Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal and under-recognized disease. This targeted literature review assessed the extent and consequences of diagnostic delay and misdiagnosis in ATTR-CM. Methods The Embase database was searched together with proceedings of eight cardiology conferences to identify publications or abstracts on ATTR-CM. Outcomes of interest were time from symptom onset to diagnosis, rates of delayed diagnosis and misdiagnosis, and costs, healthcare resource use or clinical outcomes whilst undiagnosed/misdiagnosed. Results Twenty-three articles were included. Weighted means of reported mean and median diagnostic delays were 6.1 and 3.4 years for wild-type (ATTRwt-CM) and 5.7 and 2.6 years for hereditary (ATTRv-CM). Misdiagnosis occurred in 34–57% of patients when reported. Evaluation and misdiagnosis by multiple healthcare providers before receiving an ATTR-CM diagnosis was common, and there was evidence that patients undergo unnecessary or inappropriate evaluations or treatments while misdiagnosed. Diagnostic “red flags” were reported to be underused. Data on the consequences of delay for patients and health systems were sparse, but given the progressive nature of ATTR-CM, delay is likely to have adverse consequences. Conclusion ATTR-CM patients commonly experience diagnostic delay and misdiagnosis. Efforts are required to provide timely diagnosis so that patients can benefit from earlier access to new disease-modifying therapies. Supplementary Information The online version contains supplementary material available at 10.1007/s40119-021-00219-5.

ASO treatment of patients with moderate to advanced ATTR cardiomyopathy shows indication of stabilization of disease progression and may therefore contribute to enhanced life expectancy.

Introduction Hereditary transthyretin (hATTR) amyloidosis is a progressive, degenerative disease, with peripheral neuropathy, cardiomyopathy, and other clinical manifestations. In this study we examine the impact of hATTR amyloidosis on quality of life (QOL). Methods Neuropathy‐specific QOL, measured with the Norfolk QOL‐Diabetic Neuropathy questionnaire, was compared between patients with hATTR amyloidosis and patients with type 2 diabetes, whereas generic QOL, measured with the 36‐item Short Form Health Survey version 2 (SF‐36v2), was compared between patients with hATTR amyloidosis, the general population, and patients with chronic diseases. Results Neuropathy‐specific QOL for patients with hATTR amyloidosis was nearly equivalent to that of patients with type 2 diabetes with diabetic neuropathy accompanied by a history of ulceration, gangrene, or amputation. Generic QOL was worse than that seen in the general population, with physical functioning worse than that for patients with multiple sclerosis and congestive heart failure. Discussion Patients with hATTR amyloidosis show significant burden on QOL, particularly in physical functioning. Muscle Nerve 60: 169–175, 2019

Nasal gliomas are rare congenital midline tumors composed of heterotopic neuroglial tissue. The differential diagnosis of a nasal glioma includes neurogenic tumors, ectodermal tumors, mesodermal tumors, and teratomas. Initial evaluation of a nasal glioma should include skull radiographs and either a CT or MRI scan to rule out intracranial extension. CT or MRI scans can be used, but MRI scans are preferable due to their superior soft tissue enhancement. There have been several cases reported in which nasal gliomas were misdiagnosed as capillary hemangiomas. In cases in which clinical uncertainty exists, ultrasound and Doppler flow studies can be performed to noninvasively differentiate nasal gliomas from capillary hemangiomas. Ultrasound is useful for determining if the mass is cystic or solid. Doppler flow studies of nasal gliomas reveal a characteristic low arterial flow velocity during the end-diastolic phase. Microscopic and immunohistologic studies provide definitive confirmation of a nasal glioma. Once the diagnosis of a nasal glioma is established, early surgical resection is advocated to prevent local recurrence, nasal deformity, and secondary visual involvement.

Background: Cardiomyopathy is a major cause of death in patients with systemic transthyretin amyloidosis. Long term effect of therapy designed to inhibit hepatic production of the amyloid precursor has not been established in cardiomyopathy. The purpose of this study was to evaluate the long term safety and efficacy of transthyretin specific antisense oligonucleotide therapy, inotersen, in transthyretin cardiomyopathy. Methods: Patients with hereditary or wildtype transthyretin cardiomyopathy (NYHA I-III) with an LV wall thickness ! 1.3 cm and clinical evidence of congestive heart failure were eligible for this single centre, open label protocol. Safety and cardiac structural and functional parameters were prospectively studied. Results: As of October 2018, 33 subjects have entered the study. Twenty have completed 1 year, 16 have completed 2 years, and 14 have completed three years. At the 2 year time point, mean LV mass decreased by 8.4% as measured by MRI, and exercise tolerance increased by 20.2 metres as measured by 6 minute walk test. Further positive indicators were noted at 3 years, with LV mass decreasing by 11.4% and 6MWT increasing by 16.2 metres. Conclusion: Long term treatment of amyloid cardiomyopathy with inotersen is safe and effective in inhibiting progression and potentially reversing amyloid burden.