Improvement In 6-minute Walk Distance Research Articles

Effects of supervised exercise therapy on blood pressure and heart rate during exercise, and associations with improved walking performance in peripheral artery disease: Results of a randomized clinical trial

ObjectiveSupervised exercise therapy (SET) improves walking ability in people with peripheral artery disease (PAD). However, the effects of SET on cardiovascular health in PAD remain unclear. Using data from a randomized clinical trial, this post hoc analyses investigated the effects of a 6-month SET intervention, compared with a control group, on changes in blood pressure (BP) and heart rate (HR) during a graded treadmill exercise test in people with PAD. MethodsWe randomized 210 participants with PAD to either SET (3× weekly) or control (1× weekly health lectures) for 6 months. A graded treadmill exercise test, 6-minute walk test, and Walking Impairment Questionnaire were completed at baseline and the 6-month follow-up. BP and HR were measured at the end of each 2-minute stage of the graded treadmill exercise test. Mixed effects regression models compared the overall mean 6-month change in systolic BP, diastolic BP, pulse pressure (PP), and HR during the first 5 stages of the graded treadmill exercise test between groups. ResultsOf the 210 randomized participants with PAD, 176 (67 ± 9 years; 72 [41%] female, 115 [65%] Black) completed the graded treadmill exercise test at baseline and the 6-month follow-up. Compared with the control group at the 6-month follow-up, SET significantly decreased overall mean systolic BP (–12 mm Hg; P < .001), PP (–9 mm Hg; P < .001), and HR (–7 b/min; P < .01) during a graded treadmill exercise test but not diastolic BP. Among participants randomized to SET, a greater decrease in systolic BP, PP, and HR during a graded treadmill exercise test was significantly associated with a greater improvement in 6-minute walk distance (systolic BP, r = –0.19 [P = .03] and PP, r = –0.23 [P < .01]; and HR, r = –0.21 [P < .01]) and with maximal treadmill walking distance (systolic BP, r = –0.21 [P < .01] and PP, r = –0.17 [P = .03]) at the 6-month follow-up. A greater decrease in the HR during a graded treadmill exercise test was significantly associated with a better WIQ distance score (r = –0.27; P = .03) at the 6-month follow-up. ConclusionsIn people with PAD, compared with a control group, SET improved cardiovascular health, measured by changes in BP and HR during exercise. The degree of improvement in cardiovascular health correlated with the degree of improvement in walking performance in people with PAD. NCT: 01408901.

Protein-enriched diet improved muscle endurance and marginally reduced intramuscular adiposity: Results from a randomized controlled trial among middle-aged and older adults

BackgroundMaintaining sufficient dietary protein intake is important for nutritional status, muscle mass, and healthy aging, but the clinical effects of high protein diet remained controversial.. MethodsThis 12-week randomized controlled trial enrolled community-dwelling middle-aged and older adults to evaluate clinical effects of daily diet with different protein density.. All participants received 10 frozen meals per week for 12 weeks containing either 15% daily calorie of protein (regular-protein group, RPG), or 25% daily calorie of protein (high-protein group, HPG). Bioimpedance analysis was used to assess body composition, and the magnetic resonance imaging on both mid-thighs was performed to measure muscle mass and the intramuscular adiposity. ResultsThis trial enrolled 70 participants, and data of 52 participants (mean age: 53.7 ± 8.3 years, 53.8% male; 25 in RPG and 27 in HPG) were available for analysis. Baseline demographic characteristics, functional assessment, body composition and muscle parameters, and laboratory data were similar between groups. During the study period, participants of both groups significantly reduced body weight, body mass index, total body fat percentage, and handgrip strength, but not in the relative appendicular muscle mass). Compared to participants of RPG, HPG participants showed significant improvement in 6-minute walking distance, increased high-sensitivity C-reactive protein and marginal reduction in intramuscular adiposity than RPG participants. ConclusionsHigher dietary protein intake significantly improved physical endurance and marginally reduced intramuscular adiposity, but increased the inflammatory biomarker among middle-aged and older adults. Further study is needed to explore long-term effects of high-protein diet among middle-aged and older adults..

Evolution of randomized, controlled studies of medical therapy in chronic thromboembolic pulmonary hypertension.

Although pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), many patients have inoperable disease, and some have persistent or recurrent pulmonary hypertension (PH) after surgery. Alternative options (balloon pulmonary angioplasty (BPA) and PH-targeted medical therapy) are, therefore, required. Studies of medical therapies for CTEPH have evolved since Aerosolized Iloprost Randomized (AIR), the first randomized, controlled study of a PH-targeted therapy (inhaled iloprost) to include patients with CTEPH. Key learnings from these studies include the need to evaluate CTEPH separately from other types of PH, the importance of prospective operability adjudication as part of the protocol, and the need for sufficient duration to allow treatment benefits to become apparent. The 16-week Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Study 1 (CHEST-1) study was the first to operationalize these learnings, demonstrating a significant mean improvement in 6-minute walk distance (+46 m) and improvements in hemodynamic endpoints with riociguat versus placebo. Findings from previous studies will inform the design of future studies to address key issues related to combination medical therapy. Data on combinations of macitentan with phosphodiesterase type 5 inhibitors or oral prostanoids are available from MERIT, the first study to allow such regimens. No data on combinations including riociguat, the only licensed medical therapy for CTEPH, are available. Studies are also needed for multimodality treatment, including medical therapy plus BPA, and medical therapy as a bridge to PEA in selected operable patients. To address these issues and improve patient outcomes, it is vital that we learn from current studies to improve future trial design.

Impact of targeted pulmonary arterial hypertension therapy in patients with combined post- and precapillary pulmonary hypertension

Combined post- and precapillary pulmonary hypertension (CpcPH) portends poor outcomes in pulmonary hypertension related to left heart disease (PH-LHD). While recent evidence does not support the use of targeted pulmonary arterial hypertension (PAH) therapy in PH-LHD, there is a lack of clinical data on their use in CpcPH. We evaluated the outcomes in patients with CpcPH treated with PAH therapies. Retrospectively, 50 patients meeting hemodynamic criteria of CpcPH and started on PAH-targeted drugs were identified. Fifty age- and gender-matched PAH patients were chosen as controls. We evaluated the change in 6-minute walk distance, World Health Organization functional class (FC), tricuspid annular plane systolic excursion, BNP or NT-proBNP, and pulmonary artery systolic pressure at 3, 6, 12, and 24 months of follow-up. After adjusting for age and gender, there was no improvement in World Health Organization FC in CpcPH over 2 years (odds ratio of change to FC I/II 1.01, 95% CI: 0.98-1.04). There was no significant improvement in 6-minute walk distance (β coefficient 0.21, 95% CI: -0.98 to 1.4), reduction in BNP/NT-proBNP (β coefficient -12.16, 95% CI: -30.68 to 6.37), increase in tricuspid annular plane systolic excursion (β coefficient 0.074, 95% CI: 0.010-0.139), or decrease in pulmonary artery systolic pressure (0.996, 95% CI: 0.991-1.011) in CpcPH with therapy. There was higher mortality in CpcPH compared to PAH on treatment (24% vs 4%, P = .003). There were no improvements in symptoms, exercise capacity, or echocardiographic parameters with PAH-targeted therapy in CpcPH. Further studies into potential treatments benefiting this population are needed.

Assessment of the REPLACE study composite endpoint in riociguat-treated patients in the PATENT study.

The goal of treatment in patients with pulmonary arterial hypertension is to achieve a low risk status, indicating a favorable long-term outcome. The REPLACE study investigated the efficacy of switching to riociguat in patients with pulmonary arterial hypertension and an insufficient response to phosphodiesterase-5 inhibitors. In this post hoc analysis, we applied the REPLACE composite endpoint of clinical improvement to the placebo-controlled PATENT-1 study of riociguat in pulmonary arterial hypertension and its long-term extension, PATENT-2. Clinical improvement was defined as ≥2 of the following in patients who completed the study without clinical worsening: ≥10% or ≥30 m improvement in 6-minute walking distance; World Health Organization functional class I or II; ≥30% decrease in N-terminal prohormone of brain natriuretic peptide. At PATENT-1 Week 12, patients treated with riociguat were more likely to achieve the composite endpoint vs. placebo (P < 0.0001), with similar results in pretreated (P = 0.0189) and treatment-naïve (P < 0.0001) patients. Achievement of the composite endpoint at Week 12 was associated with a 45% reduction in relative risk of death and a 19% reduction in relative risk of clinical worsening in PATENT-2. Overall, these data suggest that use of the REPLACE composite endpoint in patients with pulmonary arterial hypertension is a valid assessment of response to treatment.

Heart Failure Optimize Clinic: Improving Quality of Care In Heart Failure Patients In An Academic Medical Center

Background While heart failure (HF) is a leading cause of mortality and readmissions, only a small percentage of patients are optimized on guideline-directed medical therapy (GDMT). We developed a multidisciplinary HF clinic to optimize medications, provide education and resources and screen for medical co-morbidities in HF patients. Methods A multidisciplinary clinic composed of Advanced Practice Providers (APPs), pharmacist, nutritionists and nurses was developed and targeted patients with a 30-day HF readmission, ≥ 2 HF-related hospitalizations in last 12 months or new HF diagnosis. The OPTIMIZE clinic consisted of a total of 6 visits approximately two weeks apart seeing an APP at each visit along with pharmacy and nutrition evaluation. Echocardiographic, 6-minute walk, and health related quality of life (EQ5D) outcomes were measured at baseline and at the end of the 12 weeks. Results A total of 62 patients with heart failure with reduced ejection fraction (HFrEF) completed OPTIMIZE clinic over an average of 11.6 weeks. Patients were primarily white (62.3%) males (56.5%) with an average age of 59.1 (±15.3) years. HF etiology was primarily non-ischemic (65%) and patients had typical cardiac comorbidities - hypertension 54%, hyperlipidemia 33%, diabetes 23%, sleep apnea 15%, and chronic kidney disease 24%. Completion of OPTIMIZE clinic resulted in significant improvements in 6-minute walk distance, left ventricular ejection fraction (LVEF), and patient reported quality of life measures as assessed by the EQ5D along with significant reductions in brain natriuretic peptide (BNP) and left ventricular internal diameter in diastole (LVIDd) (Figure 1a). We also saw improved utilization of GDMT with completion of the OPTIMIZE clinic (Figure 1b). During the course of the clinic, only 7 (11%) patients were admitted for CHF exacerbation and 44 referrals were made to various other cardiology or internal medicine subspecialities, the most common being sleep clinic (14 referrals). A total of 13 (21%) patients had enough improvement in LVEF on GDMT as a result of this clinic that they no longer met criteria for implantable cardioverter defibrillator implantation. Conclusion Successful implementation of a multidisciplinary HF optimization clinic can help improve GDMT utilization, HF education, comorbidity recognition, and markers of HF severity. An OPTIMIZE clinic model can be considered in other centers as a way to increase GDMT optimization and improve clinical and functional markers of HF.

Benefits of a Short-Term Obesity Reduction Intervention Among Obese Older Adults with Prediabetes: Preliminary Evidence by Race (Black/White) from the EGGSPDITe Study

Abstract Objectives Obesity rates in older adults are rapidly climbing, especially in older African Americans, for whom it hastens functional decline and intensifies chronic health conditions like Type 2 diabetes more so than in their white counterparts. Emerging evidence suggest that increased protein intake can enhance the benefits of intentional weight loss but it is not yet known whether these effects are consistent across race. Methods The ongoing EGGSPDITe trial assess the effects of combining generous intakes of high quality animal protein (≥30 g/meal; primarily from eggs) with calorie restriction, relative to calorie restricted alone, on insulin resistance and weight loss among black and white older adults with prediabetes who are participating in this 4-month obesity reduction intervention. Results Preliminary combined-group analysis reveals significant reductions in body weight (–9.7 ± 7.6 kg), body fat (–8.1 ± 7.6 kg), and HbA1c (–0.2 ± 0.3%) and significant improvement in SF-36 physical and mental health composites (+10.8 and + 4.8, respectively; Ps &amp;lt; 0.01) at 4 months, relative to baseline. Significant improvements in 6-minute walk distance and 8-foot up and go (Ps ≤ 0.05) at 4 months; however, a significant race x time interaction (P &amp;lt; 0.05) reveals that improvements in 30-second chair stands improved among white but not black participants (+2.4 vs 0.4 stands, respectively). No other significant differences were observed between older black and white pre-diabetics. Conclusions These preliminary findings suggest that even short-term obesity reduction intervention can improve the body composition, metabolism, and self-reported health of obese older adults with prediabetes but responses may vary by race for some outcomes. Funding Sources This study was funded by the National Institute on Aging and the Egg Nutrition Council.

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.

Effectiveness of physiotherapy interventions on disease-specific and generic outcomes for individuals with cardiovascular diseases in India – a systematic review and Meta-analysis

BackgroundThe incidence of cardiovascular diseases (CVDs) is rising in India and there is a need for a systematic review to corroborate the effects of physiotherapy interventions and their cultural adaptations on CVDs in India.ObjectivesTo summarize the level of evidence for the effects of physiotherapy interventions on disease-specific and generic outcome measures in individuals with CVDs and assess cultural adaptations of these interventions in India (PROSPERO registration: CRD42019128342).MethodsEight databases were searched from inception to March 2019. Two reviewers extracted data and assessed risk of bias of the eligible studies (controlled/randomized clinical trials [RCTs]) using the Cochrane RoB2 tool. A meta-analysis was conducted using a fixed-effects model. Overall evidence was synthesized using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria.ResultsOf 1349 citations retrieved, only 4 RCTs including 165 individuals (130 men) with CVDs (post-myocardial infarction, left ventricular failure, and stable/congestive heart failure) met the inclusion criteria. The results demonstrated a significant improvement in 6-minute walk distance, blood pressure, anxiety and quality of life following physiotherapy interventions in individuals with CVDs. However, there was a high risk of bias for all outcomes. There were critical weaknesses in all domains of GRADE criteria for all outcomes which resulted in a very low evidence. The cultural adaptations of interventions were inadequately reported.ConclusionsOwing to a small number of studies with a high risk of bias and heterogeneous results, methodologically-robust RCTs are warranted for finding a more conclusive evidence on physiotherapy interventions for CVDs in India.

Early home-based pulmonary rehabilitation following acute exacerbation of COPD: A feasibility study using an action research approach.

Objective:Pulmonary rehabilitation (PR) improves function, reduces symptoms and decreases healthcare usage in people with chronic obstructive pulmonary disease (COPD) following an acute exacerbation (AECOPD). However, rehabilitation uptake rates are low. This study aimed to address barriers to uptake and completion of PR following AECOPD.Methods:An action research approach was used to reflect on study feasibility, and to plan and implement an improved protocol. Phase I tested the feasibility of home-based PR started early after AECOPD. Phase II used qualitative interviews to identified potential barriers to program uptake. Phase III re-tested the program with changes to recruitment and assessment strategies.Results:Phase I: From 97 screened patients, 26 were eligible and 10 (38%) started home-based PR. Eight participants undertook ≥70% of PR sessions, achieving clinically meaningful improvement in 6-minute walk distance (mean (SD) change 76 (60) m) and chronic respiratory disease questionnaire total score (15 (21) units). Phase II: Potential barriers to uptake of home-based PR included access issues, confidence to exercise, and lack of information about PR benefits. Phase III: From 77 screened patients, 23 were eligible and 5 (22%) started the program.Discussion:Home-based PR improved clinical outcomes, but program eligibility and uptake remain challenging. Efforts should be made to ensure PR program eligibility criteria are broad enough to accommodate patient needs, and new ways of engaging patients are needed to improve PR uptake after AECOPD.

Use of vasodilators for the treatment of pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis: A systematic review.

There are several medications available to treat pulmonary arterial hypertension (PAH): PAH-targeted drugs. However, in patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis (PVOD/PCH), rare diseases that cause pulmonary hypertension, the effectiveness and safety of vasodilators, including PAH-targeted drugs, are unclear. We searched English-language publications listed in three electronic databases (PubMed, Cochrane Library, and the Japan Medical Abstracts Society). Reports with efficacy outcomes (survival, improvement in 6-minute walk distance, and pulmonary vascular resistance) and data on development of pulmonary edema after administration of vasodilators to patients with PVOD/PCH were selected (1966 to August 2015). We identified 20 reports that met our criteria. No randomized controlled or prospective controlled studies were reported. The survival time ranged from 71 minutes to 4 years or more after initiation of vasodilators. Most of the reported cases showed an improvement in the 6-minute walk distance and pulmonary vascular resistance. Pulmonary edema was reported in 15 articles, some cases of which were lethal. The present study demonstrates the potential efficacy and difficulties in the use of vasodilators in patients with PVOD/PCH; however, drawing a firm conclusion was difficult because of the lack of randomized controlled trials. Further research is needed to ascertain if vasodilator use is beneficial and safe in patients with PVOD/PCH.

Effects of spironolactone in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials.

BackgroundHeart failure with preserved ejection fraction (HFpEF) is a common syndrome, accounting for more than one half of all heart failure patients, which is associated with high morbidity and mortality. But there is little evidence-based therapeutic strategies for the management of HFpEF. Previous studies reported the effects of spironolactone on HFpEF; however, the results were inconsistent. In this meta-analysis, we evaluated the effects of spironolactone on HFpEF.MethodsArticles were searched on PubMed, EMBASE, and COCHRANE databases before May, 2017, and were supplemented by hand searches of reference lists of included studies and review articles. Eligible articles were restricted to randomized controlled trials (RCTs). The odds ratios (ORs) of the dichotomous data, mean difference (MD) of continuous data, and 95% confidence intervals (CIs) were calculated to assess the effects of spironolactone in patients with HFpEF.ResultsA total of 7 studies including 4147 participants were analyzed. There were significant improvements on the E/e′ index (MD −1.38; 95% CI, −2.03 to −0.73; P < .0001) and E/A velocity ratio (MD −0.05; 95% CI, −0.10 to −0.00; P = .03) under spironolactone treatment compared with placebo, while there was no effect on the deceleration time (MD 1.04; 95% CI, −8.27 to 10.35; P = .83). Subgroup analyses on the E/A velocity ratio showed that there was obvious benefit from spironolactone therapy in patients with follow-up periods >6 months but not in those with follow-up periods ≤6 months. There was no reduction in all-cause mortality and hospitalization compared with placebo. And no improvement in 6-minute walk distance was seen compared with placebo.ConclusionThis meta-analysis demonstrates that the use of spironolactone improves left ventricular diastolic function in patients with HFpEF, whereas it has no effect on all-cause mortality and hospitalization, and the 6-minute walk distance. Further larger size, multicenter, RCTs are required to confirm the effects of spironolactone on patients with HFpEF.

Unrecognized Left Heart Failure in LVAD Recipients: The Role of Routine Invasive Hemodynamic Testing.

The role of routine right heart catheterizations (RHCs) in left ventricular assist device (LVAD) patients is undefined. We analyzed 105 continuous-flow LVAD recipients who underwent an RHC approximately 3 months after implant. In 38 patients, LVAD speed was ramped with the goal of optimizing hemodynamics. Our cohort consisted of 71 (68%) HeartMate II (HMII) and 34 (32%) HeartWare (HVAD) patients. Thirty patients (29%) had either a reduced cardiac index (CI ≤ 2.2 L/min/m), elevated pulmonary capillary wedge pressure (PCWP > 18 mm Hg), or both. A subgroup of 38 patients (19 with abnormal hemodynamics) underwent LVAD ramping. With LVAD ramping, normalization of hemodynamics was achieved in 13 (68%) patients with abnormal hemodynamics. In ramped patients, the CI increased from 2.1 L/min/m (2.0-2.3) to 2.5 L/min/m (2.3-2.6; p = 0.004), and the PCWP dropped from 21 mm Hg (20-26) to 18 mm Hg (14-21, p < 0.001). The 6-minute walk distance improved from 338 m (253-394) to 353 m (320-442, p = 0.041). A 400 rpm change in HMII speed was like a 130 rpm change in HVAD speed and led to a change in cardiac output (CO) of 0.3 L/min. The correlation between device-reported flow and measured CO for both the HMII (Rs = 0.50, p < 0.001) and HVAD (Rs = 0.47, p < 0.001) was moderate. At 3 months after LVAD implant, most patients have normal hemodynamics. Of those patients with abnormal hemodynamics, LVAD ramping results in normalization of hemodynamics and improvement in 6-minute walk distance.

A rehabilitation programme for people with multimorbidity versus usual care: A pilot randomized controlled trial.

Background:Multimorbidity, the coexistence of two or more chronic conditions, is common in clinical practice. Rehabilitation for people with multimorbidity may provide access to a rehabilitation programme that can address common symptoms and risk factors for multiple chronic diseases.Objective:The aims of this study were to (1) evaluate the feasibility of a rehabilitation programme compared to usual medical care (UMC) in people with multimorbidity and (2) gather preliminary data regarding clinical effects and impact on functional exercise capacity, activities of daily living, health-related quality of life and resource utilization.Design:A pilot feasibility parallel randomized controlled trial was undertaken. Adults with multimorbidity were randomized to the rehabilitation programme (intervention) or UMC (control). The duration of the rehabilitation programme was 8 weeks and comprised exercise (1 h, twice weekly) and education (1 h, once weekly). The UMC group did not participate in a structured exercise programme.Results:One hundred people were screened to recruit 16 participants, with a 71% completion rate for the intervention group. The rehabilitation group achieved a mean (standard deviation) improvement in 6-minute walk distance of 44 (41) m and the UMC group of 23 (29) m.Conclusions:This study suggests that it would be feasible to conduct a larger randomized control trial investigating a rehabilitation programme for people with multimorbidity. Low uptake of the study suggests that refinement of the inclusion criteria, recruitment sources and programme model will be needed to achieve the number of participants required.

Endoscopic lung volume reduction coil treatment in patients with very low FEV1: an observational study.

Background:Endoscopic lung volume reduction coil (LVRC) treatment is a therapeutic option for selected patients with advanced emphysema. The effects and the safety of endoscopic lung volume reduction in patients with very low forced expired volume in one second (FEV1) remain to be determined. This study was conducted to assess the effects and the safety of LVRC treatment in patients with very low FEV1.Methods:The study was performed as a retrospective observational study in the Department of Respiratory Medicine at the University Medical Center Hamburg-Eppendorf on patients with very low FEV1, defined as an FEV1 ⩽ 20% of predicted at baseline in whom LVRC treatment was performed between 1 April 2012 and 28 February 2017.Results:LVRC treatment was performed in 33 patients with very low FEV1. Of these, 45.5% were female and 54.5% were male. At baseline, mean FEV1 was 0.46 ± 0.12 liters (15 ± 3% of predicted), mean forced vital capacity (FVC) was 1.61 ± 0.62 liters (42 ± 13% of predicted), mean residual volume (RV) was 6.03 ± 0.81 liters (275 ± 51% of predicted) and 6-minute walk distance was 229 ± 102 m. Bilateral LVRC treatment was completed in 21 of these patients (63.6%). Bilateral LVRC treatment led to significant improvements in functional parameters with an increase in mean FEV1 from 0.44 ± 0.11 liters to 0.54 ± 0.12 liters (p = 0.001), equivalent to a relative improvement of 24.5 ± 26.9%, an increase in mean FVC from 1.49 ± 0.54 liters to 1.84 ± 0.49 liters (p = 0.001), a decrease in mean RV from 6.27 ± 0.83 liters to 5.83 ± 1.09 liters (p = 0.004) and an improvement in 6-minute walk distance from 218 ± 91 m to 266 ± 96 m (p = 0.01). There were no cases of respiratory failure requiring mechanical ventilation and no deaths.Conclusions:LVRC treatment was effective and safe in patients with very low FEV1.

The impact of delayed treatment on 6-minute walk distance test in patients with pulmonary arterial hypertension: A meta-analysis

BackgroundThe impact of treatment delay in stable patients with pulmonary arterial hypertension (PAH) remains unaddressed. MethodsThis meta-analysis included six datasets of PAH therapies with randomized-controlled trials (RCT) and corresponding open-label extension (OLE) studies. We evaluated the change in 6MWD at 1year in the OLE studies by active treatment versus ex-placebo group. The ex-placebo group (i.e., the patients randomized to placebo in the RCT and ultimately treated with active therapy in the OLE) represented the “delay-in-treatment” population. ResultsPatients with a treatment delay of 12–16weeks in PAH targeted therapy had an improvement in 6-minute walk distance (6MWD) test at 1year, but this improvement did not amount to the same degree of improvement as their initially treated counterparts. The difference in 6MWD was 15m to 20m at 1year. ConclusionA short-term delay in PAH targeted therapy may adversely affect functional capacity in patients with PAH. This meta-analysis provides some insight as to whether earlier treatment would benefit stable patients with PAH.

Left ventricular assist devices versus medical management in ambulatory heart failure patients: An analysis of INTERMACS Profiles 4 and 5 to 7 from the ROADMAP study

The ROADMAP study showed survival with improved functional status was better with left ventricular assist device (LVAD) therapy compared with optimal medical management (OMM) in ambulatory, non-inotrope-dependent (INTERMACS [IM] Profile 4 to 7) patients. To study more balanced cohorts and better define which patients may benefit from implantation of an LVAD, we re-evaluated the patients enrolled in ROADMAP when stratified by INTERMACS profile (Profile 4 and Profiles 5 to 7). The primary end-point (survival on original therapy with improvement in 6-minute walk distance ≥75 meters at 1 year), actuarial survival, adverse events (AEs) and health-related quality of life (HRQoL) were evaluated. For INTERMACS Profile 4 (IM4), more LVAD patients met the primary end-point compared with OMM patients (40% vs 15%; odds ratio = 3.9 [1.2 to 12.7], p = 0.024), but there was no statistically significant difference for INTERMACS Profiles IM 5 to 7 (IM5-7). Event-free survival on original therapy at 2 years was greater for LVAD than for OMM patients in both IM4 (67% vs 28%; p < 0.001) and IM5-7 (76% vs 49%; p = 0.025) profile groups. Composite end-points of survival on original therapy with improved HRQoL or depression were better with LVAD than OMM in IM4, but not IM5-7. AEs trended higher in LVAD compared with OMM patients in both profile groups. Rehospitalization rates for LVAD vs OMM were similar between treatment arms in IM4 (82% vs 86%; p = 0.780), but were higher for LVAD in IM5-7 (93% vs 71%; p = 0.016). LVAD patients in IM4, but not IM5-7, are more likely to meet the primary end-point and have improvements in HRQoL and depression compared with OMM, even with AEs generally being more frequent. LVAD therapy with current technology may be beneficial in select IM4 patients, but can be deferred for most IM5-7 patients, who should be followed closely due to the high frequency of treatment failures.

Can Breathing Reserve Predict Improvement in 6-Minute Walk Distance Following Pulmonary Rehabilitation in COPD Patients?

Can Breathing Reserve Predict Improvement in 6-Minute Walk Distance Following Pulmonary Rehabilitation in COPD Patients?

Effect of Riociguat on Pulmonary Arterial Compliance in Patients With Pulmonary Arterial Hypertension (PAH) in the Respite Study

SESSION TITLE: Pulmonary Hypertension - Advances in Management and Therapy SESSION TYPE: Original Investigation Slide PRESENTED ON: Tuesday, October 31, 2017 at 02:45 PM - 04:15 PM PURPOSE: Pulmonary arterial compliance (PAC) is defined as stroke volume/(systolic pulmonary arterial pressure-diastolic pulmonary arterial pressure) and is a measure of pulmonary stiffness and a physiological sign of ventricular afterload. This post hoc analysis of data from patients with PAH in the RESPITE (Riociguat clinical Effects Studied in Patients with Insufficient Treatment response to PDE5 inhibitors) study aimed to assess the effect on PAC of switching from phosphodiesterase type 5 inhibitors (PDE5i) to riociguat. METHODS: RESPITE (NCT02007629) was a prospective, multicenter, uncontrolled, open-label, single-arm, Phase IIIb trial. Sixty-one patients with PAH were enrolled based on prespecified criteria indicating they had an insufficient response to PDE5i therapy. Following a 1-3-day PDE5i treatment-free period, riociguat was adjusted to the optimal dose (up to 2.5 mg three times daily). Right heart catheterization was performed at baseline and at Week 24. RESULTS: At baseline, mean (standard deviation) PAC was 1.22 (0.62) mL/mmHg (n=59) which had increased by 0.22 (0.64) mL/mmHg (n=48) (95% CI 0.036-0.407; p=0.02) at Week 24. Patients who achieved WHO functional class (FC) I/II at Week 24 (n=26) showed an increase in PAC from baseline of 0.41 (0.68) mL/mmHg. However, those patients who remained in WHO FC III (n=22) showed no change (+0.002 [0.51] mL/mmHg). Additionally, the 16 patients who met the combined endpoint at Week 24 of freedom from clinical worsening, achievement of WHO FC I/II, and a ≥30 m improvement in 6-minute walking distance (6MWD), also had a greater improvement in PAC (+0.55 [0.81] mL/mmHg) than the 32 patients not achieving this endpoint (+0.06 [0.46] mL/mmHg). The change from baseline in PAC correlated significantly with change from baseline in cardiac index (r=0.46, p=0.0009), mean pulmonary arterial pressure (r=-0.55, p<0.0001), and pulmonary vascular resistance (r=-0.55, p<0.0001). No significant correlations were observed between change from baseline in PAC and in 6MWD or N-terminal prohormone of brain natriuretic peptide. CONCLUSIONS: In the RESPITE trial, riociguat was found to improve PAC in patients with PAH who had switched from PDE5i. CLINICAL IMPLICATIONS: This post hoc analysis demonstrates the clinical relevance of assessing PAC for a more complete assessment of right ventricular function, and suggests that determination of PAC may help to predict outcomes in patients with PAH. DISCLOSURE: Thenappan Thenappan: Grant monies (from sources other than industry): American Heart Association, Fiduciary position (of any organization, association, society, etc, other than ACCP: Nominal consultant fee from Gilead and Actelion Marius Hoeper: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, Gilead, GSK, Pfizer, MSD - Lectures and consultations Paul Corris: Grant monies (from industry related sources): Bayer - University Research Fund, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Actelion, GSK Hossein-Ardeschir Ghofrani: Grant monies (from industry related sources): Actelion, Bayer, Pfizer, Novartis, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, GSK, Novartis, Pfizer, Bellerophon Therapeutics - Board membership, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, GSK, Novartis, Pfizer, Bellerophon Therapeutics, United Therapeutics - Consultancy, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, GSK, Novartis, Pfizer, United Therapeutics - Paid lectures, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, GSK, Novartis, Pfizer, United Therapeutics - Travel/accomodation expenses James Klinger: Other: Actelion, Bayer, Gilead Sciences, Ikaria, Lung Biotechnology, NH-NHLBI, Pfizer, United Therapeutics - Research support , Consultant fee, speaker bureau, advisory committee, etc.: United Therapeutics, Bayer David Langleben: Consultant fee, speaker bureau, advisory committee, etc.: Bayer Healthcare Pharmaceuticals, Actelion, Gilead, GSK, Ikaria - Personal fees, Other: Bayer Healthcare Pharmaceuticals, Actelion, Gilead, GSK, Ikaria - Non-Financial Support Robert Naeije: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, GSK - Personal Fees, Grant monies (from industry related sources): Reata, Other: Actelion, Bayer, Lung Biotechnology Corporation - Advisory Board Member Fees Gérald Simonneau: Grant monies (from industry related sources): Actelion, Bayer, GSK, Novartis, Lilly, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, GSK, Novartis, Lilly, Other: Pfizer - Non-Financial Support Pavel Jansa: Other: Actelion, Bayer AG - Investigator, Consultant fee, speaker bureau, advisory committee, etc.: Bayer AG, AOP Stephan Rosenkranz: Grant monies (from industry related sources): Actelion, Bayer, Novartis, Pfizer, United Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, Gilead, GSK, Novartis, Pfizer, United Therapeutics Ekkehard Grünig: Grant monies (from industry related sources): Bayer, Actelion, GSK, Lilly, Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Miltenyi, Novartis, United Therapeutics, Other: Alexion - Non-Financial Support Christian Meier: Employee: Bayer AG Dennis Busse: Employee: Chrestos Concept GmbH & Co. KG Raymond Benza: Grant monies (from industry related sources): Bayer AG The following authors have nothing to disclose: Laura Scelsi No Product/Research Disclosure Information

Rehabilitation in patients with pulmonary arterial hypertension.

Exertional dyspnoea is a leading symptom in patients with pulmonary arterial hypertension (PAH). Patients suffering from PAH report poor quality of life, have skeletal muscle dysfunction and in the absence of advanced medical therapy deteriorate progressively due to right heart failure which can lead to death. For decades, patients with PAH were advised to avoid exercise in fear of exacerbated right heart failure. Recently, it has been shown that a highly supervised rehabilitation programme in expert centres leads to significant improvements in symptoms, quality of life, exercise capacity and may even enhance haemodynamics in selected stable patients treated with advanced regimens of PAH-targeted drugs. As a consequence of these promising results, pulmonary rehabilitation performed in an expert centre has been included in recent guidelines. The underlying mechanisms are not completely understood, but positive effects can be measured in different organ systems such as skeletal muscles, the cardiopulmonary system and immune system (inflammation), and also on the psychological level. Thus, improvements in 6-minute walking distance (6MWD), peak oxygen uptake (VO2 peak), muscle strength and muscle endurance, as well as physical and mental quality of life scores (SF-36 questionnaire) have been shown. Different training protocols have been used. Essential are qualified patient selection in expert centres, a low workload endurance and dumbbell (weight lifting) training avoiding strenuous exercise and exhaustion, thorough patient education and close supervision by experts especially during the first weeks. Adverse events may occur (e.g., pre-/syncope, arrhythmia, respiratory infections). PAH patients tend to overestimate their physical capacity, not perceiving their own limits properly, which makes education and expert advice even more important as exercise training can also worsen the right heart failure. Therefore, a core issue of the multidisciplinary rehabilitation is the close cooperation between the experienced rehabilitation clinic offering a specialised programme for PAH patients and the PAH expert centre, which takes care of the patient and is thoroughly involved in the training programme. Further multicentre international randomised trials are needed to evaluate whether this specialised programme is feasible within different healthcare systems and to assess long term effects and survival.