EFICAC-TTR Trial: Exercise and Nutritional Supplementation in Transthyretin Cardiac Amyloidosis

Change in maximal isometric handgrip strength measured in kilograms (kg) using a calibrated handheld dynamometer (best of three attempts for the dominant hand), expressed as the difference between baseline and 12 weeks.

Change in walking capacity assessed by the 6-minute walk test, measured as the difference in total distance walked (meters) between baseline and 12 weeks.

Change in total body fat mass measured in kilograms (kg) using multifrequency bioelectrical impedance analysis, expressed as the difference between baseline and 12 weeks.

Change in skeletal muscle mass measured in kilograms (kg) using multifrequency bioelectrical impedance analysis, expressed as the difference between baseline and 12 weeks.

Change in fat-free mass measured in kilograms (kg) using multifrequency bioelectrical impedance analysis, expressed as the difference between baseline and 12 weeks.

Change in phase angle measured in degrees (°) using multifrequency bioelectrical impedance analysis, expressed as the difference between baseline and 12 weeks.

Change in frailty status assessed by the FRAIL scale, a 5-item questionnaire with scores ranging from 0 to 5, where higher scores indicate greater frailty, expressed as the difference between baseline and 12 weeks.

All-cause mortality, defined as death from any cause during the follow-up period.

Change in Short Physical Performance Battery (SPPB) total score, ranging from 0 to 12 points, where higher scores indicate better physical performance, expressed as the difference between baseline and 12 weeks.

Change in frailty severity assessed by the Clinical Frailty Scale (CFS), a 9-point ordinal scale ranging from 1 (very fit) to 9 (terminally ill), where higher scores indicate greater frailty.

Change in functional independence assessed by the Barthel Index, scored from 0 to 100, where higher scores indicate greater independence.

Change in sarcopenia risk assessed by the SARC-F questionnaire, with scores ranging from 0 to 10, where higher scores indicate greater sarcopenia risk.

Change in health-related quality of life assessed by the Minnesota Living With Heart Failure Questionnaire (MLHFQ), with total scores ranging from 0 to 105, where higher scores indicate worse quality of life.

Change in comorbidity burden assessed using the Charlson Comorbidity Index, a weighted index that accounts for the number and severity of comorbid conditions, where higher scores indicate greater comorbidity burden.

Number of hospitalizations due to heart failure occurring during the follow-up period.

Hospital admissions due to causes other than heart failure during the follow-up period.

Number of emergency department visits during follow-up.

Number and type of adverse events related to exercise and/or supplementation, classified according to severity and relatedness, collected throughout the follow-up period.

Proportion of participants who discontinue study supplements.

Proportion (%) of prescribed exercise sessions completed, with adequate adherence defined as completion of at least 80% of prescribed sessions.

Proportion (%) of planned supplement doses consumed, with optimal compliance defined as 90-110%.

Change in serum GDF-15 concentration (pg/mL) measured by immunoassay.

Change in serum soluble ST2 concentration (ng/mL) measured by immunoassay.

Change in serum interleukin-6 (IL-6) concentration (pg/mL) measured by immunoassay.

Change in serum C-reactive protein (CRP) concentration (mg/L) measured by immunoassay.

Change in circulating miR-21 expression measured by quantitative PCR, expressed as relative expression (ΔΔCt).

Change in circulating miR-29 expression measured by quantitative PCR, expressed as relative expression (ΔΔCt).

Change in circulating miR-34a expression measured by quantitative PCR, expressed as relative expression (ΔΔCt).

Change in circulating miR-155 expression measured by quantitative PCR, expressed as relative expression (ΔΔCt).

Change in macrophage polarization profile assessed by flow cytometry immunophenotyping of PBMC-derived macrophages, expressed as M1/M2 ratio.

Change in gene expression of predefined pro-inflammatory (M1) markers in PBMC-derived macrophages, measured by quantitative PCR and expressed as relative expression (ΔΔCt).

Change in gene expression of predefined anti-inflammatory (M2) markers in PBMC-derived macrophages, measured by quantitative PCR and expressed as relative expression (ΔΔCt).