A Physical Activity Program for People With Heart Failure

The primary outcome is the change in functional capacity measured with a 6-minute walk test (6MWT).

Measured with the Kansas City Cardiomyopathy Questionnaire - Clinical Summary Scale (KCCQ-CSS). This is scored on a 0-100 scale, with higher scores indicating better heart failure-related health status (i.e., fewer symptoms and less physical limitation); 0 reflects the worst and 100 the best status.

Measured with blood-based high-sensitivity C-reactive protein (hs-CRP). Unit: mg/L.

Additional pro- and anti-inflammatory markers will be measured from a blood sample, e.g., Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 beta (IL-1β), Interleukin-10 (IL-10), and Interleukin-1 Receptor Antagonist (IL-RA), including novel inflammatory biomarkers that may become available up to the time of analysis.

Unit: pg/mL.

Measured with a StepWatch accelerometer as the total counts of steps/day.

Measured with a StepWatch accelerometer as minutes/day spent at light, moderate (main interest) and vigorous-intensity step cadence.

Measured with a StepWatch accelerometer as the minute with the higher number of steps.

Physical activity (primary behavior of interest), sedentary, and sleep metrics measured with a Matrix Activity Monitor .

Heart failure-related patient perceptions measured with subscales and individual domains of the Kansas City Cardiomyopathy Questionnaire (KCCQ):

• Overall Summary Scale (combines symptom, physical limitations, social limitations, and quality of life domains)
• Self-efficacy Scale. Scores are transformed to a 0-100 scale; higher scores indicate better heart-failure health status.

Measured with the Montreal Cognitive Assessment (MoCA) total score (1-30).

Measured by (i) the Trail Making Test Part A (TMT-A), where shorter completion times indicate better performance; and (ii) the Digit Symbol Substitution Test (DSST), with the outcome defined as the total number of correct responses within the time limit (120 sec).

Measured by (i) Trail Making Test Part B (TMT-B), where shorter completion times indicate better performance; (ii) Dimensional Change Card Sort (DCCS), and (iii) the Flanker test, both with computed scores representing accuracy and reaction time.

Measured by (i) the free recall item of the Montreal Cognitive Assessment (MoCA), and (ii) the Picture Sequence Memory Test (PSMT), with raw scores indicating memory performance.

Measured with magnetic resonance imaging using a T1-weighted Magnetization-Prepared Rapid Acquisition Gradient Echo (MPRAGE) structural sequence.

This outcome will be assessed only in participants without MRI incompatibilities

Measured with magnetic resonance imaging using a T1-weighted Magnetization-Prepared Rapid Acquisition Gradient Echo (MPRAGE) structural sequence.

This outcome will be assessed only in participants without MRI incompatibilities.

Measured with magnetic resonance imaging using a T1-weighted Magnetization-Prepared Rapid Acquisition Gradient Echo (MPRAGE) structural sequence.

This outcome will be assessed only in participants without MRI incompatibilities.

Measured with magnetic resonance imaging using a T1-weighted Magnetization-Prepared Rapid Acquisition Gradient Echo (MPRAGE) structural sequence.

This outcome will be assessed only in participants without MRI incompatibilities.

White matter microstructure will be assessed using diffusion-weighted magnetic resonance imaging, with metrics including mean diffusivity, fractional anisotropy, and tractography-derived measures.

This outcome will be assessed only in participants without MRI incompatibilities

White matter lesions identified as white matter hyperintensities using 3D T2-weighted Turbo Spin Echo (TSE) Fluid-Attenuated Inversion Recovery (FLAIR) magnetic resonance imaging.

This outcome will be assessed only in participants without MRI incompatibilities

Cerebral blood flow measured with magnetic resonance imaging using the technique of TGSE-pCASL (turbo gradient spin echo-pseudo continuous arterial spin labeling).

This outcome will be assessed only in participants without MRI incompatibilities

Blood Brain Barrier permeability measured by calculating the water exchange rate across the blood-brain barrier using 3D diffusion-prepared arterial spin labelled perfusion magnetic resonance imaging.

This outcome will be assessed only in participants without MRI incompatibilities

Frailty score calculated using the Fried Frailty Scale. This scale characterizes frailty as the presence of at least three of the following five components: unintentional weight loss, self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. Each component in which the participant meets the frailty criterion is scored as 1. Otherwise, it is scored as 0. The scores from the five criteria are summed up to obtain a final score, which is then used to classify the participant according to the following thresholds:

Frail: ≥3 criteria present. Prefrail: 1-2 criteria. Robust: 0 criteria

Reported by participants with the Hospital Anxiety and Depression Scale. The anxiety subscale has 7 items. Each item is rated on a 4-point scale (0-3 points). The total anxiety scores range from 0-21 points. Higher scores mean worse anxiety symptoms.

Reported by participants with the Hospital Anxiety and Depression Scale. The depression subscale has 7 items. Each item is rated on a 4-point scale (0-3 points). The total depression scores range from 0-21 points. Higher scores mean worse depression symptoms.

Cardiovascular health score calculated using the total score of Life's Essential 8, and the sub-scores related to health factors and behaviors. The health factors include body mass index, blood lipids, blood glucose and blood pressure. Health behaviors consider physical activity, diet, nicotine exposure and sleep health. It yields a cardiovascular health score based on the unweighted average of all components, ranging from 0 to 100 points. A higher score means better cardiovascular health.

Reported by participants with the Subjective Memory Decline Scale. It consists of four items assessing self-experienced increasing difficulties in everyday memory, yielding a total score ranging from 0 to 8. Higher scores indicate greater perceived memory decline.

Reported by participants with the Perceived Stress Scale (PSS). It consists of 14 items with a five-point response format. A higher score corresponds to a higher level of perceived stress.

Reported by participants with the UCLA Loneliness Scale. Items are rated using a 4-point Likert-type scale. Total scores range from 10 to 40, with higher scores indicating greater loneliness.

Reported by participants with the Multidimensional Scale of Perceived Social Support. The MSPSS is a 12-item self-administered questionnaire that evaluates perceived support from three distinct sources: family, friends, and significant other. Each item is rated on a 7-point Likert scale, with higher scores indicating greater perceived support.

Reported by participants with the Rosenberg Self-Esteem Scale. It is a 10-item self-report questionnaire that assesses global self-esteem by capturing individuals' overall sense of self-worth and self-acceptance. Items are rated on a 4-point Likert scale. Total scores range from 10 to 40, with higher scores indicating greater self-esteem.

Assessed by a trained health professional, through an interview with the participant, using the Barthel Index. The scale has 10 items covering basic activities of daily living (feeding, bathing, groomig, dressing, continence, toilet use, transfers, mobility and stairs). The total score ranges from 0 to 100 points. Higher scores indicate greater independence in basic activities of daily living.

Assessed by a trained health professional, through an interview with the participant, using the Lawton and Brody Scale. The scale has 8 items covering instrumental activities of daily living (ability to use the telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, responsibility for own medication, ability to handle finances). Each item is scored dichotomously (independent = 1, dependent = 0). The total score ranges from 0 to 8 points. Higher scores indicate greater independence in instrumental ADL.

NYHA category defined by a clinician (I-IV, higher categories denote worse symptoms and limitations), medication prescription

At the end of every month of the intervention, participants will be asked to rate their physical activity enjoyment using a short version of the Physical Activity Enjoyment Scale (PACES). Higher scores indicate greater enjoyment.

This will be assessed only in participants in the intervention group.

Every two weeks during the intervention, participants will be asked to rate their perceived exertion, thinking about when they were performing step-based physical activities, using the 6-20 Borg scale. Higher scores indicate greater exertion.

This will be assessed only in participants in the intervention group.

Measured based on participants' attendance to the coaching sessions, use of Fitbit and achievement of the goals.

These will be assessed only in participants in the intervention group

Based on the incidence of clinical events during the study, i.e., during the 9-month intervention and during the 3-month follow-up (12 months after randomization), including worsening heart failure, hospitalization (cardiovascular and non-cardiovascular related), major adverse cardiovascular events and mortality.

Incidence of clinical events 5 and 10 years after the completion of the study, including hospitalization (cardiovascular and non-cardiovascular related), major adverse cardiovascular events and mortality. This will be measured using structural funds from the research team.

Measured based on analyses of cost-effectiveness. This will be measured using structural funds from the research team.

Measured based on analyses of Social Return on Investment (SROI). This will be measured using structural funds from the research team.

Measured with peripheral blood-based biomarkers such as N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Unit: pg/dL.

Measured with peripheral blood-based biomarkers such as Brain-Derived Neurotrophic Factor (BDNF).

Unit: pg/dL.

Measured with peripheral blood-based biomarkers such as total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides.

Unit: mg/dL.

Measured with peripheral blood-based biomarkers such as Fasting Plasma Glucose. Unit: mg/dL.

Measured with peripheral blood-based glycated hemoglobin (HbA1c). Unit: %.

Estimated as the Glomerular Filtration Rate (eGFR). Unit: mL/min/1.73 m²

Measured with peripheral blood-based creatinine and urea nitrogen (BUN). Unit: mg/dL.

Measured with peripheral blood-based Uric acid. Unit: mg/dL.

Measured with peripheral blood-based Aspartate aminotransferase, Alanine aminotransferase, Gamma-glutamyl transferase, Alkaline phosphatase, Lactate dehydrogenase, Creatine kinase. Unit: U/L.

Measured with peripheral blood-based Total bilirubin. Unit: mg/dL.

Measured with peripheral blood-based Thyrotropin (TSH). Unit: mIU/L.

Measured with peripheral blood-based Parathyroid hormone (PTH, intact). Unit: pg/mL.

Measured with peripheral blood-based prothrombin time, and activated partial thromboplastin time.

Unit: seconds

Measured with peripheral blood-based fibrinogen. Unit: mg/dL

Measured with peripheral blood-based sodium, potassium, chloride. Unit: mmol/L.

Measured with peripheral blood-based calcium, phosphorus, magnesium. Unit: mg/dL

Measured with peripheral blood-based albumin and total protein. Unit: g/dL

Measured with peripheral blood-based Cancer Antigen 125 (CA 125). Unit: U/mL

Measured with peripheral blood-based iron. Unit: µg/dL

Measured with peripheral blood-based transferrin. Unit: mg/dL

Measured with transferrin saturation index. Unit: %.

Measured with peripheral blood-based Ferritin. Unit: ng/mL.

Measured with peripheral blood-based Vitamin D (25 OH). Unit: ng/mL

Measured with blood-based p-tau217. Unit: pg/mL

Measured with blood-based p-tau181. Unit: pg/mL

Measured with blood-based amyloid-β 42 to 40 ratio.

Measured with blood-based neurofilament light. Unit: pg/mL

The investigators will remain open to assessing novel blood-based biomarkers related to heart and brain health that may become available in the literature up to the time of analysis

Maximal handgrip strength measured at rest using a handheld dynamometer. Higher values indicate better strength.

Unit: kg.

Number of full stands completed in 30 seconds from a standard chair without using arms. Higher values indicate better lower-body function.

Unit: repetitions (count).

Usual-pace gait speed measured over a 4.57-meter course from a standing start. Unit: second (m/s).

Measured with an automated blood pressure monitor (OMRON). Unit: mmHg.

Measured with an automated blood pressure monitor (OMRON). Unit: mmHg.

Measured with an automated blood pressure monitor (OMRON). Unit: beats per minute.

Body mass will be measured using a SECA scale, height will be measured using a SECA height measuring system, body mass index will then be calculated (kg/m2).

Measured following standardized procedures with a Lufkin tape measure. Unit: cm.

Measured using resting ultrasound echocardiography with markers such as 2D and 3D ejection fraction, deformation measures, and additional right-ventricular indices.

Due to logistic constraints, this outcome will only be assessed in participants recruited from the hospitals in Granada city.

Measured using resting ultrasound echocardiography with markers such as E/e' ratio and left atrial strain.

Due to logistic constraints, this outcome will only be assessed in participants recruited from the hospitals in Granada city.

Measured using resting ultrasound echocardiography with markers such as left atrial volume index, and other ventricular and atrial diameters and volumes.

Unit: mL/m². Due to logistic constraints, this outcome will only be assessed in participants recruited from the hospitals in Granada city.

Gene expression analyses will be conducted using RNA blood samples.

DNA methylation analyses will be conducted using blood samples.

Measured based on patient perceptions collected using a custom usability questionnaire adapted to the intervention and population, derived from the System Usability Scale. These will be assessed only in participants in the intervention group.

Measured based on patient perceptions using semi-structured interviews, such as reported barriers and facilitators.

These will be assessed only in participants in the intervention group.

Measured based on patient perceptions using semi-structured interviews, such as ability to engage in the program as intended in daily life.

These will be assessed only in participants in the intervention group.