Role of cardiopulmonary exercise test in early diagnosis of pulmonary hypertension in scleroderma patients

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De los 16 pacientes con CPET indicativa de HAP, esta se confirmó en 5 pacientes mediante CCD de reposo y en 7 por CCD de esfuerzo. De esos 16 pacientes, 10 tenían además DETECT positivo. 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Of the 16 patients with CPET indicative of PH, PH was confirmed in 5 patients by RHC at rest and during exercise RHC in 7. Of these 16 patients, 10 were also DETECT positive. PH was confirmed at rest in 3 and during exercise in 2. gr1." ] ] ] "textoCompleto" => "IntroductionPulmonary hypertension (PH) is a proliferative small-vessel pulmonary vasculopathy that affects gas exchange and produces increased pulmonary vascular pressures and resistances.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> This results in excess afterload for the right ventricle and causes its initial adaptive hypertrophy. Finally, the right ventricle fails, dilates and causes right heart failure and premature death.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> PH is a progressive disease, whose initial symptoms occur with exercise. Attempts have been made to establish the definition of exercise PH, but there is still no consensus among experts.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>Scleroderma is a disease with low prevalence in the general population.<a class="elsevierStyleCrossRefs" href="#bib0020">4,5</a> Associated pulmonary involvement includes the pulmonary interstitium with interstitial thickening and fibrosis, and/or involvement of the pulmonary vasculature (PH), which is the main prognostic marker in the disease.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Patients with scleroderma who develop PH have worse survival.<a class="elsevierStyleCrossRefs" href="#bib0035">7,8</a>Early diagnosis and early initiation of treatment improves survival.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Therefore, screening strategies have been designed to accelerate the detection of PH. Clinical practice guidelines<a class="elsevierStyleCrossRefs" href="#bib0050">10–12</a> recommend performing an echocardiogram<a class="elsevierStyleCrossRef" href="#bib0065">13</a> annually in asymptomatic patients looking for evidence of PH. The DETECT algorithm has been recently added to the recommendation, which has shown a significant increase in PH detection sensitivity (96–100%), although with low specificity (35.3–48%).<a class="elsevierStyleCrossRefs" href="#bib0070">14,15</a>Cardiopulmonary exercise testing (CPET) is a non-invasive and accessible test that provides detailed information on cardiopulmonary physiology, aerobic capacity and ventilatory efficiency. CPET reveals a characteristic and reproducible pattern in patients with PH. It has a proven prognostic utility and evaluates the response to treatment of patients with PAH.<a class="elsevierStyleCrossRefs" href="#bib0080">16–18</a>The aim of this work is to assess the usefulness of CPET in the early detection of PH in patients with scleroderma. In addition, exercise right heart catheterization (RHC) is proposed as the most appropriate method to confirm early-stage PH, defined as that in which there is already a loss of alveolar-capillary units due to established impairment of microcirculation, with the patient being asymptomatic at rest and presenting normal screening and diagnostic tests at rest.Material and methodsA 2-year (2018–2019) prospective analysis of a total of 52 consecutive patients, diagnosed with scleroderma in our health area, coming from different hospital centres in the region. In addition to the screening recommended by clinical practice guidelines (DETECT algorithm and annual resting echocardiogram), CPET was systematically performed on a stationary bicycle with a ramped increased load protocol. No prior calculation of sample size was performed.The calculation of the sensitivity and specificity of the different screening arms was performed based on the diagnostic test established as the gold standard, assuming that this test was not performed on subjects with no evidence of pulmonary hypertension in the screening tests because it was an invasive test.DETECT algorithmThe DETECT algorithm was completed using the 2 recommended diagnostic steps. The first step includes a physical examination for telangiectasias, blood tests for NT-proBNP, anticentromere antibodies and uric acid, spirometry with measurements of forced vital capacity and pulmonary carbon monoxide diffusion, as well as an electrocardiogram. Patients with scores above 300 in the first step require an echocardiogram including measurement of right atrial area and tricuspid regurgitation velocity. If the global score in the second step is greater than 35, it is recommended to perform RHC at rest to confirm or rule out the presence of PH.Cardiopulmonary exercise testingCPET was performed on a bicycle ergometer (Ergoline 900S) adjusted to the height and length of the patient's leg, which is connected to the metabolic gas analyser (Sandro Geratherm). A maximal test was considered achieved when a respiratory quotient (peak RER) greater than 1.10 (or peak RER > 1.09 measured at 2 min of recovery) and a submaximal test when values were lower than those described. CPETs with RER < 1 were not considered acceptable, requiring their repetition in a total of 2 patients.During its performance, oxygen saturation at rest and during exercise, functional capacity measured in direct METs and peak oxygen consumption (peak VO2), RER, oxygen uptake efficiency slope (OUES), CO2 in exhaled air (PetCO2) and O2 equivalents (PetCO2), CO2 pressures in exhaled air (PetCO2) and O2 and CO2 equivalents (EqO2 and EqCO2, respectively) were monitored, as well as the relationship between ventilation and CO2 (VE/VCO2 slope), breathing reserve and estimated ventilatory classification.Parameters that evidence the presence of pulmonary vascular disease are decreased aerobic capacity and the presence of ventilatory inefficiency.Reduced aerobic capacity is evidenced by an early and reduced anaerobic threshold; progressive desaturation with exercise, more significant the more severe the disease, low VO2 peak, low pulse O2, an equally decreased OUES and slow recovery of heart rate and VO2 after exercise.<a class="elsevierStyleCrossRefs" href="#bib0095">19,20</a>Ventilatory inefficiency is expressed by an increase in ventilatory equivalents (EqO2 and EqCO2), low PetCO2, with typically decreasing slope as the exercise load increases and increasing VE/VCO2 slope, implying a highly pathological ventilatory classification. In addition, a larger dead space is observed.In case of a sharp and sustained increase in ventilation and O2 and CO2 equivalents, together with a decrease in PetCO2 and a sharp desaturation, an intracardiac shunt (patent foramen ovale) with right-to-left flow,<a class="elsevierStyleCrossRef" href="#bib0105">21</a> indicative of hemodynamic severity and poor prognosis, should be suspected.Exercise right heart catheterizationDiagnostic confirmation of PH requires performing a RHC with direct invasive measurement of pulmonary pressures, pulmonary wedge pressure, cardiac output (CO) and pulmonary vascular resistances. We performed it by introducing a Swan-Ganz catheter through the right internal jugular vein with ultrasound-guided puncture.Patients with suspected PH by CPET and/or by DETECT protocol undergo a RHC. In those patients who showed normal values at rest, the study was completed by supine bicycle exercise catheterization.All invasive procedures are performed on a supine bicycle from the beginning, which allows, if PH is not confirmed at rest, to prolong the procedure by cycling exercise, maintaining continuous invasive recording of pulmonary haemodynamics during exercise. To obtain reproducible results, the supine bicycle protocol was adapted to that previously used in CPET in each patient, mimicking the exercise intensity. Patients are kept in the supine position throughout the exercise protocol to avoid postural variations in pulmonary capillary wedge pressure (PCWP).The definition of "exercise PH" proposed at the 6th World Symposium on Pulmonary Hypertension held in Nice in 2018 was adopted. This meeting defined exercise PH as that with normal mPAP values at rest and mPAP > 30 mmHg during exercise as long as CO is less than 10 l/min, i.e., total pulmonary resistance > 3 WU. This definition was not finally agreed upon and does not appear in the official publication of the Symposium<a class="elsevierStyleCrossRef" href="#bib0110">22</a>; however, there are studies that have established possible cut-off values for healthy subjects and subjects with known disease according to age<a class="elsevierStyleCrossRef" href="#bib0115">23</a> and the appropriate discriminatory role of pulmonary vascular resistances (PVR) during exercise.<a class="elsevierStyleCrossRef" href="#bib0120">24</a>The study was approved by the accredited Clinical Research Ethics Committee of the Toledo Hospital Complex. Patients were properly informed and signed the written informed consent before starting the study.ResultsThe study included a total of 52 consecutive patients diagnosed with scleroderma and under follow-up by the Rheumatology Department. The majority were female (89% of the total), with a mean age of 60.7 ± 9.6 years (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the demographic and clinical data of the patients).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>81% of the total number of patients were asymptomatic (42 patients). Only 10 patients reported dyspnoea at rest or with light exercise, of whom only 3 were diagnosed with PH by heart catheterization (gold standard).The clinical, electrocardiographic and laboratory analysis comprising the first step of the DETECT algorithm showed 28 patients (54% of the total) as possibly suffering from PA, all of whom completed the protocol with transthoracic echocardiography. Most of the patients had tricuspid regurgitation with a visible jet (62%) that allowed estimation of pulmonary pressures at rest; all of them had estimated pulmonary artery systolic pressure <35 mmHg.After performing an echocardiogram (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>), 10 patients (17%) of the total (52 patients) showed values above the limit established in the second step of the DETECT algorithm (35 points); in all of them, a heart catheterization at rest was recommended to confirm or rule out the disease.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>CPET detected an exercise physiology behaviour compatible with PH in 16 patients (30.8% of the total). Among these 16 patients were the 10 DETECT positive patients and 6 with negative DETECT results (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>, average CPET results in the 52 patients).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The study was completed with RHC in all patients with indication according to DETECT and in all those with data indicative of PH on CPET. A total of 16 RHCs were performed. The diagnosis of PH was established on RHC at rest in 3 of the 10 patients with positive DETECT and in a total of 5 patients of the 16 with positive CPET.Of the 16 patients with CPET indicative of PH, 11 did not meet diagnostic criteria for PH at rest, so they completed the protocol with supine cycling exercise. Of those 11, a total of 7 met the definition of exercise PH proposed in Nice 2018. Of these 7 with exercise PH, 2 had positive DETECT and negative RHC at rest (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Therefore, the sensitivity of DETECT to detect PH in our sample reached 70%, while the sensitivity of CPET was 100%. We found a total of 5 false positives from the DETECT algorithm and a total of 4 in CPET. The positive predictive value of clinical dyspnoea in our patients for the diagnosis of PH was 30% (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>DiscussionPH is a progressive and incurable proliferative pulmonary vasculopathy with high mortality. The diagnosis of PH is established by RHC at rest. At the last World Expert Meeting on PH held in Nice in 2018, the hemodynamic definition of PH was updated. PH is defined by mPAP > 20 mmHg, provided that the pulmonary wedging pressure is normal (PCWP ≤ 15 mmHg) and PVRs are elevated. (>3 WU or 240 dyn/s/cm−3) At that meeting the definition of exercise PH was further revised, taking into account the variations in CO and PCWP. The diagnosis of exercise PH was proposed if mPAP exceeded 30 mmHg provided that CO was <10 bpm, which means that total pulmonary vascular resistances must be above 3 WU.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>Many factors affect the behaviour of mPAP during exercise, making it difficult to define the normal range and, therefore, the pathological threshold. mPAP increases with age and with CO elevation. Healthy athletes can reach very high COs with exercise and show significant mPAP elevations, above values considered normal. It is also difficult to measure PCWP correctly due to the patient's movements during exercise and respiratory variations. In addition, PCWP is physiologically elevated during exercise and the normal range in healthy patients has not been established, although a significant elevation is known in patients with left ventricular diastolic dysfunction. Finally, PVRs are calculated using the formula PVR = (mPAP−PCWP)/CO, with a correct measurement of PCWP being essential to determine the aetiology responsible for the increase in mPAP during exercise. It is very difficult to discriminate between pulmonary hypertension secondary to left heart disease, especially in heart failure with preserved ejection fraction,<a class="elsevierStyleCrossRef" href="#bib0125">25</a> and exercise PH due to pulmonary vascular disease by exercise catheterization. Therefore, the proposed definition of PH has not yet been validated and further research is needed.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>The diagnosis of PH remains a delayed diagnosis, despite current diagnostic techniques, in particular the resting echocardiography included in the DETECT algorithm. The symptoms of PH initially manifest with exercise, with the patient being asymptomatic at rest. To detect the presence of pulmonary vasculopathy at earlier stages, CPET is proposed as a screening test rather than a resting ECG.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>The ability of CPET in the non-invasive detection of PH in patients with scleroderma has been previously published<a class="elsevierStyleCrossRef" href="#bib0080">16</a>; however, in our study we compared for the first time the early diagnosis sensitivity of the DETECT algorithm (current established screening method) versus CPET in patients diagnosed with scleroderma; in contrast to the work of Santaniello et al.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> and Luo et al.,<a class="elsevierStyleCrossRef" href="#bib0140">28</a> the presence of PH was assessed both at rest and during exercise.The results of this study suggest that CPET, a non-invasive and safe test, detects initial involvement of the pulmonary vasculature during exercise with greater sensitivity than current established screening (100 vs. 70%), while maintaining a high specificity (90%). This is because both the echocardiogram recommended by clinical guidelines and the DETECT protocol (whose second step includes such echocardiogram) are performed at rest. CPET demonstrates greater diagnostic yield and would be very useful to incorporate into the diagnostic algorithm.Exercise heart catheterization is safe and feasible and is able to unmask the presence of pulmonary vascular damage earlier in at-risk populations, which would accelerate diagnosis and initiation of treatment, improving the prognosis of the disease. At present there is no consensus definition of exercise PH, but it would be highly beneficial if increased research and the use of exercise heart catheterisation could lead to a consensus definition. Recently Ho et al. found an association between the presence of exercise hypertension and the development of cardiovascular events during follow-up in patients studied for dyspnea.<a class="elsevierStyleCrossRef" href="#bib0145">29</a>This is a study with a limited number of patients, due to the low incidence and prevalence of scleroderma and PH in a single center and with the likelihood of selection bias, as it includes patients who require referral from the Rheumatology and Internal Medicine departments of different hospitals.Only those with evidence of early-stage PH by DETECT or CPET underwent heart catheterization at rest and during exercise, as this is an invasive test. Therefore, we can only estimate the sensitivity, specificity, and predictive values in those cases.It is necessary to select a larger number of patients and more studies to obtain greater power in the results.ConclusionsEarly diagnosis and early initiation of treatment improves the vital prognosis of patients with scleroderma and PH. Incorporation of CPET into the PH screening algorithm in at-risk populations such as scleroderma could increase the sensitivity of screening and accelerate diagnosis. Exercise RHC in patients with high suspicion of exercise PH by CPET and normal pulmonary haemodynamics at rest is safe and allows earlier detection of PH, although the definition of exercise PH needs to be agreed upon.Conflict of interestThe authors declare that they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1881921" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1631275" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1881920" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1631276" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "DETECT algorithm" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Cardiopulmonary exercise testing" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Exercise right heart catheterization" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-03-15" "fechaAceptado" => "2022-07-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1631275" "palabras" => array:5 [ 0 => "Pulmonary hypertension" 1 => "Scleroderma" 2 => "Cardiopulmonary exercise testing" 3 => "Exercise right heart catheterization" 4 => "Screening" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1631276" "palabras" => array:5 [ 0 => "Hipertensión arterial pulmonar" 1 => "Esclerodermia" 2 => "Ergoespirometría" 3 => "Cateterismo cardiaco de esfuerzo" 4 => "Diagnóstico precoz" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionPulmonary arterial hypertension (PAH) is a severe, high mortality and progressive disease. Early diagnosis and treatment improves the prognosis. Patients with Scleroderma disease presents high risk of developing PAH. Established screening strategies - echocardiogram and DETECT algorithm- recognize the disease when it is already advanced. Cardiopulmonary Exercise Testing (CPET) detects pulmonary vascular injury in earlier stages. MethodsProspective study of 52 consecutive patients diagnosed of Scleroderma in our health area, during 2 years (2018 and 2019). All of them undergo CPET, in addition to the annual systematic screening. Sensitivity of current PAH screening is compared to CPET. To confirm the presence of PAH, right heart catheterization (RHC) is performed. In case of suspected PAH in CPET, but non-confirmatory right heart catheterization at rest, patients carried out exercise RHC. Results52 CPET were performed, of which 16 suggested PAH. Resting RHC confirmed PAH in 5 patients and exercise RHC in 7 (diagnostic sensitivity of CPET together with rest and exercise catheterization of 100%). Of these 16 patients, DETECT had identified 10, of whom resting RHC confirmed PAH in 3 (guideline-based diagnostic algorithm sensitivity 70%). ConclusionsCPET and exercise RHC could detect PAH earlier than established screening in patients with Scleroderma disease, allowing early diagnosis." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónLa hipertensión arterial pulmonar (HAP) es una enfermedad grave y progresiva, con elevada mortalidad. El diagnóstico precoz e inicio de tratamiento temprano, mejora el pronóstico. Los pacientes con esclerodermia tienen riesgo elevado de desarrollar HAP. La única estrategia de cribado establecida y validada (ecocardiograma y/o algoritmo DETECT) reconoce la enfermedad cuando ya está avanzada a pesar de encontrarse en una fase preclínica. La ergoespirometría (CPET) detecta afectación vascular pulmonar en fases más precoces. MétodosEstudio prospectivo de los 52 pacientes consecutivos diagnosticados de esclerodermia de nuestra área sanitaria, durante 2 años (2018 y 2019). A todos se les realizó CPET, además del cribado sistemático anual. Se comparó la sensibilidad para detectar HAP del cribado actual frente a la ergoespirometría. Para confirmar la presencia de HAP se realizó un cateterismo cardiaco derecho (CCD). En caso de mantener la sospecha de HAP en CPET, pero con CCD en reposo no confirmatorio, se continuó con CCD de esfuerzo. ResultadosSe realizaron 52 CPET, de las cuales 16 sugirieron HAP. El CCD de reposo confirmó HAP en 5 pacientes y el CCD de esfuerzo en otros 7 (sensibilidad diagnóstica de CPET junto al cateterismo de reposo y esfuerzo del 100%). De esos 16 pacientes, DETECT habría identificado 10, de los cuales el CCD de reposo confirmó HAP en 3 y el de esfuerzo en otros 2 (sensibilidad del algoritmo diagnóstico establecido según guías del 70%). ConclusionesLa CPET y el CCD de esfuerzo podrían reconocer HAP más precozmente que el cribado establecido en pacientes con esclerodermia, permitiendo adelantar el diagnóstico." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2301 "Ancho" => 2918 "Tamanyo" => 536016 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0055" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Results. Of the 16 patients with CPET indicative of PH, PH was confirmed in 5 patients by RHC at rest and during exercise RHC in 7. Of these 16 patients, 10 were also DETECT positive. PH was confirmed at rest in 3 and during exercise in 2. gr1." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0060" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "NT-proBNP, N-terminal pro-brain natriuretic peptide." "tablatextoimagen" => array:1 [ 0 => array:1 [ "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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical presentation and systemic involvement \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">Number of patients \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">Percentage of total (52 patients) \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">Symptoms at rest or during exercise \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">10 \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 \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">Cutaneous involvement \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 \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 \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">Joint involvement \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 \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">31 \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">Pulmonary involvement \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 \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">23 \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">Gastrointestinal involvement \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 \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">23 \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">Cardiovascular involvement \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 \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 \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">Kidney failure \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 \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 \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">Raynaud's syndrome \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 \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">50 \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">Telangiectasias \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">10 \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 \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">Electrocardiogram \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><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">Right axis deviation in the electrocardiogram" \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 \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 \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">Laboratory results \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><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">Anti-centromere Ab positive in blood test \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">31 \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">60 \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">Sample mean values \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><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">NT-proBNP<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>, pg/mL \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><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">231 ± 745) \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">Uric acid<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a>, mg/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"> \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">4.8 ± 1.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Reference values in outpatients: < 125 pg/mL." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Reference values: 2.4–5.7 mg/dl." ] ] ] "descripcion" => array:1 [ "en" => "Demographic data, physical signs and laboratory parameters of included patients." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0065" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "RA, right atrium; EDD, end-diastolic diameter; TR, tricuspid regurgitation; PASP, pulmonary artery systolic pressure; TAPSE, tricuspid annular plane systolic excursion; RV, right ventricle." "tablatextoimagen" => array:1 [ 0 => array:1 [ "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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Presence of left-sided valvular heart disease (mitral and/or aortic), n \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">2 \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">EDD RV, basal segments (average), mm \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">37.11 \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">EDD RV, middle segments (average), mm \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">31.1 \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">RV area (average), cm2 \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">13.78 \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">RV area (≥18 cm2), n \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 \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">Quantifiable tricuspid regurgitation, n (%) \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">32 (62) \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">TR greater than mild (colour Doppler occupancy >20% of RV, vena contracta >3 mm, PISA radius >0.5 cm), n \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 \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">Vmax of TR (average), m/s \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">2.3 \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">PASP ≥ 35 mmHg, n \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 \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">Pulmonary regurgitation greater than mild, n \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 \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">Pulmonary artery acceleration time <100 ms, n \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 \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">Pathological TAPSE (<17 mm), n \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 \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">Presence of pericardial effusion, n \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 \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">Preserved left ventricular ejection fraction (≥53%), n (%). \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">50 (96) \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">Left ventricular ejection fraction ≥40%. \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 (4) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Resting ECG data." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0070" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "MET, metabolic equivalent of task; OUES, oxygen uptake efficiency slope; PetCO2, carbon dioxide partial pressure; PetO2, oxygen partial pressure; RER, respiratory exchange ratio; VE/VCO2, slope of the ratio between ventilation and CO2 elimination." "tablatextoimagen" => array:1 [ 0 => array:1 [ "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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline O2 saturation, % \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">98.1 \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">End O2 saturation, % \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">96.9 \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">Peak RER \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">1.06 \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">MET \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">3.49 \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">Peak VO2 (ml/min/kg) \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">16.12 \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">Peak VO2 (% predicted) \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 \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">Peak heart rate, 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">136.5 \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">Heart rate (% of predicted) reached \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">85.2 \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">O2 pulse (ml/beat) \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">7.41 \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">Baseline PetO2 \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">87.55 \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">End PetO2 \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">105.02 \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 at rest (test baseline) \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">30.53 \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">End PetCO2 \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">31 \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">Equivalent baseline CO2 \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">38.27 \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">Equivalent end CO2 \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">37.89 \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">OUES \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">1.28 \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">VE/VCO2 \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">36.07 \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">Average breathing reserve, %. \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 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Average CPET results in the 52 patients." ] ] 4 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0075" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "CPET, cardiopulmonary exercise testing." "tablatextoimagen" => array:1 [ 0 => array:1 [ "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="left" 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">Sensitivity, % \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">Specificity, % \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">Positive predictive value, % \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">Negative predictive value, % \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">DETECT algorithm \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 \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">89 \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">50 \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">95 \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">AlgorithmDETECT + CPET \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">100 \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">90 \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">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">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Sensitivity and specificity values, and positive and negative predictive values of the DETECT strategy and the DETECT strategy + CPET based on the gold standard (right heart catheterization)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: an update" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. 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Role of cardiopulmonary exercise test in early diagnosis of pulmonary hypertension in scleroderma patients

Utilidad de la ergoespirometría en el diagnóstico precoz de hipertensión pulmonar en pacientes con esclerodermia

Paula Sánchez-Aguilera Sánchez-Pauletea, María Lázaro Salvadorb,

Corresponding author

maria.lasal@gmail.com

Corresponding author.

, Alejandro Berenguel Senéna, Clara Méndez Perlesb, Luis Rodríguez Padiala

a Servicio de Cardiología, Hospital Universitario de Toledo, Toledo, Spain

b Servicio de Reumatología, Hospital Universitario de Toledo, Toledo, Spain

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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Results&#46; Of the 16 patients with CPET indicative of PH&#44; PH was confirmed in 5 patients by RHC at rest and during exercise RHC in 7&#46; Of these 16 patients&#44; 10 were also DETECT positive&#46; PH was confirmed at rest in 3 and during exercise in 2&#46; gr1&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Pulmonary hypertension &#40;PH&#41; is a proliferative small-vessel pulmonary vasculopathy that affects gas exchange and produces increased pulmonary vascular pressures and resistances&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This results in excess afterload for the right ventricle and causes its initial adaptive hypertrophy&#46; Finally&#44; the right ventricle fails&#44; dilates and causes right heart failure and premature death&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> PH is a progressive disease&#44; whose initial symptoms occur with exercise&#46; Attempts have been made to establish the definition of exercise PH&#44; but there is still no consensus among experts&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Scleroderma is a disease with low prevalence in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> Associated pulmonary involvement includes the pulmonary interstitium with interstitial thickening and fibrosis&#44; and&#47;or involvement of the pulmonary vasculature &#40;PH&#41;&#44; which is the main prognostic marker in the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Patients with scleroderma who develop PH have worse survival&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Early diagnosis and early initiation of treatment improves survival&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Therefore&#44; screening strategies have been designed to accelerate the detection of PH&#46; Clinical practice guidelines<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;12</span></a> recommend performing an echocardiogram<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> annually in asymptomatic patients looking for evidence of PH&#46; The DETECT algorithm has been recently added to the recommendation&#44; which has shown a significant increase in PH detection sensitivity &#40;96&#8211;100&#37;&#41;&#44; although with low specificity &#40;35&#46;3&#8211;48&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing &#40;CPET&#41; is a non-invasive and accessible test that provides detailed information on cardiopulmonary physiology&#44; aerobic capacity and ventilatory efficiency&#46; CPET reveals a characteristic and reproducible pattern in patients with PH&#46; It has a proven prognostic utility and evaluates the response to treatment of patients with PAH&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;18</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of this work is to assess the usefulness of CPET in the early detection of PH in patients with scleroderma&#46; In addition&#44; exercise right heart catheterization &#40;RHC&#41; is proposed as the most appropriate method to confirm early-stage PH&#44; defined as that in which there is already a loss of alveolar-capillary units due to established impairment of microcirculation&#44; with the patient being asymptomatic at rest and presenting normal screening and diagnostic tests at rest&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">A 2-year &#40;2018&#8211;2019&#41; prospective analysis of a total of 52 consecutive patients&#44; diagnosed with scleroderma in our health area&#44; coming from different hospital centres in the region&#46; In addition to the screening recommended by clinical practice guidelines &#40;DETECT algorithm and annual resting echocardiogram&#41;&#44; CPET was systematically performed on a stationary bicycle with a ramped increased load protocol&#46; No prior calculation of sample size was performed&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The calculation of the sensitivity and specificity of the different screening arms was performed based on the diagnostic test established as the gold standard&#44; assuming that this test was not performed on subjects with no evidence of pulmonary hypertension in the screening tests because it was an invasive test&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">DETECT algorithm</span><p id="par0040" class="elsevierStylePara elsevierViewall">The DETECT algorithm was completed using the 2 recommended diagnostic steps&#46; The first step includes a physical examination for telangiectasias&#44; blood tests for NT-proBNP&#44; anticentromere antibodies and uric acid&#44; spirometry with measurements of forced vital capacity and pulmonary carbon monoxide diffusion&#44; as well as an electrocardiogram&#46; Patients with scores above 300 in the first step require an echocardiogram including measurement of right atrial area and tricuspid regurgitation velocity&#46; If the global score in the second step is greater than 35&#44; it is recommended to perform RHC at rest to confirm or rule out the presence of PH&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Cardiopulmonary exercise testing</span><p id="par0045" class="elsevierStylePara elsevierViewall">CPET was performed on a bicycle ergometer &#40;Ergoline 900S&#41; adjusted to the height and length of the patient&#39;s leg&#44; which is connected to the metabolic gas analyser &#40;Sandro Geratherm&#41;&#46; A maximal test was considered achieved when a respiratory quotient &#40;peak RER&#41; greater than 1&#46;10 &#40;or peak RER &#62; 1&#46;09 measured at 2 min of recovery&#41; and a submaximal test when values were lower than those described&#46; CPETs with RER &#60; 1 were not considered acceptable&#44; requiring their repetition in a total of 2 patients&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">During its performance&#44; oxygen saturation at rest and during exercise&#44; functional capacity measured in direct METs and peak oxygen consumption &#40;peak VO<span class="elsevierStyleInf">2</span>&#41;&#44; RER&#44; oxygen uptake efficiency slope &#40;OUES&#41;&#44; CO<span class="elsevierStyleInf">2</span> in exhaled air &#40;PetCO<span class="elsevierStyleInf">2</span>&#41; and O<span class="elsevierStyleInf">2</span> equivalents &#40;PetCO<span class="elsevierStyleInf">2</span>&#41;&#44; CO<span class="elsevierStyleInf">2</span> pressures in exhaled air &#40;PetCO2&#41; and O<span class="elsevierStyleInf">2</span> and CO<span class="elsevierStyleInf">2</span> equivalents &#40;EqO<span class="elsevierStyleInf">2</span> and EqCO<span class="elsevierStyleInf">2</span>&#44; respectively&#41; were monitored&#44; as well as the relationship between ventilation and CO<span class="elsevierStyleInf">2</span> &#40;VE&#47;VCO<span class="elsevierStyleInf">2</span> slope&#41;&#44; breathing reserve and estimated ventilatory classification&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Parameters that evidence the presence of pulmonary vascular disease are decreased aerobic capacity and the presence of ventilatory inefficiency&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Reduced aerobic capacity is evidenced by an early and reduced anaerobic threshold&#59; progressive desaturation with exercise&#44; more significant the more severe the disease&#44; low VO<span class="elsevierStyleInf">2</span> peak&#44; low pulse O<span class="elsevierStyleInf">2</span>&#44; an equally decreased OUES and slow recovery of heart rate and VO<span class="elsevierStyleInf">2</span> after exercise&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Ventilatory inefficiency is expressed by an increase in ventilatory equivalents &#40;EqO<span class="elsevierStyleInf">2</span> and EqCO<span class="elsevierStyleInf">2</span>&#41;&#44; low PetCO<span class="elsevierStyleInf">2</span>&#44; with typically decreasing slope as the exercise load increases and increasing VE&#47;VCO<span class="elsevierStyleInf">2</span> slope&#44; implying a highly pathological ventilatory classification&#46; In addition&#44; a larger dead space is observed&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In case of a sharp and sustained increase in ventilation and O<span class="elsevierStyleInf">2</span> and CO<span class="elsevierStyleInf">2</span> equivalents&#44; together with a decrease in PetCO<span class="elsevierStyleInf">2</span> and a sharp desaturation&#44; an intracardiac shunt &#40;patent foramen ovale&#41; with right-to-left flow&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> indicative of hemodynamic severity and poor prognosis&#44; should be suspected&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Exercise right heart catheterization</span><p id="par0075" class="elsevierStylePara elsevierViewall">Diagnostic confirmation of PH requires performing a RHC with direct invasive measurement of pulmonary pressures&#44; pulmonary wedge pressure&#44; cardiac output &#40;CO&#41; and pulmonary vascular resistances&#46; We performed it by introducing a Swan-Ganz catheter through the right internal jugular vein with ultrasound-guided puncture&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Patients with suspected PH by CPET and&#47;or by DETECT protocol undergo a RHC&#46; In those patients who showed normal values at rest&#44; the study was completed by supine bicycle exercise catheterization&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">All invasive procedures are performed on a supine bicycle from the beginning&#44; which allows&#44; if PH is not confirmed at rest&#44; to prolong the procedure by cycling exercise&#44; maintaining continuous invasive recording of pulmonary haemodynamics during exercise&#46; To obtain reproducible results&#44; the supine bicycle protocol was adapted to that previously used in CPET in each patient&#44; mimicking the exercise intensity&#46; Patients are kept in the supine position throughout the exercise protocol to avoid postural variations in pulmonary capillary wedge pressure &#40;PCWP&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The definition of &#34;exercise PH&#34; proposed at the 6th World Symposium on Pulmonary Hypertension held in Nice in 2018 was adopted&#46; This meeting defined exercise PH as that with normal mPAP values at rest and mPAP &#62; 30 mmHg during exercise as long as CO is less than 10 l&#47;min&#44; i&#46;e&#46;&#44; total pulmonary resistance &#62; 3 WU&#46; This definition was not finally agreed upon and does not appear in the official publication of the Symposium<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#59; however&#44; there are studies that have established possible cut-off values for healthy subjects and subjects with known disease according to age<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and the appropriate discriminatory role of pulmonary vascular resistances &#40;PVR&#41; during exercise&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The study was approved by the accredited Clinical Research Ethics Committee of the Toledo Hospital Complex&#46; Patients were properly informed and signed the written informed consent before starting the study&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0100" class="elsevierStylePara elsevierViewall">The study included a total of 52 consecutive patients diagnosed with scleroderma and under follow-up by the Rheumatology Department&#46; The majority were female &#40;89&#37; of the total&#41;&#44; with a mean age of 60&#46;7 &#177; 9&#46;6 years &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the demographic and clinical data of the patients&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">81&#37; of the total number of patients were asymptomatic &#40;42 patients&#41;&#46; Only 10 patients reported dyspnoea at rest or with light exercise&#44; of whom only 3 were diagnosed with PH by heart catheterization <span class="elsevierStyleItalic">&#40;gold standard&#41;&#46;</span></p><p id="par0110" class="elsevierStylePara elsevierViewall">The clinical&#44; electrocardiographic and laboratory analysis comprising the first step of the DETECT algorithm showed 28 patients &#40;54&#37; of the total&#41; as possibly suffering from PA&#44; all of whom completed the protocol with transthoracic echocardiography&#46; Most of the patients had tricuspid regurgitation with a visible jet &#40;62&#37;&#41; that allowed estimation of pulmonary pressures at rest&#59; all of them had estimated pulmonary artery systolic pressure &#60;35 mmHg&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">After performing an echocardiogram &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; 10 patients &#40;17&#37;&#41; of the total &#40;52 patients&#41; showed values above the limit established in the second step of the DETECT algorithm &#40;35 points&#41;&#59; in all of them&#44; a heart catheterization at rest was recommended to confirm or rule out the disease&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">CPET detected an exercise physiology behaviour compatible with PH in 16 patients &#40;30&#46;8&#37; of the total&#41;&#46; Among these 16 patients were the 10 DETECT positive patients and 6 with negative DETECT results &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#44; average CPET results in the 52 patients&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">The study was completed with RHC in all patients with indication according to DETECT and in all those with data indicative of PH on CPET&#46; A total of 16 RHCs were performed&#46; The diagnosis of PH was established on RHC at rest in 3 of the 10 patients with positive DETECT and in a total of 5 patients of the 16 with positive CPET&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Of the 16 patients with CPET indicative of PH&#44; 11 did not meet diagnostic criteria for PH at rest&#44; so they completed the protocol with supine cycling exercise&#46; Of those 11&#44; a total of 7 met the definition of exercise PH proposed in Nice 2018&#46; Of these 7 with exercise PH&#44; 2 had positive DETECT and negative RHC at rest &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">Therefore&#44; the sensitivity of DETECT to detect PH in our sample reached 70&#37;&#44; while the sensitivity of CPET was 100&#37;&#46; We found a total of 5 false positives from the DETECT algorithm and a total of 4 in CPET&#46; The positive predictive value of clinical dyspnoea in our patients for the diagnosis of PH was 30&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0140" class="elsevierStylePara elsevierViewall">PH is a progressive and incurable proliferative pulmonary vasculopathy with high mortality&#46; The diagnosis of PH is established by RHC at rest&#46; At the last World Expert Meeting on PH held in Nice in 2018&#44; the hemodynamic definition of PH was updated&#46; PH is defined by mPAP &#62; 20 mmHg&#44; provided that the pulmonary wedging pressure is normal &#40;PCWP &#8804; 15 mmHg&#41; and PVRs are elevated&#46; &#40;&#62;3 WU or 240 dyn&#47;s&#47;cm<span class="elsevierStyleSup">&#8722;3</span>&#41; At that meeting the definition of exercise PH was further revised&#44; taking into account the variations in CO and PCWP&#46; The diagnosis of exercise PH was proposed if mPAP exceeded 30 mmHg provided that CO was &#60;10 bpm&#44; which means that total pulmonary vascular resistances must be above 3 WU&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Many factors affect the behaviour of mPAP during exercise&#44; making it difficult to define the normal range and&#44; therefore&#44; the pathological threshold&#46; mPAP increases with age and with CO elevation&#46; Healthy athletes can reach very high COs with exercise and show significant mPAP elevations&#44; above values considered normal&#46; It is also difficult to measure PCWP correctly due to the patient&#39;s movements during exercise and respiratory variations&#46; In addition&#44; PCWP is physiologically elevated during exercise and the normal range in healthy patients has not been established&#44; although a significant elevation is known in patients with left ventricular diastolic dysfunction&#46; Finally&#44; PVRs are calculated using the formula PVR &#61; &#40;mPAP&#8722;PCWP&#41;&#47;CO&#44; with a correct measurement of PCWP being essential to determine the aetiology responsible for the increase in mPAP during exercise&#46; It is very difficult to discriminate between pulmonary hypertension secondary to left heart disease&#44; especially in heart failure with preserved ejection fraction&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> and exercise PH due to pulmonary vascular disease by exercise catheterization&#46; Therefore&#44; the proposed definition of PH has not yet been validated and further research is needed&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The diagnosis of PH remains a delayed diagnosis&#44; despite current diagnostic techniques&#44; in particular the resting echocardiography included in the DETECT algorithm&#46; The symptoms of PH initially manifest with exercise&#44; with the patient being asymptomatic at rest&#46; To detect the presence of pulmonary vasculopathy at earlier stages&#44; CPET is proposed as a screening test rather than a resting ECG&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The ability of CPET in the non-invasive detection of PH in patients with scleroderma has been previously published<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#59; however&#44; in our study we compared for the first time the early diagnosis sensitivity of the DETECT algorithm &#40;current established screening method&#41; versus CPET in patients diagnosed with scleroderma&#59; in contrast to the work of Santaniello et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and Luo et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> the presence of PH was assessed both at rest and during exercise&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The results of this study suggest that CPET&#44; a non-invasive and safe test&#44; detects initial involvement of the pulmonary vasculature during exercise with greater sensitivity than current established screening &#40;100 vs&#46; 70&#37;&#41;&#44; while maintaining a high specificity &#40;90&#37;&#41;&#46; This is because both the echocardiogram recommended by clinical guidelines and the DETECT protocol &#40;whose second step includes such echocardiogram&#41; are performed at rest&#46; CPET demonstrates greater diagnostic yield and would be very useful to incorporate into the diagnostic algorithm&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Exercise heart catheterization is safe and feasible and is able to unmask the presence of pulmonary vascular damage earlier in at-risk populations&#44; which would accelerate diagnosis and initiation of treatment&#44; improving the prognosis of the disease&#46; At present there is no consensus definition of exercise PH&#44; but it would be highly beneficial if increased research and the use of exercise heart catheterisation could lead to a consensus definition&#46; Recently Ho et al&#46; found an association between the presence of exercise hypertension and the development of cardiovascular events during follow-up in patients studied for dyspnea&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">This is a study with a limited number of patients&#44; due to the low incidence and prevalence of scleroderma and PH in a single center and with the likelihood of selection bias&#44; as it includes patients who require referral from the Rheumatology and Internal Medicine departments of different hospitals&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Only those with evidence of early-stage PH by DETECT or CPET underwent heart catheterization at rest and during exercise&#44; as this is an invasive test&#46; Therefore&#44; we can only estimate the sensitivity&#44; specificity&#44; and predictive values in those cases&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">It is necessary to select a larger number of patients and more studies to obtain greater power in the results&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusions</span><p id="par0185" class="elsevierStylePara elsevierViewall">Early diagnosis and early initiation of treatment improves the vital prognosis of patients with scleroderma and PH&#46; Incorporation of CPET into the PH screening algorithm in at-risk populations such as scleroderma could increase the sensitivity of screening and accelerate diagnosis&#46; Exercise RHC in patients with high suspicion of exercise PH by CPET and normal pulmonary haemodynamics at rest is safe and allows earlier detection of PH&#44; although the definition of exercise PH needs to be agreed upon&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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              "titulo" => "Cardiopulmonary exercise testing"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Exercise right heart catheterization"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Results"
        ]
        7 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Conclusions"
        ]
        9 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Conflict of interest"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2022-03-15"
    "fechaAceptado" => "2022-07-07"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1631275"
          "palabras" => array:5 [
            0 => "Pulmonary hypertension"
            1 => "Scleroderma"
            2 => "Cardiopulmonary exercise testing"
            3 => "Exercise right heart catheterization"
            4 => "Screening"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1631276"
          "palabras" => array:5 [
            0 => "Hipertensi&#243;n arterial pulmonar"
            1 => "Esclerodermia"
            2 => "Ergoespirometr&#237;a"
            3 => "Cateterismo cardiaco de esfuerzo"
            4 => "Diagn&#243;stico precoz"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Pulmonary arterial hypertension &#40;PAH&#41; is a severe&#44; high mortality and progressive disease&#46; Early diagnosis and treatment improves the prognosis&#46; Patients with Scleroderma disease presents high risk of developing PAH&#46; Established screening strategies - echocardiogram and DETECT algorithm- recognize the disease when it is already advanced&#46; Cardiopulmonary Exercise Testing &#40;CPET&#41; detects pulmonary vascular injury in earlier stages&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Prospective study of 52 consecutive patients diagnosed of Scleroderma in our health area&#44; during 2 years &#40;2018 and 2019&#41;&#46; All of them undergo CPET&#44; in addition to the annual systematic screening&#46; Sensitivity of current PAH screening is compared to CPET&#46; To confirm the presence of PAH&#44; right heart catheterization &#40;RHC&#41; is performed&#46; In case of suspected PAH in CPET&#44; but non-confirmatory right heart catheterization at rest&#44; patients carried out exercise RHC&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">52 CPET were performed&#44; of which 16 suggested PAH&#46; Resting RHC confirmed PAH in 5 patients and exercise RHC in 7 &#40;diagnostic sensitivity of CPET together with rest and exercise catheterization of 100&#37;&#41;&#46; Of these 16 patients&#44; DETECT had identified 10&#44; of whom resting RHC confirmed PAH in 3 &#40;guideline-based diagnostic algorithm sensitivity 70&#37;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">CPET and exercise RHC could detect PAH earlier than established screening in patients with Scleroderma disease&#44; allowing early diagnosis&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">La hipertensi&#243;n arterial pulmonar &#40;HAP&#41; es una enfermedad grave y progresiva&#44; con elevada mortalidad&#46; El diagn&#243;stico precoz e inicio de tratamiento temprano&#44; mejora el pron&#243;stico&#46; Los pacientes con esclerodermia tienen riesgo elevado de desarrollar HAP&#46; La &#250;nica estrategia de cribado establecida y validada &#40;ecocardiograma y&#47;o algoritmo DETECT&#41; reconoce la enfermedad cuando ya est&#225; avanzada a pesar de encontrarse en una fase precl&#237;nica&#46; La ergoespirometr&#237;a &#40;CPET&#41; detecta afectaci&#243;n vascular pulmonar en fases m&#225;s precoces&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo de los 52 pacientes consecutivos diagnosticados de esclerodermia de nuestra &#225;rea sanitaria&#44; durante 2 a&#241;os &#40;2018 y 2019&#41;&#46; A todos se les realiz&#243; CPET&#44; adem&#225;s del cribado sistem&#225;tico anual&#46; Se compar&#243; la sensibilidad para detectar HAP del cribado actual frente a la ergoespirometr&#237;a&#46; Para confirmar la presencia de HAP se realiz&#243; un cateterismo cardiaco derecho &#40;CCD&#41;&#46; En caso de mantener la sospecha de HAP en CPET&#44; pero con CCD en reposo no confirmatorio&#44; se continu&#243; con CCD de esfuerzo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Se realizaron 52 CPET&#44; de las cuales 16 sugirieron HAP&#46; El CCD de reposo confirm&#243; HAP en 5 pacientes y el CCD de esfuerzo en otros 7 &#40;sensibilidad diagn&#243;stica de CPET junto al cateterismo de reposo y esfuerzo del 100&#37;&#41;&#46; De esos 16 pacientes&#44; DETECT habr&#237;a identificado 10&#44; de los cuales el CCD de reposo confirm&#243; HAP en 3 y el de esfuerzo en otros 2 &#40;sensibilidad del algoritmo diagn&#243;stico establecido seg&#250;n gu&#237;as del 70&#37;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">La CPET y el CCD de esfuerzo podr&#237;an reconocer HAP m&#225;s precozmente que el cribado establecido en pacientes con esclerodermia&#44; permitiendo adelantar el diagn&#243;stico&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "multimedia" => array:5 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2301
            "Ancho" => 2918
            "Tamanyo" => 536016
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        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0055"
            "detalle" => "Figure "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Results&#46; Of the 16 patients with CPET indicative of PH&#44; PH was confirmed in 5 patients by RHC at rest and during exercise RHC in 7&#46; Of these 16 patients&#44; 10 were also DETECT positive&#46; PH was confirmed at rest in 3 and during exercise in 2&#46; gr1&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0060"
            "detalle" => "Table "
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        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">NT-proBNP&#44; N-terminal pro-brain natriuretic peptide&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical presentation and systemic involvement&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">Number of patients&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">Percentage of total &#40;52 patients&#41;&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">Symptoms at rest or during exercise&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">10&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&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">Cutaneous involvement&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">30&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&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">Joint involvement&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&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">31&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">Pulmonary involvement&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">12&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">23&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">Gastrointestinal involvement&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">12&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">23&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">Cardiovascular involvement&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&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">12&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">Kidney failure&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&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">4&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">Raynaud&#39;s syndrome&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&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">50&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">Telangiectasias&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">10&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&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">Electrocardiogram&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><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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Right axis deviation in the electrocardiogram</span>&#34;&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"><span class="elsevierStyleBold">0</span>&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"><span class="elsevierStyleBold">0</span>&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">Laboratory results&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><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"><span class="elsevierStyleHsp" style=""></span>Anti-centromere Ab positive in blood test&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">31&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">60&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">Sample mean values&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><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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">NT-proBNP</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleItalic">&#44; pg&#47;mL</span>&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><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">231 &#177; 745&#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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Uric acid</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleItalic">&#44; mg&#47;dl</span>&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><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&#46;8 &#177; 1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Reference values in outpatients&#58; &#60; 125 pg&#47;mL&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Reference values&#58; 2&#46;4&#8211;5&#46;7 mg&#47;dl&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Demographic data&#44; physical signs and laboratory parameters of included patients&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0065"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">RA&#44; right atrium&#59; EDD&#44; end-diastolic diameter&#59; TR&#44; tricuspid regurgitation&#59; PASP&#44; pulmonary artery systolic pressure&#59; TAPSE&#44; tricuspid annular plane systolic excursion&#59; RV&#44; right ventricle&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Presence of left-sided valvular heart disease &#40;mitral and&#47;or aortic&#41;&#44; n&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">2&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">EDD RV&#44; basal segments &#40;average&#41;&#44; mm&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;11&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">EDD RV&#44; middle segments &#40;average&#41;&#44; mm&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">31&#46;1&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">RV area &#40;average&#41;&#44; cm<span class="elsevierStyleSup">2</span>&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&#46;78&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">RV area &#40;&#8805;18 cm<span class="elsevierStyleSup">2</span>&#41;&#44; n&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&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">Quantifiable tricuspid regurgitation&#44; n &#40;&#37;&#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">32 &#40;62&#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">TR greater than mild &#40;colour Doppler occupancy &#62;20&#37; of RV&#44; vena contracta &#62;3 mm&#44; PISA radius &#62;0&#46;5 cm&#41;&#44; n&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&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">Vmax of TR &#40;average&#41;&#44; m&#47;s&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&#46;3&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">PASP &#8805; 35 mmHg&#44; n&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&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">Pulmonary regurgitation greater than mild&#44; n&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&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">Pulmonary artery acceleration time &#60;100 ms&#44; n&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&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">Pathological TAPSE &#40;&#60;17 mm&#41;&#44; n&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&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">Presence of pericardial effusion&#44; n&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&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">Preserved left ventricular ejection fraction &#40;&#8805;53&#37;&#41;&#44; n &#40;&#37;&#41;&#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">50 &#40;96&#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">Left ventricular ejection fraction &#8805;40&#37;&#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">2 &#40;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Resting ECG data&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0070"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">MET&#44; metabolic equivalent of task&#59; OUES&#44; oxygen uptake efficiency slope&#59; PetCO<span class="elsevierStyleInf">2</span>&#44; carbon dioxide partial pressure&#59; PetO<span class="elsevierStyleInf">2</span>&#44; oxygen partial pressure&#59; RER&#44; respiratory exchange ratio&#59; VE&#47;VCO<span class="elsevierStyleInf">2</span>&#44; slope of the ratio between ventilation and CO<span class="elsevierStyleInf">2</span> elimination&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline O<span class="elsevierStyleInf">2</span> saturation&#44; &#37;&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">98&#46;1&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">End O<span class="elsevierStyleInf">2</span> saturation&#44; &#37;&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">96&#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">Peak RER&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">1&#46;06&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">MET&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;49&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">Peak VO<span class="elsevierStyleInf">2</span> &#40;ml&#47;min&#47;kg&#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&#46;12&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">Peak VO<span class="elsevierStyleInf">2</span> &#40;&#37; predicted&#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&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">Peak heart rate&#44; bpm&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">136&#46;5&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">Heart rate &#40;&#37; of predicted&#41; reached&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&#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">O<span class="elsevierStyleInf">2</span> pulse &#40;ml&#47;beat&#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;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">Baseline PetO<span class="elsevierStyleInf">2</span>&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">87&#46;55&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">End PetO<span class="elsevierStyleInf">2</span>&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">105&#46;02&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">PetCO<span class="elsevierStyleInf">2</span> at rest &#40;test baseline&#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">30&#46;53&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">End PetCO<span class="elsevierStyleInf">2</span>&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">31&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">Equivalent baseline CO<span class="elsevierStyleInf">2</span>&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">38&#46;27&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">Equivalent end CO<span class="elsevierStyleInf">2</span>&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;89&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">OUES&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">1&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VE&#47;VCO<span class="elsevierStyleInf">2</span>&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">36&#46;07&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">Average breathing reserve&#44; &#37;&#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">47&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">DETECT algorithm&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">70&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&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\ttable-entry\n
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                  \t\t\t\t">95&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">100&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">90&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">75&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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      "titulo" => "References"
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        0 => array:2 [
          "identificador" => "bibs0005"
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension&#58; an update"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Vonk Noordegraaf"
                            1 => "K&#46;M&#46; Chin"
                            2 => "F&#46; Haddad"
                            3 => "P&#46;M&#46; Hassoun"
                            4 => "A&#46;R&#46; Hemnes"
                            5 => "S&#46;R&#46; Hopkins"
                          ]
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                    0 => array:2 [
                      "doi" => "10.1183/13993003.01900-2018"
                      "Revista" => array:4 [
                        "tituloSerie" => "Eur Respir J&#46;"
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                ]
              ]
            ]
            1 => array:3 [
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Predicting survival in patients with pulmonary arterial hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            1 => "M&#46; Gomberg-Maitland"
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            2 => array:3 [
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                      "autores" => array:1 [
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                          "etal" => true
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            3 => array:3 [
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                0 => array:2 [
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                      "titulo" => "Systemic sclerosis"
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                    0 => array:2 [
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                    0 => array:2 [
                      "doi" => "10.12968/hmed.2019.80.9.530"
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                      "titulo" => "Causes and risk factors for death in systemic sclerosis&#58; a study from the EULAR Scleroderma Trials and Research &#40;EUSTAR&#41; database"
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                            3 => "P&#46; Airo"
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                    0 => array:2 [
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            6 => array:3 [
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                    0 => array:2 [
                      "titulo" => "Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension&#58; application of a registry approach"
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                    0 => array:2 [
                      "doi" => "10.1136/ard.62.11.1088"
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                        "tituloSerie" => "Ann Rheum Dis&#46;"
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              "identificador" => "bib0040"
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                  "contribucion" => array:1 [
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                            2 => "C&#46; Meune"
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                    0 => array:2 [
                      "doi" => "10.3899/jrheum.100245"
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