Improvement In 6-min Walk Distance Research Articles

Comparative analysis of the addition of empagliflozin versus doubling the furosemide dose in decompensated heart failure.

This study aims to compare the addition of SGLT2 inhibitors or doubling the diuretic dose in patients receiving treatment with beta-blockers, angiotensin-converting enzyme inhibitors (ACEi), or angiotensin receptor blockers (ARB), as well as mineralocorticoid receptor antagonists (MRA), for heart failure with reduced ejection fraction (HFrEF) who present to the emergency department with decompensated heart failure. This study is a single-center and prospective analysis. A total of 980 decompensated heart failure (HFrEF) patients receiving optimal medical therapy (OMT) according to the 2021 European heart failure guidelines were randomized in a 2:1 ratio into the furosemide and empagliflozin treatment arms. The analysis includes patient clinical characteristics, laboratory results, and echocardiographic data. Factors influencing rehospitalization were identified through multivariate Cox regression analysis. Log-rank analysis was employed to assess factors affecting rehospitalization. The mean age of the patients was 67.9years, with 52.1% being men. There was no significant impact of demographic, clinical, or echocardiographic factors on rehospitalization at 1 month; only the effect of treatment subgroups on rehospitalization was observed (p = 0.039). Significant echocardiographic and clinical improvements were seen in both treatment arms. The empagliflozin group exhibited significant improvements in 6-min walk distance, heart rate, body weight, NT-pro BNP levels, and eGFR level compared to the furosemide group. The rate of rehospitalization in the first month was significantly lower in those receiving empagliflozin (28.7%) compared to those receiving a double dose of furosemide (40.2%) (log-rank p = 0.013). This study provides valuable insights into the management of decompensated HFrEF and demonstrates that SGLT2 inhibitors offer benefits beyond glycemic control in this patient group. The significant reduction in rehospitalization rates and improvements in echocardiographic parameters underscore the potential of SGLT2 inhibitors in reducing acute heart failure episodes.

Nusinersen in adults with type 3 spinal muscular atrophy: long-term outcomes on motor and respiratory function.

Nusinersen was approved for 5q spinal muscular atrophy (SMA), irrespective of age, SMA type or functional status. Nonetheless, long-term data on adults with milder phenotypes are scarce. We aimed to characterize evolution on motor and respiratory function in our cohort of adults with type 3 SMA. We conducted a longitudinal retrospective single-center study, including adults (≥18years) with type 3 SMA under nusinersen for > 22months. We reported on motor scores and spirometry parameters. Ten patients were included, with a median follow-up of 34months (range = 22-46). Four patients (40%) were walkers. None used non-invasive ventilation. In Revised Upper Limb Module (RULM) and Expanded Hammersmith Functional Motor Scale (HFMSE), difference of medians increased at 6, 22 and 46months comparing to baseline (-0.5 vs. + 1.5 vs. + 2.5 in RULM; + 4.0 vs. + 7.5 vs. + 6.0 in HFMSE). Two (50%) walkers presented a clinically meaningful improvement in 6-min walk distance. We did not report any clinically meaningful decrement in motor scores. Spirometry parameters showed an increasing difference of medians in maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) (-3 vs. + 13.4 vs. + 28.7 percentage points of predicted value for MIP; + 11.8 vs. + 13.1 vs. 13.3 percentage points of predicted value for MEP). Our cohort supports a sustained benefit of nusinersen in adults with type 3 SMA, in motor and respiratory function. Multicentric studies are still warranted.

Effects of high-intensity interval training and moderate-intensity continuous training on sarcopenia-related parameters in participants with Parkinson's disease: A 24-week randomized pilot trial substudy

ObjectiveTo evaluate the potential efficacy of two different supervised exercise regimens, namely high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), on sarcopenia-related parameters in participants with Parkinson's disease (PD). MethodsWe analyzed data from a randomized controlled pilot trial (CRIS identifier: KCT0007130). An aerobic exercise intervention using a cycle ergometer (40–60 min) in combination with calisthenics (5 min) was performed in three sessions/week for 24 weeks for HIIT (60% maximum aerobic power for 30–50 s with 1-min rest intervals) and MICT (50% peak oxygen consumption) groups. Changes in sarcopenia-related parameters, including appendicular skeletal muscle mass (ASM), ASM index (ASM/height2), handgrip strength, 6-min walking distance, and 30-s chair-stand test (30CST) score, were compared among the HIIT (n = 9), MICT (n = 10), and usual care (n = 11) groups. ResultsThe HIIT group showed greater increases in leg lean mass (p = 0.011), ASM (p = 0.035), and ASM index (p = 0.025), and greater improvements in 6-min walking distance (p = 0.024) and 30CST scores (p = 0.026) compared with the usual care group. However, among these parameters, only the 30CST score significantly improved in the MICT group compared to the usual care group (p = 0.002). Three of the four (75%) sarcopenic patients who underwent HIIT showed improved sarcopenia after the 24-week exercise intervention, whereas it did not improve in the sarcopenic patients included in the MICT (n = 2) and usual care (n = 2) groups. ConclusionThis study suggests that HIIT may be superior to MICT in improving sarcopenia in patients with PD. Further large-scale investigations are required to confirm our findings.

Prognostic impact of cancer history in patients undergoing transcatheter mitral valve repair

BackgroundHistory of cancer is common in patients undergoing transcatheter mitral valve repair (TMVR).ObjectivesAim was to examine the impact of cancer history on outcomes after TMVR.MethodsIn patients of a monocentric prospective registry of TMVR history of cancer was retrospectively assessed from records. Associations with 6-week functional outcomes and clinical outcomes during a median follow-up period of 594 days were examined.ResultsOf 661 patients (mean age 79 years; age-range 37–101 years; 56.1% men), 21.6% had a history of cancer with active disease in 4.1%. Compared with non-cancer patients, cancer patients had a similar procedural success rate (reduction of mitral regurgitation to grade 2 or lower 91.6% vs. 88%; p = 0.517) and similar relevant improvement in 6-min walking distance, NYHA class, Minnesota Living with Heart Failure Questionnaire score and Short Form 36 scores. 1-year survival (83% vs. 82%; p = 0.813) and 1-year survival free of heart failure decompensation (75% vs. 76%; p = 0.871) were comparable between cancer and non-cancer patients. Patients with an active cancer disease showed significantly higher mortality compared with patients having a history of cancer (hazard ratio 2.05 [95% CI 1.11–3.82; p = 0.023]) but similar mortality at landmark analysis of 1 year.ConclusionTMVR can be performed with equal efficacy in patients with and without cancer and symptomatic mitral regurgitation. Cancer patients show comparable clinical outcome and short-term functional improvement as non-cancer patients. However, longterm mortality was increased in patients with active cancer underlining the importance of patient selection within the heart-team evaluation.Graphical abstract

The short- and long-term effects of lower limb endurance training on outpatients with chronic obstructive pulmonary disease

Objective To explore the short- and long-term effects of lower-limb endurance training on chronic obstructive pulmonary disease outpatients. Design Prospective quasi-experimental study. Setting 1383-bed teaching hospital in Taiwan. Participants Overall, 69 outpatients diagnosed with chronic obstructive pulmonary disease were enrolled. A total of 60 patients completed the study. Intervention Training group: Lower-limb endurance training; control group: Education only. Main measures The modified medical research council score, chronic obstructive pulmonary disease assessment test score, pulmonary function test, and number of acute exacerbation within a year. Results The training group showed significant improvement in the chronic obstructive pulmonary disease assessment test total score, modified medical research council score (both P < 0.001) at third month sustaining to 12th month (P < 0.001) and presented less events of acute exacerbation (P = 0.011) at 12th month. The chronic obstructive pulmonary disease assessment test decreased by 8 points sustaining to 12th month. The training group presented significant post-training functional capacity improvements in 6-min walking distance, lowest oxygen saturation during 6-min walking test, peak workload, maximum inspiratory/ expiratory pressures, and calf circumference. Conclusions The lower-limb endurance training improved perceived dyspnea in daily activity and health status after completion of training and sustaining for a year. The lower-limb endurance training alleviated disease impacted on reduced acute exacerbations.

Surrogate endpoints in pulmonary arterial hypertension trials

Why don't you just look at the pulmonary artery pressure? This question is frequently asked when we discuss endpoints in pulmonary arterial hypertension (PAH) trials with colleagues from other disease areas. Trials of antihypertensive drugs simply look at blood pressure changes, whereas pivotal trials in PAH use change in 6-min walk distance or time to clinical worsening as primary outcome measures. Why the difference? It is not just the invasiveness of right heart catheterisation but much more a question of validated surrogate endpoints. The US Food and Drug Administration (FDA) and other regulatory agencies approve drugs when they improve how patients feel, function, or survive. 1 Temple R Are surrogate markers adequate to assess cardiovascular disease drugs?. JAMA. 1999; 282: 790-795 Crossref PubMed Scopus (298) Google Scholar In systemic hypertension, lowering blood pressure predicts reductions in major adverse cardiovascular events including stroke, myocardial infarction, and cardiovascular death, and so authorities accept blood pressure reduction as a surrogate endpoint—ie, a substitute for a clinically meaningful endpoint that is expected to predict the effect of a therapy. 1 Temple R Are surrogate markers adequate to assess cardiovascular disease drugs?. JAMA. 1999; 282: 790-795 Crossref PubMed Scopus (298) Google Scholar In PAH, there is no convincing evidence that reductions in pulmonary artery pressure or pulmonary vascular resistance are directly linked to improved exercise capacity or better survival. Hence, change in 6-min walk distance is being frequently used as a primary endpoint assessing the function part of the FDA paradigm. Time to clinical worsening has been applied as well, a composite endpoint based on death, PAH-related worsening, and prespecified reductions in exercise capacity. However, these endpoints have limitations. Improvement in 6-min walk distance reflects better exercise capacity but is no surrogate of better outcomes. 2 Gabler NB French B Strom BL et al. Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials. Circulation. 2012; 126: 349-356 Crossref PubMed Scopus (185) Google Scholar Time to clinical worsening does not capture clinical improvement, and reducing clinical worsening events does not necessarily lead to better survival. 3 Sitbon O Channick R Chin KM et al. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015; 373: 2522-2533 Crossref PubMed Scopus (607) Google Scholar , 4 Galiè N Barberà JA Frost AE et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015; 373: 834-844 Crossref PubMed Scopus (750) Google Scholar , 5 Pulido T Adzerikho I Channick RN et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013; 369: 809-818 Crossref PubMed Scopus (981) Google Scholar In addition, studies designed to show improvement in time to clinical worsening require large sample sizes, a challenge in a rare disease like PAH. Hence, there is an ongoing search for surrogate endpoints. Is low-risk status a surrogate outcome in pulmonary arterial hypertension? An analysis of three randomised trialsMulticomponent risk scores have utility for the prediction of outcomes in patients with PAH. Clinical surrogacy for long-term outcomes cannot be inferred from observational studies of outcomes. Our analyses of three PAH trials with long-term follow-up suggest that further study is necessary before using these or other scores as surrogate outcomes in PAH RCTs or clinical care. Full-Text PDF

Prognostic value of improvement endpoints in pulmonary arterial hypertension trials: A COMPERA analysis.

The prognostic value of improvement endpoints that have been used in clinical trials of treatments for pulmonary arterial hypertension (PAH) needs to be further investigated. Using the COMPERA database, we evaluated the prognostic value of improvements in functional class (FC) and absolute or relative improvements in 6-min walking distance (6MWD) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). In addition, we investigated multicomponent endpoints based on prespecified improvements in FC, 6MWD and NT-proBNP that have been used in recent PAH trials. Finally, we assessed the predictive value of improvements determined by risk stratification tools. The effects of changes from baseline to first follow-up (3-12 months after initiation of PAH therapy) on consecutive survival were determined by Kaplan-Meier analysis with Log-Rank testing and Cox proportional hazard analyses. All analyses were based on 596 patients with newly diagnosed PAH for whom complete data were available at baseline and first follow-up. Improvements in FC were associated with improved survival, whereas absolute or relative improvements in 6MWD had no predictive value. For NT-proBNP, absolute declines conferred no prognostic information while relative declines by ≥35% were associated with better survival. Improvements in multicomponent endpoints were associated with improved survival and the same was found for risk stratification tools. While sole improvements in 6MWD and NT-proBNP had minor prognostic relevance, improvements in multicomponent endpoints and risk stratification tools based on FC, 6MWD, and NT-proBNP were associated with improved survival. These tools should be further explored as outcome measures in PAH trials.

Riociguat in Patients with CTEPH and Advanced Age and/or Comorbidities.

Riociguat is licensed for the therapy of inoperable chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to investigate whether age and comorbidities influence its tolerability and efficacy. Retrospectively, we analyzed data of tolerability, non-invasive, and invasive efficacy at baseline and follow up (FU) of all patients with CTEPH treated with riociguat at the Department of Internal Medicine V, University of Munich (n = 47), grouping patients according to age (<65 versus 65–79 versus ≥80 years) and risk factors for heart failure with preserved ejection fraction (HFpEF) (<2 versus ≥2 risk factors). During dose titration patients >80 years reported side effects more frequently (40%) than the other age groups (23% and 21% for patients <65 years and patients 65–79, respectively). Cessation of riociguat was rare and occurred independent of age. When looking at the total cohort of 47 patients, three patients stopped therapy and three patients had a reduced maintenance dosage, while 41/47 (87%) and all octogenarians reached the highest maintenance dosage of 7.5 mg/d. The frequency of any side effect was similar in patients in both risk factor groups, and hypotension was only observed in those with <2 risk factors. Parameters of efficacy improved significantly under riociguat treatment. Improvement in 6-min walk distance (6 mwd), N-terminal pro brain natriuretic peptide (Nt-proBNP) and hemodynamics did not differ between age or risk factor groups. In this small real-life cohort, riociguat was well-tolerated and effective in advanced age and risk factors for HFpEF.

Efficacy and safety of Bufei Huoxue capsules in the management of convalescent patients with COVID-19 infection: A multicentre, double-blind, and randomised controlled trial

BackgroundAs of September 17, 2021, coronavirus disease 2019 (COVID-19) has infected more than 226 million people in a worldwide pandemic, with conservative estimates suggesting that there are more than 204 million convalescent patients with COVID-19. Previous studies have indicated that patients in the recovery phase exhibit decreased function of multiple organs. In China, traditional Chinese medicine (TCM) treatment is recommended in the rehabilitation period of COVID-19; however, the safety and efficacy of such treatment remain to be confirmed. Aim of studyThe present study aimed to evaluate the efficacy and safety of Bufei Huoxue (BFHX) in restoring the functional status and exercise tolerance of patients recovering from COVID-19. MethodsA total of 131 patients in the rehabilitation period of COVID-19 infection were randomly divided into a Bufei Huoxue (BFHX) group (n = 66) and a placebo group (n = 65). BFHX or placebo was given orally three times a day (1.4 g/dose) for 90 days. The primary outcomes was to evaluate improvements in exercise tolerance and imaging manifestations on chest computed tomography (CT). ResultsAfter the exclusion of two patients who withdrew prior to receiving any medications, 129 patients were recruited, including 64 patients in the BFHX group and 65 patients in the placebo group. After 3 months of treatment, the BFHX group exhibited greater attenuation of pneumonia lesions on chest CT than the placebo group (P<0.05). Improvements in 6-min walk distance (6MWD) relative to baseline were also significantly better in the BFHX group than in the placebo group (P<0.01). Scores on the Fatigue Assessment Inventory (FAI) were lower in the BFHX group than in the placebo group (P<0.05). Although the rate of adverse events was higher in the BFHX group than in the placebo group (9.38% vs. 4.62%), the difference was not significant (P=0.3241). ConclusionsBFHX may exert strong rehabilitative effects on physiological activity in patients recovering from COVID-19, which may in turn attenuate symptoms of fatigue and improve exercise tolerance.

November 2021 at a glance: focus on prevention, comorbidities, cardiogenic shock and novel devices.

November 2021 at a glance: focus on prevention, comorbidities, cardiogenic shock and novel devices.

Effects of enhanced external counterpulsation on exercise capacity and quality of life in patients with chronic heart failure: A meta-analysis.

Background:This meta-analysis aimed to synthesize randomized controlled trials to evaluate the effects of enhanced external counterpulsation (EECP) on exercise capacity and quality of life in patients with chronic heart failure (CHF).Methods:Both English and Chinese databases were searched from their inception to June 30, 2020 (PubMed, EMBASE, Cochrane Library, CINAHL (EBSCO), Web of Science for English publications and Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Data for Chinese publication). Titles, abstracts, and full-text articles were screened against study inclusion criteria: randomized controlled trials studying EECP intervention for patients with CHF. The meta-analysis was conducted with Revman 5.3 or STATA 16.0.Results:Eight randomized controlled trials were included. EECP induced significant improvement in 6-min walking distance (WMD=84.79 m; 95% CI, 47.64 to 121.95; P < .00001). Moreover, EECP was beneficial for left ventricular ejection fraction (SMD = 0.64; 95% CI,0.29 to 1.00; P = .0004), and N-terminal pro brain natriuretic peptide (SMD = −0.61; 95%CI, −1.20 to −0.01; P = 0.04).However, compared with the control groups, EECP did not significantly reduce the Minnesota Living with Heart Failure Questionnaire scores(WMD, −9.28; 95% CI, −19.30 to 0.75; P = 0.07).Conclusions:Despite heterogeneity and risk of bias, this meta-analysis confirms that EECP can improve exercise capacity in CHF patients, especially the elderly. However, the evidence that EECP improves the quality of life in patients with CHF is still insufficient. More and larger well-designed randomized controlled trials are still warranted.Registration information:PROSPERO registration no. CRD 42020188848.

Effect of ivabradine on heart rate, functional capacity and pulmonary artery pressure in patients of COPD with cor pulmonale

We studied the effects of heart rate reduction by ivabradine to the ongoing therapy in patients with chronic obstructive pulmonary disease (COPD) and cor pulmonale.100 patients of COPD with cor pulmonale with sinus heart rate ≥ 90 bpm were randomly assigned to either ivabradine 5 mg twice daily (50 patients) or placebo (50 patients) alongwith standard therapy. Assessment was done at baseline and after 6 months which included 6 min walk test (6MWT), dyspnea scoring by modified borg scale, Lung function test by forced expiratory volume in 1 s (FEV1) and pulmonary artery systolic pressure (PASP) by echocardiogram. The drug group showed a significant reduction in heart rate from 95.1 ± 8.2 bpm to 71.1 ± 6.2 bpm (p < 0.001). This group also showed significant improvement in 6-min walk distance and dyspnea on modified Borg scale (p < 0.001) at 6 months follow up. However no significant difference was found between both groups regarding PASP or FEV1 at 6 months.

Telerehabilitation Programme as a Maintenance Strategy for COPD Patients: A 12-Month Randomized Clinical Trial

BackgroundThere is uncertainty regarding efficacy of telehealth-based approaches in COPD patients for sustaining benefits achieved with intensive pulmonary rehabilitation (PR). Research questionTo determine whether a maintenance pulmonary telerehabilitation (TelePR) programme, after intensive initial PR, is superior to usual care in sustaining over time benefits achieved by intensive PR. Study design and methodsA multicentre open-label pragmatic parallel-group randomized clinical trial was conducted. Two groups were created at completion of an 8-week intensive outpatient hospital PR programme. Intervention group (IG) patients were given appropriate training equipment and instructed to perform three weekly training sessions and send performance data through an app to a web-based platform. Patients in the control group (CG) were advised to exercise regularly (usual care). ResultsNinety-four patients (46 IG, 48 CG) were randomized. The analysis of covariance showed non-significant improvements in 6-min walk distance [19.9m (95% CI ∧4.1/+43.8)] and Chronic Respiratory Disease Questionnaire • Emotion score [0.4 points (0•0.8)] in the IG. Secondary linear mixed models showed improvements in the IG in Short Form-36 mental component summary [9.7, (4.0•15.4)] and Chronic Respiratory Disease Questionnaire • Emotion [0.5, (0.2•0.9)] scores, but there was no association between compliance and outcomes. Acute exacerbations were associated with a marginally significant decrease in 6-minute walk distance of 15.8m (∧32.3/0.8) in linear models. ConclusionsThe TelePR maintenance strategy was both feasible and safe but failed to show superiority over usual care, despite improvements in some HRQoL domains. Acute exacerbations may have an important negative influence on long-term physical function. ClinicalTrials.gov identifierNCT03247933.

Non-invasive ventilation intervention during exercise training in individuals with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

evidence is inconsistent for the effect of non-invasive ventilation (NIV) for individuals with chronic obstructive pulmonary disease (COPD) during exercise training. This review aimed to determine the effect of NIV in COPD individuals during exercise training on exercise capacity, quality of life, functional performance and symptoms. we searched for studies evaluating the effect of NIV on COPD individuals during exercise training published until May 2020 in 6 electronic databases (PubMed, Embase, Cochrane Library, Web of Science, clinical trial registers and Wanfang). The included studies were appraised with the Cochrane Risk of Bias tool and Downs and Black criteria. The primary outcomes were improvement in 6-min walking distance and quality of life. Mean difference (MD) or standardized mean difference (SMD) with 95% confidence intervals (CIs) was calculated. among 855 identified articles, reports for 15 studies with heterogeneous populations were eligible, with 520 individuals: 257 in the NIV group and 263 in the control group. Across studies, NIV intervention during exercise training affected exercise performance (6-min walking distance: SMD: 0.33, 95% CI: 0.06; 0.59, P=0.02; quality of life: SMD: -0.77, 95% CI: -1.01; -0.53, P<0.001). In the analysis of dyspnea, pooled estimates demonstrated improvement in the NIV versus control group. NIV intervention was also better than exercise alone in ameliorating oxygen saturation, PaO2, PaCO2, blood lactate level and breath rate. The groups did not differ in duration of exercise, BODE index, minute ventilation, heart rate and systolic blood pressure. our review suggests that NIV is a relevant adjuvant for exercise training in COPD individuals because the intervention could improve exercise performance and quality of life. The current results also demonstrate the importance of further investigations of higher methodological quality to assess the effect on exercise capacity and quality of life.

Effectiveness of epoprostenol in the management of pulmonary arterial hypertension: findings of an Australian retrospective chart review.

Pulmonary arterial hypertension (PAH) is a progressively fatal disease. Parenteral prostanoids, including intravenous (IV) epoprostenol, are the most effective therapies for PAH. As epoprostenol requires continuous infusion, therapy is challenging and use is managed by specialist units. To describe the clinical outcomes for the use of IV epoprostenol in an Australian pulmonary vascular disease unit and identify opportunities to improve its use. We conducted a retrospective chart review of all adult patients who received IV epoprostenol for PAH at Prince Charles Hospital. Data were collected at baseline, initiation of epoprostenol and quarterly to the end of the audit period or the discontinuation of epoprostenol. Descriptive statistics were performed and comparisons made to epoprostenol initiation. Kaplan-Meier curves were used to estimate survival outcomes. Thirty-nine patients received epoprostenol therapy. Most (87.2%) were female, had connective tissue disease (46.2%) or idiopathic PAH (35.9%) and had a World Health Organization functional Class of III or IV at initiation. The mean duration of epoprostenol therapy was 2.9 years. Intravenous epoprostenol was associated with favourable outcomes; 1, 3 and 5-year survival rates since initiation of 90.0, 75.8 and 68.2%; robust improvements in functional class; and improvements in 6-min walking distance of 160.4 m at 3 years; 94.9% patients experienced at least one drug-related adverse event and line complications were common. Epoprostenol therapy was associated with impressive survival rates and durable improvements in functional outcomes. Epoprostenol therapy is challenging; however, it is manageable by the majority of patients with most experiencing positive, sustainable outcomes.

Pharmacological and nonpharmacological interventions to improve symptom control, functional exercise capacity and quality of life in interstitial lung disease: an evidence synthesis.

We assessed efficacy and effectiveness of pharmacological and nonpharmacological interventions in improving symptom control, functional exercise capacity and quality of life (QoL) in people living with fibrotic interstitial lung disease (ILD).We summarised evidence from three previous reviews (to June 2014) and conducted an updated search of nine databases and grey literature (2011–2019) (registration: CRD42017065933) for prospective studies of interventions aimed to alleviate symptoms, improve QoL or functional exercise capacity in fibrotic ILD. Data were synthesised through narrative synthesis or meta-analysed as appropriate.Forty-seven studies with 2527 participants were included. From 22 pharmacological studies of 11 different interventions (n=1683), the most tested interventions were bosentan and sildenafil. From 25 nonpharmacological studies, the most tested intervention was for pulmonary rehabilitation/exercise training (PR) (22 studies, n=748). There was an improvement in 6-min walk distance immediately following PR (six studies; n=200, mean difference (MD) (95% CI) 39.9 m (18.2 to 61.5)), but not longer term (3 or 6 months, four studies; n=147, MD 5.3 m (−12.9 to 23.4). Multiple, varied outcome measures were used (e.g. 37 studies assessing dyspnoea used 10 different scales with a lack of reporting of rate of deterioration in outcomes). Evidence gap mapping highlighted the most and least researched symptoms, as dyspnoea and cough, respectively.This evidence synthesis highlights overwhelmingly that the most researched symptom is dyspnoea and the strongest evidence base is for short-term PR. The least researched symptom was cough. Research going forward must focus on prioritising and standardising meaningful outcomes and focussing interventions on neglected symptoms.

Point of care, bone marrow mononuclear cell therapy in ischemic heart failure patients personalized for cell potency: 12-month feasibility results from CardiAMP heart failure roll-in cohort

AimHeart failure following myocardial infarction (MI) is a potentially lethal problem with a staggering incidence. The CardiAMP Heart Failure trial represents the first attempt to personalize marrow-derived cell-based therapy to individuals with cell characteristics associated with beneficial responses in prior trials. Before the initiation of the randomized pivotal trial, an open-label “roll-in cohort” was completed to ensure the feasibility of the protocol's procedures. MethodsPatients with chronic post-MI heart failure (NYHA class II-III) receiving stable, guideline-directed medical therapy with a left ventricular ejection fraction between 20 and 40% were eligible. Two weeks prior to treatment, a ~ 5 mL bone marrow aspiration was performed to examine “cell potency”. On treatment day, a 60 mL bone marrow aspiration, bone marrow mononuclear cell (BM MNC) enrichment and transendocardial injection of 200 million BM MNC's was performed in a single, point of care encounter. Patients were then followed to assess clinical outcomes. ResultsThe cell potency small volume bone marrow aspirate, the 60 mL bone marrow aspirate, and transendocardial injections were well tolerated in 10 patients enrolled. There were no serious adverse events related to bone marrow aspiration or cell delivery. Improvement in 6-min walk distance was observed at 6 months (+47.8 m, P = 0.01) and trended to improvement at 12 months (+46.4, P = 0.06). Similarly, trends to improved NYHA heart failure functional class, quality of life, left ventricular ejection fraction and recruitment of previously akinetic left ventricular wall segments were observed. ConclusionAll CardiAMP HF protocol procedures were feasible and well tolerated. Favorable functional, echo and quality of life trends suggest this approach may offer promise for patients with post MI heart failure. The randomized CardiAMP Heart Failure pivotal trial is underway to confirm the efficacy of this approach. Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT02438306

Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE

BackgroundRESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement. MethodsRESPITE was a 24-week, uncontrolled pilot study (n = 61). Differences in functional, hemodynamic, and cardiac function parameters, REVEAL risk score (RRS), and biomarkers were compared between responders (free from clinical worsening, World Health Organization functional class I/II, and ≥30 m improvement in 6-min walking distance at Week 24) and non-responders. ResultsOf 51 patients (84%) completing RESPITE, 16 (31%) met the responder endpoint. At baseline, there were significant differences between responders and non-responders in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth/differentiation factor 15 (GDF-15), and RRS, whereas there were no differences in hemodynamics or cardiac function. At Week 24, responders had significant improvements in pulmonary arterial compliance, pulmonary vascular resistance, and mean pulmonary arterial pressure, while non-responders showed no significant change. Cardiac efficiency and stroke volume index significantly improved irrespective of responder status. ConclusionsNT-proBNP, GDF-15, and RRS were identified as potential predictors of response in patients switching from PDE5i to riociguat. Further prospective controlled studies are needed to confirm the association of these parameters with response.

Telerehabilitation Programme as a Maintenance Strategy for COPD Patients: A 12-Month Randomized Clinical Trial

BackgroundThere is uncertainty regarding efficacy of telehealth-based approaches in COPD patients for sustaining benefits achieved with intensive pulmonary rehabilitation (PR). Research questionTo determine whether a maintenance pulmonary telerehabilitation (TelePR) programme, after intensive initial PR, is superior to usual care in sustaining over time benefits achieved by intensive PR. Study design and methodsA multicentre open-label pragmatic parallel-group randomized clinical trial was conducted. Two groups were created at completion of an 8-week intensive outpatient hospital PR programme. Intervention group (IG) patients were given appropriate training equipment and instructed to perform three weekly training sessions and send performance data through an app to a web-based platform. Patients in the control group (CG) were advised to exercise regularly (usual care). ResultsNinety-four patients (46 IG, 48 CG) were randomized. The analysis of covariance showed non-significant improvements in 6-min walk distance [19.9m (95% CI −4.1/+43.8)] and Chronic Respiratory Disease Questionnaire – Emotion score [0.4 points (0–0.8)] in the IG. Secondary linear mixed models showed improvements in the IG in Short Form-36 mental component summary [9.7, (4.0–15.4)] and Chronic Respiratory Disease Questionnaire – Emotion [0.5, (0.2–0.9)] scores, but there was no association between compliance and outcomes. Acute exacerbations were associated with a marginally significant decrease in 6-minute walk distance of 15.8m (−32.3/0.8) in linear models. ConclusionsThe TelePR maintenance strategy was both feasible and safe but failed to show superiority over usual care, despite improvements in some HRQoL domains. Acute exacerbations may have an important negative influence on long-term physical function. ClinicalTrials.gov identifierNCT03247933.

Oxygen therapy for pulmonary arterial hypertension: We need to rethink and investigate.

Oxygen therapy for pulmonary arterial hypertension: We need to rethink and investigate.