Changes In 6-minute Walk Test Research Articles

Slow and Steady Wins the Race: Optimization of Older Adult Allogeneic Hematopoietic Cell Transplant (Allo-HCT) Candidates

Background: Allo-HCT is the only potentially curative therapy available for many hematologic malignancies, but due to its intensity and associated toxicities, is infrequently offered to older adults. This study explored the feasibility and efficacy of individualized, geriatric assessment (GA)-guided intervention among older adult candidates for allo-HCT. Methods: Patients ≥ 60 years old that were candidates for allo-HCT were recruited between June 11, 2021 and July 1, 2022. Exclusion criteria included inability to speak English, diagnosis of dementia, and planned allo-HCT in < 1 month or > 6 months. Baseline GA was completed at time of enrollment. Subjects were prescribed multi-domain personalized geriatric intervention based on results of their individual GA. Patients were continued on geriatric intervention for up to 6 months or until transplant. A post-intervention GA was conducted after 6 months or at time of admission for allo-HCT, whichever occurred first. Metrics included in GA are defined in table 1. Subjects were provided wearable accelerometer device for activity tracking. Primary outcome of interest was change in 6-minute walk test (6MWT) and secondary outcomes included improved or maintained short physical performance battery (SPPB), receipt of allo-HCT, and overall survival (OS). Wilcoxon signed rank test was used to compare GA metrics pre- and post-intervention, and OS was estimated using the Kaplan-Meier method. Exploratory analyses included univariable modeling of association of baseline GA metrics with receipt of allo-HCT and OS. Results: A total of 63 allo-HCT eligible patients were approached, 30 consented and were evaluable. Of 33 not enrolled, 17 declined (7 due to requirement to wear accelerometer device), 7 were planned for allo-HCT in < 1 month, 4 were not interested in allo-HCT, 3 had virtual appointments with incomplete GA, 1 had dementia and 1 with anticipated allo-HCT date > 6 months. The majority of enrolled subjects were male (80%) and all were non-Hispanic, white. Median age at enrollment was 68.9 years (range: 60.8-79.2). Half (n=15) were diagnosed with acute myeloid leukemia, 40% (n=12) with myelodysplastic syndrome, and one each with chronic myelomonocytic leukemia, myelofibrosis, and non-Hodgkin lymphoma. The median time from allo-HCT-eligible diagnosis to baseline GA was 4.1 months (range: 1.2-118.9). More than half (n=16, 53.3%) of subjects received allo-HCT. Median time to allo-HCT from diagnosis was 13.8 months (range: 3.3-122.1) and from baseline GA was 4.6 months (range: 0.5-10.8). No one baseline GA metric was associated with receipt of allo-HCT (table 2). Median OS from study enrollment for all subjects was not reached (95% CI: 9.8 month-NR) with median follow-up of 14.8 months (range: 10.7-19.3). At baseline, better gait speed on 6MWT (HR: 0.72; 95% CI: 0.59-0.89, p=0.0018), SPPB (HR: 0.76; 95% CI: 0.60-0.97; p=0.02), and Montreal Cognitive Assessment (MOCA; HR: 0.72; 95% CI: 0.55-0.95; p = 0.02) scores were all associated with improved OS in univariable analysis (table 2). Pre and post-intervention GA metrics are presented in table 1. Only 14 subjects completed at least partial post-intervention GA, 12 of whom received allo-HCT. Reasons for not completing post-intervention GA included subjects declining to schedule (n=6), issues of care coordination (e.g.: frequent or prolonged hospital admissions, changes to allo-HCT admission plan; n=6), and death (n=4). Twelve subjects had both pre and post-intervention 6MWT data, 83.3% (n=10) improved by at least 50 feet. Ten subjects had both pre and post-intervention SPPB and all improved by at least 1 point or maintained a normal score (>9). Discussion: Improvement in or maintenance of 6MWT and SPPB were demonstrated in the majority of subjects with measured pre and post-intervention GA. Unfortunately, attrition was a major limitation of the study. Patterns of loss to follow-up, as well as reasons for screen failure, will be important areas for further exploration and potential targets for intervention at institutional and provider levels. Importantly, age was not associated with OS. Early education about allo-HCT paired with patient-centered goals of care conversations may be useful in identifying older adults most motivated and likely to benefit from GA-guided intervention.

ThTP6.4 A systematic review of the impact of postoperative aerobic exercise training in patients undergoing surgery for intra-abdominal cancers

Abstract Introduction Enhanced recovery after surgery (ERAS) programmes which advocate early mobility after surgery have improved immediate clinical outcomes for patients undergoing abdominal cancer resections with curative intent. However, the impact of continued physical activity on patient-related outcomes and functional recovery is not well-defined. This review aims to assess the impact of postoperative aerobic exercise training, either alone or in conjunction with another exercise modality, on patients who have had surgery for intra-abdominal cancer. Methods A literature search was performed of electronic journal databases. Eligible papers needed to report an outcome of aerobic capacity in patients >18 years of age, who underwent cancer surgery with curative intent and participated in an exercise programme (not solely ERAS) that included an aerobic exercise component starting at any point in the postoperative pathway up to twelve weeks. Results Ten studies were deemed eligible for inclusion consisting of one inpatient, one mixed inpatient/outpatient and eight outpatient studies. Meta-analysis of 4 outpatient studies, each reporting change in 6-minute walk test (6MWT), showed a significant improvement in 6MWT with exercise (MD: 74.92 m, 95% CI: 48.52 to 101.31m). The impact on health-related quality of life was variable across studies. Conclusion Postoperative exercise confers benefits in improving aerobic function post-surgery and can be safely delivered in various formats (home-based or group/supervised).

Efficacy and Safety of Moderate-Intensity Continuous Training on the Improvement of Cardiopulmonary Function in Patients After Transcatheter Aortic Valve Replacement (ENERGY): A Randomized Controlled Trial

ObjectivesTo investigate the effect of moderate-intensity continuous training (MICT) on the improvement of cardiopulmonary function for patients undergoing transcatheter aortic valve replacement (TAVR). DesignRandomized controlled study. Setting and ParticipantsBetween August 20, 2021, and February 28, 2022, a total of 66 patients after TAVR were screened for inclusion and randomly divided into the MICT and control groups at a ratio of 1:1. MICT was scheduled 3 times per week for 3 months in the intervention group. Patients in the control group received one-time advice on physical activity according to the current guideline. MethodsThe primary endpoint was the 3-month change in peak oxygen consumption (peak VO2) assessed by cardiopulmonary exercise testing. The secondary endpoints included the 3-month change in 6-minute walk test (6MWT), the 12-Item Short Form Health Survey (SF-12), New York Heart Association (NYHA) class, echocardiographic parameters, and laboratory parameters. ResultsAfter 3 months, the change in peak VO2 was higher in the MICT group than that in the control group (1.63 mL/kg/min, 95% CI 0.58-2.67, P = .003). Change in 6MWT (21.55 m, 95% CI 0.38-42.71, P = .046) was higher in the MICT group compared with the control group. A significant change in favor of MICT was also observed for low-density lipoprotein cholesterol (−0.62 mmol/L, 95% CI –1.00 to −0.23, P = .002). However, there were no significant changes in other echocardiographic indices, laboratory parameters, and SF-12 between the 2 groups (all P > .05). Conclusions and ImplicationsMICT had a positive effect on the cardiopulmonary function and physical capacity of patients after TAVR.

Adjuvant testosterone therapy in chronic heart failure (ATTIC): a randomised open-label trial

IntroductionHeart failure is a major contributor to morbidity and mortality in the geriatric population, with no promising therapy currently available with considerable benefit. Testosterone therapy is an emerging viable treatment...

Change in pulmonary arterial compliance and pulmonary pulsatile stress after balloon pulmonary angioplasty.

Although the underlying pathology of chronic thromboembolic pulmonary hypertension (CTEPH) is mechanical obliteration of the major pulmonary vessels, high pulsatile stress penetrating into the normal distal pulmonary microvasculature resulting from reduced pulmonary arterial compliance (CPA) may cause progressive deterioration in pulmonary hemodynamics. Hypothetically, balloon pulmonary angioplasty (BPA) may be beneficial in reducing CPA and pulsatile stress in patients with CTEPH. In total, 26 patients with available pre- and post-BPA right heart catheterization results were included in the study. BPA was performed in a series of staged procedures by 2 experienced interventional cardiologists. The median CPA showed a 59.2% increase (1.03 to 1.64 mL/mm Hg, p=0.005). The median pre-BPA pulsatile stress product decreased by 20.7% (4,266 to 3,380 mm Hg/min, p=0.003). A linear regression model established that the percent change in CPA after BPA accounted for 21.8% of the explained variability in the change in 6-minute walk test (p=0.009). Our results indicate that BPA decreases CPA and pulmonary pulsatile stress. These changes may be partly responsible for the improvement in functional capacity after BPA.

Safety and Efficacy of Repeat Doses of Allogeneic Mesenchymal Stem Cells in Patients with Age Related Frailty

Cognitive decline and impairment among older adults have become an important public health issue. Previous research shows older women have a greater prevalence of Alzheimer's disease than Men. Among women, breast cancer is one of the most common types of cancer. Over half of breast cancer deaths occur in women aged 65 and older. Therefore, early detection of breast cancer through mammogram screening is important among older women. This study aimed to examine the influence of cognitive function on adherence to mammogram breast cancer screening among older American women aged 65 and older. Data from the Health and Retirement Study (2012-2016) was obtained and analyzed. The independent variable of the study was cognitive function (normal, not normal). Adherence to mammogram (low, moderate, high) was the dependent variable. Multinomial regression was performed to examine the association between cognitive function and adherence to mammogram after controlling for demographic covariates. In the study, 33.3% of respondents had impaired cognitive function and 21.7% showed low adherence to mammogram screening. Regression results found that older women with impaired cognitive function were more likely to be in low adherence group (OR=1.30, p=0.01) or moderate adherence group (OR=1.47, p<0.001) relatively to be in high adherence group compared to older women with normal cognitive function. The development and implementation of interventions are needed for reducing barriers to accessing cancer screening services in high-risk vulnerable populations. This submission is considered late-breaking research because study findings were obtained from a recently completed student's master's project.

Resistance training improves mobility disability in community-dwelling older adults: a meta-analysis

Mobility disability is the impairment in function that affects the performance of daily tasks due to declines in physical function. Exercise interventions, particular resistance training, may have a positive impact on mobility disability, but the evidence for the effects of resistance training in older adults with mobility disability has not been previously systematically reviewed. This study was a systematic review of evidence related to resistance training on physical function for adults over 65 years of age with mobility disability. Four databases (PEDro, MedLine, Ovid, Web of Science) were searched from inception to February 2, 2021 for randomized controlled trials. Twenty-four articles from 22 studies (3,656 participants) were included in the review. Mean participant age ranged from 63-87 years and exercise interventions ranged from 10 weeks to 12 months in duration. Greater changes in 6-minute Walk Test (6MWT) distance (n=638, p<0.0001; mean difference (MD) 16.1 metres; 95%CI 12.3-19.9), lower extremity strength (n=785, p<0.0001; standard MD 2.01; 95%CI 1.27-2.75) and usual gait speed (n=2,106, p<0.001; MD 0.05 metres/second, 95%CI 0.03-0.07) were seen with resistance training as compared to control. These results were maintained if resistance training was a sole intervention or a component of a multi-component program. Sensitivity analysis based on risk of bias concerns did not change results. This review demonstrates that resistance training improves walking capacity, strength and walking speed in community-dwelling older adults and may facilitate aging in place. Since improvements in strength and gait speed contribute to independence, our results indicate highly beneficial outcomes for older persons.

An exploratory study of vibration therapy on muscle function in patients with peripheral artery disease

ObjectiveThe purpose of this exploratory study was to determine whether a single session of vibration therapy (VT) would improve muscular and functional performance in individuals with symptomatic peripheral artery disease (PAD). MethodsIn a randomized, balanced cross-over design fourteen PAD participants with intermittent claudication (mean ± standard deviation; age, 73.9 ± 4.6 years; height, 172.6 ± 68.4 cm; body mass, 85.2 ± 15.7 kg) performed VT and control that involved repeated chair rises, timed up-and-go test, and 6-minute walk test. Each intervention was separated by at least 2 days. Wearable VT devices were positioned on the right and left lower limbs that were turned on during functional testing but were turned off for the control intervention. ResultsVT significantly improved (P < .05) repeated chair rises and timed up-and-go test compared with control with a small effect size of 0.46 and 0.45, respectively. Similarly, a significant (P < .01) and meaningful change in 6-minute walk test was noted in VT compared with control. ConclusionsThis exploratory study suggest that VT may enhance functional strength, mobility, and walking performance by extending the onset of claudication and increasing walking distance in PAD with intermittent claudication. However, further study is required to confirm and extend these preliminary findings and determine the potential mechanisms of action in VT.

Peritoneal Ultrafiltration for Heart Failure: Lessons from a Randomized Controlled Trial.

Peritoneal ultrafiltration (PuF) has been employed for severe heart failure (HF), but evidence for its benefit is lacking. The Peritoneal Dialysis for Heart Failure (PDHF) study was a multicenter prospective randomized controlled trial which aimed to investigate this issue. The trial stopped early due to inadequate recruitment. We describe methods, trial activity, and lessons learned.The trial aimed to recruit 130 participants with severe diuretic-resistant HF (New York Heart Association [NYHA] 3/4) and chronic kidney disease (CKD) stage 3/4 on optimal medical treatment for ≥ 4 weeks from 6 UK centers. Participants were randomized to either continuation of conventional HF treatment or to additionally receiving PuF (1 overnight exchange using Icodextrin dialysate). Primary outcome was change in 6-minute walk test (6MWT) between baseline and 28 weeks (end of trial). Secondary outcomes were changes in patient reported quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire, short form 36 (SF 36) health survey results, hospitalization, and mortality.Over a 2-year period, 290 patients were screened from which only 20 met inclusion criteria and 10 were recruited. Reasons for ineligibility were fluctuating estimated glomerular filtration rate (eGFR), suboptimal HF treatment, frailty, and patients being too unwell for randomization. Barriers to recruitment included patient frailty, with some participants considered only when they were at end of life, unwillingness to engage in an invasive therapy, and suboptimal coordination between cardiology and renal services. This is a challenging patient group in which to perform research, and lessons learned from the peritoneal dialysis (PD)-HF trial will be helpful in the planning of future studies in this area.

Rationale and design of the Study of Dietary Intervention Under 100 MMOL in Heart Failure (SODIUM-HF)

Patients with heart failure (HF) remain at high risk for future events despite medical and device therapy. Dietary sodium reduction is often recommended based on limited evidence. However, it is not known whether dietary sodium reduction reduces the morbidity or mortality associated with HF. The SODIUM study is a pragmatic, randomized, open-label trial assessing the efficacy of dietary sodium reduction to <1500 mg daily counseling compared to usual care for patients with chronic HF. The intervention is provided by trained personnel at the site and uses 3-day food records for directing counseling. The primary outcome is an intention-to-treat analysis on the time to first cardiovascular event or death measured at 12 months. Secondary end points include the change in quality of life (using the Kansas City Cardiomyopathy Questionnaire), change in New York Heart Association class, and change in 6-minute walk test. The first patient was enrolled in March 2014, and subsequently, 27 sites in 6 countries enrolled patients. The SODIUM-HF trial will provide a robust evaluation of the effects of dietary sodium reduction in patients with HF. Results are expected in 2020.

Meta-Analysis Comparing Catheter-Guided Ablation Versus Conventional Medical Therapy for Patients With Atrial Fibrillation and Heart Failure With Reduced Ejection Fraction

The prognostic benefit of catheter ablation (CA) for atrial fibrillation in the setting of heart failure (HF) with reduced ejection fraction (EF) is unclear. A systematic search of medical literature was limited to randomized controlled trials. The primary outcome was all-cause mortality, and secondary outcomes were HF hospitalizations, stroke, left ventricular EF improvement, change in 6-minute walk test, and change in Minnesota living with HF questionnaire (Δ MLHFQ). Random effects risk ratios (RR) were calculated for categorical outcomes and standardized mean differences (SMD) for continuous ones, using Der-Simonian and Liard model. A total of 775 ambulatory patients from 6 trials were included. The mean EF was 31% with a mean New York Heart Association classification class 2.5. At a mean follow-up of 26 months, CA was associated with lower incidences of all-cause mortality (RR 0.50, 95% confidence intervals [CI] 0.34 to 0.74, I2 = 0%, p <0.0001), and HF hospitalizations (RR 0.58, 95% CI 0.41 to 0.81, p = 0.002, I2 = 0%), with similar incidences of stroke. Left ventricular EF improvement (SMD = 2.58, 95% CI 0.88 to 4.27), and change in Minnesota living with heart failure HF questionnaire (SMD = -0.40, 95% CI -0.65 to -0.14) were also in favor of CA, with no difference noted in change in 6-minute walk test. The incidence of all reported procedural complications (including major and minor) was 7.3%. In conclusion, CA of atrial fibrillation appears to be associated with improved survival and HF hospitalizations compared with medical therapy, with evidence of low ablation-related complications.

Short-term Heart Function Change of Catheter Ablation in Persistent Atrial Fibrillation and Heart Failure: A Meta-analysis of Randomized Controlled Trials

Background: The effect of catheter ablation (CA) versus drug therapy on cardiac function improvement is not clear for patients with persistent atrial fibrillation and heart failure. To compare the short-term therapeutic effects between CA and conventional drug therapy, we conducted a meta-analysis of the current randomized controlled trials (RCTs). Objective and method: The analyses systematically collected PubMed, Embase, and the Cochrane Library for RCTs comparing catheter ablation with medical therapy in patients with persistent atrial fibrillation and heart failure. In order to reduce the impact of other factors on cardiac function, we limited the maximum follow-up time to two years. The primary outcome is changes in left ventricular ejection fraction (LEVF), second outcomes are changes in 6-minute walk test (6MWT), Minnesota Living with Heart Failure Score (MLHFQ), B-type natriuretic peptide (BNP). SMD was used for the results measured by different methods. Random-effects model or fixed-effects model was used to estimate relative risks (RRs) with 95% confidence intervals (CIs). Results: A total of six randomized controlled trials included 775 patients included in the final analysis, compared with drug therapy, catheter ablation has a better improvement in left ventricular ejection fraction (SMD, 0.57; 95% CI [0.40, 0.94], p<0.00001), 6-minute walk distance(MD 23.35, 95% CI [5.51, 41.19], p<0.00001), Minnesota Living with Heart Failure Score (MD -11.13, 95% CI [-2.52, -19.75], p=0.01), and B-type natriuretic peptide (110.93, 95% CI [82.84, 139.3], p<0.00001). Conclusion: Catheter ablation has a better improvement than medical treatment in heart function for patients with persistent atrial fibrillation and heart failure.

Ambulation Orderlies and Recovery After Cardiac Surgery: A Pilot Randomized Controlled Trial.

One potential strategy to increasing physical activity after surgery is to utilize an ambulation orderly (AO), a dedicated employee whose assures frequent patient walking. However, the impact of an AO on physical and functional recovery from surgery is unknown. We randomized post-operative cardiac surgical patients to receive either the AO or usual care. We measured average daily step count, changes in 6-minute walk test (6MWT) distance, and changes in functional independence (Barthel Index.) Our primary goal was to test protocols, measure variability in activity, and establish effect sizes. Thirty-six patients were randomized (18 per group, 45% bypass surgery). Overall, patients exhibited significant recovery of physical function from baseline to discharge in the 6MWT (from 83 to 172 meters, p < 0.001) and showed improvement in independent function (Barthel Index, 67 to 87, p <0.001). Moreover, each additional barrier to ambulation (supplemental oxygen, intravenous poles/fluid, walkers, urinary catheters, and chest tubes) reduced average daily step count by 330 steps/barrier, p = 0.04. However, the AO intervention resulted in only a small difference in average daily step counts (2718 vs. 2541 steps/day, Cohen's d = 0.16, 608 patients needed for larger trial), which we attributed to several trial factors that likely weakened the AO intervention. In this pilot study, we observed significant in-hospital physical and functional recovery from surgery, but the addition of an AO made only marginal differences in daily step counts. Future studies should consider stepped-wedge or cluster trial designs to increase intervention effectiveness. Clinicaltrials.gov unique identifier: NCT02375282.

Lower Extremity Deformity Management in MPS IVA, Morquio-Brailsford Syndrome: Preliminary Report of Hemiepiphysiodesis Correction of Genu Valgum.

Morquio-Brailsford syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an inherited metabolic disease in which skeletal deformities can be extreme. An international registry has shown that 46% of patients are unable to walk 200 m and 30% use a wheelchair. Lower limb surgery is performed to restore alignment with the expectation of maintaining mobility. We are, however, not aware of reports correlating function with alignment. This study assesses the role of orthopaedic intervention with reference to anatomic and functional outcome in MPS IV-A: specifically hemiepiphysiodesis correction of genu valgum. Interrogation of the MPS patient database identified 63 patients. Patient demographic and radiographic data were collected along with information on deformity, correction, mobility, and genotype. Genu valgum was assessed by intermalleolar distance and mobility by a standardized 6-minute walk test. Sequential hip anatomy was assessed radiographically. Twenty-six surgical hemiepiphysiodesis episodes were performed on 23 patients. There were no cases of implant failure, loosening, or infection. The average intermalleolar distance reduction was 6.12 cm (paired t test, P=0.0001) (95% confidence interval, 7.6-4.7 cm) and the mean change in 6-minute walk test was +69.5 m (P=0.0339). There was no correlation between hip subluxation/dislocation and mobility (Fisher exact test, P=1.000), although hip parameters deteriorated over time. Three patients required repeat 8-plate insertion and 1 a femoral osteotomy. Eight-plate hemiepiphysiodesis correction of genu valgum in MPS IV-A is an effective treatment with low complication rates. The insult of surgery is minimal compared with that of osteotomy which can reduce mobility further. Our outcomes suggest that mobility is maintained or improved even in severe genotypes where mobility typically worsens. We have found hip pathology to be less debilitating, but further studies are needed to assess the effect of genu valgum correction upon femoral head subluxation and collapse.We suggest hemiepiphysiodesis should be considered as part of the treatment strategy for limb alignment in MPS IV-A patients, depending on remaining growth, mobility status, and genotype. Level IV-therapeutic case series.

Rationale and design of the CONFIRM-HF study: a double-blind, randomized, placebo-controlled study to assess the effects of intravenous ferric carboxymaltose on functional capacity in patients with chronic heart failure and iron deficiency.

Iron deficiency (ID) is a common co-morbidity associated with chronic heart failure (CHF), which has unfavourable clinical and prognostic consequences. In Ferinject Assessment in Patients with IRon Deficiency and Chronic Heart Failure (FAIR-HF), the treatment with i.v. ferric carboxymaltose (FCM) improved symptoms and quality of life over a 24 week period. Ferric CarboxymaltOse evaluatioN on perFormance in patients with IRon deficiency in coMbination with chronic Heart Failure (CONFIRM-HF) was designed to test a simplifieddosage scheme of FCM during a longer follow-up period. CONFIRM-HF, a double-blind, multi-centre, prospective, randomized, two-arm study, enrolled ambulatory patients with symptomatic CHF [New York Heart Association (NYHA) class II/III] with left ventricular ejection fraction ≤45%, BNP >100 pg/mL, or NT-proBNP >400 pg/mL, presence of ID [defined as ferritin <100 ng/mL, or ferritin 100-300 ng/mL if transferrin saturation (TSAT) <20%], and haemoglobin (Hb) <15 g/dL. Patients were randomized 1:1 to treatment with FCM or placebo for 52 weeks. Primary endpoint is change in 6-minute walk test (6MWT) distance from baseline to Week 24. Secondary endpoints are: change in 6MWT from baseline to Weeks 6, 12, 36, and 52; Patient Global Assessment score at Weeks 6, 12, 24, 36, and 52; and change from baseline to Weeks 6, 12, 24, 36, and 52 in NYHA class, fatigue score, and quality of life. Safety endpoints include overall safety over the treatment period of 52 weeks. Study medication was administered in single doses as undiluted bolus injection of up to 1000 mg of iron or normal saline at Day 0 and Week 6 up to iron repletion. Further doses of study medication could be administered at Weeks 12, 24, and 36 if a patient still had ID. Overall, 304 patients were recruited in 41 centres in nine countries. This study will provide further information on the efficacy and safety of iron therapy with i.v. FCM in CHF patients with ID over a 1 year period using a simplified dosing scheme.

Sodium nitrite in patients with peripheral artery disease and diabetes mellitus: Safety, walking distance and endothelial function

Nitrite stores decrease after exercise in patients with peripheral artery disease (PAD) and diabetes represents decreased nitric oxide (NO) bioavailability that may contribute to endothelial dysfunction and limit exercise duration. The primary objective of this placebo-controlled study was the safety and tolerability of multiple doses of oral sodium nitrite in patients with PAD, predominantly with diabetes, over a period of 10 weeks. The primary efficacy endpoint was endothelial flow-mediated dilatation (FMD) and secondary efficacy endpoints included a 6-minute walk test and quality of life assessment. Of the 55 subjects, the most common side effects attributed to sodium nitrite were a composite of headache and dizziness occurring in 21% with the 40 mg dose and 44% with the 80 mg dose. There was no clinically significant elevation of methemoglobin. FMD non-significantly worsened in the placebo and 40 mg groups, but was stable in the 80 mg group. Diabetic patients receiving 80 mg had significantly higher FMD compared with the placebo and 40 mg groups. There was no significant change in 6-minute walk test or quality of life parameters over time compared to placebo. In conclusion, sodium nitrite therapy is well tolerated in patients with PAD. The possible clinical benefit of sodium nitrite should be studied in a larger and fully powered trial.

Usefulness of Beta-Blocker Therapy and Outcomes in Patients With Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a disorder in which pulmonary arterial remodeling and vasoconstriction progressively lead to right heart failure (HF), exercise intolerance, and high mortality. Beta-blockers have been shown to decrease mortality in left-sided HF, but their efficacy in isolated right HF associated with PAH is uncertain. Patients with PAH may have cardiac co-morbidities for which β-blocker therapy is indicated, and the relative risk benefit of this therapy remains to be proved. This is a prospective cohort study of 94 consecutive patients with PAH divided into 2 groups with and without β-blocker use at baseline. Rate of all-cause mortality, PAH-related hospitalization, change in 6-minute walk test, right ventricular structure and function measured by echocardiography, and hemodynamics measured by right heart catheterization were determined between subjects with and without β-blocker use. Beta-blocker use was common (28%) in this cohort. After a median follow-up of 20 months, changes in pulmonary hemodynamics and right ventricular size and function were similar between groups. There were no statistically significant differences in adverse events including PAH-related hospitalization or all-cause mortality (p = 0.19), presence of right HF by last visit (p = 0.75), or change in last 6-minute walk distance (p = 0.92). In conclusion, β-blocker use is not uncommon in a select group of patients with PAH and cardiac co-morbidities and did not appear to exert detrimental effects in clinical, functional, and hemodynamic outcomes. Further randomized data are needed to evaluate the potential benefits and risks of β-blocker use in patients with PAH.

A double-blind, randomized, controlled, multicenter study to assess the safety and cardiovascular effects of skeletal myoblast implantation by catheter delivery in patients with chronic heart failure after myocardial infarction

We sought to determine the safety and preliminary efficacy of transcatheter intramyocardial administration of myoblasts in patients with heart failure (HF). MARVEL is a randomized placebo-controlled trial of image-guided, catheter-based intramyocardial injection of placebo or myoblasts (400 or 800 million) in patients with class II to IV HF and ejection fraction <35%. Primary end points were frequency of serious adverse events (safety) and changes in 6-minute walk test and Minnesota Living With HF score (efficacy). Of 330 patients intended for enrollment, 23 were randomized (MARVEL-1) before stopping the study for financial reasons. At 6 months, similar numbers of events occurred in each group: 8 (placebo), 7 (low dose), and 8 (high dose), without deaths. Ventricular tachycardia responsive to amiodarone was more frequent in myoblast-treated patients: 1 (placebo), 3 (low dose), and 4 (high dose). A trend toward improvement in functional capacity was noted in myoblast-treated groups (Δ6-minute walk test of -3.6 vs +95.6 vs +85.5 m [placebo vs low dose vs high dose; P = .50]) without significant changes in Minnesota Living With HF scores. In HF patients with chronic postinfarction cardiomyopathy, transcatheter administration of myoblasts in doses of 400 to 800 million cells is feasible and may lead to important clinical benefits. Ventricular tachycardia may be provoked by myoblast injection but appears to be a transient and treatable problem. A large-scale outcome trial of myoblast administration in HF patients with postinfarction cardiomyopathy is feasible and warranted.

The 6-Minute Walk Test Does Not Reliably Detect Changes in Functional Capacity of Patients Awaiting Cardiac Transplantation

Peak oxygen consumption (Vo(2)peak) is a strong independent predictor of prognosis in patients with severe chronic heart failure (CHF) and is used to guide optimal timing of transplantation. However, its assessment is relatively expensive and time-consuming and requires sophisticated equipment and highly trained personnel. The purpose of this study was to determine whether changes in 6-minute walk test (6WT) distance, a simple, inexpensive potential alternative measure of functional capacity, can predict changes in Vo(2)peak in patients with severe CHF. Sixteen subjects (ejection fraction 23+/-2%, Vo(2)peak 16.2+/-1.1 ml kg (-1)min(-1)) underwent repeated 6WT and Vo(2)peak assessments that included familiarization and 4 serial measures, 6 weeks apart (baseline and at Weeks 6, 12 and 18). Analysis compared baseline performance with each subsequent testing occasion. At baseline, mean (+/-SE) VO(2)peak was 16.3+/-1.1 ml kg(-1) min(-1) and 6WT distance was 458+/-21 m. 6WT and Vo(2)peak were strongly correlated at all timepoints (average r=0.82; all p<0.05). However, mixed model analysis, assessing the capacity of the changes seen in 6WT to predict changes in Vo(2)peak, showed no statistical significance (F=0.11; p=0.74). The 6WT is commonly used to assess functional capacity in patients with heart failure. This study demonstrates that, despite a strong cross-sectional correlation with Vo(2)peak, changes in the 6WT are not a reliable predictor of changes in Vo(2)peak within patients. Therefore, the 6WT has limited utility as a serial measure to assess changes in the clinical status of patients with severe heart failure.