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Objective This study aimed to determine the effects of inspiratory muscle training (IMT) on exercise capacity, respiratory muscle strength, length of hospital stay (LOS), and quality of life (QOL) following coronary artery bypass graft surgery. Methods The search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Handbook and included the databases MEDLINE, EMBASE, CINAHL, Scopus, and CENTRAL. The review included randomized controlled trials utilizing IMT during phase 1 or 2 postoperative cardiac rehabilitation (PoCR) versus alternative treatment (active or passive control) in patients following coronary artery bypass graft surgery. Results Fifteen studies were included (11 phase 1 studies, 4 phase 2 studies) with no reported adverse events. In phase 1 PoCR, IMT reduced the LOS (−1.02 days; 95% CI = −2.00 to −0.03) and increased exercise capacity (6-minute walk distance) (+75.46 m; 95% CI = 52.34 to 98.57), and maximal inspiratory pressure (MIP) (10.46 cm H2O; 95% CI = 2.83 to 18.10), but had no effect on maximal expiratory pressure. In phase 2 PoCR, IMT increased 6-minute walk distance (45.84 m; 95% CI = 10.89 to 80.80), MIP (−23.19 cm H2O; 95% CI = −31.31 to −15), maximal expiratory pressure (20.18 cm H2O; 95% CI = 9.60 to 30.76), and QOL (−11.17; 95% CI = −17.98 to −4.36), with no effect on peak oxygen uptake. There was a high risk of bias for MIP (75% of the phase 1 studies) and 6MWT (1 of 4 phase 2 studies). The quality of the evidence ranged from very low to moderate. Conclusion IMT significantly improves exercise capacity, respiratory muscle strength, LOS, and QOL in phase 1 and 2 PoCR. Impact IMT may benefit patients during phase 1 and 2 of PoCR, considering the safety, low cost, and potential benefits. [ABSTRACT FROM AUTHOR]

Pulmonary rehabilitation (PR) is a highly effective intervention for persons with chronic respiratory diseases, resulting in improvement in exercise capacity, dyspnea, health-related quality of life, mood, reduced hospitalization, and improved survival and cost savings post-COPD hospitalization. Despite demonstrated effectiveness, PR is underutilized in part due to lack of awareness, limited access, and inadequate PR reimbursement. Poor payment is a long-standing barrier to PR's financial stability and access. Addressing PR payment, access, and utilization is a complex challenge and requires strategic, collaborative long-term approaches to meaningful solutions. Strategies to overcome payment disparities begin with legislative approaches to address limitations of Centers for Medicare and Medicaid Services coverage. Additional priorities include permanent approval for remote physician and advanced practice provider (APP) PR supervision, PR referrals by APPs, telerehabilitation using two-way audio/video technology, and elimination of the PR lifetime maximum limit of 72 h or units/patient. Methods are needed to effectively link appropriate PR prescribing and encouragement with primary care providers, hospitalists, case managers, and hospital navigators to optimize PR referrals. There is an important need to address inadequate PR access in rural settings. Potential opportunities to improve PR referrals and access include exploration of PR synergies with value-based care models that emphasize high-quality care and cost savings. Development and use of effective PR provider tools and resources may help address the above challenges as well as financially benefit PR programs. [ABSTRACT FROM AUTHOR]

Research has demonstrated concussion likely causes autonomic dysfunction leading to exercise intolerance. To measure improvement in exercise intolerance due to suspected dysautonomia associated with protracted concussion recovery, using objective measurements on a Buffalo Concussion Treadmill Test (BCTT) following participation in a prescribed exercise program. This is a retrospective cohort study of 101 patient charts post-concussion. Exercise intolerance was assessed using a BCTT to identify suspected dysautonomia and an exercise prescription was provided using guidelines for treating concussion-associated exercise intolerance. Patients without symptom improvement and/or inability to achieve 80–85% of age-expected maximum heart rate (HR) without symptom exacerbation received a repeat BCTT. Twelve patient charts met inclusion criteria and were included in data analysis. There were significant improvements from pre-intervention to post-intervention testing in: maximum BCTT stage mean scores (p =.02); maximum HR mean scores (p =.01); prescription HR (RxHR) mean scores (p =.01); and HR delta (HR $$\delta $$ δ) mean scores (p =.00). Maximum stage, HR threshold, RxHR, and newly identified HR delta (HR $$\delta $$ δ) are potential objective measurements of progress for dysautonomia treatment post-concussion. Future studies are indicated to create a tailored protocol in the management of protracted concussion-associated dysautonomia. [ABSTRACT FROM AUTHOR]

This study aims to determine whether post-hospitalization psychological distress is associated with exercise capacity, physical function and health status in COVID-19 survivors. In this observational study, hospitalized COVID patients were included and divided into two groups according to the mental component summary subscale of the 12-item Short-Form Health Survey. Patients with a score ≤ 45 were included in the psychological distress group, and patients with a score > 45 were included in the non-psychological distress group. The main variables were exercise capacity, physical function, and health status. Patients were evaluated at discharge, 3 months, and at 6 months follow-up. Finally, a total of 60 patients were included in the study. Significant differences were found in exercise capacity, physical function, and health status (p < 0.05), with worse results in the group with psychological distress at discharge and 3 months follow-up. At 6 months after discharge, COVID patients with psychological distress exhibited worse results in exercise capacity, physical function, and health status, being significant exercise capacity and physical function (p < 0.05). It can be concluded that COVID patients with psychological distress at hospital discharge reported worse exercise capacity, physical function and health status at hospital discharge, 3 months and 6 months follow-up. [ABSTRACT FROM AUTHOR]

Rationale: Being overweight or obese is common among patients with chronic obstructive pulmonary disease (COPD), but whether interventions targeted at weight loss improve functional impairments is unknown. Objectives: INSIGHT (Intervention Study in Overweight Patients with COPD) tested whether a pragmatic low-intensity lifestyle intervention would lead to better physical functional status among overweight or obese participants with COPD. Methods: The trial was a 12-month, multicenter, patient-level pragmatic clinical trial. Participants were recruited from April 2017 to August 2019 from 38 sites across the United States and randomized to receive usual care or usual care plus lifestyle intervention. The intervention was a self-directed video program delivering the Diabetes Prevention Program's Group Lifestyle Balance curriculum. Results: The primary outcome was 6-minute-walk test distance at 12 months. Priority secondary outcomes were postwalk modified Borg dyspnea at 12 months and weight at 12 months. Participants (N= 684; mean age, 67.068.0 yr [standard deviation]; 41.2% female) on average were obese (body mass index, 33.064.6 kg/m2) with moderate COPD (forced expiratory volume in 1 second % predicted, 58.1615.7%). At 12 months, participants randomized to the intervention arm walked farther (adjusted difference, 42.3 ft [95% confidence interval (CI), 7.9-76.7 ft]; P = 0.02), had less dyspnea at the end of the 6-minute-walk test (adjusted difference, 20.36 [95% CI, 20.63 to 20.09]; P = 0.008), and had greater weight loss (adjusted difference, 21.34 kg [95% CI, 22.33 to 20.34 kg]; P = 0.008) than control participants. The intervention did not improve the odds of achieving clinically meaningful thresholds of walk distance (98.4 ft) or dyspnea (1 unit) but did achieve meaningful thresholds of weight loss (3% and 5%). Conclusions: Among participants with COPD who were overweight or obese, a self-guided low-intensity video-based lifestyle intervention led to modest weight loss but did not lead to clinically important improvements in physical functional status and dyspnea. [ABSTRACT FROM AUTHOR]

Pulmonary rehabilitation (PR) is a high-value intervention for persons with COPD and other chronic lung diseases. It is associated with improvement in exercise capacity, dyspnea, health-related quality of life, and depression as well as a reduction in hospitalization and improved survival when PR follows COPD-related hospitalizations. PR is underused in the United States and other countries despite strong evidence of both clinical effectiveness and cost-effectiveness. Additional challenges include a lack of equitable reimbursement and poor access, particularly in rural settings. Models, for example, virtual PR, may be an option for improving access but coverage in the United States by Medicare is tenuous. In addition, virtual PR models have considerable heterogeneity, which challenges uniform efficacy and selection of optimal candidates. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the effectiveness and safety of a home-based pulmonary rehabilitation (HBPR) program in Veterans. Methods: Patients were evaluated from five Veteran Affairs facilities that enrolled in the 12-week program. Pre- to postchanges were completed on clinical outcomes using paired t -tests and the Wilcoxon signed rank sum test. Descriptive statistics were used for patient demographics, emergency room visits, and hospitalizations. Results: Two hundred eighty-five patients with a mean age of 69.6 ± 8.3 years enrolled in the HBPR program from October 2018 to March 2020. There was a 62% ( n  = 176) completion rate of both pre- and post assessments. Significant improvements were detected after completion of the HBPR program in dyspnea (modified Medical Research Council: 3.1 ± 1.1 vs. 1.9 ± 1.1; p  < 0.0001); exercise capacity (six-minute walk distance: 263.1 m ± 96.6 m vs. 311.0 m ± 103.6 m; p < 0.0001; Duke Activity Status Index: 13.8 ± 9.6 vs. 20.0 ± 12.7; p < 0.0001; self-reported steps per day: 1514.5 ± 1360.4 vs. 3033.8 ± 2716.2; p  < 0.0001); depression (patient health questionnaire-9: 8.3 ± 5.7 vs. 6.4 ± 5.1); nutrition habits (rate your plate, heart: 45.3 ± 9.0 vs. 48.9 ± 9.2; p < 0.0001); multicomponent assessment tools (BODE Index: 5.1 ± 2.5 vs. 3.4 ± 2.4; p < 0.0001), GOLD ABCD Assessment: p < 0.0009); and quality of life (chronic obstructive pulmonary disease assessment test: 25.4 ± 7.7 vs. 18.7 ± 8.5; p < 0.0001). No adverse events were reported due to participation in HBPR. Conclusions: The HBPR program is a safe and effective model and provides an additional option to address the gap in pulmonary rehabilitation access and utilization in the Veterans Affairs.

Rationale: Pulmonary rehabilitation (PR) is very effective in patients with chronic obstructive pulmonary disease (COPD) for improving exercise tolerance and functional capacity, alleviating dyspnea, and improving respiratory quality of life. Access to and use of PR remain poor. Objectives: To assess the trends in PR use and factors associated with PR use in adults with COPD. Methods: We retrospectively analyzed the use of PR in adults with COPD using a 20% Medicare beneficiary population from January 1, 2013, to December 31, 2019. Adults with COPD were identified by 1 ) two or more outpatient visits >30 days apart within 1 year with an encounter diagnosis of COPD or 2 ) hospitalization with COPD as the primary diagnosis or a primary diagnosis of acute respiratory failure with a secondary discharge diagnosis of COPD. PR use in each calendar year was identified using Current Procedural Terminology and Healthcare Common Procedure Coding System codes. Factors associated with PR use were tested in bivariate and multivariable logistic regression models. Results: There was a gradual but modest increase in the percentage of patients with COPD using PR; the proportion increased from 2.5% in 2013 to 4.0% in 2019. Overall, the percentage of patients using PR remained low. Factors associated with higher odds of using PR included younger age (66-74 yr), White race, higher socioeconomic status, lower comorbidity score, residence in a metropolitan urban area, and sole or comanagement by a pulmonologist. Conclusions: The use of PR by Medicare beneficiaries with COPD has not changed meaningfully in the past decade and remains low.

Background: There is a lack of mechanism-driven, clinically relevant biomarkers in chronic obstructive pulmonary disease (COPD). Mitochondrial dysfunction, a proposed disease mechanism in COPD, is associated with the release of mitochondrial DNA (mtDNA), but plasma cell-free mtDNA has not been previously examined prospectively for associations with clinical COPD measures.Methods: P-mtDNA, defined as copy number of mitochondrially-encoded NADH dehydrogenase-1 (MT-ND1) gene, was measured by real-time quantitative PCR in 700 plasma samples from participants enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Associations between p-mtDNA and clinical disease parameters were examined, adjusting for age, sex, smoking status, and for informative loss to follow-up.Results: P-mtDNA levels were higher in participants with mild or moderate COPD, compared to smokers without airflow obstruction, and to participants with severe COPD. Baseline increased p-mtDNA levels were associated with better CAT scores in female smokers without airflow obstruction and female participants with mild or moderate COPD on 1-year follow-up, but worse 6MWD in females with severe COPD. Higher p-mtDNA levels were associated with better 6MWD in male participants with severe COPD. These associations were no longer significant after adjusting for informative loss to follow-up.Conclusion: In this study, p-mtDNA levels associated with baseline COPD status but not future changes in clinical COPD measures after accounting for informative loss to follow-up. To better characterize mitochondrial dysfunction as a potential COPD endotype, these results should be confirmed and validated in future studies.Trial Registration:  ClinicalTrials.gov NCT01969344 (SPIROMICS). [ABSTRACT FROM AUTHOR]

Background: Although electronic cigarettes (e-cigarettes) were initially marketed as a potential smoking-cessation aid and a safer alternative to smoking, the long-term health effect of e-cigarette use ("vaping") is unknown. Vaping e-liquids expose the user to several potentially harmful chemicals, including diacetyl, a flavouring compound known to cause bronchiolitis obliterans with inhalational exposure ("popcorn worker's lung").Case Description: We report the case of a 17-year-old male who presented with intractable cough, progressive dyspnea and malaise after vaping flavoured e-liquids and tetrahydrocannabinol intensively. Initial physical examination showed fever, tachycardia, hypoxemia, and bibasilar inspiratory crackles on lung auscultation. Computed tomography of the chest showed diffuse centrilobular "tree-inbud" nodularity, consistent with acute bronchiolitis. Multiple cultures, including from 2 bronchoalveolar lavage samples, and biopsy stains, were negative for infection. He required intubation, invasive mechanical ventilation and venovenous extracorporeal membrane oxygenation (ECMO) for refractory hypercapnia. The patient's condition improved with high-dose corticosteroids. He was weaned off ECMO and mechanical ventilation, and discharged home after 47 days in hospital. Several months after hospital discharge, his exercise tolerance remained limited and pulmonary function tests showed persistent, fixed airflow obstruction with gas trapping. The patient's clinical picture was suggestive of possible bronchiolitis obliterans, thought to be secondary to inhalation of flavouring agents in the e-liquids, although the exact mechanism of injury and causative agent are unknown.Interpretation: This case of severe acute bronchiolitis, causing near-fatal hypercapnic respiratory failure and chronic airflow obstruction in a previously healthy Canadian youth, may represent vaping-associated bronchiolitis obliterans. This novel pattern of pulmonary disease associated with vaping appears distinct from the type of alveolar injury predominantly reported in the recent outbreak of cases of vaping-associated pulmonary illness in the United States, underscoring the need for further research into all potentially toxic components of e-liquids and tighter regulation of e-cigarettes. [ABSTRACT FROM AUTHOR]

Importance: Heart failure with preserved ejection fraction (HFpEF) lacks effective treatments. Based on preclinical studies, neladenoson bialanate, a first-in-class partial adenosine A1 receptor agonist, has the potential to improve several heart failure-related cardiac and noncardiac abnormalities but has not been evaluated to treat HFpEF.Objectives: To determine whether neladenoson improves exercise capacity, physical activity, cardiac biomarkers, and quality of life in patients with HFpEF and to find the optimal dose.Design, Setting, and Participants: Phase 2b randomized clinical trial conducted at 76 centers in the United States, Europe, and Japan. Patients (N = 305) with New York Heart Association class II or III HFpEF with elevated natriuretic peptide levels were enrolled between May 10, 2017, and December 7, 2017 (date of final follow-up: June 20, 2018).Interventions: Participants were randomized (1:2:2:2:2:3) to neladenoson (n = 27 [5 mg], n = 50 [10 mg], n = 51 [20 mg], n = 50 [30 mg], and n = 51 [40 mg]) or matching placebo (n = 76) for 20 weeks of treatment.Main Outcomes and Measures: The primary end point was change in 6-minute walk test distance from baseline to 20 weeks (minimal clinically important difference, 40 m). Key safety measures included bradyarrhythmias and adverse events. To evaluate the effects of varying doses of neladenoson, a multiple comparison procedure with 5 modeling techniques (linear, Emax, 2 variations of sigmoidal Emax, and quadratic) was used to evaluate diverse dose-response profiles.Results: Among 305 patients who were randomized (mean age, 74 years; 160 [53%] women; mean 6-minute walk test distance, 321.5 m), 261 (86%) completed the trial and were included in the primary analysis. After 20 weeks of treatment, the mean absolute changes from baseline in 6-minute walk test distance were 0.2 m (95% CI, -12.1 to 12.4 m) for the placebo group; 19.4 m (95% CI, -10.8 to 49.7 m) for the 5 mg of neladenoson group; 29.4 m (95% CI, 3.0 to 55.8 m) for 10 mg of neladenoson group; 13.8 m (95% CI, -2.3 to 29.8 m) for 20 mg of neladenoson group; 16.3 m (95% CI, -1.1 to 33.6 m) for 30 mg of neladenoson group; and 13.0 m (95% CI, -5.9 to 31.9 m) for 40 mg of neladenoson group. Because none of the neladenoson groups achieved the clinically relevant 40-m increase in 6-minute walk test distance from baseline, an optimal dose of neladenoson was not identified. There was no significant dose-response relationship for the change in 6-minute walk test distance among the 5 different dose-response models (P = .05 for Emax; P = .18 for quadratic; P = .21 for sigmoidal Emax 1; P = .39 for linear; and P = .52 for sigmoidal Emax 2). Serious adverse events were similar among the neladenoson groups (61/229 [26.6%]) and the placebo group (21/76 [27.6%]).Conclusions and Relevance: Among patients with HFpEF, there was no significant dose-response relationship detected for neladenoson with regard to the change in exercise capacity from baseline to 20 weeks. In light of these findings, novel approaches will be needed if further development of neladenoson for the treatment of patients with HFpEF is pursued.Trial Registration: ClinicalTrials.gov Identifier: NCT03098979. [ABSTRACT FROM AUTHOR]

Hope is a vital human resource. From antiquity to the present, scientists and poets alike have viewed hope as a necessity for navigating the vicissitudes of life. In modern psychological science, there is increasing empirical evidence that positive emotions such as hope can have a direct impact on physical and psychological well-being, from increasing stress tolerance and performance in work and academic settings to altering health habits and even immune functioning. In the present study, we translated a comprehensive, multidimensional measure of hope into Italian, and we assessed the psychometric parameters of this version. Our sample included 1,280 Italian adults (males = 553, females = 727), ages 18 to 77. In addition to the Comprehensive State Hope Scale (CHS-S; Scioli, Ricci, Nyugen, & Scioli, 2011), participants received two goal-oriented measures of hope, a measure of optimism, and a generalized self-efficacy scale. The Italian translated CHS-S demonstrated strong reliability and significant, positive correlations with (goal-focused) hope, optimism, and self-efficacy as well as a significant, negative correlation with pessimism. Exploratory and confirmatory factor analyses partially replicated the original U.S.-derived factor structure but also suggested some potentially important cultural differences in the social construction of hope in Italy versus the United States. [ABSTRACT FROM AUTHOR]

Background: Impaired physical capacity increases peri-liver transplant complications. Patient perceptions regarding exercise prior to transplantation are not known.Aims: This study aimed to assess patient and caregiver activity levels, perceptions of willingness to exercise, and of provider advice.Methods: Consecutive patients listed for liver transplant and caregivers presenting for routine outpatient visits were evaluated over a 3-month interval. Anonymous surveys adapted to patients and caregivers addressed the importance and safety of exercise, type and duration of exercise performed, barriers, willingness to wear a monitoring device, and perceived provider recommendations. Responses were logged on a Likert scale from 1 to 5.Results: Three hundred and sixty-eight responses were received. Most participants perceived exercise as important. Patients exercised three times per week for 30 min. Eighty percent endorsed walking (median response: 2-agree; IQR 1-2). Most did not jog, swim, cycle, or strength train. Fatigue, reported by 70%, was the major barrier (2, IQR 1-3). Over 90% of caregivers endorsed exercise as important (1-strongly agree, IQR 1-2) and encouraged exercise (median response 2, IQR 1-2). Over 60% of patients (median response 2, IQR 1-3) and caregivers (median response 2, IQR 2-3) felt providers encouraged exercise.Conclusions: Patients and caregivers are willing to exercise to optimize physical fitness prior to liver transplantation. [ABSTRACT FROM AUTHOR]

Aim: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease.", Methods: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline., Structure: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Background: In nonrandomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), fewer symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and midrange or preserved ejection fraction (EF ≥40%). We conducted the first randomized sham-controlled trial to evaluate the IASD in HF with EF ≥40%.Methods: REDUCE LAP-HF I (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association class III or ambulatory class IV HF, EF ≥40%, exercise PCWP ≥25 mm Hg, and PCWP-right atrial pressure gradient ≥5 mm Hg. Participants were randomized (1:1) to the IASD versus a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness end point was exercise PCWP at 1 month. The primary safety end point was major adverse cardiac, cerebrovascular, and renal events at 1 month. PCWP during exercise was compared between treatment groups using a mixed-effects repeated measures model analysis of covariance that included data from all available stages of exercise.Results: A total of 94 patients were enrolled, of whom 44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years, and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared with sham control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mm Hg in the treatment group versus 0.5±5.0 mm Hg in the control group (P=0.14). There were no peri-procedural or 1-month major adverse cardiac, cerebrovascular, and renal events in the IASD group and 1 event (worsening renal function) in the control group (P=1.0).Conclusions: In patients with HF and EF ≥40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation.Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02600234. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effects of an aldosterone antagonist on exercise intolerance in older adults with heart failure and preserved ejection fraction ( HFp EF). Design Randomized, placebo-controlled, double-blind trial. Setting Academic medical center, Winston-Salem, North Carolina. Participants Older adults (N = 80, aged 71 ± 1; 80% female) with stable compensated HFp EF and controlled blood pressure ( BP). Measurements Participants were randomized into a 9-month treatment of spironolactone 25 mg/d vs placebo. Assessments were peak exercise oxygen consumption ( VO2), 6-minute walk test, Minnesota Living with Heart Failure Questionnaire ( MLHFQ), cardiac magnetic resonance imaging, Doppler echocardiography, and vascular ultrasound. Results Seventy-one participants completed the trial: 37 in the spironolactone group and 34 in the placebo group. Adherence according to pill count was excellent (spironolactone 95%, placebo 97%). Mean spironolactone dose was 24.3 ± 2.9 mg/d and was well tolerated. Spironolactone significantly reduced systolic and diastolic BP at rest and peak exercise. At 9-month follow-up, baseline-adjusted peak VO2, the primary outcome, was 13.5 ± 0.3 mL/kg per minute in the spironolactone group versus 13.9 ± 0.3 mL/kg per minute in the placebo group (adjusted mean difference −0.4 mL/kg per minute; 95% confidence interval = −1.1-0.4 mL/kg per minute; P = .38). The 95% confidence intervals of spironolactone's effect on peak VO2 (−8.2% to 3.2%) excluded a clinically significant beneficial effect. There were also no significant differences in 6-minute walk distance, arterial stiffness, left ventricular ( LV) mass, LV mass/end-diastolic volume, or MLHFQ score. Conclusion In older adults with stable compensated HFp EF, 9 months of spironolactone 25 mg/d was well tolerated and reduced BP but did not improve exercise capacity, quality of life, LV mass, or arterial stiffness. [ABSTRACT FROM AUTHOR]

Background: The safety and efficacy of aerobic exercise in heart failure (HF) patients with atrial fibrillation (AF) has not been well evaluated.Objectives: This study examined whether outcomes with exercise training in HF vary according to AF status.Methods: HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) randomized 2,331 ambulatory HF patients with ejection fraction ≤35% to exercise training or usual care. We examined clinical characteristics and outcomes (mortality/hospitalization) by baseline AF status (past history of AF or AF on baseline electrocardiogram vs. no AF) using adjusted Cox models and explored an interaction with exercise training. We assessed post-randomization AF events diagnosed via hospitalizations for AF and reports of serious arrhythmia caused by AF.Results: Of 2,292 patients with baseline rhythm data, 382 (17%) had AF, 1,602 (70%) had sinus rhythm, and 308 (13%) had "other" rhythm. Patients with AF were older and had lower peak Vo2. Over a median follow-up of 2.6 years, AF was associated with a 24% per year higher rate of mortality/hospitalization (hazard ratio [HR]: 1.53; 95% confidence interval [CI]: 1.34 to 1.74; p < 0.001) in unadjusted analysis; this did not remain significant after adjustment (HR: 1.15; 95% CI: 0.98 to 1.35; p = 0.09). There was no significant difference in AF event rates by randomized treatment assignment in the overall population or by baseline AF status (all p > 0.10). There was no interaction between AF and exercise training on measures of functional status or clinical outcomes (all p > 0.10).Conclusions: AF in patients with chronic HF was associated with older age, reduced exercise capacity at baseline, and a higher overall rate of clinical events, but not a differential response to exercise training for clinical outcomes or changes in exercise capacity. (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]; NCT00047437). [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research., (Copyright © 2023 The American Heart Association , Inc. , and the American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Increasingly end-organ injury is being demonstrated late after institution of the Fontan circulation, particularly liver fibrosis and cirrhosis. The exact mechanisms for these late phenomena remain largely elusive. Hypothesizing that exercise induces precipitous systemic venous hypertension and insufficient cardiac output for the exercise demand, that is, a possible mechanism for end-organ injury, we sought to demonstrate the dynamic exercise responses in systemic venous perfusion (SVP) and concurrent end-organ perfusion. Ten stable Fontan patients and 9 control subjects underwent incremental cycle ergometry-based cardiopulmonary exercise testing. SVP was monitored in the right upper limb, and regional tissue oxygen saturation was monitored in the brain and kidney using near-infrared spectroscopy. SVP rose profoundly in concert with workload in the Fontan group, described by the regression equation 15.97 + 0.073 watts per mm Hg. In contrast, SVP did not change in healthy controls. Regional renal (p <0.01) and cerebral tissue saturations (p <0.001) were significantly lower and decrease more rapidly in Fontan patients. We conclude that in a stable group of adult patients with Fontan circulation, high-intensity exercise was associated with systemic venous hypertension and reduced systemic oxygen delivery. This physiological substrate has the potential to contribute to end-organ injury. [ABSTRACT FROM AUTHOR]

Objective: Pain and functional decline are hallmarks of knee osteoarthritis (OA). Nevertheless, longitudinal studies unexpectedly reveal stable or improved physical function. The aim of this study was to impute missing and pre-total knee replacement (TKR) values to describe physical function over time among people with symptomatic knee OA.Methods: We included participants from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) with incident symptomatic knee OA, observed during the first 30 months in MOST and 36 months in OAI. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function (WOMAC-PF), the 5-times sit-to-stand test, and the 20-meter-walk test were assessed at 4 and 5 years in MOST and at 6 years in OAI. We used a multiple imputation method for missing visits, and estimated pre-TKR values close to the time of TKR, using a fitted local regression smoothing curve. In mixed-effect models, we investigated the physical function change over time, using data before and after imputation and calculation of pre-TKR values.Results: In MOST, 225 (8%) had incident knee OA, with corresponding 577 (12.7%) in OAI. After adjusting for pre-TKR values and imputing missing values, we found that WOMAC-PF values remained stable or slightly declined over time, and the 20-meter-walk test results changed from stable in nonimputed analyses to worsening using imputed data.Conclusion: Data from MOST and OAI showed stable to worsening physical function over time in people with incident symptomatic knee OA after imputing missing values and adjusting pre-TKR values. [ABSTRACT FROM AUTHOR]

Older adults move less, making them prone to deconditioning and a host of other consequences including stiffness, weakness, cardiovascular changes, decreased balance, cognitive disorders, insomnia, mood changes, and adverse effects on appetite, to name a few. Because the benefits of aerobic exercise and physical activity are so powerful and pervasive in reversing the consequences of inactivity, the Centers for Disease Control and Prevention (CDC) have established guidelines for all adults of 150 minutes of moderate-intensity physical activity comprising aerobic and strengthening activity. Yet, the majority of older adults do not engage in any aerobic activity (CDC, 2013). Aerobic exercise is so important for health and chronic disease management that its prescription is a core competency for most health-care providers. This chapter reviews the effects of aging on aerobic capacity, the benefits of aerobic exercise across many common chronic diseases, and an evidence-based exercise prescription based on appropriate screening for a variety of conditions common to older adults. [ABSTRACT FROM AUTHOR]

Objective: Ngoma ceremonies are used throughout Central and South Africa to help people address 'difficult issues,' including medical illness. They are examples of ceremonies that use strong rhythms and dance for this purpose in indigenous cultures throughout the world. This study sought to modify an ngoma ceremony to make it appropriate for biomedical use and to determine its acceptance and potential for benefit for people living in the United States. Methods: The Congolese Zebola ceremony, an African healing practice, was modified to be religion-neutral and to involve only moderate exercise. Seventeen participants were recruited for the current study. Most participants were living with a chronic illness ( n=15), and a few had no medical diagnoses ( n=2). Participants spent 10 minutes in a focused activity, such as meditation, yoga, or prayer. They then danced to the Congolese rhythm Zebola for an hour and a half, with a rest every 20 minutes. Afterward, they indicated whether the experience was positive, neutral, or negative and wrote a narrative describing their experience and what they saw as strengths and weaknesses of the ceremony. They then participated in a focus group discussion. Data from the narrative and focus group discussion were coded, tabulated, and analyzed for themes. Results: Sixteen of seventeen participants found the ceremony to be a positive experience. None found the form uncomfortably foreign or disturbing. Participants described diverse benefits, including increased exercise tolerance, stress reduction, feelings of group support, and beneficial spiritual experiences. Conclusions: Further study of the modified ngoma ceremony is warranted. Global health programs should consider the potential benefits of transferring technologies in both directions rather than only from technologically advanced countries to less technologically advanced ones. [ABSTRACT FROM AUTHOR]

The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and the Academic Research Consortium (ARC) composed of patients, academic investigators from the United States and Europe, the U.S. Food and Drug Administration, the National Institutes of Health, payers, and industry. Members discussed the measure, remote capture, and clinical utility of functional and quality-of-life endpoints for use in clinical trials of heart failure and cardiovascular therapeutics, with the goal of improving the efficiency of heart failure and cardiovascular clinical research, evidence generation, and thereby patient quality of life, functional status, and survival. Assessments of patient-reported outcomes and maximal and submaximal exercise tolerance are standardized and validated, but actigraphy remains inconsistent as a potential endpoint. This paper details those discussions and consensus recommendations., Competing Interests: Funding Support and Author Disclosures The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the FDA or the U.S. Department of Health and Human Services. Dr Abraham has received consulting fees from Boehringer Ingelheim and Zoll Respicardia, speaker honoraria from Impulse Dynamics, salary support from V-Wave Medical, and research support from the U.S. National Institutes of Health/National Heart, Lung, and Blood Institute. Dr Filippatos has received consulting income from Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor; and has received lecture fees from Merck. Dr Lindenfeld has received consulting fees from Novartis, Abbott, ResMed, V-Wave, CVRx, and Cytokinetics. Dr Ahmad has received consulting fees from Amgen, Cytokinetics, Relypsa, and Novartis. Dr Felker has received research grants from the National Heart, Lung, and Blood Institute, the American Heart Association, Amgen, Merck, Cytokinetics, and Roche Diagnostics; and has received consulting fees from Novartis, Amgen, Bristol Myers Squibb, Cytokinetics, Medtronic, Cardionomic, Relypsa, V-Wave, Myokardia, Innolife, EBR Systems, Arena, Abbott, Sphingotec, Roche Diagnostics, Alnylam, LivaNova, Windtree Therapeutics, Rocket Pharma, and SC Pharma. Dr Kitzman has received consulting fees from AstraZeneca, Bayer, Novartis, Merck, Pfizer, Boehringer Ingelheim, AbbVie, DCRI, and Corvia; has received grant support from AstraZeneca, Bayer, and Novartis; and has stock in Gilead. Dr Lewis has received consulting fees from Novartis; and has received institutional research grant support from Amgen, Novartis, and Sanofi. Dr Mentz has received consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Boston Scientific, Janssen, Luitpold, Medtronic, Merck, Novartis, and Sanofi; and has received research grants from Akros, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, GlaxoSmithKline, Gilead, InnoLife, Luitpold/American Reagent, Novartis, Otsuka, ResMed, and the National Institutes of Health (grants U01HL125511-01A1 and R01AG045551-01A1). Dr Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, the National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and has received consulting fees from Akros, Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Corvia, Cytokinetics, Gilead, GlaxoSmithKline, Ironwood, Merck Sharpe & Dohme, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, and Cardiac Dimensions. Dr Teerlink has received consulting fees from Amgen, Bayer, Cytokinetics, Novartis, and Stealth Health; and has received research funding from Abbott, Amgen, Bayer, Bristol Myers Squibb, Novartis, and scPharma. Dr Unger’s employer, Hyman, Phelps & McNamara, has contracts with many companies, some of which are developing treatments for HF. Dr Whellan has received grant support from the National Institutes of Health (grant R01AG045551). Dr Wittes’s employer, Wittes LLC, has contracts with many companies, some of which are developing treatments for HF. Dr Anker has received fees from Abbott, Bayer, Boehringer Ingelheim, Cardiac Dimension, Cordio, Impulse Dynamics, Novartis, Occlutech, Servier, and Vifor Pharma; and has received grant support from Abbott and Vifor Pharma. Dr O’Connor has received grant or research support from Roche Diagnostics and Merck; and has received consulting fees from Merck, Bayer, Bristol Myers Squibb, Abiomed, and Windtree. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Approximately 6 million individuals have heart failure in the United States alone and 15 million in Europe. Left ventricular assist devices (LVAD) improve survival in these patients, but functional capacity may not fully improve. This article examines the hypothesis that patients supported by LVAD experience persistent reductions in functional capacity and explores mechanisms accounting for abnormalities in exercise tolerance., (Copyright © 2022 by the American College of Sports Medicine.)

The article reports on the benefits that heart failure patients can obtain from participating in exercise training and discusses recommendations which have been issued on aerobic, resistance an inspiratory muscle training for heart failure patients. Research which has investigated the impact that exercise training has on heart failure patients is discussed. Challenges which are associated with providing exercise training for heart failure patients are examined.

The aim of the study is to compare the cardiorespiratory response during the 6-min walk test (6MWT) with a symptom-limited cardiopulmonary exercise test (CPET) in patients with varying degrees of heart failure. Thirty-seven patients with heart failure (New York Heart Association I-III) were asked to complete a 6MWT and a CPET on a cycle ergometer. Respiratory gases were measured during both the tests and patients were grouped into tertiles according to their VO(2peak) reached during the CPET prior to performing statistical analysis of all other respiratory parameters. Patients were grouped into the following tertiles: Group 1 (VO(2peak) >25.2 ml/kg per min, N = 13), Group 2 (VO(2peak) >17.5-25.2 ml/kg per min), and Group 3 (VO(2peak) < or =17.5 ml/kg per min). Despite the good overall correlation between 6MWT VO(2) and CPET VO(2peak) (r = 0.72, P < 0.001), significant differences were seen within Groups 1 and 3 (P < 0.05). In Group 1, 6MWT VO(2) was significantly lower compared with CPET VO(2peak), whereas Group 3 showed significantly higher 6MWT VO(2) compared with CPET VO(2peak). In conclusion, the use of the 6MWT to evaluate exercise capacity in patients with heart failure is highly dependent on the degree of functional impairment. In patients with advanced heart failure, the 6MWT elicits a maximum exercise response, whereas it only constitutes a sub-maximal exercise test in patients with mild heart failure and no functional limitations. This must be taken into consideration when using the 6MWT in large epidemiological studies to evaluate therapy outcome and clinical prognosis in patients with varying degrees of clinical disabilities. [ABSTRACT FROM AUTHOR]

In the United States, latest projections indicate the number of adults 65 years of age and older is expected to double by 2050. Given that increased oxidative stress is a hallmark of aging, it is understandable that waning nitric oxide and chronic degenerative disease arise in tandem. To this end, translational evidence-based strategies are needed to mitigate the impending toll on personal and public health. Dietary nitrate supplementation, particularly in the form of beetroot juice, is an active area of inquiry that has gained considerable attention in recent years. Compelling evidence has revealed beetroot juice can elicit potent physiological responses that may offer associated health benefits for multiple clinical disorders including hypertension, dementia, and sarcopenia. Even in the absence of overt disease, age-related impairments in cardiovascular and skeletal muscle function may uniquely benefit from beetroot juice supplementation as evidence has shown blood pressure lowering effects and improved muscle function/contractility - presumably from increased nitric oxide bioavailability. This, in turn, presents a practical opportunity for susceptible populations to support ease of movement and exercise tolerance, both of which may promote free-living physical activity. A theoretical rationale details the potential health effects of dietary nitrate supplementation, wherein a working framework hypothesizes beetroot juice consumption prior to structured exercise training may offer synergistic benefits to aid healthy aging and independent-living among older adults. [ABSTRACT FROM AUTHOR]

Background: Accelerated tPA (tissue-type plasminogen activator) dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis improve short-term computed tomographic-measured right ventricular (RV)-to-left ventricular diameter ratio in massive and submassive pulmonary embolism. The impact on RV remodeling, functional status, and quality of life over the long-term remains unclear., Methods: To study 1-year changes in RV remodeling, functional status, and quality of life, we assessed patients with acute submassive pulmonary embolism randomly assigned to 1 of 4 tPA dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis in the OPTALYSE-PE trial (Optimum Duration and Dose of r-tPA With the Acoustic Pulse Thrombolysis Procedure for Intermediate-Risk Pulmonary Embolism; 8 mg/2 hours, 8 mg/4 hours, 12 mg/6 hours, and 24 mg/6 hours). Echocardiographic assessment included RV-to-left ventricular diameter ratio within 4 hours of treatment end, and at 48 hours, 30 days, 90 days, and 1 year. Functional status was assessed by 6-minute walk test at 30 days, 90 days, and 1 year and PROMIS-PF-6b scores at 30 days, 90 days, 180 days, 270 days, and 1 year. Quality of life was evaluated by PEmb-QOL scores at 30 days, 90 days, 180 days, 270 days, and 1 year., Results: Mean RV-to-left ventricular diameter ratio decreased from baseline to 4 hours and further at 48 hours and 30 days, with reductions maintained at 90 days and 1 year in all groups. Mean 6-minute walk distance, PROMIS-PF-6b, and PEmb-QOL scores improved over the course of 1 year in all groups., Conclusions: Accelerated lower-dose tPA regimens for ultrasound-facilitated, catheter-directed fibrinolysis resulted in sustained recovery of RV-to-left ventricular diameter ratio and tricuspid annular plane systolic excursion and improvements in functional status and quality of life over 1 year. Registration: URL: https://www.ClinicalTrials.gov. Unique Identifier: NCT02396758.

Objectives: The aim of this study was to investigate whether therapeutic intravascular ultrasound pulmonary artery denervation (PDN) is safe and reduces pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH) on a minimum of dual oral therapy., Background: Early studies have suggested that PDN can reduce PVR in patients with PAH., Methods: TROPHY1 (Treatment of Pulmonary Hypertension 1) was a multicenter, international, open-label trial undertaken at 8 specialist centers. Patients 18 to 75 years of age with PAH were eligible if taking dual oral or triple nonparenteral therapy and not responsive to acute vasodilator testing. Eligible patients underwent PDN (TIVUS System). The primary safety endpoint was procedure-related adverse events at 30 days. Secondary endpoints included procedure-related adverse events, disease worsening and death to 12 months, and efficacy endpoints that included change in pulmonary hemodynamic status, 6-min walk distance, and quality of life from baseline to 4 or 6 months. Patients were to remain on disease-specific medication for the duration of the study., Results: Twenty-three patients underwent PDN, with no procedure-related serious adverse events reported. The reduction in PVR at 4- or 6-month follow-up was 94 ± 151 dyn·s·cm -5 (p = 0.001) or 17.8%, which was associated with a 42 ± 63 m (p = 0.02) increase in 6-min walk distance and a 671 ± 1,555 step (p = 0.04) increase in daily activity., Conclusions: In this multicenter early feasibility study, PDN with an intravascular ultrasound catheter was performed without procedure-related adverse events and was associated with a reduction in PVR and increases in 6-min walk distance and daily activity in patients with PAH on background dual or triple therapy., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The NuPulseCV intravascular ventricular assist system (iVAS) provides extended duration ambulatory counterpulsation via a durable pump placed through the distal subclavian artery., Methods: We performed a prospective, single-arm, multicenter, US Food and Drug Administration-approved feasibility trial of iVAS therapy as a bridge to transplant or decision following the FIH (First-In-Human) trial., Results: Forty-seven patients were enrolled, and 45 patients (median 61 years old, 37 males, and 30 listed on United Network of Organ Sharing) received iVAS support for median 44 (25-87) days. There were no intraoperative complications. Success was defined as survival or transplant on iVAS therapy free from disabling stroke. Outcome success at 30 days (the primary end point of this study) and at 6 months was 89% and 80%, respectively. During 6 months of iVAS support, 2 patients died and 2 patients experienced disabling neurological dysfunction. Six-minute walk distance, 2-minute step test, and Kansas City Cardiomyopathy Questionnaire score improved during 4-week iVAS support., Conclusions: This feasibility trial demonstrated promising short-term outcomes of iVAS therapy with improved functional capacity and quality of life during the therapy. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02645539.

The 6-minute walk distance (6MWD) test is a useful prognostic tool in chronic heart failure. Its usefulness after percutaneous coronary intervention is unknown. In a prospective observational study, patients underwent a 6MWD test within 2 weeks after percutaneous coronary intervention. The primary endpoint was major adverse cardiovascular events (MACE) (death, acute coronary syndrome, and heart failure admission) at one year. Receiver operating characteristic curves and area under the curve were used to determine the 6MWD test's predictive power, and the Youden index was used to measure its effectiveness. A total of 212 patients were enrolled (98% men; mean age, 65 ± 9 yr). Major comorbidities were hypertension in 187 patients (88%), dyslipidemia in 186 (88%), and diabetes mellitus in 95 (45%). Among the 176 patients (83%) who completed the 6MWD test, the incidence of MACE at one year was 22% (acute coronary syndrome in 17%; heart failure admission in 4%; and death in 3%). The area under the curve for MACE was 0.59, and 6MWD was shorter for patients with MACE than for those without (290 vs 326 m; P =0.03). For 39 patients with previous heart failure who completed the 6MWD test, the area under the curve was 0.64 for MACE and 0.78 for heart failure admission. The 6MWD test predicted reasonably well the incidence of MACE one year after percutaneous coronary intervention. In a subgroup of patients with previous heart failure, it fared even better in predicting heart failure admission. Larger studies are needed to confirm these findings., (© 2020 by the Texas Heart® Institute, Houston.)

Purpose: Clinical interventions in programs such as cardiac rehabilitation (CR) are guided by clinical characteristics of participating patients. This study describes changes in CR participant characteristics over 20 yr., Methods: To examine changes in patient characteristics over time, we analyzed data from 1996 to 2015 (n = 5396) garnered from a systematically and prospectively gathered database. Linear, logistic, multinomial logistic or negative binomial regression was used, as appropriate. Effects of sex and index diagnosis were considered both as interactions and as additive effects., Results: Analyses revealed that mean age increased (from 60.7 to 64.2 yr), enrollment of women increased (from 26.8% to 29.6%), and index diagnosis has shifted; coronary artery bypass surgery decreased (from 37.2% to 21.6%), whereas heart valve repair/replacement increased (from 0% to 10.6%). Risk factors also shifted with increases in body mass index (28.7 vs 29.6 kg/m), obesity (from 33.2% to 39.6%), hypertension (from 51% to 62.5%), type 2 diabetes mellitus (from 17.3% to 21.7%), and those reporting current smoking (from 6.6% to 8.4%). Directly measured peak aerobic capacity remained relatively stable throughout. The proportion of patients on statin therapy increased from 63.6% to 98.9%, coinciding with significant improvements in lipid levels., Conclusions: Compared with 1996, participants entering CR in 2015 were older, more overweight, and had a higher prevalence of coronary risk factors. Lipid values improved substantially concurrent with increased statin use. While the percentage of female participants increased, they continue to be underrepresented. Patients with heart valve repair/replacement now constitute 10.6% of the patients enrolled. Clinical programs need to recognize changing characteristics of attendees to best tailor interventions.

Aims: The small number of studies that have investigated the relationship between serum vitamin D levels and cardiorespiratory fitness (CRF) have reported conflicting results. We investigated the association between vitamin D levels and CRF in a representative sample of the US population using data from the National Health and Nutrition Survey (2001-2004)., Methods: We included participants between the ages of 20 and 49 years and excluded those with vitamin D levels at the 5% extremes of the distribution. We used survey-weighted linear regression without and with adjustment for age, sex, race, body mass index, hypertension, diabetes, smoking, C-reactive protein, hemoglobin, and glomerular filtration rate to examine the relationship between the maximal oxygen consumption (VO 2 max) (as a surrogate for CRF) and vitamin D levels., Results: Of the 1995 participants, 45.2% were women, 49.1% were white, 13% had hypertension, and 4% had diabetes. The mean ± SD age was 33 ± 8.6 years, with a mean ± SD vitamin D level of 58 ± 5.3 nmol/L and a mean ± SD VO 2 max of 40 ± 9.7 ml/kg/min. Participants in the highest quartile of vitamin D levels had a significantly higher CRF than participants in the lowest quartile (difference 4.3, 95% confidence interval (CI) 3.0-5.5; P < 0.001). After adjustment for potential confounders, the difference between the highest and lowest vitamin D quartiles remained significant (difference 2.9, 95% CI 1.6-4.1; P < 0.001). In unadjusted and adjusted linear regression, each 10 nmol/L increase in vitamin D level was associated with a significant increase in VO 2 max (β = 0.78 ml/kg/min, 95% CI 0.55-1.01; P < 0.001; β = 0.51 ml/kg/min, 95% CI 0.23-0.79; P = 0.001, respectively)., Conclusions: We found an independent and robust association between serum vitamin D levels and CRF, but our results need to be validated with clinical trials examining the effect of vitamin D supplementation on CRF.

Crouse, SF, Tolson, H, Lytle, J, Johnson, KA, Martin, SE, Green, JS, Oliver, J, Carbuhn, A, Lambert, B, and Bramhall, JP. Predicting V[Combining Dot Above]O2max from treadmill performance in American-style football athletes. J Strength Cond Res 33(4): 1028-1034, 2019-Prediction equations are often used to estimate V[Combining Dot Above]O2max in the general population but are lacking for American-style football (ASF) athletes. We sought to develop a regression model to estimate V[Combining Dot Above]O2max from treadmill exercise time in ASF athletes and compare our football V[Combining Dot Above]O2max model with 2 published prediction equations (Foster et al., 1984, and Bruce, 1973). American-style football athletes (N = 472, age = 18 ± 1 year, height = 186.1 ± 8.2 cm, and body mass = 101.8 ± 20.4 kg) underwent treadmill exercise to voluntary exhaustion (Bruce protocol). Maximal exercise time was recorded in minutes (Tmin), and V[Combining Dot Above]O2max was simultaneously measured (M-V[Combining Dot Above]O2max, mlO2·kg·min) by an automated gas-analysis system. Athletes were then randomly divided into validation and cross-validation groups (n = 236). Linear regression yielded estimates of V[Combining Dot Above]O2max from Tmin as follows: validation V[Combining Dot Above]O2max = 4.012 × Tmin - 4.628 (r = 0.678, p < 0.001, and SEE = 4.07); cross-validation V[Combining Dot Above]O2max = 4.025 × Tmin - 4.693 (r = 0.661, p < 0.001, and SEE = -4.16). These equations had a cross-validation coefficient of 0.813 and a double cross-validation coefficient of 0.823. Differences between the slopes of the 2 equations were not significant (t-test, p = 0.9603). Because validation and cross-validation groups were not statistically different on any variables measured (multivariate analysis of variance, p > 0.05), all athletes were combined to yield our final prediction equation: football V[Combining Dot Above]O2max = 4.017 × Tmin - 4.644 (r = 0.670, p < 0.001, and SEE = 4.11). Repeated-measures analysis of variance demonstrated significant differences (p < 0.001) in estimates of V[Combining Dot Above]O2max among Foster (44.1 ± 6.1), Bruce (47.1 ± 5.5), and our football (45.1 ± 5.8) equations. Foster and Bruce V[Combining Dot Above]O2max estimates were also significantly different from M-V[Combining Dot Above]O2max ((Equation is included in full-text article.)diff = -0.975 and 1.995, respectively, p < 0.001). V[Combining Dot Above]O2max of ASF athletes can be reasonably estimated by our football prediction equation using maximal treadmill time as the predictor.

Objectives: This study sought to determine whether pulmonary artery intervention in patients with unilateral proximal pulmonary artery stenosis (PAS) improves exercise capacity, abnormal ventilatory response to exercise, and symptoms., Background: Stenosis of the branch pulmonary arteries results in pulmonary blood flow maldistribution (PBFM). The resulting ventilation-perfusion mismatch is associated with an increased ventilatory response to exercise and decreased exercise capacity. It is unclear if technical success in relieving branch PAS translates to clinical improvement in exercise capacity and ventilatory response., Methods: Twenty patients with biventricular circulation and a minimum 10% PBFM who underwent transcatheter relief of PAS were enrolled in a multi-institutional prospective cohort study. Pre- and post-procedure assessment of the degree of PBFM, exercise capacity, ventilatory response to exercise, and subjective assessment of breathlessness were collected and analyzed., Results: Technical success was achieved in all patients with significant angiographic improvement in minimal lumen diameter (p = 0.001) and peak gradient (p = 0.001). Median PBFM improved (19.5% [range 12.0% to 31.0%] before vs. 7.0% [range 0% to 33.0%] after; p = 0.003). Exercise capacity was low at baseline and improved significantly post-intervention; percent predicted peak oxygen consumption improved from 70% (range 45% to 96%) to 83% (range 47% to 121%) (p = 0.02). Percent predicted oxygen pulse improved (p = 0.02). Ventilatory response to exercise improved; ventilatory equivalent of carbon dioxide slope post-intervention decreased to 29.3 versus 32.5 pre-intervention (p = 0.01). Subjective assessment of dyspnea improved. Five patients with minimal improvement in PBFM also showed minimal improvement in exercise parameters., Conclusions: Successful relief of unilateral branch PAS results in significant improvements in exercise capacity, ventilatory efficiency, and symptoms., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

An exercise ankle-brachial index (ABI) test can provide further insight into the functional significance of peripheral artery disease (PAD). The variability in its use, associated patient factors and its relation to patients' symptoms are unknown. From the international PORTRAIT registry, we identified 1131 patients with PAD. We fit a hierarchical logistic regression model, adjusting for patient factors, country and site, to examine predictors of and variation in ordering exercise ABI testing. We also examined the associations between test components and health status as quantified by the Peripheral Artery Questionnaire (PAQ) using semi-parametric regression methods. Testing was ordered in 22% in the United States versus 80% in the Netherlands and 90% in Australia. Testing was likely to be performed if the patient was male, younger, had typical symptoms and a higher resting ABI, with substantial variability across sites (median odds ratio=5.9, 95% CI: 3.2-19.5). Adjusting for country and site, the resting ABI and all exercise ABI metrics were associated with the PAQ Physical Limitation score. In addition, important components of the test, namely time to onset of claudication, pain-free walking distance (PFWD), and maximum walking distance (MWD), were also associated with PAQ Symptoms and Summary scores. More importantly, even after adjusting for resting ABI, a patient with a post-exercise ABI of 0.29 (25th percentile), compared to 0.61 (75th percentile), achieved 4.4 (95% CI: 0.4-8.4, p=0.031) points less on the PAQ Physical Limitation score. Exercise ABI test use is remarkably variable, and less used in the United States. Its data, specifically PFWD and MWD, might help in objectively assessing the impact of PAD on patients' functioning and quality of life.

Objective: This study compared the clinical features, cardiac structure and function evaluated by echocardiography, cardiopulmonary response to exercise and long-term clinical outcomes between patients with heart failure (HF) induced by cancer therapy (CTHF) and heart failure not induced by cancer therapy (NCTHF)., Methods: We evaluated 75 patients with CTHF and 894 with NCTHF who underwent clinically indicated cardiopulmonary exercise testing, and followed these individuals for a median of 4.5 (3.0-5.8) years, during which 187 deaths and 256 composite events (death, heart transplantation and left ventricular (LV) assistant device implantation) occurred., Results: Compared with NCTHF, patients with CTHF were younger, with lower prevalence of cardiovascular comorbidities, higher LV ejection fraction (LVEF), but similar global longitudinal strain. LV diastolic function (higher E/e' ratio) and compliance (higher end-diastolic pressure/LV end-diastolic volume index ratio) were worse in CTHF and were both associated with adverse outcomes. Despite a favourable clinical profile, peak VO 2 and VE/VCO 2 slope were similarly impaired in CTHF and NCTHF. In multivariable Cox regression analysis including clinical characteristics, cardiopulmonary exercise testing variables and LVEF, CTHF was associated with a significantly higher risk of death (HR 2.64; 95% CI 1.53 to 4.55; p=0.001) and composite events (HR 1.79; 95% CI 1.10 to 2.91; p=0.019) compared with NCTHF., Conclusions: CTHF is characterised by a distinct clinical profile, better LVEF but worse LV diastolic properties, and similarly impaired global longitudinal strain, functional capacity and ventilatory efficiency. Accounting for differences in clinical characteristics, CTHF was associated with worse long-term prognosis than NCTHF., Competing Interests: Competing interests: AMS reports receiving research support from Novartis and Bellerophron, and consulting fees from Philips Ultrasound. The other authors have nothing to disclose., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background Maximal oxygen uptake (VO 2 max) is a powerful predictor of health outcomes. Valid and portable reference values are integral to interpreting measured VO 2 max; however, available reference standards lack validation and are specific to exercise mode. This study was undertaken to develop and validate a single equation for normal standards for VO 2 max for the treadmill or cycle ergometer in men and women. Methods Healthy individuals ( N = 10,881; 67.8% men, 20-85 years) who performed a maximal cardiopulmonary exercise test on either a treadmill or a cycle ergometer were studied. Of these, 7617 and 3264 individuals were randomly selected for development and validation of the equation, respectively. A Brazilian sample (1619 individuals) constituted a second validation cohort. The prediction equation was determined using multiple regression analysis, and comparisons were made with the widely-used Wasserman and European equations. Results Age, sex, weight, height and exercise mode were significant predictors of VO 2 max. The regression equation was: VO 2 max (ml kg -1  min -1 ) = 45.2 - 0.35*Age - 10.9*Sex (male = 1; female = 2) - 0.15*Weight (pounds) + 0.68*Height (inches) - 0.46*Exercise Mode (treadmill = 1; bike = 2) ( R = 0.79, R 2  = 0.62, standard error of the estimate = 6.6 ml kg -1  min -1 ). Percentage predicted VO 2 max for the US and Brazilian validation cohorts were 102.8% and 95.8%, respectively. The new equation performed better than traditional equations, particularly among women and individuals ≥60 years old. Conclusion A combined equation was developed for normal standards for VO 2 max for different exercise modes derived from a US national registry. The equation provided a lower average error between measured and predicted VO 2 max than traditional equations even when applied to an independent cohort. Additional studies are needed to determine its portability.

Purpose: Various exercise tests have been used to assess the response to pulmonary rehabilitation (PR) in patients with chronic obstructive pulmonary disease (COPD). Few studies have compared exercise tests in the same subjects to determine the relative responsiveness of various tests. The goal of this pilot study was to examine the responsiveness of different exercise tests in patients with COPD completing PR., Methods: Fifteen male patients with COPD underwent PR. All subjects completed 6-minute walk test (6MWT), incremental shuttle walk test (ISWT), endurance shuttle walk test (ESWT), maximal incremental exercise test (MIET), constant workload exercise test (CWET), and maximal arm ergometry tests before and after PR. The Chronic Respiratory Disease Questionnaire was also completed before and after PR., Results: The number of participants who exceeded the minimal clinically important difference was similar for each of the different exercise tests. Effect sizes for the MIET and CWET were slightly higher, 0.82 and 0.97, respectively, than for the 6MWT, ISWT, and ESWT, 0.72, 0.65, and 0.60, respectively. Effect sizes were not significantly different between the 6MWT and the ESWT. The changes in exercise test results were not significantly correlated with the changes in quality of life. The improvement in laboratory cycling tests did not significantly correlate with the improvement in shuttle walk tests., Conclusions: On the basis of these data, all exercise measures were responsive to PR. Indices derived from cycling in the laboratory appeared more responsive than indices derived from walking in the field when assessed by effect size, but this finding and its possible clinical significance requires confirmation in a larger study.

Objective: To examine the association of cardiorespiratory fitness (CRF) with risk of coronary heart disease (CHD) while controlling for an individual's Framingham Risk Score (FRS)-predicted CHD risk., Patients and Methods: The study included 29,854 men from the Aerobics Center Longitudinal Study, who received a baseline examination from January 1, 1979, to December 31, 2002. Coronary heart disease events included self-reported myocardial infarction or revascularization or CHD death. Multivariable survival analysis investigated the association between CRF, FRS, and CHD. Cardiorespiratory fitness was analyzed as both a continuous and a categorical variable. The population was stratified by "low" and "moderate or high" risk of CHD to test for differences in the FRS stratified by CRF., Results: Compared with men without incident CHD, men with incident CHD were older (mean age, 51.6 years vs 44.6 years), had lower average maximally achieved fitness (10.9 metabolic equivalent of tasks vs 12.0 metabolic equivalent of tasks [METs]), and were more likely to have moderate or high 10-year CHD risk (P<.001). Cardiorespiratory fitness, defined as maximal METs, exhibited a 20% lower risk of CHD (hazard ratio, 0.80; 95% CI, 0.77-0.83) for each 1-unit MET increase. Among men in the low CRF strata, individuals with moderate or high 10-year CHD risk, according to the FRS, had a higher CHD risk (hazard ratio, 6.55; 95% CI, 3.64-11.82) than men with low CHD risk according to the FRS., Conclusion: Clinicians should promote physical activity to improve CRF so as to reduce CHD risk, even to patients with otherwise low CHD risk., (Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Patient-reported outcomes are receiving increased attention as the search for successful treatment agents of chronic graft versus host disease continues. There is currently an ongoing multicenter, prospective cohort study lead by the Chronic GVHD Consortium of patients with chronic graft versus host disease. This paper summarizes published findings to date reporting factors impacting quality of life, symptom burden, and physical functioning in this cohort. Middle age, versus younger or older age, is associated with worse quality of life, despite lower symptom burden. The presence of chronic graft versus host disease at study enrollment was associated with lower quality of life, and improvement in severity does not always change quality of life. Other factors negatively impacting quality of life include the presence of overlap syndrome, specific gastrointestinal and joint and fascia manifestations, and poorer functional status and exercise tolerance. Collecting valid and concise quality of life data is essential in developing treatment strategies for chronic graft versus host disease.

Purpose: Cardiac rehabilitation (CR) has been shown to generally increase functional capacity and lower cardiovascular morbidity in patients with ischemic heart disease. The effectiveness of CR in female participants, however, is unclear. We thus examined whether improvement in functional capacity after CR differs between men and women with ischemic heart disease., Methods: Our study was a retrospective cohort study that included 1104 participants (346 women and 758 men) enrolled in CR from 2002 through 2011. We measured change in metabolic equivalents (METs) after CR to assess improvement in functional capacity in male and female participants. We considered various potential confounders, including baseline METs, CR referral indication, age, race, body mass index, baseline cholesterol, and home zip code average prosperity., Results: Men experienced a greater improvement in METs following CR in all models, including the unadjusted model (2.16 METs in men, 1.65 METs in women; P = .0001), the model adjusting for CR indication only (2.15 METs in men, 1.67 METs in women; P = .0003), and the model adjusting for age, body mass index, and CR indication (2.12 METs in men, 1.66 METs in women; P = .0004)., Conclusions: We show that men obtain greater benefit from current CR programs than do women. This implies that tailoring CR programs to women may yield further improvement in functional capacity for female CR participants.

Impaired exercise capacity is common after the Fontan procedure and is attributed to cardiovascular limits. The Fontan circulation, however, is also distinctively vulnerable to unfavorable lung mechanics. This study aimed to define the prevalence and physiological relevance of pulmonary dysfunction in patients with Fontan physiology. We analyzed data from the Pediatric Heart Network Fontan Cross-Sectional Study to assess the prevalence and pattern of abnormal spirometry in Fontan patients (6-18 yr old) and investigated the relationship between low forced vital capacity (FVC) and maximum exercise variables, including peak O2 consumption (Vo2peak), among those who demonstrated adequate effort (n = 260). Average ages at the time of exercise testing and Fontan completion were 13.2 ± 3.0 and 3.5 ± 2.2 yr old, respectively. Aerobic capacity was reduced (Vo2peak: 67.3 ± 15.6% predicted). FVC averaged 79.0 ± 14.8% predicted, with 45.8% having a FVC less then the lower limit of normal. Only 7.8% demonstrated obstructive spirometry. Patients with low FVC had lower Vo2peak (64.4 ± 15.9% vs. 69.7 ± 14.9% predicted, P < 0.01); low FVC independently predicted lower Vo2peak after adjusting for relevant covariates. Among those with Vo2peak < 80% predicted (n = 204/260), 22.5% demonstrated a pulmonary mechanical contribution to exercise limitation (breathing reserve < 20%). Those with both low FVC and ventilatory inefficiency (minute ventilation/CO2 production > 40) had markedly reduced Vo2peak (61.5 ± 15.3% vs. 72.0 ± 14.9% predicted, P < 0.01) and a higher prevalence of pulmonary mechanical limit compared with patients with normal FVC and efficient ventilation (36.1% vs. 4.8%). In conclusion, abnormal FVC is common in young patients after the Fontan procedure and is independently associated with reduced exercise capacity. A large subset has a pathologically low breathing reserve, consistent with a pulmonary mechanical contribution to exercise limitation., (Copyright © 2014 the American Physiological Society.)

Background: This study investigates the impact of sex on angioplasty and primary stenting for the treatment of claudicants with femoropopliteal occlusive disease (FPOD)., Methods: Two hundred eighty-seven patients enrolled in the Safety and Effectiveness Study of EverFlex Stent to Treat Symptomatic Femoral-popliteal Atherosclerosis (DURABILITY II) trial (a prospective, nonrandomized, core laboratory audited, and independently adjudicated investigational device exemption trial) were stratified by sex (190 men and 97 women) and reviewed., Results: Women presented with FPOD at an older age than men (71.3 ± 11.2 vs. 65.9 ± 9.9 years; P < 0.001). Men were more likely to be hyperlipidemic (89.5% vs. 79.4%; P = 0.030). No other statistically significant differences were observed with regard to periprocedural comorbidities and demographics. Clinically, women presented more often with severe claudication (64.9% vs. 51.1%; P = 0.033) as compared with men that had more moderate claudication (44.2% vs. 29.9%; P = 0.022). The incidence of rest pain and tissue loss was low and did not vary between sexes. Angiographically, women had smaller reference vessels (4.4 ± 0.8 mm vs. 5.0 ± 0.9 mm; P < 0.001). Longer lesions (91.6 ± 46.8 mm vs. 87.8 ± 43.9 mm) and higher primary (79.0% vs. 76.5%), primary-assisted (90.6% vs. 85.1%), and secondary patency (90.6% vs. 85.7%) rates in women did not achieve statistical significance (P = NS). Mean percent stenosis and occlusion rates were similar between groups, but men were more likely to have severe calcification (47.9% vs. 34.0%; P = 0.020). Inter-Society Consensus for the Management of Peripheral Arterial Disease II classifications were similar between groups. The target lesion revascularization, major adverse event, and mortality rates were similar between groups. At baseline, the absolute claudication distance was 0.29 miles for men, while women only reached 0.14 miles (P < 0.0001). Walking improvement questionnaire scores were also compared; women had significantly lower scores at baseline and at 1 year., Conclusions: Despite presenting with FPOD at a later age, with more severe claudication, a shorter absolute claudication distance, and smaller vessels than men, women achieved equal patency rates using angioplasty and primary stenting with similar target lesion revascularization, major adverse event, and mortality rates. Despite these findings, women subjectively have worse symptoms at baseline and at 1 year., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Physical activity (PA) and exercise training (ET) have great potential in the prevention, management, and rehabilitation of a variety of diseases, but this potential has not been fully realized in clinical practice. The health care system (HCS) could do much more to support patients in increasing their PA and ET. However, counseling on ET is not used widely by the HCS owing partly to attitudes but mainly to practical obstacles. Extensive searches of MEDLINE, the Cochrane Library, the Database of Abstracts of Reviews of Effects, and ScienceDirect for literature published between January 1, 2000, and January 31, 2013, provided data to assess the critical characteristics of ET counseling. The evidence reveals that especially brief ET counseling is an efficient, effective, and cost-effective means to increase PA and ET and to bring considerable clinical benefits to various patient groups. Furthermore, it can be practiced as part of the routine work of the HCS. However, there is a need and feasible means to increase the use and improve the quality of ET counseling. To include PA and ET promotion as important means of comprehensive health care and disease management, a fundamental change is needed. Because exercise is medicine, it should be seen and dealt with in the same ways as pharmaceuticals and other medical interventions regarding the basic and continuing education and training of health care personnel and processes to assess its needs and to prescribe and deliver it, to reimburse the services related to it, and to fund research on its efficacy, effectiveness, feasibility, and interactions and comparability with other preventive, therapeutic, and rehabilitative modalities. This change requires credible, strong, and skillful advocacy inside the medical community and the HCS., (Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: The prevalence of obesity is 33% and is expected to reach 50% based on current US trends. Bariatric surgery is effective in producing long-term weight loss, yet it requires adherence to the recommended diet and physical activity. This study assessed whether the short-form International Physical Activity Questionnaire (IPAQ-SF) data at 1 year postbariatric surgery would correlate with success (defined as more than 50% excess weight loss (EWL)) after surgery., Methods: The IPAQ-SF questionnaire provided assessment of subjects' activity level over the last 7 days, in four separate activity domains: vigorous, moderate, walking, and sitting., Results: Questionnaires were completed and collected at the 1-year postbariatric surgery group visit. Then, 118 subjects who completed the IPAQ-SF were subdivided based on loss of greater than or less than 50% of their excess weight, which in turn was based on ideal body weight. In subjects with ≥50% EWL (n = 49), we noted 67.1 ± 8.8% EWL versus 33.2 ± 9.4% in those with <50% EWL (n = 69) (p < 0.001). The ≥50% EWL group performed 420 (216-960) min of total activity per week versus 300 (172-718) min for the <50% group. The ≥50% EWL group engaged in 120 (8-180) min of vigorous activity, 150 (28-330) min of moderate activity, and 233 (109-512) min of walking versus 40 (0-255), 68 (0-204), and 188 (83-341) min, respectively, for the <50% EWL group., Conclusions: Physical activity does correlate with success after bariatric surgery, as measured by excess weight loss (≥50% EWL).

Background: Patients with claudication secondary to peripheral artery disease have a substantial impairment in walking capacity. This study evaluated factors suspected to be correlated with treadmill walking performance in an effort to gain insights into the pathophysiology of the impairment., Methods: A multivariate model was developed to define the associations between clinical and laboratory biomarkers with treadmill peak walking time (PWT) in patients enrolled in three clinical trials. The model was initially developed in a cohort of 385 patients from one trial using 23 candidate-independent variables and then tested in the combined data from the other two trials (351 patients)., Results: The final model was built from 14 variables that met the predefined univariate criteria of P < .15. Main effects remaining in the model were age, resting ankle-brachial index, smoking status, hypertension, statin use, country (United States vs non-United States countries), and high-sensitivity C-reactive protein. The model was highly statistically significant (P < .0001) but explained only a limited portion of the population heterogeneity (r(2) = 0.173). The main effects plus interaction terms had an r(2) = 0.2178. The main effects model was tested in an independent cohort of 351 patients from two other clinical trials in peripheral arterial disease that did not include high-sensitivity C-reactive protein. The model successfully fit the data set, based on prospectively defined root mean squared error and was statistically significant (P = .0005) but had lower overall explanatory power than in the index cohort (r(2) = 0.0687)., Conclusions: As expected, age and ankle-brachial index contributed to exercise limitation among patients with PAD. The association of C-reactive protein, hypertension, and smoking with PWT is consistent with a role for inflammation or oxidative stress in determining treadmill walking performance. In contrast to previous reports from smaller and more homogenous populations, clinical attributes and biomarkers explain only a small portion of PWT heterogeneity., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)