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Summary Introduction Inducible laryngeal obstruction is a common and challenging cause of exertional dyspnea. We report a case of an unanticipated cardiac condition that presented with symptoms suggestive of inducible laryngeal obstruction. Discussion A 55-year-old man was evaluated for progressive exertional dyspnea and throat tightness, unexplained after multiple medical evaluations. Resting laryngeal examination was suspicious for laryngopharyngeal reflux and mild vocal fold adduction during quiet expiration. Given progressive and refractory symptoms, maximal cardiopulmonary exercise testing with intermittent laryngeal examination was performed. This study excluded laryngeal causes of exercise limitation and led to an unexpected diagnosis of persistent atrial flutter and hypertrophic cardiomyopathy. Conclusion Cardiopulmonary exercise testing with laryngeal examination can identify unexpected and life-threatening mimics of inducible laryngeal obstruction that may be missed by unmonitored exercise challenges. Suspicion for inducible laryngeal obstruction at rest may not predict the true nature of exercise limitation on cardiopulmonary exercise testing.

IntroductionSeveral studies report that pulmonary oxygen uptake (V̇O 2 ) at the respiratory compensation point (RCP) is equivalent to the V̇O 2 at critical power (CP), suggesting that the variables can be used interchangeably to demarcate the threshold between heavy and severe intensity domains. However, if RCP is a valid surrogate for CP, their values should correspond even when assessed in patients with chronic obstructive pulmonary disease (COPD) in whom the "normal" mechanisms linking CP and RCP are impeded. The aim of this study was to compare V̇O 2 at CP with V̇O 2 at RCP in patients with COPD.MethodsTwenty-two COPD patients (14 male/8 female; forced expiratory volume in 1 s, 46% ± 17% pred) performed ramp-incremental cycle ergometry to intolerance (5-10 W·min -1 ) for the determination of gas exchange threshold (GET) and RCP. CP was calculated from the asymptote of the hyperbolic power-duration relationship from 3-5 constant-power exercise tests to intolerance. CP was validated with a 20-min constant-power ride.ResultsGET was identified in 20 of 22 patients at a V̇O 2 of 0.93 ± 0.18 L·min -1 (75% ± 13% V̇O 2peak ), whereas RCP was identified in just 3 of 22 patients at a V̇O 2 of 1.40 ± 0.39 L·min -1 (85% ± 2% V̇O 2peak ). All patients completed constant-power trials with no difference in peak physiological responses relative to ramp-incremental exercise ( P > 0.05). CP was 46 ± 22 W, which elicited a V̇O 2 of 1.04 ± 0.29 L·min -1 (90% ± 9% V̇O 2peak ) during the validation ride. The difference in V̇O 2 at 15 and 20 min of the validation ride was 0.00 ± 0.04 L, which was not different from a hypothesized mean of 0 ( P = 0.856), thereby indicating a V̇O 2 steady state.ConclusionsIn COPD patients, who present with cardiopulmonary and/or respiratory-mechanical dysfunction, CP can be determined in the absence of RCP. Accordingly, CP and RCP are not equivalent in this group.

Pulmonary arterial hypertension (PAH) is characterised by pathological pulmonary vascular remodelling and increased resistance leading to right heart failure and death [1]. It is thought that exercise intolerance in PAH arises from an impairment in oxygen transport and delivery, driven by a reduced stroke volume [2]., In precapillary pulmonary hypertension, exercising muscles extract oxygen to a similar level seen in healthy individuals. Exercise limitation is a result of impaired oxygen delivery, which is matched to any impairment in skeletal muscle oxygen extraction. https://bit.ly/3hQUY8m

Exercise intolerance represents a typical feature of heart failure with preserved ejection fraction (HFpEF), and is associated with a poor quality of life, frequent hospitalizations, and increased all-cause mortality. The cardiopulmonary exercise test is the best method to quantify exercise intolerance, and allows detection of the main mechanism responsible for the exercise limitation, influencing treatment and prognosis. Exercise training programs improve exercise tolerance in HFpEF. However, studies are needed to identify appropriate type and duration. This article discusses the pathophysiology of exercise limitation in HFpEF, describes methods of determining exercise tolerance class, and evaluates prognostic implications and potential therapeutic strategies.

Chronic kidney disease (CKD), especially end-stage kidney disease (ESKD), is associated with an increased risk for cardiovascular events and all-cause mortality. Exercise intolerance as well as reduced cardiovascular reserve is extremely common in patients with CKD. Cardiopulmonary exercise testing (CPET) is a non-invasive, dynamic technique that provides an integrative evaluation of cardiovascular, pulmonary, neuropsychological and metabolic function during maximal or submaximal exercise, allowing the evaluation of functional reserves of these systems. This assessment is based on the principle that system failure typically occurs when the system is under stress and thus CPET is currently considered to be the gold standard for identifying exercise limitation and differentiating its causes. It has been widely used in several medical fields for risk stratification, clinical evaluation and other applications, but its use in everyday practice for CKD patients is scarce. This article describes the basic principles and methodology of CPET and provides an overview of important studies that utilized CPET in patients with ESKD, in an effort to increase awareness of CPET capabilities among practicing nephrologists.

Gas exchange inefficiency and dynamic hyperinflation contributes to exercise limitation in chronic obstructive pulmonary disease (COPD). It is also characterized by an elevated fraction of physiolo...

International audience; Introduction: Exercise limitation in chronic obstructive pulmonary disease (COPD) is multi-factorial; however, growing evidence indicates that muscle dysfunction may contribute in some patients.Areas covered: This work outlines current evidence for and against increased peripheral muscle fatigability in COPD through a comprehensive review of relevant literature available on PubMed/MEDLINE until May 2020. The authors first discuss key methodological issues relative to muscle fatigue assessment by non-volitional techniques, particularly magnetic stimulation. The authors then provide a detailed discussion of critical studies to have objectively measured skeletal muscle fatigue in individuals with COPD.Expert opinion: Current evidence indicates that localized (knee extension) and cycling exercise are associated with increased quadriceps fatigability in most COPD patients. Increased fatigability, however, has not been consistently found in response to walking, likely reflecting the tendency of 'central' respiratory constraints to overshadow potential functional impairments in the appendicular muscles in this form of exercise. Thus, addressing skeletal muscle abnormalities may be critical to translate improvements in lung mechanics (e.g., due to bronchodilator therapy) into better exercise tolerance. The positive effects of pulmonary rehabilitation on muscle fatigability are particularly encouraging and suggest a role for these measurements to test the efficacy of emerging adjunct training strategies focused on the peripheral muscles.

Mitral annular calcification (MAC) is increasingly encountered, particularly among the elderly and those with chronic kidney disease, and is often associated with a transvalvular gradient. In contrast to rheumatic mitral stenosis relatively little is known about mitral stenosis due to MAC. We aimed to clarify whether exercise limitation in this group is primarily due to valvular obstruction or ventricular dysfunction resulting from multiple comorbidities. 20 patients with severe MAC (bulky calcium deposits which restricted leaflet motion) were submitted to supine bicycle exercise, measuring Doppler and echocardiographic parameters at baseline and during exercise. They were compared 1:1 to subjects matched for age, sex, and left ventricular wall thickness. At baseline MAC subjects had higher mean mitral valve gradients (MVG) than comparison subjects (7.5 ± 3.8 vs 1.6 ± 0.8 mm Hg, p 60 mm Hg. MAC subjects also had relative chronotropic incompetence. Patients with severe MAC and a transvalvular gradient experience large increases in MVG and pulmonary pressure with exercise, similar to what has been described in rheumatic mitral stenosis. MAC may be an under-recognized cause of dyspnea and exercise intolerance in older patients.

We describe the respiratory complications of bronchopulmonary dysplasia (BPD) in childhood and adolescence. The pathophysiology of bronchopulmonary dysplasia has evolved in the era of modern neonatal intensive care. In this review, we aim to summarise the contemporary evidence base and describe the common respiratory morbidities related to BPD including; home oxygen therapy, rehospitalisation, asthma and exercise limitation.

Las pruebas de función pulmonar evalúan los volúmenes y capacidades pulmonares, la resistencia de la vía aérea y la respuesta del sistema respiratorio al ejercicio. El objetivo de este artículo es abordar fisiológicamente la realización e interpretación de las pruebas dinámicas, la curva flujo-volumen y la caminata de los 6 minutos. Tanto en las pruebas dinámicas como en la curva flujo – volumen se refleja la resistencia de la vía aérea, aquellos factores que influyen en la resistencia afectarán los resultados de estas pruebas. El ejercicio produce un aumento del flujo sanguíneo pulmonar y de la ventilación alveolar, fenómenos que normalmente no deberían producir alteración de la conducción y difusión del O2 a los tejidos y del CO2 hacia el aire alveolar. La caminata de los 6 minutos no permite identificar las causas de la limitación al ejercicio, pero permite la valoración global de la tolerancia al ejercicio de una persona.

Pulmonary arterial hypertension (PAH) is a chronic disease that is associated with a significant and progressive limitation of exercise tolerance. The pathophysiological mechanisms of exercise intolerance during exercise are complex, multifactorial, and in fact not limited to the pulmonary circulation and the right ventricle. Disturbance of autonomic nervous function leads to an enhanced chemosensitivity, as well as respiratory and peripheral muscle weakness, and systemic endothelial dysfunction, which together play important roles in PAH pathophysiology and symptomatology. This article is focused on the different pathophysiological mechanisms of exercise intolerance in PAH, their interactions, and their relevance for clinical practice.

We examine 2 means by which the healthy respiratory system contributes to exercise limitation. These include the activation of respiratory and locomotor muscle afferent reflexes, which constrain blood flow and hasten fatigue in both sets of muscles, and the excessive increases in pulmonary vascular pressures at high cardiac outputs, which constrain O2 transport and precipitate maladaptive right ventricular remodeling in endurance-trained subjects.

Pulmonary arterial hypertension (PAH) is a pulmonary vasculopathy that causes right ventricular dysfunction and exercise limitation and progresses to death. New findings from translational studies have suggested alternative pathways for treatment. These avenues include sex hormones, genetic abnormalities and DNA damage, elastase inhibition, metabolic dysfunction, cellular therapies, and anti-inflammatory approaches. Both novel and repurposed compounds with rationale from preclinical experimental models and human cells are now in clinical trials in patients with PAH. Findings from these studies will elucidate the pathobiology of PAH and may result in clinically important improvements in outcome.

Background Although various determinants of exercise limitation in Fontan patients have been studied, most research has been performed in patients who underwent different surgical procedures with differing haemodynamic characteristics. The aim of the current study was to evaluate non-invasively measured cardiovascular parameters and their influence on exercise performance in paediatric Fontan patients with an extracardiac conduit and moderate-good systolic ventricular function. Methods Fontan patients, between 8 and 18 years of age, with moderate to good systolic ventricular function and an extracardiac conduit were included. Exercise performance and cardiovascular assessment, comprising echocardiography, aortic stiffness measurement and ambulatory measurement of cardiac autonomous nervous activity were performed on the same day. Healthy subjects served as controls. Results Thirty-six Fontan patients (age 14.0 years) and thirty-five healthy subjects (age 12.8 years) were included. Compared to controls, Fontan patients had reduced diastolic ventricular function and increased arterial stiffness. No differences were found in heart rate (HR) and cardiac parasympathetic nervous activity. In Fontan patients, maximal as well as submaximal exercise capacity was impaired, with the percentage of predicted capacity ranging between 54 and 72%. Chronotropic competence, however, was good with a peak HR of 174 (94% of predicted). Lower maximal and submaximal exercise capacity was correlated with a higher HR at rest, higher pulse wave velocity of the aorta and a lower ratio of early and late diastolic flow velocity. Conclusion Contemporary paediatric Fontan patients have an impaired exercise capacity with preserved chronotropic competence. Exercise performance correlates with heart rate at rest, diastolic function and aortic stiffness.

Physiological effects of high-flow nasal cannula (HFNC) were suspected to be useful to reverse or limit some pathological problems leading to exercise limitation in chronic respiratory disease, above all in patients affected by chronic obstructive pulmonary disease (COPD). In particular the improvement of ventilatory efficiency by reducing dead-space ventilation, the ability to keep constant the FiO2 and the increase of expiratory resistances could be advantageous in this subgroup of patients with a limited exercise capacity. The short-time effect of HFNC was shown to improve exercise endurance in a subset of patients with moderate-to-severe airway obstruction. When this intervention is applied to a training program, it leads to a significant improvement of walking distance but not of the endurance time. Little evidences show usefulness of HFNC in improving walking in very dependent COPD patients. One important limit for the application of this technology during effort is represented by the absence of an internal battery. More studies are needed to define the best application of HFNC in pulmonary rehabilitation.

Patients with chronic obstructive pulmonary disease receive a range of treatments including but not limited to inhaled bronchodilators, inhaled and systemic corticosteroids, supplemental oxygen, and pulmonary rehabilitation. Pulmonary rehabilitation is a multidisciplinary intervention that seeks to combine patient education, exercise, and lifestyle changes into a comprehensive program. Programs 6 to 8 weeks in length have been shown to improve health, reduce dyspnea, increase exercise capacity, improve psychological well-being, and reduce healthcare utilization and hospitalization. Although the use of pulmonary rehabilitation is widely supported by the literature, controversy still exists regarding what should be included in the programs. The goal of this review was to summarize the evidence for pulmonary rehabilitation and identify the areas that hold promise in improving its utilization and effectiveness.

Introduction: Children with congenital cardiac disease may require surgery via sternotomy. Residual cardiac pathology can limit exercise, but sternotomy may alter thoracic cage dynamics, causing breathing pattern disorders (BPD) and exercise limitation. Cardiopulmonary exercise testing (CPET) allows objective assessment of exercise capacity and BPD. Aim: To assess if BPDs contribute to exercise limitation in patients with total cavopulmonary connection (TCPC). Methods: Retrospective audit of children with TCPC who underwent incremental maximal CPET for exercise limitation over 5 years (2011-2015) at Royal Brompton Hospital, London. Medical record data was extracted & analysed via SPSS software. Results: 13 patients (8 male; mean age 10.7yrs [7-15]) had TCPC & subsequent CPET (treadmill; Bruce protocol). All reached AT but 8 (62%) had exercise limitation with early AT & low VO2 peak. 3 (23%) had low ventilatory reserve, indicating ventilatory limitation; all others were cardiovascularly limited. 6 (46%) demonstrated BPD: 4 (67%) had hyperventilation syndrome; 2 (33%) had large VT without tachypnoea. Baseline spirometry & ventilatory limitation did not predict BPD on CPET. Conclusions: Our data shows nearly 50% of children with TCPC have BPD, possibly adding to exercise limitation. BPD are under-recognized in this group and longitudinal studies are required to assess specialist physiotherapy intervention.

Introduction: TBM is defined by a 50% reduction of the trachea lumen during expiration. However, no data supports this threshold and it may not reflect exercise limitation. The aim of our study was to assess whether endoscopic morphometric parameters could predict exercise limitation in these patients. Methods: We reviewed all the endoscopic recordings of patients referred in our center for the clinical management of TBM between January 2017 and January 2019. For each patient, we measured: the decrease in lumen area (DLA) from inspiration to expiration, the angulation α between the posterior and the lateral wall during expiration as well as the anteroposterior distance (apD). These measurements were made during tidal breathing (TB) and during forced vital capacity maneuvers (FVC). These measurements were compared to the 6-minute walking distance (6MWD) whilst self-venting. Results: We included 16 patients. The DLA was 24±8% during TB and 38±10% during FVC (p Conclusion: The 50% expiratory collapse commonly used to diagnose TBM is poorly correlated to exercise limitation. Airway collapse during TB is correlated to the 6MWD and therefore may be a more relevant marker of the burden of the disease.

Purpose Clinical cardiopulmonary exercise testing can determine causes of exercise limitation. The slope of heart rate (fC) versus oxygen uptake (V˙O2), which we call the chronotropic index (CI), can help identify cardiovascular impairment. We aimed to develop a reference equation for CI based on a large number of subjects considered to have normal exercise responses. Methods From a database of 13,728 incremental cycle ergometry exercise tests, we identified 1280 normal tests based on the absence of a clinical diagnosis, normal body mass index, and normal aerobic performance plus absence of cardiovascular disease, medications, or ventilatory limitation. A linear mixed-model approach was used to analyze the relationship between CI and other variables. Results Subjects were age 18-84 yr, and 693 (54.1%) were men. Mean ± SD CI in men was lower than in women, 41.2 ± 9.3 beats per liter versus 63.4 ± 15.7 L. Age (in years), sex (0, male; 1, female), height (in centimeters), and weight (in kilograms) were significant predictors for CI:CIi = 106.9 + 0.16 × agei + 14.3 × sexi - 0.31 × heighti - 0.24 × weighti. The SE of estimates ranged from 10.6 to 11.2 L (median of 10.7 L). Conclusions We report a reference equation for CI derived from normal subjects. The CI can be used in conjunction with V˙O2max to interpret maximal cardiopulmonary exercise tests. We consider a high CI to be cardiovascular impairment and a low CI plus low V˙O2max to be chronotropic insufficiency.

AIMS Peak exercise oxygen uptake (VO2 ) and cardiac output (CO) are strong prognostic indexes in heart failure (HF) but unrelated to real-life physical activity, which is associated to submaximal effort. METHODS AND RESULTS We analysed maximal cardiopulmonary exercise test with rest, mid-exercise, and peak exercise non-invasive CO measurements (inert gas rebreathing) of 231 HF patients and 265 healthy volunteers. HF patients were grouped according to exercise capacity (peak VO2

Annual review exercise testing is recommended by the Cystic Fibrosis (CF) Trust. Testing to date has focused on evaluating aerobic fitness, a key prognostic indicator. Tests available range from simple field tests, to comprehensive evaluations of aerobic exercise (dys)function – cardiopulmonary exercise testing (CPET).‘Field tests’, although easy to perform are limited in the information they provide. Whereas CPET, the ‘gold standard’ measure of aerobic fitness, is recommended as the first choice exercise test by the European CF Society Exercise Working Group. CPET offers a precise cardiovascular, respiratory and metabolic evaluation of exercise capacity, including assessment of mechanism(s) of exercise limitation.

PURPOSE Although it has been well documented that the progressive exercise limitation associated with chronic obstructive pulmonary disease can be helped with an assistive device, such as a rollator, many individuals use it infrequently. This study seeks to explore the views of individuals with chronic obstructive pulmonary disease regarding the use of rollators. METHODS A qualitative study design was used. Twelve individuals with moderate to very severe chronic obstructive pulmonary disease were recruited from an outpatient pulmonary rehabilitation program to participate in semistructured interviews. Inductive thematic analysis was applied. RESULTS Analysis revealed 5 themes: (1) "acquiring a rollator" reflecting the process of obtaining a device either via a health care professional or self-referral; (2) "acceptance versus resistance" describing opposing views regarding rollator usage; (3) "rollator roadblocks" describing practical barriers to use; (4) "participation" reflecting how rollators can promote reintegration into society; and (5) "revising perceptions" whereby participants embodied an eventual acceptance of rollators. CONCLUSION Rollator acquisition appeared to be a unilateral, prescriptive process. Individuals described initial resistance to use, although in the long-term, negative perceptions were outweighed by the functional and social benefits of rollator use. Encouraging users to participate in deciding whether to use a rollator and providing adequate education on its indications, benefits, barriers, and facilitators are likely to promote optimal use of a rollator.

Resume Introduction Les etudes portant sur l’aptitude aerobie sous-maximale des patients atteints de polyarthrite rhumatoide sont quasi-inexistantes. Objectif principal Evaluer l’aptitude aerobie sous-maximale chez ces patients, a travers les donnees du test de marche de 6 minutes, et l’âge estime de la chaine cardiorespiratoire et musculaire. Methodes Trente-sept patients consecutifs, âges entre 20 et 60 ans et ayant une polyarthrite rhumatoide nouvellement diagnostiquee seront inclus. Les criteres de non-inclusion seront : la prise de medicaments (methotrexate, betabloquants…), des antecedents orthopediques ou rhumatologiques autres que la polyarthrite rhumatoide qui genent la marche, des infections recentes. Les criteres d’exclusion seront : les contre-indications du test de marche et la realisation imparfaite des manœuvres pratiques demandees. Les signes d’intolerance a la marche seront : arret lors du test, distance parcourue inferieure a la limite inferieure de la normale, dyspnee en fin de test ≥ 5/10 sur une echelle visuelle analogique, chute de la saturation de l’hemoglobine en oxygene (SpO 2 ) ≥ 5 %, frequence cardiaque en fin du test ≤ 60 % de la theorique maximale. Un âge estime de la chaine cardiorespiratoire et musculaire superieur a l’âge chronologique sera un signe d’acceleration du vieillissement. Resultats attendus Un pourcentage eleve de patients atteints de polyarthrite rhumatoide exprimerait des signes d’intolerance lors de la marche. Nous etablirons la correlation entre les donnees du test de marche de 6 minutes et les parametres cliniques, biologiques, radiologiques et fonctionnels respiratoires, ainsi que la qualite de vie.

Background: The impact of hyperoxia on exercise limitation is still incompletely understood. Objectives: We investigated to which extent breathing hyperoxia enhances the exercise performance of healthy subjects and which physiologic mechanisms are involved. Methods: A total of 32 healthy volunteers (43 ± 15 years, 12 women) performed 4 bicycle exercise tests to exhaustion with ramp and constant-load protocols (at 75% of the maximal workload [Wmax] on FiO2 0.21) on separate occasions while breathing ambient (FiO2 0.21) or oxygen-enriched air (FiO2 0.50) in a random, blinded order. Workload, endurance, gas exchange, pulse oximetry (SpO2), and cerebral (CTO) and quadriceps muscle tissue oxygenation (QMTO) were measured. Results: During the final 15 s of ramp exercising with FiO2 0.50, Wmax (mean ± SD 270 ± 80 W), SpO2 (99 ± 1%), and CTO (67 ± 9%) were higher and the Borg CR10 Scale dyspnea score was lower (4.8 ± 2.2) than the corresponding values with FiO2 0.21 (Wmax 257 ± 76 W, SpO2 96 ± 3%, CTO 61 ± 9%, and Borg CR10 Scale dyspnea score 5.7 ± 2.6, p < 0.05, all comparisons). In constant-load exercising with FiO2 0.50, endurance was longer than with FiO2 0.21 (16 min 22 s ± 7 min 39 s vs. 10 min 47 s ± 5 min 58 s). With FiO2 0.50, SpO2 (99 ± 0%) and QMTO (69 ± 8%) were higher than the corresponding isotime values to end-exercise with FiO2 0.21 (SpO2 96 ± 4%, QMTO 66 ± 9%), while minute ventilation was lower in hyperoxia (82 ± 18 vs. 93 ± 23 L/min, p < 0.05, all comparisons). Conclusion: In healthy subjects, hyperoxia increased maximal power output and endurance. It improved arterial, cerebral, and muscle tissue oxygenation, while minute ventilation and dyspnea perception were reduced. The findings suggest that hyperoxia enhanced cycling performance through a more efficient pulmonary gas exchange and a greater availability of oxygen to muscles and the brain (cerebral motor and sensory neurons).

Congenital heart disease (CHD)-related heart failure is common and associated with significant morbidity, mortality, and resource utilization. In adults with CHD (ACHD), exercise limitation is often underestimated. Quantitative assessment with cardiopulmonary exercise testing (CPET) provides a comprehensive evaluation of exercise capacity and can help risk stratify patients, particularly across serial testing. CPET parameters must be interpreted within the context of the underlying anatomy, specifically for patients with either single ventricle physiology and/or cyanosis. Acknowledging differences in CPET parameters between ACHD and non-ACHD patients with heart failure are also important considerations when evaluating the overall benefit of advanced heart failure therapies. CPET testing can also guide safe exercise recommendation, including those with ACHD-related heart failure.

Introduction Left Ventricular Assist Devices (LVAD) improve survival and functional capacity in patients with advanced heart failure (HF). However, there are potential complications. Purpose We sought to determine parameters of exercise intolerance in a group of patients with the HeartWare LVAD (HVAD) compared to a group of HF patients. Methods This was a single-centre parallel prospective group-study. Briefly, echocardiograms, right heart catheterisation (RHC) and cardiopulmonary exercise tests were performed in forty-two patients admitted for a heart transplant assessment between August2017 and October2018.Of them 20 belonged to the HVAD group and 22 to the HF group. Results In our study, HVAD patients had a better exercise capacity than HF patients, although no significant differences were noted (14.0±5.0 ml/kg/min vs 11.3±3.9 ml/kg/min, p=0.06). To determine exercise tolerance, both HVAD and HF groups were subdivided into 2 groups based on the median peak exercise oxygen consumption (peakVO2) for that group. The table shows the comparison between preserved and non-preserved exercise tolerance in HF and HVADpatients. First of all, in the HVADgroup, all resting RHC pressures were significantly lower in the preserved exercise capacity group. However, in HFpatients there were no statistically significant differences between both subgroups in right-sided pressures, but Thermodilution exercise-induced change in cardiac output (ΔCO) and cardiac index (ΔCI) was significantly higher in the patients with preserved exercise tolerance. Secondly, in the HVADgroup the right ventricle was significantly larger in the reduced exercise tolerance subgroup. Moreover, patients with lower peak VO2 had more significant tricuspid regurgitation. Nevertheless, in HFpatients none of the echocardiographic parameters were related to the exercise capacity. HF HVAD > Median Peak V02 < Median Peak V02 p > Median Peak V02 < Median Peak V02 p Thermodilution CO, l/min: • Rest 4.3±1.0 4.4±1.8 0.82 4.8±0.8 4.2±1.2 0.21 • Exercise 5.6±1.7 4.8±1.8 0.36 7.1±3.2 4.8±0.8 0.05 • ΔCO 1.26±1.0 0.26±0.7 0.02 2.2±2.5 0.4±0.7 0.05 Right Atrium pressure, mmHg 7.0±4.5 6.8±4.10 0.92 4.3±3.2 10.6±6.40 0.02 Mean Pulmonary Artery pressure, mmHg 26.4±12.6 26.5±10.9 0.97 16.8±5.4 30.5±12.5 0.01 Tricuspid Regurgitation, n (%): • None 1 (9) 1 (9) 1 (12) 0 (0) • Mild 7 (64) 8 (73) 7 (88) 4 (44) • Moderate 2 (18) 0 (0) 0 (0) 4 (44) • Severe 1 (9) 2 (18) 0.36 0 (0) 1 (12) 0.03 Right Ventricle Basal Diastolic Diameter, cm 4.0±1.0 4.1±1.0 0.83 3.7±0.5 4.4±0.5 0.02 Conclusion Right-sided parameters in the echocardiogram and RHC pressures discriminate between preserved and non-preserved exercise capacity in HVADpatients, but not in HFpatients. In these last patients only ΔCO and ΔCI were statistically correlated with peak exercise oxygen consumption Acknowledgement/Funding N. Bouzas-Cruz would like to thank the Spanish Society of Cardiology (Sociedad Española de Cardiología), for her research grant and fellowship

Introduction: Although pulmonary endarterectomy (PEA) in chronic thromboembolic pulmonary hypertension (CTEPH) is a highly effective treatment with significant improvements in hemodynamics and right ventricular function, persistent exercise limitation is frequent with many unknowns regarding its mechanisms. Aims: In an observational analysis we aimed to analyze the changes in exercise parameters post-PEA and identify persistent exercise pathology typical for CTEPH. Methods: We analyzed 68 CTEPH patients with cardiopulmonary exercise testing 6 months post-PEA. Results: 6 months post-PEA max load and peakVO2 significantly improved compared to baseline; circulatory and gas exchange parameters (O2 pulse, PETCO2, VE/VCO2, SpO2) improved, while ventilatory parameters remained unchanged. 42/68 (62%) had persistent exercise limitation 6 months post-PEA (peakVO2 Conclusions: In 68 CTEPH patients exercise capacity significantly improved after PEA; improvements were mainly in the circulatory and gas exchange domain. Persistent exercise limitation was frequent and mainly due to cardiocirculatory pathology. Signs typical of pulmonary vascular limitation during exercise were frequent after PEA in CTEPH.

Proper adjustment of the arterial oxygen saturation (SaO2) during daily activities in ILD patients requiring oxygen therapy is challenging. Arterial blood analysis at rest is not representative of an adequate SaO2 during exercise. Six-minute walk test (6MWT) results complicated for some patients with exercise limitation and may not represent their real oxygen needs. We sought to assess the correlation of different SaO2 parameters measured with a home oxymeter for 48 hours compared to the standard monitoring performed during the 6MWT in ILD patients with and without oxygen therapy. We conducted a prospective observational study in patients with ILDs. After a clinical characterization, we provided a portable oximeter (NONIN WristOx2 3150) to monitor the patient during 48 hours. Subsequently, 6MWT was performed to compare SaO2 parameters to those obtained during home monitoring. We divided patients into two groups according to whether or not they have home oxygen prescribed. We included 30 patients with different ILDs, half of them on oxygen therapy. We observed a lower mean SaO2 (%) during the 6MWT compared with daily activities monitored by an oxymeter [Non-OT: 90 +/-5 vs 93 +/-2(p= 0.015); OT: 87+/-4 vs 91+/-2(p 6MWT may overestimate the oxygen needs required in ILDs as compared with daily activities. Oxygen home monitoring may be a future tool to assess SaO2 during “real life” activities

Rationale: Dyspnea and exercise limitation are common symptoms in Systemic Sclerosis (SSc) patients. Multiorgan involvement and disease activity could lead patients to different clinical complications and affect prognosis. Aim of this study was to explore the role of cardiopulmonary exercise test (CPET) in the evaluation of exercise limitation and in the characterization of specific phenotypes of organ involvement in SSc patients. Methods: 24 consecutive patients (23 women, 51.3 ± 2.0 mean age) diagnosed with clinically stable SSc (EULAR 2013) underwent resting echocardiography and maximal symptom-limited incremental CPET. Patients were categorized into three groups: A (interstitial lung disease on CT scan), B (pulmonary vascular diesase), C (left ventricular dysfunction). Results were compared with those of 23 healthy controls and among SSc groups. Results: Compared to controls, SSc patients exhibited a significant reduction in functional capacity, ventilatory limitation and a higher estimated pulmonary pressure at echocardiography. Group A (3 patients) exhibited reduced ventilation, lower VO2max, higher PetCO2, and a worse oxygen uptake efficiency slope. Group B (6 patients) was charaterized by higher VE/VCO2 slope, reduced exercise capacity and a peculiar breathing pattern with the presence of exercise oscillatory ventilation. Group C (15 patients) showed lower ventilation, VO2max and VO2/work slope. Conclusion: CPET can unmask early exercise limitation and can be useful in the identification of different clinical phenotypes in SSc patients.

We sought to investigate the role of group III/IV muscle afferents in limiting endurance exercise performance, independently of their role in optimizing locomotor muscle O2 delivery. While breathing 100% O2 to ensure a similar arterial O2 content ([Formula: see text]) in both trials, eight male cyclists performed 5-km time trials under control conditions (HCTRL) and with lumbar intrathecal fentanyl (HFENT) impairing neural feedback from the lower limbs. After each time trial, common femoral artery blood flow (FBF) was quantified (Doppler ultrasound) during constant-load cycling performed at the average power of the preceding time trial. The assessment of end-tidal gases, hemoglobin content and saturation, and FBF facilitated the calculation of leg O2 delivery. Locomotor muscle activation during cycling was estimated from vastus lateralis EMG. With electrical femoral nerve stimulation, peripheral and central fatigue were quantified by pre- to postexercise decreases in quadriceps twitch torque (ΔQtw) and voluntary activation (ΔVA), respectively. FBF (~16 mL·min−1·W−1; P = 0.6), [Formula: see text] (~24 mL O2/dL; P = 0.9), and leg O2 delivery (~0.38 mL O2·min−1·W−1; P = 0.9) were not different during HCTRL and HFENT. Mean power output and time to completion were significantly improved by 9% (~310 W vs. ~288 W) and 3% (~479 s vs. ~463 s), respectively, during HFENT compared with HCTRL. Quadriceps muscle activation was 9 ± 7% higher during HFENT compared with HCTRL ( P < 0.05). ΔQtw was significantly greater in HFENT compared with HCTRL (54 ± 8% vs. 39 ± 9%), whereas ΔVA was not different (~5%; P = 0.3) in both trials. These findings reveal that group III/IV muscle afferent feedback limits whole body endurance exercise performance and peripheral fatigue by restricting neural activation of locomotor muscle. NEW & NOTEWORTHY Group III/IV muscle afferent feedback facilitates endurance performance by optimizing locomotor muscle O2 delivery but also limits performance by restricting neural drive to locomotor muscle. To isolate the performance-limiting effect of these sensory neurons, we pharmacologically attenuated their central projection during a cycling time trial while controlling for locomotor muscle O2 delivery. With no difference in leg O2 delivery, afferent blockade attenuated the centrally mediated restriction in motoneuronal output and improved cycling performance.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, with pulmonary and extra-pulmonary factors contributing to exercise intolerance. The primary self-reported exercise-limiting symptom may reflect the primary pathophysiological factor contributing to exercise intolerance. We compared physiological and perceptual responses at the symptom-limited peak of incremental cardiopulmonary cycle exercise testing between people with COPD reporting breathlessness (B, n = 34), leg discomfort (LD, n = 16), or a combination of B and LD (BOTH, n = 42) as their main exercise-limiting symptom(s). Despite similarly impaired health status, symptomology and peak exercise capacity, the B group had greater restrictive constraints on tidal volume expansion at end-exercise and was more likely to report unpleasant qualities of exertional breathlessness than LD and BOTH groups. In conclusion, reporting breathlessness as the primary exercise-limiting symptom indicated the presence of distinct lung pathophysiology and symptom perception during exercise in people with COPD. Refereed/Peer-reviewed

Background: A poor relationship between perceived respiratory symptoms and objective evidence of exercise-induced bronchoconstriction (EIB) in athletes is often reported; however, the reasons for this disconnect remain unclear. The primary aim of this study was to utilise a qualitative-analytical approach to compare respiratory symptoms in athletes with and without objectively confirmed EIB.Methods: Endurance athletes who had previously undergone bronchoprovocation test screening for EIB were divided into sub-groups, based on the presence or absence of EIB ± heightened self-report of dyspnoea: (i) EIB-Dys- (ii) EIB þ Dysþ (iii) EIB þ Dys- (iv) EIB-Dysþ. All athletes underwent a detailedsemi-structured interview.Results: Twenty athletes completed the study with an equal distribution in each sub-group (n=5).Thematic analysis of individual narratives resulted in four over-arching themes: 1) Factors aggravating dyspnoea, 2) Exercise limitation, 3) Strategies to control dyspnoea, 4) Diagnostic accuracy. Theanatomical location of symptoms varied between EIB + Dys + athletes and EIB-Dys + athletes. All EIB-Dys + reported significantly longer recovery times following high-intensity exercise in comparison to all other sub-groups. Finally, EIB + Dys + reported symptom improvement following beta-2 agonist therapy,whereas EIB-Dys + deemed treatment ineffective.Conclusion: A detailed qualitative approach to the assessment of breathlessness reveals few features that distinguish between EIB and non-EIB causes of exertional dyspnoea in athletes. Important differencesthat may provide value in clinical work-up include (i) location of symptoms, (ii) recovery time following exercise and (iii) response to beta-2 agonist therapy. Overall these findings may inform clinical evaluation and development of future questionnaires to aid clinic-based assessment of athletes withdyspnoea.

Purpose To determine parameters of exercise intolerance in a group of patients with HeartWare Ventricular Assist Device(HVAD) compared to a group of heart failure(HF)patients Methods This was a single-centre parallel prospective group-study.Echocardiograms,right heart catheterisation(RHC) and cardiopulmonary exercise tests were performed in 42patients admitted for a heart transplant assessment between August2017 and October2018:20 belonged to the HVAD group and 22 to the HF group Results HVADpatients had a better exercise capacity than HFpatients, although no significant differences were noted(14.0±5.0ml/kg/min vs 11.3±3.9ml/kg/min, p=0.06).To determine exercise tolerance,both HVAD and HFgroups were subdivided into 2 groups based on the median peakVO2.The table shows the comparison between preserved and non-preserved exercise tolerance in HF and HVADpatients. In the HVAD group,all resting RHC pressures were significantly lower in the preserved exercise capacity group.However,in HFpatients there were no statistically significant differences between both subgroups in right-sided pressures,but Thermodilution exercise-induced change in cardiac output(ΔCO) and cardiac index(ΔCI) was significantly higher in the patients with preserved exercise tolerance.In the HVADgroup the right ventricle was significantly larger in the reduced exercise tolerance subgroup.Patients with lower peakVO2 had more significant tricuspid regurgitation.Nevertheless,in HFpatients none of the echocardiographic parameters were related to the exercise capacity Conclusion Right-sided parameters in the echocardiogram and RHC pressures discriminate between preserved and non-preserved exercise capacity in HVADpatients,but not in HFpatients.In these last patients only ΔCO and ΔCI were statistically correlated with peak exercise oxygen consumption.

Background: Sensitivity and specifity of Wasserman’s cardio-pulmonary exercise test (CPET) protocol for categorization of mechanism of dyspnea/exercise limitation was studied Material and Methods: Patients with unexplained dyspnea/exercise limitation referred to our pulmonary lab for CPET from March to December 2017 with at least three-month follow-up by their physicians were included. The Wasserman’s CPET categorization compared with physician diagnosis after three-month follow-up. Results: 83(44 female, 39 male, age=41.7y) had completed the study. Figure 1 shows patient’s categorization by Wasserman’s protocol and clinicians’ follow-up. Protocol sensitivity and specifity for cardiovascular disease was 66.67% ;75.32% respectively. It9s sensitivity and specifity for pulmonary disease was 32.14% ; 92.73% respectively. Overall agreement between protocol and physician diagnosi was 31.33 (Kappa=0.12). Discussion: Wasserman’s protocol has been proposed to direct physicians to determine which organ/system could be responsible for dyspnea/exercise limitation. It has been used for ease of CPET interpretation. However, disregarding clinical data and many of the expected trends for multiple variables over the course of progressive exercise in any protocol could be misleading in many situations. Further work is needed to define new parameters or new cut of points to improve CPET interpretation protocols. Also, alternative methods such as pattern recognition could be used by more experinced physicians for CPET interpretation.

Exercise tolerance may be significantly impaired in severe COPD. NIV increases the walking distance; however a 35% of patients do not tolerate it (Walker DJ et al. COPD 2015;1:546-51). Recently, it has been demonstrated that high flow nasal cannula (HFNC) improves the endurance time in severe COPD patients (Cirio S et al. Respir Med. 2016 Sep;118:128-132). However, the lack of an internal battery has limited its use for moving. Our study aimed to investigate if HFNC powered by an external battery increases the walking distance in COPD patients with exercise limitation. Thirteen stable COPD patients with a walking distance lower than 70% of predicted value associated to a modified Borg dyspnea SB ≥5 at 6-minute walk test (6MWT), were included. They performed two consecutive 6MWTs, in a randomised cross-over design: with and without HFNC at the same oxygen inhaled fraction. Twelve patients (one dropped-out) (mean ±SD age 69.5 ±10.3 yrs, forced expiratory volume in 1 second 25±5.6% predicted) were analysed. Walking distance was significantly higher using HFNC (median 306m (IQR 246-342) compare to no-HFNC (267m (IQR 228-294) (p In conclusion, HFNC may be safely used also during walking. In severe COPD with exercise limitation it improves the walking distance without worsening of dynamic hyperinflation.

Local symptoms of chronic venous insufficiency after deep vein thrombosis (DVT) are well described, but little is known about the effect of residual venous obstruction on exercise capacity. We tested our hypothesis that chronic residual iliofemoral vein occlusion (IFVO) after DVT may impair exercise capacity. Nine post-DVT patients with residual IFVO and effort intolerance were studied; a comparison cohort consisted of 11 healthy volunteers. Exercise tolerance was assessed by bimodality incremental symptom-limited cardiopulmonary testing, using leg and arm ergometers. In healthy subjects, leg vein obstruction was modelled by application to the thighs of cuff tourniquets inflated to 30-40 mmHg. Leg exercise tolerance as measured by oxygen uptake at peak exercise (peak ⩒'O

Background Little data exist regarding the functional capacity of patients following acute pulmonary embolism. We sought to characterize the natural history of symptom burden, right ventricular ( RV ) structure and function, and exercise capacity among survivors of massive and submassive pulmonary embolism. Methods and Results Survivors of submassive or massive pulmonary embolism (n=20, age 57±13.3 years, 8/20 female) underwent clinical evaluation, transthoracic echocardiography, and cardiopulmonary exercise testing at 1 and 6 months following hospital discharge. At 1 month, 9/20 (45%) patients had New York Heart Association II or greater symptoms, 13/20 (65%) demonstrated either persistent RV dilation or systolic dysfunction, and 14/20 (70%) had objective exercise impairment as defined by a peak oxygen consumption ( V ˙ O 2 ) of RV structure or function, and peak V ˙ O 2 (17.45 [14.08–22.48] mL/kg per minute, P = NS ) were observed. No patients demonstrated an exercise limitation attributable to either RV /pulmonary vascular coupling, as defined by a VE / VCO 2 slope >33, or a pulmonary mechanical limit to exercise at either time point. Similarly, persistent RV dilation or dysfunction was not significantly related to symptom burden or peak V ˙ O 2 at either time point. Conclusions Persistent symptoms, abnormalities of RV structure and function, and objective exercise limitation are common among survivors of massive and submassive pulmonary embolism. Functional impairment appears to be attributable to general deconditioning rather than intrinsic cardiopulmonary limitation, suggesting an important role for prescribed exercise rehabilitation as a means toward improved patient outcomes and quality of life.

The origin of fatigue has been the focus of studies involved in sports performance, due to the necessity to clarify the mechanistic bases for the reduced capacity to perform considerable effort intensities. According to the traditional conception of fatigue, mechanisms may encompass peripheral and central sites of fatigue. Peripheral fatigue is understood as events related to an inefficient tissue oxygen delivery, metabolic accumulation, muscular acidosis and muscle substrate depletion. In contrast, the central fatigue is mostly related to events in the central nervous system (CNS) that may involve neurotransmitters changes, altered metabolic profile and elevated temperature. Therefore, the current review aimed to discuss the peripheral and central mechanisms of fatigue, thus driving interpretations of the phenomenon. A etiologia da fadiga tem sido objeto de estudo em pesquisas relacionadas ao desempenho esportivo em função da necessidade de esclarecer os mecanismos que reduzem a capacidade de manutenção do desempenho em intensidades elevadas de esforço. A concepção tradicional de fadiga assume que os mecanismos possam ser desencadeados em sítios de ação central ou periférica. A fadiga periférica é compreendida como uma oferta inadequada de oxigênio tecidual acelerando a acidose muscular. A fadiga central, por sua vez, oriunda do sistema nervoso central (SNC), apresenta alterações nos neurotransmissores, podendo alterar o perfil metabólico e temperatura do SNC. Desta forma, a presente revisão tem como intuito abordar os mecanismos de fadiga central e periférica, norteando futuras interpretações sobre o fenômeno.

Background/Aims: Chronic obstructive pulmonary disease (COPD) is widely recognised as a multi-system disease that extends beyond the lung and can further impair functional capacity, including that of the musculoskeletal system. While it has been reported that these changes may contribute to exercise limitation and disability, there has been little research to describe the nature and extent of changes in the musculoskeletal system. Therefore, the aim of this study was to examine differences in posture, joint mobility and muscle sensitivity in subjects with COPD compared with a matched group of healthy subjects. A secondary aim was to explore whether a relationship exists between pulmonary function and musculoskeletal changes. Finally, the data were used to evaluate whether an association exists between cervicothoracic posture, joint mobility and muscle sensitivity, and having diagnosed COPD. Methods: A prospective observational study was reported in accordance with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Participants with stable COPD (n=33; mean±SD age: 67 ± 9 years; FEV1% predicted: 50.94 ±19.40%) and age-matched controls (n=55; mean±SD age: 67 ± 6 years; FEV1% predicted: 104.53 ±16.86%) were recruited from primary and secondary care sources. Pulmonary function and performance-based outcome measures (predictors) included posture, spinal joint mobility, and accessory respiratory muscle sensitivity. Sociodemographic data and confounding variables were assessed using questionnaires and performance-based measures. Results: Reduced thoracic (pConclusions: This is the first study to examine musculoskeletal changes in patients with COPD. The results show that musculoskeletal changes are evident in the cervicothoracic region and may contribute to exercise limitation and disability reported in this patient population.

Background: Stage B heart failure (SBHF) describes asymptomatic ventricular disease that may presage the development of heart failure (HF) symptoms. This entity has been largely defined by ...

Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature that leads to exercise limitation, right heart failure, and death. There is a need for biomarkers that can aid in early detection, disease surveillance, and treatment monitoring in PAH. Several potential molecules have been investigated; however, only brain natriuretic peptide is currently recommended at diagnosis and for follow-up of PAH patients. This review will focus on potential biomarkers in PAH and will discuss their pathophysiology, prognostic significance, as well as their limitations.

Respiratory muscle dysfunction is common and contributes to dyspnea and exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Improving dynamic function of respiratory muscles during exercise might help to reduce symptoms and improve exercise capacity. Areas covered: The aims of this review are to 1) summarize physiological mechanisms linking respiratory muscle dysfunction to dyspnea and exercise limitation; 2) provide an overview of available therapeutic approaches to better maintain load-capacity balance of respiratory muscles during exercise; and 3) to summarize current knowledge on potential mechanisms explaining effects of interventions aimed at optimizing dynamic respiratory muscle function with a special focus on inspiratory muscle training. Expert commentary: Several mechanisms which are potentially linking improvements in dynamic respiratory muscle function to symptomatic and functional benefits have not been studied so far in COPD patients. Examples of underexplored areas include the study of neural processes related to the relief of acute dyspnea and the competition between respiratory and peripheral muscles for limited energy supplies during exercise. Novel methodologies are available to non-invasively study these mechanisms. Better insights into the consequences of dynamic respiratory muscle dysfunction will hopefully contribute to further refine and individualize therapeutic approaches in patients with COPD.

INTRODUCTION FEV1 is often considered the gold standard to monitor lung disease in cystic fibrosis (CF). Recently, there has been increasing interest in multiple breath washout (MBW) and cardiopulmonary exercise testing (CPET) as alternative or even more sensitive techniques. However, limited data exist on associations among the above methods. AIM To evaluate the correlations between outcome measures of MBW and CPET and to examine if ventilation inhomogeneity can predict exercise intolerance. SUBJECTS AND METHODS Ninety-seven children and adults with CF (47 males, mean [range] age 14.9 (6.6; 26.7) years, mean FEV1 : 90.8% predicted, mean lung clearance index [LCI]: 11.4, and mean peak oxygen uptake [VO2 peak]: 82.4% predicted) performed spirometry, MBW, and CPET on the same day during their admission or outpatient visit. RESULTS LCI, m1 /m0 , and m2 /m0 (P