Diagnosis and management of transthyretin amyloidosis (ATTRv) across ATTRv-PN and mixed phenotype: an international delphi consensus

Abstract Background Transthyretin amyloidosis is a progressive, potentially fatal genetic disorder primarily associated with polyneuropathy (ATTRv-PN) or cardiomyopathy (ATTR-CM). Disease presentation is heterogenous. Patients often present with a mixed phenotype. Although recent clinical recommendations for ATTR-CM management are well established, there is limited updated guidance for the diagnosis and management of ATTRv-PN or mixed phenotype ATTRv. This study aimed to identify gaps in practice and establish expert consensus to support optimal care. Methods A steering committee (SC) of four international experts experienced in ATTR amyloidosis management was convened. Three priority domains were identified and 45 statements were developed. Statements were distributed internationally as a 4-point Likert survey to neuromuscular neurologists and heart failure cardiologists experienced in managing ATTR amyloidosis. Pre-defined stopping criteria included a target of 100 responses and a threshold of ≥75% agreement. Surveys were fully anonymized. Results were discussed by the SC and recommendations were formulated based on observed agreement. Results A total of 100 clinicians participated,including neurologists (n=74) and cardiologists (n=26) from the United States (n=50), Canada (n=10), France, Germany, Italy, Spain, and the United Kingdom (n=8 each). Respondents stated high levels of experience with n=62 having ≥11 years in role and n=49 managing ≥16 patients with ATTR-PN or ATTR with mixed phenotype annually. Consensus (≥75% agreement) was achieved for 43 of 45 statements meeting the stopping criteria and obviating further Delphi rounds. Agreement levels were consistent across roles and regions, with the highest concordance among clinicians managing higher patient volumes (>25 patients per year). Conclusion This international consensus provides a practical framework to support timely diagnosis and standardized management of ATTRv-PN and ATTRv with a mixed phenotype, addressing an important unmet need in ATTR amyloidosis care.