NCT07501143

Effects of Physical Training in Patients With Advanced Heart Failure

To Evaluate Whether a Rehabilitation Protocol Improves Functional Status and Exercise Tolerance in Hospitalized Patients Awaiting Heart Transplantation While Receiving Positive Inotropic Support. Functional Tests and Scales Will be Used for Assessment. Patients Will Follow an 8-week Rehabilitation Program With Aerobic and Resistance Exercises Distributed Throughout the Week. A New Evaluation Will be Conducted at the End of the Intervention. Keywords: Heart Failure; Heart Transplantation; Physical Exercise

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 22 (estimated)
• Sponsor: University of Nove de Julho · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Heart failure is a condition where the heart cannot pump blood effectively. This can happen due to changes in the heart's structure or function, leading to symptoms like shortness of breath, fatigue, and reduced ability to exercise. These symptoms often worsen the patient's quality of life and increase hospital visits. Exercise is known to help people with heart failure by improving blood flow to the muscles and increasing physical strength. Starting exercise early, even during hospitalization, may help prevent the negative effects of being inactive and improve recovery. Some patients with advanced heart failure may need a heart transplant. While waiting for a transplant, these patients often receive intravenous medications to support heart function. However, they may become weaker and lose physical capacity during this time. This study will test whether a supervised exercise program during hospitalization can help improve physical ability and exercise tolerance in patients with advanced heart failure who are on the heart transplant waiting list and receiving intravenous medication. The goal is to help these patients stay stronger and more stable while they wait for a transplant.

Detailed description

Methods Type of Study This is a non-randomized clinical trial. Sample Size The primary objective of the study is to compare the results of the 6-Minute Walk Test (6MWT) before and after the intervention, using a single-arm design. The null hypothesis assumes no difference between pre- and post-intervention. The alternative hypothesis will test for differences of 20, 25, or 30 meters to calculate potential sample sizes. The analysis will consider the dependence between pre- and post-measurements, represented by a correlation coefficient of 0.5. The standard deviation will be based on the study by Forestieri (2016), which identified a value of 42.4. Assuming a Type I error rate of 5%, sample size estimates will be calculated according to the expected differences and statistical power, 22 patients Data Collection Data for this study will be obtained through an assessment form that includes epidemiological data, functional tests such as the 6-Minute Walk Test (6MWT) and Sit-to-Stand Test (TSL1), and evaluations including manovacuometry, dynamometry, bioimpedance, and the DEMMI (De Morton Mobility Index). Measurements of quadriceps muscle thickness will be performed using ultrasound. Endothelial function will be assessed by measuring brachial artery dilation following a brief period of forearm ischemia, also evaluated via ultrasound. Additional instruments include the Minnesota Living with Heart Failure Questionnaire to assess quality of life, the Feeling Scale to measure satisfaction during physical activity, and the Modified Borg Scale to assess perceived exertion. As an additional evaluation, a blood sample will be collected to assess oxidative stress. Data Collection Instruments Assessment Form The following variables will be collected: Full name Hospital registration number Age (in years) Sex (female, male, other) Race/ethnicity (Black, Brown, White, Indigenous, Asian) Religion Educational level Comorbidities (systemic arterial hypertension - SAH, dyslipidemia - DLP, diabetes mellitus - DM, chronic kidney disease - CKD, stroke - with or without sequelae) Etiology of heart failure Lifestyle habits and their frequency (smoking, alcohol consumption, physical activity prior to hospitalization) Weight (kg), height (m), body mass index (BMI in kg/m²) Physical examination components (heart rate, respiratory rate, peripheral oxygen saturation, blood pressure, Modified Borg Scale) Inotropic dosage used Hospitalization-related data will include: Length of hospital stay Use and duration of oxygen therapy Need and duration of invasive and/or non-invasive mechanical ventilation Use of intra-aortic balloon pump (IABP) Laboratory test values during hospitalization (urea, creatinine, brain natriuretic peptide - BNP) Left ventricular ejection fraction (LVEF) and pulmonary artery systolic pressure (PASP) from admission echocardiogram Data from manometry, cardiopulmonary exercise testing, and cardiac MRI when available 6-Minute Walk Test (6MWT) This submaximal test is used to assess functional capacity. The participant will be guided by a physical therapist, who will explain the procedure and its relevance to cardiopulmonary outcomes (ATS Statement, 2002). The patient will walk for 6 minutes along a 30-meter corridor in the unit. The following parameters will be measured before, during, and after the test: Blood pressure Heart rate Peripheral oxygen saturation Perceived dyspnea and fatigue using the Borg Scale (Cahalin et al., 1996) The primary outcome will be the distance walked in meters. To evaluate performance, the predicted distance will be calculated using the Enright \& Sherrill equations: Men and Women Performance levels will be categorized as follows: Level I: \>450 meters Level II: 300-450 meters Level III: \<300 meters (ATS Statement, 2002) Functional and Physiological Assessment Tools One-Minute Sit-to-Stand Test (TSL1): This test is used to assess functional capacity. It was adapted from the study by Ozalevli et al. (2007). Upon the examiner's signal, the participant must stand up and sit down on a chair without using their arms, repeating the movement as safely and quickly as possible. The goal is to perform the maximum number of repetitions within one minute. Manovacuometry: This test measures respiratory muscle strength through Maximum Inspiratory Pressure (MIP) and Maximum Expiratory Pressure (MEP), with results adjusted for sex and age. The evaluation is performed with the patient seated, knees at 90°, and spine upright. For MIP, the patient is instructed to exhale completely and then perform a sustained maximal inhalation. For MEP, the patient inhales maximally and then performs a sustained maximal exhalation. At least three attempts are performed or until a drop in measured value is observed. The highest value is selected and compared to reference values. Predicted values are calculated using the equations by Neder et al. (1999): Men: MIP = -0.80 × age + 155.3 MEP = -0.81 × age + 165.3 Women: MIP = -0.49 × age + 110.4 MEP = -0.61 × age + 115.6 The device used in this study will be the Digital Manovacuometer MVD300-U by Homed. Handgrip Strength (Manual Dynamometry): Handgrip strength is an isometric strength measure involving force exertion on an object. It is assessed using a digital handgrip dynamometer (Camry Digital Handgrip Dynamometer), which will be calibrated before each testing session to ensure accuracy. For the test, the patient will be seated with knees at 90°, spine upright, arms unsupported, shoulder in adduction and neutral rotation, elbow flexed at 90°, forearm in semi-pronation, and wrist in a neutral position on the dominant hand. After receiving instructions, the patient will apply force for 3 seconds. Three trials will be conducted, and the final value will be the average of the three attempts. Body Composition Assessment (Bioimpedance): Bioimpedance is a widely used and validated method across various populations. It is practical, reproducible, non-invasive, and clinically relevant-especially for evaluating fluid overload in hospitalized cardiac patients. The assessment will be performed using the Model 450 Biodynamics device. This equipment emits a low-intensity electrical current that travels through the patient's body and provides the following parameters: Resistance Reactance Phase angle Lean mass Fat mass Intracellular and extracellular water For the test, the patient will lie in a comfortable supine position, and four electrodes will be placed: two on the right foot and two on the right hand, being connected to the monitor via a sensor cable. (Oliveira et al., 2023). Peripheral Muscle Ultrasound Muscle assessment using ultrasound is a reliable and accurate technique, non-invasive and easily reproducible, performed bedside. It allows quantification of both the quantity and quality of a muscle group. The evaluation will be conducted using an ultrasound device with a linear transducer in B-mode. The patient will be positioned supine with knees extended and relaxed. The transducer will be placed longitudinally and transversely on the anterior margin of the thigh to measure muscle thickness, muscle echogenicity, cross-sectional area, and pennation angle. Reference points will be between the anterior superior iliac spine and the superior border of the patella (Azevedo et al., 2024; Toledo et al., 2017; Lima et al., 2020). Flow-Mediated Dilation (FMD) FMD is a non-invasive assessment of endothelial function using ultrasound. It measures brachial artery dilation following a temporary forearm ischemia. FMD reflects endothelium-dependent dilation of conduit arteries, largely mediated by nitric oxide (NO), in response to increased blood flow and shear stress. The patient will be positioned supine with the left upper limb abducted and forearm supinated. A cuff will be placed on the forearm distal to the brachial artery. The artery will be located via ultrasound and monitored for 1 minute. The cuff will then be inflated to 50 mmHg above baseline systolic pressure and maintained for 5 minutes. Upon rapid deflation, vasodilation will be assessed for 3 minutes. Shear stress activates endothelial cells, triggering NO production. Data will be analyzed using FMD Studio software (Niemeyer, 2024). Blood Collection for Oxidative Stress Analysis The enzymatic defense system includes enzymes that prevent or control the formation of free radicals and non-radical species released due to oxidative damage. These enzymes are essential for maintaining cellular integrity and antioxidant balance. Physical activity increases oxygen consumption, promoting oxidant production, but also triggers adaptive mechanisms that minimize oxidative damage. This adaptive response (elevated serum antioxidant levels) suggests a physiological adjustment to exercise. Blood samples will be collected for analysis in an external laboratory. One 6 mL heparinized tube will be used for plasma collection. Samples will be kept at room temperature if processed immediately or refrigerated for up to 48 hours. Preparation includes red blood cell washing, hemolysate preparation, and enzyme solution processing. Blood collection will occur during the initial evaluation and be performed by a single research nurse. Samples will be labeled and stored in the hospital lab, then sent to the Laboratory of the Research Incentive Fund Association at the Federal University of São Paulo (UNIFESP). Plasma will be analyzed for TBARS, carbonyls, FRAP, and nitrites; erythrocytes will be tested for SOD, CAT, and FRAP (Barbosa et al., 2010). Minnesota Living with Heart Failure Questionnaire (MLHFQ) This is a disease-specific quality of life scale for heart failure patients. It consists of 21 questions covering physical, emotional, and other domains that impact quality of life. Each item is scored from 0 (no limitation) to 5 (maximum limitation). The total score reflects overall quality of life, with lower scores indicating worse outcomes. The questionnaire will be administered at baseline and after eight weeks of exercise (Carvalho et al., 2009). Spirometry Spirometry is a pulmonary function test that measures the volume and flow of air entering and exiting the lungs. The device used will be the EasyOne model 2001, calibrated before each session per manufacturer specifications. Measurements will include Forced Expiratory Volume in one second (FEV1), Forced Vital Capacity (FVC), and the FEV1/FVC ratio. The test will be performed with the patient seated, elbows flexed, and wearing a nasal clip to prevent air leakage. The patient will be instructed to perform a maximal inhalation followed by a maximal forced exhalation. Three trials of six seconds each will be conducted, and the highest value will be recorded (Di Naso et al., 2011; Forgiarini Jr et al., 2007). De Morton Mobility Index (DEMMI) DEMMI is a mobility scale developed specifically for hospitalized patients. It assesses 15 hierarchical mobility activities divided into five categories: bed mobility, chair mobility, static balance, walking, and dynamic balance. Scoring is based on performance and whether assistance was required. Scores range from 0 (low mobility) to 100 (high mobility) (Tavares LS et al., 2020). Feeling Scale (FS) The Feeling Scale measures the self-perception of pleasure or displeasure during exercise using a single item. Participants respond on a scale from -5 (very bad) to +5 (very good), reflecting their perceived intensity and emotional response to the activity (Brito et al., 2022; Prado, Raul et al., 2021). Modified Borg Rating of Perceived Exertion (BORG) This tool monitors physical effort intensity and is widely used in both elite sports and physical rehabilitation. It evaluates and quantifies sensations of exertion, also known as RPE (Rate of Perceived Exertion). It helps track exercise-induced changes in the cardiorespiratory, metabolic, and neuromuscular systems (Zamunér et al., 2011; Williams, 2017). One-Repetition Maximum Test (1RM) The 1RM test dynamically assesses muscular strength. The participant performs a movement with the maximum load they can lift without assistance. A percentage of the 1RM value is used to define the rehabilitation protocol and guide load progression. In this study, load will increase every two weeks, starting at 10% of 1RM and progressing to 70% (Materko et al., 2007; Ramalho et al., 2011). Rehabilitation Protocol The rehabilitation protocol will be conducted from Monday to Friday, with one session per day. It includes resistance exercises, aerobic training, and respiratory muscle training, distributed throughout the week as follows: Monday and Thursday: Upper limb exercises and respiratory muscle training Tuesday and Friday: Lower limb exercises Wednesday: Aerobic training Each resistance exercise session will consist of 3 sets of 15 repetitions, with 1-minute rest intervals between sets. Upper limb exercises (performed bilaterally and in standing position) include: Elbow flexion Elbow extension Shoulder flexion up to 90° Shoulder elevation up to 90° Shoulder adduction and abduction Lower limb exercises (performed unilaterally) include: Triple flexion up to 90° (hip flexion + knee flexion + ankle dorsiflexion) Hip abduction Knee extension in seated position Calf raises Squats (performed in standing position) The adapted Borg Rating of Perceived Exertion Scale will be applied before, during, and after each session. Exercise load and progression will be adjusted based on the patient's reported Borg score. Aerobic Training Protocol Aerobic exercise will be performed through a functional circuit consisting of four stations: Stationary running Lateral marching Sit-to-stand chair training Step training (stepping up and down) Each station will last 1 minute, and the patient will complete two full rounds of the circuit, totaling 10 minutes of exercise, followed by a rest period. Respiratory Muscle Training Protocol Respiratory muscle training will be conducted twice per week using the POWERbreathe Classic device. The training load will be based on manovacuometry results, set at: 30% of maximal inspiratory pressure (MIP) during the first month 50% of MIP during the second month Training will be performed in a seated position with knees at 90° and the spine upright. The patient will inhale quickly and forcefully through the mouth, then exhale slowly through the mouth. The protocol includes 4 sets of 15 repetitions, with 30-second rest intervals between sets. Exercise Interruption Criteria Exercise sessions or functional tests (e.g., 6-minute walk test or sit-to-stand test) will be interrupted if the patient shows signs of exercise intolerance, such as: Low cardiac output (cyanosis, pallor, cold extremities, sweating, nausea) Bradycardia (drop of 20 bpm compared to baseline) Drop in systolic blood pressure \>15 mmHg from baseline Excessive rise in systolic blood pressure (\>200 mmHg) Rise in diastolic blood pressure during exercise (\>110 mmHg) Chest pain Risks and Benefits Benefits: This protocol aims to improve exercise tolerance, functional capacity, and muscle strength, helping patients maintain adequate physical condition for heart transplantation. Risks: Patients may experience muscle or joint pain typical of physical exercise, as well as fatigue during or after sessions. Data Collection Procedure Hospitalized patients who are on the heart transplant waiting list will be invited to participate in the study. Upon agreeing to participate, the researcher will provide the Informed Consent Form (ICF). After signing the form, patients will undergo an initial evaluation before beginning the rehabilitation protocol. The evaluation will be divided into two days: Day 1: Completion of the assessment form, application of the Minnesota Living with Heart Failure Questionnaire, DEMMI (De Morton Mobility Index), and Enjoyment Scale (FE). Additionally, the 6-Minute Walk Test (6MWT), spirometry, and manovacuometry will be performed. Day 2: Sit-to-Stand Test (TSL1), muscle strength assessment using dynamometry, body composition analysis via bioimpedance, quadriceps ultrasound, and flow-mediated dilation (FMD) measurement. After completing the evaluations, patients will begin the rehabilitation protocol, which will be conducted once daily for one hour. The protocol includes resistance and aerobic exercises distributed throughout the week. Exercise intensity will be moderate, ranging from 4 to 7 METs. After eight weeks of the rehabilitation program, patients will be re-evaluated using the same instruments applied during the initial assessment. Data Collection and Analysis Data Collection Procedure Hospitalized patients on the heart transplant waiting list will be invited to participate in the study. Upon agreeing to participate, the researcher will provide the Informed Consent Form (ICF). After signing the form, patients will undergo an initial evaluation before starting the rehabilitation protocol. The evaluation will be divided into two days: Day 1: Completion of the assessment form, application of the Minnesota Living with Heart Failure Questionnaire, DEMMI (De Morton Mobility Index), and Enjoyment Scale (FE), followed by the 6-Minute Walk Test (6MWT), spirometry, and manovacuometry. Day 2: Sit-to-Stand Test (TSL1), muscle strength assessment using dynamometry, body composition analysis via bioimpedance, quadriceps ultrasound, and flow-mediated dilation (FMD) measurement. After the evaluations, patients will begin the rehabilitation protocol, performed once daily for one hour. The protocol includes resistance and aerobic exercises distributed throughout the week. Exercise intensity will be moderate, ranging from 4 to 7 METs (see Annex VI). After eight weeks, patients will be re-evaluated using the same instruments. Statistical Analysis Statistical analysis will be performed using SPSS Statistical Package for the Social Sciences for Windows®, version 26.0 (SPSS Inc., Chicago, IL, USA). The level of statistical significance will be set at 5% (p \< 0.05). Data normality will be assessed using the Shapiro-Wilk test, with a significance level of α = 0.05. Epidemiological data will be presented in tables, with mean and standard deviation calculated for parametric variables, and median and interquartile range (25-75%) for non-parametric variables. To compare groups (pre- and post-intervention), the Student's t-test will be used for parametric variables, and the paired Wilcoxon test for non-parametric variables, with a significance level of p \< 0.05. Ethical Considerations All participants will receive detailed information about the procedures involved in the study. They will be guided through the process of signing two copies of the Informed Consent Form, one of which will remain with the participant.

Conditions

• Insuficiência Cardíaca
• Transplante Cardíaco
• Exercício Físico

Interventions

Type	Name	Description
OTHER	physical training	Protocol of aerobic and resistance exercises for patients with advanced heart failure on the heart transplant waiting list, and an evaluation of muscle strength, exercise tolerance, peripheral ultrasonography, and oxidative stress will be performed before and after completing 8 weeks of the protocol.

Timeline

• Start date: 2026-05-30
• Primary completion: 2026-06-30
• Completion: 2029-10-31
• First posted: 2026-03-30
• Last updated: 2026-04-08

Locations

1 site across 1 country: Brazil