似患者的心脏，以及ATTRwt的早期检测和治疗是否会改善预后，这将需要积累类似病例。
