Comparable Ventilatory Inefficiency at Maximal and Submaximal Performance in COPD vs. CHF subjects: An Innovative Approach. / Ineficiência Ventilatória Comparável no Desempenho Máximo e Submáximo em Indivíduos com DPOC e ICC: Uma Abordagem Inovadora.

BACKGROUND: Currently, excess ventilation has been grounded under the relationship between minute-ventilation/carbon dioxide output ( V ˙ E - V ˙ CO 2 ). Alternatively, a new approach for ventilatory efficiency ( η E V ˙ ) has been published. OBJECTIVE: Our main hypothesis is that comparatively low levels of η E V ˙ between chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are attainable for a similar level of maximum and submaximal aerobic performance, conversely to long-established methods ( V ˙ E - V ˙ CO 2 slope and intercept). METHODS: Both groups performed lung function tests, echocardiography, and cardiopulmonary exercise testing. The significance level adopted in the statistical analysis was 5%. Thus, nineteen COPD and nineteen CHF-eligible subjects completed the study. With the aim of contrasting full values of V ˙ E - V ˙ CO 2 and η V ˙ E for the exercise period (100%), correlations were made with smaller fractions, such as 90% and 75% of the maximum values. RESULTS: The two groups attained matched characteristics for age (62±6 vs. 59±9 yrs, p>.05), sex (10/9 vs. 14/5, p>0.05), BMI (26±4 vs. 27±3 Kg m2, p>0.05), and peak V ˙ O 2 (72±19 vs. 74±20 %pred, p>0.05), respectively. The V ˙ E - V ˙ CO 2 slope and intercept were significantly different for COPD and CHF (27.2±1.4 vs. 33.1±5.7 and 5.3±1.9 vs. 1.7±3.6, p<0.05 for both), but η V ˙ E average values were similar between-groups (10.2±3.4 vs. 10.9±2.3%, p=0.462). The correlations between 100% of the exercise period with 90% and 75% of it were stronger for η V ˙ E (r>0.850 for both). CONCLUSION: The η V ˙ E is a valuable method for comparison between cardiopulmonary diseases, with so far distinct physiopathological mechanisms, including ventilatory constraints in COPD.

FUNDAMENTO: Atualmente, o excesso de ventilação tem sido fundamentado na relação entre ventilação-minuto/produção de dióxido de carbono ( V ˙ E − V ˙ CO 2 ). Alternativamente, uma nova abordagem para eficiência ventilatória ( η E V ˙ ) tem sido publicada. OBJETIVO: Nossa hipótese principal é que níveis comparativamente baixos de η E V ˙ entre insuficiência cardíaca crônica (ICC) e doença pulmonar obstrutiva crônica (DPOC) são atingíveis para um nível semelhante de desempenho aeróbico máximo e submáximo, inversamente aos métodos estabelecidos há muito tempo (inclinação V ˙ E − V ˙ CO 2 e intercepto). MÉTODOS: Ambos os grupos realizaram testes de função pulmonar, ecocardiografia e teste de exercício cardiopulmonar. O nível de significância adotada na análise estatística foi 5%. Assim, dezenove indivíduos elegíveis para DPOC e dezenove indivíduos elegíveis para ICC completaram o estudo. Com o objetivo de contrastar valores completos de V ˙ E − V ˙ CO 2 e η E V ˙ para o período de exercício (100%), correlações foram feitas com frações menores, como 90% e 75% dos valores máximos. RESULTADOS: Os dois grupos tiveram características correspondentes para a idade (62±6 vs 59±9 anos, p>.05), sexo (10/9 vs 14/5, p>0,05), IMC (26±4 vs 27±3 Kg m2, p>0,05), e pico V ˙ O 2 (72±19 vs 74±20 % pred, p>0,05), respectivamente. A inclinação V ˙ E − V ˙ CO 2 e intercepto foram significativamente diferentes para DPOC e ICC (207,2±1,4 vs 33,1±5,7 e 5,3±1,9 vs 1,7±3,6, p<0,05 para ambas), mas os valores médios da η E V ˙ foram semelhantes entre os grupos (10,2±3,4 vs 10,9±2,3%, p=0,462). As correlações entre 100% do período do exercício com 90% e 75% dele foram mais fortes para η E V ˙ (r>0,850 para ambos). CONCLUSÃO: A η E V ˙ é um método valioso para comparação entre doenças cardiopulmonares, com mecanismos fisiopatológicos até agora distintos, incluindo restrições ventilatórias na DPOC.

Effect of body mass index on exercise capacity following pediatric heart transplantation.

BACKGROUND: Obesity and impaired exercise tolerance following heart transplantation increase the risk of post-transplant morbidity and mortality. The aim of this study was to evaluate the effect of body mass index on markers of exercise capacity in pediatric heart transplant recipients and compare this effect with a healthy pediatric cohort. METHODS: A retrospective analysis of cardiopulmonary exercise test data between 2004 and 2022 was performed. All patients exercised on a treadmill using the Bruce protocol. Inclusion criteria included patients aged 6-21 years, history of heart transplantation (transplant cohort) or no cardiac diagnosis (control cohort) at the time of testing, and a maximal effort test. Patients were further stratified within these two cohorts as underweight, normal, overweight, and obese based on body mass index groups. Two-way analyses of variance were performed with diagnosis and body mass index category as the independent variables. RESULTS: A total of 250 exercise tests following heart transplant and 1963 exercise tests of healthy patients were included. Heart transplant patients across all body mass index groups had higher resting heart rate and lower maximal heart rate, heart rate recovery at 1 min, exercise duration, and peak aerobic capacity (VO2peak). Heart transplant patients in the normal and overweight body mass index categories had higher VO2peak and exercise duration when compared to underweight and obese patients. CONCLUSION: Underweight status and obesity are strongly associated with lower VO2peak and exercise duration in heart transplant patients. Normal and overweight heart transplant patients had the best markers of exercise capacity.

High-intensity exercise training using a rotarod instrument (RotaHIIT) significantly improves exercise capacity in mice.

Voluntary or forced exercise training in mice is used to assess functional capacity as well as potential disease-modifying effects of exercise over a range of cardiovascular disease phenotypes. Compared to voluntary wheel running, forced exercise training enables precise control of exercise workload and volume, and results in superior changes in cardiovascular performance. However, the use of a shock grid with treadmill-based training is associated with stress and risk of injury, and declining compliance with longer periods of training time for many mouse strains. With these limitations in mind, we designed a novel, high-intensity interval training modality (HIIT) for mice that is carried out on a rotarod. Abbreviated as RotaHIIT, this protocol establishes interval workload intensities that are not time or resource intensive, maintains excellent training compliance over time, and results in improved exercise capacity independent of sex when measured by treadmill graded exercise testing (GXT) and rotarod specific acceleration and endurance testing. This protocol may therefore be useful and easily implemented for a broad range of research investigations. As RotaHIIT training was not associated cardiac structural or functional changes, or changes in oxidative capacity in cardiac or skeletal muscle tissue, further studies will be needed to define the physiological adaptations and molecular transducers that are driving the training effect of this exercise modality.

Changes in physical activity in people with idiopathic pulmonary fibrosis before and after virtual pulmonary rehabilitation: a feasibility study.

BACKGROUND: Pulmonary rehabilitation (PR) is recommended for the treatment of people with idiopathic pulmonary fibrosis (IPF). Physical activity is an important health behaviour, closely linked to survival in people with IPF. Little is known about the impact of virtual (V) PR on physical activity in people with IPF. OBJECTIVE: To explore the feasibility of conducting a trial to explore effect of virtual PR on objectively measured physical activity in people with IPF. METHODS: All patients with a diagnosis of IPF in a stable phase of the disease were invited to participate in VPR: a 10 week exercise programme delivered twice-weekly for one hour. Data were collected at baseline (BL) and post VPR (10 weeks): Kings Brief Interstitial Lung Disease (K-BILD), Exercise capacity (6-minute walk test (6MWT) or 1-minute sit-to-stand (STS)) and Physical Activity. Physical activity was measured with a triaxial accelerometer for seven days. Screening, recruitment, adherence and safety data were collected. RESULTS: 68 people were screened for this study. N = 16 participants were recruited to the study. There was one dropout. N = 15 completed VPR. All results reported in mean (standard deviation) (SD). Participants attended 18.1(2.0) of the 20 sessions. No adverse events were detected. The mean age of participants was 71.5(11.5) years, range: 47-95 years; 7 M:9 F. Mean (SD) FEV1 2.3(0.3)L, FVC 2.8(0.7)L. No statistically significant changes were observed in outcome measures apart from exercise capacity. Light physical activity increased from 152(69.4) minutes per day (n = 16) to 161.9(88.7) minutes per day (n = 14), mean change (SD) (CI) p-value: 9.9 (39.8) [-12.3 to 30.9] p = 0.4. Moderate-to-vigorous physical activity increased from 19.1(18.6) minutes per day (n = 16) to 25.7(28.3) minutes per day (n = 14), mean change (SD) (CI) p-value: 6.7 (15.5) [-2.1 to 15.1] p = 0.1. Step count increased from 3838(2847) steps per day (n = 16) to 4537(3748) steps per day (n = 14), mean change (SD) (CI) p-value: 738 (1916) [-419.3 to 1734.6] p = 0.2. K-BILD (n = 15) increased from 55.1(7.4) at BL to 55.7(7.9) post VPR mean change (SD) [95% confidence interval] (CI) p-value: 1.7(6.5) [-1.7 to 5.3], p = 0.3. 6MWT (n = 5) increased from 361.5(127.1) to 452.2(136.1) meters, mean change (SD) (CI) p-value: 63.7 (48.2) [-3.8 to 123.6], p = 0.04 and 1-minute STS increased from 17.6(3.0) (n = 11) to 23.7(6.3) (n = 10), mean change (SD) (CI) p-value 5.8 (4.6) [2.6 to 9.1], p = 0.003. CONCLUSION: VPR can improve physical activity in people with IPF. A number of important feasibility issues included recruitment, retention, adherence and safety have been reported which are crucial for future research in this area. A fully powered trial is needed to determine the response of people with IPF to PR with regard to physical activity.

Re-evaluating the Need for Routine Maximal Aerobic Capacity Testing within Fighter Pilots.

INTRODUCTION: There is a current belief in aviation suggesting that aerobic training may reduce G-tolerance due to potential negative impacts on arterial pressure response. Studies indicate that increasing maximal aerobic capacity (V˙o2 max) through aerobic training does not hinder G-tolerance. Moreover, sustained centrifuge training programs revealed no instances where excessive aerobic exercise compromised a trainee's ability to complete target profiles. The purpose of this review article is to examine the current research in the hope of establishing the need for routine V˙o2-max testing in air force pilot protocols.METHODS: A systematic search of electronic databases including Google Scholar, PubMed, the Aerospace Medical Association, and Military Medicine was conducted. Keywords related to "human performance," "Air Force fighter pilots," "aerobic function," and "maximal aerobic capacity" were used in various combinations. Articles addressing exercise physiology, G-tolerance, physical training, and fighter pilot maneuvers related to human performance were considered. No primary data collection involving human subjects was conducted; therefore, ethical approval was not required.RESULTS: The V˙o2-max test provides essential information regarding a pilot's ability to handle increased Gz-load. It assists in predicting G-induced loss of consciousness by assessing anti-G straining maneuver performance and heart rate variables during increased G-load.DISCUSSION: V˙o2-max testing guides tailored exercise plans, optimizes cardiovascular health, and disproves the notion that aerobic training hampers G-tolerance. Its inclusion in air force protocols could boost readiness, reduce health risks, and refine training for fighter pilots' safety and performance. This evidence-backed approach supports integrating V˙o2-max testing for insights into fitness, risks, and tailored exercise.Zeigler Z, Acevedo AM. Re-evaluating the need for routine maximal aerobic capacity testing within fighter pilots. Aerosp Med Hum Perform. 2024; 95(5):273-277.

Effects of Ninjin'yoeito on Patients with Chronic Obstructive Pulmonary Disease and Comorbid Frailty and Sarcopenia: A Preliminary Open-Label Randomized Controlled Trial.

Purpose: To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured. Results: VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin'yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively). Conclusion: Overall, Ninjin'yoeito significantly improved patients' quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin'yoeito may improve frailty and sarcopenia in patients with COPD.

The acute effect of inhaled nitric oxide on the exercise capacity of patients with advanced interstitial lung disease: a randomized controlled trial.

BACKGROUND: Inhaled nitric oxide (iNO) selectively acts on the pulmonary vasculature of ventilated lung tissue by reducing pulmonary vascular resistance and intrapulmonary shunt. This effect may reduce ventilation/perfusion mismatch and decrease pulmonary hypertension in patients with interstitial lung disease. METHODS: In a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests (6MWT): one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension. RESULTS: Overall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265-409) vs 371 m (IQR 250-407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWT distance with iNO and placebo, median 339 (256-402) vs 332 (238-403) for the iNO and placebo tests respectively (P=0.50). No correlation was observed between mean pulmonary artery pressure values and the change in 6MWT distance with iNO versus placebo (spearman correlation Coefficient 0.24, P=0.33). CONCLUSION: In patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects. TRIAL REGISTRATION: (NCT03873298, MOH_2018-04-24_002331).

Effects of nordic walking training on gait and exercise tolerance in male ischemic heart disease patients.

This technique-focused observational study explores the impact of a 6-week Nordic Walking (NW) program on physiological and biomechanical aspects in ischemic heart disease (IHD) patients. Twelve male IHD patients (66.2 ± 5.2 years, 12.2 ± 7.5 years of disease duration) were evaluated pre- and post-training for (i) gait parameters, (ii) exercise tolerance using electrocardiographic (ECG) stress test, (iii) a 6-min walk test (6MWT). The NW training, adhering to IHD patient guidelines, involved a 100-m walk at a self-selected, preferred speed without sticks, with classic NW sticks and mechatronic sticks. A mechatronic measuring system, specifically engineered for measuring, diagnosing and monitoring the patient's gait, was integrated into mechatronic sticks. Post-training, significant enhancements were observed in ECG stress test duration, metabolic equivalency, and 6MWT distance, irrespective of the stick type. However, no significant changes were noted in spatiotemporal parameters concerning the measured side, stick utilisation, or type. The results suggest that NW training boosts exercise capacity and refines gait mechanics in male IHD patients. However, the improvement in exercise capacity was not linked to changes in gait mechanics from NW training but rather to the movement during NW gait. Hence, the key to enhancing exercise capacity in IHD patients is the movement during NW gait, not the quality of gait mechanics.

Chronotropic incompetence is associated with reduced aerobic conditioning and sedentary behavior in patients with post-acute COVID-19 syndrome.

Post-acute COVID-19 syndrome, or long COVID, presents with persistent symptoms, including cough, dyspnea, and fatigue, extending beyond one month after SARS-CoV-2 infection. Cardiac complications such as chest pain and arrhythmias have raised concerns, with chronotropic incompetence (CI), an inadequate heart rate increase during exercise, emerging as a significant condition contributing to diminished exercise tolerance and quality of life. This study estimated the prevalence of CI and explored its association with aerobic capacity and physical activity levels in long COVID patients. A cross-sectional study was conducted at a private hospital in Sergipe, Brazil, involving 93 patients over 18 years old with persistent post-COVID-19 symptoms after confirmed SARS-CoV-2 infections. Exclusion criteria included beta-blocker use, inadequate respiratory exchange ratio, and inability to complete cardiopulmonary exercise testing (CPET). Clinical histories, CPET results, and chronotropic index calculation were used to identify CI, with logistic regression analyzing associated factors. Of the participants (mean age 45 years; average duration since COVID-19 diagnosis 120 days), 20.4% were diagnosed with CI. Logistic regression identified a strong association between CI and sedentary behavior (OR 11.80; 95% CI 2.54 to 54.78; p=0.001). Patients with CI showed lower predicted peak heart rates and maximal oxygen uptake. The prevalence of CI among long COVID patients in this study was approximately 20%, associated with decreased aerobic capacity and increased sedentary behavior. These findings highlight the need for timely diagnosis and therapeutic interventions, including cardiopulmonary rehabilitation, to enhance the quality of life in post-COVID patients with CI. The study's cross-sectional design and its specific context have limited causality inference and generalizability, underscoring the importance of further research in diverse settings.

Cardiac diastolic maladaptation is associated with the severity of exercise intolerance in sickle cell anemia patients.

This pilot study focusing on Sickle Cell Anemia (SCA) patients offers a comprehensive and integrative evaluation of respiratory, cardiovascular, hemodynamic, and metabolic variables during exercise. Knowing that diastolic dysfunction is frequent in this population, we hypothesize that a lack of cardiac adaptation through exercise might lead to premature increase in blood lactate concentrations in SCA patients, a potential trigger for acute disease complication. SCA patients were prospectively included in PHYSIO-EXDRE study and underwent a comprehensive stress test with a standardized incremental exercise protocol up to 4 mmol L-1 blood lactate concentration (BL4). Gas exchange, capillary lactate concentration and echocardiography were performed at baseline, during stress test (at ∼ 2 mmol L-1) and BL4. The population was divided into two groups and compared according to the median value of percentage of theoretical peak oxygen uptake (% V ˙ O 2 p e a k t h ) at BL4. Twenty-nine patients were included (42 ± 12 years old, 48% of women). Most patients reached BL4 at low-intensity exercise [median value of predicted power output (W) was 37%], which corresponds to daily life activities. The median value of % V ˙ O 2 p e a k t h at BL4 was 39%. Interestingly, diastolic maladaptation using echocardiography during stress test along with hemoglobin concentration were independently associated to early occurrence of BL4. As BL4 occurs for low-intensity exercises, SCA patients may be subject to acidosis-related complications even during their daily life activities. Beyond assessing physical capacities, our study underlines that diastolic maladaptation during exercise is associated with an early increase in blood lactate concentration.

Efficacy and safety of semaglutide in patients with heart failure with preserved ejection fraction and obesity.

BACKGROUND: Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has shown promise in weight management and cardiovascular outcomes in other populations. This study aimed to evaluate the efficacy of semaglutide in heart failure with preserved ejection fraction (HFpEF) patients with obesity. METHODS: A retrospective study analyzed 318 patients with HFpEF, of which 104 received semaglutide and 214 received placebo. Primary endpoints included evaluating changes in exercise capacity and weight management. RESULTS: Semaglutide treatment led to significant improvements in the primary endpoints. Patients in the semaglutide group demonstrated substantial enhancements in exercise capacity, as measured by the 6-min walk distance, compared to the placebo group (mean difference 15.1 meters, 95% CI 5.8 to 24.4, p = 0.002). Additionally, semaglutide resulted in substantial weight loss compared to placebo (mean difference -2.9%, 95% CI -4.1--1.7, p = 0.001). Several secondary endpoints, including reductions in C-reactive protein levels and improvements in other clinical parameters, further supported the efficacy of semaglutide. Adverse events were generally well-tolerated, with no unexpected safety concerns. CONCLUSION: Semaglutide demonstrated significant clinical benefits in HFpEF patients with obesity, as evidenced by improved symptoms, physical function, and weight reduction.

Predicting the effects of surgically determined parameters on exercise tolerance in Fontan patients.

The Fontan physiology is a surgically created circulation for patients with a single functioning ventricle. Patients with this circulation tend to have lower exercise tolerance compared to those with a normal circulation. Important computational and experimental work has been done to investigate this reduction in exercise tolerance. However, there are few systematic modeling studies that focus on the effect of several surgically determined parameters within the same framework. We propose a mathematical model to describe the Fontan circulation under exercise. We then formulate a heuristic based on clinical data from Fontan patients to estimate exercise tolerance. The model is used to investigate the effect of three important surgically determined parameters on exercise tolerance: the systemic arterial compliance, the systemic-venous to pulmonary-venous fenestration, and the resistance of the total cavopulmonary connection.

Oxygen therapy for exercise capacity in fibrotic interstitial lung disease: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Fibrotic interstitial lung disease (fILD) is characterised primarily by impaired lung function and quality of life. The present study investigated whether oxygen therapy could improve exercise capacity among patients with fILD. METHODS: Previously published randomised controlled trials (RCTs) were surveyed. A systematic review and meta-analysis was conducted to evaluate the effectiveness of oxygen therapy in improving the exertional capacity of patients with fILD. The primary outcome was peripheral oxygen saturation (SpO2) during exercise. The effects of oxygen therapy on fatigue, dyspnoea, heart rate, and exercise duration or distance were also analysed. RESULTS: Fourteen RCTs involving 370 patients were included. Oxygen therapy improved SpO2 during exercise (mean difference, MD = 6.26 %), exercise duration (MD = 122.15 s), fatigue (standard mean difference, SMD = -0.30), and dyspnoea (MD = -0.75 Borg score units). High-flow oxygen systems tended to be more effective than low-flow systems in improving exercising SpO2, duration, fatigue, dyspnoea, and heart rate. High-flow nasal cannulas (HFNCs) yielded better outcomes regarding SpO2 and fatigue than did high-flow Venturi masks (MD = 1.60 % and MD = -1.19 Borg score units, respectively). No major adverse events were reported. CONCLUSION: The evidence from RCTs supports the short-term use of oxygen supplementation to improve SpO2, exercise capacity, fatigue, and dyspnoea among patients with fILD. Further analyses demonstrates that HFNCs yield more favourable outcomes, yet not reaching statistical significance except for improving SpO2 and fatigue. However, the long-term effects of oxygen therapy on quality of life and mortality remain unclear.

Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial.

BACKGROUND: XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina. METHODS: In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery. RESULTS: There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients were related to the surgical procedure. Total exercise duration increased from a mean±SD of 359.9±105.55 seconds at baseline to 448.2±168.45 (3 months), 449.2±175.9 (6 months), and 477.6±174.7 (12 months; +88.3 [95% CI, 37.1-139.5], +84.5 [95% CI, 34.1-134.9], and +115.5 [95% CI, 59.1-171.9]). Total myocardial perfusion deficit on positron emission tomography imaging decreased by 10.2% (95% CI, -3.1% to 23.5%), 14.3% (95% CI, 2.8%-25.7%), and 10.2% (95% CI, -0.8% to -21.2%). Angina frequency decreased from a mean±SD 12.2±12.5 episodes to 5.2±7.2 (3 months), 5.1±7.8 (6 months), and 2.7±4.8 (12 months), with an average decrease of 7.7 (95% CI, 4.1-11.3), 6.6 (95% CI, 3.5-9.7), and 8.8 (4.6-13.0) episodes at 3, 6, and 12 months. Angina class improved in 81% of participants at 6 months. CONCLUSIONS: XC001 administered via transepicardial delivery is safe and generally well tolerated. Exploratory improvements in total exercise duration, ischemic burden, and subjective measures support a biologic effect sustained to 12 months, warranting further investigation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04125732.

Effects of different inspiratory muscle training protocols on functional exercise capacity and respiratory and peripheral muscle strength in patients with chronic kidney disease: a randomized study.

BACKGROUND: Pathological changes were observed in the diaphragm due to abnormal renal function in chronic kidney disease (CKD). Inspiratory muscle training (IMT) has been suggested for patients with CKD; however, the most appropriate intensity for IMT has not been determined. Therefore, this study aimed to investigate the effects of different IMT protocols on respiratory muscle strength, quadriceps femoris muscle strength (QMS), handgrip muscle strength (HGS), functional exercise capacity, quality of life (QoL), pulmonary function, dyspnoea, fatigue, balance, and physical activity (PA) levels in patients with CKD. METHODS: This randomized, controlled, single-blind study included 47 patients and they were divided into three groups: Group 1 (n = 15, IMT with 10% maximal inspiratory pressure (MIP)), Group 2 (n = 16, IMT with 30% MIP), and Group 3(n = 16; IMT with 60% MIP). MIP, maximal expiratory pressure (MEP), 6-min walking test (6-MWT), QMS, HGS, QoL, pulmonary function, dyspnoea, fatigue, balance, and PA levels were assessed before and after eight weeks of IMT. RESULTS: Increases in MIP, %MIP, 6-MWT distance, and %6-MWT were significantly higher in Groups 2 and 3 than in Group 1 after IMT (p < 0.05). MEP, %MEP, FEF25-75%, QMS, HGS, and QoL significantly increased; dyspnoea and fatigue decreased in all groups (p < 0.05). FVC, PEF, and PA improved only in Group 2, and balance improved in Groups 1 and 2 (p < 0.05). CONCLUSIONS: IMT with 30% and 60% MIP similarly improves inspiratory muscle strength and functional exercise capacity. IMT with 30% is more effective in increasing PA. IMT is a beneficial method to enhance peripheral and expiratory muscle strength, respiratory function, QoL and balance, and reduce dyspnoea and fatigue. IMT with %30 could be an option for patients with CKD who do not tolerate higher intensities. TRIAL REGISTRATION: This study was retrospectively registered (NCT06401135, 06/05/2024).

HF Etiology and cardiac contractility modulation therapy.

OBJECTIVES: Our study aimed to assess the safety and efficacy of cardiac contractility modulation (CCM) therapy in patients with heart failure with reduced ejection fraction (HFrEF) depending on HF etiology. METHODS: We enrolled 166 patients with optimal medical therapy-resistant HFrEF (median age 59 years, 83.7% males, median NYHA class - 2, median left ventricular ejection fraction (LVEF) - 29.0%) who underwent CCM therapy device implantation from 2013 to 2019 in four medical centers in Russia. The HF etiology was determined based on invasive coronary angiography or cardiac MRI data. Transthoracic echocardiography (TTE), 6-minute walking test (6MWT), and NTproBNP-tests were performed at a baseline and 12 months after the implantation. RESULTS: The ischemic etiology of HF was revealed in 100 patients (61.5%) (ICM group); the non-ischemic group (NICM) evolved 66 patients (38.5%). Patients in the ICM group were significantly older (61[57-69] vs. 55 [42.8-61], p < 0.001), more frequently had hypertension (79% vs. 42.4%, p < 0.001) and chronic kidney disease (43% vs. 22.7%, p = 0.012). Patients in the NICM group had significantly more often atrial fibrillation (AF) (58% vs. 74%, p = 0.048), larger end-diastolic volume (EDV) (249 [208-309] vs. 220 [192-271], p = 0.019) and end-systolic volume (ESV) (183 [147-230] vs. 154 [128-199], p = 0.003). There were no significant differences in mortality between ICM and NICM groups (14.4 vs. 10.8%, p = 0.51). In 12 months, there was a significant increase in LVEF in the NICM group (+ 2.0 [2-6] vs. +7.7 [2-12], p < 0.001), while the improvement in the 6MWT (+ 75 [22-108] vs. +80 [10-160], p = 0.851) and NYHA class did not reach the level of significance. The subanalysis between patients with improved NYHA class and those without improvement revealed that patients without improvement more frequently had AF (56% vs. 89%; p < 0.01), chronic obstructive lung disease (18% vs. 35% p = 0.047), higher blood pressure (110 [105-120] vs. 120[110-129]; p = 0.032). CONCLUSION: In this multicenter retrospective study, patients with non-ischemic HFrEF showed a significantly higher improvement in LVEF and LV reverse remodeling following CCM therapy device implantation. There was no significant association between HF etiology and survival in drug-resistant HFrEF patients following CCM therapy.

Pulmonary rehabilitation in Iranian outpatients with mustard gas lung disease: a randomised controlled trial.

OBJECTIVE: People with mustard gas lung disease experience cough, sputum, breathlessness and exercise limitation. We hypothesised that pulmonary rehabilitation (PR) would be beneficial in this condition. DESIGN: An assessor-blind, two-armed, parallel-design randomised controlled clinical trial. SETTING: Secondary care clinics in Iran. PARTICIPANTS: 60 men with breathlessness due to respiratory disease caused by documented mustard gas exposure, mean (SD) age 52.7 (4.36) years, MRC dyspnoea score 3.5 (0.7), St. George's Respiratory Questionnaire (SGRQ) 72.3 (15.2). INTERVENTIONS: Participants were allocated either to a 6-week course of thrice-weekly PR (n=31) or to usual care (n=29), with 6-week data for 28 and 26, respectively. OUTCOME MEASURES: Primary endpoint was change in cycle endurance time at 70% baseline exercise capacity at 6 weeks. Secondary endpoints included 6 min walk distance, quadriceps strength and bulk, body composition and health status. For logistical reasons, blood tests that had been originally planned were not performed and 12-month follow-up was available for only a small proportion. RESULTS: At 6 weeks, cycle endurance time increased from 377 (140) s to 787 (343) s with PR vs 495 (171) s to 479 (159) s for usual care, effect size +383 (231) s (p<0.001). PR also improved 6 min walk distance+103.2 m (63.6-142.9) (p<0.001), MRC dyspnoea score -0.36 (-0.65 to -0.07) (p=0.016) and quality of life; SGRQ -8.43 (-13.38 to -3.48) p<0.001, as well as quadriceps strength+9.28 Nm (1.89 to 16.66) p=0.015. CONCLUSION: These data suggest that PR can improve exercise capacity and quality of life in people with breathlessness due to mustard gas lung disease and support the wider provision of this form of care. TRIAL REGISTRATION NUMBER: IRCT2016051127848N1.

Maintenance Pulmonary Rehabilitation: An Update and Future Directions.

The Global Initiative for Chronic Obstructive Lung Disease guidelines recommend pulmonary rehabilitation (PR) for individuals with COPD to improve exercise capacity and health-related quality of life (HRQOL) and reduce symptoms of dyspnea. For cost-effectiveness in COPD care, PR is second only to smoking cessation. However, PR programs typically last 9-12 weeks. The benefits of PR in terms of exercise capacity and HRQOL often decrease toward pre-PR levels as early as 3-6 months after completing PR if patients do not continue to engage in exercise. This review will (1) briefly summarize the efficacy data that informed the 2023 American Thoracic Society (ATS) clinical practice guidelines for maintenance PR, (2) discuss exercise components of maintenance PR studied since 2020 when the last papers were included in the ATS guidelines, (3) explore future directions for delivery of maintenance PR using technology-mediated models, and (4) examine the need for behavior change techniques informed by theoretical models that underpin long-term behavior change. This review will focus on persons with COPD who have completed an out-patient core initial PR program as most of the data on maintenance PR have been published in this patient population. Core PR typically implies a facility-based initial intensive structured program. All patients who complete a core initial PR program should be counseled by PR staff at the discharge visit to engage in ongoing exercise. This usual care is equally as important as referral to a formal PR maintenance program. It is critical to emphasize that usual care after core initial PR means all patients should be supported to participate in regular ongoing exercise, regardless of whether supervised maintenance PR is available. Currently, the optimal frequency, exercise and/or physical activity content, and delivery mode for maintenance PR in persons with COPD and other chronic respiratory diseases remain unknown. Patient safety and degree of in-person supervision required due to the severity of the underlying lung disease need to be considered. Future research of maintenance PR should be underpinned by behavior change techniques. Finally, in the setting of finite resources, balancing the competing priorities of core initial programs with those of maintenance PR programs needs to be achieved.

Respiratory Assist Devices in Pulmonary Rehabilitation.

Patients with advanced lung disease, especially patients with COPD, suffer from dyspnea at rest that worsens during the performance of even limited physical activities. The causes of dyspnea are multifactorial and are related to structural changes found in the parenchymal compartment of the lung as well as the airway and pulmonary vasculature. Alterations in any of the lung compartments may have negative consequences for the physiological performance of exercise. Respiratory assist devices that attenuate the pathophysiological derangements induced by the underlying lung disease, and/or unload the increased work of breathing, can enhance the performance of exercise, and help to produce more robust training effects in patients with lung disease. Herein we review the data that examines these approaches using respiratory assist devices to improve exercise outcomes in patients with COPD.

The long-term effect of elexacaftor/tezacaftor/ivacaftor on cardiorespiratory fitness in adolescent patients with cystic fibrosis: a pilot observational study.

BACKGROUND: Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated. METHODS: We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients. RESULTS: We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters. CONCLUSION: Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.