Poor Exercise Capacity Research Articles

Nocturnal hypoxia in patients with idiopathic pulmonary arterial hypertension.

BackgroundSleep-disordered breathing causes a variety of cardiovascular complications and increases the risk of a poor prognosis in patients. There is still some controversy regarding the clinical diagnosis and treatment of sleep-disordered breathing in patients with pulmonary hypertension. The aim of this study was to determine the incidence of desaturation in idiopathic pulmonary arterial hypertension (IPAH) patients, evaluate the effect of desaturation on the clinical status of patients with IPAH, and identify possible influencing factors.MethodsPatients with IPAH diagnosed by right heart catheterization who underwent overnight cardiorespiratory monitoring from January 2018 to July 2019 were enrolled. Nocturnal hypoxic time was defined as the time that oxygen saturation remained below 90%. Desaturation was defined as a nocturnal oxygen saturation level less than 90% for more than 10% of the total recording time. Baseline clinical characteristics and parameters were collected to compare IPAH patients with and without desaturation. In addition, logistic regression was performed to identify possible factors associated with desaturation in IPAH patients.ResultsFifty patients with IPAH were included. Among them, 17 patients presented desaturation. Patients with desaturation were older, had a shorter six-min walking distance (6MWD), had a higher mean right atrial pressure, and had a lower daytime arterial oxygen partial pressure than patients without desaturation, and there were significant differences in the VE/VCO2 and VE/VCO2 slope (P < 0.05). The multivariate logistic regression analysis indicated that the 6 MWD (OR = 0.971, 95% CI: 0.948–0.994, P = 0.013) and; VE/VCO2 slope (OR = 1.095, 95% CI: 1.010–1.307, P = 0.032) were independently associated with desaturation after adjusting for age, sex, and body mass index.ConclusionNocturnal hypoxia is common in IPAH patients. Desaturation may aggravate the clinical situation of patients with IPAH. In IPAH patients, a poor exercise capacity (6 MWD) and the VE/VCO2 slope can predict desaturation after adjusting for age, sex, and body mass index.

Thoracoscopic segmentectomy with simple routine bronchoscopic inflation for intersegmental plane identification: short and mid-term outcomes compared with lobectomy.

BackgroundThe technical concepts of thoracoscopic segmentectomy are still evolving. In this study we present a simple bronchoscopy-based intersegmental demarcation technique with short- and mid-term outcomes compared between thoracoscopic segmentectomy and lobectomy.MethodsAll 105 consecutive patients with lung cancer intended to treat with video-assisted thoracoscopic surgery (VATS) segmentectomy were compared to 110 consecutive VATS lobectomies. Short- and mid-term outcome comparison included complications, length of hospital stay, pulmonary functions, and 3-year progression-free and overall survival. Mid-term outcomes were adjusted for age, sex, comorbidities, pulmonary functions, histology, stage and adjuvant treatment.ResultsSegmentectomy patients had more comorbidities (P=0.006), worse pulmonary functions (FEV1%, P=0.005; DLCO/va, P=0.011), poor exercise capacity (P=0.043) and were considered high-risk patients more often (41.9% vs. 25.5%, P=0.011). Major complication rates did not differ between the groups (P=0.718). Mean length of hospital stay decreased after segmentectomy (4.7 vs. 5.9 days, P=0.033). Following segmentectomy, FEV1% slightly improved (1.0%). After lobectomy, the mean decline of FEV1% was 8.1% (P<0.001). Respectively, in high-risk patients, 2.1% improvement and 9.9% decline (P=0.027) were observed. Overall mortality hazard after segmentectomy was similar to that for lobectomy (unadjusted HR 0.80, 95% CI: 0.45–1.44, adjusted HR 0.87, 95% CI: 0.43–1.76). When considering only stage I non-small cell lung cancer, 3-year overall survival after segmentectomy and lobectomy were 86.8% vs. 79.8% (P=0.412) and 3-year recurrence-free survival 93.0% vs. 89.7%, P=0.450.ConclusionsFollowing segmentectomy, regardless of worse surgical candidates, hospital stay was shorter. Furthermore, preservation of lung function also in high-risk patients, was observed without compromising mid-term oncologic outcomes.

Characteristics of patients at initiation of renal replacement therapy - experience of a hemodialysis center.

The monitoring and care of patients with chronic kidney disease (CKD) before the dialysis initiation contribute to a better survival rate and an improvement in quality of life. The patients who do not benefit from a good predialysis management have a worse short and long-term prognosis. A retrospective, unicentric study was performed to evaluate the status of patients with stage 5 CKD at the time of initiation of renal replacement treatment. A total of 109 patients were included in the study. The evaluation of the patients included the clinical manifestations leading to hemodialysis initiation, the clinical and laboratory data of the patients when the hemodialysis was started. Based on the obtained data, a statistical analysis was performed using the Chi-square test, Fisher's exact test, ANOVA, and Kruskal-Wallis H test. The mean age of the patients was 64.61±13.59 years. Of the patients 51.38% were women. Vascular nephropathies and diabetes mellitus dominated the etiology of CKD. The comorbidities were high blood pressure, ischemic heart disease, history of myocardial infarction, heart failure, history of stroke, peripheral artery disease or atrial fibrillation. Only 43 (39.45%) of our patients were monitored before the hemodialysis initiation. Hemodialysis was initiated on central venous catheter (in most cases non-tunneled) in 78.90% of the patients. Most of the patients had an altered general status, fatigue/tiredness with poor exercise capacity when hemodialysis was initiated. Most of the patients (98.17%) had anemia, the average level of hemoglobin being 8.69±1.85 g/dl. In conclusion, careful monitoring of patients in the early stages of CKD would result in lower morbidity and mortality. These objectives can be achieved by implementing screening programs and early interventions.

Relationship of left atrial expansion index to exercise tolerance, pretest probability of restenosis, and positive predictive value of treadmill test in coronary artery disease.

Whether left atrial (LA) expansion index is associated with coronary restenosis, and exercise capacity (EC) reduction in coronary artery disease has not been established. This study analyzed 342 consecutive patients who had received a coronary stent implant. A treadmill exercise test (TET) was administered in all participants. The LA expansion indices were measured immediately before and after TET. Maximal EC measured on a breath-by-breath basis by a metabolic cart with gas analyzers and recorded as metabolic equivalent task. All patients with positive TET results received angiography, and those with restenosis received complete revascularization by either percutaneous coronary intervention (PCI) or bypass surgery. The LA expansion index and EC before and 1month after PCI were then compared. Out of 342 patients, 74 had positive TET results, and 54 had restenosis in angiography. Low LA expansion index was associated with poor EC. In patients with LA expansion index>200%, only 5% had restenosis with 38.5% positive predictive value (PPV) of TET. In patients with LA expansion index<100%, however, 64.3% had restenosis with 94.7% PPV of TET. Restenosis induced low pre-TET LA expansion index and further decline during TET. The LA expansion index significantly (P .001) improved from 133±64% before PCI to184±86% after PCI, and the improvement corresponded with EC recovery. A 10% reduction in LA expansion index was associated with a 15% increase in pretest probability of restenosis. The LA expansion index is associated with EC, pretest probability of restenosis, and PPV of TET. Revascularization improves both EC and LA expansion index.

P246 Exercise E/e refines diagnosis of diastolic impairment in patients with chronic kidney disease

Abstract Background Diastolic dysfunction is common in chronic kidney disease (CKD) patients and is associated with reduced exercise capacity. The ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e’) correlates with invasively measured left ventricular pressures, both at rest and during exercise. The aim of our study was to evaluate the relationship of resting and exercise E/e’ to exercise capacity in patients with stage 3 and 4 CKD. Methods CKD patients were prospectively recruited. All patients were required to be in sinus rhythm, without previous cardiac disease and with normal LVEF. The E/e’ ratio was assessed at rest and patients were stratified into 3 groups based on conventional clinical classifications (normal: ≤8, indeterminate: 8-14, raised: &amp;gt;14). Patients then underwent a symptom limited exercise stress echocardiogram whereby patients with resting E/e’ &amp;lt;14 additionally had post exercise E/e’ measured. Exercise capacity was assessed as metabolic equivalents (METs). A raised exercise E/e’ was defined as exercise E/e’ of ≥13. Lastly, we grouped patients based on abnormalities of baseline and exercise E/e’ (resting E/e’&amp;lt;14 &amp; exercise E/e’&amp;lt;13, resting E/e’&amp;lt;14 &amp; exercise E/e ≥13, resting E/e’ ≥14) and the relationship to METs achieved was evaluated. Results The cohort consisted of 156 CKD patients (62.8 ± 10.6 yrs, male 62%). 85% had hypertension and 39% had diabetes mellitus. 52/156 (34%) CKD patients had resting E/e’ of ≥14. Of the 104/156 (66%) CKD patients with normal/indeterminate resting E/e’, 66/104(63%) had normal exercise E/e’ &amp;lt;13 whilst 38/104(37%) had exercise E/e’ ≥13. Patients with resting E/e" &amp; raised exercise E/e’ ≥13 achieved significantly lower METs compared to CKD patients with resting E/e’ &amp;lt;14 &amp; exercise E/e’ &amp;lt;13 (5.0 ± 2.2 vs 8.8 ± 2.5, p&amp;lt; 0.01). Of note, METs achieved in this group were comparable to that achieved by CKD patients with raised resting E/e’ ≥ 14 (5.0 ± 2.2 METs vs 5.3 ± 2.6 METs, p = 0.55). Conclusion In CKD patients with normal/indeterminate resting E/e’, there is utility in performing exercise E/e’, which was increased in 37% of patients. Raised exercise E/e’ is associated with poorer exercise capacity and is a potential tool to refine diastolic abnormalities in patients with CKD. Group Total (n,%) METs Achieved Exercise Duration (minutes) Resting E/e’ ≤ 14 &amp; Exercise E/e’ ≤ 13 66/156 (42%) 8.8 ± 2.5 8.4 ± 3.1 Resting E/e’ ≤ 14 &amp; Exercise E/e’ ≥ 13 38/156 (24%) 5.0 ± 2.2 6.0 ± 3.1 Resting E/e’ ≥ 14 52/156 (34%) 5.3 ± 2.6 5.6 ± 2.2

Selenium and outcome in heart failure.

AimsSevere deficiency of the essential trace element selenium can cause myocardial dysfunction although the mechanism at cellular level is uncertain. Whether, in clinical practice, moderate selenium deficiency is associated with worse symptoms and outcome in patients with heart failure is unknown.Methods and resultsBIOSTAT‐CHF is a multinational, prospective, observational cohort study that enrolled patients with worsening heart failure. Serum concentrations of selenium were measured by inductively coupled plasma mass spectrometry. Primary endpoint was a composite of all‐cause mortality and hospitalization for heart failure; secondary endpoint was all‐cause mortality. To investigate potential mechanisms by which selenium deficiency might affect prognosis, human cardiomyocytes were cultured in absence of selenium, and mitochondrial function and oxidative stress were assessed. Serum selenium concentration (deficiency) was <70 μg/L in 485 (20.4%) patients, who were older, more often women, had worse New York Heart Association class, more severe signs and symptoms of heart failure and poorer exercise capacity (6‐min walking test) and quality of life (Kansas City Cardiomyopathy Questionnaire). Selenium deficiency was associated with higher rates of the primary endpoint [hazard ratio (HR) 1.23; 95% confidence interval (CI) 1.06–1.42] and all‐cause mortality (HR 1.52; 95% CI 1.26–1.86). In cultured human cardiomyocytes, selenium deprivation impaired mitochondrial function and oxidative phosphorylation, and increased intracellular reactive oxygen species levels.ConclusionsSelenium deficiency in heart failure patients is independently associated with impaired exercise tolerance and a 50% higher mortality rate, and impaired mitochondrial function in vitro, in human cardiomyocytes. Clinical trials are needed to investigate the effect of selenium supplements in patients with heart failure, especially if they have low plasma concentrations of selenium.

Analysis of key components in the rehabilitation diagnosis of acute stroke patients

Introduction. There are key problems that limit patients’ functioning in the period after insult. The content of these problems determines the structure of multidisciplinary team. The objective of the study was to describe key problems that limited patients’ functioning in the period after insult and determine the structure of multidisciplinary team for resolving these problems efficiently. Material and methods. The study was observational. The sample size was 81 patients. Inclusion criteria: acute phase of post ischemic or hemorrhagic stroke (0–14 days after onset), mRs score 2 and more at admission to the hospital, the age over 18 years. Exclusion criteria: patients with transient ischemic attack, subarachnoid haemorrhage, Glasgow coma scale 2 and more at admission to the hospital. All patients – research participants received medical care in according to clinical guidelines, and multidisciplinary rehabilitation. In the course of rehabilitation, the first and second key problems that limited patients’ functioning in the period after insult were dedicated in each patient. We also investigated these problems and explored, which specialists must have been included in the structure of multidisciplinary team. Results. The key problems were non-medical in 24 % cases, poor exercise capacity were presented in 27 % cases, environment issues – 6 % cases, swallowing and speech disorders – 17 %, nursery problems – 4 %. The next specialists were needed to resolve the key problems: psychologist – 38 % cases, physical therapist– 69 % cases, occupational therapist – 28 % cases, neurologist – 27 % cases, physical medicine and rehabilitation physician – 27 % cases. Conclusion. Medical (rehabilitation physician, specialist, nurse) and non-medical specialists (occupational therapist, physical therapist, psychologist, logopaedist, etc.) must have been included in multidisciplinary team.

P4986Quadruple imaging exercise stress echocardiography in unexplained dyspnoea

Abstract Background Current guidelines recommend the use of exercise stress echocardiography (ESE) in patients with unexplained dyspnoea. The methodological standard of ESE was recently reshaped with the quadruple imaging protocol, mainly tested in patients with chest pain. Aim of this study was to define the ESE pattern of response in patients with dyspnoea as the main symptom Methods From the initial population on a 1-year cohort of 604 patients referred in a single center for clinically-driven semi-supine ESE, we selected a subset of 93 consecutive patients (age 63±9 years, 52 females, resting Ejection fraction = 64±7%) with exertional dyspnea (shortness of breath, exertional fatigue or poor exercise capacity). All underwent quadruple imaging ESE: 1- Regional wall motion abnormalities (RWMA, step A) assessment (with wall motion score index, WMSI); 2- B-lines (step B) with simplified 4-site scan, each space scored from 0 = black, to 10= white (positivity criterion: stress score &gt; rest for at least 2 points); 3- Left ventricle contractile reserve (LVCR, step C) assessment with stress/rest ratio of LV force measured as systolic blood pressure/end-systolic volume (positivity criterion:&lt;2.0); 4- Pulsed-wave Doppler coronary flow velocity reserve (CFVR, step D) assessment in mid-distal LAD (positivity criterion: stress/rest diastolic peak flow velocity &lt;2.0). Readers were accredited for each parameter upstream to recruitment via a web-based system. Results Feasibility was 100% for steps A, B and C, and 82% for step D. RWMA were present in 56 patients (60%). Of them, 27 underwent coronary angiography verification, showing significant coronary artery disease in 81%. B-lines positivity occurred in 35 patients (38%), an abnormal LVCR in 63 patients (68%), and a reduced CFVR in 44 pts (55%). At least one positivity criterion was observed in 80 patients (86%). Conclusions Patients with unexplained dyspnea are a reason of referral to ESE, accounting for 15% of contemporary testing. Quadruple imaging is useful to document the origin of dyspnoea as an ischemic equivalent (A positivity) and/or its cardiogenic origin for acute backward failure with pulmonary congestion (B positivity), myocardial function abnormalities (C positivity), and reduction of CFVR of microvascular-epicardial-myocardial origin (D positivity). Dyspnoea of unexplained origin is a multifactorial problem, and a more comprehensive assessment of these patients during ESE expands the clinical potential of the method.

Predicting exercise capacity recovery immediately after mitral valve surgery.

This study presents the exercise capacity of postmitral valve surgery patients and determines predictors capable of affecting recovery. A total of 302 patients with mitral regurgitation who had undergone mitral surgery at the Heart Center in Taiwan from 1 August 2013 to 31 December 2015 were included in the present study. Data related to specific predictors of operative outcome were collected, including demographic data, intraoperative factors, exercise tolerance, echocardiogram data, concurrent cardiovascular disease history, comorbidities, lifestyle risk factors, and surgery types. Postoperative exercise capacity was presented as peak oxygen consumption (VO2 ; mL of O 2 /kg/min) determined by exercise tests 3 weeks after surgery. Subjects were separated into two groups: a preserved recovery (peak VO 2 ≥ 65% of predicted VO 2max ) group and a poor recovery group (peak VO 2 < 65% of predicted VO 2max ). Preliminary univariate analysis was performed to test for possible relationships between predictive variables and exercise capacity. An analysis of all items shown to be significantly different between the two groups was then subjected to multivariate logistic regression analysis. Detected differences with P < .05 were considered significant. Among the 302 patients sampled, female sex (odds ratio [OR], 2.65; 95% confidence interval [95% CI], 1.58-4.47), obesity (OR, 0.26; 95% CI, 0.10-0.64), sedentary lifestyle (OR, 0.47; 95% CI, 0.28-0.79), and high preoperative New York Heart Association Functional Classification level (OR, 0.52; 95% CI, 0.31-0.87) were significant predictors of poor exercise capacity. Without complicated clinical procedures, physicians and medical teams could easily use these items of information to screen the exercise capacity of mitral valve surgery patients and prepare a suitable after surgery plan if needed or request a consultation as early as possible.

Uric-Acid Lowering Treatment by a Xanthine Oxidase Inhibitor Improved the Diastolic Function in Patients with Hyperuricemia

Objective Hyperuricemia is often observed in patients with chronic heart failure (CHF), and it is predictive of poor exercise capacity, inflammation and increased mortality. The uric acid (UA)-generating enzyme xanthine oxidase (XO) is a major source of reactive oxygen species (ROS) generation, and increased ROS has been accounted for multiple adverse effects in CHF pathophysiology. Therapeutic inhibition of XO with allopurinol reduced serum UA (SUA) levels and showed a range of beneficial effects in CHF with left ventricular (LV) systolic dysfunction. However, it is unclear if UA-lowering therapy by XO inhibition is beneficial in patients with LV diastolic dysfunction. Therefore, we evaluated the effects of the specific XO inhibitor febuxostat on LV diastolic function compared with the uricosuric agent benzbromarone. Methods and Results The effects of febuxostat and benzbromarone (24 weeks each) were tested in 20 hyperuricemic patients (SUA > 7.0mg/dL) with LV diastolic dysfunction in a double-blind, randomized crossover study design. Both febuxostat and benzbromarone significantly decreased SUA levels (-35% and -41%, respectively, both p Conclusions XO inhibition with febuxostat might improve LV diastolic function, especially in patients with high SUA levels. This effect may be related to the decreased oxidative stress by febuxostat.

Improvement in 6-min Walk Test Distance Following Treatment for Behavioral Weight Loss and Disinhibited Eating: an Exploratory Secondary Analysis.

Poor functional exercise capacity is common among those with obesity; however, objective measures of exercise capacity are rarely examined in behavioral treatments targeting obese individuals. We examined whether a 4-week acceptance and commitment therapy (ACT) intervention for disinhibited eating or a behavioral weight loss (BWL) intervention improved exercise capacity and explored demographic and disinhibited eating variables related to exercise capacity. Veterans (n = 61), randomized to receive ACT or BWL, completed an assessment of exercise capacity via the 6-min walk test (6MWT) at baseline and 6-month follow-up. Measures of disinhibited eating patterns and body mass index (BMI), at baseline and post-treatment, were also collected. Change in 6MWT distance and treatment group differences were examined using mixed ANOVAs. Characteristics related to baseline 6MWT and predictors of improvement in 6MWT at 6months were examined with hierarchical multiple regression. There were overall significant improvements on the 6MWT from baseline to 6-month follow-up (F(1,59) = 11.14, p = .001, ηp2 = .159) but no differences between the ACT and BWL groups. Baseline BMI (β = - .33, p = .005) was the only variable related to baseline 6MWT. Improvements on the 6MWT were related to younger age (β = - .41, p = 0.001), female gender (β = .36, p = .001), and treatment-related increases in dietary restraint behaviors (β = .42, p = .001). Functional exercise capacity improved among participants completing behavioral interventions for weight and disinhibited eating. Improvements in dietary behavior regulatory skills may have generalized to improved regulation in other behavioral domains associated with exercise capacity.

Cardiopulmonary Exercise Testing Provides Additional Prognostic Information in Cystic Fibrosis.

The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors, is unclear. To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake ( o2peak) following rigorous adjustment for other predictors. Data from 10 CF centers in Australia, Europe, and North America were collected retrospectively. A total of 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation was analyzed using Cox proportional hazards regression. In addition, phenotyping using hierarchical Ward clustering was performed to characterize high-risk subgroups. Cox regression showed, even after adjustment for sex, FEV1% predicted, body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model, that o2peak in % predicted (hazard ratio [HR], 0.964; 95% confidence interval [CI], 0.944-0.986), peak work rate (% predicted; HR, 0.969; 95% CI, 0.951-0.988), ventilatory equivalent for oxygen (HR, 1.085; 95% CI, 1.041-1.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007-1.115) (all P < 0.05) were significant predictors of death or lung transplantation at 10-year follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high-risk cluster characterized by poor lung function, nutritional status, and exercise capacity. CPET provides additional prognostic information to established predictors of death/lung transplantation in CF. High-risk patients may especially benefit from regular monitoring of exercise capacity and exercise counseling.

Effect of PPARγ agonist on aerobic exercise capacity in relation to body fat distribution in men with type 2 diabetes mellitus and coronary artery disease: a 1-yr randomized study.

Targeting metabolic determinants of exercise performance with pharmacological agents that would mimic/potentiate the effects of exercise represents an attractive clinical alternative to counterbalance the poor exercise capacity in patients with type 2 diabetes mellitus (T2DM). We examined the effect of 1-yr treatment with the insulin sensitizer peroxisome proliferator-activated receptor (PPAR)γ agonist rosiglitazone on aerobic exercise capacity and body fat composition/distribution in men with T2DM and stable coronary artery disease (CAD). One-hundred four men (age: 64 ± 7 yr; body mass index: 30.0 ± 4.4 kg/m2) with T2DM and CAD were randomized to receive rosiglitazone or placebo for 1 yr. Aerobic exercise capacity (exercise duration) was assessed with a maximal treadmill test, and body composition/distribution were assessed by dual-energy X-ray absorptiometry/computed tomography scans. At 1 yr, patients with T2DM under PPARγ agonist treatment showed a reduction in aerobic exercise capacity compared with the control group (exercise duration change, -31 ± 8 versus 7 ± 11 s, P = 0.009). Significant increases in body fat mass (3.1 ± 0.4 kg, 12%), abdominal and mid-thigh subcutaneous adipose tissue (AT) levels, and mid-thigh skeletal muscle fat were found (all P < 0.01), whereas no effect on visceral AT levels was observed (P > 0.05) under treatment. Subcutaneous fat mass gained under PPARγ agonist was the strongest predictor of the worsening in aerobic exercise capacity (P > 0.0001); no association was found with skeletal muscle fat infiltration nor visceral AT. Treatment with the insulin sensitizer PPARγ agonist rosiglitazone in patients with T2DM and CAD is associated with a worsening in aerobic exercise capacity, which seems to be mainly attributable to weight gain and subcutaneous fat mass expansion.

TIGAR regulates mitochondrial functions through SIRT1-PGC1α pathway and translocation of TIGAR into mitochondria in skeletal muscle.

TP53-induced glycolysis and apoptosis regulator (TIGAR), a glycolytic inhibitor, plays vital roles in regulating cellular metabolism and oxidative stress. However, the role of highly expressed TIGAR in skeletal muscle remains unexplored. In the present study, TIGAR levels varied in different skeletal muscles and fibers. An exhaustive swimming test with a load corresponding to 5% of body weight was utilized in mice to assess the effects of TIGAR on exercise-induced fatigue and muscle damage. The running time and metabolic indicators were significantly greater in wild-type (WT) mice compared with TIGAR knockout (KO) mice. Poor exercise capacity was accompanied by decreased type IIA fibers in TIGAR KO mice. Decreased mitochondrial number and mitochondrial oxidative phosphorylation were observed more in TIGAR KO mice than in WT mice, which were involved in sirtuin 1 (SIRT1)-mediated deacetylation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), and resveratrol treatment in TIGAR KO mice can increase mitochondrial content and exercise time. Much more TIGAR was also detected in mitochondria during exhaustive exercise. In addition, TIGAR, rather than mitochondria-targeted TIGAR achieved by in vitro plasmid transfection, promoted SIRT1-PGC1α pathway. Glutathione S-transferase-TIGAR pull-down assay followed by liquid chromatography mass spectrometry found that TIGAR interacted with ATP synthase F1 subunit α (ATP5A1), and its binding to ATP5A1 increased during exhaustive exercise. Overexpression of mitochondrial-TIGAR enhanced ATP generation, maintained mitochondrial membrane potential and reduced mitochondrial oxidative stress under hypoxia condition. Taken together, our results uncovered a novel role for TIGAR in mitochondrial regulation in fast-twitch oxidative skeletal muscle through SIRT1-PGC1α and translocation into mitochondria, which contribute to the increase in exercise endurance of mice.-Geng, J., Wei, M., Yuan, X., Liu, Z., Wang, X., Zhang, D., Luo, L., Wu, J., Guo, W., Qin, Z.-H. TIGAR regulates mitochondrial functions through SIRT1-PGC1α pathway and translocation of TIGAR into mitochondria in skeletal muscle.

Greater Sleep Fragmentation Is Associated With Less Physical Activity in Adults With Cystic Fibrosis.

Sleep quality in people with cystic fibrosis (CF) is known to be poor, whereas participating in regular physical activity is associated with less decline in lung function (forced expiratory volume in 1 sec [FEV1]). The relationship between sleep quality and physical activity in people with CF is unknown. Secondary analysis of sleep and activity data collected via actigraphy. Adults with CF in stable health, participating in a study of physical activity (including assessment of exercise capacity), completed 7 d of activity and sleep assessment (SenseWear Armband [SWA]; BodyMedia). Sleep characteristics were derived from accelerometer positional data and registration of sleep state by the SWA, determined by energy expenditure. Sleep and activity data were available for 47 participants [n = 28 male; mean ± standard deviation age = 29 ± 8 yr; median (IQR) FEV1 = 60 (50, 82) % predicted]. More fragmented sleep was associated with poorer exercise capacity (rs = -0.303, P = .04), less time spent in moderate-vigorous physical activity (rs = -0.337, P = .020), and poorer FEV1 (rs = -0.344, P = .018). Regression analysis showed that less fragmented sleep was an independent predictor of more total daily activity time (β = -1.0, standard error [SE] of β = .4, P = .02) and trended toward significance for more moderate-vigorous physical activity (β = -.3, SE of β = -.26, P = .08). Greater total sleep time and sleep efficiency were related to better exercise capacity and lung function (P < .05). This secondary analysis demonstrated a modest relationship between sleep parameters and physical activity and exercise capacity in adults with CF. Future studies of interventions to promote physical activity participation in this group should consider the relationship between sleep and activity performance.

Pulmonary effects on exercise testing in tetralogy of Fallot patients repaired with a transannular patch.

A transannular patch is often used in the contemporary surgical repair of tetralogy of Fallot. This can lead to significant pulmonary insufficiency and increased right ventricular volumes and ultimately pulmonary valve replacement. Cardiopulmonary exercise testing is used to assess exercise capacity in tetralogy of Fallot patients before pulmonary valve replacement. There is only few published literatures on how lung function affects functional capacity in tetralogy of Fallot patients repaired with a transannular patch. A retrospective chart review was done from 2015 to 2017 on patients with tetralogy of Fallot who underwent maximal effort cardiopulmonary exercise testing with cycle ergometry and with concurrent pulmonary function testing. Tetralogy of Fallot patients repaired with a transannular patch without pulmonary valve replacement were compared with age, gender, and size-matched normal controls. In the tetralogy of Fallot group, 24 out of 57 patients underwent primary repair with a transannular patch. When compared to the normal controls, they demonstrated abnormal predicted forced expiratory volume in one second (79 ± 23.1% versus 90.7 ± 14.1%, p&lt;0.05), predicted maximal voluntary ventilation (74 ± 18% versus 90.5 ± 16.2%, p&lt;0.05) while having low-normal predicted forced vital capacity (80.5 ± 17.2% versus 90.2 ± 12.4%, p&lt;0.05) and normal breathing reserve percentage (50.3 ± 11.3% versus 47.5 ± 17.3%, p = 0.52). Cardiopulmonary exercise testing abnormalities included significantly lower percent predicted oxygen consumption (63.2 ± 12.2% versus 87 ± 12.1%, p&lt;0.05), maximal heart rate (171.8 ± 18.9 versus 184.6 ± 13.6, p&lt;0.05), and percent predicted maximum workload (61.7 ± 15.9% versus 88.3 ± 21.5%, p&lt;0.05). Tetralogy of Fallot patients repaired with a transannular patch can have abnormal pulmonary function testing with poor exercise capacity in addition to chronotropic incompetence and impaired muscular power.

A High Degree of Dyspnea Is Associated With Poor Maximum Exercise Capacity in Subjects With COPD With the Same Severity of Air-Flow Obstruction.

In patients with COPD, limited data have been reported concerning the association between dyspnea perception and exercise tests. Moreover, the perception of dyspnea has not been analyzed in patients with the same severity of air-flow obstruction. The aim of our study was to evaluate the relationship between the degree of dyspnea and exercise capacity in subjects with COPD who had the same severity of air-flow obstruction. We assessed dyspnea perception and maximum exercise capacity by using the modified Medical Research Council dyspnea scale (mMRC) questionnaire and by using the symptom-limited incremental cardiopulmonary exercise test, respectively. A propensity score matching was used to obtain the balance between the subjects with COPD and with an mMRC questionnaire score <2 and ≥2 (mMRC score) according to the severity of air-flow obstruction. A total of 249 ambulatory adult patients with stable COPD (mean age, 68 y) were considered in the full cohort. After propensity score analysis, 160 subjects (65% men; mean ± SD FEV1, 47.5 ± 12.8% of predicted) were included in our study cohort. The subjects with an mMRC questionnaire score ≥2 in comparison with those with an mMRC questionnaire score <2 showed lower values in oxygen uptake at peak (VO2 max) (P = .002) and in maximum work load (P < .001). In the regression models, the mMRC questionnaire score was able to predict oxygen uptake at peak (P < .001) and at maximum work load (P < .001). In subjects with COPD and with the same severity of air-flow obstruction, a high score in dyspnea was related to a poor maximum exercise capacity. Our results support the view that, in COPD, the severity of air-flow obstruction was less informative than symptoms in the combined assessment of the disease.

Inspiratory muscle weakness contributes to exertional dyspnea in chronic thromboembolic pulmonary hypertension.

Determination of potentially-reversible factors contributing to exertional dyspnea remains an unmet clinical need in chronic thromboembolic pulmonary hypertension (CTEPH). Therefore, we aimed to evaluate the influence of inspiratory muscle weakness (IMW) on exercise capacity and dyspnea during effort in patients with CTEPH. We performed a prospective cross-sectional study that included thirty-nine consecutive patients with CTEPH (48 ± 15 yrs, 61% female) confirmed by right heart catheterization that underwent an incremental cardiopulmonary exercise test, 6-minute walk test and maximum inspiratory pressure (MIP) measurement. MIP < 70%pred was found in 46% of patients. On a multiple linear regression analysis, MIP was independently associated with 6MWD and . Patients with MIP < 70% presented greater than those with MIP ≥ 70%. Additionally, they also presented stronger sensations of dyspnea throughout exercise, even when adjusted for ventilation. At rest and at different levels of exercise, mean inspiratory flow (VT/TI) was significantly higher in patients with MIP < 70%. In conclusion, IMW is associated with a rapid increase of dyspnea, higher inspiratory load and poor exercise capacity in patients with CTEPH.

Impact of Epicardial Adipose Tissue in Heart Failure with Preserved Ejection Fraction

IntroductionObesity is a strong risk factor for heart failure (HF) with preserved ejection fraction (HFpEF). HFpEF patients with obesity display distinct structural and functional changes in the heart compared to non-obese HFpEF. In addition to generalized obesity, fat distribution may also be important. Prior studies have shown that epicardial adipose tissue (EAT) is associated with inflammation, atrial fibrillation and cardiac fibrosis. Based upon its location, EAT might also influence hemodynamics and ventricular interaction via direct mechanical effects. However, no study has directly evaluated the impact of EAT content in HFpEF.HypothesisWe hypothesized that among patients with obesity and HFpEF, those with excess EAT (EAT+, n=77) would display more deranged hemodynamics compared to obese HFpEF patients without excess EAT (EAT−, n=92).MethodsPatients underwent invasive hemodynamic cardiopulmonary exercise testing and echocardiography. Obesity was defined by BMI≥30 kg/m2 and excess EAT was defined by EAT thickness ≥9mm by echocardiography. Ventricular interaction was assessed by the left ventricular eccentricity index (LVecc), where higher values indicate greater interdependence.ResultsEAT+ and EAT− patients displayed similar cardiac structure and function (Table). However, compared to EAT−, LVecc were elevated in EAT+. Right atrial (RA), pulmonary artery (PA), and pulmonary capillary wedge pressures (PCWP) were higher at rest and during exercise in EAT+ compared to EAT−, despite similar diastolic chamber stiffness (β) among EAT+ and EAT−. Peak VO2 was reduced in both groups, but was significantly lower in EAT+ compared to EAT−.ConclusionAmong patients with the obese phenotype of HFpEF, the presence of increased EAT is associated with more profound hemodynamic derangements at rest and exercise, greater pericardial restraint, and poorer exercise capacity (VO2). Further study is needed to understand the biology and potential treatment of excessive EAT in patients with HFpEF. Obesity is a strong risk factor for heart failure (HF) with preserved ejection fraction (HFpEF). HFpEF patients with obesity display distinct structural and functional changes in the heart compared to non-obese HFpEF. In addition to generalized obesity, fat distribution may also be important. Prior studies have shown that epicardial adipose tissue (EAT) is associated with inflammation, atrial fibrillation and cardiac fibrosis. Based upon its location, EAT might also influence hemodynamics and ventricular interaction via direct mechanical effects. However, no study has directly evaluated the impact of EAT content in HFpEF. We hypothesized that among patients with obesity and HFpEF, those with excess EAT (EAT+, n=77) would display more deranged hemodynamics compared to obese HFpEF patients without excess EAT (EAT−, n=92). Patients underwent invasive hemodynamic cardiopulmonary exercise testing and echocardiography. Obesity was defined by BMI≥30 kg/m2 and excess EAT was defined by EAT thickness ≥9mm by echocardiography. Ventricular interaction was assessed by the left ventricular eccentricity index (LVecc), where higher values indicate greater interdependence. EAT+ and EAT− patients displayed similar cardiac structure and function (Table). However, compared to EAT−, LVecc were elevated in EAT+. Right atrial (RA), pulmonary artery (PA), and pulmonary capillary wedge pressures (PCWP) were higher at rest and during exercise in EAT+ compared to EAT−, despite similar diastolic chamber stiffness (β) among EAT+ and EAT−. Peak VO2 was reduced in both groups, but was significantly lower in EAT+ compared to EAT−. Among patients with the obese phenotype of HFpEF, the presence of increased EAT is associated with more profound hemodynamic derangements at rest and exercise, greater pericardial restraint, and poorer exercise capacity (VO2). Further study is needed to understand the biology and potential treatment of excessive EAT in patients with HFpEF.

Depressive Symptoms, Exercise Capacity, and Clinical Outcomes After Lung Transplantation.

Depressive symptoms are common among lung transplant recipients and have been associated with worse clinical outcomes. However, few studies have examined the association between depressive symptoms assessed at multiple time points or behavioral mechanisms by which posttransplant depressive symptoms may confer greater clinical risk. We therefore examined the associations between depressive symptoms, exercise capacity, chronic lung allograft dysfunction (CLAD), and mortality prospectively in a large sample of lung transplant recipients. Between July 2009 and February 2016, 251 lung transplant recipients were assessed before transplantation and again approximately 3 weeks and 3 months after transplant. Depressive symptoms were assessed using the Centers for Epidemiologic Studies of Depression scale. Functional exercise capacity was assessed using the 6-minute walk test. Cox proportional hazards models were used to examine the associations between depressive symptoms, exercise capacity, CLAD, and mortality. During a median (range) follow-up of 4.5 (0.1 to 6.3) years, 53 participants (21%) died. Greater depressive symptoms (hazard ratio [HR] = 1.39 [95% CI = 1.05 to 1.84], p = .021) and poorer exercise capacity (HR = 0.58 [95% CI = 0.38 to 0.90], p = .021) assessed 3 months after transplant were both independently associated with mortality. Although greater depressive symptoms were associated with lower exercise capacity (β = -0.14, p = .039), exercise capacity did not mediate the association between depressive symptoms and mortality. In secondary analyses, depressive symptoms were independently predictive of CLAD (HR = 1.29 [95% CI = 1.01 to 1.65], p = .045) and the composite outcome of CLAD and mortality in a clustered event model (HR = 1.30 [1.09 to 1.56], p = .005). Depressive symptoms are associated with mortality and CLAD after lung transplantation, independent of exercise capacity.