Effects of Physical Training in Patients With Advanced Heart Failure

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.