Change In 6-minute Walk Distance Research Articles

Safety and Efficacy of the Soluble Guanylate Cyclase Stimulator Praliciguat in Patients with Heart Failure with Preserved Ejection Fraction (Capacity HFpEF): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial

Introduction Heart failure with preserved ejection fraction (HFpEF) is associated with poor quality of life and increased mortality with exercise intolerance being the main symptom. Hypothesis The soluble guanylate cyclase (sGC) stimulator praliciguat (PRL) may help restore deficient NO-sGC-cGMP signaling and improve exercise capacity. Methods CAPACITY HFpEF was a phase 2, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of PRL over 12 weeks in patients with HFpEF and at least 2 of 4 conditions potentially associated with NO deficiency (diabetes, hypertension, obesity, age >70 years). Patients were randomized to PRL or placebo. The primary endpoints were change from baseline to week 12 in peak oxygen consumption (pVO2) by cardiopulmonary exercise testing and treatment-emergent adverse events (TEAEs). Secondary endpoints included the change in 6-minute walk distance (6MWD), ventilatory efficiency (VE/VCO2 slope), and the proportion of pVO2 responders (change ≥1.5 mL/kg/min). Health status was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Results Among 196 patients randomized (mean age 70.3 years, 57% men), 169 completed. For the evaluable population (completed 8 weeks of dosing with no dose reduction), mean baseline pVO2 was 13.3 and 12.8 mL O2/kg/min in PRL 40 mg (N=65) and placebo (N=78) groups, respectively. Placebo-adjusted least squares mean changes from baseline to week 12 [95% CI] were pVO2 (-0.30 mL O2/kg/min [-0.95, 0.35] p=0.37), 6MWD (-16.7 m [-47.4, 13.9]) and VE/VCO2 slope (-0.30 [-1.59, 1.00]). The odds ratio for pVO2 response [95% CI] was 0.91 [0.40, 2.1]. KCCQ overall and domain scores did not improve in the PRL group versus the placebo group. PRL was generally well tolerated; headache, dizziness, and hypotension TEAEs were reported more frequently in the PRL group. The frequency of serious TEAEs was similar between groups. Conclusion In a population selected to enrich for the metabolic/NO-deficient profile of HFpEF, PRL was well tolerated but did not affect pVO2, 6MWD, VE/VCO2 slope, proportion of pVO2 responders or KCCQ scores over 12 weeks compared to placebo.

Changes in 6-minute walking distance in lung transplant candidates while participating in a home-based pre-habilitation program-A retrospective chart review.

Home-based exercise programs may offer a less costly alternative to providing exercise pre-transplant to a large number of patients. We describe the changes in 6-minute walk distance (6MWD) in lung transplant candidates who participated in a home-based exercise program and their relationship to post-transplant outcomes. Retrospectively, we investigated 159 individuals while awaiting transplantation who performed the surgery between 2011 and 2015. Primary outcome was 6MWD at time of assessment for transplant, last test prior to transplant and one-month post-transplant. 6MWD decreased by 28±93.9m between the time of assessment and the last 6MWD prior to transplantation (P<.001). Forty-one patients (25.8%) increased their 6MWD (mean+85.8±42.8m); 72 patients (45.3%) decreased their 6MWD (mean -109.8±71.2m); and 46 patients (28.9%) had no change in 6MWD (-1.5±15.7m). There was a moderate correlation (r=.528; P<.001) between the last 6MWD prior to transplant and 6MWD post-transplant. Change in 6MWD prior to transplant weakly correlated with length of time on mechanical ventilation (r=-.185; P=.034). When adjusted for covariates, change in 6MWD prior to transplant was not associated with length of time on mechanical ventilation, total hospital LOS, or intensive care unit LOS. The majority of the patients were able to either increase or maintain their 6MWD while participating in a home-based pre-habilitation program during the waiting list period. Prospective research is needed to evaluate the effects of home-based pre-habilitation program for lung candidates.

Pulmonary Hypertension Roundtable: Drug Development and Negative Clinical Trial Results

Pulmonary Hypertension Roundtable: Drug Development and Negative Clinical Trial Results

Functional Capacity Of Patients One Year Post Cardiac Rehabilitation

BACKGROUND: Cardiac rehabilitation (CR) improves functional capacity (FC), quality of life (QoL), psychosocial well-being, and reduces cardiovascular risk factors using lifestyle management strategies. Despite well known benefits, little is known about the long-term effects of CR on risk factor management and changes in FC following discharge. Therefore, the purpose of this retrospective cross-sectional investigation was to examine changes in 6-minute walk distance (6MWD) 11-15 months following CR. METHODS: Patients referred to the UAB Cardiac Rehabilitation Program from 2016-2019 who completed 24-36 sessions and 6-minute walk tests (6MWT) at intake, discharge, and post-discharge were included in this pilot investigation. Twenty-two patients were included with the following CVD diagnoses: myocardial infarction, angina, PCI, CABS, or valve replacement. Repeated measures analysis of variance (ANOVA) was used to examine differences over time for 6MWD with least significance difference (LSD) post-hoc testing (SPSS, v25). RESULTS: 6MWD increased by 30% from intake to discharge (388 ± 96 m to 504 ± 123 m, P < 0.0001). Post-discharge walking distance (519 ± 118 m) remained higher than intake (P < 0.0001) but was similar to discharge (P = 0.091). Body weight, waist circumference, systolic blood pressure (SBP), and diastolic blood pressure (DBP) all returned to baseline intake values post-discharge. CONCLUSIONS: The results of this study suggest that CR may produce lifestyle and behavioral changes that promote long-term maintenance of FC. While an extensive examination of other risk factors was not performed, increases in body weight and blood pressure observed 11-15 months post-discharge are discouraging. A thorough examination of the long-term consequences of these findings with preserved FC will be needed to explore the interaction between FC and other risk factors as it relates to secondary prevention of CVD. Sponsor: UAB Departments of Human Studies and Cardiopulmonary Rehabilitation

Clinical characteristics and response to supervised exercise therapy of people with lower extremity peripheral artery disease

BackgroundAmong people with lower extremity peripheral artery disease (PAD), little is known about variation in response to supervised exercise therapy (SET). Clinical characteristics associated with greater responsiveness to SET have not been identified. MethodsData from participants with PAD in two randomized clinical trials comparing SET vs nonexercising control were combined. The exercise intervention consisted of three times weekly supervised treadmill exercise. The control groups received lectures on health-related topics. ResultsOf 309 unique participants randomized (mean age, 67.9 years [standard deviation, 9.3 years]; 132 [42.7%] women; 185 [59.9%] black), 285 (92%) completed 6-month follow-up. Compared with control, those randomized to SET improved 6-minute walk distance by 35.6 meters (95% confidence interval, 21.4-49.8; P < .001). In the 95 (62.1%) participants who attended at least 70% of SET sessions, change in 6-minute walk distance varied from −149.4 to +356.0 meters. Thirty-four (35.8%) had no 6-minute walk distance improvement. Among all participants, age, sex, race, body mass index, prior lower extremity revascularization, and other clinical characteristics did not affect the degree of improvement in 6-minute walk distance after SET relative to the control group. Participants with 6-minute walk distance less than the median of 334 meters at baseline had greater percentage improvement in 6-minute walk distance compared with those with baseline 6-minute walk distance above the median (+20.5% vs +5.3%; P for interaction = .0107). ConclusionsAmong people with PAD, substantial variability exists in walking improvement after SET. Shorter 6-minute walk distance at baseline was associated with greater improvement after SET, but other clinical characteristics, including age, sex, prior lower extremity revascularization, and disease severity, did not affect responsiveness to exercise therapy.

Ambulatory Oxygen in Fibrotic Interstitial Lung Disease: A Pilot, Randomized, Triple-Blinded, Sham-Controlled Trial

Despite a lack of evidence, ambulatory oxygen therapy is frequently prescribed for patients with interstitial lung disease (ILD) and exertional desaturation. Patients often prefer portable oxygen concentrators to oxygen cylinders. This study aimed to examine the feasibility of conducting a clinical trial of ambulatory oxygen delivered via portable concentrators in patients with ILD. Is it feasible to conduct a clinical trial of ambulatory oxygen delivered via portable concentrators in patients with ILD? In this randomized, triple-blinded, sham-controlled trial, 30 participants with ILD and isolated exertional desaturation to< 90%on 6-minute walk tests were randomized to 12-week ambulatory oxygen or air delivered via portable concentrators, with assessments performed at baseline and weeks 4, 12, and 18. Primary outcomes were trial feasibility and the change in 6-minute walk distance (6MWD) on room air at week12. Study recruitment was completed within 18months, with six withdrawals. Participant blinding was successful, with the Bang's Blinding Index being 0 (95%CI, -0.40 to 0.40) for the oxygen group and 0 (95% CI, -0.42 to 0.42) for the sham group. No significant difference in 6MWD was seen between groups at week 12 (mean difference of -34m [95%CI, -105 to 36], P= .34). For secondary outcomes, compared with the sham group, the oxygen group had a significantly higher Leicester Cough Questionnaire psychological domain score, indicating better cough-related quality of life (mean difference of 0.9 [95%CI, 0.2 to 1.6], P= .01), but a shorter duration of moderate-to-vigorous activities (mean difference of -135 [95%CI, -267 to -3], P= .04) at week12. Based on the results of this pilot study, a definitive randomized controlled trial with a longer intervention duration is warranted to clarify therapeutic impacts of ambulatory oxygen in patients with ILD. Australian New Zealand Clinical Trials Registry; No.: ACTRN12617000054314; URL: www.anzctr.org.au/.

A single-centre, placebo-controlled, double-blind randomised cross-over study of nebulised iloprost in patients with Eisenmenger syndrome: A pilot study

BackgroundPulmonary arterial hypertension (PAH), is a rare and progressive disease with a high morbidity and mortality. Prostanoid pulmonary vasodilators are the most effective treatment for idiopathic and connective tissue associated PAH. Nonetheless, data examining their safety and efficacy in patients with Eisenmenger syndrome the most severe form of PAH, that is, related to cyanotic congenital heart disease (CHD-PAH) remains limited. AimTo evaluate safety and the clinical efficacy of nebulised iloprost in patients with Eisenmenger syndrome who are on maximum background oral PAH therapy. MethodsThis pilot study was a randomised, double-blind, placebo-controlled, cross-over study. Patients were randomised to receive nebulised placebo or iloprost for 12 weeks and were then crossed over, with a 7–14-day washout. The primary endpoint was a change in 6-minute walk distance (6MWD). ResultsSixteen patients (11 females, aged 47.3 ± 9.8 year) were recruited, twelve completed the study. All were in WHO-FC III, with a resting oxygen saturation of 84 [81–87] % and a median 6MWD of 290 [260–300] m. There was no significant difference in the primary endpoint between nebulised iloprost (0[−4–9]m) and placebo (10 [−15–51]m), p = 0.58. There were no safety concerns with nebulised iloprost. ConclusionsOur pilot study provides preliminary evidence that the addition of nebulised iloprost to maximum oral PAH therapy did not improve the primary endpoint of 6MWD. Nebulised iloprost was well tolerated with no significant safety concerns in CHD-PAH.

Mobile Health Management Platform-Based Pulmonary Rehabilitation for Patients With Non-Small Cell Lung Cancer: Prospective Clinical Trial.

BackgroundLung cancer patients experience various symptoms during treatment. Although pulmonary rehabilitation is an effective way to improve these symptoms, a medical environment of limited availability makes it difficult to provide seamless and adequate rehabilitation for lung cancer patients.ObjectiveThis study aimed to investigate the effects of a personalized pulmonary rehabilitation program using real-time mobile patient health data for patients with non–small cell lung cancer.MethodsWe conducted a prospective clinical trial in 64 patients with non–small cell lung cancer aged between 20 and 80 years at a large tertiary hospital in Seoul, South Korea. A 12-week personalized pulmonary rehabilitation program, called efil breath, was administered to determine the effectiveness of the newly developed rehabilitation app. Participants were randomly allocated to the fixed exercise or fixed-interactive exercise group (which received the personalized program). We measured changes in 6-minute walk distance (6MWD) and dyspnea (modified Medical Research Council [mMRC] score) at 6 weeks; and quality of life and service satisfaction at 12 weeks. We used the paired t test to analyze the variables.ResultsPatients used the newly developed mobile health pulmonary rehabilitation app and a real-time patient monitoring website. In all participants, significant changes were observed in 6MWD at 12 weeks from a mean of 433.43m (SD 65.60) to 471.25m (SD 75.69; P=.001), and mMRC from a mean score of 0.94 (0.66) to 0.61 (SD 0.82; P=.02). The intervention significantly improved their quality of life (EuroQol-visual analog scale [EQ-VAS]) compared with baseline (mean score 76.05, SD 12.37 vs 82.09, SD 13.67, respectively; P=.002).ConclusionsA personalized mobile health–based pulmonary rehabilitation app for recording and monitoring real-time health data of patients with non–small cell lung cancer can supplement traditional health care center–based rehabilitation programs. This technology can encourage improvement of physical activity, dyspnea, and quality of life.

MON-120 Effect of Weight Loss on Physical Function Measured by the 6-Minute Walking Distance Test in Individuals with Obesity: Results from the SCALE IBT Trial of Liraglutide 3.0 Mg

In clinical trials for weight management, changes in physical function are typically assessed with self-report HRQoL questionnaires. In this trial we aimed to objectively measure the effect of weight loss on walking capacity, as measured with the 6-minute walk test, a sub-maximal exercise test used to assess cardiopulmonary and musculoskeletal systems. The SCALE IBT trial (NCT02963935) was a 56-week, randomized, double-blind, US-based multicenter trial of liraglutide 3.0 mg vs placebo, with intensive behavior therapy (IBT) (i.e. reduced calorie intake, increased physical activity [max target: 250 min/week], and 23 counseling visits) in both arms. A key secondary endpoint was the change in 6-minute walking distance (6MWD), a test for walking capacity measured by total distance walked along a 20-m marked walkway over 6 minutes. To our knowledge, this is the first trial with pharmacological weight management to explore changes in the 6MWD in response to treatment. This post-hoc analysis examined the association between baseline body mass index (BMI) and 6MWD, and change in weight and 6MWD. For the trial, individuals aged ≥18 y with a BMI ≥30 kg/m2 and without diabetes were randomized 1:1 to IBT plus liraglutide 3.0 mg or placebo. The change in body weight and 6MWD from baseline to week 56 was calculated using analysis of covariance (ANCOVA), with treatment, gender and BMI as factors and baseline endpoint [body weight or 6MWD] as a covariate. Linear regression was used for the correlation analysis of the association between 6MWD and BMI. There were 282 individuals in the full analysis set (47 y, 17% male, BMI 39 kg/m2), of whom 142 were randomized to liraglutide 3.0 mg and 140 to placebo. At 56 weeks, mean weight loss was 7.5% with liraglutide 3.0 mg and 4.0% with placebo, estimated treatment difference (ETD [95% CI] 3.5% [1.6, 5.3]; p=0.0003). Improvement in 6MWD was 49.5 m vs. 46.4 m, respectively, from a mean baseline of 439 m (ETD [95% CI] 3.1 [-12.7, 18.9]; p=0.70). The post-hoc correlation analysis showed a linear relationship between 6MWD and BMI. Linear regression of baseline 6MWD vs. baseline BMI showed that on average an individual with a BMI that was 1 kg/m2 lower compared to another individual was able to walk 4.9 m longer in 6 minutes (slope [95% CI] -4.9 m/(kg/m2) [-6.2, -3.6]; p<0.0001). This relationship was also demonstrated in a linear regression analysis of change in 6MWD at 56 weeks vs. change in BMI at 56 weeks, where on average an individual improved 6MWD by 5.0 m for each BMI decrease of 1 kg/m2 (slope [95% CI] -5.0 m/(kg/m2) [-7.6, -2.5]; p<0.0001). The intercept (i.e. change in 6MWD with no change in BMI) was 36.3 m, most likely primarily reflecting the effect of increased physical activity as a part of the IBT intervention. This post-hoc analysis showed that greater weight loss was associated with greater improvements in 6MWD in a linear manner, indicating gains in walking capacity. Supported by Novo Nordisk.

Clinical Features and Outcomes of Patients with Sarcoidosis-associated Pulmonary Hypertension

The presence of pulmonary hypertension (PH) significantly worsens outcomes in patients with advanced sarcoidosis, but its optimal management is unknown. We aimed to characterize a large sarcoidosis-associated pulmonary hypertension (SAPH) cohort to better understand patient characteristics, clinical outcomes, and management strategies including treatment with PH therapies. Patients at Duke University Medical Center with biopsy-proven sarcoidosis and SAPH confirmed by right heart catheterization (RHC) were identified from 1990–2010. Subjects were followed for up to 11 years and assessed for differences by treatment strategy for their SAPH, including those who were not treated with PH-specific therapies. Our primary outcomes of interest were change in 6-minute walk distance (6MWD) and change in N-terminal pro-brain natriuretic peptide (NT-proBNP) by after therapy. We included 95 patients (76% women, 86% African American) with SAPH. Overall, 70% of patients had stage IV pulmonary sarcoidosis, and 77% had functional class III/IV symptoms. Median NT-proBNP value was elevated (910 pg/mL), and right ventricular dysfunction was moderate/severe in 55% of patients. Median values for mean pulmonary artery pressure (49 mmHg) and pulmonary vascular resistance (8.5 Woods units) were consistent with severe pulmonary hypertension. The mortality rate over median 3-year follow-up was 32%. Those who experienced a clinical event and those who did not had similar overall echocardiographic findings, hemodynamics, 6MWD and NT-proBNP at baseline, and unadjusted analysis showed that only follow-up NT-proBNP was associated with all-cause hospitalization or mortality. A sign test to evaluate the difference between NT-Pro-BNP before and after PH therapy produced evidence that a significant difference existed between the median pre- and post-NT-Pro-BNP (−387.0 (IQR: −1373.0-109), p = 0.0495). Use of PH-specific therapy may be helpful in selected patients with SAPH and pre-capillary pulmonary vascular disease. Prospective trials are needed to characterize responses to PH-specific therapy in this subset of patients with SAPH.

Utility of ultrasound assessment of diaphragmatic function before and after pulmonary rehabilitation in COPD patients

BackgroundPulmonary rehabilitation (PR) may improve respiratory symptoms and skeletal muscle strength in patients with COPD. We aimed to evaluate changes in ultrasound (US) measurements of diaphragmatic mobility and thickness after PR in COPD patients and to test its correlation with PR outcomes.MethodsTwenty-five COPD patients were enrolled and underwent a diaphragm US assessment before and after a 12-week PR program.ResultsWe found a correlation between the intraindividual percentage of change in the diaphragmatic length of zone of apposition at functional residual capacity (ΔLzapp%) and the change in 6-minute walking distance (6MWD) after PR (rho=0.49, P=0.02). ΔLzapp% was significantly higher in patients with improved 6MWD and COPD Assessment Test (CAT) score (mean rank=12.03±2.57 vs 6.88±4.37; P=0.02). A ΔLzapp% of ≥10% was able to discriminate among patients with improved 6MWD, with a sensitivity of 83% and a specificity of 74%. The area under the receiver operating characteristic curve for ΔLzapp% was 0.83. A cutoff value of ≥9% of ΔLzapp% had a positive predictive value in discriminating a reduction in ≥2 points of CAT score after PR, with a sensitivity and a specificity of 80% and 62%, respectively.ConclusionDiaphragm US assessment represents a useful prognostic marker of PR outcomes in COPD patients.

Effect of Exercise and Nutrition Prehabilitation on Functional Capacity in Esophagogastric Cancer Surgery

Preserving functional capacity is a key element in the care continuum for patients with esophagogastric cancer. Prehabilitation, a preoperative conditioning intervention aiming to optimize physical status, has not been tested in upper gastrointestinal surgery to date. To investigate whether prehabilitation is effective in improving functional status in patients undergoing esophagogastric cancer resection. A randomized clinical trial (available-case analysis based on completed assessments) was conducted at McGill University Health Centre (Montreal, Quebec, Canada) comparing prehabilitation with a control group. Intervention consisted of preoperative exercise and nutrition optimization. Participants were adults awaiting elective esophagogastric resection for cancer. The study dates were February 13, 2013, to February 10, 2017. The primary outcome was change in functional capacity, measured with absolute change in 6-minute walk distance (6MWD). Preoperative (end of the prehabilitation period) and postoperative (from 4 to 8 weeks after surgery) data were compared between groups. Sixty-eight patients were randomized, and 51 were included in the primary analysis. The control group were a mean (SD) age, 68.0 (11.6) years and 20 (80%) men. Patients in the prehabilitation group were a mean (SD) age, 67.3 (7.4) years and 18 (69%) men. Compared with the control group, the prehabilitation group had improved functional capacity both before surgery (mean [SD] 6MWD change, 36.9 [51.4] vs -22.8 [52.5] m; P < .001) and after surgery (mean [SD] 6MWD change, 15.4 [65.6] vs -81.8 [87.0] m; P < .001). Prehabilitation improves perioperative functional capacity in esophagogastric surgery. Keeping patients from physical and nutritional status decline could have a significant effect on the cancer care continuum. ClinicalTrials.gov Identifier: NCT01666158.

Effect of Recombinant Human Pentraxin 2 vs Placebo on Change in Forced Vital Capacity in Patients With Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Approved therapies do not halt disease progression. To determine the effect of recombinant human pentraxin 2 vs placebo on change from baseline to week 28 in mean forced vital capacity (FVC) percentage of predicted value. Phase 2, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 7 countries of eligible patients with IPF (N = 117; aged 40-80 years; FVC ≥50% and ≤90% predicted; ratio of forced expiratory volume in the first second/FVC >0.70; diffusing capacity for carbon monoxide [Dlco] ≥25% and ≤90% predicted; and distance of ≥150 m on the 6-minute walk test). Study period was August 2015-May 2017. Patients were randomized to receive either recombinant human pentraxin 2 (10 mg/kg intravenous every 4 weeks, n = 77) or placebo (n = 39) for 24 weeks, and stratified by concurrent IPF treatment status. The primary end point was the least-squares mean change in FVC percentage of predicted value from baseline to week 28 (minimal clinically important difference, decline of 2%-6%). Secondary end points included mean change in lung volumes (total, normal, and interstitial lung abnormalities) on high-resolution computed tomography (HRCT) and 6-minute walk distance (minimal clinically important difference, 24-45 m). Of 117 randomized patients, 116 received at least 1 dose of study drug (mean age, 68.6 years; 81.0% men; mean time since IPF diagnosis, 3.8 years), and 111 (95.7%) completed the study. The least-squares mean change in FVC percentage of predicted value from baseline to week 28 in patients treated with recombinant human pentraxin 2 was -2.5 vs -4.8 for those in the placebo group (difference, +2.3 [90% CI, 1.1 to 3.5]; P = .001). No significant treatment differences were observed in total lung volume (difference, 93.5 mL [90% CI, -27.7 to 214.7]), quantitative parenchymal features on HRCT (normal lung volume difference, -1.2% [90% CI, -4.4 to 1.9]; interstitial lung abnormalities difference, 1.1% [90% CI, -2.2 to 4.3]), or measurement of Dlco (difference, -0.4 [90% CI, -2.6 to 1.7]). The change in 6-minute walk distance was -0.5 m for patients treated with recombinant human pentraxin 2 vs -31.8 m for those in the placebo group (difference, +31.3 m [90% CI, 17.4 to 45.1]; P < .001). The most common adverse events in the recombinant human pentraxin 2 vs placebo group were cough (18% vs 5%), fatigue (17% vs 10%), and nasopharyngitis (16% vs 23%). In this preliminary study, recombinant human pentraxin 2 vs placebo resulted in a slower decline in lung function over 28 weeks for patients with idiopathic pulmonary fibrosis. Further research should more fully assess efficacy and safety. clinicaltrials.gov Identifier: NCT02550873.

Effect of a Home-Based Exercise Intervention of Wearable Technology and Telephone Coaching on Walking Performance in Peripheral Artery Disease

Clinical practice guidelines support home-based exercise for patients with peripheral artery disease (PAD), but no randomized trials have tested whether an exercise intervention without periodic medical center visits improves walking performance. To determine whether a home-based exercise intervention consisting of a wearable activity monitor and telephone coaching improves walking ability over 9 months in patients with PAD. Randomized clinical trial conducted at 3 US medical centers. Patients with PAD were randomized between June 18, 2015, and April 4, 2017, to home-based exercise vs usual care for 9 months. Final follow-up was on December 5, 2017. The exercise intervention group (n = 99) received 4 weekly medical center visits during the first month followed by 8 months of a wearable activity monitor and telephone coaching. The usual care group (n = 101) received no onsite sessions, active exercise, or coaching intervention. The primary outcome was change in 6-minute walk distance at 9-month follow-up (minimal clinically important difference [MCID], 20 m). Secondary outcomes included 9-month change in subcomponents of the Walking Impairment Questionnaire (WIQ) (0-100 score; 100, best), SF-36 physical functioning score, Patient-Reported Outcomes Measurement Information System (PROMIS) mobility questionnaire (higher = better; MCID, 2 points), PROMIS satisfaction with social roles questionnaire, PROMIS pain interference questionnaire (lower = better; MCID range, 3.5-4.5 points), and objectively measured physical activity. Among 200 randomized participants (mean [SD] age, 70.2 [10.4] years; 105 [52.5%] women), 182 (91%) completed 9-month follow-up. The mean change from baseline to 9-month follow-up in the 6-minute walk distance was 5.5 m in the intervention group vs 14.4 m in the usual care group (difference, -8.9 m; 95% CI, -26.0 to 8.2 m; P = .31). The exercise intervention worsened the PROMIS pain interference score, mean change from baseline to 9 months was 0.7 in the intervention group vs -2.8 in the usual care group (difference, 3.5; 95% CI, 1.3 to 5.8; P = .002). There were no significant between-group differences in the WIQ score, the SF-36 physical functioning score, or the PROMIS mobility or satisfaction with social roles scores. Among patients with PAD, a home-based exercise intervention consisting of a wearable activity monitor and telephone coaching, compared with usual care, did not improve walking performance at 9-month follow-up. These results do not support home-based exercise interventions of wearable devices and telephone counseling without periodic onsite visits to improve walking performance in patients with PAD. clinicaltrials.gov Identifier: NCT02462824.

The CardiAMP Heart Failure trial: A randomized controlled pivotal trial of high-dose autologous bone marrow mononuclear cells using the CardiAMP cell therapy system in patients with post–myocardial infarction heart failure: Trial rationale and study design

BackgroundHeart failure following myocardial infarction is a common, disabling, and deadly condition. Direct injection of autologous bone marrow mononuclear cells into the myocardium may result in improved functional recovery, relieve symptoms, and improve other cardiovascular outcomes. MethodsCardiAMP-HF is a randomized, double-blind, sham-controlled, pivotal trial designed to investigate the safety and efficacy of autologous bone marrow mononuclear cells treatment for patients with medically refractory and symptomatic ischemic cardiomyopathy. The primary end point is change in 6-minute walk distance adjusted for major adverse cardiovascular events at 12 months following treatment. Particularly novel aspects of this trial include a cell potency assay to screen subjects who have bone marrow cell characteristics that suggest a favorable response to treatment, a point-of-care treatment method, a high target dose of 200 million cells, and an efficient transcatheter intramyocardial delivery method that is associated with high cell retention. ConclusionsThis novel approach may lead to a new treatment for those with ischemic heart disease suffering from medically refractory heart failure.

Change in 6-minute walking distance before and after lung resection

Change in 6-minute walking distance before and after lung resection

Effect of Granulocyte-Macrophage Colony-Stimulating Factor With or Without Supervised Exercise on Walking Performance in Patients With Peripheral Artery Disease

Benefits of granulocyte-macrophage colony-stimulating factor (GM-CSF) for improving walking ability in people with lower extremity peripheral artery disease (PAD) are unclear. Walking exercise may augment the effects of GM-CSF in PAD, since exercise-induced ischemia enhances progenitor cell release and may promote progenitor cell homing to ischemic calf muscle. To determine whether GM-CSF combined with supervised treadmill exercise improves 6-minute walk distance, compared with exercise alone and compared with GM-CSF alone; to determine whether GM-CSF alone improves 6-minute walk more than placebo and whether exercise improves 6-minute walk more than an attention control intervention. Randomized clinical trial with 2 × 2 factorial design. Participants were identified from the Chicago metropolitan area and randomized between January 6, 2012, and December 22, 2016, to 1 of 4 groups: supervised exercise + GM-CSF (exercise + GM-CSF) (n = 53), supervised exercise + placebo (exercise alone) (n = 53), attention control + GM-CSF (GM-CSF alone) (n = 53), attention control + placebo (n = 51). The final follow-up visit was on August 15, 2017. Supervised exercise consisted of treadmill exercise 3 times weekly for 6 months. The attention control consisted of weekly educational lectures by clinicians for 6 months. GM-CSF (250 μg/m2/d) or placebo were administered subcutaneously (double-blinded) 3 times/wk for the first 2 weeks of the intervention. The primary outcome was change in 6-minute walk distance at 12-week follow-up (minimum clinically important difference, 20 m). P values were adjusted based on the Hochberg step-up method. Of 827 persons evaluated, 210 participants with PAD were randomized (mean age, 67.0 [SD, 8.6] years; 141 [67%] black, 82 [39%] women). One hundred ninety-five (93%) completed 12-week follow-up. At 12-week follow-up, exercise + GM-CSF did not significantly improve 6-minute walk distance more than exercise alone (mean difference, -6.3 m [95% CI, -30.2 to +17.6]; P = .61) or more than GM-CSF alone (mean difference, +28.7 m [95% CI, +5.1 to +52.3]; Hochberg-adjusted P = .052). GM-CSF alone did not improve 6-minute walk more than attention control + placebo (mean difference, -1.4 m [95% CI, -25.2 to +22.4]; P = .91). Exercise alone improved 6-minute walk compared with attention control + placebo (mean difference, +33.6 m [95% CI, +9.4 to +57.7]; Hochberg-adjusted P = .02). Among patients with PAD, supervised treadmill exercise significantly improved 6-minute walk distance compared with attention control + placebo, whereas GM-CSF did not significantly improve walking performance, either when used alone or when combined with supervised treadmill exercise. These results confirm the benefits of exercise but do not support using GM-CSF to treat walking impairment in patients with PAD. clinicaltrials.gov Identifier: NCT01408901.

Impact of declining renal function on outcomes in pulmonary arterial hypertension: A REVEAL registry analysis

Renal dysfunction is associated with abnormal cardiopulmonary hemodynamics, in-hospital death and poor survival in patients with pulmonary arterial hypertension (PAH), and thus it may be a prognostic biomarker. In our analysis we assess the relationship between change in estimated glomerular filtration rate (eGFR) and outcomes in PAH patients in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL). Overall 2,368 patients were classified into chronic kidney disease (CKD) stages based on baseline eGFR: normal or Stages 1 or 2 (n = 1,699); Stage 3a (n = 399); Stage 3b (n = 196); and Stages 4 or 5 (n = 74). We evaluated the relationship between baseline CKD stage and survival, as well as the composite end-point of survival and freedom from all-cause hospitalization. The relationships between change in eGFR at ≥1 year and these clinical end-points were also evaluated. Patients with a ≥10% decline in eGFR from baseline over ≥1 year had a significantly increased risk of death (hazard ratio 1.66; p < 0.0001) and the composite of all-cause hospitalization and death (hazard ratio 1.33; p = 0.002). This decline predicted survival independently of changes in 6-minute walk distance and functional class. However, a ≥10% increase in eGFR was not significantly associated with either end-point. In REVEAL, a ≥10% decline in eGFR over ≥1 year independently predicted poorer survival. Thus, eGFR may be a simple and economical biomarker in PAH.

Macitentan for treatment of CTEPH: why MERIT merits attention

This issue of The Lancet Respiratory Medicine brings new data on pharmacological treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Hossein-Ardeschir Ghofrani and colleagues 1 Ghofrani H-A Simonneau G D'Armini AM et al. on behalf of the MERIT study investigatorsMacitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med. 2017; (published online Sept 11.)http://dx.doi.org/10.1016/S2213-2600(17)30305-3 PubMed Google Scholar randomly assigned 80 patients with inoperable CTEPH to receive either placebo or oral macitentan, an endothelin-1 receptor antagonist approved for the treatment of pulmonary arterial hypertension. The primary endpoint was resting pulmonary vascular resistance (PVR) at week 16. Secondary endpoints included change in 6-minute walking distance at week 24. Macitentan (10 mg once a day) significantly improved PVR and exercise capacity with a good safety profile. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled studyIn MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. Full-Text PDF CorrectionsTorbicki A. Macitentan for treatment of CTEPH: why MERIT merits attention. Lancet Respir Med 2017; 5: 762–3— text “(geometric means ratio 0·84, 95% CI 0·69–1·03, p=0·041)” has been edited to “(geometric means ratio 0·84, 95% CI 0·69–1·03)” because the p value was originally added erroneously. This correction has been made to the printed Article, and to the online version as of Sept 29, 2017. Full-Text PDF

Group Enrollment and Open Gym Format Decreases Cardiac Rehabilitation Wait Times.

Wait times for the first cardiac rehabilitation (CR) session are inversely related to CR participation rates. We hypothesized that changing from individually scheduled appointments to a group enrollment and open gym format, in which patients were enrolled during group intake sessions and could arrive for subsequent CR sessions any time during open gym periods, would decrease wait times. A total of 603 patients enrolled in CR at Vanderbilt University Medical Center from July 2012 to December 2014 were included in the study. We evaluated the effect of changing to a group enrollment and open gym format after adjusting for referral diagnosis, insurance status, seasonality, and other factors. We compared outcomes, including exercise capacity and quality of life, between the 2 groups. Patients in the group enrollment and open gym format had significantly lower average wait times than those receiving individual appointments (14.9 vs 19.5 days, P < .001). After multivariable adjustment, the new CR delivery model was associated with a 22% (3.7 days) decrease in average wait times (95% CI, 1.9-5.6, P < .001). Patients completing CR had equally beneficial changes in 6-minute walk distance and Patient Health Questionnaire scores between the 2 groups, although there was no significant difference in participation rates or the number of sessions attended. Implementation of a group enrollment and open gym format was associated with a significant decrease in wait times for first CR sessions. This CR delivery model may be an option for programs seeking to decrease wait times.