What this trial measures

• Demographic characteristics (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  * Age * Sex as determined by the investigator (male/female) * Race and ethnicity, where allowed

• Treatment patterns (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following treatments will be assessed: * ATTR amyloidosis treatment: Tafamidis, Diflunisal, Acoramidis, Vutrisiran, Patisiran, Inotersen, Eplontersen, Doxycycline and taurodesoxycholic acid, Liver transplant * Heart failure/arrhythmia-related treatment: Diuretics, Angiotensin converting enzyme inhibitor, Angiotensin receptor blocker, Angiotensin receptor-neprilysin inhibitor, Anticoagulation, Beta-blockers, Sodium-glucose co-transporter-2 inhibitor, Mineralocorticoid receptor antagonist, Digoxin, Pacemaker use, Implantable cardioverter-defibrillator, Left ventricular assist device, Cardiac transplant, Transcatheter aortic valve replacement, Surgical aortic valve replacement * Polyneuropathy-related treatment: Antiepileptics (gabapentin, pregabalin, carbamazepine, phenytoin), Antidepressants, Topical pain treatments, Opioids, Tetrahydrocannabinol * Other: Medications for gastrointestinal symptoms, Vitamin A supplementation, Dialysis

• Clinical characteristics (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following clinical characteristics will be assessed: * Modified body mass index (mBMI) * Medical history * TTR genetic test results * Family history of ATTR * Time period between the first symptoms to date of diagnosis of ATTR * Time since diagnosis of ATTR

• Findings from biopsy (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following biopsy information will be collected: * Type of biopsy * Amyloid identification result (Positive, Negative, Inconclusive for amyloid) * Method of amyloid typing * Result of the biopsy (Normal/Abnormal) * Reason for considering the biopsy result abnormal

• Findings from Cardiovascular magnetic resonance imaging (CMR) (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following information will be collected: extracellular volume (ECV), contrast use, left ventricular (LV) end-diastolic volume, LV end-systolic volume, LV ejection fraction, LV Mass Index, interventricular wall thickness, right ventricular Free Wall Thickness, LV Free Wall Thickness, left Atrial Volume Index, native T1 mapping, CMR result (Normal/Abnormal), reason for considering the result abnormal.

• Findings from Bone tracer cardiac scintigraphy (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following information will be collected: Type of tracer, Heart to contralateral lung ratio (H/CL), Perugini grade, scintigraphy result (Normal/Abnormal), reason for considering the result abnormal.

• Findings from Echocardiography (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following information will be collected: LV ejection fraction, LV End Diastolic Volume, LV End Systolic Volume LV End Diastolic Dimension, LV End Systolic Dimension, Interventricular Septal Thickness End Diastole, Posterial Wall Thickness End Diastole, Left Ventricular Mass Index, Left Atrial Volume, Left Atrial Volume Index, Mitral valve regurgitation, Aortic valve regurgitation, Tricuspid valve regurgitation, Pulmonic valve regurgitation, LV Outflow Gradient, Stroke Volume, Lateral early diastolic myocardial velocity (e' lateral), Medial early diastolic myocardial velocity (e' medial), Mitral E/e' Ratio, Early diastolic mitral inflow velocity (E), Late diastolic mitral inflow velocity (A), Mitral Peak E/A Ratio, Global LV longitudinal strain, Pulmonary artery systolic pressure, RV Free Wall Thickness Severity of Aortic stenosis, Severity of Mitral stenosis.

• ECG variables (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following ECG information will be collected: * Interpretation of the ECG (Normal/Abnormal/Borderline) * Heart rhythm * Presence of extrasystoles * Presence of conduction abnormalities * Evidence of left ventricular hypertrophy (LVH)

• Sural nerve and tibial nerve amplitude (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  Sural nerve and tibial nerve amplitude will be measured in overall and in patients initiating a treatment with eplontersen

• Biomarker results (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following biomarker results will be collected: * Serum TTR levels * Complete blood count * Hemoglobin * Troponin I * Cystatin * Creatinine * Reported glomerular filtration rate (GFR) * Albumin * Liver enzymes: alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), total bilirubin * N-terminal pro B-type natriuretic peptide (NT-proBNP) * Vitamin A level * Neurofilament light chain (NfL) * International normalized ratio (INR) test

• Urine test results (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following test results will be collected: * Urine albumin-creatinine ratio (UACR) * Urine protein creatinine ratio (UPCR)

• Clinical manifestations (signs and symptoms) of ATTR amyloidosis (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following clinical manifestations will be assessed: ischemic heart disease, acute myocardial infarction, heart failure, atrial fibrillation, arrhythmias, conduction system disease, aortic valve stenosis polyneuropathy, carpal tunnel syndrome, autonomic neuropathy, nephrotic syndrome, subnephrotic proteinuria, gastrointestinal dysfunction, chronic kidney disease / acute kidney injury, spinal stenosis, spinal stenosis surgery, hepatomegaly, ascites, oedema, other amyloidosis related manifestations (e.g., Popeye's sign, tendon rupture)

• 36-Item Short Form Health Survey Version 2 (SF-36v2) Physical Component Summary score (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  The SF-36v2 is a 36-item, generic health survey that provides scores for eight health domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) and two summary scores; the physical component summary (PCS) score and the mental component summary (MCS) score. Higher scores indicate a better health state.

• Norfolk Quality of Life-Diabetic Neuropathy total score (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  The Norfolk QOL-DN is a 35-item, disease-specific instrument that provides scores for five domains (symptoms, large fiber neuropathy, small fiber neuropathy, autonomic neuropathy, and activities of daily living) and a total score. Higher scores indicate a worse health state.

• Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  The KCCQ is a 23-item, disease-specific questionnaire that assesses seven domains (physical limitations, symptom stability, symptom frequency, symptom burden, self-efficacy, quality of life, and social limitation) and provides three summary scores (total symptom score, clinical summary score, and overall summary score). Higher scores indicate a better health state.

• New York Heart Association (NYHA) classification (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  I=No symptoms; II=Symptoms with ordinary physical activity; III=Symptoms with less than ordinary physical activity; IV=Symptoms at rest.

• National Amyloidosis Centre (NAC) ATTR staging or Mayo staging (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  For NAC staging, Stage I: N-terminal pro-brain natriuretic peptide (NT-proBNP) ≤3000 ng/L and estimated glomerular filtration rate (eGFR) ≥45 ml/min; Stage III: NT-proBNP \>3000 ng/L and eGFR \<45 ml/min; Stage IV:NT-proBNP ≥10,000 ng/L; Stage II: remainder of patients For Mayo staging, Stage I: Both and biomarker values are below the established thresholds; Stage II: Either troponin T or NT-proBNP is above the threshold; Stage III: Both troponin T and NT-proBNP biomarker values are above the threshold. Biomarker Thresholds: Troponin T: \>0.05 mg/mL and NT-proBNP: \>3000 pg/mL.

• Familial amyloid polyneuropathy (FAP) (Coutinho) staging (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  Stage 0: No symptoms; Stage I: Unimpaired ambulation; mostly mild sensory, motor and autonomic neuropathy in the lower limbs; Stage II: Assistance with ambulation required, mostly moderate impairment progression to the lower limbs, upper limbs, and trunk; Stage III: Wheelchair-bound or bedridden; severe sensory, motor, and autonomic involvement of all limbs.

• Polyneuropathy disability (PND) score (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  Stage 0=No symptoms; Stage I=Sensory disturbances but preserved walking capabilities; Stage II=Impaired walking capacity, but ability to walk without a stick or crutches; Stage IIIA=Walking with help of 1 stick or crutch; Stage IIIB=Walking with the help of 2 sticks or crutches; Stage IV=confined to wheel chair or bedridden.

• Left Ventricular Ejection Fraction (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  Left Ventricular Ejection Fraction will be measured in overall and in patients initiating a treatment with eplontersen

• 6-minute walk test (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  To address this objective, the distance walked in 6 minutes will be measured.

• Charlson comorbidity index (CCI) and CCI components (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address CCI, most recent score and all CCI componenet will be measured * Myocardial infarction * Congestive heart failure * Peripheral vascular disease * Cerebrovascular disease * Dementia * Chronic pulmonary disease * Rheumatic disease * Peptic ulcer disease * Diabetes (None, Without chronic complications, With chronic complications) * Hemiplegia or paraplegia * Renal disease * Any malignancy, including lymphoma and leukemia, except malignant neoplasm of skin (None, Localized, Metastatic) * Liver disease (None, Mild, Moderate, Severe) * Metastatic solid tumor * Acquired immune deficiency syndrome (AIDS) / Human immunodeficiency virus (HIV)

• Other comorbidities of interest (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following information will be collected: * Percentage of patients with depression * Percentage of patients with fibromyalgia * Percentage of patients with paraproteinemia

• Healthcare resource utilization (overall and in patients initiating a treatment with eplontersen)From time of enrollment for up to 7 years

  In order to address this objective, the following information will be collected: * Number of emergency department visits * Number of outpatient visits * Inpatient care/hospitalization general ward (non-intensive): number of inpatient stays, number of bed days * Inpatient care/hospitalization intensive ward: number of inpatient stays, number of bed days

• Mortality (overall and in patients initiating a treatment with eplontersen)Throughout study follow-up (up to 7 years)

  Mortality during study follow-up (all-cause, related to ATTR amyloidosis), overall and by NYHA/NAC or Mayo/FAP stage

• Liver Disease and Live TransplantFrom time of Enrollment for up to 7 Years

  * Liver disease (for patients with mild, moderate or severe liver disease: Child Pugh score, Child Pugh class, ascites, encephalopathy) * Liver transplantation (reason for transplant, type of transplant)