Integrative Assessment of Cardiopulmonary Fitness Using Cardiopulmonary Exercise Test With Supine Bicycle Echocardiography in Patients Presenting Dyspnea.

BACKGROUND: Cardiopulmonary exercise test (CPET) with supine bicycle echocardiography (SBE) enables comprehensive physiologic assessment during exercise. We characterized cardiopulmonary fitness by integrating CPET-SBE parameters and evaluated its prognostic value in patients presenting with dyspnea. METHODS AND RESULTS: We retrospectively reviewed 473 consecutive patients who underwent CPET-SBE for dyspnea evaluation. A dimensionality reduction process was applied, transforming 24 clinical and CPET-SBE parameters into a 2-dimensional feature map, followed by patient clustering based on the data distribution. Clinical and exercise features were compared among the clusters in addition to the 5-year risk of clinical outcome (a composite of cardiovascular death and heart failure hospitalization). Maximum exercise effort (R >1) was achieved in 95% of cases. Through dimensionality reduction, 3 patient clusters were derived: Group 1 (n=157), 2 (n=104), and 3 (n=212). Median age and female proportion increased from Group 1 to 2, and 3, although resting echocardiography parameters showed no significant abnormalities among the groups. There was a worsening trend in the exercise response from Group 1 to 2 and 3, including left ventricular diastolic function, oxygen consumption, and ventilatory efficiency. During follow-up (median 6.0 [1.6-10.4] years), clinical outcome increased from Group 1 to 2 and 3 (5-year rate 3.7% versus 7.0% versus 13.0%, respectively; log-rank P=0.02), with higher risk in Group 2 (hazard ratio, 1.94 [95% CI, 0.52-7.22]) and Group 3 (3.92 [1.34-11.42]) compared with Group 1. CONCLUSIONS: Comprehensive evaluation using CPET-SBE can reveal distinct characteristics of cardiopulmonary fitness in patients presenting with dyspnea, potentially enhancing outcome prediction.

How to interpret a cardiorespiratory fitness assessment - Key measures that provide the best picture of health, disease status and prognosis.

Graded exercise testing is a widely accepted tool for revealing cardiac ischemia and/or arrhythmias in clinical settings. Cardiopulmonary exercise testing (CPET) measures expired gases during a graded exercise test making it a versatile tool that helps reveal underlying physiologic abnormalities that are in many cases only present with exertion. It also characterizes one's health status and clinical trajectory, informs the therapeutic plan, evaluates the efficacy of therapy, and provides submaximal and maximal information that can be used to tailor an exercise intervention. Practitioners can also modify the mode and protocol to allow individuals of all ages, fitness levels, and most disease states to perform a CPET. When used to its full potential, CPET can be a key tool used to optimize care in primary and secondary prevention settings.

SMART System in the Assessment of Exercise Tolerance in Adults.

Health-oriented physical activity should meet two key criteria: safety and an optimal level of exercise. The system of monitoring and rationalization of training (SMART) was designed to meet them. SMART integrates a custom-configured inertial measurement unit (IMU) and a sensor with real-time heart rate measurement (HR) using a proprietary computer application. SMART was used to evaluate the safety and exercise load with 115 study participants: 51 women (44.35%) and 64 men (55.65%) aged 19 to 65 years. The exercise test was the 6MWT test. In 35% of the participants, the mean HR exceeded the recognized safe limit of HR 75% max. Ongoing monitoring of HR allows for optimal exercise and its safety. Step count data were collected from the SMART system. The average step length was calculated by dividing the distance by the number of steps. The aim of the present study was to assess the risk of excessive cardiovascular stress during the 6MWT test using the SMART system.

Effects of Training on Running Cost and Aerobic Capacity in Individuals with Obesity.

This study investigated running cost (CRun), peak oxygen consumption (V̇ O2peak), and ventilatory threshold (VT1) responses to exercise programs for individuals with obesity. Ninety-four individuals (38.2±7.7 years; 33.4±2.9 kg/m²) were assigned into strength (n=24), endurance (n=26), combined (n=22), and physical activity (control, n=22) groups for 22 weeks, plus diet recommendation. The V̇ O2peak, VT1, and CRun were assessed through a maximal incremental step test. The change of V̇ O2peak in combined (9.9%) differed from the other groups, with lower values in women than men (0.7% vs. 6.2%). The VT1 change in combined (16.4%) differed from the strength (4.9%) and physical activity (1.2%) groups, with the change in endurance (12.7%) also being higher than the physical activity group. Only men in the combined group increased absolute V̇ O2peak, while both sexes increased VT1 in the endurance and combined groups. No effects for groups and sex were significant for CRun in moderate (VT1) running zones, despite CRun changes in VT1 zones correlated with the alterations of V̇ O2peak and VT1 (r²=0.29-0.59). Therefore, moderate aerobic exercise stimulus is suitable for VT1 improvement in individuals with obesity, with the increase in CRun associated to the chances of increasing V̇ O2peak in men and when combining strength with aerobic exercises.

Effects of plyometric- and cycle-based high-intensity interval training on body composition, aerobic capacity, and muscle function in young females: a field-based group fitness assessment.

High-intensity interval training (HIIT) is an effective alternative to moderate intensity continuous training for improvements in body composition and aerobic capacity; however, there is little work comparing different modalities of HIIT. The purpose of this study was to compare the effects of plyometric- (PLYO) and cycle-oriented (CYC) HIIT on body composition, aerobic capacity, and skeletal muscle size, quality, and function in recreationally trained females. Young (21.7 ± 3.1 yrs), recreationally active females were quasi-randomized (1:1 ratio) to 8 weeks of twice weekly PLYO (n = 15) or CYC (n = 15) HIIT. Body composition (four-compartment model), VO2peak, countermovement jump performance, muscle size, and echo intensity (muscle quality), as well as strength and power of the knee extensors and plantar flexors were measured before and after training. Both groups showed a similar decrease in body fat percentage (p < 0.001; η p 2   = 0.409) and echo intensity (p < 0.001; η p 2 = 0.558), and an increase in fat-free mass (p < 0.001; η p 2   = 0.367) and VO2peak (p = 0.001; η p 2 = 0.318). Muscle size was unaffected (p > 0.05), whereas peak torque was reduced similarly in both groups (p = 0.017; η p 2 = 0.188) and rapid torque capacity was diminished only for the knee extensors after CYC (p = 0.022; d = -0.67). These results suggest that PLYO and CYC HIIT are similarly effective for improving body composition, aerobic capacity, and muscle quality, whereas muscle function may express moderate decrements in recreationally active females. ClinicalTrials.gov (NCT05821504).

Prognostic Value of Pace Variability, a Novel 6MWT-Derived Feature, in Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The 6-minute walk test (6MWT) is often used to evaluate chronic obstructive pulmonary disease (COPD) patients' functional capacity, with 6-minute walk distance (6MWD) and related measures being linked to mortality and hospitalizations. This study investigates the prognostic value of pace variability, a significant indicator in sports medicine, during the 6MWT for COPD patients. Patients and Methods: We retrospectively screened consecutive COPD patients who had been prospectively enrolled in a pay-for-performance program from January 2019 to May 2020 to determine their eligibility. Patient characteristics, including demographics, exacerbation history, and 6MWT data, were analyzed to investigate their potential associations with prognosis. The primary outcome was a composite of adverse events, including overall mortality or hospitalizations due to exacerbations during a 1-year follow-up period. To analyze the 6MWT data, we divided it into three 2-minute epochs and calculated the average walk speed for each epoch. We defined pace variability as the difference between the maximum and minimum average speed in a single 2-minute epoch, divided by the average speed for the entire 6-minute walk test. Results: A total of 163 patients with COPD were included in the study, and 19 of them (12%) experienced the composite adverse outcome. Multivariable logistic regression analyses revealed that two predictors were independently associated with the composite outcome: % predicted 6MWD <72 (adjusted odds ratio [aOR] 7.080; 95% confidence interval [CI] 1.481-33.847) and pace variability ≥0.39 (aOR 9.444; 95% CI 2.689-33.170). Patients with either of these adverse prognostic features had significantly worse composite outcome-free survival, with both log-rank P values less than 0.005. Notably, COPD patients with both adverse features experienced an especially poor outcome after 1 year. Conclusion: Patients with COPD who exhibited greater pace variability during the 6MWT had a significantly higher risk of overall mortality and COPD-related hospitalizations, indicating a worse prognosis.

Pulmonary Rehabilitation in Persons With COPD.

Pulmonary rehabilitation (PR) is a high-value intervention for persons with COPD and other chronic lung diseases. It is associated with improvement in exercise capacity, dyspnea, health-related quality of life, and depression as well as a reduction in hospitalization and improved survival when PR follows COPD-related hospitalizations. PR is underused in the United States and other countries despite strong evidence of both clinical effectiveness and cost-effectiveness. Additional challenges include a lack of equitable reimbursement and poor access, particularly in rural settings. Models, for example, virtual PR, may be an option for improving access but coverage in the United States by Medicare is tenuous. In addition, virtual PR models have considerable heterogeneity, which challenges uniform efficacy and selection of optimal candidates.

Mobile Health Pulmonary Rehabilitation Compared to a Center-Based Program for Cost-Effectiveness and Effects on Exercise Capacity, Health Status, and Quality of Life in People With Chronic Obstructive Pulmonary Disease: A Protocol for a Randomized Controlled Trial.

OBJECTIVE: The use of digital health is a novel way to improve access to comprehensive pulmonary rehabilitation for people with chronic obstructive pulmonary disease (COPD). This study aims to determine if a home-based pulmonary rehabilitation program supported by mobile health (mHealth) technology is equivalent to center-based pulmonary rehabilitation in terms of improvements in exercise capacity and health status in people with COPD. METHODS: This study is a prospective, multicenter, equivalence randomized controlled trial (RCT) with intention-to-treat analysis. A hundred participants with COPD will be recruited from 5 pulmonary rehabilitation programs. Following randomization, participants will be assigned in a concealed manner to receive either home-based pulmonary rehabilitation supported by mHealth or center-based pulmonary rehabilitation. Both programs will be 8 weeks and will include progressive exercise training, disease management education, self-management support, and supervision by a physical therapist. Co-primary outcome measures will be the 6-Minute Walk Test and the COPD Assessment Test. Secondary outcome measures will include the St George's Respiratory Questionnaire, the EuroQol 5 Dimension 5 Level, the modified Medical Research Council dyspnea scale, the 1-minute sit-to-stand test, the 5 times sit-to-stand test, the Hospital Anxiety and Depression Scale, daily physical activity levels, health care utilization, and costs. Outcomes will be measured at baseline and at the end of the intervention. Participant experience will be assessed through semi-structured interviews at the end of the intervention. Utilization of health care and costs will be measured again after 12 months. IMPACT: This study will be the first rigorous RCT to examine the effects of a home-based pulmonary rehabilitation program supported by mHealth technology that includes comprehensive clinical outcome evaluation, assessment of daily physical activity, a health economic analysis, and qualitative analysis. If findings demonstrate that there is equivalence in clinical outcomes, that the mHealth program costs the least amount (and is thus cost-effective), and that the mHealth program is acceptable to participants, such programs should be widely implemented to improve access to pulmonary rehabilitation.

Assessment of exercise capacity using field walking tests in patients after the Fontan procedure: A case-control study.

BACKGROUND: Despite the frequent use of the 6-minute walk test (6MWT), exercise capacity has not been assessed with the incremental shuttle walk test (ISWT) in patients who have undergone the Fontan procedure. It is unclear whether these tests cause clinically relevant cardiorespiratory responses in these patients. OBJECTIVES: We aimed to assess cardiorespiratory responses to the 6MWT and ISWT in Fontan patients, compare the responses with those in the controls, and examine the agreement between the two field tests. METHODS: Submaximal exercise capacity was assessed using the 6MWT, maximal exercise capacity using the ISWT, quadriceps isometric muscle strength with a hand dynamometer, and body composition using a bioelectrical impedance device. RESULTS: Twenty-one Fontan patients (16.42±6.63 years, 5F/16M) and 21 controls (16.57±4.30 years, 7F/14M) were included. While body composition was similar between the groups (p>0.05), quadriceps isometric muscle strength and 6MWT and ISWT distance were lower in the Fontan patients than in the controls (p<0.05). In both the 6MWT and ISWT, pre- and post-test heart rate (HR), oxygen saturation (SpO2), dyspnea, and leg fatigue differed significantly between the Fontan patients and the controls (p<0.05). In addition, the ISWT resulted in a more significant change in HR, SpO2, and leg fatigue than the 6MWT in the Fontan patients (p<0.05). Bland-Altman plots for the 6MWT vs. the ISWT indicated agreement between the two tests. CONCLUSION: There were remarkable changes in HR, SpO2, dyspnea, and leg fatigue in both tests. With similar safety to the 6MWT but with more caution applied for adverse events, the ISWT can also be performed as a field test to evaluate exercise capacity and identify more pronounced exercise-induced responses (especially oxygen desaturation) in Fontan patients.

Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.

Supervised Exercise Training for Chronic Heart Failure With Preserved Ejection Fraction: A Scientific Statement From the American Heart Association and American College of Cardiology.

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.

The Relationship between Exertional Desaturation and Pulmonary Function, Exercise Capacity, or Medical Costs in Chronic Obstructive Pulmonary Disease Patients.

Background and Objectives: Exertional desaturation (ED) is common and is associated with poorer clinical outcomes in chronic obstructive pulmonary disease (COPD). The age, dyspnea, airflow obstruction (ADO) and body mass index, airflow obstruction, dyspnea, and exercise (BODE) indexes are used to predict the prognosis of COPD patients. This study aimed to investigate the relationship between these indexes, pulmonary function, medical costs, and ED in COPD patients. Materials and Methods: Data were collected from the electronic database of the Kaohsiung Chang Gung Memorial Hospital. This retrospective study included 396 patients categorized as either ED (n = 231) or non-ED (n = 165). Variables (including age, smoking history, body mass index (BMI), pulmonary function test, maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP), six minutes walking test distance (6MWD), SpO2, COPD Assessment Test (CAT) score, ADO index, BODE index, Charlson comorbidity index (CCI), and medical costs) were compared between the two groups, and their correlations were assessed. ED was defined as SpO2 less than 90% or SpO2 decrease of more than 4% compared to baseline levels during 6MWT. Results: A significant statistical difference was found regarding a lower score of the ADO index and the BODE index (both p < 0.001), better pulmonary function (forced expiratory volume in the first second (FEV1), p < 0.001; FEV1/ forced vital capacity (FVC), p < 0.001; diffusion capacity of the lung for carbon monoxide (DLCO), p < 0.001), and higher minimal oxygen saturation (p < 0.001) in non-ED COPD patients. No difference was found in the distance of the 6MWT (p = 0.825) and respiratory muscle strength (MIP; MEP, p = 0.86; 0.751). However, the adjusted multivariate logistic regression analysis showed that only SpO2 (minimal) had a significant difference between of the ED and non-ED group (p < 0.001). There was either no difference in the medical expenses between ED and non-ED COPD patients. Conclusions: SpO2 (minimal) during the 6MWT is the independent factor for ED. ED is related to BODE and ADO indices, but is not related to medical expense.

A Case for Unifying Accelerometry-Derived Movement Behaviors and Tests of Exercise Capacity for the Assessment of Relative Physical Activity Intensity.

Albert Einstein taught us that "everything is relative." People's experience of physical activity (PA) is no different, with "relativism" particularly pertinent to the perception of intensity. Markers of absolute and relative intensities of PA have different but complimentary utilities, with absolute intensity considered best for PA guideline adherence and relative intensity for personalized exercise prescription. Under the paradigm of exercise and PA as medicine, our Technical Note proposes a method of synchronizing accelerometry with the incremental shuttle walking test to facilitate description of the intensity of the free-living PA profile in absolute and relative terms. Our approach is able to generate and distinguish "can do" or "cannot do" (based on exercise capacity) and "does do" or "does not do" (based on relative intensity PA) classifications in a chronic respiratory disease population, facilitating the selection of potential appropriate individually tailored interventions. By synchronizing direct assessments of exercise capacity and PA, clearer insights into the intensity of PA performed during everyday life can be gleaned. We believe the next steps are as follows: (1) to determine the feasibility and effectiveness of using relative and absolute intensities in combination to personalize the approach, (2) to determine its sensitivity to change following interventions (eg, exercise-based rehabilitation), and (3) to explore the use of this approach in healthier populations and in other long-term conditions.

Assessment of Exercise Capacity of Individuals with Long COVID: A Cross-sectional Study.

BACKGROUND: Clinical investigations of long-term effects of coronavirus disease 2019 (COVID-19) are rarely translated to objective findings. OBJECTIVES: To assess the functional capacity of individuals reported on deconditioning that hampered their return to their pre-COVID routine. METHODS: Assessment included the 6-minute walk test (6MWT) and the 30-second sit-to-stand test (30-STST). We compared the expected and observed scores using the Wilcoxon signed-rank test. Predictors of test scores were identified using linear regression models. RESULTS: We included 49 individuals, of whom 38 (77.6%) were recovering from mild COVID-19. Twenty-seven (55.1%) individuals had a 6MWT score lower than 80% of expected. The average 6MWT scores were 129.5 ± 121.2 meters and 12.2 ± 5.0 repeats lower than expected scores, respectively (P < 0.001 for both). The 6MWT score was 107.3 meters lower for individuals with severe COVID-19 (P = 0.013) and rose by 2.7 meters per each 1% increase in the diffusing capacity of carbon monoxide (P = 0.007). The 30-STST score was 3.0 repeats lower for individuals who reported moderate to severe myalgia (P = 0.038). CONCLUSIONS: Individuals with long COVID who report on deconditioning exhibit significantly decreased physical capacity, even following mild acute illness. Risk factors include severe COVID-19 and impaired diffusing capacity or myalgia during recovery.

The COPD assessment test and the modified Medical Research Council scale are not equivalent when related to the maximal exercise capacity in COPD patients.

INTRODUCTION: The management and treatment of Chronic Obstructive Pulmonary Disease (COPD) are based on a cutoff point either of ≥ 10 on the COPD Assessment Test (CAT) or of ≥ 2 of the Medical Research Council (mMRC). Up to now, no study has assessed the equivalence between CAT and mMRC, as related to exercise tolerance in COPD. The aim of this study was to investigate as primary outcome the relationship between CAT and mMRC and maximal exercise capacity in COPD patients. We also evaluated as secondary outcome the agreement between CAT (≥ 10) and mMRC (≥ 2) to categorize patients according to their exercise tolerance. MATERIAL AND METHODS: 118 consecutive COPD patients (39 females), aged between 47 and 85 years with a wide range of airflow obstruction and lung hyperinflation were studied. Maximal exercise capacity was assessed by cardiopulmonary exercise test. RESULTS: CAT and mMRC scores were significantly related to VO2 peak (p<0.01). CAT (≥ 10) and mMRC (≥ 2) have a high likelihood to be associated to a value of VO2 peak less than 15.7 and 15.6 mL/kg/min, respectively. The interrater agreement between CAT (≥ 10) and mMRC (≥ 2) was found to be fair (κ = 0.20) in all patients but slight when they were subdivided in those with VO2 peak < 15 mL/kg/min and in those with VO2 peak ≥ 15 mL/kg/min (κ = 0.10 and κ = 0.20 respectively). CONCLUSION: This study shows that CAT and mMRC are useful tools to predict exercise tolerance in COPD, but they cannot be considered as supplementary measures.

Assessment of respiratory function and exercise tolerance at 4-6 months after COVID-19 infection in patients with pneumonia of different severity.

BACKGROUND: The evaluation of COVID-19 systemic consequences is a wide research field in which respiratory function assessment has a pivotal role. However, the available data in the literature are still sparse and need further strengthening. AIM: To assess respiratory function 4-6 months after hospital discharge based on lung disease severity in patients who overcome COVID-19 pneumonia. METHODS: Patients hospitalised either in the Internal Medicine Department (IMD) for moderate to severe disease or in the Intensive Care Unit (ICU) for critical disease underwent spirometry with maximal flow-volume curve, lung volumes, lung diffusion capacity (DLCO ) and six-minute walking test (6-MWT). RESULTS: Eighty-eight patients were analysed: 40 from the IMD and 48 from the ICU. In both cohorts, there was a greater prevalence of male patients. In the IMD cohort, 38% of patients showed at least one altered respiratory parameter, while 62% in the ICU cohort did so (P < 0.05). Total lung capacity (TLC) and DLCO were the most frequently altered parameters: 15% and 33% from IMD versus 33% and 56% from ICU, respectively (P < 0.05). In IMD patients, 5% had only restrictive deficit, 22% had only lung diffusion impairment and 10% had both. In ICU patients, 6% had only restrictive deficit, 29% had only lung diffusion impairment and 27% had both (P < 0.05). ICU patients showed a higher frequency of abnormal 6-MWT (P < 0.05). CONCLUSION: Lung function tests and 6-MWT are highly informative tools for monitoring the negative consequences of COVID-19 pneumonia, which were more frequent and more complex in patients discharged from ICU.

A Methodological Perspective on the Function and Assessment of Peripheral Chemoreceptors in Heart Failure: A Review of Data from Clinical Trials.

Augmented peripheral chemoreceptor sensitivity (PChS) is a common feature of many sympathetically mediated diseases, among others, and it is an important mechanism of the pathophysiology of heart failure (HF). It is related not only to the greater severity of symptoms, especially to dyspnea and lower exercise tolerance but also to a greater prevalence of complications and poor prognosis. The causes, mechanisms, and impact of the enhanced activity of peripheral chemoreceptors (PChR) in the HF population are subject to intense research. Several methodologies have been established and utilized to assess the PChR function. Each of them presents certain advantages and limitations. Furthermore, numerous factors could influence and modulate the response from PChR in studied subjects. Nevertheless, even with the impressive number of studies conducted in this field, there are still some gaps in knowledge that require further research. We performed a review of all clinical trials in HF human patients, in which the function of PChR was evaluated. This review provides an extensive synthesis of studies evaluating PChR function in the HF human population, including methods used, factors potentially influencing the results, and predictors of increased PChS.