Six-minute Walk Distance Research Articles

Effects of Exercise Rehabilitation on Cardiorespiratory Fitness in Long-COVID-19 Survivors: A Meta-Analysis.

Background: Poor cardiorespiratory fitness poses the highest risk of mortality. Long-COVID-19 survivors exhibit a reduced cardiorespiratory fitness (CRF). While exercise rehabilitation, such as cardiopulmonary exercise, is used for long-COVID-19 survivors, the effects of exercise on CRF in this population remain inconclusive. In this study, we aim to systematically summarise and synthesise whether exercise rehabilitation improves CRF among long-COVID-19 survivors. Methods: A comprehensive search was performed through PubMed, CINAHL, Embase, Scopus, and the Cochrane Library (since their inception to November 2023) and study reference lists. Studies presenting the effects of exercise rehabilitation on CRF (peak oxygen consumption (VO2peak) and six-minute walk distance (6MWD)) in long-COVID-19 survivors were identified. The standardised mean difference (SMD), mean difference (MD), and 95% confidence interval (CI) were used for analyses. The certainty of evidence was measured using a Grading of Recommendation Assessment, Development and Evaluation approach. Results: Twelve eligible studies (five RCTs and seven non-RCTs) with 682 participants were analysed. The meta-analysis showed significantly improved 6MWDs (MD 76.47, 95% CI 59.19-93.71, low certainty) and significantly greater 6MWDs (SMD 0.85, 95% CI 0.11-1.59, very low certainty) in the exercise rehabilitation group compared to the control group. A significantly improved 6MWD was found in subgroups of young to middle-aged adults and subgroups of patients who undertook aerobic exercise combined with resistance and respiratory exercise and centre-based training programs. Conclusions: Exercise rehabilitation is effective for improving CRF, as measured by the 6MWD in long-COVID-19 survivors. Improvements are likely to be more pronounced in specific subgroups of young to middle-aged adults and patients undertaking aerobic exercise combined with resistance and respiratory exercise and centre-based training programs. However, recommendations for clinical practice are limited due to the very low evidence certainty.

The Impact of Cardiac Rehabilitation on Psychosocial Factors, Functional Capacity, and Left Ventricular Function in Patients with Coronary Artery Disease: Systematic Review and Meta-Analysis

Background Cardiac rehabilitation is a multifaceted program implemented after adverse events. It aims at facilitating the return to normal life. This review aimed to examine the impact of cardiac rehabilitation on psychosocial risk factors, functional capacity, and left ventricular function. Methods The following databases: CINAHL, Scopus, PubMed, and Cochrane Library have been searched to retrieve the randomized controlled trials that investigate the effectiveness of cardiac rehabilitation versus usual care on anxiety, depression, peak oxygen consumption, six-minute walk distance, left ventricular ejection fraction, and left ventricular end-systolic and diastolic dimensions. Filters were set to retrieve trials that were published in the English Language between 2000 and 2024. Risk of bias was assessed using the Cochrane risk-of-bias tool (Rob2). Data were analysed meta-analytically. Results Twenty two (22) trials were included, randomized 2283 participants. A significant improvement favouring intervention groups was observed in anxiety SMD = -0.3890 (95% CI: -0.5640 to -0.2140; p˂0.001), depression SMD = -0.4032 (95% CI: -0.7114 to -0.0950; p= 0.002), peak oxygen consumption MD = 1.2471 (95% CI: 0.3963 to 2.0979; p = 0.004), six-minute walk distance MD = 36.0290 (95% CI: 7.7497 to 64.3082; p = 0.013), and left ventricular ejection fraction MD = 3.0650 (95% CI: 1.1279 to 5.0022; p = 0.001), Although cardiac rehabilitation had no significant effect in decreasing left ventricular end-diastolic dimension MD = -0.0480 (95% CI: -0.2609 to 0.1648; p = 0.658) and left ventricular end-systolic and MD = -0.0670 (95% CI: -0.2829 to 0.1489; p = 0.543) a favourable trend toward intervention group was seen. Risk of bias was high in 1 study and unclear in 7 studies. Conclusion For patients with Coronary Artery Disease, cardiac rehabilitation demonstrated effectiveness in improving psychological symptoms such as anxiety and depression, functional capacity as measured by peak oxygen consumption and six-minute walk test, and left ventricular function.

Unlocking the Therapeutic Symphony: A Systematic Review Exploring the Role of Levosimendan in the Management of Heart Failure.

Levosimendan, a novel drug, a calcium-sensitizing inotrope, has emergedas a potential therapeutic modulator for heart failure (HF). This review appraises the efficacy and safety of levosimendan in managing HF, in different clinical settings. The study aims to examine the clinical outcomes reported in the selected trials to determine the effectiveness of levosimendan in improving key parameters related to HF. Seven relevant studies encompassing 1200 participants were identified from three databases. Inclusion criteria included clinical trials that investigated the therapeutic efficacy of levosimendan in the treatment of HF, and studies involving both adult and pediatric participants. Exclusion criteria involved studies with insufficient data, studies other than clinical trials, case reports, letters to the editor, conference papers, grey literature, and studies published in a language other than English. Upon evaluating the included studies, it was found that levosimendan shows improved hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy. Levosimendan enhanced right ventricular (RV) function in patients with RV dysfunction after mitral valve (MV) surgeries and decreased the amount of N-terminalpro-B-typenatriuretic peptide (NT-ProBNP) innon-ST elevated myocardial infarction (NSTEMI) patients with elevated NT-proBNP, all without increasing the overall cost or duration of hospitalization. Despite variations in study designs and participant characteristics, evidence suggests levosimendan significantly improves left ventricular ejection fraction (LVEF) and exercise tolerance measured by a six-minute walk distance. Notably, its safety profile appears favorable with minimal arrhythmic events and comparable rates of adverse effects to a placebo. This systematic review highlights levosimendan's promising potential for HF management, warranting further research to solidify its clinical role.

Mobile health–supported comprehensive intervention model (CIMmH) improved physical fitness of patients with esophageal cancer after esophagectomy: Prospective randomized controlled trial.

1634 Background: Esophageal cancer (EC) significantly impacts patients’ quality of life (QOL) post-esophagectomy, with malnutrition, reduced physical activity, and psychological distress being common. Our preliminary study indicated that a Mobile Health-Supported Comprehensive Intervention Model (CIMmH) is safe, feasible, and efficacious in improving QOL and physical fitness for EC patients. This randomized controlled trial (RCT) evaluates the effectiveness of CIMmH in promoting post-surgery recovery for EC patients. Methods: EC patients undergoing modified McKeown esophagectomy were randomly allocated to either the intervention group, receiving the CIMmH protocol (nutrition, exercise, psychological support), or the control group, receiving standard postoperative care. Outcomes were assessed at baseline, 1 month, and 3 months post-surgery. Key metrics included sarcopenia (assessed via skeletal muscle index and psoas muscle thickness on CT scans), quality of survival (EORTC-QLQ-C30 and EORTC-QLQ-QES-18), physical fitness (six-minute walk distance, SMWD), and nutritional status (body weight). Results: Of 111 screened patients, 80 were enrolled (40 per group). Follow-up assessments were completed by 76 patients at 1 month and 69 at 3 months. At 1 month, the intervention group showed a significant improvement in SMWD compared to the control group ( P=0.020), though no difference was observed at 3 months ( P=0.835). The intervention group also demonstrated a significant increase in the skeletal muscle index at 3 months ( P=0.039), alongside notable improvements in the 30-second arm curl test and cough symptom relief ( P=0.027 and P=0.045, respectively). No significant differences in QOL scores or body weight were observed between groups at any time point. Conclusions: CIMmH significantly enhances short-term physical fitness in EC patients post-esophagectomy. These findings suggest the need for further refinement and optimization of the intervention to maximize its long-term effectiveness and impact on QOL. Clinical trial information: ChiCTR2000041007 .

Preacinar Arterial Dilation Mediates Outcomes of Quantitative Interstitial Abnormalities in COPDGene.

Quantitative interstitial abnormalities (QIA) are a computed tomography (CT) measure of early parenchymal lung disease associated with worse clinical outcomes including exercise capacity and symptoms. The presence of pulmonary vasculopathy in QIA and its role in the QIA-outcome relationship is unknown. To quantify radiographic pulmonary vasculopathy in quantitative interstitial abnormalities (QIA) and determine if this vasculopathy mediates the QIA-outcome relationship. Ever-smokers with QIA, outcome, and pulmonary vascular mediator data were identified from the COPDGene cohort. CT-based vascular mediators were: right ventricle-to-left ventricle ratio (RV/LV), pulmonary artery-to-aorta ratio (PA/Ao), and pre-acinar intraparenchymal arterial dilation (PA volume 5-20mm2 in cross-sectional area, normalized to total arterial volume). Outcomes were: six-minute walk distance (6MWD) and modified Medical Council Research Council (mMRC) Dyspnea score ≥2. Adjusted causal mediation analyses were used to determine if the pulmonary vasculature mediated the QIA effect on outcomes. Associations of pre-acinar arterial dilation with select plasma biomarkers of pulmonary vascular dysfunction were examined. Among 8,200 participants, QIA burden correlated positively with vascular damage measures including pre-acinar arterial dilation. Pre-acinar arterial dilation mediated 79.6% of the detrimental impact of QIA on 6MWD (56.2-100%, p<0.001). PA/Ao was a weak mediator and RV/LV was a suppressor. Similar results were observed in the QIA-mMRC relationship. Pre-acinar arterial dilation correlated with increased pulmonary vascular dysfunction biomarker levels including angiopoietin-2 and NT-proBNP. Parenchymal quantitative interstitial abnormalities (QIA) deleteriously impact outcomes primarily through pulmonary vasculopathy. Pre-acinar arterial dilation may be a novel marker of pulmonary vasculopathy in QIA.

Novel Liver Injury Phenotypes and Outcomes in Clinical Trial Participants with Pulmonary Hypertension.

Rationale: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) cause right ventricular dysfunction, which can impact other solid organs. However, the profiles and consequences of hepatic injury resulting from PAH and CTEPH have not been well studied. Objectives: We aimed to identify underlying patterns of liver injury in a cohort of patients with PAH and CTEPH enrolled in 15 randomized clinical trials conducted between 1998 and 2014. Methods: We used unsupervised machine learning to identify liver injury clusters in 13 trials and validated the findings in two additional trials. We then determined whether these liver injury clusters were associated with clinical outcomes or treatment effect heterogeneity. Measurements and Main Results: Our training dataset included 4,219 patients and our validation dataset included 1,756 patients with serum total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and albumin data. Using k-means clustering, we identified phenotypes with no liver injury, hepatocellular injury, cholestatic injury, and combined injury patterns. Patients in the cholestatic injury liver cluster had the shortest time to clinical worsening and the highest risk of mortality. The cholestatic injury group also experienced the greatest placebo-corrected treatment effect on 6-minute-walk distance. Randomization to the experimental arm transitioned patients to a healthier liver status. Conclusions: Liver injury was associated with adverse outcomes in patients with PAH and CTEPH. Randomization to active treatment had beneficial effects on liver health compared with placebo. The role of liver disease (often subclinical) in determining outcomes warrants prospective studies.

Evaluating the Impact of Pulmonary Arterial Hypertension Therapies on Pericardial Effusion and Patient Survival.

To evaluate the impact of Pulmonary Arterial Hypertension (PAH) therapies on the incidence of pericardial effusion and its prognostic implications for patient survival. This retrospective cohort study included 60 patients diagnosed with PAH at a high-volume tertiary care center, treated with intravenous or subcutaneous prostanoids. Data were collected from 2015 to 2019, including echocardiographic assessments, right heart catheterization, World Health Organization functional class evaluations, six-minute walk distance tests, and biomarkers such as brain natriuretic peptide and N-terminal prohormone of brain natriuretic peptide. Follow-up was conducted at least 90 days post-treatment initiation. Pericardial effusion was observed in 31.7% of patients before therapy. Patients with moderate to large effusions had a significantly higher mortality risk (HR = 1.92; 95% CI 1.1-44.78; p =0.0044), while small effusions appeared protective (HR = 0.27; 95% CI 0.15-0.48; p =0.006). Survival rates declined from 89% at one year to 71% at three years post-therapy, with effusion presence correlating with more severe PAH manifestations. Initial pericardial effusion severity is a critical predictor of mortality in PAH patients. Early assessment and stratified management of pericardial effusion are essential for optimizing therapeutic outcomes in PAH management. Future research should explore targeted interventions for managing pericardial effusion to improve patient prognosis.

Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial.

Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. We aimed to determine whether anastrozole improved six-minute walk distance (6MWD) at six months in pulmonary arterial hypertension (PAH). We performed a randomized, double-blind, placebo-controlled Phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four post-menopausal women and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at six months. Using intent-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. Forty-one subjects were randomized to placebo and 43 to anastrozole and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued study drug. There was no significant difference in the change in 6MWD at six months (placebo-corrected treatment effect -7.9 m, 95%CI -32.7 - 16.9, p = 0.53). There was no difference in adverse events between the groups. Anastrozole did not show a significant effect on 6MWD compared to placebo in post-menopausal women and men with PAH. Anastrozole was safe and did not show adverse effects. Clinical trial registration available at www. gov, ID: NCT03229499.

ROLE OF RIGHT VENTRICULAR–PULMONARY ARTERY COUPLING IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION

Objectives: To describe the clinical characteristics, right ventricular pulmonary artery (RV-PA) coupling and assess the correlation between RV-PA coupling and six-minute walk distance (6-MWD) in patients with heart failure with reduced ejection fraction (HFrEF). Subjects and methods: A prospective study with 39 patients with heart failure with HFrEF was recruited at 108 Central Military Hospital from December 2022 to October 2023. Results: A total of 39 patients were enrolled to the study with a majority of male (76.9%), mean age 63.7±15.7 years. Based on univariate and multivariate analysis, there is no correlation between right ventricular pulmonary artery coupling and 6-MWD, as evidenced by parameters including TAPSE/PASP (r=0.111, β=37.09, p=0.499), FAC/RVSP (r=0.012, β=1.29, p=0.944), and S’/RVSP (r=0.216, β=105, p=0.186). Nevertheless, there is a negative correlation between FAC/RVSP and S'/RVSP with LAVi, with respective values of (r = -0.522, β = -11.97, p-value = 0.001) and (r= -0.487, β = -0.005, p-value = 0.002). Conclusion: RVPAc cannot be used to predict exercise in HFrEF. Among echocardiographic RVPAc ratios, FAC/RVSP and S'/RVSP are correlated with left atrial volume index.

Exploration of quantitative-effectiveness association between acupuncture temporal parameters and stable chronic obstructive pulmonary disease: A systematic review and dose-response meta-analysis of randomized controlled trials

IntroductionChronic Obstructive Pulmonary Disease (COPD) is a globally common chronic respiratory disease with a high morbidity and mortality rate. Acupuncture has been proven effective for COPD. A dose-response meta-analysis was conducted to assess the correlation between the acupuncture temporal parameters(session, frequency, and duration) and its effectiveness in patients with stable COPD. MethodsAcupuncture randomized controlled trials on COPD were searched in eight databases from their inception to June 2023. The "doses" were defined as the acupuncture session, frequency, and duration. The outcomes mainly included Forced Expiratory Volume in one-second rate (FEV1%) and Six-minute Walking Distance (6MWD). The assessment of bias risk and literature quality were conducted independently using the Cochrane risk of bias tool and the Standards for reporting interventions in clinical trials of acupuncture. The dose-response relationship was modeled using robust error element regression, and meta-analysis was operated by R 4.3.1 and Stata 15.0. The protocol was registered in PROSPERO with the registration number CRD42023401406. ResultOut of 1669 records, 17 RCTs with 1165 participants were finally included in the meta-analysis. There was notable heterogeneity among the studies, but sensitivity analysis demonstrated good robustness. The findings revealed a significant improvement in the following outcomes for stable COPD patients in the acupuncture group: FEV1% (MD=3.50, 95%CI: 2.05–4.95), 6MWD (MD=47.39, 95%CI: 29.29–65.50), St. George's respiratory questionnaire (SGRQ; MD=−8.25, 95%CI: −11.38 to −5.12); COPD assessment test (CAT; MD=−2.91, 95%CI: −3.99 to −1.83). The relationship between the acupuncture session, duration, and FEV1%, 6MWD followed a "Λ" curve pattern, while the relationship between acupuncture frequency and FEV1%, 6MWD exhibited logarithmic growth. Firstly, After 12 acupuncture sessions, FEV1% and 6MWD increased by 7.06% (95%CI: 4.56–9.55) and 36.28 m (95%CI: 20.37–52.20), respectively. The peak improvement in FEV1% and 6MWD was observed after 18 acupuncture sessions (MD=7.89, 95% CI: 5.33–10.45) and 45 sessions (MD=125.43, 95% CI: 72.80–178.07) each. Additionally, weekly acupuncture resulted in a 4.14% improvement in FEV1% (95% CI: 2.55–5.72) and a 42.49 m increase in 6MWD (95%CI: 17.16–67.81). Notably, the maximum effects on FEV1% and 6MWD improvement were achieved with different acupuncture frequencies, specifically three times a week (MD=6.00, 95% CI: 5.34–6.66) and once a day(MD=112.41, 95% CI: 77.27–147.56), respectively. Furthermore, after a 28-day duration of acupuncture treatment, FEV1% increased by 4.74% (95% CI: 3.73–5.75) and 6MWD increased by 47.34 m (95%CI: 22.01–72.67). During 60 days of acupuncture treatment, the FEV1% and 6MWD improvement reached their highest levels at 8.76% (95% CI: 7.05–10.47) and 88.06 m (95% CI: 45.96–130.16), respectively. ConclusionAcupuncture was effective in improving FEV1%, 6MWD, SGRQ, and CAT in patients with stable COPD. There was a dose-response relationship between the time parameters of acupuncture (session, frequency, and duration) and the efficacy of COPD treatment (FEV1% and 6MWD). The minimal clinically important difference could be achieved after 12 acupuncture sessions. Acupuncture with a medium-frequency (2–3 times per week) over 60 days may result in the greatest improvement in FEV1%, while higher-frequency acupuncture (5–7 times per week) for 2 months may lead to the maximum improvements in 6MWD. It indicated that the optimal acupuncture duration for different indicators remains consistent, while the optimal frequencies may differ. To confirm these results, it is necessary to conduct multicenter, large-scale randomized controlled trials. Ethics and disseminationEthical approval is not required for literature-based studies. The results will be published in peer-reviewed journals or conferences.

Effects of inspiratory muscle training on thoracoabdominal volume regulation in older adults: A randomised controlled trial

ObjectivesWe investigated the effect of inspiratory muscle training (IMT) on inspiratory muscle strength, functional capacity and respiratory muscle kinematics during exercise in healthy older adults. Methods24 adults were randomised into an IMT or SHAM-IMT group. Both groups performed 30 breaths, twice daily, for 8 weeks, at intensities of ∼50 % maximal inspiratory pressure (PImax; IMT) or <15 % PImax (SHAM-IMT). Measurements of PImax, breathing discomfort during a bout of IMT, six-minute walk distance, physical activity levels, and balance were assessed pre- and post-intervention. Respiratory muscle kinematics were assessed via optoelectronic plethysmography (OEP) during constant work rate cycling. ResultsPImax was significantly improved (by 20.0±11.9 cmH2O; p=0.001) in the IMT group only. Breathing discomfort ratings during IMT significantly decreased (from 3.5±0.9–1.7±0.8). Daily sedentary time was decreased (by 28.0±39.8 min; p=0.042), and reactive balance significantly improved (by 1.2±0.8; p<0.001) in the IMT group only. OEP measures showed a significantly greater contribution of the pulmonary and abdominal rib cage compartments to total tidal volume expansion post-IMT. ConclusionsIMT significantly improves inspiratory muscle strength and breathing discomfort in this population. IMT induces greater rib cage expansion and diaphragm descent during exercise, thereby suggesting a less restrictive effect on thoracic expansion and increased diaphragmatic power generation.

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

BackgroundInhaled 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.MethodsIn 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.ResultsOverall, 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).ConclusionIn 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).

Six-Minute Walk Test among obese and nonobese subjects: A comparative analysis among apparently healthy volunteers

Abstract Context: The Six-Minute Walk Test (6MWT) is a simple measure for objective assessment of physical fitness and exercise tolerance. It has also been standardized to follow up on the prognosis and progression of chronic cardiovascular and respiratory diseases. Though there are standardized formulas for analyzing the 6MWT results concerning age, height, weight, regional, and ethnic population these should be revisited considering the wider variations of subjects in the reference studies. Aim: This article aims to compare the 6MWT performance among obese and nonobese, apparently healthy volunteers. Settings and Design: A cross-sectional study was conducted in the Physiology Department, AIIMS Kalyani, West Bengal, India. Materials and Methods: Age and sex-matched apparently healthy volunteers were included in the study after their consent. After collection of anthropometric data, they were divided into two groups; group A with body mass index (BMI) &lt;30 kg/m2 and group B with BMI &gt;30 kg/m2. The 6MWT was implemented according to standard guidelines; the Six-Minute Walk Distance (6MWD) and other parameters were noted. Statistical analysis was performed by Statistical Package for the Social Sciences software version 17 (IBM Corp., Chicago, IL, USA). Results: The results revealed that a comparison was done between actual values and predicted values of 6MWD. Among obese groups, the actual 6MWD covered was significantly lesser than the predicted values. Significant differences were also found between the two groups concerning Borg score, Calculated volume of oxygen max, systolic and diastolic blood pressures, respiratory rate, heart rate, and Peripheral capillary oxygen saturation. Conclusions: The results revealed that our result shows that the weight-based reference equation for interpretation of 6MWT may not be sufficient for obese subjects.

Ventilatory Variability Is Increased at Rest in Pulmonary Arterial Hypertension

Ventilatory instability is associated with adverse outcomes in left heart failure, with periodic breathing during awake, rest, sleep and exercise (exercise oscillatory ventilation) associated with increased mortality. Increased peripheral and central chemoreflex sensitivities and impairment of cardiac output have been implicated as causative mechanisms of ventilatory instability in heart failure. As these factors are also present in pulmonary arterial hypertension (PAH), we tested the hypothesis that variability of breath-by-breath ventilation at rest would be increased in PAH compared with healthy controls. In fourteen patients with PAH (9 female, age 48.4±12.8 years, mean ± SD) and 14 healthy participants (9 female, age 49.4±14.2 years) breath-by-breath measurement of tidal volume and breathing frequency was undertaken with a pneumotachometer connected via a mouthpiece with nose-clip for 10 minutes while they rested awake and supine. Ventilatory (V̇E) variability was assessed using root mean square of successive differences (RMSSD), standard deviation (SD), average real variability (ARV, i.e., sum of absolute differences in successive observations), coeffcient of variation (CoV), as well as Poincaré analysis and compared between PAH and healthy controls (Student’s t-test). Correlations between measures of ventilatory variability and pulmonary hemodynamic characteristics, exercise capacity and function were assessed with Pearson’s correlation coeffcient. Resting V̇E was higher in PAH compared to healthy controls (14.3±1.1 and 12.1±0.5 L·min−1 respectively; p=0.009). Measures of variability for V̇E were increased in PAH compared to healthy controls. More specifically, RMSSD (3.59±1.36 vs. 2.48±0.87 L·min−1, p=0.017), SD (2.92±1.14 vs. 1.98±0.53 L·min−1, p=0.012), ARV (2.47±0.97 vs. 1.67±0.60 L·min−1, p=0.016), Poincaré SD1 (short-term variability, p=0.020) and SD2 (long-term variability, p=0.028) were increased in PAH compared to healthy controls, respectively. No correlations were found between measures of ventilatory variability and pulmonary hemodynamics (mean pulmonary artery pressure, pulmonary vascular resistance, and cardiac output), six-minute walk distance or WHO functional class. In summary, resting ventilatory variability is increased in PAH and not associated with haemodynamic factors and exercise capacity. Whether such raised ventilatory variability in PAH is related to increased chemoreflex sensitivity requires exploration. This study received funding support from the Greenlane Research and Educational Fund (21/01/4153), Health Research Council of New Zealand (19/687), and the Sidney Taylor Trust. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

EXPLORING THE ROLE OF SKELETAL MUSCLE MICROVASCULAR BLOOD FLOW IN EXERCISE CAPACITY AMONG INDIVIDUALS WITH CONTROLLED TYPE 2 DIABETES

INTRODUCTION &amp; AIMS The cardiac and macrovascular system is vital for human exercise capacity, yet the microvascular network is primarily responsible for delivering nutrients and oxygen to metabolically active tissues like skeletal muscle. Due to methodological limitations, few studies have investigated the role of muscle microvascular blood flow in determining exercise capacity or intolerance in individuals with chronic conditions such as type 2 diabetes. Our aim was to use modern contrast-enhanced ultrasound to directly measure microvascular blood flow in skeletal muscle at rest and after a maximal treadmill exercise test in individuals with controlled type 2 diabetes. METHODS Fifteen adults with controlled type 2 diabetes (age: 62.5 ± 8.0 years [M ± SD]; BMI: 31.6 ± 6.9 kg/m2; HbA1c: 6.7 ± 0.9%; 13 females and 2 male) attended the laboratory after a 2-hour fast and completed a Modified Bruce treadmill exercise test until exhaustion. Microvascular blood velocity, volume, and flow in the vastus lateralis muscle was assessed at rest, immediately post-exercise, and 30 minutes post-exercise via contrast-enhanced ultrasound during a constant-rate intravenous contrast agent infusion (DEFINITY®). Participants also completed a whole-body dual x-ray absorptiometry scan and a six-minute walk test (6MWT). RESULTS Microvascular blood velocity, volume, and flow increased immediately after exercise (∼230%, ∼79%, and ∼529%, respectively; all p&amp;lt;0.001), and remained elevated above baseline levels 30 minutes post-exercise (∼79%, ∼25%, and ∼139%, respectively; all p≤0.003). Resting and post-exercise skeletal muscle microvascular blood flow measures were not associated with VO2peak (ml/min/kg), time to exhaustion, or six-minute walk distance (all p&amp;gt;0.05). CONCLUSION Muscle microvascular blood flow remains elevated for up to 30 minutes following maximal aerobic exercise in individuals with controlled type 2 diabetes. The lack of association between muscle microvascular blood flow and exercise capacity is not clear but may indicate considerable blood flow redundancy or reserve within the vascular network.

FREQUENCY OF POST-EXERTIONAL MALAISE AMONG INDIVIDUALS WITH POST ACUTE SEQUELAE OF SARS-COV-2 INFECTION

INTRODUCTION AND AIM Post acute sequelae of SARS-CoV-2 infection (PASC) is a multifaceted disorder with varying symptoms. Fatigue is commonly reported; however, it is unclear if similarities exist between PASC and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We sought to determine the frequency of post-exertional malaise in individuals with PASC; a hallmark symptom of ME/CFS. METHODS 116 participants (Age: 53.4±8.4, 36% Male) were identified to have PASC through medical screening. The Duke Activity Status Index (DASI) subjectively evaluated functional capacity, and participants achieving &amp;lt;100% of age and sex defined norms were eligible for the study. Participants attended one of three sites across Victoria and Tasmania to complete Cardiopulmonary Exercise Testing (CPET). Two days post CPET they were asked to complete the DePaul Symptom Questionnaire (DSQ) post-exertional malaise (PEM). PEM was defined as a score ≥ 2 for frequency and severity on DSQ-PEM items 1-5. A personalised exercise rehabilitation program is currently underway for participants, with results on responses to training to be available at the time of the conference. RESULTS 106 (91%) of the participants who completed a CPET achieved less than 85% of predicted relative VO2peak (21.79±5.72ml.min-1.kg-1). The DSQ-PEM questionnaire was completed in 75% (n=79) of participants. Among these individuals 78% (n=62) met the threshold for PEM. The PEM group were older (53±8 vs 48±8 years, p=0.04), had higher BMI (30.5±7.6 vs 26.7±3.9kg.m2, p=0.02), lower VO2peak (21.6±5.7 vs 25.6±5.4ml.min-1.kg-1, p=0.01) and six-minute walk distance (491±131 vs 583±112m, p=0.02). There was a similar proportion of men and women between both groups. CONCLUSION Like with ME/CFS, PEM is a common symptom in PASC. Additionally, these individuals are more deconditioned than PASC sufferers without PEM. Thus, practitioners should carefully consider the impact of PEM and deconditioning when developing rehabilitation programs.

Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial

BackgroundPulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC). However, it is unknown if PH-specific therapy is beneficial in SSc patients with mildly elevated pressure (SSc-MEP, mPAP 21–24 mmHg).MethodsThe SEPVADIS trial is a randomized, double-blind, placebo-controlled phase 2 trial of sildenafil in SSc-MEP patients with a target enrollment of 30 patients from two academic sites in the United States. The primary outcome is change in six-minute walk distance after 16 weeks of treatment. Secondary endpoints include change in pulmonary arterial compliance by RHC and right ventricular function by cardiac magnetic resonance imaging at 16 weeks. Echocardiography, serum N-terminal probrain natriuretic peptide, and health-related quality of life is being measured at 16 and 52 weeks.DiscussionThe SEPVADIS trial will be the first randomized study of sildenafil in SSc-MEP patients. The results of this trial will be used to inform a phase 3 study to investigate the efficacy of treating patients with mild elevations in mPAP.Trial registrationClinicalTrials.gov Identifier NCT04797286.

Stride Velocity 95th Centile Detects Decline in Ambulatory Function Over Shorter Intervals than the 6-Minute Walk Test or North Star Ambulatory Assessment in Duchenne Muscular Dystrophy.

Stride Velocity 95th Centile (SV95C) is the first wearable device-derived clinical outcome assessment (COA) to receive European Medicines Agency (EMA) qualification as a primary endpoint in ambulant patients with Duchenne muscular dystrophy (DMD) aged ≥4 years. To compare SV95C-in its first-ever clinical trial application as a secondary endpoint-with established motor function COAs used in the trial (Four-Stair Climb [4SC] velocity, North Star Ambulatory Assessment [NSAA], and Six-Minute Walk Distance [6MWD]). SV95C was a secondary endpoint in a subset (n = 47) of participants in the SPITFIRE/WN40227 trial of taldefgrobep alfa, which was discontinued due to lack of clinical benefit. Participants in the ≤48-week SV95C sub-study were 6-11 years old and received corticosteroids for ≥6 months pre-treatment. Pearson correlations were used to compare SV95C with the other COAs. Responsiveness and changes over time were respectively assessed via standardized response means (SRMs) based on absolute changes and mixed models for repeated measures. SV95C change at Week 24 was -0.07 m/s, with limited variability (standard deviation: 0.16, n = 27). The SRM for SV95C indicated moderate responsiveness to clinical change at the earliest timepoint (Week 12, n = 46), while those of the other COAs did not indicate moderate responsiveness until Week 36 (6MWD, n = 33) or Week 48 (4SC velocity, n = 20; NSAA total score, n = 20). Baseline correlations between SV95C and other COAs were strong (r = 0.611-0.695). Correlations between SV95C change from baseline to Week 48 and changes in other COAs were moderate to strong (r = 0.443-0.678).∥. Overall, SV95C demonstrated sensitivity to ambulatory decline over short intervals, low variability, and correlation with established COAs. Although the negative trial precluded demonstration of SV95C's sensitivity to drug effect, these findings support the continued use of SV95C in DMD clinical trials.

Effectiveness of Exercise Interventions on Body Composition, Exercise Capacity, Fatigue, and Quality of Life in Patients with Liver Cirrhosis: A Meta-Analysis of Randomized Controlled Trials.

Diminished muscle protein synthesis in cirrhosis leads to reduced strength and mass, impacting daily activities and overall quality of life. This study aimed to examine the effectiveness of exercise intervention in body composition, exercise capacity, fatigue, and quality of life in patients with liver cirrhosis. A systematic search of medical databases, including PubMed, Embase, Cochrane, and CINAHL, was executed from their inception to November 2022. The inclusion criteria were randomized controlled trials comparing exercise interventions with a control group that did not receive exercise interventions. From the initially identified 2,565 articles, eight studies with a total of 220 patients were eligible for inclusion in this meta-analysis. According to the meta-analysis, exercise significantly improved the six-minute walk distance (6MWD) by 68.93m (95% CI 14.29-123.57) compared to the control group. Furthermore, the subgroup analysis revealed that combing exercise with amino acid supplementation had a greater positive effect on the 6MWD (MD = 144.72, 95% CI 87.44-202.01). Exercise also significantly increased thigh circumference (MD = 1.26, 95% CI 0.12-2.39) and the thigh ultrasound average compression index (MD = 0.07, 95% CI 0.00-0.14). Moreover, exercise significantly decreased fatigue levels by 0.7 points in patients with liver cirrhosis (95% CI 0.38-1.03). However, no significant effects were observed on body mass index (BMI), fat mass, fat-free mass, and quality of life. Exercise can improve exercise capacity, thigh muscle thickness, and fatigue in patients with cirrhosis, but it does not have a significant impact on fat mass, BMI, or quality of life.

Evaluation of the European Society of Cardiology Risk Assessment Score in Incident Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

Patients with pulmonary arterial hypertension (PAH) may be stratified as low, intermediate, or high risk of 1-year mortality. In 2022, the European Society of Cardiology (ESC) updated and simplified its risk stratification tool, based on three variables: World Health Organization functional class, serum N-terminal pro-brain type natriuretic peptide and six-minute walk distance, applied at follow-up visits, intended to guide therapy over time. We applied the 2022 ESC risk assessment tool at baseline and follow-up (within 2 years) to a multinational incident cohort of systemic sclerosis-associated PAH (SSc-PAH). Kaplan-Meier curves, Cox hazards regression, and accelerated failure time models were used to evaluate survival by risk score. At baseline (n = 260), the majority of SSc-PAH (72.2%) were graded as intermediate risk of death according to the 2022 tool. At follow-up, according to 2022 tool, half (55.5%) of the cohort were classified as low or intermediate-low risk. The 2022 risk model at follow-up was able to differentiate survival between risk strata. All three individual parameters (World Health Organization functional class, N-terminal pro-brain type natriuretic peptide, six-minute walk distance) were significantly associated with mortality at baseline and/or follow-up. The 2022 ESC risk assessment strategy applied at baseline and follow-up predicts survival in SSc-PAH. Treatment decisions for SSc-PAH should include risk assessments, aiming to achieve low-risk status according to the 2022 ESC guidelines.