Impaired Exercise Capacity Research Articles

Evaluation of fitness capacities of children and young adults with Marfan and related conditions

Early diagnosis of Marfan syndrome (MFS) leads us to a comprehensive approach to the multisystem damage related to connective tissue fragility. Impairment in exercise capacity has a great impact on quality of life (QoL) and rehabilitation programs need to address his ultimate causes. We have analysed fitness capacities of patients from a young age until early adulthood, and analysed the causes of limitation. This study included 28 Marfan or associated syndrome patients between 7 and 20 years (average 12.6 years), with mild aortic dilatation for 50% (mean z -score +2,4), no major valvulopathy, no cardiac impairment and history of pneumothorax for 3 of them; most where under preventive betablocker treatment (93%). All of them performed a cardiopulmonary exercise test (CPET) on step incremental cycloergometer. All but one patient reached maximum effort. Results confirm the disease's significant impact on the exercise capacity from a young age. The VO2max values were severely impaired in this population, on average reaching 63.4% of the expected values (mean peak of 104 Watts, 72% of expected work), with a limitation occurring in 71% and resulting from peripheral muscle deconditioning beside chronotropic limitation from betablockers (mean heart rate at peak of 163 bpm, 80.7% of the theoretical maximum). No intrinsic cardiac or pulmonary limitation was observed whereas dyspnoea was a major limiting factor in our patients, over muscular fatigue (dotted 6.5/10 vs. 5.8/10, respectively). These results were correlated to QoL when compared to a control population. The impact of the Marfan syndrome's multisystemic damage and physical impairment through muscular deconditioning is evident from a young age and should not be neglected. Namely, the care provided to patients should include adapted physical activity programs from a young age.

Effect of intravenous ferric carboxymaltose on exercise capacity and quality of life in patients with COPD : Apilot study.

Chronic obstructive pulmonary disease (COPD) is associated with reduced exercise capacity. In COPD iron deficiency is found in up to 50% of patients and may impair exercise capacity, the potential therapeutic effect is yet unknown. We aimed to estimate the beneficial effect of intravenous ferric carboxymaltose on exercise capacity and quality of life in patients with COPD. In this non-randomized, interrupted time series pilot trial we enrolled outpatients with stable COPD (GOLDII andIII) and nonanemic iron deficiency (i.e., ferritin level < 100 μg/l or ferritin level 100-300 μg/l if transferrin saturation < 20%). Patients with cardiovascular-or inflammatory diseases were excluded. Participants performed 6‑minute walking test (6-MWT) and cardiopulmonary exercise testing (CPET) and completed the St. George's Respiratory Questionnaire (SGRQ). From 35screened patients, 11 (72% male, 63 ± 8years, FEV1%predicted 44 ± 14) were included. Mean ferritin and hemoglobin were 70 ± 41 µg/l and 13.8 ± 1.7 g/dl, respectively. Four weeks after iron administration the 6‑MWT distance increased by 34.7 ± 34.4 m (95% CI, 10.0-59.3); p = 0.011. The VO2max increased by 1.87 ± 1.2 ml/kg/min (95% CI, 0.76-3); p = 0.006. Mean score of SGRQ was reduced by 7.56 ± 6.12units (95% CI, 3 to 11); p = 0.004. The insignificant alteration in hemoglobin did not correlate with increase in exercise capacity. Administration of intravenous iron was associated with improved exercise capacity and quality of life in stable COPD patients independent of hemoglobin. Our data provide abasis to calculate astatistically sufficient sample size for arandomized controlled follow-up study.

Physiologic responses to exercise in survivors of critical illness: an exploratory pilot study

BackgroundICU survivors suffer from impaired physical function and reduced exercise capacity, yet the underlying mechanisms are poorly understood. The goal of this exploratory pilot study was to investigate potential mechanisms of exercise limitation using cardiopulmonary exercise testing (CPET) and 6-min walk testing (6MWT).MethodsWe enrolled adults aged 18 years or older who were treated for respiratory failure or shock in medical, surgical, or trauma ICUs at Vanderbilt University Medical Center (Nashville, TN, United States). We excluded patients with pre-existing cardiac dysfunction, a contraindication to CPET, or the need for supplemental oxygen at rest. We performed CPET and 6MWT 6 months after ICU discharge. We measured standard CPET parameters in addition to two measures of oxygen utilization during exercise (VO2-work rate slope and VO2 recovery half-time).ResultsWe recruited 14 participants. Low exercise capacity (i.e., VO2Peak < 80% predicted) was present in 11 out of 14 (79%) with a median VO2Peak of 12.6 ml/kg/min [9.6–15.1] and 6MWT distance of 294 m [240–433]. In addition to low VO2Peak, CPET findings in survivors included low oxygen uptake efficiency slope, low oxygen pulse, elevated chronotropic index, low VO2-work rate slope, and prolonged VO2 recovery half-time, indicating impaired oxygen utilization with a hyperdynamic heart rate and ventilatory response, a pattern seen in non-critically ill patients with mitochondrial myopathies. Worse VO2-work rate slope and VO2 recovery half-time were strongly correlated with worse VO2Peak and 6MWT distance, suggesting that exercise capacity was potentially limited by impaired muscle oxygen utilization.ConclusionsThese exploratory data suggest ICU survivors may suffer from impaired muscular oxygen metabolism due to mitochondrial dysfunction that impairs exercise capacity long-term. These findings should be further characterized in future studies that include direct assessments of muscle mitochondrial function in ICU survivors.

Impaired functional exercise capacity and greater cardiovascular response to the 6-min walk test in congenital generalized lipodystrophy

BackgroundCongenital Generalized Lipodystrophy (CGL) is an ultra-rare disease characterized by metabolic disorders. However, the evaluation of functional exercise capacity, cardiovascular (CV) response to exercise, and peripheral arterial disease (PAD) in CGL is scarce. Here we evaluated the performance and CV response to exercise and their association with PAD in CGL compared to healthy individuals.MethodsTwelve CGL and 12 healthy subjects matched for age and gender were included. Functional exercise capacity, CV response, and PAD were measured using the six-minute walk test (6MWT) and ankle-brachial index (ABI), respectively.ResultsAt baseline, CGL subjects showed reduced predicted walked distance (6MWD) (p = 0.009) and increased heart rate (HR), systolic (SBP), and diastolic (DBP) pressures compared to healthy subjects (p < 0.05). Most CGL subjects presented normal ABI values (1.0 ≤ ABI ≤ 1.4). Only 25% (n = 3) had ABI ≤ 0.9. CGL subjects did not present changes in ABI and blood pressure 12 months after metreleptin (MLP) replacement, but they walked a greater 6MWD than baseline (p = 0.04). Further, 6MWD and right ABI measurements were positively correlated in CGL subjects (p = 0.03). Right ABI negatively correlated with glucose, triglycerides, and VLDL-c (p < 0.05).ConclusionsWe observed that CGL subjects had lower functional exercise capacity and higher cardiovascular effort for similar performance of 6MWT, suggesting that strategies for decreasing exercise effort in this population should be essential. Furthermore, better physical performance was associated with high ABI in CGL. Additional studies are needed to clarify leptin's role in preserving functional exercise capacity in CGL.

Right ventricular-pulmonary arterial coupling impairment and exercise capacity in obese adults.

BackgroundObesity-related exercise intolerance may be associated with pulmonary vascular and right ventricular dysfunction. This study tested the hypothesis that decreased pulmonary vascular reserve and right ventricular (RV)-pulmonary arterial (PA) uncoupling contributes to exercise limitation in subjects with obesity.MethodsSeventeen subjects with obesity were matched to normo-weighted healthy controls. All subjects underwent; exercise echocardiography, lung diffusing capacity (DL) for nitric oxide (NO) and carbon monoxide (CO) and an incremental cardiopulmonary exercise test. Cardiac output (Q), PA pressure (PAP) and tricuspid annular plane systolic excursion (TAPSE) were recorded at increasing exercise intensities. Pulmonary vascular reserve was assessed by multipoint mean PAP (mPAP)/Q relationships with more reserve defined by lesser increase in mPAP at increased Q, and RV-PA coupling was assessed by the TAPSE/systolic PAP (sPAP) ratio.ResultsAt rest, subjects with obesity displayed lower TAPSE/sPAP ratios (1.00 ± 0.26 vs. 1.19 ± 0.22 ml/mmHg, P < 0.05), DLCO and pulmonary capillary blood volume (52 ± 11 vs. 64 ± 13 ml, P < 0.01) compared to controls. Exercise was associated with steeper mPAP-Q slopes, decreased TAPSE/sPAP and lower peak O2 uptake (VO2peak). The changes in TAPSE/sPAP at exercise were correlated to the body fat mass (R = 0.39, P = 0.01) and VO2peak (R = 0.44, P < 0.01).ConclusionObesity is associated with a decreased pulmonary vascular and RV-PA coupling reserve which may impair exercise capacity.

Could SGLT2 Inhibitors Improve Exercise Intolerance in Chronic Heart Failure?

Despite the constant improvement of therapeutical options, heart failure (HF) remains associated with high mortality and morbidity. While new developments in guideline-recommended therapies can prolong survival and postpone HF hospitalizations, impaired exercise capacity remains one of the most debilitating symptoms of HF. Exercise intolerance in HF is multifactorial in origin, as the underlying cardiovascular pathology and reactive changes in skeletal muscle composition and metabolism both contribute. Recently, sodium-related glucose transporter 2 (SGLT2) inhibitors were found to improve cardiovascular outcomes significantly. Whilst much effort has been devoted to untangling the mechanisms responsible for these cardiovascular benefits of SGLT2 inhibitors, little is known about the effect of SGLT2 inhibitors on exercise performance in HF. This review provides an overview of the pathophysiological mechanisms that are responsible for exercise intolerance in HF, elaborates on the potential SGLT2-inhibitor-mediated effects on these phenomena, and provides an up-to-date overview of existing studies on the effect of SGLT2 inhibitors on clinical outcome parameters that are relevant to the assessment of exercise capacity. Finally, current gaps in the evidence and potential future perspectives on the effects of SGLT2 inhibitors on exercise intolerance in chronic HF are discussed.

Persistent dyspnea after COVID-19 is not related to cardiopulmonary impairment; a cross-sectional study of persistently dyspneic COVID-19, non-dyspneic COVID-19 and controls.

Background: Up to 53% of individuals who had mild COVID-19 experience symptoms for >3-month following infection (Long-CoV). Dyspnea is reported in 60% of Long-CoV cases and may be secondary to impaired exercise capacity (VO2peak) as a result of pulmonary, pulmonary vascular, or cardiac insult. This study examined whether cardiopulmonary mechanisms could explain exertional dyspnea in Long-CoV. Methods: A cross-sectional study of participants with Long-CoV (n = 28, age 40 ± 11 years, 214 ± 85 days post-infection) and age- sex- and body mass index-matched COVID-19 naïve controls (Con, n = 24, age 41 ± 12 years) and participants fully recovered from COVID-19 (ns-CoV, n = 14, age 37 ± 9 years, 198 ± 89 days post-infection) was conducted. Participants self-reported symptoms and baseline dyspnea (modified Medical Research Council, mMRC, dyspnea grade), then underwent a comprehensive pulmonary function test, cardiopulmonary exercise test, exercise pulmonary diffusing capacity measurement, and rest and exercise echocardiography. Results: VO2peak, pulmonary function and cardiac/pulmonary vascular parameters were not impaired in Long- or ns-CoV compared to normative values (VO2peak: 106 ± 25 and 107 ± 25%predicted, respectively) and cardiopulmonary responses to exercise were otherwise normal. When Long-CoV were stratified by clinical dyspnea severity (mMRC = 0 vs mMRC≥1), there were no between-group differences in VO2peak. During submaximal exercise, dyspnea and ventilation were increased in the mMRC≥1 group, despite normal operating lung volumes, arterial saturation, diffusing capacity and indicators of pulmonary vascular pressures. Interpretation: Persistent dyspnea after COVID-19 was not associated with overt cardiopulmonary impairment or exercise intolerance. Interventions focusing on dyspnea management may be appropriate for Long-CoV patients who report dyspnea without cardiopulmonary impairment.

Differences in Pulmonary and Extra-Pulmonary Traits between Women and Men with Chronic Obstructive Pulmonary Disease.

Background: Evidence suggests sex-related differences in chronic obstructive pulmonary disease (COPD). Whether these differences are reflected in the prevalence of treatable traits remains unknown. Methods: Two samples of patients referred to secondary (n = 530) or tertiary care (n = 2012) were analyzed. Men and women were matched for age, forced expiratory volume in 1 s and body mass index. Sex-related differences were tested using t-tests, Mann-Whitney U, or chi-square tests. Results: Frequent exacerbations (30.5 vs. 19.7%), high cardiovascular risk (88.1 vs. 66.2%) and activity-related severe dyspnea (50.9 vs. 34.8%) were more prevalent in women in secondary care (p < 0.05). Severe hyperinflation (43.0 vs. 25.4%), limited diffusing capacity (79.6 vs. 70.1%), impaired mobility (44.0 vs. 28.7%), frequent exacerbations (66.8 vs. 57.4%), frequent hospitalizations (47.5 vs. 41.6%), severe activity-related dyspnea (89.1 vs. 85.0%), symptoms of anxiety (56.3 vs. 42.0%) and depression (50.3 vs. 44.8%), and poor health status (79.9 vs. 71.0%) were more prevalent in women in tertiary care (p < 0.05). Severe inspiratory muscle weakness (14.6 vs. 8.2%) and impaired exercise capacity (69.1 vs. 59.6%) were more prevalent among men (p < 0.05) in tertiary care. Conclusions: Sex-related differences were found, with most traits more prevalent and severe among women. Care providers should be aware of these differences to adjust treatment.

Impaired exercise outcomes with significant bronchodilator responsiveness in children with prematurity-associated obstructive lung disease.

IntroductionPreterm‐born children have their normal in‐utero lung development interrupted, thus are at risk of short‐ and long‐term lung disease. Spirometry and exercise capacity impairments have been regularly reported in preterm‐born children especially those who developed chronic lung disease of prematurity (CLD) in infancy. However, specific phenotypes may be differentially associated with exercise capacity. We investigated exercise capacity associated with prematurity‐associated obstructive (POLD) or prematurity‐associated preserved ratio of impaired spirometry (pPRISm) when compared to preterm‐ and term‐controls with normal lung function.Materials and MethodsPreterm‐ and term‐born children identified through home screening underwent in‐depth lung function and cardiorespiratory exercise testing, including administration of postexercise bronchodilator, as part of the Respiratory Health Outcomes in Neonates (RHiNO) study.ResultsFrom 241 invited children, aged 7–12 years, 202 underwent exercise testing including 18 children with POLD (percent predicted (%)FEV1 and FEV1/FVC < LLN); 12 pPRISm (%FEV1 < LLN and FEV1/FVC ≥ LLN), 106 preterm‐controls (PTc, %FEV1 ≥ LLN) and 66 term‐controls (Tc, %FEV1 > 90%). POLD children had reduced relative workload, peak O2 uptake, CO2 production, and minute ventilation compared to Tc, and used a greater proportion of their breathing reserve compared to both control groups. pPRISm and PTc children also had lower O2 uptake compared to Tc. POLD children had the greatest response to postexercise bronchodilator, improving their %FEV1 by 19.4% (vs 6.3%, 6% 6.3% in pPRISm PTc,Tc, respectively; p < .001).ConclusionPreterm‐born children with obstructive airway disease had the greatest impairment in exercise capacity, and significantly greater response to postexercise bronchodilators. These classifications can be used to guide treatment in children with POLD.

Impaired exercise capacity in post–COVID-19 syndrome: the role of VWF-ADAMTS13 axis

AbstractPost-COVID syndrome (PCS), or long COVID, is an increasingly recognized complication of acute SARS-CoV-2 infection, characterized by persistent fatigue, reduced exercise tolerance, chest pain, shortness of breath, and cognitive slowing. Acute COVID-19 is strongly linked with an increased risk of thrombosis, which is a prothrombotic state quantified by an elevated von Willebrand factor (VWF) antigen (Ag)/ADAMTS13 ratio that is associated with severity of acute COVID-19 infection. We investigated whether patients with PCS also had evidence of a prothrombotic state associated with symptom severity. In a large cohort of patients referred to a dedicated post-COVID-19 clinic, thrombotic risk, including VWF(Ag)/ADAMTS13 ratio, was investigated. An elevated VWF(Ag)/ADAMTS13 ratio (≥1.5) was present in nearly one-third of the cohort and was 4 times more likely to be present in patients with impaired exercise capacity, as evidenced by desaturation ≥3% and/or an increase in lactate level >1 from baseline on a 1-minute sit-to-stand test and/or a 6-minute walk test (P < .0001). Of 276 patients, 56 (20%) had impaired exercise capacity, of which 55% (31/56) had a VWF(Ag)/ADAMTS13 ratio ≥1.5 (P < .0001). Factor VIII and VWF(Ag) were elevated in 26% and 18%, respectively, and support a hypercoagulable state in some patients with PCS. These findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS and suggest a role for antithrombotic therapy in the treatment of these patients.

Are there correlations between lung volume and exercise capacity in children and adolescents with native Ebstein's anomaly?

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with Ebstein’s Anomaly (EA) represent a wide clinical range with patients needing surgery in infancy and others needing no surgery throughout life. Exercise capacity in EA is often impaired. However, lung function is rarely investigated. Purpose This study examines lung volumes in native EA and their correlation with exercise capacity. Methods This retrospective study investigated 35 children with native EA (14 ± 4 years, 17 female), who underwent a cardiopulmonary exercise test (CPET) including spirometry to examine peak oxygen uptake (peakV’O2), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and its ratio (FEV/FVC). Percentage in peakV’O2 &amp;lt;80% represents a reduced exercise capacity, and values &amp;lt;60% are defined as impaired. Z-scores below -1.64 categorize restrictive (FVC) or obstructive (FEV1/FVC) patterns. To analyse correlations between CPET and lung volumes Spearman’s rank test was performed. Results Reduced exercise capacity was found in 17 children (47%), and further seven (20%) children showed impaired exercise capacity. Seven patients (20%) had a restrictive lung volume pattern and three patients (9%) showed obstructive patterns. One patient showed both. Eleven (92%) patients with an impaired lung function had at least a reduced exercise capacity with a median of 64 [53;73] %predicted. Lung volumes correlate significantly with %peakV’O2 (z-FVC: r=0.500, p=0.002 and z-FEV1: r=0.443, p=0.008). Conclusions Most young patients with native EA have impaired results in exercise capacity and a third has reduced lung volumes. Low lung volumes correlate with worse exercise capacity. Thus, the lung function should also be taken into consideration when looking at the performance of these and medical aftercare.

Role of oxidation of excitation-contraction coupling machinery in age-dependent loss of muscle function in Caenorhabditis elegans.

Age-dependent loss of body wall muscle function and impaired locomotion occur within 2 weeks in Caenorhabditis elegans (C. elegans); however, the underlying mechanism has not been fully elucidated. In humans, age-dependent loss of muscle function occurs at about 80 years of age and has been linked to dysfunction of ryanodine receptor (RyR)/intracellular calcium (Ca2+) release channels on the sarcoplasmic reticulum (SR). Mammalian skeletal muscle RyR1 channels undergo age-related remodeling due to oxidative overload, leading to loss of the stabilizing subunit calstabin1 (FKBP12) from the channel macromolecular complex. This destabilizes the closed state of the channel resulting in intracellular Ca2+ leak, reduced muscle function, and impaired exercise capacity. We now show that the C. elegans RyR homolog, UNC-68, exhibits a remarkable degree of evolutionary conservation with mammalian RyR channels and similar age-dependent dysfunction. Like RyR1 in mammals, UNC-68 encodes a protein that comprises a macromolecular complex which includes the calstabin1 homolog FKB-2 and is immunoreactive with antibodies raised against the RyR1 complex. Furthermore, as in aged mammals, UNC-68 is oxidized and depleted of FKB-2 in an age-dependent manner, resulting in 'leaky' channels, depleted SR Ca2+ stores, reduced body wall muscle Ca2+ transients, and age-dependent muscle weakness. FKB-2 (ok3007)-deficient worms exhibit reduced exercise capacity. Pharmacologically induced oxidization of UNC-68 and depletion of FKB-2 from the channel independently caused reduced body wall muscle Ca2+ transients. Preventing FKB-2 depletion from the UNC-68 macromolecular complex using the Rycal drug S107 improved muscle Ca2+ transients and function. Taken together, these data suggest that UNC-68 oxidation plays a role in age-dependent loss of muscle function. Remarkably, this age-dependent loss of muscle function induced by oxidative overload, which takes ~2 years in mice and ~80 years in humans, occurs in less than 2-3 weeks in C. elegans, suggesting that reduced antioxidant capacity may contribute to the differences in lifespan among species.

Red cell distribution width as a predictor of impaired exercise capacity in patients with heart failure

Aim To test a hypothesis that increased values of red cell distribution width (RDW) in patients with chronic heart failure (CHF) can be related with low exercise tolerance.Material and methods 102 patients were evaluated who had CHF with mid-range and reduced left ventricular ejection fraction (LV EF) without anemia (72% men, mean age 66±10.2 years). Cardiopulmonary stress test (CPST), echocardiography, 6‑min walk test (6MWT), blood count, and measurements of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and serum iron were performed.Results The average LV EF was 39±8.7 %; the peak oxygen consumption (VO2peak) was 13.7±4.8 ml /kg /min; and the median NT-pro-BNP was 595.3 pg /ml (Q1-3 1443-2401). RDW variables, including the RDW coefficient of variation (RDW-CV) and RDW standard deviation (RDW-SD), were not significantly related with serum iron or hemoglobin concentrations. A one-factor linear regression analysis showed a significant correlation of VO2peak with RDW-SD (р=0.039). A multivariate linear regression analysis with adjustments for LV EF, hemoglobin concentration, and age did not reveal any significant correlation of VO2peak with RDW variables. The distance covered in the 6MWT was significantly associated with RDW-CV both in the one-factor analysis and with adjustments for LV EF, hemoglobin and serum iron concentrations, and age.Conclusion This study showed that high RDW values in CHF patients without anemia predicted low exercise tolerance regardless of the age, LV systolic function, and hemoglobin and serum iron concentrations. A 16% increase in RDW-CV significantly decreased the likelihood of covering a distance longer than 360 m during 6 min.

Lactiplantibacillus plantarum fermented barley extracts ameliorate high-fat-diet-induced muscle dysfunction via mitophagy.

A reduced level of fatty acid oxidation (FAO) by skeletal muscle leads to the accumulation of intermuscular fat (IMF), which is linked to impaired exercise capacity. Previously, we have reported that Lactiplantibacillus plantarum fermented barley extract (LFBE) has effective anti-obesity properties. In this study, the effects of LFBE on muscle were investigated. LFBE improved running endurance and muscle strength, which was caused by the elevation of FAO in muscle. In addition, LFBE renovated muscle regeneration through the upregulation of paired box 7 and myogenic differentiation 1 expression avoiding the injury of skeletal muscle fibers. Furthermore, total polyphenol isolated from LFBE (FTP) reinforced mobility and showed a significant protective effect on maintaining muscle fiber morphogenesis in Caenorhabditis elegans. Transmission electron microscope observation suggested FTP induced mitophagy in C.elegans body wall muscle, which was strongly connected with enhanced FAO in mitochondria. Our findings highlighted the beneficial bioactivities of FTP and its potential application for stimulating mitophagy and muscle function in obese individuals. © 2022 Society of Chemical Industry.

Comparison of the effects of high and low levels of solar radiations on exercise capacity in hot outdoor environments.

High solar radiation from the sun in the heat outdoor may be impaired exercise capacity. This study aimed to compare the effects of different levels of solar radiation on exercise capacity and evaluate skin temperature responses in the heat. Seven male participants performed cycling exercise at 60% of their maximal oxygen uptake until volitional exhaustion in hot outdoor environments (approximately 33-35°C, 40-50% relative humidity) under both clear sky (high solar radiation trial: 1062±50 W/m2) and under thick clouds (low solar radiation trial: 438±52 W/m2). The time to exhaustion of the participants was shorter in the high solar radiation trial (32.0±12.4 min) than in the low solar radiation trial (39.2±18.0 min: P=0.045). Mean skin temperature was significantly higher in the high solar radiation trial than that in the low solar radiation trial (P<0.05); however, the rectal temperature did not differ significantly between the two trials. The high solar radiation trial had narrower core-to-skin temperature gradient, greater the body heat gain from the sun, and higher rating of perceived exertion than the low solar radiation trial. These results indicate that high solar radiation during outdoor exercise in the heat causes a greater increase in skin temperature and body heat gain from the sun than low solar radiation and consequently impairs exercise capacity.

Relationships among norepinephrine levels, exercise capacity, and chronotropic responses in heart failure patients.

In heart failure (HF) patients, the pathophysiological mechanisms of severe exercise intolerance and impaired exercise capacity are related to both central and peripheral abnormalities. The central abnormalities in HF patients include impaired cardiac function and chronotropic incompetence (CI). Indeed, CI, the inability to adequately increase heart rate (HR) from rest to exercise often exhibited by HF patients, is related to activation of the sympathetic nervous system (SNS) yielding a rise in circulating norepinephrine (NE). CI may result from downregulation of β-adrenergic receptors, β-blocker usage, high baseline HR, or due to a combination of factors. This paper discusses the role of elevated NE in altering chronotropic responses in HF patients and consequently resulting in impaired exercise capacity. We suggest that future research should focus on the potential treatment of CI with rate-adaptive pacing, using a sensor to measure physical activity, without inducing deleterious hormonal activation of the sympathetic system.

Identification of factors impairing exercise capacity after severe COVID-19 pulmonary infection: a 3-month follow-up of prospective COVulnerability cohort

BackgroundPatient hospitalized for coronavirus disease 2019 (COVID-19) pulmonary infection can have sequelae such as impaired exercise capacity. We aimed to determine the frequency of long-term exercise capacity limitation in survivors of severe COVID-19 pulmonary infection and the factors associated with this limitation.MethodsPatients with severe COVID-19 pulmonary infection were enrolled 3 months after hospital discharge in COVulnerability, a prospective cohort. They underwent cardiopulmonary exercise testing, pulmonary function test, echocardiography, and skeletal muscle mass evaluation.ResultsAmong 105 patients included, 35% had a reduced exercise capacity (VO2peak < 80% of predicted). Compared to patients with a normal exercise capacity, patients with reduced exercise capacity were more often men (89.2% vs. 67.6%, p = 0.015), with diabetes (45.9% vs. 17.6%, p = 0.002) and renal dysfunction (21.6% vs. 17.6%, p = 0.006), but did not differ in terms of initial acute disease severity. An altered exercise capacity was associated with an impaired respiratory function as assessed by a decrease in forced vital capacity (p < 0.0001), FEV1 (p < 0.0001), total lung capacity (p < 0.0001) and DLCO (p = 0.015). Moreover, we uncovered a decrease of muscular mass index and grip test in the reduced exercise capacity group (p = 0.001 and p = 0.047 respectively), whilst 38.9% of patients with low exercise capacity had a sarcopenia, compared to 10.9% in those with normal exercise capacity (p = 0.001). Myocardial function was normal with similar systolic and diastolic parameters between groups whilst reduced exercise capacity was associated with a slightly shorter pulmonary acceleration time, despite no pulmonary hypertension.ConclusionThree months after a severe COVID-19 pulmonary infection, more than one third of patients had an impairment of exercise capacity which was associated with a reduced pulmonary function, a reduced skeletal muscle mass and function but without any significant impairment in cardiac function.

Decreased incremental shuttle walk test distance characterized by fibrocavitary lesions in non-tuberculous mycobacterial pulmonary disease

Background Patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) have impaired exercise capacity, but the underlying factors are unknown. We investigated the characteristics of patients with NTM-PD and impaired exercise capacity. Methods In total, 149 patients with NTM-PD participated in this study. Patients completed the incremental shuttle walk test (ISWT) to assess exercise capacity. Peripheral muscle strength and pulmonary function were also assessed. Radiological findings were classified into three phenotypes: non-cavitary nodular bronchiectatic (NC-NB) form, cavitary nodular bronchiectatic form, and fibrocavitary (FC) form. Results The median ISWT distance (ISWD) and %ISWD were 450 meters and 88%. Participants were classified into three groups according to %ISWD, with %ISWD <60% as the severely decreased group, 60%-80% as the moderately decreased group, and >80% as the normal or mildly decreased group. In a comparison of %ISWD among phenotypes, FC form had significantly lower %ISWD than those with NC-NB form. In the severely decreased group, peripheral muscle strength and pulmonary function were significantly lower than the other two groups. From a radiological standpoint, significantly more patients had FC form in the group with severely decreased %ISWD. Conclusions Decreased ISWD is characterized by a deterioration in physical function and the presence of FC lesions in NTM-PD.

Novel European Heart Failure Guidelines - Change in Treatment Paradigms

The diagnostic algorithm has been simplified for HFpEF, which requires not only signs and symptoms of HF, but also a LVEF ≥ 50 % and additionally objective criteria for a structural and/or functional abnormalities with diastolic dysfunction, elevated filling pressures and elevated natriuretic peptides. Etiology of HFpEF should be evaluated. There is no change in the treatment recommendations of HFpEF in contrast to 2016, but a short-term revision of the guidelines can be expected. The primary recommendation for atrial fibrillation is anticoagulation with NOAKs. The value of PVI has been upgraded. The decision for transcatheter therapy of secondary mitral regurgitation should be made in the heart team if appropriate criteria are present. For the diagnosis of advanced heart failure four key criteria were defined, including severe and persistent symptoms (NYHA III or IV), a severe cardiac dysfunction, episodes of congestion treated with i. v. diuretics and/or inotropes, malignant arrhythmias and a severe impairment of exercise capacity. There is a new treatment algorithm for these patients, in which the importance of mechanical support was upgraded. For patients with acute heart failure, integration into a disease management program and a multimodal, multiprofessional therapy concept is recommended after discharge from inpatient treatment.

The hepatokine TSK maintains myofiber integrity and exercise endurance and contributes to muscle regeneration.

Mammalian skeletal muscle contains heterogenous myofibers with different contractile and metabolic properties that sustain muscle mass and endurance capacity. The transcriptional regulators that govern these myofiber gene programs have been elucidated. However, the hormonal cues that direct the specification of myofiber types and muscle endurance remain largely unknown. Here, we uncover the secreted factor Tsukushi (TSK) as an extracellular signal that is required for maintaining muscle mass, strength, and endurance capacity and that contributes to muscle regeneration. Mice lacking TSK exhibited reduced grip strength and impaired exercise capacity. Muscle transcriptomic analysis revealed that TSK deficiency results in a remarkably selective impairment in the expression of myofibrillar genes, characteristic of slow-twitch muscle fibers, that is associated with abnormal neuromuscular junction formation. AAV-mediated overexpression of TSK failed to rescue these myofiber defects in adult mice, suggesting that the effects of TSK on myofibers are likely restricted to certain developmental stages. Finally, mice lacking TSK exhibited diminished muscle regeneration following cardiotoxin-induced muscle injury. These findings support a crucial role of TSK as a hormonal cue in the regulation of contractile gene expression, endurance capacity, and muscle regeneration.