6MW Test Research Articles

Transthoracic Echocardiography and 6-Minute Walk Test in Kuwaiti Sickle Cell Disease Patients

Objective: The aim of this study was to investigate cardiac abnormalities in Kuwaiti sickle cell disease (SCD) patients using markers such as tricuspid regurgitant jet velocity (TRJV), pulmonary artery systolic pressure (PASP), and the 6-minute walk (6MW) test and correlate these findings with clinical, hematological, and biochemical parameters. Materials and Methods: Seventy-three patients with SCD and 70 matched controls were studied. The cardiac status was investigated using transthoracic echocardiography in 57 patients; the 6MW test was carried out in patients and controls. Complete blood counts and hemolytic parameters were assessed. Results: Reticulocytes, bilirubin, and lactate dehydrogenase were significantly higher (p < 0.0001) in patients, while hemoglobin (Hb) and haptoglobin were lower (p < 0.0001) than in controls. The mean fetal Hb among patients was 15.85 ± 8.7%. Of the 57 patients, 14 (24.5%) and 15 (26%) had mild tricuspid and mitral regurgitation, respectively. The mean ejection fraction, TRJV, and PASP were 63.9 ± 6.3%, 1.7 ± 0.5 m/s, and 23.0 ± 7.3 mm Hg, respectively. Three (5.2%) patients had mildly raised TRJV (2.6-2.97 m/s, normal range <2.5 m/s) while 8 (14%) had high PASP (mean 35.3 ± 5.1 mm Hg, normal range <30 mm Hg). Hb, hematocrit, and reticulocytes were different (p = 0.010, p = 0.006, and p = 0.011, respectively) between patients with normal and high PASP. All 3 patients who had a high TRJV had a high PASP, and 2 of these patients died during follow-up. The systolic and diastolic blood pressure, oxygen saturation before and after the 6MW test, and distance walked were lower (p = 0.006, p = 0.000, p = 0.002, p = 0.000, and p = 0.000, respectively) in patients compared to controls. Conclusion: Raised PASP was common in Kuwaiti SCD patients while raised TRJV was not.

Minimally Invasive Total Knee Arthroplasty Does Not Improve Outcomes 1 Year after Surgery: A Randomized Controlled Trial

Background: Within the past few years, minimally invasive surgical (MIS) techniques fortotal knee arthroplasy (TKA) have emerged as promising alternatives to conventional TKA, possibly because of less surgical trauma to the quadriceps. The purpose of this investigation was to evaluate the efficacy of MIS TKA outcomes compared to conventional TKA. Methods: Forty-four patients, aged 50-85 years (64.3 ± 8.4 mean ± SD; 22 females, 22 males) who were scheduled for a unilateral TKA secondary to osteoarthritis were enrolled in a prospective randomized controlled trial. Patients were excluded if they had cardiopulmonary, neurological, or other unstable orthopedic conditions that limited function; uncontrolled diabetes; or a BMI ≥ 40 kg/m2. Patients were blinded and randomly assigned to one of two surgical groups: MIS or conventional. All patients completed a standardized course of rehabilitation following surgery. Patients were assessed preoperatively and 4, 12, 26, and 52 weeks postoperatively by a blinded evaluator; the 26- and 52-week outcomes are the focus of the present manuscript. Outcomes included isometric quadriceps strength (primary outcome), isometric hamstrings strength, quadriceps activation, active knee range of motion (AROM), the six-minute walk (6MW) test, pain at rest and with 6MW, timed-up-and-go test (TUG), the stair climbing test, the Short Form 36 Health Status questionnaire (SF-36) the Western Ontario and McMaster Osteoarthritis Index (WOMAC), and leg muscle mass. Results: There were no differences between groups at baseline. At 26 and 52 weeks postoperatively, there were no difference between MIS and control groups for any outcome measure. Conclusions: Although the MIS surgical technique for TKA may lead to faster recovery of strength in patients undergoing TKA (previously reported at 4 weeks postoperatively), there is no apparent benefit of MIS on the longerterm recovery of strength or functional performance. Therefore, the benefits of MIS TKA may not outweigh the risks associated with limited surgical visualization.

Randomized controlled trial of physical activity, cognition, and walking in multiple sclerosis

The present study adopted a randomized controlled trial design and examined the effect of a physical activity behavioral intervention on cognitive and walking performance among persons with MS who have mild or moderate disability status. A total of 82 MS patients were randomly allocated into intervention or wait-list control conditions. The intervention condition received a theory-based program for increasing physical activity behavior that was delivered via the Internet, and one-on-one video chat sessions with a behavior-change coach. Participants completed self-report measures of physical activity and disability status, and underwent the oral Symbol Digit Modalities Test (SDMT) and 6-minute walk (6MW) test before and after the 6-month period. Analysis using mixed-model ANOVA indicated a significant time×condition×disability group interaction on SDMT scores (p=0.02, partial-η (2)=0.08), such that persons with mild disability in the intervention condition demonstrated a clinically meaningful improvement in SDMT scores (~6 point change). There was a further significant time×condition interaction on 6MW distance (p=0.02, partial-η (2)=0.07), such that those in the intervention condition demonstrated an increase in 6MW distance relative to those in the control group. The current study supports physical activity as a promising tool for managing cognitive impairment and impaired walking performance in persons with MS, and suggests that physical activity might have specific effects on cognition and non-specific effects on walking performance in this population.

Resistance exercise combined with essential amino acid supplementation improved walking ability in elderly people

We investigated the effects of resistance exercise combined with essential amino acid supplementation on psoas major muscle (PMM) hypertrophy and walking ability in elderly individuals. Twenty-nine healthy elderly individuals were assigned to 3 groups: (1) E (exercise), (2) A3 (exercise combined with 3.0 g of essential amino acid supplementation), and (3) A6 (exercise combined with 6.0 g of essential amino acid supplementation). To evaluate walking ability, the participants underwent the following 3 types of tests: the (1) 10-meter walk (10-W), (2) 10-meter walk involving crossing of obstacles (10-W + O), and (3) 6-minute walk (6M-W) tests. The 6-month training program resulted in significant PMM hypertrophy in all groups independent of amino acid supplementation. The extent of hypertrophy in the participants who took amino acids was dose-dependent, although the differences were not significant. Groups A3 and A6 demonstrated improvements in the 10-W and 10-W + O tests, whereas no improvement was observed in group E, regardless of PMM hypertrophy. Furthermore, group A6 showed an improvement in the 6M-W test. These results suggest that our training program causes PMM hypertrophy, whereas the training program combined with essential amino acid supplementation improves walking ability.

Gait and six-minute walk performance in persons with multiple sclerosis

The six-minute walk (6MW) has been established as a clinic-based, performance measure of walking endurance that reflects community ambulation in multiple sclerosis (MS). Consequently, identifying the contribution of variables to 6MW performance may provide targets for improving real-life walking in MS, and these variables may differ as a function of disability. This study examined cadence and stride length as gait variables that explain differences in 6MW performance between persons with MS and controls, and by level of disability. 256 community-residing persons with MS and 49 non-MS controls performed a standard 6MW test and completed 2 trials of comfortable walking on an electronic walkway for quantifying gait. Regression analyses indicated that cadence and stride length explain differences in 6MW performance between MS and controls, and by level of disability in MS. The contribution of cadence and stride length to walking endurance differed as a function of disability, such that cadence and to a greater extent stride length explained variance in 6MW performance in mild MS, whereas cadence and stride length explained approximately an equivalent amount of variance in 6MW performance in moderate-to-severe MS. We provide evidence for intervention strategies that are specific to disability level to improve walking endurance in MS.

Deficits in Physical Function Among Young Childhood Cancer Survivors

Childhood cancer survivors (CCSs) are at risk for physical disability. The aim of this investigation was to characterize and compare physical performance among CCSs and a group of siblings age < 18 years and determine if diagnosis, treatment, and physical activity levels were associated with lower performance scores. CCSs ≥ 5 years from diagnosis and a sibling comparison group were recruited and evaluated for strength, mobility, and fitness. Physical performance measures were compared in regression models between survivors and siblings by diagnosis and among survivors by treatment exposures and physical activity levels. CCSs (n = 183; mean age ± standard deviation [SD], 13.5 ± 2.5 years; 53% male) scored lower than siblings (n = 147; mean age ± SD, 13.4 ± 2.4 years; 50% male) on lower-extremity strength testing, the timed up-and-go (TUG) test, and the 6-minute walk (6MW) test, despite reporting similar levels and types of habitual physical activity. The lowest scores were prevalent among survivors of CNS tumors and bone and soft tissue sarcomas on strength testing (score ± SD: CNS tumors, 76.5 ± 4.7; sarcoma 67.1 ± 7.2 v siblings, 87.3 ± 2.4 Newton-meters quadricep strength at 90° per second; P = .04 and .01, respectively) and among CNS tumor survivors on the TUG (score ± SD: 5.1 ± 0.1 v siblings, 4.4 ± 0.1 seconds; P < .001) and 6MW tests (score ± SD: 533.3 ± 15.6 v siblings, 594.1 ± 8.3 m; P < .001). CCSs may have underlying physiologic deficits that interfere with function that cannot be completely overcome by participation in regular physical activity. These survivors may need referral for specialized exercise interventions in addition to usual counseling to remain physically active.

FRI0299 Heart rate recovery predicts outcomes in patients with pulmonary arterial hypertension associated with connective tissue diseases

BackgroundWe have previously reported that heart rate recovery (HRR) after a six-minute walk test (6MWT) is a free and easily measured biomarker that can accurately predict clinical worsening in patients...

The six-minute walk test is an excellent predictor of functional ambulation after total knee arthroplasty

BackgroundThe Six-minute walk (6MW) and Timed-Up-and-Go (TUG) are short walk tests commonly used to evaluate functional recovery after total knee arthroplasty (TKA). However, little is known about walking capacity of TKA recipients over extended periods typical of everyday living and whether these short walk tests actually predict longer, more functional distances. Further, short walk tests only correlate moderately with patient-reported outcomes. The overarching aims of this study were to compare the performance of TKA recipients in an extended walk test to healthy age-matched controls and to determine the utility of this extended walk test as a research tool to evaluate longer term functional mobility in TKA recipients.MethodsThe mobility of 32 TKA recipients one year post-surgery and 43 healthy age-matched controls were assessed using the TUG, 6MW and 30-minute walk (30MW) tests. The latter test was repeated one week later. Self-reported function was measured using the WOMAC Index and a physical activity questionnaire.Results30MW distance was significantly shorter amongst TKA recipients (mean 2108 m [95% CI 1837 to 2381 m]; Controls 3086 m [2981 to 3191 m], P < 0.001). Test-retest repeatability was high (ICC = 0.97, TKA; 0.96, Controls). Amongst TKA recipients, the 30MW distance correlated strongly with the shorter tests (6MW, r = 0.97, P < 0.001; TUG, r = −0.82, P < 0.001). Multiple regression modeling found 6MW distance to be the only significant predictor (P < 0.001) of 30MW distance, explaining 96% of the variability. The TUG test models were moderate predictors of WOMAC function (55%) and physical activity (36%) and were stronger predictors than 6MW and 30 MW tests.ConclusionsThough TKA recipients are able to walk for 30 minutes one year post-surgery, their performance falls significantly short of age-matched norms. The 30MW test is strongly predicted by 6MW test performance, thus providing strong construct validity for the use of the 6MW test in the TKA population. Neither a short nor long walk test is a strong predictor of patient-reported function after TKA.

Cardiopulmonary fitness in patients undergoing hematopoietic SCT: a pilot study

Hematopoietic cell transplantation (HCT) is a life-saving treatment for patients with high-risk hematological malignancies. Prognostic measures to determine fitness for HCT are needed to inform decision-making and interventions. VO(2peak) is obtained by measuring gas exchange during cycle ergometry and has not been studied as a prognostic factor in HCT. Thirty-two autologous and allogeneic HCT patients underwent VO(2peak) and 6 Minute Walk (6MW) testing before HCT, and provided weekly symptom and health-related quality of life (HRQOL) assessments before HCT and concluding at Day 100. Twenty-nine patients completed pre-HCT testing. Pre-HCT VO(2peak) was positively correlated with pre-HCT 6MW (r=0.65, P<0.001) and negatively correlated with number of chemotherapy regimens and months of chemotherapy. Patients with lower VO(2peak) reported higher symptom burden and inferior HRQOL at baseline and during early post-HCT period. Patients with pre-HCT VO(2peak) <16 mL/kg/min had higher risk of mortality post HCT (entire cohort: hazard ratio (HR) 9.1 (1.75-47.0), P=0.01; allogeneic HCT patients only: HR 6.70 (1.29-34.75), P=0.02) and more hospitalized days before Day 100 (entire cohort: median 33 vs 19, P=0.003; allogeneic HCT patients only: median 33 vs 21, P=0.004). VO(2peak) pre-HCT is feasible and might predict symptom severity, HRQOL and mortality. Additional studies are warranted.

The Effect of Exercise on Fitness and Performance-Based Tests of Function in Intermittent Claudication: A Systematic Review

Exercise is a widely accepted treatment known to improve walking ability in persons with peripheral arterial disease (PAD); however, it has not been confirmed as to whether exercise improves fitness and performance-based function and, consequently, performance of activities of daily living (ADL). This systematic review aims to identify whether any mode of structured exercise improves physical fitness or performance-based tests of function and whether improvement in walking ability is related to an improvement in these outcomes. Eligible studies included randomized controlled trials (RCTs) using an exercise intervention for the treatment of intermittent claudication with fitness (including the 6-min walk (6MW), aerobic capacity, shuttle and muscle strength) tests and performance-based tests of function as the outcomes. STUDY APPRAISAL AND METHODS: Assessment of study quality was performed using a modified version of the Physiotherapy Evidence Database Scale (PEDro). Relative effect sizes, mean differences (MDs) and 95 % confidence intervals were calculated and adjusted via Hedges' bias-corrected for small sample sizes. Regression analyses were performed to establish relationships between walking ability and fitness outcomes. Twenty-four RCTs met the inclusion criteria: 19 aerobic training interventions and 5 progressive resistance training (PRT). In total 924 participants (71 % male) were studied; with few participants over 75 years of age and the mean ankle brachial index was mean ± standard deviation (SD) 0.66 ± 0.06. The most common outcome measured was aerobic capacity (52 % of trials), which improved by 8.3 % ± 8.7 % on average. Although there were no significant relationships, up to 16 % of the variance in walking distances can be explained by changes in walking economy. Muscle strength was measured in only five trials, improving by 42 % ± 74 % on average. There was a strong significant relationship between change in plantar flexor muscle strength and change in initial claudication time (r = 0.99; p = 0.001) and absolute claudication time (r = 0.75; p = 0.05) measured on a treadmill across trials measuring this muscle group. The 6MW distance was measured in only 14 % of trials. Walking and PRT significantly improved 6MW initial claudication distance (MD range 52-129 m) and total walking distance (MD range 36-108 m) in studies that measured this outcome. Only one trial assessed performance-based tests of function, and they did not improve significantly. Although data are limited, there is a strong significant relationship between plantar flexor muscle strength and treadmill walking ability. More research is needed to assess improvements in walking economy at specific timepoints and whether this translates to improvements in claudication outcomes and measurements pertaining to muscle strength. Future trials should focus on interventions that improve lower limb muscle strength and assess muscle strength, power and endurance across a variety of lower extremity muscle groups in order to understand these relationships further. The 6MW, muscle strength and performance-based tests of function such as chair stand, balance scale, stair climb and gait speed are understudied in PAD. Future trials should examine the effects of exercise on performance-based tests of function, which may predict actual ADL performance and incident disability.

Capacidade funcional em pacientes com diabetes mellitus no município de Matinhos, Paraná

O diabetes mellitus (DM) é decorrente de um inadequado funcionamento metabólico crônico, caracterizado por hiperglicemia com distúrbio dos carboidratos, gordura e metabolismo da proteína. O DM tem impacto substancial no perfil físico-funcional dos pacientes, entre os quais se destaca o teste de caminhada de seis minutos (TC6'). O objetivo do estudo foi analisar a capacidade funcional, por meio da distância percorrida no TC6', dos pacientes com DM tipo 1 (DM1) e 2 (DM2) cadastrados em Estratégias de Saúde da Família (ESFs) e Programas de Agentes Comunitários de Saúde (PACS) do município de Matinhos, Paraná. De 800 pacientes cadastrados nas ESF e PACS, foram contatados 497, e 153 participaram do estudo, sendo 1,30% com DM1 e 98,69% com DM2. Os avaliados tiveram média de 60,49±11,24 anos, a glicemia foi 173,18 mg/dL e as médias de massa corporal, estatura e índice de massa corpórea foram respectivamente: 76,69±14,07 kg, 1,62±0,08 m e 29,11±4,61 kg/m². Não houve correlação entre nível glicêmico e idade (r=0,023), entre idade e TC6' (r=-0,056), e nível glicêmico e TC6' (r=0,11). Observou-se que 28,10% apresentavam doença cardiovascular, 60,13% eram hipertensos e 16,99% tabagistas. O tratamento medicamentoso prevaleceu sobre os tratamentos dieta e exercício. Houve diferença estatística (p&lt;0,0001) entre a distância prevista e a percorrida no TC6', indicando que os pacientes com DM não atingiram os níveis esperados neste teste. Seria necessário realizar um programa multidisciplinar direcionado a essa população, com ações em atividade física e dieta, com o intuito de minimizar os efeitos do DM sobre os aspectos funcionais desses pacientes.

6-Min Walk Test Provides Prognostic Utility Comparable to Cardiopulmonary Exercise Testing in Ambulatory Outpatients With Systolic Heart Failure

The goal of this study was to compare the prognostic efficacy of the 6-min walk (6MW) and cardiopulmonary exercise (CPX) tests in stable outpatients with chronic heart failure (HF). CPX and 6MW tests are commonly applied as prognostic gauges for systolic HF patients, but few direct comparisons have been conducted. Stable New York Heart Association (NYHA) functional class II and III systolic HF patients (ejection fraction ≤ 35%) from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial were studied. 6MW distance (6MWD) and CPX indices (peak oxygen consumption [VO(2)] and ventilatory equivalents for exhaled carbon dioxide [VE/VCO(2)] slope) were compared as predictors of all-cause mortality/hospitalization and all-cause mortality over 2.5 years of mean follow-up. A total of 2,054 HF-ACTION participants underwent both CPX and 6MW tests at baseline (median age 59 years; 71% male; 64% NYHA functional class II and 36% NYHA functional class III/IV). In unadjusted models and in models that included key clinical and demographic covariates, C-indices of 6MWD were 0.58 and 0.65 (unadjusted) and 0.62 and 0.72 (adjusted) in predicting all-cause mortality/hospitalization and all-cause mortality, respectively. C-indices for peak VO(2) were 0.61 and 0.68 (unadjusted) and 0.63 and 0.73 (adjusted). C-indices for VE/VCO(2) slope were 0.56 and 0.65 (unadjusted) and 0.61 and 0.71 (adjusted); combining peak VO(2) and VE/VCO(2) slope did not improve the C-indices. Overlapping 95% confidence intervals and modest integrated discrimination improvement values confirmed similar prognostic discrimination by 6MWD and CPX indices within adjusted models. In systolic HF outpatients, 6MWD and CPX indices demonstrated similar utility as univariate predictors for all-cause hospitalization/mortality and all-cause mortality. However, 6MWD or CPX indices added only modest prognostic discrimination to models that included important demographic and clinical covariates.

Predicting poor physical performance after total knee arthroplasty

The purpose of this study was to develop a preliminary decision algorithm predicting functional performance outcomes to aid in the decision of when to undergo total knee arthroplasty (TKA). One hundred and nineteen patients undergoing primary unilateral TKA were evaluated before and 6 months after TKA. A regression tree analysis using a recursive partitioning function was performed with the Timed Up and Go (TUG) time, Six-Minute Walk (6MW) distance, and Stair Climbing Test (SCT) time as measured 6 months after TKA as the primary outcomes. Preoperative measures of functional performance, joint performance, anthropometrics, demographics, and self-reported status were evaluated as predictors of the primary outcomes 6 months after surgery. Individuals taking ≥10.1 s on the TUG and aged 72 years or older before surgery had the poorest performance on the TUG 6 months after surgery. Individuals walking <314 meters on the 6MW before surgery had the poorest performance on the 6MW test 6 months after surgery. Individuals taking ≥17 s to complete the SCT and scoring <40 on the SF-36 mental component score before surgery had the poorest performance on the SCT 6 months after surgery. Poorer performance preoperatively on the 6MW, SCT, and TUG, was related to poorer performance in the same measure after TKA. Age and decreased mental health were secondary predictors of poorer performance at 6 months on the TUG and SCT, respectively. These measures may help further develop models predicting thresholds for poor outcomes after TKA.

219 Walk Speed Trends in Patients with End-Stage Lung Disease Awaiting and after Lung Transplantation

With the implementation of the LAS in 2004, the only variable used from the six-minute walk test is the distance walked. Current research indicates that walk speed may have better prognostic value than distance alone. The purpose of this study was to examine the 6MW test performance for speed and distance and the relationship to LAS in an urban transplant center.

Over-ground walking in Parkinson’s disease: A pilot study utilizing a portable metabolic analyzer

Alterations in gait biomechanics are common during early stages of Parkinson’s disease (PD), potentially elevating energy requirements of walking and leading to impaired economy of gait. Although gait economy is traditionally assessed during treadmill walking with simultaneous ox-ygen consumption (VO2) monitoring, treadmill gait mechanics, particularly in PD, may be different from over-ground walking mechanics, possibly providing a distorted picture of true gait economy. Currently, no studies have directly examined the energy cost of over-ground walking in PD patients. The purpose of this study was to test the feasibility of measuring energy expenditure during over-ground walking in mild to moderate PD using portable gas exchange monitoring technology. Additionally, we sought to determine whether energy expenditure, as assessed through VO2 measures, related to disease severity for PD. Seventeen PD patients underwent separate 6-minute walk (6MW) tests both with and without the COSMED K4b2 portable oxygen monitoring system. Gait economy was calculated as measured VO2 during 6MW divided by the predicted VO2 for non-PD age-matched subjects, according to a standard estimation equation utilizing ground speed. Distance covered during the 6MW with the portable system (420 ± 12 meters) was highly correlated (r = 0.96, p 2 peak for normal floor walking, and show impaired gait economy relative to prediction equations. Interestingly, the degree of elevated energy expenditure during gait did not relate to disease severity.

Heart Rate Recovery Predicts Clinical Worsening in Patients with Pulmonary Arterial Hypertension

Reduced heart rate recovery after exercise is associated with increased mortality in cardiopulmonary diseases. We sought to evaluate the association between heart rate recovery at 1 minute of rest (HRR1) after 6-min walk test (6MW test) and clinical worsening in patients with idiopathic pulmonary arterial hypertension (IPAH). HRR1 was defined as the difference in heart rate at the end of 6MW test and at 1 minute after completion of the 6MW test. Between August 1, 2009 and March 30, 2010, 75 consecutive patients with IPAH underwent 6MW test and were included in the analysis. Compared with patients with HRR1 ≥ 16 (n = 45 [60%]), those with HRR1 less than 16 (n = 30 [40%]) were more likely to have clinical worsening (odds ratio, 9.7; 95% confidence interval [CI], 3-30; P < 0.001) and shorter time to first clinical worsening event (TCW) (6.7 mo vs. 13 mo; P < 0.001) during follow-up. By multivariable analysis, the best predictors of clinical worsening were HRR1 less than 16 (hazard ratio, 5.2; 95% CI, 1.8-14.8; P = 0.002) and mean pulmonary arterial pressure (hazard ratio, 1.04; 95% CI, 1.007-1.08; P = 0.02). Compared with the distance walked during the 6MW test (6MWD), HRR1 less than 16 was a better predictor of clinical worsening (C statistic 0.757 vs. 0.703) and TCW (C index 0.730 vs. 0.696). The addition of HRR1 increased the ability of 6MWD to predict clinical worsening events. HRR1 after 6MW test is a strong predictor of clinical worsening and TCW in patients with IPAH. The addition of HRR1 to 6MWD increases the capacity of 6MWD to predict clinical worsening and TCW in patients with IPAH.

Non-Cardiopulmonary Factors Affecting the Six-Minute Walk Distance in Patients with Sickle Cell Disease: Results From the Walk-PHaSST Study

Abstract 1074▪▪This icon denotes a clinically relevant abstractNon-Cardiopulmonary Factors Affecting the Six-Minute Walk Distance in Patients with Sickle Cell Disease: Results from the Walk-PHaSST Study. INTRODUCTION:The six-minute walk (6MW) test is frequently used to assess exercise capacity. Patients with sickle cell disease (SCD) can have decreased 6MW distance (6MWD) compared to controls. The 6MWD in conjunction with the TR-jet velocity (TRV) and NT-proBNP have recently been proposed to have a greater predictive value for screening SCD patients suspected of having pulmonary hypertension (PH) than TRV alone. (Parent et al, NEJM, 365; 1, 2011 365 (1):44–53). The American Thoracic Society guidelines recommend caution in controlling for sources of variability in the 6MWD (Am J Respir Crit Care Med 166. 111–117, 2002). Age and height are known confounders of the 6MWD. However, non-cardiopulmonary factors including skeletal-mechanics and pain may also impact the 6MWD. AIM:This study explores whether non-cardiopulmonary factors affect the 6MWD in SCD patients. METHODS:We analyzed data from subjects screened for the walk-PHaSST trial. Walk-PHaSST was a multi-center, placebo-controlled, double-blind, 16-week trial evaluating the safety and efficacy of oral sildenafil for the treatment of Doppler-defined PH (TRV ’2.7m/s) in subjects with SCD aged >12 years. The primary endpoint in the trial was change in 6MWD. During screening, subjects were evaluated by self-reported medical history, physical examination, blood sampling, echocardiography and 6MWD. Univariate and multivariable linear regression was performed. A two sided p value <0.05 was considered significant. RESULTS:Of the 673 subjects screened, 671 had a 6MW test. The median (inter-quartile range) of 6MWD was 438m (503 – 381m = 122 m).On univariate analysis, there was no statistically significant effect of the SCD genotype on the 6MWD (p=0.26). Further, when combining the severe genotypes (HbSS and HbSβ0 thalassemia) vs the less severe genotypes, there was no significant difference in the 6MWD (p=0.22).By multivariable linear regression (Table 1), after adjusting for age, gender and TRV, the presence of the following (self-reported by subjects) were independently associated with an estimated decrease in the 6MWD: a) chronic pain (n = 260/671, 38.9%) by 24.3m (95% CI: 9.1–39.4m, p-value <0.01), b) history of avascular necrosis (AVN) of the hip (N =127/671, 18.9%) by 27.8m (95% CI: 9.2–46.4m, p-value <0.01), and c) osteopenia (N = 46/671,6.9% ) by 31.2m (95% CI: 2.7.-59.6m, p-value <0.05) There were no significant two-way interactions between chronic pain, AVN of the hip and/or osteopenia. History of leg ulcers, osteomyelitis and rheumatoid arthritis were not significant predictors of the 6MWD.Table 1:Predictors of Six-minute Walk Distance in Patients With Sickle Cell Disease: Results From The Walk-PHaSST Study.Variables*EstimateWald 95% Confidence Limitsp-valueIntercept586.4538.2634.6<0.0001Self Reported Chronic Pain (Yes vs. No)−24.3−39.4−9.10.0017Self Reported Avascular Necrosis of Hip (Yes vs. No)−27.8−46.4−9.20.0034Self-Reported Osteopenia (Yes vs. No)−31.2−59.6−2.70.0316Tricuspid Regurgitant Velocity (per m/s)−31.9−50.6−13.30.0008Age (per 10 years increase)−7.5−13.4−1.70.0113Female (as compared to male)−40.5−55.0−26.0<.0001*All the above were simultaneously included in the multivariable model DISCUSSION:In this multi-center study of patients with SCD, history of self-reported: 1) chronic pain 2) AVN of the hip and 3) osteopenia were independently associated with decreased functional capacity (as assessed by the 6MW test), after adjusting for age, gender, and TRV.While the 6MWD in patients with SCD is significantly related to cardiac function (i.e., PH and LV diastolic dysfunction), the potential effects of pain, osteonecrosis and osteopenia on 6MWD suggest that if using the 6MW test as the primary endpoint in future trials, one should consider documentation of the presence of these factors and use a stratified randomization based on a composite of these non-cardiopulmonary variables. Disclosures:Hassell:NIH:. Gladwin:Patents filed related to treating hemolysis.: Patents & Royalties.

Sildenafil therapy for pulmonary hypertension: a prospective study

To explore the safety and efficacy of oral sildenafil therapy for pulmonary arterial hypertension (PAH), and to provide evidence for sildenafil treatment for Chinese patients with PAH. In this 12-week, prospective, open-label, uncontrolled study, 56 patients with PAH were given oral sildenafil (25 mg, tid). The primary end point was change from baseline to 12 weeks in exercise capacity assessed by 6 min walk (6MW) test. Secondary end points included changes in WHO class and cardiopulmonary hemodynamics. Clinical worsening was defined as death, transplantation, hospitalization for PAH, or initiation of additional therapies for PAH, such as intravenous epoprostenol or oral bosentan. After 12 weeks, the compliance was good in 56 patients. Significant improvement was seen in NYHA heart function class and WHO class as compared to baseline (P < 0.01): from class IV to class III in 2, from class III to class II in 8 and to class I in 2 cases, and from class II to class I in 5 cases. No NYHA heart function class and WHO PAH function class deterioration were observed. Oral sildenafil increased 6MW distance, from (352 ± 80) m to (396 ± 78) m, with a change of (44 ± 70) m (P < 0.01). Significant improvement was seen in hemodynamics (mean pulmonary artery pressure, P < 0.01; cardiac index, P < 0.01; pulmonary vascular resistance, P < 0.01) at week 12 as compared with baseline. Mean right atrial pressure decreased (3 ± 11) mm Hg (1 mm Hg = 0.133 kPa), mean pulmonary arterial pressure decreased (6 ± 14) mm Hg, cardiac output increased (1.1 ± 2.0) L/min, cardiac index increased (0.7 ± 1.1) L×min(-1)×m(-2), and total pulmonary resistance decreased (490 ± 831) Dys×s×cm(-5). Side effects were mild and consistent with those reported with sildenafil treatment. No statistically significant clinical worsening was observed with sildenafil therapy for PAH patients. Sildenafil improves exercise capacity, WHO functional class, and hemodynamics in patients with pulmonary arterial hypertension.

Randomized phase III clinical trial of two different arms of a combined treatment with carnitine plus celecoxib with or without megestrol acetate for patients with cancer-related anorexia/cachexia syndrome (CACS).

e19733 Background: Cancer-related anorexia/cachexia syndrome (CACS) is a multifactorial syndrome characterized by loss of lean body mass (LBM), metabolic alterations, chronic inflammation and fatigue. Methods: In October 2009 we started a phase III randomised study to establish which was the most effective and safest treatment to improve the “key” variables of CACS: increase of LBM, decrease of resting energy expenditure (REE), improvement of fatigue (MFSI-SF) and physical activity (ArmBand). As secondary endpoints we evaluated: grip strength, six minute walk test (6MW), appetite, serum levels of IL-6 and TNF-a, EORTC-QLQ-C30, Glasgow Prognostic Score (GPS), ECOG PS. All patients received as basic oral treatment poliphenols + alpha lipoic acid + carbocysteine + Vitamins A,C,E and were then randomly assigned to: L-carnitine 4 g/d + Celecoxib 300 mg/d (Arm 1) or the same treatment + megestrol acetate (MA) 320 mg/d (Arm 2). Treatment duration: 4 months. The planned sample size was 70 patients for each arm. An interim analysis (intent-to treat) was planned. Results: Sixty cachectic patients (mean age 65.2 ± 8.7 years) with tumors at different sites were enrolled and 57 were evaluable (3 died early due to disease progression). Analysis of changes from baseline showed that LBM assessed by DEXA as well as by L3-CT improved in both arms. Fatigue improved significantly in both arms. REE and physical activity did not show significant changes. As for secondary endpoints, the 6MW test, appetite, GPS and ECOG PS improved significantly. The comparison between the 2 arms by ANOVA test did not show a significant difference. Toxicity was substantially negligible and comparable between arms (1 grade 3 diarrhea in arm 1 and 2, which led to the withdrawal of carnitine for 2 weeks). Conclusions: Both arms showed to be effective as for primary efficacy endpoints (improvement of LBM and fatigue) and some important secondary endpoints. The results of the present trial confirm the efficacy of a combined approach for the treatment of CACS: arm 1, without MA, could be the treatment of choice as it was effective and easier to administer. The trial is ongoing.

The 6-Min Walk Test

The 6-min walk (6MW) is a self-paced test for measuring functional capacity. Lower 6MW distances have been associated with adverse outcomes in patients with heart failure. The purpose of this article is to describe the history of the 6MW test and to evaluate its reliability, validity, and predictive value as well as the responsiveness of the test to therapies. In the literature we reviewed, reliability was affected by several factors including learning effects and protocol deviations. The 6MW distance was moderately correlated with peak oxygen consumption derived from cardiopulmonary exercise stress testing. In some studies the 6MW distance was predictive of hospitalization and mortality. In pharmacological and cardiac resynchronization trials the 6MW distance did not consistently detect clinical improvements. Despite limitations, the 6MW test is a viable alternative to stress testing for objectively evaluating functional capacity in some settings. We provide recommendations for using the 6MW test in future studies.