Evaluation of novel indices of walking performance taking oxygen desaturation into account during six-minute walk test in cardiovascular disease patients.

In pulmonary disease patients since oxygen desaturation during 6-min walk test (6MWT) affects walk distance (6MWD), some novel indices such as desaturation/distance ratio [DDR, oxygen desaturation area (DAO2)/6MWD] and distance-saturation product [DSP, 6MWD × minimum peripheral oxygen saturation (SpO2)] are evaluated. However, there has been no study examining these indices that consider exercise-induced desaturation (EID) in patients with cardiovascular disease. In 94 cardiovascular disease patients without pulmonary complications, 6MWT and echocardiography were performed at the entry of cardiac rehabilitation. SpO2 was measured during 6MWT using a continuously monitorable pulse oximeter, and DSP and DDR were calculated using minimum SpO2 and DAO2 [sum of (100-SpO2) per second during 6MWT], respectively. EID was defined as SpO2 decrease of ≥ 4% or minimum SpO2 of < 90% during 6MWT. DSP was slightly lower and DDR was markedly higher in patients with EID than in those without. When examining correlations of DSP and DDR with their components, DSP was correlated with 6MWD much closely than minimum SpO2, while DDR was correlated as closely with DAO2 as 6MWD. Furthermore, DAO2, but not minimum SpO2, had a direct correlation with 6MWD. As for associations with cardiac function, DSP was correlated with several cardiac parameters, but DDR was not correlated with any of these parameters. Our findings suggest that oxygen desaturation during 6MWT affects walking distance in cardiovascular disease patients even without pulmonary complications and that DDR is more appropriate than DSP as an index of walking performance that takes EID into consideration, independently of cardiac function.

Minimal clinically important differences in six-minute walking distance in late-onset Pompe disease.

BACKGROUND: The minimal clinically important difference (MCID) is the smallest change in outcome that physicians or patients would consider meaningful and is relevant when evaluating disease progression or the efficacy of interventions. Studies of patients with late-onset Pompe disease (LOPD) have used the 6-min walk distance (6MWD) as an endpoint to assess motor function. However, an MCID for 6MWD (% predicted and meters) has yet to be established in LOPD. The objective of the study was to derive 6MWD MCID (% predicted and meters) with different analysis methods and for subgroups of different disease severity for LOPD. METHODS: Data from the PROPEL trial were used to calculate 6MWD MCID in the overall PROPEL population and subgroups of baseline severity as assessed by walking distance and body mass index (BMI), using anchor- and distribution-based approaches. RESULTS: The 6MWD MCIDs varied widely, depending on the method and subgroup, ranging from 2.27%-8.11% predicted for the overall LOPD population (23.7 m-57.2 m). For patients with baseline 6MWD < 150 m, MCIDs ranged from -0.74%-3.37% (-2.1 m-11.3 m). MCIDs increased with distance walked at baseline until a plateau was reached. For BMI subgroups, the MCIDs were generally lowest in obese patients. CONCLUSION: Our analysis shows that MCID depends on the chosen method and disease severity. The findings suggest that applying a single MCID to all patients can be misleading; consequently, a range of possible MCIDs should be considered. This may also be highly relevant for other neuromuscular diseases. This study provides a range of 6MWD MCIDs for LOPD, with lower MCIDs for more severe patients.

Five multivariate Duchenne muscular dystrophy progression models bridging six-minute walk distance and MRI relaxometry of leg muscles.

The study aimed to provide quantitative information on the utilization of MRI transverse relaxation time constant (MRI-T2) of leg muscles in DMD clinical trials by developing multivariate disease progression models of Duchenne muscular dystrophy (DMD) using 6-min walk distance (6MWD) and MRI-T2. Clinical data were collected from the prospective and longitudinal ImagingNMD study. Disease progression models were developed by a nonlinear mixed-effect modeling approach. Univariate models of 6MWD and MRI-T2 of five muscles were developed separately. Age at assessment was the time metric. Multivariate models were developed by estimating the correlation of 6MWD and MRI-T2 model variables. Full model estimation approach for covariate analysis and five-fold cross validation were conducted. Simulations were performed to compare the models and predict the covariate effects on the trajectories of 6MWD and MRI-T2. Sigmoid Imax and Emax models best captured the profiles of 6MWD and MRI-T2 over age. Steroid use, baseline 6MWD, and baseline MRI-T2 were significant covariates. The median age at which 6MWD is half of its maximum decrease in the five models was similar, while the median age at which MRI-T2 is half of its maximum increase varied depending on the type of muscle. The models connecting 6MWD and MRI-T2 successfully quantified how individual characteristics alter disease trajectories. The models demonstrate a plausible correlation between 6MWD and MRI-T2, supporting the use of MRI-T2. The developed models will guide drug developers in using the MRI-T2 to most efficient use in DMD clinical trials.

Effect of Adding Early Bedside Cycling to Inpatient Cardiac Rehabilitation on Physical Function and Length of Stay After Heart Valve Surgery: A Randomized Controlled Trial.

OBJECTIVE: To assess whether adding bedside cycling to inpatient cardiac rehabilitation (CR) early after heart valve surgery could lead to better physical function and shorter length of hospital stays. DESIGN: This is a single-centered, randomized, controlled, parallel-group intervention study. SETTINGS: This study was conducted at the National Heart Institute from December 2022 to June 2023. PARTICIPANTS: Thirty-one patients following heart valve surgery completed this study after being randomized into 2 groups: an intervention group (n1=16) and an active control group (n2=15). Eligibility criteria were heart valve surgery with median sternotomy, clinical stability, and age from 20 to 40 years. INTERVENTIONS: The intervention group received early bedside cycling for the lower limbs, using a mini bike, in addition to an inpatient CR program, and the control group received the inpatient CR program alone. MAIN OUTCOME MEASURE: The primary outcome was the physical functional capacity assessed by the 6-minute walk distance (6MWD). The secondary outcomes were the Barthel Index (BI), the forced vital capacity (FVC), the length of intensive care unit (ICU) stay, the total length of hospital stay, and the physical component summary (PCS) of the 12-item Short Form (SF-12) Health Survey. RESULTS: Compared with the control group, the intervention group showed significantly greater 6MWD (P<.001), BI score (P<.001), and FVC (P=.006) at hospital discharge, and shorter ICU stay (P=.002) and total hospital stay (P=.015). At 1-month follow-up, the intervention group showed a non-significantly higher PCS mean score than the control group (P=.057). CONCLUSION: Adding early bedside cycling to a usual inpatient CR program after heart valve surgery could induce significantly greater short-term physical functional capacity as assessed by the 6MWD, better activities of daily living as evaluated by the BI, higher pulmonary function as measured by the FVC, and shorter lengths of ICU and total hospital stays than the usual inpatient CR program alone.

Correlation Between Diaphragmatic Excursion and Exercise Tolerance Improvement Following Pulmonary Rehabilitation in Patients with Chronic Obstructive Pulmonary Disease-Obstructive Sleep Apnea Overlap Syndrome.

Purpose: We assess the predictive value of diaphragm excursion (DE) in enhancing exercise tolerance following pulmonary rehabilitation (PR) among patients with COPD-OSA overlap syndrome. Material and Methods: This prospective cohort study enrolled 63 patients diagnosed with COPD-OSA overlap syndrome who actively participated in a PR program from January 2021 to May 2023. Among these, 58 patients successfully completed the 20-week PR program, with exercise tolerance assessed through the measurement of six-minute walk distance (6MWD), and DE evaluated by ultrasonography. The responder to PR in terms of exercise ability was defined as a patient who showed an increase of >30m in 6MWD. The cutoff value for predicting PR response based on DE was determined using receiver operating characteristic (ROC) curves. Results: Following the PR program, significant improvements were observed in mMRC, 6MWD, DE during deep breathing, and diaphragm thickness fraction (DTF). Of the participants, 33 patients (57%) were classified as responders, while 25 patients (43%) were considered non-responders. Baseline values of FEV1% predicted, 6MWD, DE during deep breathing, DTF, and PaO2 exhibited a significant elevation in responders as compared to non-responders. The changes of 6MWD were positively associated with the baseline values of DTF and DE during deep breathing, FEV1% predicted and PaO2, while negatively correlated with baseline value of mMRC. The predictive performance in terms of the area under the ROC curve for determining responder's DTF was found to be 0.769, accompanied by a sensitivity of 85% and specificity of 68%, using a cutoff value at 17.26%. Moreover, it was observed that DE during deep breathing could predict the area under the ROC curve for responders to be 0.753, with a sensitivity of 91% and specificity of 56% at a cutoff value of 3.61cm. Conclusion: Diaphragm excursion serves as a valuable predictor for determining the enhancement of exercise tolerance following PR in patients with COPD-OSA overlap syndrome. Trial Registration: ChiCTR1800020257, www.chictr.org.cn/index.aspx.

Effects of Comprehensive Outpatient Cardiac Rehabilitation on Exercise Capacity, Functional Status, and Quality of Life in People With Heart Failure: A Systematic Review and Meta-Analysis.

PURPOSE: The purpose of this study was to systematically review and conduct a meta-analysis to examine the impact of comprehensive outpatient cardiac rehabilitation on exercise capacity, functional status, and quality of life in patients with heart failure. METHODS: PubMed, Embase, and CINAHL were searched using keywords and MeSH terms on heart failure and cardiac rehabilitation. Randomized clinical trials published in English using outpatient exercise-based cardiac rehabilitation in patients with heart failure were included. The Grading of Recommendations Assessment, Development, and Evaluation was utilized for quality appraisal. Pooled estimates were computed using standardized mean differences (SMDs) and 95% CIs. Primary outcomes were functional status (6-minute walk distance, quality of life, exercise capacity using peak oxygen consumption, muscle strength, and endurance). RESULTS: Eleven randomized controlled trials including 1523 participants ranging from 45 to 80 years old and an intervention duration ranging from 2 to 26 weeks were analyzed. Pooled results indicated significant improvements with comprehensive cardiac rehabilitation on 6-minute walk distance (SMD = 0.30; 95% CI = 0.06 to 0.54) and oxygen consumption (SMD = 0.23; 95% CI = 0.06 to 0.40). However, there was no additional benefit for the quality of life beyond that seen in the comparison groups. CONCLUSION: Results of this study suggest that comprehensive outpatient cardiac rehabilitation is associated with significantly better clinical outcomes than single-component exercise programs in cardiac rehabilitation settings, multicomponent exercise in noncardiac rehabilitation settings, or no exercise. IMPACT: Heart failure is significantly associated with an increased risk of poor exercise tolerance. Despite the proven benefit of cardiac rehabilitation on exercise tolerance and physical activities from individual randomized clinical trials, questions regarding its impact on clinical outcomes such as exercise capacity, functional status, and quality of life remain inadequate. This systematic review and meta-analysis provides strong evidence supporting comprehensive outpatient cardiac rehabilitation for improving clinical outcomes in heart failure.

Respiratory function in healthy long-term meditators: A cross-sectional comparative study.

Purpose: Respiratory function is thought to improve with long-term meditation. This study aimed to assess respiratory function in a cohort of healthy long-term meditators and non-meditators in Sri Lanka. Methods: Respiratory function of healthy, skilled long-term meditators (n = 20) practicing Buddhist meditation consistently >3 years, and age-sex matched non-meditators (n = 20) were assessed by assessing resting respiratory rate, spirometry, breath-holding time and six-minute-walk distance. Data were analyzed with SPSS-23 statistical software. Results: The long-term meditators; 45% male, mean (SD) total lifetime meditation experience 12.8 (6.5) years, aged 45.8 (8.74) years, BMI 23.68 (2.23) kgm-2, and non-meditators; 45% male, mean (SD) age 45.3 (8.05) years, BMI 23.68 (3.28) kgm-2, were comparable. Long-term meditators had slower resting respiratory rates [mean (SD); 13.35 (1.9) vs. 18.37 (2.31) breaths/minute; p < 0.001], higher peak expiratory flow rates [mean (SD); 9.89 (2.5) vs. 8.22 (2.3) L/s; p = 0.03], and higher inspiratory breath-holding times [mean (SD); 74 (29.84) vs. 53.61 (26.83) seconds, p = 0.038] compared to non-meditators. There was no significant difference in the six-minute-walk distance and estimated maximal oxygen consumption between the two groups.Resting respiratory rate of long-term meditators, showed a significant negative correlation with total lifetime meditation practice in years (r = -0.444, p = 0.049), and the average length of a meditation session per day (r = -0.65, p = 0.002). The long-term meditators with longer duration of retreat participation demonstrated lower resting respiratory rate (r = -0.522, p = 0.018) and higher tidal volumes (r = 0.474, p = 0.04). Conclusions: Long-term meditators had significantly slower resting respiratory rates and longer breath-holding times, with better spirometry parameters than non-meditators. Greater practice duration and retreat experience appear to be associated with improved resting respiratory function in long-term meditators.

Longitudinal significance of six-minute walk test in patients with nontuberculous mycobacterial pulmonary disease: an observational study.

BACKGROUND: The long-term exercise tolerance changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) are of great interest because of its chronic course. This study aimed to characterize the associations between changes over time in six-minute walking test (6MWT) parameters and clinical parameters in patients with NTM-PD. METHODS: Overall, 188 patients with NTM-PD, visiting outpatient clinics at Keio University Hospital from April 2012 to March 2020 were included in the study. Data were collected using the St. George's Respiratory Questionnaire (SGRQ), pulmonary function test (PFT), blood tests, and the 6MWT at registration and at least once after that. The association of the anchors and clinical indicators with the 6MWT parameters was assessed. RESULTS: The median age [interquartile range] of the patients was 67 [63-74] years. The median baseline six-minute walk distance (6MWD) and final Borg scale (FBS) were 413 [361-470] m and 1 [0-2], respectively. In the correlation analysis, ΔSGRQ total/year (yr), Δforced vital capacity (FVC, % predicted)/yr, Δforced expiratory volume in 1 s (FEV1, % predicted)/yr, and Δdiffusing capacity for carbon monoxide (DLCO, % predicted)/yr correlated with both Δ6MWD/yr and ΔFBS/yr in the longitudinal analysis (|Rho| > 0.20). When stratified into three quantiles of changes in each anchor, the 6MWT parameters worsened over time in the bottom 25% group by mixed-effects model. Specifically, Δ6MWD was affected by SGRQ activity, SGRQ impacts, PFT (FVC, FEV1, and DLCO), and C-reactive protein (CRP). ΔFBS was affected by all SGRQ components, total score, and PFT. Anchor scores and variables at baseline that worsened Δ6MWD were higher SGRQ scores, lower FVC (% predicted), lower DLCO (% predicted), higher Krebs von den Lungen-6, old age, and undergoing treatment at registration. Similarly, these clinical parameters and elevated CRP, excluding undergoing treatment at registration, worsened ΔFBS. CONCLUSIONS: The decreased walking distance and exacerbation of dyspnea on exertion over time in patients with NTM-PD may reflect a deterioration of health-related quality of life and pulmonary function. Thus, the change in 6MWT over time can be used as an indicator to accurately assess the patient's condition and tailor their healthcare environment.

Predictive equation for six-minute walk test in Indian children, adolescents, and adults.

Background: Post-COVID residual dysfunction has been observed in a majority of people, with reduction in cardiopulmonary endurance emerging as a primary symptom. The Six-Minute Walk Test is a simple, reliable, and valid test that is used routinely on people with chronic respiratory dysfunction. In the current COVID-19 pandemic situation, reference values and a predictive equation developed from a large sample across a large age group, from 6 to 75 years, will enable one to establish goals of treatment for post-COVID rehabilitation. Methods: Following institutional ethical clearance, we recruited 1369 participants for the study (685 females and 684 males). Participants were classified according to biological age into group 1 (6-12 years), group 2 (13-17 years), group 3 (18-40 years), group 4 (41-65 years), and group 5 (>65 years). Informed consent was sought and participants were screened using a health history questionnaire. Demographic features, namely, age, height, weight, and body mass index (BMI) were noted. The Six-Minute Walk Test was administered as per ATS guidelines. Clinical parameters, namely, pulse rate, respiratory rate, systolic blood pressure, diastolic blood pressure, and rate of perceived exertion were recorded. Results: The Six-Minute Walk Test (6MWT) was significantly influenced by age and gender (r = 0.257, P = 0.00 and r = 0.501, P = 0.00, respectively). Walking distance was longest in 13-17-year-old males, whereas females demonstrated a linear decline after 12 years. In each age group, males walked a greater distance than females. Stepwise linear regression analysis was used to derive the following predictive equation: 6MWT = 491.93 - (2.148 × age) + (107.07 × gender) (females = 0, males = 1). Conclusion: The study confirmed variability of the Six-Minute Walk Test, with age and gender being predominant predictors. Reference values, equations, and percentile charts generated from the study can be utilised to guide clinical decision-making while exercise prescription for patients with post COVID dysfunction.

Is the six-minute walk test still reliable compared to cardiopulmonary exercise test for exercise capacity in children with congenital heart disease?

Objectives: We aimed to assess the validity of the six-minute walk test (6MWT) to reflect the functional capacity of children with congenital heart disease (CHD), evaluate a possible correlation between the 6MWT distance with cardiopulmonary exercise test (CPET) variables, as well as to find a cutoff value to stratification the physical fitness in this population. Methods: We enrolled 459 children with CHD, 6-18 years old, who performed a complete CPET and 6MWT on the same day in a cross-sectional observational study. Correlations between variables of CPET and six-minute walking distance (6MWD) were analyzed and cutoff values of 6MWD were identified for the classification of the physical fitness in the population. Results: The mean distance ambulated during the 6MWT was 578 ± 65 m, 590 ± 65 m for boys, and 562 ± 62 m for girls (p < 0.001). Both VO2max and %predicted VO2max showed a correlation with the 6MWT distance (r = 0.35, p < 0.001 and r = 0.51, p < 0.001, respectively), and an inverse correlation was found between VE/VCO2 slope and the 6MWT distance (r = -0.31; p < 0.001). There appeared to be a linear association between 6MWD and VO2max up to a 6MWD of approximately 600 m. We divided the population into 4 subgroups (boys <130 cm; boys ≥130 cm; girls <130 cm; girls ≥130 cm), and get the cutoff values (554 m, 617 m, 549 m, 587 m) respectively equivalent to 80% of predicted VO2max. The 6MWT distances of another 102 patients were applied for external verification of the cutoff values. Conclusions: Our study provided evidence on when a 6MWT should be considered as a convincing complementary test in the pediatric population with CHD and explored the classification of exercise tolerance using a 6MWD value. The cut-off values for 6MWD may be qualified as an intervention target for exercise rehabilitation.

Transitioning Stable Patients with Pulmonary Arterial Hypertension from Parenteral Prostanoids to Oral Selexipag.

Introduction: Parenteral prostanoids are the most potent therapies for pulmonary arterial hypertension (PAH) but are associated with complications and lifestyle limitations. Carefully selected stable patients may be considered for a transition from parenteral prostanoids to a more convenient oral regimen. We present our experience transitioning patients on parenteral prostanoids to selexipag on an outpatient basis. Methods: This was a retrospective cohort study of all group 1 PAH patients on parenteral prostanoids who transitioned to selexipag using a standardized outpatient-based protocol. Hospitalization and routine prognostic data were recorded. Results: Fourteen patients were followed for a median of 1,240 (1,052-1,528) days; all were functional class (FC) II (n = 9) or III (n = 5). Thirteen patients completed the transition, including 11 who underwent catheterization 376 (321-735) days after discontinuing parenteral therapy. Three patients had unfavorable transitions requiring reinitiation of parenteral treatment. Overall, pulmonary vascular resistance increased (3.3-4.5 WU, p = 0.01), cardiac index fell (4.0-2.8 L/min/m2, p = 0.01), N-terminal pro-hormone of brain natriuretic peptide worsened (111-205 pg/dL, p = 0.03), but PAH-related hospitalizations improved (27-8, p = 0.02). Cardiac imaging, FC, and 6-min walk distance (6MWD) were unchanged. Patients who failed were older (64 vs. 56 years old) with shorter 6MWD (274 vs. 392 m) and higher REVEAL 2.0 scores (11 vs. 3). Conclusions: Transition from parenteral prostanoids to oral selexipag in carefully selected low-risk patients was well-tolerated in many patients, with up to 5 years of follow-up. Overall, the hemodynamic response to transition is unpredictable and close monitoring, particularly in the first year of follow-up, is recommended. Additional evaluation of potential predictors of success is necessary.

Whole-Body Vibration or Aerobic Exercise in Patients with Bronchiectasis? A Randomized Controlled Study.

Background and Objectives: The whole-body vibration (WBV) technique is an exercise training method. It has been reported to improve muscle strength, exercise capacity, and the quality of life. However, there is no study on the use of the WBV technique in bronchiectasis. The aim of the present study is to compare the effect of aerobic exercise with whole-body vibration on exercise capacity, respiratory function, dyspnea, and quality of life (QoL) in bronchiectasis patients. Materials and Methods: Clinically stable bronchiectasis patients aged 18−74 years participated in this study. A pulmonary function test, 6 minute walk test (6MWT), five times sit-to-stand test (FTSST), Modified Medical Research Council (mMRC) Scale, an, St. Georges Respiratory Questionnaire (SGRQ) were used in the evaluation. In total, 41 patients (WBV group: 20, aerobic group: 21) completed the study. The patients were treated for eight weeks. Results: When the two groups were compared after the treatment, there was a significant difference between the mMRC scores in favor of the WBV group (p < 0.05). When the results of the WBV group were examined before and after treatment, a significant difference was found between the 5SST and 6MWT (p < 0.05). When the aerobic group was compared before and after the treatment, it was observed that there was a significant difference in FVC, FVC%, 5SST, 6MWT, and SGRQ total score, and activity and impact scores, which are the sub-parameters (p < 0.05). Conclusions: Eight weeks of WBV exercise can lead to significant improvements in patients with bronchiectasis, exercise capacity, and dyspnea. Larger studies are needed to define the optimal intensity and duration of WBV, as well as to investigate its possible long-term effects.

Inspiratory Muscle Training Improves Aerobic Fitness in Active Children.

Research on the effect of inspiratory muscle training (IMT) on exercise performance is inconsistent. IMT has not been applied to fit child athletes, who are more likely to develop inspiratory muscle fatigue, and, consequently, to benefit from IMT. Methods: Thirty children (mean age: 10.7 ± 1.2 years) were recruited and randomly assigned to a high-intensity (HG), a low-intensity (LG), or a control group (CG). For both training groups, a double-blind procedure was applied. In the HG, 80% of maximal inspiratory pressure (MIP) was used as the level of training intensity. The LG used 30% MIP. Training groups were trained at 6 breaths a set, 4 sets a day, totaling 24 breaths a day for 6 weeks. Exercise capacity outcomes include maximal and submaximal aerobic capacity, as measured as VO2max and distance from six-minute walk test (6MWD). Results show improvement in MIP, VO2max, and 6MWD only in the HG. MIP in the HG significantly increases from 108.7 (100.8-143.3) to 144.4 (130.0-175.6) cmH2O. VO2max in the HG increases from 43.0 (40.5-45) to 53.0 (46-63) mL·kg-1·min-1. The 6MWD increases from 792.0 (737.5-818.0) to 862.0 (798.5-953.5) m. Data are presented as median (interquartile range). No difference is found in the LG or CG. Conclusion: high-intensity IMT increases MIP, maximal, and submaximal exercise capacity in the HG, but no difference is found in the LG or CG. Therefore, high-intensity type of IMT improves aerobic fitness in fit children by appropriately applying inspiratory muscle strength training.

A Mobile Application to Perform the Six-Minute Walk Test (6MWT) at Home: A Random Walk in the Park Is as Accurate as a Standardized 6MWT.

The six-minute walk test (6MWT) provides an objective measurement of a person's functional exercise capacity. In this study, we developed a smartphone application that allows cardiac patients to do a self-administered 6MWT at home on a random trajectory. In a prospective study with 102 cardiovascular disease patients, we aimed to identify the optimal circumstances to perform a smartphone-measured 6MWT, i.e., the best algorithm and the best position to wear the smartphone during the test. Furthermore, we investigated if a random walk is as accurate as a standardized 6MWT. When considering both the reliability and accuracy of the distance walked, the best circumstances to perform a standardized smartphone-measured 6MWT are wearing the smartphone in a strap around the patient's arm and using an algorithm that relies on the processed step count data acquired from Google Fit. Furthermore, we demonstrated that a smartphone-measured walk along a random trajectory is as accurate to determine a cardiac patient's functional exercise capacity as a standardized (smartphone-measured) 6MWT. We conclude this paper by presenting how our 6MWT application can be used in a home setting to remotely follow up on cardiac patients' functional exercise capacity.

Deflazacort dose optimization and safety evaluation in Duchenne muscular dystrophy (DOSE): A randomized, double-blind non-inferiority trial.

BACKGROUND: US food and drug administration has recently approved deflazacort for Duchenne muscular dystrophy (DMD) and recommended the dosage of 0.9 mg/kg/d for patients aged ≥5years. However, data assessing the minimal efficacious dose and need of dose-titration based on age or disease severity is limited. OBJECTIVE: To determine whether deflazacort 0.45 mg/kg/d (proposed lower dosage) is non-inferior to 0.9 mg/kg/d among newly diagnosed patients with DMD. METHOD: A double-blinded, non-inferiority, randomized trial, conducted between December 2018 and July 2020. Newly diagnosed patient aged 5-15 years with genetic or muscle biopsy confirmed DMD and baseline 6-min walk distance (6MWD) > 150 m were screened. Patients were randomly assigned (1:1), stratified to prespecified subgroups by age (≤7years and >7years), and baseline 6MWD (≤350 m and >350 m), to receive either 0.45 mg/kg/d or 0.9 mg/kg/d regimens. The primary endpoint was the change in 6MWD, from baseline to week-24 of intervention. The trial was powered with a predefined, non-inferiority margin of 30 m. The analyses were by modified intention-to-treat (mITT). RESULT: A total of 97 patients were enrolled, 40 receiving 0.45 mg/kg/d and 45 receiving 0.9 mg/kg/d deflazacort comprised of mITT population. For primary endpoint analysis the mean (SD) change in 6MWD from baseline to week-24 was 9.7 m (41.5) in deflazacort 0.45 mg/kg/d, and 34.7 m (43.5) for 0.9 mg/kg/d. The mean difference in change in 6MWD across the group was 24.8 m (95% CI 6.7 to 43, p value 0.008). The mean difference in change in 6MWD in the subgroups of boys ≤7 years of age was 21.8 m (95% CI -0.82, 44.5, p = 0.059), with baseline 6MWD of >350 m was 19.9 m (95% CI -2.4, 42.4; p = 0.08). The incidence of combined moderate to severe treatment-related adverse events was significant in the 0.9 mg/kg/d group by week 24 (odds ratio 0.36 [95% CI, 0.14 to 0.89], p = 0.03). DISCUSSION: The efficacy of proposed low dose deflazacort in comparison to the standard dose did not meet the prespecified criteria for non-inferiority. The low dose deflazacort was non-inferior in subgroup of patients with age ≤7 years and baseline 6MWD of >350 m. TRIAL REGISTRATION: Clinical Trial Registry-India Identifier: CTRI/2019/02/017388.

An Alternative Prediction Equation for Evaluation of Six-Minute Walk Distance in Stable Coronary Artery Disease Patients.

Background: As cardio-vascular diseases are the leading cause of death worldwide, establishing measures to improve cardiovascular health is of crucial importance. Exercise plays an essential role in cardiac rehabilitation of patients with coronary artery disease (CAD), in whom an evaluation of the cardiorespiratory fitness (CRF) is necessary. CRF of CAD patients could be assessed using 6-min walk test (6MWT), and the results interpreted by using Enright-Sherill prediction equation which has mainly been designed and evaluated for a healthy population. Hypothesizing that the Enright-Sherill prediction equation might not be best suited for CAD patients, our aim was to reevaluate this equation in CAD patients, and potentially establish a more accurate 6MWD prediction equation to be applied in these patients. Methods: 6MWD was measured in a cross-sectional study in 67 CAD patients (44 women) who were members of the Coronary club Ljubljana, Slovenia. In addition, the predicted 6MWD was calculated for men and women using Enright-Sherill gender specific regression equation. Multivariate regression analysis was used to obtain a new prediction equation, and the agreement between the measured and the predicted 6MWD analyzed using the repeated measures ANOVA. Results: Men achieved 451 ± 122 m and women 485 ± 69 m without significant differences between sexes (F = 0.022, p = 0.882) when adjusted for age, height, body mass, and waist circumference. When comparing the measured (473 ± 91 m) and the predicted (422 ± 57 m) values of 6MWD in CAD patients we found that the Enright-Sherill prediction equation significantly (F = 27.734, p < 0.001) underestimated the 6MWD by 52 ± 81 m. A significant regression equation was established [F (3,63) = 44.663, p < 0.001], with a R 2 of 0.680 where 6MWD equals 1,057 m-4.966 x age (years)-0.614 x WC (cm)-68.629 x NYHA class. Conclusion: The results of this study stress the importance of regular and actual walking ability testing in patients with stable CAD to obtain their CRF, rather than simply predicting it from regression equations obtained from non-representative or non-comparable samples. Our developed prediction equation warrants additional validation and may represent a good substitute for currently used predictions obtained from a healthy population.

The six-minute walk test in sarcoidosis associated pulmonary hypertension: Results from an international registry.

INTRODUCTION: Sarcoidosis associated pulmonary hypertension (SAPH) is a leading contributor to sarcoidosis-related mortality. The 6-min walk test (6MWT) is widely used in assessment of cardiorespiratory conditions. A reduced 6-min walk distance (6MWD) has been associated with increased mortality in SAPH. We examined patients from the Registry of Sarcoidosis Associated Pulmonary Hypertension (ReSAPH) who had performed 6MWT at enrollment to identify variables that affect 6MWD, and the prognostic value of 6MWT variables regarding death or lung transplantation. MATERIAL AND METHODS: ReSAPH patients with available 6MWT were included. Variables analyzed using pre-defined cutoffs included 6MWD, initial and end of test Borg dyspnea score, oxygen saturation, and heart rate at beginning, end, and after 1-min recovery, absolute change in oxygen saturation, modified distance-saturation product (mDSP), and the heart rate recovery at 1-min (HRR). FINDINGS: 174 patients met inclusion criteria; 48 patients died and 8 underwent lung transplantation. Patients with 6MWD<300 m had a higher chance of dying or undergoing transplantation compared to those with 6MWD>300 m (p = 0.012). No associations with outcome were observed with mDSP cutoff 200 m%, desaturation≥5% and oxygen saturation<88% at end of 6MWT, or multiple HRR cutoffs (13,14,16). 6MWD correlated with initial Borg score, (p = 0.001), DLCO% (p = 0.0001) and sPAP (p = 0.031) on multivariate analysis. These variables were significant for both pre- and post-capillary PH subgroups. 6MWD also correlated with fatigue assessment scale (FAS) (p = 0.015). CONCLUSION: Of the parameters evaluated, 6MWD had the greatest prognostic value in SAPH which correlated with other physiologic and hemodynamic variables. 6MWT captures the multidimensional effects of sarcoidosis.

Supervised hospital based pulmonary rehabilitation outcome in long COVID-experience from a tertiary care hospital.

Introduction: Some patients suffer from various multisystem symptoms even after active process of COVID-19 illness has settled lasting more than four weeks called as long COVID. Pulmonary rehabilitation therapy is the proposed option in those patients. This study aims to study the impact of pulmonary rehabilitation on outcome of long COVID patients through improvement in mMRC dyspnea scale, oxygen saturation, cough score, six-minute walk distance and biomarkers of inflammation. Materials and Methods: A retrospective observational study was carried out from the data of electronic medical records among 71 Long COVID patients. Parameters like Spo2, MMRC scale, cough score, six-minute walking distance along with blood levels of D-dimer, C-reactive protein (CRP), leucocyte count at the time of admission and after three weeks of pulmonary rehabilitation were collected. The outcome among the patients was divided into full recovery and partial recovery group. Statistical analysis was done using SPSS software version 19.0. Result: Among 71 cases in our study 60 (84.50%) where male with mean age was 52.7 ± 13.23 years. Biomarkers like CRP and d-Dimer were elevated in 68 (95.7%) and 48 (67.6%) patients, respectively, at the time of admission. After 3 weeks of pulmonary rehabilitation mean SPO2, cough score, 6MWD showed significant improvement and normalization of biomarkers in recovered group of 61 out of 71 which was statistically significant. Conclusion: Significant improvement of oxygen saturation, mMRC grade, cough score, six-minute walk distance and normalization of biomarkers were marked following pulmonary rehabilitation. Thus, pulmonary rehabilitation therapy should be offered to all long COVID cases.

Diaphragmatic excursion is correlated with the improvement in exercise tolerance after pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the maximum level of diaphragm excursion (DEmax) is correlated with dynamic lung hyperinflation and exercise tolerance. This study aimed to elucidate the utility of DEmax to predict the improvement in exercise tolerance after pulmonary rehabilitation (PR) in patients with COPD. METHODS: This was a prospective cohort study. Of the 62 patients with stable COPD who participated in the outpatient PR programme from April 2018 to February 2021, 50 completed the programme. Six-minute walk distance (6MWD) was performed to evaluate exercise tolerance, and ultrasonography was performed to measure DEmax. Responders to PR in exercise capacity were defined as patients who demonstrated an increase of > 30 m in 6MWD. The receiver operating characteristic (ROC) curve was used to determine the cut-off point of DEmax to predict responses to PR. RESULTS: Baseline levels of forced expiratory volume in 1 s, 6MWD, maximum inspiratory pressure, DEmax and quadriceps muscle strength were significantly higher, and peak dyspnoea of modified Borg (mBorg) scale score was lower in responders (n = 30) than in non-responders (n = 20) to PR (p < 0.01). In multivariate analysis, DEmax was significantly correlated with an increase of > 30 m in 6MWD. The area under the ROC curve of DEmax to predict responders was 0.915, with a sensitivity and specificity of 83% and 95%, respectively, at a cut-off value of 44.9 mm of DEmax. CONCLUSION: DEmax could adequately predict the improvement in exercise tolerance after PR in patients with COPD.