Transthyretin Amyloidosis Outcome Survey (THAOS)

Modified Polyneuropathy Disability (mPND) is a score that categorizes participants into six stages (0, I,II, IIIa, IIIb, IV) based on mobility status. 0 = No sensory disturbances in the feet and able to walk without difficulty; I=Sensory disturbances in the feet but able to walk without difficulty; II=Some difficulties with walking but can walk without aid; IIIa=Able to walk with 1 stick or crutch; IIIb=Able to walk with 2 sticks or crutches; IV=Not ambulatory, confined to a wheelchair or bedridden. Higher stage indicates lower mobility status.

Coutinho disease stages is the most common classification used to capture ATTR (Transthyretin Amyloidosis) disease progression. Participants with stage 0 disease are asymptomatic, Participants with stage 1 (mild) disease are ambulatory, Participants with stage 2 (moderate) disease are ambulatory but require assistance and/or have involvement of the upper limbs, and Participants with stage 3 (severe) disease are bedridden or wheelchair-bound.

Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 10 level score which ranges between 10 (moribund) to 100 (normal, no evidence of disease). Higher score means higher ability to perform daily tasks.

Heart failure, also known as congestive heart failure is a cardiovascular event.

New York Health Association (NYHA) functional classification included: Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity; fatigue, palpitation, or dyspnea with ordinary physical activity), Class III (marked limitation of physical activity; fatigue, palpitation, or dyspnea with less than ordinary physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest).

Participants diagnosed with Transthyretin Amyloidosis (ATTR) at baseline with assessed category of yes, no, and unknown.

Number of participants with ATTR and participants who had prior misdiagnosis at the baseline were reported.

Genetic mutation leads to misfolding of protein transthyretin (TTR) which results in ATTR. In this outcome, number of participants with ATTRv mutation type and wild type TTR were reported.

Number of participants had previous or current participant in any clinical trials at the baseline.

Number of participants being allowed for the use of Tafamidis when under strict conditions, Tafamidis was in development and made available to groups of participants who have a disease with no satisfactory authorised therapies and who cannot enter clinical trials.

Number of participants whether with family history of symptomatic ATTR amyloidosis at Baseline were reported.

The mean of affected generations in participants with a known family history was reported.

Neuropathy Impairment Score - Lower Limb (NIS-LL) assessed motor, sensory and reflex activity specifically in the lower limbs and combined total scores for the lower limbs were collected and reported. Derived NIS LL score extends from 0 (normal functions) to a maximum possible value of 88 points, the scale is additive for all deficits and is applied bilaterally for each modality tested: 1) muscle strength: 0 (normal)-4 (paralysis), higher score = more weakness; 2) sensory and 3) reflex testings: 0=normal, 1=decreased, or 2=absent. Reflex score: 0 (normal)-10 (present), higher score =present in more anatomic sites; Motor score: 0-160 (full range of motion with maximum resistance across all anatomical sites), higher score=more impairment. Sensory Score has a range of 0 to the normal value of 124 where ratings are coded as 0=absent; 1=decreased; 2=normal.

BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m^2).

mBMI was calculated by multiplying BMI by serum albumin levels [gram/liter (g/L)]. mBMI was measured as kg/m^2*g/L. A progressive decline in mBMI indicated worsening of disease severity.

BP (Blood Pressure) is the pressure of the blood within the arteries. It is produced primarily by the contraction of the heart muscle. BP measurement is recorded by 2 numbers: systolic BP (SBP, BP when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle) and diastolic BP (DBP, BP when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles). Available sitting SBP and DBP at Baseline were reported.

Cardiac amyloidosis is attributable to intramyocardial amyloid infiltration, which leads to a progressive increase of ventricular wall thickness and stiffness. A left ventricular (LV) wall thickness ≥12 mm plus at least one red flag should raise the suspicion of cardiac amyloidosis.

Left ventricular dysfunction, a condition in which the left ventricle of the heart exhibits a decreased functionality, was assessed based on systolic ejection fraction. Systolic ejection fraction was the fraction of the end-diastolic volume (EDV) that was ejected out of left ventricle with each contraction.

EQ-5D-3L VAS: participant rated questionnaire to assess generic health status in two parts: single utility score and visual analog scale. The VAS component rated the current health state on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicating a better health state.

The EQ-5D-3L VAS derived index is calculated by subtracting the values of the descriptive EQ-5D system from the numerical value. This corresponds to the best possible health status, the scale of the Derived Index is 0 [death] to 1 [perfect health]. EQ-5D-3L VAS overall health score and derived score data were sourced from different part of the EQ-5D questionnaire and are conceptually different from each other as EQ VAS is a 0-100 scale and EQ-5D index is a value attached to an EQ-5D profile according to a set of weights that reflect, on average, participant's preferences about how good or bad the state is. More data were collected for EQ-5D index score compared to EQ VAS overall health score at the baseline.

Norfolk QOL: 35-item participant-rated questionnaire used to assess impact of neuropathy on the quality of life of participants diagnosed with ATTR. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: activities of daily living, large fiber neuropathy/physical functioning, small fiber neuropathy, autonomic neuropathy, and symptoms. TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life.

Following parameters were analyzed: heart rate, PR interval, QT interval, QRS interval and QT interval corrected using Fridericia's formula (QTcF). Abnormal findings in ECG were based on investigator's discretion.

Number of participants with atrial fibrillation/flutter (rapid, irregular heart rhythm), implanted artificial cardiac pacemaker, and implantable cardioverter-defibrillator (ICD) (detects and stops irregular heartbeats, also called arrhythmias) were reported.