Neurological affection and serum neurofilament light chain in wild type transthyretin amyloidosis.

In contrast to inherited transthyretin amyloidosis (A-ATTRv), neuropathy is not a classic leading symptom of wild type transthyretin amyloidosis (A-ATTRwt). However, neurological symptoms are increasingly relevant in A-ATTRwt as well. To better understand the role of neurological symptoms in A-ATTRwt, A-ATTRwt patients were prospectively characterized at Amyloidosis Center Charité Berlin (ACCB) between 2018 and 2023 using detailed neurological examination, quality of life questionnaires, and analysis of age- and BMI-adapted serum neurofilament light chain (NFL) levels. 16 out of 73 (21.9%) patients presented with a severe neuropathy which we defined by a Neuropathy Impairment Score (NIS) of 20 or more. In this group, quality of life was reduced, peripheral neuropathy was more severe, and spinal stenosis and joint replacements were frequent. Age- and BMI matched serum NFL levels were markedly elevated in patients with a NIS ≥ 20. We therefore conclude that highly abnormal values in neuropathy scores such as the NIS occur in A-ATTRwt, and have an important impact on quality of life. Both peripheral neuropathy and spinal canal stenosis are likely contributors. Serum NFL may serve as a biomarker for neurological affection in patients with A-ATTRwt. It will be important to consider neurological aspects of A-ATTRwt for diagnosis, clinical follow-up, and future treatment development.

mRNA vaccines for COVID-19 are safe and clinically effective in patients with cardiac amyloidosis.

INTRODUCTION: Amyloidosis is a rare disease in which malformed proteins are deposited in tissues occurring mostly commonly in older age. These deposits can lead to severe organ dysfunction e.g. in the myocardium with great impact on prognosis. The Covid-19 pandemic has caused excess mortality worldwide since 2020. Risk factors for a severe course include pre-existing cardiac diseases like heart failure and advanced age. Therefore, vaccination against Sars-CoV2 viruses is highly recommended for patients with cardiac amyloidosis. However, since there are no specific data on mRNA vaccines in patients with cardiac amyloidosis, some patients have concerns about cardiac adverse events following immunization (AEFI), such as myocarditis. PURPOSE: The purpose of the study is to assess the safety and efficacy of mRNA vaccines in patients with cardiac amyloidosis. METHODS: Patients of the Amyloidosis Center Charité Berlin (ACCB) were assessed about the vaccination, its tolerability and clinical effectiveness. To date, we included 62 patients (54 men) with a median age of 82,5 years (range 37 to 92). 46 patients had wtATTR amyloidosis, ten patients had hATTR amyloidosis, and six patients had AL amyloidosis. The mean systolic left ventricular function was 51% (range 30 to 62) with a mean global strain of -11,5% (range -18,5 to -3,1). The mean NT-pro-BNP was 1145 ng/l (range 24 to 48297). RESULTS: 59 patients were triple vaccinated and three patients so far are double vaccinated. Three of the patients were unvaccinated. 171 of the vaccine doses administered were mRNA vaccines and eight doses were a viral vector-vaccine. None of the patients reported severe side effects. Thirteen patients reported feeling of pressure and pain at the injection site after vaccination and four patients had fever of maximum two days, eight patients reported lower general condition of maximum five days. One patient reported malaise for 14 days after each vaccination, which resolved spontaneously. There was no clinical or laboratory evidence of suspected vaccine-induced myocarditis. Five patients reported of a COVID-19 breakthrough infection, all of which with a mild course of disease. None of the patients had symptoms of worsening heart failure in temporal relation to the vaccination. Most of the vaccinations (103) were performed at an official vaccination center, 59 were performed at a general practitioner. CONCLUSION: In patients with cardiac amyloidosis, mRNA vaccines for COVID-19 are safe with respect to severe cardiac adverse events and show effective protection against clinically relevant SARS-CoV2 infection.