Peak Exercise Oxygen Uptake (VO2peak)

VO2peak indexed to body weight (mL/kg/min) will be the co-primary outcome for the trial. VO2peak is a gold-standard measure of aerobic exercise capacity and will be measured by maximal exercise test using a previously established ergometer protocol

Baseline, 3months, 6months, and 9months

Short Physical Performance Battery (SPPB)

SPPB will be a co-primary outcome for the trial. Score ranges from 0 to 12, with 0 indicating the worst performance and 12 indicating the best.

Baseline, 3months, 6months, and 9months

Kansas City Cardiomyopathy Questionnaire 12 (KCCQ-12)

Health-related quality of life will be assessed using the KCCQ-12 questionnaire. This is a self-administered questionnaire that assesses a patient's perception of their heart failure with regard to the psychological, physical, and socioeconomic aspects of life. Scores range from 0 to 100, where 0 indicates the worst possible health status and 100 indicates the best.

Baseline, 3months, 6months, and 9months

6 Minute Walk Distance (6MWD)

6MWD is a simple and well-validated measure of submaximal exercise capacity and does not require any exercise equipment or advanced training for technicians

Baseline, 3months, 6months, and 9months

General Quality of Life - EQ-5D-5L

Change in general health-related quality of life assessed using the EuroQol 5 Dimension 5 Level (EQ-5D-5L) instrument. The EQ-5D-5L uses a descriptive system to measure health-related quality of life across five key dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on five levels of severity-ranging from no problems (Level 1) to extreme problems or inability to function (Level 5). A respondent's answers generate a five-digit health state profile that reflects their unique combination of responses (e.g., 12345), representing one of 3,125 possible health states. This descriptive system enables consistent and standardized assessment of an individual's health status.

Baseline, 3months, 6months, and 9months

Thirty Second Chair Test

The 30-second chair stand test measures lower-body strength and endurance by counting how many times a person can stand up from a chair and sit down within 30 seconds.

Baseline, 3months, 6months, and 9months

Fried Frailty Phenotype

The Fried frailty phenotype defines frailty based on five criteria-unintentional weight loss, exhaustion, weakness, slow walking speed, and low physical activity. Each criterion met adds one point to the total score. The Fried Frailty scale has a score range of 0 to 5. A score of 0 means the person is robust or not frail, a score of 1 or 2 indicates pre-frailty (intermediate risk), and a score of 3 or more means the person is considered frail.

Baseline, 3months, 6months, and 9months

Resting cardiac output

Assess with echocardiography to measure stroke volume and heart rate during rest

Baseline, 3months, 6months, and 9months

Exercise cardiac output

Assess with echocardiography to measure stroke volume and heart rate responses with graded physical stress.

Baseline, 3months, 6months, and 9months

Intramyocellular fat

Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans will be used to measure the radiodensity of muscle tissue, quantified in Hounsfield Units (HU). Skeletal muscle tissue is assigned a range of HU values (-29 to +150). Higher fat content lowers the overall muscle density, resulting in lower HU values

Baseline, 3months, 6months, and 9months

Intermuscular Adipose Tissue (IMAT)

Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans quantify intermuscular adipose tissue (IMAT) using the Hounsfield unit (HU) scale, where IMAT is classified as fat density within a range of -250 to -30 HU. The area of fat deposits is then quantified in square centimeters (cm\^2)

Baseline, 3months, 6months, and 9months

Subcutaneous adiposity deposits

Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans quantify fat deposits using the Hounsfield unit (HU) scale, where fat is defined as a density within a range of -250 to -30 HU. The area of fat deposits is then quantified in square centimeters (cm\^2)

Baseline, 3months, 6months, and 9months

Visceral Adiposity Deposits

Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans quantify fat deposits using the Hounsfield unit (HU) scale, where fat is defined as a density within a range of -250 to -30 HU. The area of fat deposits is then quantified in square centimeters (cm\^2)

Baseline, 3months, 6months, and 9months

Pericardial Adiposity Deposits

Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans quantify fat deposits using the Hounsfield unit (HU) scale, where fat is defined as a density within a range of -250 to -30 HU. The area of fat deposits is then quantified in square centimeters (cm\^2)

Baseline, 3months, 6months, and 9months

Lower Body Adiposity Deposits

Assessed with non-contrast CT scans of the chest, abdomen, and pelvis. These scans quantify fat deposits using the Hounsfield unit (HU) scale, where fat is defined as a density within a range of -250 to -30 HU. The area of fat deposits is then quantified in square centimeters (cm\^2)

Baseline, 3months, 6months, and 9months

E/e': Ratio of early mitral inflow velocity (E) to early diastolic mitral annular velocity (e')

Exercise echocardiography to measure E/e' ratio to assess left ventricular filling pressures at rest and during graded physical stress

Baseline, 3months, 6months, and 9months

Left atrial reservoir strain

Assessed using echocardiography at rest and during graded physical stress

Baseline, 3months, 6months, and 9months

Left ventricular global longitudinal strain (LV GLS)

Assessed using echocardiography at rest and during graded physical stress

Baseline, 3months, 6months, and 9months

GAD 7 score

Change in anxiety symptoms assessed using the Generalized Anxiety Disorder-7 (GAD-7) scale. Total scores range from 0 to 21, with higher scores indicating more severe anxiety symptoms.

Baseline, 3months, 6months, and 9months

PHQ 9 score

This is a self-administered questionnaire that assesses the severity of depressive symptoms. The PHQ-9 (Patient Health Questionnaire-9) ranges from 0 to 27, with higher scores indicating more severe depressive symptoms.

Baseline, 3months, 6months, and 9months

NT-proBNP

Serum level of NT-proBNP (N-terminal pro-brain natriuretic peptide), a biomarker that reflects cardiac stress.

Baseline, 3months, 6months, and 9months

High-sensitivity troponin I

Serum high-sensitivity troponin I reflects ongoing low-grade myocardial injury and is a marker of disease severity and prognosis in chronic heart failure.

Baseline, 3months, 6months, and 9months