Gas Exchange and Ventilatory Efficiency During Exercise in Pulmonary Vascular Diseases

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"identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:8 [ 0 => array:3 [ "entidad" => "University of Calgary, Department of Medicine, Division of Respirology, Calgary, Alberta, Canada" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Service de Pneumologie, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Service de Physiologie, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Sorbonne Université, INSERM, UMRS1158 Neurophysiologie respiratoire expérimentale et clinique, F-75005 Paris, France" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "APHP.Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service des Explorations Fonctionnelles de la Respiration, de l’Exercice et de la Dyspnée, Hôpitaux Universitaires Pitié-Salpêtrière, Tenon et Saint-Antoine, Département Médico-Universitaire “APPROCHES”, F-75013 Paris, France" "etiqueta" => "h" "identificador" => "aff0040" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Intercambio de gases y eficiencia de ventilación durante el ejercicio en enfermedades vasculares pulmonares" ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0030" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 955 "Ancho" => 1333 "Tamanyo" => 52736 ] ] ] ] "textoCompleto" => "IntroductionThe main determinants of the exercise ventilatory response (V′E) are the pulmonary carbon dioxide (CO2) output (V′CO2), the arterial partial pressure of CO2 (PaCO2), the dead space fraction of each tidal breath (VD/VT) and the extent to which the ventilatory system is constrained by abnormal respiratory mechanics.<a class="elsevierStyleCrossRef" href="#bib0175">1</a> An indicator of the efficiency of exercise V′E is the steepness with which V′E rises with respect to VCO2, i.e., the V′E/V′CO2 slope. Pulmonary vascular disease patients often hyperventilate at rest and during exercise,<a class="elsevierStyleCrossRef" href="#bib0175">1</a> and ventilatory inefficiency (high V′E/V′CO2) is a hallmark that predicts higher mortality independent from other exercise-related prognostic factors such as peak oxygen uptake (VO2).<a class="elsevierStyleCrossRefs" href="#bib0180">2–6</a> The V′E/V′CO2 slope is fundamentally determined by two factors: (1) the tidal volume (VT) fraction going to dead space (VD), (i.e., the VD/VT); and (2) the direction and magnitude of change in the PaCO2 during exercise.A low resting PaCO2 predicts a worse prognosis in pulmonary arterial hypertension (PAH).<a class="elsevierStyleCrossRef" href="#bib0205">7</a> However, high VD/VT does not cause low resting PaCO2, therefore an altered PaCO2 set-point, increased neural respiratory drive, and/or increased chemosensitivity must explain hypocapnia and consequently, the high V′E/V′CO2 slope. The PaCO2 set-point is influenced by factors such as metabolic acidosis, hypoxemia, baroreceptors in the pulmonary vasculature and sympathetic nervous system hyperactivity.<a class="elsevierStyleCrossRefs" href="#bib0210">8–13</a> The assessment of chemosensitivity and/or the PaCO2 set-point during exercise is not straightforward and can be problematic. Few studies have attempted to evaluate the PaCO2 set-point “non-invasively” by evaluating the maximal end-tidal CO2 pressure (maximal PETCO2) value between the anaerobic threshold (AT) and respiratory compensation point (RCP) where PETCO2 is constant and, therefore, is supposed to truly reflect the real PaCO2 set-point.<a class="elsevierStyleCrossRefs" href="#bib0240">14–17</a>The aim of the study was to test the relationships between gas exchange variables that reflect high chemosensitivity and/or the PaCO2 set-point, exercise capacity and markers of disease severity in pulmonary vascular disease patients according to the presence of resting hypocapnia (PaCO2 ≤ 34mmHg) or normocapnia (PaCO2=35–45mmHg).MethodsThis retrospective study complied with the Declaration of Helsinki. Although French law does not require ethics committee approval or informed consent for retrospective data collection, the data collected were anonymized and complied according to the requirements of the Commission Nationale Informatique et Liberté (CNIL), the organization dedicated to privacy, information technology and civil rights in France.Study populationWe reviewed patients>18 years of age with PAH, chronic thromboembolic pulmonary hypertension (CTEPH), or pulmonary veno-occlusive disease (PVOD) who underwent cardiopulmonary exercise testing (CPET) with arterial blood gas (ABG) sampling at rest and maximal exercise at our institution between 2010 and 2016. All patients were diagnosed according to current guidelines with right heart catheterization. Patients were prevalent, treated with PAH therapies with clinical stability during the preceding 3 months and in New York Heart Association (NYHA) function class I–III. Patients with a history of smoking, forced expiratory volume in 1-second to forced vital capacity (FEV1/FVC) ratio <0.7, and those without peak exercise ABG measurements were excluded.CPET testingSpirometry, single breath DLCO and static lung volumes were performed on the same day prior to CPET. All patients underwent a symptom-limited incremental cycle ergometer CPET and were encouraged to continue until exhaustion. Arterial blood gas (ABG) measurements were obtained via a radial artery puncture at rest before and at peak exercise, while still pedaling. Pulmonary function tests were performed using automated equipment (Masterscreen MS Body and Diffusion, tyb B/IEC 601-1/IP20, Jaeger, Germany). Symptom-limited incremental CPETs were conducted on an electrically braked cycle ergometer (Ergoline 100P mitBD; Medisoft, Sorinnes, Belgium) with a cardiopulmonary exercise testing system (Ergocard model E, Medisoft, Sorinnes, Belgium). Breath-by-breath cardiopulmonary and metabolic data were collected at baseline and throughout exercise while subjects breathed through a mouthpiece with nasal passages occluded by a nose-clip. Exercise variables were measured and averaged over the last 20s of each minute and at peak exercise. Exercise variables were compared with predicted normal values .<a class="elsevierStyleCrossRef" href="#bib0260">18</a> The AT was determined individually using the V-slope method.<a class="elsevierStyleCrossRef" href="#bib0265">19</a> We estimated the CO2 set-point noninvasively from the highest value of end-tidal PCO2 (maximal PETCO2) observed between the AT and the RCP, when PETCO2 remains constant, as previously described (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<a class="elsevierStyleCrossRefs" href="#bib0240">14–17</a> In cases where the RCP was not clearly evident, the highest value occurring after AT was used. Ventilatory efficiency was obtained from the V′E/V′CO2 slope, which was determined for each patient using linear regression. The physiologic dead space (VD/VT) was calculated using the Enghoff modification of the Bohr equation<a class="elsevierStyleCrossRef" href="#bib0270">20</a>:<elsevierMultimedia ident="eq0005"></elsevierMultimedia>where VD=dead space volume, VT=tidal volume, PaCO2=arterial partial pressure of carbon dioxide and PECO2=mixed expired carbon dioxide partial pressure.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Statistical analysisPatients were grouped according to resting PaCO2, defined as being hypocapnic (PaCO2 ≤ 34mmHg) or normocapnic (PaCO2=35–45mmHg). Continuous variables are expressed as mean±standard deviation or median with interquartile range (IQR25–75%) according to normality. The Shapiro–Wilk test was used to assess normality of data. Categorical variables are expressed as absolute and relative frequencies. Between-group comparisons were made using two-sample t-tests, Wilcoxon rank sum tests, and the chi-squared test, where appropriate. Relationships between V′E, VD/VT, arterial-to-end-tidal PCO2 difference (P(a-ET)CO2), maximal PETCO2, resting cardiac index (CI), and V′E/V′CO2 slope were assessed using linear regression. A p-value <0.05 was considered significant. Statistical analyses were performed using STATA (version 13.1, StataCorp, College Station, Texas, USA).ResultsA total of 59 patients were included. Demographics, clinical and hemodynamic characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Compared to normocapnic patients, a greater proportion of hypocapnic patients had CTEPH or PVOD as opposed to PAH, and both DLCO/VA and CI were lower in hypocapnic patients. Peak oxygen consumption (V′O2peak) was lower and V′E/V′CO2 was higher in hypocapnic patients. Characteristics and gas exchange variables according to etiology of pulmonary hypertension are shown in <a class="elsevierStyleCrossRef" href="#sec0065">Online Supplemental Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Gas exchange variables at rest and at peak exercise are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. In hypocapnic patients, peak VD/VT did not significantly change during exercise and P(a-ET)CO2 increased, whereas VD/VT and P[a-ET]CO2 both decreased from rest to peak exercise among the normocapnic patients (<a class="elsevierStyleCrossRef" href="#sec0065">Online Supplemental Figure 1</a>). The CO2 set-point, as estimated by the maximal PETCO2 between AT and the RCP, was significantly lower among hypocapnic patients (23.6±4.1 vs. 33.8±3.7mmHg, p<0.001). In the overall population, the CO2 set-point (maximal PETCO2) was the strongest correlate of V′O2peak, peak work rate (WRpeak) and V′E/V′CO2 slope (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). V′O2peak (mL/kg/min) could be estimated from the maximal PETCO2 with the equation:<elsevierMultimedia ident="eq0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>In the overall population, the maximal PETCO2 discriminated patients with low-risk value for V′O2peak of>15mL/kg/min (area under the receiver operating curve [AUC] 0.88, 95%CI 0.79–0.96) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) and V′O2peak>65% predicted (AUC 0.64, 95% CI 0.47–0.80).<a class="elsevierStyleCrossRef" href="#bib0275">21</a> A maximal PETCO2 value of ≥25mmHg had 90% sensitivity and 72% specificity for a V′O2peak of>15mL/kg/min. The maximal PETCO2 AUC for V′O2peak of>15mL/kg/min was 0.89 in the normocapnic group and 0.77 in the hypocapnic group (<a class="elsevierStyleCrossRef" href="#sec0065">Online Supplemental Figure 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Peak V′E was related to peak exercise PaO2 (r2=0.29, p=0.02) and PaCO2 (r2=0.3, p=0.01) in normocapnic patients but not in hypocapnic patients. The V′E/V′CO2 slope was related to peak exercise VD/VT, P(a-ET)CO2 and maximal PETCO2 in hypocapnic patients but not significantly correlated to VD/VT in normocapnic patients (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The VD/VT and P(a-ET)CO2 at peak exercise and PETCO2 max correlated with resting CI only in hypocapnic patients (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). Maximal PETCO2 modestly correlated with resting CI but to a greater extent than resting or peak exercise PaCO2 in the overall population (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). In hypocapnic patients, maximal exercise capacity (V′O2peak), was related the PETCO2 max (r2=0.37, p<0.0001) and to peak VD/VT (r2=0.27, p=0.001) (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>), whereas these variables were not related to V′O2peak in the normocapnic group. Similar correlations were seen with WRpeak as the dependent variable (<a class="elsevierStyleCrossRef" href="#sec0065">Online Supplemental Figure 3</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia>DiscussionIn this study we tested the relationships between exercise variables, hemodynamics, markers of chemosensitivity, and the CO2 setpoint in a group of 59 patients with pulmonary vascular disease who performed CPET with peak exercise ABG sampling. We examined these relationships in the overall population and according to the presence of resting hypocapnia or resting normocapnia. The main findings of this study were: (1) the majority of CTEPH, all PVOD patients and 47% of PAH patients had resting hypocapnia, (2) hypocapnic patients were characterized by a lower CI, lower DLCO, worse exercise capacity, higher V′E/V′CO2 and more pronounced exertional hypoxemia than normocapnic patients, (3) the maximal PETCO2 was the strongest correlate of exercise capacity and ventilatory efficiency slope in the overall population and particularly in hypocapnic patients. These results provide insights into the relative influence of an altered PaCO2 setpoint and VD/VT on exercise capacity and ventilatory inefficiency during exercise in pulmonary vascular disease. Furthermore, the stronger relationship between maximal PETCO2 with peak exercise capacity and V′E/V′CO2 compared to resting or peak exercise blood gases suggests that maximal PETCO2 could be used as a non-invasive marker of CO2 setpoint and disease severity even during a submaximal effort.The finding of resting hypocapnia is well known in pulmonary vascular diseases<a class="elsevierStyleCrossRefs" href="#bib0280">22–27</a> and 66% of patients had a resting PaCO2 <35mmHg in our study. Approximately half of the PAH patients had hypocapnia, while nearly all CTEPH patients and all PVOD patients were hypocapnic. The mechanisms of hypoxemia at rest and during exercise in these diseases include ventilation-perfusion inequality, shunt, and lower mixed venous oxygen saturation.<a class="elsevierStyleCrossRefs" href="#bib0280">22,23</a> Less is known about the mechanisms or clinical importance of resting hypocapnia. It is generally accepted that high physiologic dead space due to ventilation-perfusion heterogeneity and vascular obstruction accounts for the excessive ventilatory response during exercise in pulmonary vascular diseases, however, this does not adequately explain resting hypocapnia. Hypocapnia is likely a marker of more advanced or extensive pulmonary vascular disease in our population: 1) the lower DLCO/VA in hypocapnic patients may reflect lower capillary volume from more extensive pulmonary vascular involvement and 2) there was a slightly higher PVR in hypocapnic versus normocapnic patients, which would also support this notion. Hoeper et al. previously demonstrated that resting PaCO2 was not correlated to mPAP and only weakly related to cardiac index and mixed venous oxygen saturation in idiopathic PAH, with lower resting PaCO2 associated with worse survival.<a class="elsevierStyleCrossRef" href="#bib0205">7</a> In our study of mixed etiologies of pulmonary vascular disease, patients with resting hypocapnia had more severe functional impairment as indicated by lower exercise capacity and worse cardiac function. Similarly to Hoeper et al.,<a class="elsevierStyleCrossRef" href="#bib0205">7</a> PaCO2 at rest and peak exercise were also weakly correlated to resting cardiac index, and to a lesser extent than the maximal PETCO2 or VD/VT. This suggests an important and complex interaction between right ventricular function, hyperventilation at rest, chemosensitivity and exercise capacity. Patients with CTEPH who undergo pulmonary thromboendarterectomy (a procedure which reduces or eliminates pulmonary vascular bed obstruction) have improvements in pulmonary hemodynamics, hypoxemia and ventilation-perfusion inequalities on multiple inert gas testing, with a parallel increase in the resting PaCO2.<a class="elsevierStyleCrossRefs" href="#bib0300">26,27</a> However, it is not known whether improvement in resting PaCO2 is driven by changes in hemodynamics, sympathetic tone, ventilation-perfusion matching, or all of these mechanisms together.Pulmonary vascular disease leads to right ventricular dysfunction and a low cardiac output state, similar to left heart failure, and there is increased sympathetic activity in PAH<a class="elsevierStyleCrossRef" href="#bib0230">12</a> to a similar degree as in left heart failure. However, the V′E/V′CO2 tends to be higher in pulmonary vascular disease, while left heart failure patients are not typically hypocapnic at rest and do not desaturate during exercise.<a class="elsevierStyleCrossRefs" href="#bib0310">28-30</a> Our study provides certain insights into these underlying mechanisms of resting hypocapnia and high V′E/V′CO2 in pulmonary vascular disease. Patients with resting hypocapnia were different from normocapnic patients in several ways and showed evidence of different mechanisms of exercise limitation. First, hypocapnic patients had higher resting V′E but similar levels of peak ventilation and peak exercise respiratory rates despite having lower exercise capacity, highlighting the increased ventilatory drive at rest and during exercise in these patients. Second, most patients with resting hypocapnia had a PaO2> 60mmHg, and resting PaO2 did not correlate with peak V′E, indicating that stimulation of peripheral chemoreceptors is unlikely to be the explanation for resting hypocapnia. Therefore, other mechanisms, such as an altered central PaCO2 setpoint or other sympathetic reflexes are probably responsible for the low PaCO2 at rest. Our results suggest that an altered CO2 setpoint could play an important role. Indeed, maximal exercise performance was most highly related to the maximal PETCO2 value between the AT and RCP, an indicator of the CO2 setpoint,<a class="elsevierStyleCrossRefs" href="#bib0245">15–17</a> in the overall population and in hypocapnic patients, but not normocapnic patients. The normocapnic patients still had reduced peak exercise capacity but likely are limited by other mechanisms than impaired gas exchange or ventilatory inefficiency. Similarly, the PETCO2 max was a stronger correlate of V′E/V′CO2 and V′O2peak than the VD/VT or P(a-ET)CO2. In fact, V′E/V′CO2 was not correlated with peak exercise VD/VT whereas maximal PETCO2 explained 61% of the variability in V′E/VCO2 slope among hypocapnic patients. This contrast with a study by Kee et al., where high VD/VT was the main mediator of exercise capacity and V′E/V′CO2 in systolic heart failure patients.<a class="elsevierStyleCrossRef" href="#bib0325">31</a> This suggests that the CO2 set-point is at least as important as VD/VT in determining exercise capacity and ventilatory inefficiency in pulmonary vascular diseases. The V′O2peak is a strong predictor of mortality<a class="elsevierStyleCrossRefs" href="#bib0190">4,5,32</a> and is a recommended variable for comprehensive risk assessment and monitoring treatment,<a class="elsevierStyleCrossRef" href="#bib0275">21</a> however many patients with pulmonary vascular disease may not achieve a maximal effort during CPET. The maximal PETCO2 also had excellent discrimination for identifying patients who had a “low-risk” V′O2peak (>15mL/kg/min) value for mortality,<a class="elsevierStyleCrossRef" href="#bib0275">21</a> which could be useful in risk assessment when there is a submaximal effort. However, the prognostic value of maximal PETCO2 and the effect of targeted interventions on this variable remain to be explored and should be studied in the future.Autonomic dysfunction, increased sympathetic nervous system activity, and an altered CO2 set-point are related to chemoreflex sensitivity. Our results are supportive of a recent study by Farina et al., who performed minute-to-minute blood gas analysis during exercise in 18 patients with pulmonary vascular disease.<a class="elsevierStyleCrossRef" href="#bib0335">33</a> They performed hypoxic and hypercapnic challenge tests to evaluate peripheral and central chemosensitivity and found that, although chemoreceptor sensitivity was increased in PAH and CTEPH, peripheral chemoreceptor responses to hypoxia and hypercapnia did not correlate with any exercise parameter. However, central chemoreceptor sensitivity to hypercapnia did correlate with the VA/VCO2 slope during exercise, suggesting that the higher VA due to a lower central CO2 setpoint could be the main explanation for resting hypocapnia. We extend and confirm their results that the CO2 setpoint is likely an important underlying mechanism of inefficient ventilation to a much larger population. Together, we and Farina et al.,<a class="elsevierStyleCrossRef" href="#bib0335">33</a> imply that hypocapnic patients and/or those with low maximal PETCO2 during exercise have autonomic dysfunction and a lower CO2 setpoint. Thus, resting PaCO2 or maximal PETCO2 could be used to identify patients with probably autonomic dysfunction as inclusion criteria or to help enrich future studies that target the sympathetic nervous system in pulmonary vascular disease.LimitationsOur study has limitations given its retrospective nature. Autonomic function and chemoreflex responses were not specifically tested in our study, therefore, we may only generate additional hypotheses about the relative role these reflexes in the high ventilatory inefficiency in our population. However, our results and conclusions are supportive of a recent smaller study by Farina et al., which did test chemoreflexes. Although the distinction and definitions of normocapnia and hypocapnia were made a priori, there was a smaller number of patients in the normocapnic group (n=20), which may have affected statistical significance in comparing certain patient characteristics or correlations. The different proportion of etiologies between the hypo and normocapnic groups and their different sizes may also explain some of the weaker correlations and conclusions. We also did not have resting or exertional echocardiographic data to exclude a patent foramen ovale in patients with exercise-related desaturation and high V′E/V′CO2, which could be a contributing mechanism of inefficient ventilation in some patients.<a class="elsevierStyleCrossRef" href="#bib0340">34</a>ConclusionsPatients with resting hypocapnia have worse cardiac function and more severe gas exchange abnormalities during exercise. High chemosensitivity and an altered PaCO2 setpoint are likely explanations for resting hypocapnia and high V′E/V′CO2. The PaCO2 setpoint, estimated by the maximal PETCO2 was the strongest correlate of peak exercise capacity and V′E/V′CO2, suggesting that this variable could be used as a non-invasive measure of CO2 setpoint and disease severity even during submaximal exercise.Conflicts of InterestsDr. Weatherald reports grants, personal fees and non-financial support from Actelion and Janssen Inc., personal fees and non-financial support from Bayer, personal fees from Novartis, grants from grants from Canadian Vascular Network, outside the submitted work; grants from European Respiratory Society related to the current work. Dr. Boucly reports personal fees and non-financial support from Actelion Pharmaceuticals, non-financial support from Bayer HealthCare, non-financial support from GlaxoSmithKline, personal fees and non-financial support from Merck, outside the submitted work. Dr. Montani reports grants and personal fees from Actelion Pharmaceuticals, grants and personal fees from Bayer HealthCare, personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Pfizer, personal fees from BMS, outside the submitted work. Dr. Jaïs reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, grants, personal fees and non-financial support from Bayer HealthCare, grants, personal fees and non-financial support from GlaxoSmithKline, grants, personal fees and non-financial support from MSD, outside the submitted work. Dr. Savale reports grants and personal fees from Actelion Pharmaceuticals, grants and personal fees from Bayer HealthCare, personal fees from GlaxoSmithKline, personal fees from Merck, outside the submitted work. Dr. Humbert reports personal fees from Actelion, grants and personal fees from Bayer, grants and personal fees from GSK, personal fees from Merck, from United Therapeutics, outside the submitted work. Dr. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, personal fees from Acceleron Pharmaceuticals, personal fees from Arena Pharmaceuticals, grants and personal fees from Bayer HealthCare, grants, personal fees and non-financial support from GlaxoSmithKline, personal fees from Gossamer Bio, grants and personal fees from Merck, outside the submitted work. Dr. Garcia has nothing to disclose. Dr. Laveneziana reports personal fees from NOVARTIS France, personal fees from BOEHRINGER France, outside the submitted work." "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres1386458" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres1386459" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Background and Objective" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1272228" "titulo" => "Keywords" ] 3 => array:2 [ "identificador" => "xpalclavsec1272229" "titulo" => "Abbreviations" ] 4 => array:3 [ "identificador" => "xres1386460" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Contexto general y objetivo" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Conclusiones" ] ] ] 5 => array:2 [ "identificador" => "xpalclavsec1272230" "titulo" => "Palabras clave" ] 6 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 7 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "CPET testing" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 9 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 10 => array:2 [ "identificador" => "sec0040" "titulo" => "Limitations" ] 11 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusions" ] 12 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of Interests" ] 13 => array:2 [ "identificador" => "xack481893" "titulo" => "Acknowledgements" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-08-06" "fechaAceptado" => "2019-12-22" "PalabrasClave" => array:2 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1272228" "palabras" => array:7 [ 0 => "Exercise" 1 => "Pulmonary hypertension" 2 => "Chemosensitivity" 3 => "Ventilatory efficiency" 4 => "Pathophysiology" 5 => "Hypocapnia" 6 => "Arterial blood gas" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1272229" "palabras" => array:17 [ 0 => "ABG" 1 => "AT" 2 => "CPET" 3 => "CTEPH" 4 => "Mpap" 5 => "NYHA" 6 => "PAH" 7 => "PĒCO2" 8 => "PETCO2" 9 => "PVOD" 10 => "PVR" 11 => "RCP" 12 => "V′CO2" 13 => "VD/VT" 14 => "V′E/V′CO2" 15 => "V′O2" 16 => "WR" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1272230" "palabras" => array:7 [ 0 => "Ejercicio" 1 => "Hipertensión pulmonar" 2 => "Quimiosensibilidad" 3 => "Eficiencia ventilatoria" 4 => "Fisiopatología" 5 => "Hipocapnia" 6 => "Gasometría arterial" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Background and ObjectiveVentilatory inefficiency (high V′E/V′CO2) and resting hypocapnia are common in pulmonary vascular disease and are associated with poor prognosis. Low resting PaCO2 suggests increased chemosensitivity or an altered PaCO2 set-point. We aimed to determine the relationships between exercise gas exchange variables reflecting the PaCO2 set-point, exercise capacity, hemodynamics and V′E/V′CO2. MethodsPulmonary arterial hypertension (n=34), chronic thromboembolic pulmonary hypertension (CTEPH, n=19) and pulmonary veno-occlusive disease (PVOD, n=6) patients underwent rest and peak exercise arterial blood gas measurements during cardiopulmonary exercise testing. Patients were grouped according to resting PaCO2: hypocapnic (PaCO2 ≤34mmHg) or normocapnic (PaCO2 35–45mmHg). The PaCO2 set-point was estimated by the maximal value of end-tidal PCO2 (maximal PETCO2) between the anaerobic threshold and respiratory compensation point. ResultsThe hypocapnic group (n=39) had lower resting cardiac index (3.1±0.8 vs. 3.7±0.7L/min/m2, p<0.01), lower peak V′O2 (15.8±3.5 vs. 20.7±4.3mL/kg/min, p<0.01), and higher V′E/V′CO2 slope (60.6±17.6 vs. 38.2±8.0, p<0.01). At peak exercise, hypocapic patients had lower PaO2, higher VD/VT and higher P(a-ET)CO2. Maximal PETCO2 (r=0.59) and VD/VT (r=−0.59) were more related to cardiac index than PaO2 or PaCO2 at rest or peak exercise. Maximal PETCO2 was the strongest correlate of V′E/V′CO2 slope (r=−0.86), peak V′O2 (r=0.64) and peak work rate (r=0.49). ConclusionsResting hypocapnia is associated with worse cardiac function, more ventilatory inefficiency and reduced exercise capacity. This could be explained by elevated chemosensitivity and lower PaCO2 set-point. Maximal PETCO2 may be a useful non-invasive marker of PaCO2 setpoint and disease severity even with submaximal effort." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Background and Objective" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "Contexto general y objetivoLa ineficiencia ventilatoria (V’E/V’CO2 alta) y la hipocapnia en reposo son comunes en la enfermedad vascular pulmonar y se asocian con un mal pronóstico. La PaCO2 baja en reposo sugiere una mayor quimiosensibilidad o una alteración en el ajuste fisiológico de la PaCO2. Nuestro objetivo fue determinar las relaciones entre las variables de intercambio de gases que reflejan el ajuste de la PaCO2 durante el ejercicio, la capacidad de ejercicio, la hemodinámica y la V’E/V’CO2. MétodosSe realizaron mediciones de gases en sangre arterial durante las pruebas de ejercicio cardiopulmonar a pacientes con hipertensión arterial pulmonar (n=34), hipertensión pulmonar tromboembólica crónica (HPTEC, n=19) y enfermedad venooclusiva pulmonar (EVOP, n=6). Los pacientes se agruparon de acuerdo con su PaCO2 en reposo: hipocapnia (PaCO2 ≤34mmHg) o normocapnia (PaCO2 35–45mmHg). El ajuste de la PaCO2 se estimó mediante el valor máximo de PCO2 exhalado (PETCO2 máximo) entre el umbral anaeróbico y el punto de compensación respiratoria. ResultadosEl grupo hipocápnico (n=39) tenía un índice cardíaco en reposo más bajo (3,1±0,8 vs. 3,7±0,7L/min/m2, p<0,01), un pico de V’O2 más bajo (15,8±3,5 vs 20,7±4,3mL/kg/min, p<0,01), y mayor pendiente de V’E/V’CO2 (60,6±17,6 vs. 38,2±8,0, p<0,01). En el punto de ejercicio máximo, los pacientes hipocápnicos tenían una PaO2 más baja, un VD/VT más alto y una P(a-ET) CO2 más alta. La PETCO2 máxima (r=0,59) y la VD/VT (r=-0,59) estaban más relacionadas con el índice cardíaco que la PaO2 o la PaCO2 en reposo o en el punto de máximo esfuerzo. La PETCO2 máxima fue la que mayor correlación tuvo con la pendiente V’E/V’CO2 (r=-0,86), la V’O2 máxima (r=0.64) y la tasa de esfuerzo máximo (r=0,49). ConclusionesLa hipocapnia en reposo se asocia a una peor función cardíaca, una mayor ineficiencia ventilatoria y una capacidad disminuída de ejercicio. Esto podría explicarse por una quimiosensibilidad elevada y un ajuste fisiológico más bajo de la PaCO2. La PETCO2 máxima puede ser un marcador no invasivo útil del ajuste de PaCO2 y la gravedad de la enfermedad incluso con un esfuerzo submáximo." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Contexto general y objetivo" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Part of this study has been presented in abstract form at the European Respiratory Society Congress in Milan, Italy, on September 11, 2017." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0065" ] ] ] ] "multimedia" => array:12 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 878 "Ancho" => 1583 "Tamanyo" => 72847 ] ] "descripcion" => array:1 [ "en" => "Example of maximal PETCO2 calculation. The PaCO2 setpoint was estimated noninvasively from the highest value of end-tidal PCO2 (maximal PETCO2) observed between the anaerobic threshold (AT) and the respiratory compensation point (RCP), when PETCO2 remains constant." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1138 "Ancho" => 1591 "Tamanyo" => 69409 ] ] "descripcion" => array:1 [ "en" => "Receiver operating characteristic curve for discriminating a low-risk peak V′O2>15mL/kg/min according to the maximal PETCO2 value observed between the anaerobic threshold and the respiratory compensation point." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1392 "Ancho" => 2925 "Tamanyo" => 219355 ] ] "descripcion" => array:1 [ "en" => "V′E/V′CO2 slope versus VD/VT at peak exercise, P(a-ET)CO2 at peak exercise, and maximal PETCO2 (PETCO2 Max) in patients with resting hypocapnia (HC) and resting normocapnia (NC). Shaded areas indicate 95% confidence intervals." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1395 "Ancho" => 2925 "Tamanyo" => 211315 ] ] "descripcion" => array:1 [ "en" => "VD/VT and P(a-ET)CO2 at peak exercise versus resting cardiac index in patients with resting hypocapnia (HC) and resting normocapnia (NC). Shaded areas indicate 95% confidence intervals." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1395 "Ancho" => 2925 "Tamanyo" => 196573 ] ] "descripcion" => array:1 [ "en" => "Peak exercise capacity (peak V′O2) versus VD/VT at peak exercise, P(a-ET)CO2 at peak exercise and PETCO2max in patients with resting hypocapnia (HC) and resting normocapnia (NC). Shaded areas indicate 95% confidence intervals." ] ] 5 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "BMI: body mass index; PAH: pulmonary arterial hypertension; CTEPH: chronic thromboembolic pulmonary hypertension; PVOD: pulmonary veno-occlusive disease; NYHA: New York Heart Association functional class; 6MWT: 6-minute walk test distance; mPAP: mean pulmonary arterial pressure; PAWP: pulmonary artery wedge pressure; CI: cardiac index; PVR: pulmonary vascular resistance; DLCO/VA: diffusion capacity for carbon monoxide adjusted for alveolar volume; Hg: hemoglobin; V′E/V′CO2: minute ventilation/carbon dioxide output; WR peak: work rate at peak exercise; V′O2 peak: oxygen consumption at peak exercise." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">All \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Hypocapnic \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Normocapnic \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N=59 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N=39 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N=20 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (y) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 (28–57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 (29–60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.5 (28–54) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 (55.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 (66.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (35.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI (kg/m2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (21–27) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (21–28) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (22–26) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Etiology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PAH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 (57.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (41.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (90.0)<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CTEPH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (32.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (43.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (10.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PVOD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (10.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (15.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NYHA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (24.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (21.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (30.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (48.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (44.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (55.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (27.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (15.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6MWT (m) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">529.5±101.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">508.9±96.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">566.0±104.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">mPAP (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48.0±13.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47.6±10.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48.9±17.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PAWP (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.8±3.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.6±3.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.2±3.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CI (L/min/m2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.3±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.1±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.7±0.7<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PVR (Wood units) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.0±3.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.6±3.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.0±2.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DLCO/VA (%pred) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72.1±22.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67.1±23.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83.0±14.5<a class="elsevierStyleCrossRef" href="#tblfn0010">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hg (g/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.6 (13.4–15.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.4 (13.4–16.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.6 (13.4–15.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V′E/V′CO2 slope \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47.0 (40.0–61.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58.6 (46.6–68.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.1 (32.5–43.4)<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">WR peak (Watts) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85 (67–110) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 (65–95) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">110 (78–140)<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V′O2 peak (mL/kg/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17.4±4.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.8±3.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20.7±4.3<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VO2 peak (%pred) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.9±17.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.4±17.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61.8±17.4<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2379904.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "p<0.01 vs hypocapnic group." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "‡" "nota" => "p<0.05 vs hypocapnic group." ] ] ] "descripcion" => array:1 [ "en" => "Patient characteristics." ] ] 6 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "V′E: minute ventilation; PETO2: end-tidal partial pressure of oxygen tension; PETCO2: end-tidal partial pressure of carbon dioxide; VD/VT: physiologic dead space fraction; P(a-ET)CO2: arterial-end-tidal PCO2 difference; P(ET-a)O2: end-tidal-arterial PO2 difference; P(A-a)O2: alveolar-arterial oxygen difference." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Hypocapnic (n=39)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Normocapnic (n=20)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rest \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Peak \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Rest \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Peak \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PaO2 (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74.5±11.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63.1±15.2<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83.6±12.4<a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">81.5±13.7 <a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PaCO2 (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29.6±2.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.8±3.1<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.2±2.2 <a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.3±3.2<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a><a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V′E (L/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.6±6.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">76.1±18.5<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.4±2.6 <a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70.1±20.8<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Respiratory frequency (bpm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.1±3.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38±7.2<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.7±2.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35.0±8.1<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PETO2 (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120.3±6.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">128.5±4.3<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">111.6±5.1<a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">119.1±5.9<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a>,<a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PETCO2 (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22.7±4.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.9±4.2<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.1±3.0 <a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28.6±5.0 <a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VD/VT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.45±0.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.48±0.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.44±0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.34±0.08<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a>,<a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P(a-ET)CO2 (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.9±4.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.1±3.2<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.6±6.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.7±3.3 <a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P(ET-a)O2 (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.8±4.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65.5±17.1<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.5±12.5<a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.3±18.2<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a>,<a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">P(A-a)O2 (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38.5±10.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52.2±15.4<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21.1±11.8<a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.9±14.0 <a class="elsevierStyleCrossRef" href="#tblfn0020">‡</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2379903.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "*" "nota" => "p<0.05 vs Rest." ] 1 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "‡" "nota" => "p<0.05 vs Hypocapnic group." ] ] ] "descripcion" => array:1 [ "en" => "Gas Exchange variables at rest and peak exercise." ] ] 7 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "PETCO2: end-tidal partial pressure of carbon dioxide; VD/VT: physiologic dead space fraction; P(a-ET)CO2: arterial-end-tidal PCO2 difference; VO2: oxygen consumption; WR: work rate; V′E/V′CO2: minute ventilation/carbon dioxide output; CI: resting cardiac index." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PaCO2rest \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PaCO2peak \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PETCO2peak \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Maximal PETCO2 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">VD/VTpeak \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">P(a-ET)CO2peak \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VO2peak (mL/kg/min)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">r \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.411 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p-value \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">WRpeak (W)</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">r \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p-value \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">V′E/V′CO2 Slope</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">r \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.66 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p-value \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CI</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">r \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.45 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p-value \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2379905.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Correlations between exercise gas exchange variables, exercise capacity, ventilatory efficiency and cardiac index in the overall population (n=59)." ] ] 8 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 311297 ] ] 9 => array:5 [ "identificador" => "fig0030" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 955 "Ancho" => 1333 "Tamanyo" => 52736 ] ] ] 10 => array:6 [ "identificador" => "eq0005" "etiqueta" => "(1)" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "VD/Vt=PaCO2−PECO2PaCO2" "Fichero" => "STRIPIN_si1.jpeg" "Tamanyo" => 2117 "Alto" => 33 "Ancho" => 164 ] ] 11 => array:6 [ "identificador" => "eq0010" "etiqueta" => "(2)" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:5 [ "Matematica" => "V'O2 peak=0.4544968 (maximal PETCO2)+5.155365(r2=0.413, p<0.001)" "Fichero" => "STRIPIN_si2.jpeg" "Tamanyo" => 4904 "Alto" => 43 "Ancho" => 408 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:34 [ 0 => array:3 [ "identificador" => "bib0175" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ventilatory response to exercise in cardiopulmonary disease: the role of chemosensitivity and dead space" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. 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Original Article

Gas Exchange and Ventilatory Efficiency During Exercise in Pulmonary Vascular Diseases

Intercambio de gases y eficiencia de ventilación durante el ejercicio en enfermedades vasculares pulmonares

Jason Weatheralda,b,c,d,e, Athénaïs Bouclyc,d,e, David Montanic,d,e, Xavier Jaïsc,d,e, Laurent Savalec,d,e, Marc Humbertc,d,e, Olivier Sitbonc,d,e, Gilles Garciac,e,f, Pierantonio Lavenezianag,h,

Corresponding author

pierantonio.laveneziana@aphp.fr

Corresponding author.

a University of Calgary, Department of Medicine, Division of Respirology, Calgary, Alberta, Canada

b Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada

c Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France

d Service de Pneumologie, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France

e INSERM U999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France

f Service de Physiologie, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France

g Sorbonne Université, INSERM, UMRS1158 Neurophysiologie respiratoire expérimentale et clinique, F-75005 Paris, France

h APHP.Sorbonne Université, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service des Explorations Fonctionnelles de la Respiration, de l’Exercice et de la Dyspnée, Hôpitaux Universitaires Pitié-Salpêtrière, Tenon et Saint-Antoine, Département Médico-Universitaire “APPROCHES”, F-75013 Paris, France

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The main determinants of the exercise ventilatory response &#40;<span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#41; are the pulmonary carbon dioxide &#40;CO<span class="elsevierStyleInf">2</span>&#41; output &#40;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span>&#41;&#44; the arterial partial pressure of CO<span class="elsevierStyleInf">2</span> &#40;PaCO<span class="elsevierStyleInf">2</span>&#41;&#44; the dead space fraction of each tidal breath &#40;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>&#41; and the extent to which the ventilatory system is constrained by abnormal respiratory mechanics&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a> An indicator of the efficiency of exercise <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span> is the steepness with which <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span> rises with respect to VCO<span class="elsevierStyleInf">2</span>&#44; i&#46;e&#46;&#44; the <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> slope&#46; Pulmonary vascular disease patients often hyperventilate at rest and during exercise&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a> and ventilatory inefficiency &#40;high <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span>&#41; is a hallmark that predicts higher mortality independent from other exercise-related prognostic factors such as peak oxygen uptake &#40;<span class="elsevierStyleItalic">V</span>O<span class="elsevierStyleInf">2</span>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">2&#8211;6</span></a> The <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> slope is fundamentally determined by two factors&#58; &#40;1&#41; the tidal volume &#40;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>&#41; fraction going to dead space &#40;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#41;&#44; &#40;i&#46;e&#46;&#44; the <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>&#41;&#59; and &#40;2&#41; the direction and magnitude of change in the PaCO<span class="elsevierStyleInf">2</span> during exercise&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">A low resting PaCO<span class="elsevierStyleInf">2</span> predicts a worse prognosis in pulmonary arterial hypertension &#40;PAH&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> However&#44; high <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> does not cause low resting PaCO<span class="elsevierStyleInf">2</span>&#44; therefore an altered PaCO<span class="elsevierStyleInf">2</span> set-point&#44; increased neural respiratory drive&#44; and&#47;or increased chemosensitivity must explain hypocapnia and consequently&#44; the high <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> slope&#46; The PaCO<span class="elsevierStyleInf">2</span> set-point is influenced by factors such as metabolic acidosis&#44; hypoxemia&#44; baroreceptors in the pulmonary vasculature and sympathetic nervous system hyperactivity&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">8&#8211;13</span></a> The assessment of chemosensitivity and&#47;or the PaCO<span class="elsevierStyleInf">2</span> set-point during exercise is not straightforward and can be problematic&#46; Few studies have attempted to evaluate the PaCO<span class="elsevierStyleInf">2</span> set-point &#8220;non-invasively&#8221; by evaluating the maximal end-tidal CO<span class="elsevierStyleInf">2</span> pressure &#40;maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span>&#41; value between the anaerobic threshold &#40;AT&#41; and respiratory compensation point &#40;RCP&#41; where <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> is constant and&#44; therefore&#44; is supposed to truly reflect the real PaCO<span class="elsevierStyleInf">2</span> set-point&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">14&#8211;17</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The aim of the study was to test the relationships between gas exchange variables that reflect high chemosensitivity and&#47;or the PaCO<span class="elsevierStyleInf">2</span> set-point&#44; exercise capacity and markers of disease severity in pulmonary vascular disease patients according to the presence of resting hypocapnia &#40;PaCO<span class="elsevierStyleInf">2</span> &#8804; 34<span class="elsevierStyleHsp" style=""></span>mmHg&#41; or normocapnia &#40;PaCO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>35&#8211;45<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This retrospective study complied with the Declaration of Helsinki&#46; Although French law does not require ethics committee approval or informed consent for retrospective data collection&#44; the data collected were anonymized and complied according to the requirements of the Commission Nationale Informatique et Libert&#233; &#40;CNIL&#41;&#44; the organization dedicated to privacy&#44; information technology and civil rights in France&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study population</span><p id="par0025" class="elsevierStylePara elsevierViewall">We reviewed patients<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>18 years of age with PAH&#44; chronic thromboembolic pulmonary hypertension &#40;CTEPH&#41;&#44; or pulmonary veno-occlusive disease &#40;PVOD&#41; who underwent cardiopulmonary exercise testing &#40;CPET&#41; with arterial blood gas &#40;ABG&#41; sampling at rest and maximal exercise at our institution between 2010 and 2016&#46; All patients were diagnosed according to current guidelines with right heart catheterization&#46; Patients were prevalent&#44; treated with PAH therapies with clinical stability during the preceding 3 months and in New York Heart Association &#40;NYHA&#41; function class I&#8211;III&#46; Patients with a history of smoking&#44; forced expiratory volume in 1-second to forced vital capacity &#40;FEV1&#47;FVC&#41; ratio &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;7&#44; and those without peak exercise ABG measurements were excluded&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">CPET testing</span><p id="par0030" class="elsevierStylePara elsevierViewall">Spirometry&#44; single breath D<span class="elsevierStyleInf">L</span>CO and static lung volumes were performed on the same day prior to CPET&#46; All patients underwent a symptom-limited incremental cycle ergometer CPET and were encouraged to continue until exhaustion&#46; Arterial blood gas &#40;ABG&#41; measurements were obtained via a radial artery puncture at rest before and at peak exercise&#44; while still pedaling&#46; Pulmonary function tests were performed using automated equipment &#40;Masterscreen MS Body and Diffusion&#44; tyb B&#47;IEC 601-1&#47;IP20&#44; Jaeger&#44; Germany&#41;&#46; Symptom-limited incremental CPETs were conducted on an electrically braked cycle ergometer &#40;Ergoline 100P mitBD&#59; Medisoft&#44; Sorinnes&#44; Belgium&#41; with a cardiopulmonary exercise testing system &#40;Ergocard model E&#44; Medisoft&#44; Sorinnes&#44; Belgium&#41;&#46; Breath-by-breath cardiopulmonary and metabolic data were collected at baseline and throughout exercise while subjects breathed through a mouthpiece with nasal passages occluded by a nose-clip&#46; Exercise variables were measured and averaged over the last 20<span class="elsevierStyleHsp" style=""></span>s of each minute and at peak exercise&#46; Exercise variables were compared with predicted normal values &#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a> The AT was determined individually using the V-slope method&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> We estimated the CO<span class="elsevierStyleInf">2</span> set-point noninvasively from the highest value of end-tidal PCO<span class="elsevierStyleInf">2</span> &#40;maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span>&#41; observed between the AT and the RCP&#44; when <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> remains constant&#44; as previously described &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">14&#8211;17</span></a> In cases where the RCP was not clearly evident&#44; the highest value occurring after AT was used&#46; Ventilatory efficiency was obtained from the <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> slope&#44; which was determined for each patient using linear regression&#46; The physiologic dead space &#40;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>&#41; was calculated using the Enghoff modification of the Bohr equation<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">20</span></a>&#58;<elsevierMultimedia ident="eq0005"></elsevierMultimedia>where <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>dead space volume&#44; <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>tidal volume&#44; PaCO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>arterial partial pressure of carbon dioxide and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">E</span>CO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>mixed expired carbon dioxide partial pressure&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0035" class="elsevierStylePara elsevierViewall">Patients were grouped according to resting PaCO<span class="elsevierStyleInf">2</span>&#44; defined as being hypocapnic &#40;PaCO<span class="elsevierStyleInf">2</span> &#8804; 34<span class="elsevierStyleHsp" style=""></span>mmHg&#41; or normocapnic &#40;PaCO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>35&#8211;45<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#46; Continuous variables are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation or median with interquartile range &#40;IQR25&#8211;75&#37;&#41; according to normality&#46; The Shapiro&#8211;Wilk test was used to assess normality of data&#46; Categorical variables are expressed as absolute and relative frequencies&#46; Between-group comparisons were made using two-sample <span class="elsevierStyleItalic">t</span>-tests&#44; Wilcoxon rank sum tests&#44; and the chi-squared test&#44; where appropriate&#46; Relationships between <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#44; <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>&#44; arterial-to-end-tidal PCO<span class="elsevierStyleInf">2</span> difference &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">&#40;a-ET&#41;</span>CO<span class="elsevierStyleInf">2</span>&#41;&#44; maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span>&#44; resting cardiac index &#40;CI&#41;&#44; and <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> slope were assessed using linear regression&#46; A <span class="elsevierStyleItalic">p</span>-value &#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered significant&#46; Statistical analyses were performed using STATA &#40;version 13&#46;1&#44; StataCorp&#44; College Station&#44; Texas&#44; USA&#41;&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">A total of 59 patients were included&#46; Demographics&#44; clinical and hemodynamic characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Compared to normocapnic patients&#44; a greater proportion of hypocapnic patients had CTEPH or PVOD as opposed to PAH&#44; and both D<span class="elsevierStyleInf">L</span>CO&#47;V<span class="elsevierStyleInf">A</span> and CI were lower in hypocapnic patients&#46; Peak oxygen consumption &#40;<span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2<span class="elsevierStyleHsp" style=""></span>peak</span>&#41; was lower and <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> was higher in hypocapnic patients&#46; Characteristics and gas exchange variables according to etiology of pulmonary hypertension are shown in <a class="elsevierStyleCrossRef" href="#sec0065">Online Supplemental Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Gas exchange variables at rest and at peak exercise are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; In hypocapnic patients&#44; peak <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> did not significantly change during exercise and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">&#40;a-ET&#41;</span>CO<span class="elsevierStyleInf">2</span> increased&#44; whereas <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">&#91;a-ET&#93;</span>CO<span class="elsevierStyleInf">2</span> both decreased from rest to peak exercise among the normocapnic patients &#40;<a class="elsevierStyleCrossRef" href="#sec0065">Online Supplemental Figure 1</a>&#41;&#46; The CO<span class="elsevierStyleInf">2</span> set-point&#44; as estimated by the maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> between AT and the RCP&#44; was significantly lower among hypocapnic patients &#40;23&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;1 vs&#46; 33&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;7<span class="elsevierStyleHsp" style=""></span>mmHg&#44; <span class="elsevierStyleItalic">p</span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In the overall population&#44; the CO<span class="elsevierStyleInf">2</span> set-point &#40;maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span>&#41; was the strongest correlate of <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">peak</span>&#44; peak work rate &#40;WR<span class="elsevierStyleInf">peak</span>&#41; and <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> slope &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">peak</span> &#40;mL&#47;kg&#47;min&#41; could be estimated from the maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> with the equation&#58;<elsevierMultimedia ident="eq0010"></elsevierMultimedia></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">In the overall population&#44; the maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> discriminated patients with low-risk value for <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">peak</span> of<span class="elsevierStyleHsp" style=""></span>&#62;15<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;min &#40;area under the receiver operating curve &#91;AUC&#93; 0&#46;88&#44; 95&#37;CI 0&#46;79&#8211;0&#46;96&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; and <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">peak</span><span class="elsevierStyleHsp" style=""></span>&#62;65&#37; predicted &#40;AUC 0&#46;64&#44; 95&#37; CI 0&#46;47&#8211;0&#46;80&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">21</span></a> A maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> value of &#8805;25<span class="elsevierStyleHsp" style=""></span>mmHg had 90&#37; sensitivity and 72&#37; specificity for a <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">peak</span> of<span class="elsevierStyleHsp" style=""></span>&#62;15<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;min&#46; The maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> AUC for <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">peak</span> of<span class="elsevierStyleHsp" style=""></span>&#62;15<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;min was 0&#46;89 in the normocapnic group and 0&#46;77 in the hypocapnic group &#40;<a class="elsevierStyleCrossRef" href="#sec0065">Online Supplemental Figure 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Peak <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span> was related to peak exercise PaO<span class="elsevierStyleInf">2</span> &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;29&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; and PaCO<span class="elsevierStyleInf">2</span> &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;3&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; in normocapnic patients but not in hypocapnic patients&#46; The <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> slope was related to peak exercise <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">&#40;a-ET&#41;</span>CO<span class="elsevierStyleInf">2</span> and maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> in hypocapnic patients but not significantly correlated to <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> in normocapnic patients &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">&#40;a-ET&#41;</span>CO<span class="elsevierStyleInf">2</span> at peak exercise and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> max correlated with resting CI only in hypocapnic patients &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; Maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> modestly correlated with resting CI but to a greater extent than resting or peak exercise PaCO<span class="elsevierStyleInf">2</span> in the overall population &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; In hypocapnic patients&#44; maximal exercise capacity &#40;<span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">peak</span>&#41;&#44; was related the <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> max &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;37&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; and to peak <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;27&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#44; whereas these variables were not related to <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">peak</span> in the normocapnic group&#46; Similar correlations were seen with WR<span class="elsevierStyleInf">peak</span> as the dependent variable &#40;<a class="elsevierStyleCrossRef" href="#sec0065">Online Supplemental Figure 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">In this study we tested the relationships between exercise variables&#44; hemodynamics&#44; markers of chemosensitivity&#44; and the CO<span class="elsevierStyleInf">2</span> setpoint in a group of 59 patients with pulmonary vascular disease who performed CPET with peak exercise ABG sampling&#46; We examined these relationships in the overall population and according to the presence of resting hypocapnia or resting normocapnia&#46; The main findings of this study were&#58; &#40;1&#41; the majority of CTEPH&#44; all PVOD patients and 47&#37; of PAH patients had resting hypocapnia&#44; &#40;2&#41; hypocapnic patients were characterized by a lower CI&#44; lower D<span class="elsevierStyleInf">L</span>CO&#44; worse exercise capacity&#44; higher <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> and more pronounced exertional hypoxemia than normocapnic patients&#44; &#40;3&#41; the maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> was the strongest correlate of exercise capacity and ventilatory efficiency slope in the overall population and particularly in hypocapnic patients&#46; These results provide insights into the relative influence of an altered PaCO<span class="elsevierStyleInf">2</span> setpoint and <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> on exercise capacity and ventilatory inefficiency during exercise in pulmonary vascular disease&#46; Furthermore&#44; the stronger relationship between maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> with peak exercise capacity and <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> compared to resting or peak exercise blood gases suggests that maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> could be used as a non-invasive marker of CO<span class="elsevierStyleInf">2</span> setpoint and disease severity even during a submaximal effort&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The finding of resting hypocapnia is well known in pulmonary vascular diseases<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">22&#8211;27</span></a> and 66&#37; of patients had a resting PaCO<span class="elsevierStyleInf">2</span> &#60;<span class="elsevierStyleHsp" style=""></span>35<span class="elsevierStyleHsp" style=""></span>mmHg in our study&#46; Approximately half of the PAH patients had hypocapnia&#44; while nearly all CTEPH patients and all PVOD patients were hypocapnic&#46; The mechanisms of hypoxemia at rest and during exercise in these diseases include ventilation-perfusion inequality&#44; shunt&#44; and lower mixed venous oxygen saturation&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">22&#44;23</span></a> Less is known about the mechanisms or clinical importance of resting hypocapnia&#46; It is generally accepted that high physiologic dead space due to ventilation-perfusion heterogeneity and vascular obstruction accounts for the excessive ventilatory response during exercise in pulmonary vascular diseases&#44; however&#44; this does not adequately explain resting hypocapnia&#46; Hypocapnia is likely a marker of more advanced or extensive pulmonary vascular disease in our population&#58; 1&#41; the lower D<span class="elsevierStyleInf">L</span>CO&#47;V<span class="elsevierStyleInf">A</span> in hypocapnic patients may reflect lower capillary volume from more extensive pulmonary vascular involvement and 2&#41; there was a slightly higher PVR in hypocapnic versus normocapnic patients&#44; which would also support this notion&#46; Hoeper et al&#46; previously demonstrated that resting PaCO<span class="elsevierStyleInf">2</span> was not correlated to mPAP and only weakly related to cardiac index and mixed venous oxygen saturation in idiopathic PAH&#44; with lower resting PaCO<span class="elsevierStyleInf">2</span> associated with worse survival&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> In our study of mixed etiologies of pulmonary vascular disease&#44; patients with resting hypocapnia had more severe functional impairment as indicated by lower exercise capacity and worse cardiac function&#46; Similarly to Hoeper et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> PaCO<span class="elsevierStyleInf">2</span> at rest and peak exercise were also weakly correlated to resting cardiac index&#44; and to a lesser extent than the maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> or <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>&#46; This suggests an important and complex interaction between right ventricular function&#44; hyperventilation at rest&#44; chemosensitivity and exercise capacity&#46; Patients with CTEPH who undergo pulmonary thromboendarterectomy &#40;a procedure which reduces or eliminates pulmonary vascular bed obstruction&#41; have improvements in pulmonary hemodynamics&#44; hypoxemia and ventilation-perfusion inequalities on multiple inert gas testing&#44; with a parallel increase in the resting PaCO<span class="elsevierStyleInf">2</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">26&#44;27</span></a> However&#44; it is not known whether improvement in resting PaCO<span class="elsevierStyleInf">2</span> is driven by changes in hemodynamics&#44; sympathetic tone&#44; ventilation-perfusion matching&#44; or all of these mechanisms together&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Pulmonary vascular disease leads to right ventricular dysfunction and a low cardiac output state&#44; similar to left heart failure&#44; and there is increased sympathetic activity in PAH<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">12</span></a> to a similar degree as in left heart failure&#46; However&#44; the <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> tends to be higher in pulmonary vascular disease&#44; while left heart failure patients are not typically hypocapnic at rest and do not desaturate during exercise&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">28-30</span></a> Our study provides certain insights into these underlying mechanisms of resting hypocapnia and high <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> in pulmonary vascular disease&#46; Patients with resting hypocapnia were different from normocapnic patients in several ways and showed evidence of different mechanisms of exercise limitation&#46; First&#44; hypocapnic patients had higher resting <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span> but similar levels of peak ventilation and peak exercise respiratory rates despite having lower exercise capacity&#44; highlighting the increased ventilatory drive at rest and during exercise in these patients&#46; Second&#44; most patients with resting hypocapnia had a PaO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#62; 60<span class="elsevierStyleHsp" style=""></span>mmHg&#44; and resting PaO<span class="elsevierStyleInf">2</span> did not correlate with peak <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#44; indicating that stimulation of peripheral chemoreceptors is unlikely to be the explanation for resting hypocapnia&#46; Therefore&#44; other mechanisms&#44; such as an altered central PaCO<span class="elsevierStyleInf">2</span> setpoint or other sympathetic reflexes are probably responsible for the low PaCO<span class="elsevierStyleInf">2</span> at rest&#46; Our results suggest that an altered CO<span class="elsevierStyleInf">2</span> setpoint could play an important role&#46; Indeed&#44; maximal exercise performance was most highly related to the maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> value between the AT and RCP&#44; an indicator of the CO<span class="elsevierStyleInf">2</span> setpoint&#44;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">15&#8211;17</span></a> in the overall population and in hypocapnic patients&#44; but not normocapnic patients&#46; The normocapnic patients still had reduced peak exercise capacity but likely are limited by other mechanisms than impaired gas exchange or ventilatory inefficiency&#46; Similarly&#44; the <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> max was a stronger correlate of <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> and <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">peak</span> than the <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> or <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">&#40;a-ET&#41;</span>CO<span class="elsevierStyleInf">2</span>&#46; In fact&#44; <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> was not correlated with peak exercise <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> whereas maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> explained 61&#37; of the variability in <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>CO<span class="elsevierStyleInf">2</span> slope among hypocapnic patients&#46; This contrast with a study by Kee et al&#46;&#44; where high <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> was the main mediator of exercise capacity and <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> in systolic heart failure patients&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">31</span></a> This suggests that the CO<span class="elsevierStyleInf">2</span> set-point is at least as important as <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> in determining exercise capacity and ventilatory inefficiency in pulmonary vascular diseases&#46; The <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">peak</span> is a strong predictor of mortality<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">4&#44;5&#44;32</span></a> and is a recommended variable for comprehensive risk assessment and monitoring treatment&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">21</span></a> however many patients with pulmonary vascular disease may not achieve a maximal effort during CPET&#46; The maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> also had excellent discrimination for identifying patients who had a &#8220;low-risk&#8221; <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">peak</span> &#40;&#62;15<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;min&#41; value for mortality&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">21</span></a> which could be useful in risk assessment when there is a submaximal effort&#46; However&#44; the prognostic value of maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> and the effect of targeted interventions on this variable remain to be explored and should be studied in the future&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Autonomic dysfunction&#44; increased sympathetic nervous system activity&#44; and an altered CO<span class="elsevierStyleInf">2</span> set-point are related to chemoreflex sensitivity&#46; Our results are supportive of a recent study by Farina et al&#46;&#44; who performed minute-to-minute blood gas analysis during exercise in 18 patients with pulmonary vascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a> They performed hypoxic and hypercapnic challenge tests to evaluate peripheral and central chemosensitivity and found that&#44; although chemoreceptor sensitivity was increased in PAH and CTEPH&#44; peripheral chemoreceptor responses to hypoxia and hypercapnia did not correlate with any exercise parameter&#46; However&#44; central chemoreceptor sensitivity to hypercapnia did correlate with the <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">A</span>&#47;<span class="elsevierStyleItalic">V</span>CO<span class="elsevierStyleInf">2</span> slope during exercise&#44; suggesting that the higher <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">A</span> due to a lower central CO<span class="elsevierStyleInf">2</span> setpoint could be the main explanation for resting hypocapnia&#46; We extend and confirm their results that the CO<span class="elsevierStyleInf">2</span> setpoint is likely an important underlying mechanism of inefficient ventilation to a much larger population&#46; Together&#44; we and Farina et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a> imply that hypocapnic patients and&#47;or those with low maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> during exercise have autonomic dysfunction and a lower CO<span class="elsevierStyleInf">2</span> setpoint&#46; Thus&#44; resting PaCO<span class="elsevierStyleInf">2</span> or maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> could be used to identify patients with probably autonomic dysfunction as inclusion criteria or to help enrich future studies that target the sympathetic nervous system in pulmonary vascular disease&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Limitations</span><p id="par0080" class="elsevierStylePara elsevierViewall">Our study has limitations given its retrospective nature&#46; Autonomic function and chemoreflex responses were not specifically tested in our study&#44; therefore&#44; we may only generate additional hypotheses about the relative role these reflexes in the high ventilatory inefficiency in our population&#46; However&#44; our results and conclusions are supportive of a recent smaller study by Farina et al&#46;&#44; which did test chemoreflexes&#46; Although the distinction and definitions of normocapnia and hypocapnia were made a priori&#44; there was a smaller number of patients in the normocapnic group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&#44; which may have affected statistical significance in comparing certain patient characteristics or correlations&#46; The different proportion of etiologies between the hypo and normocapnic groups and their different sizes may also explain some of the weaker correlations and conclusions&#46; We also did not have resting or exertional echocardiographic data to exclude a patent foramen ovale in patients with exercise-related desaturation and high <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span>&#44; which could be a contributing mechanism of inefficient ventilation in some patients&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">34</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0085" class="elsevierStylePara elsevierViewall">Patients with resting hypocapnia have worse cardiac function and more severe gas exchange abnormalities during exercise&#46; High chemosensitivity and an altered PaCO<span class="elsevierStyleInf">2</span> setpoint are likely explanations for resting hypocapnia and high <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span>&#46; The PaCO<span class="elsevierStyleInf">2</span> setpoint&#44; estimated by the maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> was the strongest correlate of peak exercise capacity and <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span>&#44; suggesting that this variable could be used as a non-invasive measure of CO<span class="elsevierStyleInf">2</span> setpoint and disease severity even during submaximal exercise&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of Interests</span><p id="par0090" class="elsevierStylePara elsevierViewall">Dr&#46; Weatherald reports grants&#44; personal fees and non-financial support from Actelion and Janssen Inc&#46;&#44; personal fees and non-financial support from Bayer&#44; personal fees from Novartis&#44; grants from grants from Canadian Vascular Network&#44; outside the submitted work&#59; grants from European Respiratory Society related to the current work&#46; Dr&#46; Boucly reports personal fees and non-financial support from Actelion Pharmaceuticals&#44; non-financial support from Bayer HealthCare&#44; non-financial support from GlaxoSmithKline&#44; personal fees and non-financial support from Merck&#44; outside the submitted work&#46; Dr&#46; Montani reports grants and personal fees from Actelion Pharmaceuticals&#44; grants and personal fees from Bayer HealthCare&#44; personal fees from GlaxoSmithKline&#44; personal fees from Novartis&#44; personal fees from Pfizer&#44; personal fees from BMS&#44; outside the submitted work&#46; Dr&#46; Ja&#239;s reports grants&#44; personal fees and non-financial support from Actelion Pharmaceuticals&#44; grants&#44; personal fees and non-financial support from Bayer HealthCare&#44; grants&#44; personal fees and non-financial support from GlaxoSmithKline&#44; grants&#44; personal fees and non-financial support from MSD&#44; outside the submitted work&#46; Dr&#46; Savale reports grants and personal fees from Actelion Pharmaceuticals&#44; grants and personal fees from Bayer HealthCare&#44; personal fees from GlaxoSmithKline&#44; personal fees from Merck&#44; outside the submitted work&#46; Dr&#46; Humbert reports personal fees from Actelion&#44; grants and personal fees from Bayer&#44; grants and personal fees from GSK&#44; personal fees from Merck&#44; from United Therapeutics&#44; outside the submitted work&#46; Dr&#46; Sitbon reports grants&#44; personal fees and non-financial support from Actelion Pharmaceuticals&#44; personal fees from Acceleron Pharmaceuticals&#44; personal fees from Arena Pharmaceuticals&#44; grants and personal fees from Bayer HealthCare&#44; grants&#44; personal fees and non-financial support from GlaxoSmithKline&#44; personal fees from Gossamer Bio&#44; grants and personal fees from Merck&#44; outside the submitted work&#46; Dr&#46; Garcia has nothing to disclose&#46; Dr&#46; Laveneziana reports personal fees from NOVARTIS France&#44; personal fees from BOEHRINGER France&#44; outside the submitted work&#46;</p></span></span>"
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              "titulo" => "Background and Objective"
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          "titulo" => "Abbreviations"
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          "titulo" => "Resumen"
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          "titulo" => "Introduction"
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              "titulo" => "Study population"
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              "titulo" => "CPET testing"
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              "titulo" => "Statistical analysis"
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          "titulo" => "Conclusions"
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          "titulo" => "Conflicts of Interests"
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    "fechaRecibido" => "2019-08-06"
    "fechaAceptado" => "2019-12-22"
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          "clase" => "keyword"
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            0 => "Exercise"
            1 => "Pulmonary hypertension"
            2 => "Chemosensitivity"
            3 => "Ventilatory efficiency"
            4 => "Pathophysiology"
            5 => "Hypocapnia"
            6 => "Arterial blood gas"
          ]
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        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec1272229"
          "palabras" => array:17 [
            0 => "ABG"
            1 => "AT"
            2 => "CPET"
            3 => "CTEPH"
            4 => "Mpap"
            5 => "NYHA"
            6 => "PAH"
            7 => "P&#274;CO<span class="elsevierStyleInf">2</span>"
            8 => "P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span>"
            9 => "PVOD"
            10 => "PVR"
            11 => "RCP"
            12 => "<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span>"
            13 => "<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>"
            14 => "<span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span>"
            15 => "<span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span>"
            16 => "WR"
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          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1272230"
          "palabras" => array:7 [
            0 => "Ejercicio"
            1 => "Hipertensi&#243;n pulmonar"
            2 => "Quimiosensibilidad"
            3 => "Eficiencia ventilatoria"
            4 => "Fisiopatolog&#237;a"
            5 => "Hipocapnia"
            6 => "Gasometr&#237;a arterial"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Background and Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Ventilatory inefficiency &#40;high <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span>&#41; and resting hypocapnia are common in pulmonary vascular disease and are associated with poor prognosis&#46; Low resting PaCO<span class="elsevierStyleInf">2</span> suggests increased chemosensitivity or an altered PaCO<span class="elsevierStyleInf">2</span> set-point&#46; We aimed to determine the relationships between exercise gas exchange variables reflecting the PaCO<span class="elsevierStyleInf">2</span> set-point&#44; exercise capacity&#44; hemodynamics and <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span>&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Pulmonary arterial hypertension &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34&#41;&#44; chronic thromboembolic pulmonary hypertension &#40;CTEPH&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41; and pulmonary veno-occlusive disease &#40;PVOD&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; patients underwent rest and peak exercise arterial blood gas measurements during cardiopulmonary exercise testing&#46; Patients were grouped according to resting PaCO<span class="elsevierStyleInf">2</span>&#58; hypocapnic &#40;PaCO<span class="elsevierStyleInf">2</span> &#8804;34<span class="elsevierStyleHsp" style=""></span>mmHg&#41; or normocapnic &#40;PaCO<span class="elsevierStyleInf">2</span> 35&#8211;45<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#46; The PaCO<span class="elsevierStyleInf">2</span> set-point was estimated by the maximal value of end-tidal PCO<span class="elsevierStyleInf">2</span> &#40;maximal P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span>&#41; between the anaerobic threshold and respiratory compensation point&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The hypocapnic group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#41; had lower resting cardiac index &#40;3&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;0&#46;8 vs&#46; 3&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;0&#46;7<span class="elsevierStyleHsp" style=""></span>L&#47;min&#47;m<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44; lower peak <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span> &#40;15&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5 vs&#46; 20&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;3<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;min&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#44; and higher <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> slope &#40;60&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;6 vs&#46; 38&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;0&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; At peak exercise&#44; hypocapic patients had lower PaO<span class="elsevierStyleInf">2</span>&#44; higher <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> and higher P<span class="elsevierStyleInf">&#40;a-ET&#41;</span>CO<span class="elsevierStyleInf">2</span>&#46; Maximal P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;59&#41; and <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;59&#41; were more related to cardiac index than PaO<span class="elsevierStyleInf">2</span> or PaCO<span class="elsevierStyleInf">2</span> at rest or peak exercise&#46; Maximal P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> was the strongest correlate of <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> slope &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;86&#41;&#44; peak <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span> &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;64&#41; and peak work rate &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;49&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Resting hypocapnia is associated with worse cardiac function&#44; more ventilatory inefficiency and reduced exercise capacity&#46; This could be explained by elevated chemosensitivity and lower PaCO<span class="elsevierStyleInf">2</span> set-point&#46; Maximal P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> may be a useful non-invasive marker of PaCO<span class="elsevierStyleInf">2</span> setpoint and disease severity even with submaximal effort&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Background and Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusions"
          ]
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      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Contexto general y objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La ineficiencia ventilatoria &#40;V&#8217;<span class="elsevierStyleInf">E&#47;</span>V&#8217;CO<span class="elsevierStyleInf">2</span> alta&#41; y la hipocapnia en reposo son comunes en la enfermedad vascular pulmonar y se asocian con un mal pron&#243;stico&#46; La PaCO<span class="elsevierStyleInf">2</span> baja en reposo sugiere una mayor quimiosensibilidad o una alteraci&#243;n en el ajuste fisiol&#243;gico de la PaCO<span class="elsevierStyleInf">2</span>&#46; Nuestro objetivo fue determinar las relaciones entre las variables de intercambio de gases que reflejan el ajuste de la PaCO<span class="elsevierStyleInf">2</span> durante el ejercicio&#44; la capacidad de ejercicio&#44; la hemodin&#225;mica y la V&#8217;<span class="elsevierStyleInf">E&#47;</span>V&#8217;CO<span class="elsevierStyleInf">2</span>&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se realizaron mediciones de gases en sangre arterial durante las pruebas de ejercicio cardiopulmonar a pacientes con hipertensi&#243;n arterial pulmonar &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34&#41;&#44; hipertensi&#243;n pulmonar tromboemb&#243;lica cr&#243;nica &#40;HPTEC&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>19&#41; y enfermedad venooclusiva pulmonar &#40;EVOP&#44; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;&#46; Los pacientes se agruparon de acuerdo con su PaCO<span class="elsevierStyleInf">2</span> en reposo&#58; hipocapnia &#40;PaCO<span class="elsevierStyleInf">2</span> &#8804;34<span class="elsevierStyleHsp" style=""></span>mmHg&#41; o normocapnia &#40;PaCO<span class="elsevierStyleInf">2</span> 35&#8211;45<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#46; El ajuste de la PaCO<span class="elsevierStyleInf">2</span> se estim&#243; mediante el valor m&#225;ximo de PCO<span class="elsevierStyleInf">2</span> exhalado &#40;P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> m&#225;ximo&#41; entre el umbral anaer&#243;bico y el punto de compensaci&#243;n respiratoria&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El grupo hipoc&#225;pnico &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#41; ten&#237;a un &#237;ndice card&#237;aco en reposo m&#225;s bajo &#40;3&#44;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;8 vs&#46; 3&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;7<span class="elsevierStyleHsp" style=""></span>L&#47;min&#47;m<span class="elsevierStyleSup">2</span>&#44; <span class="elsevierStyleItalic">p</span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#44; un pico de V&#8217;O<span class="elsevierStyleInf">2</span> m&#225;s bajo &#40;15&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#44;5 vs 20&#44;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;3<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;min&#44; <span class="elsevierStyleItalic">p</span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#44; y mayor pendiente de V&#8217;<span class="elsevierStyleInf">E&#47;</span>V&#8217;CO<span class="elsevierStyleInf">2</span> &#40;60&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#44;6 vs&#46; 38&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;0&#44; <span class="elsevierStyleItalic">p</span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; En el punto de ejercicio m&#225;ximo&#44; los pacientes hipoc&#225;pnicos ten&#237;an una PaO<span class="elsevierStyleInf">2</span> m&#225;s baja&#44; un V<span class="elsevierStyleInf">D</span>&#47;V<span class="elsevierStyleInf">T</span> m&#225;s alto y una P<span class="elsevierStyleInf">&#40;a-ET&#41;</span> CO<span class="elsevierStyleInf">2</span> m&#225;s alta&#46; La P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> m&#225;xima &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;59&#41; y la V<span class="elsevierStyleInf">D</span>&#47;V<span class="elsevierStyleInf">T</span> &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>-0&#44;59&#41; estaban m&#225;s relacionadas con el &#237;ndice card&#237;aco que la PaO<span class="elsevierStyleInf">2</span> o la PaCO<span class="elsevierStyleInf">2</span> en reposo o en el punto de m&#225;ximo esfuerzo&#46; La P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> m&#225;xima fue la que mayor correlaci&#243;n tuvo con la pendiente V&#8217;<span class="elsevierStyleInf">E&#47;</span>V&#8217;CO<span class="elsevierStyleInf">2</span> &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>-0&#44;86&#41;&#44; la V&#8217;O<span class="elsevierStyleInf">2</span> m&#225;xima &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;64&#41; y la tasa de esfuerzo m&#225;ximo &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;49&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusiones</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La hipocapnia en reposo se asocia a una peor funci&#243;n card&#237;aca&#44; una mayor ineficiencia ventilatoria y una capacidad disminu&#237;da de ejercicio&#46; Esto podr&#237;a explicarse por una quimiosensibilidad elevada y un ajuste fisiol&#243;gico m&#225;s bajo de la PaCO<span class="elsevierStyleInf">2</span>&#46; La P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> m&#225;xima puede ser un marcador no invasivo &#250;til del ajuste de PaCO<span class="elsevierStyleInf">2</span> y la gravedad de la enfermedad incluso con un esfuerzo subm&#225;ximo&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Contexto general y objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Part of this study has been presented in abstract form at the European Respiratory Society Congress in Milan&#44; Italy&#44; on September 11&#44; 2017&#46;</p>"
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0110" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0065"
          ]
        ]
      ]
    ]
    "multimedia" => array:12 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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            "Alto" => 878
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Example of maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> calculation&#46; The PaCO<span class="elsevierStyleInf">2</span> setpoint was estimated noninvasively from the highest value of end-tidal PCO<span class="elsevierStyleInf">2</span> &#40;maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span>&#41; observed between the anaerobic threshold &#40;AT&#41; and the respiratory compensation point &#40;RCP&#41;&#44; when <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> remains constant&#46;</p>"
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1138
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            "Tamanyo" => 69409
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Receiver operating characteristic curve for discriminating a low-risk peak <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;min according to the maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> value observed between the anaerobic threshold and the respiratory compensation point&#46;</p>"
        ]
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        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1392
            "Ancho" => 2925
            "Tamanyo" => 219355
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        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> slope versus <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> at peak exercise&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">&#40;a-ET&#41;</span>CO<span class="elsevierStyleInf">2</span> at peak exercise&#44; and maximal <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> Max&#41; in patients with resting hypocapnia &#40;HC&#41; and resting normocapnia &#40;NC&#41;&#46; Shaded areas indicate 95&#37; confidence intervals&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 1395
            "Ancho" => 2925
            "Tamanyo" => 211315
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        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">&#40;a-ET&#41;</span>CO<span class="elsevierStyleInf">2</span> at peak exercise versus resting cardiac index in patients with resting hypocapnia &#40;HC&#41; and resting normocapnia &#40;NC&#41;&#46; Shaded areas indicate 95&#37; confidence intervals&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Fig&#46; 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 1395
            "Ancho" => 2925
            "Tamanyo" => 196573
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        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Peak exercise capacity &#40;peak <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span>&#41; versus <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> at peak exercise&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">&#40;a-ET&#41;</span>CO<span class="elsevierStyleInf">2</span> at peak exercise and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span><span class="elsevierStyleInf">max</span> in patients with resting hypocapnia &#40;HC&#41; and resting normocapnia &#40;NC&#41;&#46; Shaded areas indicate 95&#37; confidence intervals&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index&#59; PAH&#58; pulmonary arterial hypertension&#59; CTEPH&#58; chronic thromboembolic pulmonary hypertension&#59; PVOD&#58; pulmonary veno-occlusive disease&#59; NYHA&#58; New York Heart Association functional class&#59; 6MWT&#58; 6-minute walk test distance&#59; mPAP&#58; mean pulmonary arterial pressure&#59; PAWP&#58; pulmonary artery wedge pressure&#59; CI&#58; cardiac index&#59; PVR&#58; pulmonary vascular resistance&#59; D<span class="elsevierStyleInf">L</span>CO&#47;V<span class="elsevierStyleInf">A</span>&#58; diffusion capacity for carbon monoxide adjusted for alveolar volume&#59; Hg&#58; hemoglobin&#59; <span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span>&#58; minute ventilation&#47;carbon dioxide output&#59; WR peak&#58; work rate at peak exercise&#59; <span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span> peak&#58; oxygen consumption at peak exercise&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">All&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Hypocapnic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Normocapnic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;y&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44 &#40;28&#8211;57&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44 &#40;29&#8211;60&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#46;5 &#40;28&#8211;54&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;55&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;66&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;35&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;21&#8211;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;21&#8211;28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;22&#8211;26&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etiology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PAH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;57&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;41&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;90&#46;0&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CTEPH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;32&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;43&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;10&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PVOD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;10&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;15&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NYHA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;24&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;21&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;30&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;48&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;44&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;55&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;27&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;15&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6MWT &#40;m&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">529&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>101&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">508&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>96&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">566&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>104&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">mPAP &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PAWP &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CI &#40;L&#47;min&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PVR &#40;Wood units&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">D<span class="elsevierStyleInf">L</span>CO&#47;V<span class="elsevierStyleInf">A</span> &#40;&#37;pred&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;5<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hg &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;6 &#40;13&#46;4&#8211;15&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;4 &#40;13&#46;4&#8211;16&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#46;6 &#40;13&#46;4&#8211;15&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">V</span>&#8242;<span class="elsevierStyleInf">E</span>&#47;<span class="elsevierStyleItalic">V</span>&#8242;CO<span class="elsevierStyleInf">2</span> slope&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#46;0 &#40;40&#46;0&#8211;61&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#46;6 &#40;46&#46;6&#8211;68&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#46;1 &#40;32&#46;5&#8211;43&#46;4&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">WR peak &#40;Watts&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85 &#40;67&#8211;110&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">80 &#40;65&#8211;95&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">110 &#40;78&#8211;140&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">V</span>&#8242;O<span class="elsevierStyleInf">2</span> peak &#40;mL&#47;kg&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">81&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;7 <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6 <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">70&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#46;8<a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">16&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;2<a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">111&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;1<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">119&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;9<a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;</a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">18&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;2<a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">&#40;ET-a&#41;</span>O<span class="elsevierStyleInf">2</span> &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">65&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;1<a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">27&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;5<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">37&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;2<a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;</a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">&#40;A-a&#41;</span>O<span class="elsevierStyleInf">2</span> &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">52&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;4<a class="elsevierStyleCrossRef" href="#tblfn0015">&#42;</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">21&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;8<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">26&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;0 <a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">r</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;37&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8722;0&#46;47&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 15792129
Original language: English

DOI:10.1016/j.arbr.2019.12.013

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