Effectiveness of a Cardiac Rehabilitation Program in Elderly Patients With Heart Failure.

Sarcopenia Clinical Trial

— FUNNEL+  

Official title:

Effectiveness of a Cardiac Rehabilitation Program on Biomechanical, Imaging, and Physiological Biomarkers in Elderly Patients With Heart Failure.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05393362
• Other study ID #: Funnel+ Study
• Status: Recruiting
• Phase: N/A
• Start date: March 7, 2023
• Est. completion date: March 2024

Study information

• Verified date: March 2023
• Source: University of Malaga
• Contact: Cuesta Vargas A Antonio Ignacio, PhD
• Phone: 952137551
• Email: acuesta[@]uma.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of the study is to assess the effectiveness of a cardiac rehabilitation program on functionality, measured by kinematic analysis, cardiorespiratory capacity, and ventricular ejection fraction in elderly patients with heart failure (HF). Other objectives will be; 1) to validate the kinematic analysis as an objective functional assessment that allows performing a functional stratification based on the severity of impairment ("kinematic phenotypes"), as well as to identify those patients who responders or are not responders to the cardiac rehabilitation program; 2) to develop a functional index that includes objective functional parameters, biomechanical biomarkers (heart and musculoskeletal echography) and physiological biomarkers (maximum consumption of oxygen (VO2 max), maximum heart rate (HR max) and blood lactate levels; 3) to analyse the degree of concordance of biomechanical biomarkers with functional tests normally used in clinical practice and with imaging and physiological biomarkers. A randomized, controlled, crossover clinical trial will be carried out at the Hospital Regional Universitario de Málaga. Clinically stable HF patients ≥70 years old will be included. The cardiac rehabilitation program will last 12 weeks and will follow the recommendations of the European Association of Cardiovascular Prevention and Rehabilitation. The patients will perform different functional tests, which will be at baseline, at 3 months and 6 months of follow-up.

Description:

Cardiovascular diseases continue to be the main cause of years of life disability-adjusted disability and the leading cause of death, especially in countries with longer life expectancy. Within cardiovascular diseases, Heart Failure (HF) represents a health problem of the first order, with figures of incidence and increasing prevalence associated with the progressive aging of the population and the significant advances in the treatment of chronic diseases associated with HF. HR reaches high morbidity and mortality and is one of the most common reasons for hospital admission common in elderly people, among whom frailty and sarcopenia are commonly associated. All this means that HF has a great impact both at the care level, personal as well as social and economic for public health systems. HF is a chronic disease characterized by structural cardiac involvement and/or the function that leads to a decrease in cardiac output, which leads to an inability to satisfy the metabolic demands of the organism. Under this circumstance, they end up producing alterations that lead to dyspnea and fatigue, among other manifestations, which functionally limit patients. These patients have a number of characteristics. Distinctive functional characteristics such as reduced aerobic capacity, decreased speed of gait, decreased muscle strength predominantly in the lower limbs, low physical activity, and intolerance to exercise, so they affect the performance of their activities of daily life and their quality of life. These alterations have been associated independently with survival and risk of admission in patients with HF. In the assessment of physiological biomarkers or cardiovascular functional parameters, maximal oxygen uptake (Peak VO₂) obtained from a cardiopulmonary exercise test (CPET) was considered the reference test to determine cardiovascular functional capacity, exercise tolerance, and prognosis in patients with HF. Various tests have been used useful for the indirect assessment of functionality and prognosis in patients with HR. Among them is the 6-minute walk test (6-MWT), the short battery of physical performance (SPPB), and the Timed Up and Go (TUG) test to evaluate capacity cardiopulmonary and frailty in patients with HF. Cardiac rehabilitation (CR) is a multidimensional treatment designed to promote changes in lifestyle and physical activity, optimize medical treatment, control risk factors, and address post-developmental social and psychological issues of heart disease. These CR programs have a strong recommendation (Class I) by the guidelines of the European Society of Cardiology (ESC), the American Association of Heart Association (AHA), and the American College of Cardiology (ACC) in the treatment of patients with chronic HF. In addition, it is a cost-effective intervention in HF, since it improves the prognosis by reducing recurrent hospitalizations and health spending, while it has been associated with an increase in survival. They have also shown benefits in the control of cardiovascular risk factors, in anthropometric variables, in blood, physiological (Peak VO₂), and cardiac imaging biomarkers such as ejection fraction ventricular. However, biomechanical biomarkers, as an objective measure of the functionality of these patients and, therefore, the benefits of the cardiac rehabilitation programs on these biomechanical biomarkers. These biomarkers could make it possible to quantify normal and pathological movements, the degree of deterioration, plan rehabilitation strategies and evaluate the effect of various interventions. Therefore, they could be useful to identify objective parameter functions that could be affected in patients with HF, help to stratify patients with HF based on different levels of functional impairment, in addition, to identify those responders and non-responders to CR programs. To do this, the sensors inertial sensors have been shown to be a precise and reliable method for kinematic evaluation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: March 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

Inclusion Criteria:

• Subjects older than 70 years.
• Subjects diagnosed with Heart Failure (HF) followed by the Heart Failure Unit.
• Subjects will be able or filling out questionnaires and perform functional tasks;
• Clinical stability.
• Patients receive optimal treatment.

Exclusion Criteria:

• Participants with cardiac pathologies that do not have an HF situation
• Score on the NYHA scale equal to 4.
• Hospitalization in a period of time equal to or less than 3 months.
• Score on the Mini-Mental scale (MMSE) below 24.
• Inability to get up from the chair at least 5 times
• Inability to walk.
• Inability to walk independently without a gait assist device (cane, crutch, or walker).
• Participation in an experimental study where they receive treatment.
• Inability to provide informed consent.

Related Conditions & MeSH terms

• Comorbidities and Coexisting Conditions
• Frail Elderly Syndrome
• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Sarcopenia

Intervention

Procedure:
• Cardiac Rehabilitation Program (CR)
Strength exercises: strengthe exercise will be performed twice a week for 12 weeks, 4-6 series at 60% RM at the beginning of the program, with a progression towards 85% RM in each functional movement at the end of the intervention. The patients will rest for 90 seconds between series and 3 minutes between exercises. Each session has an estimated duration of between 45-60 min. Aerobic exercise: aerobic exercise it will be performed twice a week for twelve weeks, between 45-60 min each session of aerobic exercise. It will be developed on a treadmill or cycle ergometer at 50% of HR max at the beginning of the program with a progression towards 80% of HR max at the end, continuously or internally. The Borg scale will prevail over the objective data to adjust the intensity of each patient, Borg = 10/20 or mBorg = 5/10 at the beginning, with progression to Borg = 14/20 or mBorg = 8/10 at the end.

Behavioral:
• Control Group (CG)
The control group will receive two education sessions per week for twelve weeks on the complications derived from Heart Failure (HF), functional deterioration, and healthy lifestyle habits.

Locations

Country	Name	City	State
Spain	Antonio Cuesta Vargas	Málaga

Sponsors (1)

Lead Sponsor	Collaborator
University of Malaga

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sociodemographic variables	Instruments: questionnaire, interview.; Measure: Age; Gender; Civil Status; Educational Level	Baseline
Other	Anthropometric variables_ Height	Instruments: Weighing machine, measuring tape, calculator Measure: height (cm)	Baseline
Other	Anthropometric variables_ Weight	Instruments: Weighing machine, measuring tape, calculator Measure: Weight (Kg)	Baseline
Other	Anthropometric variables_Body Mass Index (BMI).	Instruments: Weighing machine, measuring tape, calculator Measure: body mass index (BMI).	Baseline
Other	Clinical Variables_Comorbidities	Measure: Comorbidities, specifying number and types Instruments: Comorbidity Index of Charlson	Baseline
Other	Clinical Variables_Medication	Measure: Medication (specifying number of drugs and types),	Baseline
Other	Clinical Variables_ Characteristics of the heart failure (HF)_NYHA	Measure: Characteristics of the heart failure (HF) -main cause (ischemic/non-ischemic) Instruments: Grade of the New York Heart Association (NYHA) and symptom score from the Kansas-City questionnaire	Baseline
Other	Clinical Variables_Hospitalizations in the last 12 months	Measure: Hospitalizations in the last 12 months (number and reason: any cause/HF decompensated),	Baseline
Other	Clinical Variables_Consultation in the emergency department in the last 12 months	Measure: Consultation in the emergency department in the last 12 months (number and reason: any cause/decompensated HF)	Baseline
Other	Clinical Variables_Number of falls in the last 12 months	Measure: Number of falls in the last 12 months	Baseline
Other	Clinical Variables_ Characteristics of the heart failure (HF)_Kansas-City Questionnaire	Measure: Characteristics of the heart failure (HF) -main cause (ischemic/non-ischemic) Instruments: symptom score from the Kansas-City questionnaire	Baseline
Other	Clinical Variables_Toxic habits	Measure: toxic habits (tobacco, alcohol...).	Baseline
Primary	Physiological biomarkers_Cardiopulmonary Exercise Testing (CPET)-(Peak VO2)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: the maximum volume of oxygen intake [VO2,(ml/kg/min)]	Baseline
Primary	Physiological biomarkers_Cardiopulmonary Exercise Testing (CPET)-(Peak VO2)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: the maximum volume of oxygen intake [VO2,(ml/kg/min)]	Post intervention_difference (12 weeks after baseline)
Primary	Physiological biomarkers_Cardiopulmonary Exercise Testing (CPET)-(Peak VO2)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: the maximum volume of oxygen intake [VO2,(ml/kg/min)]	Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Bioelectrical Impedance Analysis (BIA)- (PhA)	Instrument: Nutrilab Bioimpedance device (Akern 2016 with Biatrodes, Akern electrodes) Bioelectrical Phase Angle (PhA) - as derived from equations related to the parameters of BIVA - recently surged as a possible biomarker for patients with HF. Studies provided data about the application of PhA in the clinical management and in the overall risk stratification of HF patients.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Bioelectrical Impedance Analysis (BIA)- (R)	Instrument: Nutrilab Bioimpedance device (Akern 2016 with Biatrodes, Akern electrodes) Resistance (R, in Ohm)- is related to the amount of body fluids in the sum of intra- (ICW) and extracellular (ECW) water.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Bioelectrical Impedance Analysis (BIA)- (Xc)	Instrument: Nutrilab Bioimpedance device (Akern 2016 with Biatrodes, Akern electrodes) Reactance (Xc, in Ohm)-is mainly linked to the inner characteristics of the cell membranes.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Bioelectrical Impedance Analysis (BIA)- (FFM)	Instrument: Nutrilab Bioimpedance device (Akern 2016 with Biatrodes, Akern electrodes) Fat-free mass (FFM, kg)- represents the sum of bone mineral content (BMC) and total lean tissue measurements.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Bioelectrical Impedance Analysis (BIA)- (FM)	Instrument: Nutrilab Bioimpedance device (Akern 2016 with Biatrodes, Akern electrodes) Fat mass (FM, Kg) - is the total weight of the body minus the weight of any fat measured. This gives an indication of the water, bone, skin, and internal organs as a combined weight.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Bioelectrical Impedance Analysis (BIA)- (BCM)	Instrument: Nutrilab Bioimpedance device (Akern 2016 with Biatrodes, Akern electrodes) Body cell mass (BCM,Kg) -is the metabolically active cell mass involved in O2 consumption, CO2 production and energy expenditure. BCM measurement has been suggested as a tool for the evaluation of nutritional status. Since BCM is closely related to energy expenditure, it could also represent a good reference value for the calculation of nutrient needs	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Bioelectrical Impedance Analysis (BIA)- (ECW)	Instrument: Nutrilab Bioimpedance device (Akern 2016 with Biatrodes, Akern electrodes) Extracellular water (ECW, L/m) - is the aqueous component that surrounds cells and reflects clinical status in patients with acute or chronic diseases.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Bioelectrical Impedance Analysis (BIA)- (TBW)	Instrument: Nutrilab Bioimpedance device (Akern 2016 with Biatrodes, Akern electrodes) Total body water (TBW, L/m)- is integral to clinical care. It has significant implications for patient care that include the dosing of medications, assessment and treatment of dehydration, fluid, and energy requirements for parenteral nutrition, and dialysis prescriptions.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Bioelectrical Impedance Analysis (BIA)- (ECW/TBW)	Instrument: Nutrilab Bioimpedance device (Akern 2016 with Biatrodes, Akern electrodes) Extracellular Water/Total Body Water Analysis (ECW/TBW)-ratio of Extracellular Water(ECW) to Total Body Water(TBW); an important indicator of body water balance. In a healthy state, ECW/TBW ratio should fall within the range 0.360 to 0.390	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Spirometric assessment-(TV)	Instrument: Spirometry device (Spiro USB and MicroRPM, Micro Medical) Tidall Volume (TV)-the amount of air moved in a normal inspiration or exhalation [TV,(mL/Kg)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Spirometric assessment-(VC)	Instrument: Spirometry device (Spiro USB and MicroRPM, Micro Medical) Vital Capacity (VC)-The amount of air that is moved in a maximal unforced inspiration or expiration. [VC,(L)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Spirometric assessment-(IRV)	Instrument: Spirometry device (Spiro USB and MicroRPM, Micro Medical) Inspiratory reserve volume(IRV)-Difference between the maximum volume that can be breathed in during a normal breath and in a maximal breath [IRV,(L)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Spirometric assessment-(ERV)	Instrument: Spirometry device (Spiro USB and MicroRPM, Micro Medical) Inspiratory reserve volume(IRV)-Difference between the maximum volume that can be exhaled in a normal breath and in a maximal breath [ERV,(L)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Spirometric assessment-(IC)	Instrument: Spirometry device (Spiro USB and MicroRPM, Micro Medical) Inspiratory Capacity (IC)-The amount of air that can be breathed in after a normal exhalation [IC,(L)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Spirometric assessment-(FVC)	Instrument: Spirometry device (Spiro USB and MicroRPM, Micro Medical) Forced Vital Capacity (FVC)-The amount of air moved in a maximal forced inspiration or expiration [FVC,(%)]; [FVC,(L)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Spirometric assessment-(FEV1)	Instrument: Spirometry device (Spiro USB and MicroRPM, Micro Medical) Forced Espiratory Volume1, (FEV1)-The amount of air moved in the first second of a forced exhalation; [FEV1,(mL/seg)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Spirometric assessment-(PEF)	Instrument: Spirometry device (Spiro USB and MicroRPM, Micro Medical) Peak Espiratory Flow, (PEF)-The maximum amount of air that can be exhaled per second in a forced exhalation.[PEF,(mL/seg)]; [PEF,(%)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Spirometric assessment-(MIP)	Instrument: Spirometry device (Spiro USB and MicroRPM, Micro Medical) Maximal inspiratory pressure(MIP)-the pressure generated during maximal inspiratory effort against a closed system.[MIP,(cm H2O)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Spirometric assessment-(MEP)	Instrument: Spirometry device (Spiro USB and MicroRPM, Micro Medical) Maximal Espiratory Pressure (MEP)-the pressure generated during maximal espiratory effort against a closed system.[MEP,(cm H2O)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Dynamometric assesment-(MDR-Hd-sEMG)	Instrument: High-Density electromyography device (HDEMG) (64-channel EMG amplifier; OT Bioelettronica+) Mean Discharge Rate of Tibialis Anterior Motor Units [MDR-Hd-sEMG,(Hz)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Dynamometric assesment-(VC-Hd-sEMG)	Instrument: High-Density electromyography device (HDEMG) (64-channel EMG amplifier; OT Bioelettronica+) Speed of propagation of Tibialis Anterior Motor Units [VC-Hd-sEMG,(m/s)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Dynamometric assesment- (F-Iso-FD-din)	Instrument: Dynamometer (J Tech Medical, Powertrack II Commander) Isometric strength in dorsiflexion of the ankle in both limbs during a 5-second maximal test using a digital hand-held dynamometer [F-Iso.FD-din,(N)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Dynamometric assesment- (F-Iso-FD-S)	Instrument: S-Type load cell (Biometrics Ltd) Isometric strength in dorsiflexion of the ankle in both limbs tests using S-Type load cell. The signal shall be analysed and processed using the required software. [F-Iso.FD-S].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Dynamometric assesment-Timed Up and Go (TUG)	Instruments: a long corridor, a chair, a cone and a chronometer Measure: Time (seg) it takes to get up from a chair, walk 3 meters, turn around, return to the chair and sit down again.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Dynamometric assesment-Six minute walk test (6-MWT)	Instruments: a long corridor and a chronometer Measure: Evaluate the distance (m) a participant can walk for 6 minutes.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Dynamometric assesment-Short Physical performance Battery (SPPB)	Instruments: a long corridor, a chair, and a chronometer Measure: A set of short tests that time the time it takes to cover a short distance (4 m), repeat 5 times sit-stand up from the chair, and a set of balance tests (feet together, semi-tandem, and tandem). The end result is a score.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Metabolic biomarkers_Blood lactate	Instruments: Lactate Pro 2 Blood Lactate Analyzer Measure. Blood lactate (mmol/L)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(Peak HR)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Peak of Heart Rate [Peak HR,(bpm)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(HRR)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Heart Rate Reserve (HRR)- the difference between the predicted maximal heart rate and the heart rate measured in VO2peak. [HRR,(bpm)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(VO2-VT1)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Ventilatory threshold oxygen consumption (VO2-VT1)- submaximal parameter of cardiorespiratory fitness [VO2-VT1,(mL/min)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(VO2/HR,O2 pulse)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Oxygen pulse [O2 pulse] is the ratio between VO2 (mLO2/min) and heart rate (HR - bpm).	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(CRE)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Chronotropic Response to Exercise (CRE)-percentage of the chronotropic index [CRE,(%)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)- (OUES)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Oxygen uptake efficiency slope (OUES)- the ratio of VO2 to the logarithm in base 10 of VE. OUES can be extracted from submaximal tests. [OUES]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(RER)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: The respiratory exchange ratio [RER] is the ratio of VCO2/VO2	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(PeakW)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Peak W (Peak work rate)- highest work rate achieved during a maximum of 30 seconds during a stress test [PeakW,(W/min)].	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(?VO2/?WR)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: [?VO2/?WR] Relationship. It is defined as the relationship between VO2 (Y-axis in mL.min-1) and workload (X-axis in Watts), measured only during exercise on a cycle ergometer with ramp protocol, whose value is progressively and linearly incremented until maximal effort.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(PeakVE)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Peak Pulmonary Ventilation (PeakVE)- highest volume of air moved in and out of the lung [PeakVE,(L/min)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(Vd/Vt)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Physiologic dead space over tidal volume (Vd/Vt) - a routine measurement, expressing the ratio of dead-space ventilation (VD) to tidal ventilation (VT)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(VE/MVV)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Breathing reserve [VE/MVV] represents the ratio between maximal ventilation during exercise (VE) and maximum voluntary ventilation (MVV) at rest, both variables in L/min.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(PETCO2)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: End-tidal CO2 partial pressure [PETCO2, (mmHg)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(PETO2)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: End-tidal O2 partial pressure [PETO2, (mmHg)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(VE/VCO2)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Ventilatory equivalents for oxygen [VE/VO2], the ratios between pulmonary ventilation and CO2 production(VE/VCO2)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers _Cardiopulmonary Exercise Testing (CPET)-(VE/VO2)	Instruments: Cardiopulmonary Exercise Testing at Ciclo-ergometer Measure: Ventilatory equivalents for oxygen [VE/VO2], the ratios between pulmonary ventilation and O2 consumption (VE/VO2)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_hematocrit	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: hematocrit (%)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_hemoglobin	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: hemoglobin 1AC, blood (%)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_Mean Corpuscular Volume (MCV)	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: mean corpuscular volume [MCV,(fL)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_Mean Corpuscular Hemoglobin (MCH)	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: mean corpuscular hemoglobin [MCH,(pg)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_Mean Corpuscular Hemoglobin Concentration (MCHC)	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: mean corpuscular hemoglobin [MCHC,(g/dL)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_Leukocytes	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: leukocytes (mg/dL)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_Platelet count	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: platelet count (units/mcL)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_Glomerular Filtration Rate (GFR)	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: glomerular filtration rate [GFR, (mL/min/1.73m²)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_Creatinine	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: creatinine (mg/dL)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_Glucose	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: glucose (mmol/L)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_Uric Acid	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: uric acid (mg/dL)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_sodium, potassium, calcium	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: sodium, potassium, and calcium (mmol/L)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_transaminases -ALT, AST, GGT, FA	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure:transaminases; Aminotransferase, alanine [ALT, (U/L)]; Aminotransferase, aspartate [AST,(U/L)]; Gamma-glutamyl transpeptidase [GGT,(U/L)]; Alpha fetoprotein[FA,(mcg/L)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_glycated hemoglobin	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: glycated hemoglobin (mmol/mol)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_ferritin	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: ferritin (ng/mL)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_iron	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: iron (mcg/dL)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_Index of transferrin saturation	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: index of transferrin saturation (%)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_transferrin	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: transferrin (mg/dL)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_ vitamin B12	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: vitamin B12 (pg/mL)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_ folic acid	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: folic acid (ng/mL)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_ HDL	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: High-density lipoprotein [HDL,(mg/dL)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_ TSH	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: TSH (mclU/mL)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_ Total cholesterol (TC)	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: total cholesterol [TC,(mg/dL)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_ LDL	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: Low-density lipoprotein [LDL,(mg/dL)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_ albumin	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: albumin (g/dL)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_ triglycerides	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: triglycerides (mg/dL9	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_ NT-proBNP	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure:N-Terminal propeptide of BNP[NT-proBNP,(pg/mL)]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Physiological biomarkers_Blood biomarkers_ Complete Blood Cell Count (CBC)_ vitamin D.	Instruments: The blood test. The extraction of the blood sample must be carried out by a qualified professional (Physician or Nurse). For data analysis, the samples will be sent to the laboratory to recounter de sample.; Measure: vitamin D (ng/ml)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Biomechanical biomarkers _ RGB-D camera (depth camera)_Trunk linear acceleration	Instruments: RGB-D camera or depth camera. Kinematic analysis by 3D motion capture.; Measure: Trunk linear acceleration (m/s2)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Biomechanical biomarkers_ RGB-D camera (depth camera)_Trunk angular displacement	Instruments: RGB-D camera or depth camera. Kinematic analysis by 3D motion capture.; Measure: Trunk angular displacement (°)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Biomechanical biomarkers _ RGB-D camera (depth camera)_Trunk angular velocity	Instruments: RGB-D camera or depth camera. Kinematic analysis by 3D motion capture.; Measure: Trunk angular velocity (°/s)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Biomechanical biomarkers_ Shimmer3_Step and stride length	Instruments: Inertial sensor (Accelerometer, Gyroscope, and Magnetometer) included in the Shimmer3 instrument.; Measure: Step and stride length	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Biomechanical biomarkers_ Shimmer3_Step and stride time	Instruments: Inertial sensor (Accelerometer, Gyroscope, and Magnetometer) included in the Shimmer3 instrument.; Measure: Step and stride time (seg)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Biomechanical biomarkers _ Shimmer3_Step and stride widths stride	Instruments: Inertial sensor (Accelerometer, Gyroscope, and Magnetometer) included in the Shimmer3 instrument.; Measure: Step and stride widths stride	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Biomechanical biomarkers _ Shimmer3_Swing phase time gait	Instruments: Inertial sensor (Accelerometer, Gyroscope, and Magnetometer) included in the Shimmer3 instrument.; Measure: Swing phase time gait	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Biomechanical biomarkers _ Shimmer3_Gait speed (m/s)	Instruments: Inertial sensor (Accelerometer, Gyroscope, and Magnetometer) included in the Shimmer3 instrument.; Measure: Gait speed (m/s)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Biomechanical biomarkers _ Shimmer3_Stance phase	Instruments: Inertial sensor (Accelerometer, Gyroscope, and Magnetometer) included in the Shimmer3 instrument.; Measure: Stance phase	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Biomechanical biomarkers _ Shimmer3_Step speed and stride.	Instruments: Inertial sensor (Accelerometer, Gyroscope, and Magnetometer) included in the Shimmer3 instrument.; Measure: Step speed and stride.	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Biomechanical biomarkers _ Shimmer3_Step symmetry	Instruments: Inertial sensor (Accelerometer, Gyroscope, and Magnetometer) included in the Shimmer3 instrument.; Measure: Step symmetry	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Imaging biomarkers _Cardiac-Echocardiogram (LVEF)	Instruments: Echocardiogram Measure:Left ventricular Ejection Fraction (%), LVEF	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Imaging biomarkers _Cardiac-Echocardiogram (Dilatation and Diameter of the left atrium and left ventricle)	Instruments: Echocardiogram Measure: Dilatation of the left atrium, Dilatation of the left ventricle, Diameter of the left atrium, Diameter of the left ventricle (cm)	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Imaging biomarkers _Muscular-Echocardiographic (Muscle Thickness)	Instruments: B-mode ultrasonography device (SonoSite 180 Plus, SonoSite Japan, Tokyo, Japan) Measure: Muscular thickness of the quadriceps rectus muscle ,the diaphragm muscle thickness obtained at the end of inspiration (at total lung capacity; DT-insp) and at resting expiration (at functional residual capacity; DT-exp) through Matlab software (CodigoEco)-[Muscle Thickness]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Imaging biomarkers _Displacement-Echocardiographic (Slide-pL)	Instruments: B-mode ultrasonography device (SonoSite 180 Plus, SonoSite Japan, Tokyo, Japan) Measure: Pleural displacement (Slide-pL, mm) during a complete respiratory cycle through Matlab software (CodigoEco)-[Slide-pL]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Imaging biomarkers_Muscular-Echocardiographic (Fat Thickness)	Instruments: B-mode ultrasonography device (SonoSite 180 Plus, SonoSite Japan, Tokyo, Japan) Measure: Fat thickness of the quadriceps rectus muscle through Matlab software (CodigoEco)-[Fat Thickness]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Imaging biomarkers_Muscular-Echocardiographic (Muscle Echo-Intensity)	Instruments: B-mode ultrasonography device (SonoSite 180 Plus, SonoSite Japan, Tokyo, Japan) Measure: Muscle Echo-intensity of the quadriceps rectus muscle through Matlab software (CodigoEco)- [Muscle His]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Imaging biomarkers_Muscular-Echocardiographic (Fat Echo-Intensity)	Instruments: B-mode ultrasonography device (SonoSite 180 Plus, SonoSite Japan, Tokyo, Japan) Measure: Fat Echo-intensity of the quadriceps rectus muscle through Matlab software (CodigoEco)- [Fat His]	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Self-reported_ Borg Rating of Perceived Exertion (RPE)-Borg Scale	Instruments: Borg Rating of Perceived Exertion (RPE)- Borg Scale Measure: The Borg Rating of Perceived Exertion (RPE) is a way of measuring physical activity intensity level. Perceived exertion is how hard you feel like your body is working. It is based on the physical sensations a person experiences during physical activity, including increased heart rate, increased respiration or breathing rate, increased sweating, and muscle fatigue. Although this is a subjective measure, your exertion rating based on a 6 to 20 rating scale, may provide a fairly good estimate of your actual heart rate during physical activity	Baseline, Post-intervention (12 weeks after baseline) and Follow up (12 weeks after post-intervention)
Secondary	Self-reported_Sarcopenia Questionnaire (SARC-F)	Instruments: SARC-F questionnaire Measure: It is a simple questionnaire to rapidly diagnose Sarcopenia. It is composed by 5 components: Strength, Assistance to walk, Get up from a chair, Climb stairs and Falls. Scores range from 0 to 10, with 0 to 2 points for each component. A score equal to or greater than 4 could predict sarcopenia and poor results.	Baseline, Post-intervention (12 weeks after baseline)
Secondary	Self-reported_abbreviated Comprehensive Geriatric Assessment (aCGA):	Instruments: abbreviated Comprehensive Geriatric Assessment (aCGA): a questionnaire formed by items originating from four different scales.; Measure: 4 instruments such as: the Geriatric Depression Scale (GDS),; the Mini-Mental State Examination (MMSE),; Activities of Daily Living (ADL) using the Katz index and instrumental activities of daily living (IADL) using the Lawnton & Brody scale.; The score varies from 0 to 30 points, giving 1 point to each of the items of the GDS (4 points in total), 12 to the 3 items from the scale of Lawton & Brody, 8 points to the 4 items from the MMSE and 6 points to the 3 items from the Katz index.	Baseline, Post-intervention (12 weeks after baseline)