Psycho-Emotional Profile and Disease Burden in Wild-Type Transthyretin Amyloidosis

Background/Objectives: Patients with transthyretin amyloidosis frequently experience reduced quality of life, distress, anxiety and depression. But the evidence is inconsistent and the constructs are often not clearly separated. This study assessed quality of life and mental health symptoms in wild-type transthyretin amyloidosis (ATTRwt). Methods: Within the amyloidosis cohort study AmyKoS, 113 patients with confirmed ATTRwt amyloidosis completed a structured survey between July 2020 and February 2024, assessing quality of life (Short Form (36) Health Survey, SF-36), distress (Distress Thermometer), anxiety (Generalized Anxiety Disorder-7, GAD-7), depression (Patient Health Questionnaire-9, PHQ-9), fear of progression (Fear of Progression Questionnaire, short form; PA-F-KF), fatigue and dyspnea. Results: Of 113 patients (age 78.95 ± 5.90 years, 14.2% female), 88.4% reported restricted quality of life and 62.7% screened positive for distress. Overall, 26.4% screened positive for anxiety and/or depression and 9.2% for fear of progression. Both SF-36 summary scales were reduced to a comparable degree relative to the age-matched general population: physical component summary 36.9 ± 9.8 versus 43.5 ± 11.8 and mental component summary 46.8 ± 9.1 versus 52.2 ± 10.3 (both p < 0.001, Cohen's d = -0.59 and -0.54). Notably, 59.4% of distress-positive patients screened positive for neither anxiety nor depression, and fatigue was the key predictor. Conclusions: In ATTRwt amyloidosis, both dimensions of health-related quality of life are substantially impaired. Stepwise screening should be routine, and many burdened patients are likely to benefit primarily from symptom control and rehabilitation rather than psychiatric treatment.