Left ventricular dysfunction and arrhythmias in asymptomatic patients with systemic sclerosis

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Abbreviations: EQ-5D-5L: EuroQol 5-dimension health questionnaire with 5 levels; FACIT-FATIGUE: Fatigue questionnaire; GHS: Global Health Status; HAQ: Health Assesment Questionnaire; SLEDAI: Systemic Lupus Erythematosus Disease Activity Index." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Elena Grau García, Jorge Juan Fragío Gil, Jose Ivorra Cortes, Francisco Miguel Ortiz Sanjuan, Inmaculada Chalmeta Verdejo, Jose Andrés Román Ivorra" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Elena" "apellidos" => "Grau García" ] 1 => array:2 [ "nombre" => "Jorge Juan" "apellidos" => "Fragío Gil" ] 2 => array:2 [ "nombre" => "Jose" "apellidos" => "Ivorra Cortes" ] 3 => array:2 [ "nombre" => "Francisco Miguel" "apellidos" => "Ortiz Sanjuan" ] 4 => array:2 [ "nombre" => "Inmaculada" "apellidos" => "Chalmeta Verdejo" ] 5 => array:2 [ "nombre" => "Jose Andrés" "apellidos" => "Román Ivorra" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775322006753?idApp=UINPBA00004N" "url" => "/00257753/0000016000000010/v2_202305172125/S0025775322006753/v2_202305172125/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Left ventricular dysfunction and arrhythmias in asymptomatic patients with systemic sclerosis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "434" "paginaFinal" => "442" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Lilian López Núñez, Irene Carrión-Barberà, Luis Molina, Isabel Padró, Manel Ciria, Laura Tío, Tarek Carlos Salman-Monte, Ana Pros" "autores" => array:8 [ 0 => array:3 [ "nombre" => "Lilian" "apellidos" => "López Núñez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Irene" "apellidos" => "Carrión-Barberà" "email" => array:2 [ 0 => "ipirenaica@gmail.com" 1 => "mcarrion@parcdesalutmar.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Luis" "apellidos" => "Molina" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Isabel" "apellidos" => "Padró" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Manel" "apellidos" => "Ciria" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Laura" "apellidos" => "Tío" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 6 => array:3 [ "nombre" => "Tarek Carlos" "apellidos" => "Salman-Monte" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "Ana" "apellidos" => "Pros" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Rheumatology Department, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Cardiology Department, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Cellular Research Group on Inflammation and Cartilage of the Hospital del Mar Medical Research Institute of Barcelona (IMIM), Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Disfunción ventricular izquierda y arritmias en pacientes asintomáticos con esclerosis sistémica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1859 "Ancho" => 2925 "Tamanyo" => 379948 ] ] "descripcion" => array:1 [ "en" => "Algorithm that shows patient selection and the examinations performed. SSc: systemic sclerosis; DILD, diffuse interstitial lung disease; PFT: pulmonary function tests; HRCT: high-resolution computed tomography; LVSD: left ventricular systolic dysfunction; LVEF: left ventricular ejection fraction; PAH: pulmonary hypertension; mPAP: mean pulmonary artery pressure; CVRF: cardiovascular risk factors; DM: diabetes mellitus; DLP: dyslipidaemia; AHT: arterial hypertension; CKD: chronic kidney disease; GFR: glomerular filtration rate; mRSS: modified Rodnan skin score; EKG: electrocardiogram." ] ] ] "textoCompleto" => "IntroductionSystemic sclerosis (SSc) is a chronic immune-mediated disease that affects several organs, including the heart. For decades, the existence of a primary heart condition in SSc was questioned, until in 1976 Bulkley et al. detected foci of myocardial necrosis with patchy distribution in pathological studies, which suggested that the myocardial injury could be due to a phenomenon of vasospasm of the intramural coronary microcirculation called coronary Raynaud's phenomenon. It was from then on that scleroderma-related myocardial involvement was considered a defined and relatively frequent entity<a class="elsevierStyleCrossRef" href="#bib0155">1</a>.Primary heart disease in SSc usually presents early during the first three years of disease onset, being clinically silent in most cases and recognized only in 15–25%<a class="elsevierStyleCrossRef" href="#bib0160">2</a>. It can affect any cardiac structure and manifest variously, even as sudden death (SD) in 5–54% of patients<a class="elsevierStyleCrossRef" href="#bib0165">3</a>. Cardiac involvement is one of the main causes of mortality in SSc (14–31% according to series<a class="elsevierStyleCrossRef" href="#bib0170">4</a>).Arrhythmias and conduction disturbances are frequent forms of cardiac involvement in SSc<a class="elsevierStyleCrossRef" href="#bib0175">5</a>. In unselected patients with SSc, the prevalence of electrocardiographic abnormalities ranges between 32 and 52% according to findings in electrocardiogram (EKG) and between 62 and 90% on the 24-h Holter EKG (Holter)<a class="elsevierStyleCrossRef" href="#bib0180">6</a>. Rokas et al. observed that even up to 57% of asymptomatic SSc patients without evidence of arrhythmias by EKG or Holter, presented significant tachyarrhythmias when performing invasive electrophysiological studies<a class="elsevierStyleCrossRef" href="#bib0185">7</a>. Ventricular arrhythmias are frequently found in SSc patients (up to 90% when using a Holter) and are generally acknowledged to have a poor prognosis when associated with impaired myocardial function, particularly multiform and/or repetitive ventricular premature beats. However, despite its frequent occurrence, sudden cardiac death is not very common in SSc<a class="elsevierStyleCrossRef" href="#bib0175">5</a>.Additionally, the Holter allows the study of cardiac autonomic dysfunction (CAD) by measuring heart rate variability as a proxy for cardiac sympathetic and parasympathetic activity. CAD is described in up to 42% of patients with SSc, and could indicate patients at high risk of developing arrhythmias<a class="elsevierStyleCrossRef" href="#bib0190">8</a>.In SSc, arrhythmias and conduction disturbances are more prevalent in patients with pulmonary arterial hypertension (PAH) and with ventricular dysfunction<a class="elsevierStyleCrossRef" href="#bib0195">9</a>. Some authors argue that myocardial fibrosis is a clear arrhythmogenic substrate and that, depending on its extension, it can lead to the development of ventricular dysfunction<a class="elsevierStyleCrossRef" href="#bib0200">10</a>. Although there exists ample evidence of diastolic and systolic involvement of both ventricles, even in early stages of SSc, there are few studies that have correlated these findings with arrhythmias.The prevalence of left ventricle diastolic dysfunction (LVDD) in SSc can reach 34% and it is associated with an increased risk of mortality (HR 3.2–3.7)<a class="elsevierStyleCrossRefs" href="#bib0205">11,12</a>. Several studies have concluded that LVDD and an increased left atrium as an indirect sign, in the absence of other causes, reflect a primary disease of the myocardium in SSc<a class="elsevierStyleCrossRef" href="#bib0215">13</a>. LVDD is progressive and precedes the appearance of remodeling, so it occurs much earlier than alterations in systolic function. When LVDD is suspected, Tissue Doppler echocardiography (TDE) is a useful method that allows an early assessment. However, in the detection of left ventricular systolic dysfunction (LVSD), the analysis of the left ventricular ejection fraction (LVEF) has shown to be scarcely sensitive, identifying only 5% of patients with SSc suffering from this alteration, usually in advanced stages<a class="elsevierStyleCrossRef" href="#bib0220">14</a>. Nevertheless, TDE is also used to determine other measurements such as the myocardial velocity and deformation through the global longitudinal strain (GLS), which allows physicians to perform a direct and early assessment of the systolic function. It is suggested that LVSD measured by GLS could predict the development of ventricular arrhythmias<a class="elsevierStyleCrossRef" href="#bib0195">9</a>.Regarding cardiac biomarkers, cardiac troponin T (TnTc) is a marker of cardiac damage, either due to ischemia or due to myocardial inflammation. Elevated levels have been related to the presence of frequent ventricular extrasystoles (VE) (>1190/24h), these being a factor of poor prognosis, SD or of the need for implantation of a defibrillator<a class="elsevierStyleCrossRef" href="#bib0225">15</a>. On the other hand, the N-terminal brain natriuretic propeptide (NT-proBNP) is the most studied biomarker in SSc, being currently part of the PAH screening guidelines. It is widely known that its elevation is also present, not only in response to right ventricular dysfunction, but also to left ventricular systolic and diastolic dysfunction (DD). Both markers have been reported to be elevated in patients with SSc compared to controls, even in patients without cardiovascular risk factors (CVRF), have been associated with cardiac involvement and have been postulated as biomarkers for its early detection. Allanore et al. propose the NT-ProBNP value>125pg/mL in patients<75 years, and >450pg/mL in older patients, as a threshold to use in SSc patients screening for silent cardiomyopathy<a class="elsevierStyleCrossRef" href="#bib0230">16</a>.It is evident that the presence of arrhythmias in SSc worsens the prognosis and increases mortality, which forces us to try to identify tools that help us to early diagnose and promptly establish appropriate treatment and/or follow-up.Our objective is to study the prevalence of left ventricular dysfunction and arrhythmias in our cohort of patients with SSc who do not have cardiac symptoms, a history of PAH or any known cardiac pathology, as well as to analyze whether there is an association between both entities or with other variables that could be predictors for the development of these complications.Materials and methodsProspective study on a cohort of SSc patients who met the SSc 2013 SSc ACR/EULAR classification criteria<a class="elsevierStyleCrossRef" href="#bib0235">17</a>. Patient's selection flowchart and tests performed per study protocol are detailed in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. Exclusion criteria involved previous diagnosis of a heart condition, which included any type of cardiomyopathy, arrhythmias, LVSD, treatment with arrhythmogenic drugs, previous diagnosis of PAH by right heart disease catheterization or suspicion of PAH according to any signs or symptoms or finding of a mean pulmonary artery pressure by echocardiogram>36mmHg, known cardiovascular risk factors or renal disease with a glomerular filtration rate<60mL/min. Patients diagnosed with diffuse interstitial lung disease (DILD) by chest high-resolution computed tomography (HRCT) were not excluded, nor were those with a restrictive alteration in pulmonary function tests assessed by a forced vital capacity (FVC) or carbon monoxide transfer factor (DLco)<80% of the predicted value) and normal HRCT.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Demographic and clinical data were collected through review of the medical history and directed anamnesis, including the subtype of SSc (limited SSc, diffuse SSc, pre-scleroderma, SSc sine scleroderma) and the autoantibody profile (anti-centromere, anti-topoisomerase, anti-RNA polymerase I and III, anti-PM/scl), the presence of digital ulcers and DILD, DLco values, previously undiagnosed CVRF, current medications and other non-cardiovascular comorbidities. In all patients a modified Rodnan skin score (mRSS), was performed, as well as an EKG, Holter, and echocardiogram and a quantification of biomarkers in peripheral blood (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Lung involvement was assessed using HRCT. All patients signed the informed consent form. The protocol for our study was consistent with the provisions of the Declaration of Helsinki and was approved by the ethics committee of the Hospital del Mar (CEIm-PSMAR). From our initial cohort of 111 SSc patients, 36 fulfilled inclusion criteria and were included in the study after signing the informed consent.Assessment of skin involvementThe assessment of skin involvement was performed using the mRSS. According to Verrecchia et al.<a class="elsevierStyleCrossRef" href="#bib0240">18</a> who correlated the extent of fibrosis seen in skin biopsies with the mRSS, we classified it as mild (0–14) or not mild (≥15), after evaluating 17 body domains.Evaluation of left ventricular cardiac dysfunctionLeft ventricular function was assessed using TDE [Sonos 2000® (Hewlett Packard, Andover, MA, USA) and Sonos 5500®, (Agilent Technology, Santa Clara, CA, USA)] with a 5–10Hz probe, according to the guidelines of the American Society for Echocardiography. A single blinded expert sonographer carried out the measurements according to a pre-established protocol. LVSD was defined as LVEF<55% by Simpson or a GLS<−20%, since to date there is no consensus about the threshold to consider pathological in the latter. We considered that patients had LVDD if the relation between transmitral peak E-wave velocity (E) and peak early diastolic velocity (Ea) (E/Ea)>8<a class="elsevierStyleCrossRef" href="#bib0245">19</a>, since the presence of an E/Ea ratio<8 is usually associated with normal left ventricle filling pressures.ElectrocardiogramAll patients were evaluated by a standard 12-lead EKG, interpreted by an experienced and blinded cardiologist. Alterations were classified as major and minor, and clinically significant arrhythmias (CSA) or not, according to EKG, following the Minnesota Code Manual.24-h Holter electrocardiogram monitoring and study of cardiac dysautonomiaAll patients underwent a 24-h Holter EKG (3-lead; HolCARD 24W® system). The recordings were edited manually, excluding artifacts and noise. Twenty patients (55.6%) Holter trace abnormalities were interpreted by an expert cardiologist and classified into CSA—frequent atrial extrasystoles, non-benign VE, atrioventricular block (AVB), and nonsustained supraventricular tachycardia—and arrhythmias without clinical significance, according to the Minnesota Code Manual.Peripheral blood biomarkers analysisSerum concentrations of TnTc, NT-proBNP and collagen degradation products were determined. We set the cut-off value for NT-proBNP at ≥125pg/mL<a class="elsevierStyleCrossRef" href="#bib0230">16</a>, for troponin T at the 99th percentile of the general population (>14ng/L) and for procollagen type III aminoterminal propeptide levels at ≥0.8mcg/L.Statistical analysisThe categorical variables were described as frequencies and percentages, and the continuous variables as means and standard deviations. The association between variables was evaluated using the chi-squared test for categorical variables, Pearson's correlation coefficient for continuous variables, and the comparison of means by Student's t-test. In statistically significant associations, a multivariate linear regression study was performed to rule out confounding factors. In addition, a multivariate analysis was performed in some cases according to previously described confounding factors in the literature, independently that they were statistically significant in our cohort. Statistical analysis was carried out using IBM® SPSS 25.0. All analysis were two-tailed and p-values were considered significant if <0.05.ResultsThe demographic data and clinical characteristics of the 36 patients included are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, classified according to those who had any alteration on the EKG, those who did in the Holter and those with CSA vs those without. The mean age was 56.7±12.3 years and the female/male ratio was 35/1. Twenty-four patients (66%) belonged to the limited SSc subtype, one to the SSc sine scleroderma subtype and the rest to the diffuse one. Regarding autoimmunity, 23 patients (63.9%) were found to be positive for anti-centromere antibodies, 11 (30%) for anti-topoisomerase, 1 for anti-PM/Scl and another one for anti-RNA polymerase III antibodies. Mean duration of the disease from the onset of the first non-Raynaud's symptom was 7.0±4.1 years. We found the presence of Raynaud's phenomenon in 100% of the patients, telangiectasias in 20 (55.6%), myositis and acroosteolysis in 2 (5%), symptomatic gastroesophageal reflux disease in 19 (53%) and DILD in 13 (36.1%) with a DLco of 83.9±16.8 and a FVC of 84.75±16.2. Thirty-one patients (86.1%) had an mRSS≤29 and 21 (58.3%) had a nailfold capillaroscopy with a pattern consistent with SSc, whether active, early, or late. No patient had calcinosis cutis or arthritis at the time of the study, although 1 and 6, respectively, have had those manifestations in the past. In relation to peripheral blood biomarkers, we found that 19 patients (51.4%) had at least one of the three biomarkers studied elevated. Although classic cardiovascular risk factors were part of the exclusion criteria, 3 patients were found to have high serum cholesterol levels in the clinical evaluation of the study and 4 elevated blood pressure, 3 were active smokers and 7 were obese.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>EchocardiogramGeneral echocardiographic findings are described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. One patient showed an altered LVEF of 40% (mean 62.5±6.6%) while 8/36 (22%) presented abnormal GLS values suggestive of LVSD (mean −17.5±2.5%), 7 of them with normal LVEF and none with left ventricular hypertrophy.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Ten patients (27.8%) had LVDD (mean E/Ea 10.9±2.7), and in 4 (11.1%) LVSD and LVDD coexisted. Atrial and ventricular diameters measured by TDE were normal in all patients.Associations between LVDD and/or LVSD and EKG/Holter findings are described in the Holter results section. We did find a statistically significant correlation between the E/Ea and the NT-proBNP values (p=0.001).ElectrocardiogramEighteen patients (50%) presented changes that are described in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. The most frequent alteration was a minimal prolonged corrected QT interval (QTc>440ms) in 11 patients (30.5%), being in 7 of them the only found EKG alteration. The rest of patients had other isolated alterations like incomplete right bundle branch block (RBBB)<a class="elsevierStyleCrossRef" href="#bib0170">4</a>, nonspecific changes in ST/T<a class="elsevierStyleCrossRef" href="#bib0165">3</a>, incomplete left bundle branch block (LBBB)<a class="elsevierStyleCrossRef" href="#bib0165">3</a>, abnormal QRS prolongation in the precordial leads<a class="elsevierStyleCrossRef" href="#bib0155">1</a> or complete LBBB<a class="elsevierStyleCrossRef" href="#bib0155">1</a>. Four patients had two simultaneous EKG alterations (QT prolongation+incomplete RBBB, incomplete RBBB+left anterior fascicular block (LAFB), and 2 a QT prolongation+LAFB), and one patient three alterations at the same time (QT prolongation+LAFB+left ventricular hypertrophy). Eight out of the eighteen patients who showed abnormalities (44%) had CSA defined by EKG.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>24-h Holter electrocardiogramTwenty patients (55.6%) presented alterations in the 24-h Holter (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 5</a>), of which 15/20 (75%) were CSA defined by Holter. The most frequent alterations found were isolated supraventricular extrasystoles in 7 patients, as well as benign VE in 4, and non-benign in 4 other patients. Other findings were frequent supraventricular extrasystoles<a class="elsevierStyleCrossRef" href="#bib0165">3</a>, VE of two morphologies<a class="elsevierStyleCrossRef" href="#bib0160">2</a>, sinus tachycardia<a class="elsevierStyleCrossRef" href="#bib0160">2</a>, doublets of ventricular extrasystoles<a class="elsevierStyleCrossRef" href="#bib0155">1</a>, accelerated idioventricular rhythm<a class="elsevierStyleCrossRef" href="#bib0155">1</a> and first-degree AVB<a class="elsevierStyleCrossRef" href="#bib0155">1</a>. We analyzed whether newly diagnosed CVRF predominated in the group that showed CSA by Holter, with no differences found between groups. Only three (8.3%) presented CSA by both EKG and Holter.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>In <a class="elsevierStyleCrossRef" href="#tbl0025">Table 6</a> is described the univariate analysis between patients who presented CSA by EKG, Holter, either of them or by both simultaneously and different characteristics, paying special attention to those with LVDD and/or LVSD. A marginal correlation (p=0.085) was found between LVSD associated with elevated NT-proBNP values and the presence of CSA detected by EKG or Holter indistinctly. No correlation was found between both double ventricular dysfunction and the presence of CSA. There was also no association between CSA and any clinical parameter. We did not find a statistically significant association between LVDD and the presence of CSA, not even in those patients who presented LVDD associated with elevated NT-proBNP values.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia>Study of cardiac dysautonomia through heart rate variabilitySDNN was decreased (<100ms) in six patients (16.7%). No correlation was found between autonomic dysfunction and any other clinical o cardiac characteristic.Analysis of peripheral blood biomarkersFourteen patients (38.8%) presented elevated NT-proBNP) with a mean of 140.5±125.5pg/mL, five (13.9%) showed elevated TnTc values>14ng/L, and seven (19.4%) elevated levels of procollagen (mean 0.85±1.12mcg/L).Regarding the univariate analysis of cardiac biomarkers, the elevation of TnTc>14ng/L showed a significant correlation with the presence of CSA detected by both methods, both by Holter and EKG (p=0.008), and a marginal correlation with the presence of CSA detected only by Holter (p=0.056) (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 6</a>). A marginal correlation (p=0.066) was also found between TnTc levels>14ng/mL and the presence of LVDD, and a significant correlation between TnTc levels>14ng/mL and elevation of NT-proBNP (p=0.006).We also found an association between the patients in treatment with any kind of immunosuppressant drug and normal levels of procollagen type III aminoterminal propeptide (p=0.002), whose meaning is yet to be elucidated.Other univariate associationsOut of the aim of the study which is the assessment of cardiac parameters, correlations between other clinical/serological variables were analyzed, finding an inverse correlation between mRSS and DLco (p=0.002) and DLco and the presence of digital ulcers (p=0.001), and a positive correlation between digital ulcers and mRSS (p=0.002).Multivariate analysisNone of the potential confounding variables examined were statistically significant in the univariate analysis, and therefore did not warrant inclusion in a multivariate analysis.However we did perform in the multivariate analysis according to clinically criteria and confounding factors already described in the literature, where we found a statistically significant correlation between the E/Ea and the NT-proBNP values (p=0.001), which persisted despite including confounding factors such as age or the duration of the disease.DiscussionThe observed data confirm a high prevalence of left ventricular dysfunction and arrhythmias in patients with SSc who are asymptomatic from the cardiac perspective and without previous heart disease, CVRF or PAH.Regarding left ventricular dysfunction, it is reported in the literature that LVSD is a rare finding. A large multicenter study with 570 patients determined a prevalence of 1.4%, compared with 17.7% of LVDD<a class="elsevierStyleCrossRef" href="#bib0250">20</a>. Another study with 7073 patients, found a prevalence of a reduced LVEF of 5.4%<a class="elsevierStyleCrossRef" href="#bib0220">14</a>. This low prevalence could be due to the methodology used (LVEF). It has been widely demonstrated that the detection of LVSD through LVEF abnormalities by TDE (<55%) occurs in around 7% and that it doubles with the use of the GLS<a class="elsevierStyleCrossRef" href="#bib0255">21</a>. In our study, only one patient presented LVSD (2.8%) when evaluated by low LVEF, while 8 (22%) according to GLS. Despite the short time since disease onset in our patients, compared with other series (duration of the disease 13.9±3.7 years), we found a prevalence of LVSD greater than expected in asymptomatic patients, highlighting the importance of conducting an early cardiologic evaluation and in a silent phase. The high prevalence detected by GLS calls attention to the need of using additional electrocardiographic techniques, such as GLS, to the ones used routinely, in order to increase the sensitivity in LVSD diagnosis in patients with SSc, even in patients without other apparent risk factors for heart disease.We did not find a correlation between the presence of LVSD and CSA. Follansbee et al. found an association between LVSD and isolated complete LBBB or RBBB associated with LAFB<a class="elsevierStyleCrossRef" href="#bib0260">22</a>. In our series, only one patient had a LBBB and she was the only one who presented a decreased LVEF besides a double left ventricular dysfunction. No patient had RBBB and LAFB. However, we did find a marginally significant correlation between LVSD associated with elevated NT-proBNP and the presence of CSA by EKG or Holter regardless of the diagnostic method (p=0.085). According to these findings, the presence of LVSD associated with NT-proBNP alterations could be used as a tool to select those patients who may have a higher risk for developing CSA and who would be candidates for a more thorough arrhythmogenic study.Regarding LVDD, the percentage of patients with LVDD was 27.8%, similar to that reported (17–30%)<a class="elsevierStyleCrossRef" href="#bib0205">11</a>. Although it has been described that DD can contribute to a potential reentry mechanism for the development of tachyarrhythmias secondary to myocardial fibrosis and ventricular stiffness, we did not find a correlation between LVDD and ventricular tachyarrhythmias, or other CSA. In a recent study, DD was also associated with a high risk of presenting death secondary to an arrhythmic event, independently of the LVEF<a class="elsevierStyleCrossRef" href="#bib0265">23</a>. We could not corroborate this in our series due to several facts: our patients did not have any previous heart diseases while 75% of the patients studied by Pezawas et al. had a history of cardiomyopathy and, even the 25% without, had been selected because they presented typical coronary symptoms and/or abnormal echocardiogram or cardiac magnetic resonance (CMR) findings. In our study, patients with both previously known heart diseases or coronary disease symptoms, or suspicion of heart disease according to test's abnormalities were excluded, so both populations cannot be compared. Pezawas et al. found that 89% had DD, which was independently associated with an increased risk of arrhythmic or resuscitated cardiac death, while in our series only 27.8% had DD. The mean age was similar in both studies (around 55y±13y) but the mortality of our cohort was very low, probably because of a relatively short follow-up time since the diagnosis of the disease, a data not provided in Pezawas’ work.Several studies have shown that the presence of LVDD accompanied by elevation of NT-proBNP correlates with a greater number of arrhythmias or a greater complexity and/or significance of these, being this association considered a risk factor for the development of arrhythmias, mortality and cardiovascular events<a class="elsevierStyleCrossRef" href="#bib0270">24</a>. In our study, 7/10 (70%) of the patients with LVDD, presented elevated NT-proBNP (240±192pg/mL), and 2 of the 7 patients with elevation of these levels (28.6%) presented CSA, without being statistically significant the correlation. Thus, we cannot confirm that the association of LVSD and elevation of NT-proBNP is a risk factor for CSA. However, we did find a correlation between LVDD and the elevation of NT-proBNP. In the general population, it has been described that NT-proBNP values are related to LVDD, but usually influenced by the simultaneous presence of left ventricular hypertrophy or LVSD<a class="elsevierStyleCrossRef" href="#bib0275">25</a>. In patients with SSc, it has been observed that this correlation may disappear when adjusting for age as the main confounding factor. In our study, a multivariate logistic regression analysis was performed in which the association persisted after adjusting for age, LVSD and other factors whose relationship with LVDD is described in SSc, such as duration of the disease and CVRF. For this reason, we hypothesize that, in populations similar to our series, NT-proBNP could serve as an indirect, highly accessible and early biomarker of LVDD.Many studies suggest that LVSD precedes LVSD, the latter being late, possibly related to greater structural damage to the myocardium. In our study, only 50% of patients with LVSD had concomitant LVSD.Regarding electrocardiographic abnormalities, 18 (50%) had EKG abnormalities, a prevalence similar to that previously reported<a class="elsevierStyleCrossRef" href="#bib0280">26</a>, which increased to 20 (55.6%) when evaluating the alterations through a Holter, being the prevalence of CSA 22.2% using EKG and 41.7% using Holter.The most frequent electrocardiographic alterations were QT prolongations (47.8% of all electrocardiographic abnormalities) and conduction alterations, evidenced in 30.6% and 19.4% of all patients, respectively. The most prevalent electrocardiographic abnormalities reported in patients with SSc are LAFB (16%) and first degree AVBs (8%) according to Roberts et al.,<a class="elsevierStyleCrossRef" href="#bib0180">6</a> and non-specific ST changes (12 .1%) according to Draeger et al.<a class="elsevierStyleCrossRef" href="#bib0285">27</a> In our case, we observed non-specific ST changes in 8.3%, with incomplete RBBB being the most frequent conduction alteration (11.8%).Regarding Holter results, the most frequent alterations found were supraventricular arrhythmias (36.1%), results similar to the study by Roberts et al., in which there were supraventricular tachyarrhythmias (32%), followed by conduction alterations (14%), doublets of ventricular extrasystoles (14%) and ventricular tachycardias (10%) <a class="elsevierStyleCrossRef" href="#bib0180">6</a>. In the ventricles, our work showed that both conduction alterations and doublets of extrasystoles were very infrequent (2.7% each), the most frequent being isolated VE with a non-benign nature in 11.1%, slightly lower than that published<a class="elsevierStyleCrossRef" href="#bib0280">26</a>, probably because our patients belonged to a selected cohort of asymptomatic patients, with no previous cardiac pathology or CVRF.Six patients (16.7%) had a 24-h decrease in SSDN, a lower prevalence than that reported in the literature<a class="elsevierStyleCrossRef" href="#bib0290">28</a>. Some studies has shown that CAD could have a predictive role in the identification of patients at high risk of developing arrhythmias<a class="elsevierStyleCrossRef" href="#bib0190">8</a>. In our study, no correlation was found between CDA and CSA.With regard to cardiac biomarkers, it is known the association between elevated NT-proBNP and both CSA and ventricular arrhythmias<a class="elsevierStyleCrossRef" href="#bib0295">29</a>. Muresan et al. even establish an NT-proBNP threshold>287pg/mL as highly specific for the presence of complex and frequent ventricular arrhythmias<a class="elsevierStyleCrossRef" href="#bib0270">24</a>. In our case, neither the elevation of NT-proBNP (in 38.9% and 50% of those with CSA), nor the threshold of 287pg/mL showed a statistically significant association with CSA, in general, nor with ventricular arrhythmias.The elevation of TnTc showed a statistically significant correlation with CSA detected by both diagnostic methods, both by Holter and EKG (p=0.008), as well as a marginal correlation with CSA by Holter (p=0.056). A marginal correlation (p=0.066) was also found between TnTc levels>14ng/mL and LVDD. Taking into account that TnTc is a marker of myocardial damage, whose high levels in SSc could be due to increased permeability of myocytes secondary to inflammatory changes, and that these elevated levels have been previously associated with systolic dysfunction, with RBBB, VE and with worse prognosis<a class="elsevierStyleCrossRef" href="#bib0225">15</a>, these patients with elevated TnTc would probably be candidates for a myocardial study with CMR.We found no correlation between the cardiac findings and any clinical characteristic. Cardiac involvement in SSc has been related to the presence of anti-scl70 antibodies, the diffuse skin subtype, and the severity of the skin involvement. Although none of these characteristics predominated in our series, we still found a high prevalence of cardiac alterations, further enhancing the importance of performing an active screening for cardiac involvement in all patients, regardless of their phenotype.The lack of correlation in our results between CSA according to different diagnostic methods, as well as between CSA and the echocardiographic findings, suggests that it is not possible to predict the presence of CSA using a single diagnostic technique and reinforces the importance of performing a complete cardiac evaluation with at least EKG, TDE and Holter in these patients. Although asymptomatic and with no history of heart diseases or risk factors, to rule out silent cardiac involvement. In addition, the absence of clinical parameters that associate with cardiac findings makes it impossible to distinguish who will develop a cardiac manifestation, so the screening should be performed routinely as we already do with PAH or DILD screenings. Rises in serologic biomarkers could be an add-on reason to perform the heart disease assessment.This study has several limitations. First of all, not having performed a CMR as of the diagnostic procedures, which is currently considered the gold standard for studying SSc heart involvement. CMR seem to be a faster, noninvasive tool to determine subclinical myocardiocal involvement in SSc by detecting right and left systolic and diastolic volumes and right and LVEF, being its sensitivity higher compared to ecochardiography. In relation to the detection of arrhythmias, CMR allows the identification of myocardial edema and fibrosis, being myocardial fibrosis the most common substrate for re-entrant arrhythmias. CMR can thus potentially translate the Holter findings to distinguishable structural myocardial abnormalities functioning as arrhythmogenic foci, as myocardial fibrosis identified by CMR is the most common arrhythmogenic substrate. Some CMR parameters as the T2 ratio and the percentage of late gadolinium enhancement have been associated to life-threatening ventricular rhythm disturbances in SSc patients<a class="elsevierStyleCrossRef" href="#bib0300">30</a>, which allow doctors to diminish the uncertainty of other diagnostic methods like the Holter which can depend on presenting the rhythm disturbance at the time of the test.Other limitations of our study include the relatively small sample size, due to strict inclusion criteria; we could only analyze the impact of treatments as two general groups (immunosuppressants yes/no, vasodilator drugs yes/no), due to the sample size and the high variability in treatments taken. The definition of major and minor EKG abnormalities given by the Minnesota Code could be limitative, since there are other alterations (AVBs, QRS duration in LBBB, etc.) that could also have an important impact on prognosis. Troponin T and NT-proBNP are non-specific biomarkers, especially out of a specific clinical context. We did not measure any SSc activity indexes to investigate whether left ventricular dysfunction and/or arrhythmias were associated to disease activity. Holter monitoring was only performed during a 24-h period; if longer monitoring had been done, the diagnostic yield would have been greater, due to the fact that there is a day-to-day variability in the frequency of premature atrial contractions and ventricular contraction. Finally, we did not use a control group to evaluate if the recorded arrhythmias are specific for the 36 selected patients or can be found also in the general SSc population or even in another age-matched population without SSc.ConclusionsWe found a high prevalence of left ventricular dysfunction and arrhythmias, even in a cohort of SSc selected patients, without symptoms or heart disease, CVRF or PAH. We evidenced an up to 10 times higher prevalence of LVSD than that previously reported, probably due to the use of GLS, which reinforces the importance of incorporating GLS measurements in the routine echocardiographic study of these patients.According to our results, both TnTc and NT-proBNP could be used routinely as markers in the study of LVDD, and TnTc also as a minimally invasive and highly available biomarker in the detection of CSA in populations similar to ours.The absence of correlation between left ventricular dysfunction and CSA, as well as the presence of a normal atrial and ventricular diameter in all patients, indicate that the arrhythmias could be due, not only to a supposed structural alteration of the myocardium, but also to an independent and early cardiac involvement related to SSc being probably arrhythmogenic per se. Those patients with LVSD and elevation of NT-proBNP could present an increased risk of CSA, so they would be eligible for a complete cardiac study to early detection of arrhythmias.The lack of correlation between CSA according to different diagnostic methods or with any echocardiographic findings, suggests that it is not possible to predict the presence of CSA using a single diagnostic technique and reinforces the importance of performing a complete cardiac evaluation in these patients to rule out silent cardiac involvement.One-sentence summaryThe novelty of this article lies on the study of arrhythmias and left ventricular dysfunction in patients with systemic sclerosis without other cardiac risk factors apart from the disease itself, and on the analysis of the relationship between both entities and with other characteristics of the patients and the disease.Ethical considerationsAll patients signed the informed consent form. The protocol for our study was consistent with the provisions of the Declaration of Helsinki and was approved by the ethics committee of the Hospital del Mar (CEIm-PSMAR).Data availability statementThe data underlying this article are available in the article and in its online supplementary material.FundingThe research leading to these results has not received any funding.Conflict of interestThe authors declare that they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres1899619" "titulo" => "Abstract" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and aims" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods and results" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1643297" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1899620" "titulo" => "Resumen" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0020" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0025" "titulo" => "Métodos y resultados" ] 2 => array:2 [ "identificador" => "abst0030" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1643298" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Assessment of skin involvement" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Evaluation of left ventricular cardiac dysfunction" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Electrocardiogram" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "24-h Holter electrocardiogram monitoring and study of cardiac dysautonomia" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Peripheral blood biomarkers analysis" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Echocardiogram" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Electrocardiogram" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "24-h Holter electrocardiogram" ] 3 => array:2 [ "identificador" => "sec0065" "titulo" => "Study of cardiac dysautonomia through heart rate variability" ] 4 => array:2 [ "identificador" => "sec0070" "titulo" => "Analysis of peripheral blood biomarkers" ] 5 => array:2 [ "identificador" => "sec0075" "titulo" => "Other univariate associations" ] 6 => array:2 [ "identificador" => "sec0080" "titulo" => "Multivariate analysis" ] ] ] 7 => array:2 [ "identificador" => "sec0085" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0090" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0095" "titulo" => "One-sentence summary" ] 10 => array:2 [ "identificador" => "sec0100" "titulo" => "Ethical considerations" ] 11 => array:2 [ "identificador" => "sec0105" "titulo" => "Data availability statement" ] 12 => array:2 [ "identificador" => "sec0110" "titulo" => "Funding" ] 13 => array:2 [ "identificador" => "sec0115" "titulo" => "Conflict of interest" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-09-14" "fechaAceptado" => "2022-11-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1643297" "palabras" => array:6 [ 0 => "Systemic sclerosis" 1 => "Scleroderma" 2 => "Arrhythmias" 3 => "Left ventricular dysfunction" 4 => "Dysautonomia" 5 => "Cardiac involvement" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1643298" "palabras" => array:6 [ 0 => "Esclerosis sistémica" 1 => "Esclerodermia" 2 => "Arritmias" 3 => "Disfunción ventricular izquierda" 4 => "Disautonomía" 5 => "Afectación cardiaca" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Introduction and aimsCardiac involvement in systemic sclerosis (SS) is frequently silent and a major cause of mortality in these patients. This work aims to study the prevalence and associations of left ventricular dysfunction (LVD) and arrhythmias in SS. Methods and resultsProspective study of SS patients (n=36), excluding those with symptoms of (or) cardiac disease, pulmonary arterial hypertension or cardiovascular risk factors (CVRF). A clinical, analytical, electrocardiogram (EKG), Holter, and echocardiogram with global longitudinal strain (GLS) assessment were performed. Arrhythmias were classified into clinically significant arrhythmias (CSA) and non-significant.Twenty-eight percent had left ventricular diastolic dysfunction (LVDD), 22% LV systolic dysfunction (LVSD) according to the GLS, 11.1% both, and 16.7% cardiac dysautonomia. Fifty percent presented alterations by EKG (44% CSA), 55.6% by Holter (75% CSA) and 8.3% CSA by both. An association was found between the elevation of troponin T (TnTc) and CSA and between the elevation of both NT-proBNP and TnTc with LVDD. ConclusionsWe found a higher prevalence of LVSD than in the literature, detected by GLS and being 10 times higher than that detected by LVEF, which justifies the need to incorporate this technique in the routine evaluation of these patients. The association of TnTc and NT-proBNP with LVDD suggests that they can be used as minimally invasive biomarkers of this affectation. The absence of correlation between LVD and CSA indicates that the arrhythmias could be due, not only to a supposed structural alteration of the myocardium, but to an independent and early cardiac involvement, which should be actively investigated even in asymptomatic patients without CVRF." "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and aims" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods and results" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "Introducción y objetivosLa afectación cardiaca en la esclerosis sistémica (ES) es frecuentemente asintomática y se asocia con una mortalidad importante. Este trabajo tiene como objetivo estudiar la prevalencia y las asociaciones de la disfunción ventricular izquierda (DVI) y las arritmias en la ES. Métodos y resultadosEstudio prospectivo de pacientes con ES (n = 36), excluyendo aquellos con síntomas o enfermedad cardiaca, hipertensión arterial pulmonar o factores de riesgo cardiovascular (FRCV). Se les realizó una evaluación clínica, analítica, con electrocardiograma (ECG), Holter y ecocardiograma con strain longitudinal global (SLG). Las arritmias se clasificaron en arritmias clínicamente significativas (ACS) y no significativas.De los pacientes estudiados, 27,8% presentaba disfunción diastólica del ventrículo izquierdo (DDVI), 22% disfunción sistólica del VI (DSVI) según el SLG, 11,1% ambas y 16,7% disautonomía cardiaca; 50% presentó alteraciones por ECG (44% ACS), 55,6% por Holter (75% ACS) y 8,3% ACS por ambos. Se encontró una asociación entre la elevación de troponina T (TnTc) y ACS y entre la elevación NT-proBNP y TnTc con la DDVI. ConclusionesEncontramos una prevalencia de DSVI mayor que en la literatura, detectada por SLG y siendo 10 veces superior a la detectada por FEVI, lo que justifica la necesidad de incorporar esta técnica en la evaluación rutinaria de estos pacientes. La asociación de TnTc y NT-proBNP con DDVI sugiere que pueden ser utilizados como biomarcadores mínimamente invasivos de esta afectación. La ausencia de correlación entre DVI y ACS indica que las arritmias podrían deberse, no solo a una supuesta alteración estructural del miocardio, sino a un compromiso cardiaco independiente y temprano, que debe investigarse activamente incluso en pacientes asintomáticos sin FRCV." "secciones" => array:3 [ 0 => array:2 [ "identificador" => "abst0020" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0025" "titulo" => "Métodos y resultados" ] 2 => array:2 [ "identificador" => "abst0030" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1859 "Ancho" => 2925 "Tamanyo" => 379948 ] ] "descripcion" => array:1 [ "en" => "Algorithm that shows patient selection and the examinations performed. SSc: systemic sclerosis; DILD, diffuse interstitial lung disease; PFT: pulmonary function tests; HRCT: high-resolution computed tomography; LVSD: left ventricular systolic dysfunction; LVEF: left ventricular ejection fraction; PAH: pulmonary hypertension; mPAP: mean pulmonary artery pressure; CVRF: cardiovascular risk factors; DM: diabetes mellitus; DLP: dyslipidaemia; AHT: arterial hypertension; CKD: chronic kidney disease; GFR: glomerular filtration rate; mRSS: modified Rodnan skin score; EKG: electrocardiogram." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "AHT: arterial hypertension; dSS: diffuse systemic sclerosis; lSS: limited systemic sclerosis; DLco: diffusing capacity for carbon monoxide; FVC: forced vital capacity; SD: standard deviation; pro-BNP: N-terminal brain natriuretic peptide; TnTc: cardiac troponin T; PIIINP: procollagen type III aminoterminal propeptide; ACE inhibitors: angiotensin converting enzyme inhibitors. Y: years; ACE: angiotensin-converting enzyme.Qualitative variables are expressed with absolute numbers and percentages and quantitative ones with means±standard deviation." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Have EKG alterations</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Have Holter alterations</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Have clinically significant arrhythmias</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No \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">Yes \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">No \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">Yes \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">No \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">Yes \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.3±12.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.2±12.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.2±10.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.3±13.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.7±13.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.7±12.3 \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">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (94%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (95%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (95%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systemic sclerosis subtype</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">Limited cutaneous subtype \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (72%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (61%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (81%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (55%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (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">Diffuse cutaneous subtype \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (28%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (33%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (19%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (25%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (35%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-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">Duration since 1st non-Raynaud symptom \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.7±2.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.4±4.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.1±3.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.7±4.6 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.1±2.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.8±4.8 \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">Raynaud \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (100%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (61%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (67%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (56%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (56%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (70%) \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">Calcinosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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">Arthritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (22%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (11%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (19%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (15%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (19%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (15%) \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">Myositis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (11%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (10%) \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">Acroosteolysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (10%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Modified Rodnan skin score</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">Not mild (≥15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (61%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (44%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (65%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (56%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (55%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-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">Severe digital ischemia or previous ulcer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (28%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (28%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (19%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (35%) \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">Scleroderma pattern in nailfold capillaroscopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (53%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (71%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (73%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (53%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (53%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (68%) \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">Gastroesophageal reflux \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (56%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (56%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (56%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (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">Diffuse interstitial lung disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (28%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (22%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (35%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (19%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (30%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DLco \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">81.8±15.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">86±18.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85.5±16.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82.6±17.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83.4±18.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">84.3±16.3 \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">FVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80.0±13.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89.7±17.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">86.5±19.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">83.2±12.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">81.5±19.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87.4±12.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Biomarkers</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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">150±130 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">130±123 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">104±65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">170±154 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">108±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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">167±152 \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">TnTc \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.6±4.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.5±4.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.2±0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.6±5.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.2±0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.8±5.9 \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">PIIINP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.03±1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.2±1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.9±1.0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.2±1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0±1.2 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.1±1.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Autoantibodies</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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (67%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (61%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (69%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (60%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (69%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (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">Anti-topoisomerase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (28%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (22%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (19%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (25%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (25%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vasodilator drugs</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">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (11%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (29%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (33%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (10%) \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">ACE inhibitors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (61%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (60%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (56%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (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">History of prostaglandin treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (17%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (3%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (15%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (10%) \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">Bosentan \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (17%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (22%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (25%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (19%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (20%) \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">Calcium antagonists \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (61%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (39%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (44%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (55%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (50%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-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">Hydroxychloroquine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Azathioprine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (11%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (45%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 25%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (35%) \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">Glucocorticoids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (11%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (33%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (19%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (25%) \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">None of the 3 treatments above \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (44%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (56%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (69%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (35%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (56%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (45%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiovascular risk factors</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">Active smokers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (11%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (12.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (12.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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">Elevated cholesterol level<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (11%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (15%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (15%) \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">Elevated blood pressure<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (11%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (11%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (15%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (15%) \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">Obesity (BMI>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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (22%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (17%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (25%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (15%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (10%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3174393.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Without a previous diagnosis of dyslipidemia." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Without previous diagnosis of AHT and without ventricular hypertrophy." ] ] ] "descripcion" => array:1 [ "en" => "Demographic and clinical characteristics of patients with SS (N=36), classified according to those who had any alteration on the echocardiogram (EKG), those who did in the 24h-Holter and those with clinically significant arrhythmias (CSA) vs those without." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "TAPSE: Tricuspid Annular Plane Systolic Excursion; E wave: peak velocity blood flow from left ventricular relaxation in early diastole; A wave: peak velocity flow in late diastole caused by atrial contraction; E/A: ratio between E and A waves; E/Ea: the relation between transmitral peak E-wave velocity and peak early diastolic velocity; LEVF: left ventricle ejection fraction measured by Simpson." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Means±Standard deviation \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">Left atrium area (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.4±3.4 \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">Right atrium area (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.7±3.1 \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">Right ventricle area (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.8±3.1 \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">TAPSE (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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.1±3.5 \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">E wave \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.06±0.1 \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">A wave \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.85±0.2 \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">EA wave \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.3±3.7 \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">E/A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.04±0.05 \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">E/Ea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.2±2.9 \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">Mitral deceleration time \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">182.2±46.7 \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">LVEF (Simpson) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62.5±6.6 \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">Global longitudinal strain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20.9±4.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3174394.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Echocardiogram findings." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "LBBB: left bundle branch block; RBBB: right bundle branch block." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of alteration \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="" 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">Number of 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">Major \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Complete LBBB<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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">Minor \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abnormal QRS prolongation in the precordial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nonspecific changes in ST/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="char" 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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Incomplete LBBB<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Incomplete RBBB<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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">Other \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Minimal prolongation of the QT segment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3174395.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "Indicates that they are considered clinically significant arrhythmias." ] ] ] "descripcion" => array:1 [ "en" => "EKG abnormalities (N=18)." ] ] 4 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of alteration \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">Subtype \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></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">Supraventricular extrasystoles \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Infrequent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Frequent<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mono or polymorphic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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">Nonsustained supraventricular tachycardia<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \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">Ventricular extrasystoles \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Benign \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Not benign<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Doublets \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Two morphologies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Accelerated idioventricular rhythm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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">1st degree atrioventricular block<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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">Sinus tachycardia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3174392.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "a" "nota" => "Indicates that they are considered clinically significant arrhythmias." ] ] ] "descripcion" => array:1 [ "en" => "Types of electrocardiographic abnormalities detected by the 24-h Holter (N=20)." ] ] 5 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "CSA Holter: clinically significant arrhythmias by Holter; SDNN: standard deviation of all RR sinus normal intervals (NN) in milliseconds; pro-BNP: N-terminal brain natriuretic peptide; LVDD: left ventricle diastolic dysfunction; LVSD: left ventricular systolic dysfunction; ref. v.: reference value.p-Value is significant if <0.05 (bold). Underlined p-values indicate marginally significant associations between 0.05 and 0.1." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">CSA EKG \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">CSA Holter \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">CSA EKG and Holter \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">CSA EKG or Holter \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-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">p-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">p-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">p-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">Modified Rodnan skin score ≥15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.720 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.650 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.686 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.940 \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">Digital ulcers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.486 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.166 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.116 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.279 \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">SDNN alteration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.720 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.174 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.418 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.549 \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">Pro-BNP>125pg/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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.511 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.324 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.324 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.332 \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">Troponin T>14ng/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.245 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.056 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.189 \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">LVDD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.842 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.166 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.822 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.279 \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">LVSD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.239 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.278 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.629 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.720 \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">LVSD+LVDD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.887 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.720 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.201 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.813 \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+LVDD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.653 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.355 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.526 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.346 \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+LVSD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.898 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.278 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.309 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.085 \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">Collagen degradation products>ref v. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.628 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.892 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.614 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.810 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3174396.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Associations between clinically significant arrhythmias by electrocardiogram, by Holter, by either of them or by both simultaneously and different characteristics of the patients." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Myocardial lesions of progressive systemic sclerosis. 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Left ventricular dysfunction and arrhythmias in asymptomatic patients with systemic sclerosis

Disfunción ventricular izquierda y arritmias en pacientes asintomáticos con esclerosis sistémica

Lilian López Núñeza, Irene Carrión-Barberàa,

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ipirenaica@gmail.com
mcarrion@parcdesalutmar.cat

Corresponding author.

, Luis Molinab, Isabel Padróa, Manel Ciriaa, Laura Tíoc, Tarek Carlos Salman-Montea, Ana Prosa

a Rheumatology Department, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain

b Cardiology Department, Hospital del Mar/Parc de Salut Mar, Barcelona, Spain

c Cellular Research Group on Inflammation and Cartilage of the Hospital del Mar Medical Research Institute of Barcelona (IMIM), Barcelona, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Systemic sclerosis &#40;SSc&#41; is a chronic immune-mediated disease that affects several organs&#44; including the heart&#46; For decades&#44; the existence of a primary heart condition in SSc was questioned&#44; until in 1976 Bulkley et al&#46; detected foci of myocardial necrosis with patchy distribution in pathological studies&#44; which suggested that the myocardial injury could be due to a phenomenon of vasospasm of the intramural coronary microcirculation called coronary Raynaud&#39;s phenomenon&#46; It was from then on that scleroderma-related myocardial involvement was considered a defined and relatively frequent entity<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Primary heart disease in SSc usually presents early during the first three years of disease onset&#44; being clinically silent in most cases and recognized only in 15&#8211;25&#37;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a>&#46; It can affect any cardiac structure and manifest variously&#44; even as sudden death &#40;SD&#41; in 5&#8211;54&#37; of patients<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a>&#46; Cardiac involvement is one of the main causes of mortality in SSc &#40;14&#8211;31&#37; according to series<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a>&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Arrhythmias and conduction disturbances are frequent forms of cardiac involvement in SSc<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a>&#46; In unselected patients with SSc&#44; the prevalence of electrocardiographic abnormalities ranges between 32 and 52&#37; according to findings in electrocardiogram &#40;EKG&#41; and between 62 and 90&#37; on the 24-h Holter EKG &#40;Holter&#41;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a>&#46; Rokas et al&#46; observed that even up to 57&#37; of asymptomatic SSc patients without evidence of arrhythmias by EKG or Holter&#44; presented significant tachyarrhythmias when performing invasive electrophysiological studies<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a>&#46; Ventricular arrhythmias are frequently found in SSc patients &#40;up to 90&#37; when using a Holter&#41; and are generally acknowledged to have a poor prognosis when associated with impaired myocardial function&#44; particularly multiform and&#47;or repetitive ventricular premature beats&#46; However&#44; despite its frequent occurrence&#44; sudden cardiac death is not very common in SSc<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Additionally&#44; the Holter allows the study of cardiac autonomic dysfunction &#40;CAD&#41; by measuring heart rate variability as a proxy for cardiac sympathetic and parasympathetic activity&#46; CAD is described in up to 42&#37; of patients with SSc&#44; and could indicate patients at high risk of developing arrhythmias<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In SSc&#44; arrhythmias and conduction disturbances are more prevalent in patients with pulmonary arterial hypertension &#40;PAH&#41; and with ventricular dysfunction<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a>&#46; Some authors argue that myocardial fibrosis is a clear arrhythmogenic substrate and that&#44; depending on its extension&#44; it can lead to the development of ventricular dysfunction<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a>&#46; Although there exists ample evidence of diastolic and systolic involvement of both ventricles&#44; even in early stages of SSc&#44; there are few studies that have correlated these findings with arrhythmias&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The prevalence of left ventricle diastolic dysfunction &#40;LVDD&#41; in SSc can reach 34&#37; and it is associated with an increased risk of mortality &#40;HR 3&#46;2&#8211;3&#46;7&#41;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11&#44;12</span></a>&#46; Several studies have concluded that LVDD and an increased left atrium as an indirect sign&#44; in the absence of other causes&#44; reflect a primary disease of the myocardium in SSc<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a>&#46; LVDD is progressive and precedes the appearance of remodeling&#44; so it occurs much earlier than alterations in systolic function&#46; When LVDD is suspected&#44; Tissue Doppler echocardiography &#40;TDE&#41; is a useful method that allows an early assessment&#46; However&#44; in the detection of left ventricular systolic dysfunction &#40;LVSD&#41;&#44; the analysis of the left ventricular ejection fraction &#40;LVEF&#41; has shown to be scarcely sensitive&#44; identifying only 5&#37; of patients with SSc suffering from this alteration&#44; usually in advanced stages<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a>&#46; Nevertheless&#44; TDE is also used to determine other measurements such as the myocardial velocity and deformation through the global longitudinal strain &#40;GLS&#41;&#44; which allows physicians to perform a direct and early assessment of the systolic function&#46; It is suggested that LVSD measured by GLS could predict the development of ventricular arrhythmias<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Regarding cardiac biomarkers&#44; cardiac troponin T &#40;TnTc&#41; is a marker of cardiac damage&#44; either due to ischemia or due to myocardial inflammation&#46; Elevated levels have been related to the presence of frequent ventricular extrasystoles &#40;VE&#41; &#40;&#62;1190&#47;24<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; these being a factor of poor prognosis&#44; SD or of the need for implantation of a defibrillator<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a>&#46; On the other hand&#44; the N-terminal brain natriuretic propeptide &#40;NT-proBNP&#41; is the most studied biomarker in SSc&#44; being currently part of the PAH screening guidelines&#46; It is widely known that its elevation is also present&#44; not only in response to right ventricular dysfunction&#44; but also to left ventricular systolic and diastolic dysfunction &#40;DD&#41;&#46; Both markers have been reported to be elevated in patients with SSc compared to controls&#44; even in patients without cardiovascular risk factors &#40;CVRF&#41;&#44; have been associated with cardiac involvement and have been postulated as biomarkers for its early detection&#46; Allanore et al&#46; propose the NT-ProBNP value<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>125<span class="elsevierStyleHsp" style=""></span>pg&#47;mL in patients<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>75 years&#44; and &#62;450<span class="elsevierStyleHsp" style=""></span>pg&#47;mL in older patients&#44; as a threshold to use in SSc patients screening for silent cardiomyopathy<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">It is evident that the presence of arrhythmias in SSc worsens the prognosis and increases mortality&#44; which forces us to try to identify tools that help us to early diagnose and promptly establish appropriate treatment and&#47;or follow-up&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Our objective is to study the prevalence of left ventricular dysfunction and arrhythmias in our cohort of patients with SSc who do not have cardiac symptoms&#44; a history of PAH or any known cardiac pathology&#44; as well as to analyze whether there is an association between both entities or with other variables that could be predictors for the development of these complications&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Materials and methods</span><p id="par0050" class="elsevierStylePara elsevierViewall">Prospective study on a cohort of SSc patients who met the SSc 2013 SSc ACR&#47;EULAR classification criteria<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a>&#46; Patient&#39;s selection flowchart and tests performed per study protocol are detailed in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; Exclusion criteria involved previous diagnosis of a heart condition&#44; which included any type of cardiomyopathy&#44; arrhythmias&#44; LVSD&#44; treatment with arrhythmogenic drugs&#44; previous diagnosis of PAH by right heart disease catheterization or suspicion of PAH according to any signs or symptoms or finding of a mean pulmonary artery pressure by echocardiogram<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>36<span class="elsevierStyleHsp" style=""></span>mmHg&#44; known cardiovascular risk factors or renal disease with a glomerular filtration rate<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#46; Patients diagnosed with diffuse interstitial lung disease &#40;DILD&#41; by chest high-resolution computed tomography &#40;HRCT&#41; were not excluded&#44; nor were those with a restrictive alteration in pulmonary function tests assessed by a forced vital capacity &#40;FVC&#41; or carbon monoxide transfer factor &#40;DLco&#41;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>80&#37; of the predicted value&#41; and normal HRCT&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Demographic and clinical data were collected through review of the medical history and directed anamnesis&#44; including the subtype of SSc &#40;limited SSc&#44; diffuse SSc&#44; pre-scleroderma&#44; SSc sine scleroderma&#41; and the autoantibody profile &#40;anti-centromere&#44; anti-topoisomerase&#44; anti-RNA polymerase I and III&#44; anti-PM&#47;scl&#41;&#44; the presence of digital ulcers and DILD&#44; DLco values&#44; previously undiagnosed CVRF&#44; current medications and other non-cardiovascular comorbidities&#46; In all patients a modified Rodnan skin score &#40;mRSS&#41;&#44; was performed&#44; as well as an EKG&#44; Holter&#44; and echocardiogram and a quantification of biomarkers in peripheral blood &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Lung involvement was assessed using HRCT&#46; All patients signed the informed consent form&#46; The protocol for our study was consistent with the provisions of the Declaration of Helsinki and was approved by the ethics committee of the Hospital del Mar &#40;CEIm-PSMAR&#41;&#46; From our initial cohort of 111 SSc patients&#44; 36 fulfilled inclusion criteria and were included in the study after signing the informed consent&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Assessment of skin involvement</span><p id="par0060" class="elsevierStylePara elsevierViewall">The assessment of skin involvement was performed using the mRSS&#46; According to Verrecchia et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> who correlated the extent of fibrosis seen in skin biopsies with the mRSS&#44; we classified it as mild &#40;0&#8211;14&#41; or not mild &#40;&#8805;15&#41;&#44; after evaluating 17 body domains&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Evaluation of left ventricular cardiac dysfunction</span><p id="par0065" class="elsevierStylePara elsevierViewall">Left ventricular function was assessed using TDE &#91;Sonos 2000&#174; &#40;Hewlett Packard&#44; Andover&#44; MA&#44; USA&#41; and Sonos 5500&#174;&#44; &#40;Agilent Technology&#44; Santa Clara&#44; CA&#44; USA&#41;&#93; with a 5&#8211;10<span class="elsevierStyleHsp" style=""></span>Hz probe&#44; according to the guidelines of the American Society for Echocardiography&#46; A single blinded expert sonographer carried out the measurements according to a pre-established protocol&#46; LVSD was defined as LVEF<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>55&#37; by Simpson or a GLS<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#8722;20&#37;&#44; since to date there is no consensus about the threshold to consider pathological in the latter&#46; We considered that patients had LVDD if the relation between transmitral peak <span class="elsevierStyleItalic">E</span>-wave velocity &#40;<span class="elsevierStyleItalic">E</span>&#41; and peak early diastolic velocity &#40;<span class="elsevierStyleItalic">E</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">a</span></span>&#41; &#40;<span class="elsevierStyleItalic">E</span>&#47;<span class="elsevierStyleItalic">E</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">a</span></span>&#41;<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>8<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a>&#44; since the presence of an <span class="elsevierStyleItalic">E</span>&#47;<span class="elsevierStyleItalic">E</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">a</span></span> ratio<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>8 is usually associated with normal left ventricle filling pressures&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Electrocardiogram</span><p id="par0070" class="elsevierStylePara elsevierViewall">All patients were evaluated by a standard 12-lead EKG&#44; interpreted by an experienced and blinded cardiologist&#46; Alterations were classified as major and minor&#44; and clinically significant arrhythmias &#40;CSA&#41; or not&#44; according to EKG&#44; following the Minnesota Code Manual&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">24-h Holter electrocardiogram monitoring and study of cardiac dysautonomia</span><p id="par0075" class="elsevierStylePara elsevierViewall">All patients underwent a 24-h Holter EKG &#40;3-lead&#59; <span class="elsevierStyleItalic">HolCARD 24W</span>&#174; system&#41;&#46; The recordings were edited manually&#44; excluding artifacts and noise&#46; Twenty patients &#40;55&#46;6&#37;&#41; Holter trace abnormalities were interpreted by an expert cardiologist and classified into CSA&#8212;frequent atrial extrasystoles&#44; non-benign VE&#44; atrioventricular block &#40;AVB&#41;&#44; and nonsustained supraventricular tachycardia&#8212;and arrhythmias without clinical significance&#44; according to the Minnesota Code Manual&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Peripheral blood biomarkers analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">Serum concentrations of TnTc&#44; NT-proBNP and collagen degradation products were determined&#46; We set the cut-off value for NT-proBNP at &#8805;125<span class="elsevierStyleHsp" style=""></span>pg&#47;mL<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a>&#44; for troponin T at the 99th percentile of the general population &#40;&#62;14<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#41; and for procollagen type III aminoterminal propeptide levels at &#8805;0&#46;8<span class="elsevierStyleHsp" style=""></span>mcg&#47;L&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0085" class="elsevierStylePara elsevierViewall">The categorical variables were described as frequencies and percentages&#44; and the continuous variables as means and standard deviations&#46; The association between variables was evaluated using the chi-squared test for categorical variables&#44; Pearson&#39;s correlation coefficient for continuous variables&#44; and the comparison of means by Student&#39;s <span class="elsevierStyleItalic">t</span>-test&#46; In statistically significant associations&#44; a multivariate linear regression study was performed to rule out confounding factors&#46; In addition&#44; a multivariate analysis was performed in some cases according to previously described confounding factors in the literature&#44; independently that they were statistically significant in our cohort&#46; Statistical analysis was carried out using IBM&#174; SPSS 25&#46;0&#46; All analysis were two-tailed and <span class="elsevierStyleItalic">p</span>-values were considered significant if &#60;0&#46;05&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0090" class="elsevierStylePara elsevierViewall">The demographic data and clinical characteristics of the 36 patients included are detailed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; classified according to those who had any alteration on the EKG&#44; those who did in the Holter and those with CSA vs those without&#46; The mean age was 56&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;3 years and the female&#47;male ratio was 35&#47;1&#46; Twenty-four patients &#40;66&#37;&#41; belonged to the limited SSc subtype&#44; one to the SSc sine scleroderma subtype and the rest to the diffuse one&#46; Regarding autoimmunity&#44; 23 patients &#40;63&#46;9&#37;&#41; were found to be positive for anti-centromere antibodies&#44; 11 &#40;30&#37;&#41; for anti-topoisomerase&#44; 1 for anti-PM&#47;Scl and another one for anti-RNA polymerase III antibodies&#46; Mean duration of the disease from the onset of the first non-Raynaud&#39;s symptom was 7&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;1 years&#46; We found the presence of Raynaud&#39;s phenomenon in 100&#37; of the patients&#44; telangiectasias in 20 &#40;55&#46;6&#37;&#41;&#44; myositis and acroosteolysis in 2 &#40;5&#37;&#41;&#44; symptomatic gastroesophageal reflux disease in 19 &#40;53&#37;&#41; and DILD in 13 &#40;36&#46;1&#37;&#41; with a DLco of 83&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;8 and a FVC of 84&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;2&#46; Thirty-one patients &#40;86&#46;1&#37;&#41; had an mRSS<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>29 and 21 &#40;58&#46;3&#37;&#41; had a nailfold capillaroscopy with a pattern consistent with SSc&#44; whether active&#44; early&#44; or late&#46; No patient had calcinosis cutis or arthritis at the time of the study&#44; although 1 and 6&#44; respectively&#44; have had those manifestations in the past&#46; In relation to peripheral blood biomarkers&#44; we found that 19 patients &#40;51&#46;4&#37;&#41; had at least one of the three biomarkers studied elevated&#46; Although classic cardiovascular risk factors were part of the exclusion criteria&#44; 3 patients were found to have high serum cholesterol levels in the clinical evaluation of the study and 4 elevated blood pressure&#44; 3 were active smokers and 7 were obese&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Echocardiogram</span><p id="par0095" class="elsevierStylePara elsevierViewall">General echocardiographic findings are described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; One patient showed an altered LVEF of 40&#37; &#40;mean 62&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;6&#37;&#41; while 8&#47;36 &#40;22&#37;&#41; presented abnormal GLS values suggestive of LVSD &#40;mean &#8722;17&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;5&#37;&#41;&#44; 7 of them with normal LVEF and none with left ventricular hypertrophy&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Ten patients &#40;27&#46;8&#37;&#41; had LVDD &#40;mean <span class="elsevierStyleItalic">E</span>&#47;<span class="elsevierStyleItalic">E</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">a</span></span> 10&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;7&#41;&#44; and in 4 &#40;11&#46;1&#37;&#41; LVSD and LVDD coexisted&#46; Atrial and ventricular diameters measured by TDE were normal in all patients&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Associations between LVDD and&#47;or LVSD and EKG&#47;Holter findings are described in the Holter results section&#46; We did find a statistically significant correlation between the <span class="elsevierStyleItalic">E</span>&#47;<span class="elsevierStyleItalic">E</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">a</span></span> and the NT-proBNP values &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Electrocardiogram</span><p id="par0110" class="elsevierStylePara elsevierViewall">Eighteen patients &#40;50&#37;&#41; presented changes that are described in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; The most frequent alteration was a minimal prolonged corrected QT interval &#40;QTc<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>440<span class="elsevierStyleHsp" style=""></span>ms&#41; in 11 patients &#40;30&#46;5&#37;&#41;&#44; being in 7 of them the only found EKG alteration&#46; The rest of patients had other isolated alterations like incomplete right bundle branch block &#40;RBBB&#41;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a>&#44; nonspecific changes in ST&#47;T<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a>&#44; incomplete left bundle branch block &#40;LBBB&#41;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a>&#44; abnormal QRS prolongation in the precordial leads<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> or complete LBBB<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a>&#46; Four patients had two simultaneous EKG alterations &#40;QT prolongation<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>incomplete RBBB&#44; incomplete RBBB<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>left anterior fascicular block &#40;LAFB&#41;&#44; and 2 a QT prolongation<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>LAFB&#41;&#44; and one patient three alterations at the same time &#40;QT prolongation<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>LAFB<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>left ventricular hypertrophy&#41;&#46; Eight out of the eighteen patients who showed abnormalities &#40;44&#37;&#41; had CSA defined by EKG&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">24-h Holter electrocardiogram</span><p id="par0115" class="elsevierStylePara elsevierViewall">Twenty patients &#40;55&#46;6&#37;&#41; presented alterations in the 24-h Holter &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 5</a>&#41;&#44; of which 15&#47;20 &#40;75&#37;&#41; were CSA defined by Holter&#46; The most frequent alterations found were isolated supraventricular extrasystoles in 7 patients&#44; as well as benign VE in 4&#44; and non-benign in 4 other patients&#46; Other findings were frequent supraventricular extrasystoles<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a>&#44; VE of two morphologies<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a>&#44; sinus tachycardia<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a>&#44; doublets of ventricular extrasystoles<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a>&#44; accelerated idioventricular rhythm<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> and first-degree AVB<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a>&#46; We analyzed whether newly diagnosed CVRF predominated in the group that showed CSA by Holter&#44; with no differences found between groups&#46; Only three &#40;8&#46;3&#37;&#41; presented CSA by both EKG and Holter&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">In <a class="elsevierStyleCrossRef" href="#tbl0025">Table 6</a> is described the univariate analysis between patients who presented CSA by EKG&#44; Holter&#44; either of them or by both simultaneously and different characteristics&#44; paying special attention to those with LVDD and&#47;or LVSD&#46; A marginal correlation &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;085&#41; was found between LVSD associated with elevated NT-proBNP values and the presence of CSA detected by EKG or Holter indistinctly&#46; No correlation was found between both double ventricular dysfunction and the presence of CSA&#46; There was also no association between CSA and any clinical parameter&#46; We did not find a statistically significant association between LVDD and the presence of CSA&#44; not even in those patients who presented LVDD associated with elevated NT-proBNP values&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Study of cardiac dysautonomia through heart rate variability</span><p id="par0125" class="elsevierStylePara elsevierViewall">SDNN was decreased &#40;&#60;100<span class="elsevierStyleHsp" style=""></span>ms&#41; in six patients &#40;16&#46;7&#37;&#41;&#46; No correlation was found between autonomic dysfunction and any other clinical o cardiac characteristic&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Analysis of peripheral blood biomarkers</span><p id="par0130" class="elsevierStylePara elsevierViewall">Fourteen patients &#40;38&#46;8&#37;&#41; presented elevated NT-proBNP&#41; with a mean of 140&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>125&#46;5<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; five &#40;13&#46;9&#37;&#41; showed elevated TnTc values<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>14<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#44; and seven &#40;19&#46;4&#37;&#41; elevated levels of procollagen &#40;mean 0&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;12<span class="elsevierStyleHsp" style=""></span>mcg&#47;L&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Regarding the univariate analysis of cardiac biomarkers&#44; the elevation of TnTc<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>14<span class="elsevierStyleHsp" style=""></span>ng&#47;L showed a significant correlation with the presence of CSA detected by both methods&#44; both by Holter and EKG &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41;&#44; and a marginal correlation with the presence of CSA detected only by Holter &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;056&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 6</a>&#41;&#46; A marginal correlation &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;066&#41; was also found between TnTc levels<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>14<span class="elsevierStyleHsp" style=""></span>ng&#47;mL and the presence of LVDD&#44; and a significant correlation between TnTc levels<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>14<span class="elsevierStyleHsp" style=""></span>ng&#47;mL and elevation of NT-proBNP &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">We also found an association between the patients in treatment with any kind of immunosuppressant drug and normal levels of procollagen type III aminoterminal propeptide &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#44; whose meaning is yet to be elucidated&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Other univariate associations</span><p id="par0145" class="elsevierStylePara elsevierViewall">Out of the aim of the study which is the assessment of cardiac parameters&#44; correlations between other clinical&#47;serological variables were analyzed&#44; finding an inverse correlation between mRSS and DLco &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41; and DLco and the presence of digital ulcers &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; and a positive correlation between digital ulcers and mRSS &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Multivariate analysis</span><p id="par0150" class="elsevierStylePara elsevierViewall">None of the potential confounding variables examined were statistically significant in the univariate analysis&#44; and therefore did not warrant inclusion in a multivariate analysis&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">However we did perform in the multivariate analysis according to clinically criteria and confounding factors already described in the literature&#44; where we found a statistically significant correlation between the <span class="elsevierStyleItalic">E</span>&#47;<span class="elsevierStyleItalic">E</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">a</span></span> and the NT-proBNP values &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; which persisted despite including confounding factors such as age or the duration of the disease&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">The observed data confirm a high prevalence of left ventricular dysfunction and arrhythmias in patients with SSc who are asymptomatic from the cardiac perspective and without previous heart disease&#44; CVRF or PAH&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Regarding left ventricular dysfunction&#44; it is reported in the literature that LVSD is a rare finding&#46; A large multicenter study with 570 patients determined a prevalence of 1&#46;4&#37;&#44; compared with 17&#46;7&#37; of LVDD<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a>&#46; Another study with 7073 patients&#44; found a prevalence of a reduced LVEF of 5&#46;4&#37;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a>&#46; This low prevalence could be due to the methodology used &#40;LVEF&#41;&#46; It has been widely demonstrated that the detection of LVSD through LVEF abnormalities by TDE &#40;&#60;55&#37;&#41; occurs in around 7&#37; and that it doubles with the use of the GLS<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a>&#46; In our study&#44; only one patient presented LVSD &#40;2&#46;8&#37;&#41; when evaluated by low LVEF&#44; while 8 &#40;22&#37;&#41; according to GLS&#46; Despite the short time since disease onset in our patients&#44; compared with other series &#40;duration of the disease 13&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;7 years&#41;&#44; we found a prevalence of LVSD greater than expected in asymptomatic patients&#44; highlighting the importance of conducting an early cardiologic evaluation and in a silent phase&#46; The high prevalence detected by GLS calls attention to the need of using additional electrocardiographic techniques&#44; such as GLS&#44; to the ones used routinely&#44; in order to increase the sensitivity in LVSD diagnosis in patients with SSc&#44; even in patients without other apparent risk factors for heart disease&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">We did not find a correlation between the presence of LVSD and CSA&#46; Follansbee et al&#46; found an association between LVSD and isolated complete LBBB or RBBB associated with LAFB<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>&#46; In our series&#44; only one patient had a LBBB and she was the only one who presented a decreased LVEF besides a double left ventricular dysfunction&#46; No patient had RBBB and LAFB&#46; However&#44; we did find a marginally significant correlation between LVSD associated with elevated NT-proBNP and the presence of CSA by EKG or Holter regardless of the diagnostic method &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;085&#41;&#46; According to these findings&#44; the presence of LVSD associated with NT-proBNP alterations could be used as a tool to select those patients who may have a higher risk for developing CSA and who would be candidates for a more thorough arrhythmogenic study&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Regarding LVDD&#44; the percentage of patients with LVDD was 27&#46;8&#37;&#44; similar to that reported &#40;17&#8211;30&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a>&#46; Although it has been described that DD can contribute to a potential reentry mechanism for the development of tachyarrhythmias secondary to myocardial fibrosis and ventricular stiffness&#44; we did not find a correlation between LVDD and ventricular tachyarrhythmias&#44; or other CSA&#46; In a recent study&#44; DD was also associated with a high risk of presenting death secondary to an arrhythmic event&#44; independently of the LVEF<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a>&#46; We could not corroborate this in our series due to several facts&#58; our patients did not have any previous heart diseases while 75&#37; of the patients studied by Pezawas et al&#46; had a history of cardiomyopathy and&#44; even the 25&#37; without&#44; had been selected because they presented typical coronary symptoms and&#47;or abnormal echocardiogram or cardiac magnetic resonance &#40;CMR&#41; findings&#46; In our study&#44; patients with both previously known heart diseases or coronary disease symptoms&#44; or suspicion of heart disease according to test&#39;s abnormalities were excluded&#44; so both populations cannot be compared&#46; Pezawas et al&#46; found that 89&#37; had DD&#44; which was independently associated with an increased risk of arrhythmic or resuscitated cardiac death&#44; while in our series only 27&#46;8&#37; had DD&#46; The mean age was similar in both studies &#40;around 55y<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13y&#41; but the mortality of our cohort was very low&#44; probably because of a relatively short follow-up time since the diagnosis of the disease&#44; a data not provided in Pezawas&#8217; work&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Several studies have shown that the presence of LVDD accompanied by elevation of NT-proBNP correlates with a greater number of arrhythmias or a greater complexity and&#47;or significance of these&#44; being this association considered a risk factor for the development of arrhythmias&#44; mortality and cardiovascular events<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a>&#46; In our study&#44; 7&#47;10 &#40;70&#37;&#41; of the patients with LVDD&#44; presented elevated NT-proBNP &#40;240<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>192<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41;&#44; and 2 of the 7 patients with elevation of these levels &#40;28&#46;6&#37;&#41; presented CSA&#44; without being statistically significant the correlation&#46; Thus&#44; we cannot confirm that the association of LVSD and elevation of NT-proBNP is a risk factor for CSA&#46; However&#44; we did find a correlation between LVDD and the elevation of NT-proBNP&#46; In the general population&#44; it has been described that NT-proBNP values are related to LVDD&#44; but usually influenced by the simultaneous presence of left ventricular hypertrophy or LVSD<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a>&#46; In patients with SSc&#44; it has been observed that this correlation may disappear when adjusting for age as the main confounding factor&#46; In our study&#44; a multivariate logistic regression analysis was performed in which the association persisted after adjusting for age&#44; LVSD and other factors whose relationship with LVDD is described in SSc&#44; such as duration of the disease and CVRF&#46; For this reason&#44; we hypothesize that&#44; in populations similar to our series&#44; NT-proBNP could serve as an indirect&#44; highly accessible and early biomarker of LVDD&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Many studies suggest that LVSD precedes LVSD&#44; the latter being late&#44; possibly related to greater structural damage to the myocardium&#46; In our study&#44; only 50&#37; of patients with LVSD had concomitant LVSD&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Regarding electrocardiographic abnormalities&#44; 18 &#40;50&#37;&#41; had EKG abnormalities&#44; a prevalence similar to that previously reported<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a>&#44; which increased to 20 &#40;55&#46;6&#37;&#41; when evaluating the alterations through a Holter&#44; being the prevalence of CSA 22&#46;2&#37; using EKG and 41&#46;7&#37; using Holter&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The most frequent electrocardiographic alterations were QT prolongations &#40;47&#46;8&#37; of all electrocardiographic abnormalities&#41; and conduction alterations&#44; evidenced in 30&#46;6&#37; and 19&#46;4&#37; of all patients&#44; respectively&#46; The most prevalent electrocardiographic abnormalities reported in patients with SSc are LAFB &#40;16&#37;&#41; and first degree AVBs &#40;8&#37;&#41; according to Roberts et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> and non-specific ST changes &#40;12 &#46;1&#37;&#41; according to Draeger et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> In our case&#44; we observed non-specific ST changes in 8&#46;3&#37;&#44; with incomplete RBBB being the most frequent conduction alteration &#40;11&#46;8&#37;&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Regarding Holter results&#44; the most frequent alterations found were supraventricular arrhythmias &#40;36&#46;1&#37;&#41;&#44; results similar to the study by Roberts et al&#46;&#44; in which there were supraventricular tachyarrhythmias &#40;32&#37;&#41;&#44; followed by conduction alterations &#40;14&#37;&#41;&#44; doublets of ventricular extrasystoles &#40;14&#37;&#41; and ventricular tachycardias &#40;10&#37;&#41; <a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a>&#46; In the ventricles&#44; our work showed that both conduction alterations and doublets of extrasystoles were very infrequent &#40;2&#46;7&#37; each&#41;&#44; the most frequent being isolated VE with a non-benign nature in 11&#46;1&#37;&#44; slightly lower than that published<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a>&#44; probably because our patients belonged to a selected cohort of asymptomatic patients&#44; with no previous cardiac pathology or CVRF&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Six patients &#40;16&#46;7&#37;&#41; had a 24-h decrease in SSDN&#44; a lower prevalence than that reported in the literature<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#46; Some studies has shown that CAD could have a predictive role in the identification of patients at high risk of developing arrhythmias<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a>&#46; In our study&#44; no correlation was found between CDA and CSA&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">With regard to cardiac biomarkers&#44; it is known the association between elevated NT-proBNP and both CSA and ventricular arrhythmias<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a>&#46; Muresan et al&#46; even establish an NT-proBNP threshold<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>287<span class="elsevierStyleHsp" style=""></span>pg&#47;mL as highly specific for the presence of complex and frequent ventricular arrhythmias<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a>&#46; In our case&#44; neither the elevation of NT-proBNP &#40;in 38&#46;9&#37; and 50&#37; of those with CSA&#41;&#44; nor the threshold of 287<span class="elsevierStyleHsp" style=""></span>pg&#47;mL showed a statistically significant association with CSA&#44; in general&#44; nor with ventricular arrhythmias&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">The elevation of TnTc showed a statistically significant correlation with CSA detected by both diagnostic methods&#44; both by Holter and EKG &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41;&#44; as well as a marginal correlation with CSA by Holter &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;056&#41;&#46; A marginal correlation &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;066&#41; was also found between TnTc levels<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>14<span class="elsevierStyleHsp" style=""></span>ng&#47;mL and LVDD&#46; Taking into account that TnTc is a marker of myocardial damage&#44; whose high levels in SSc could be due to increased permeability of myocytes secondary to inflammatory changes&#44; and that these elevated levels have been previously associated with systolic dysfunction&#44; with RBBB&#44; VE and with worse prognosis<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a>&#44; these patients with elevated TnTc would probably be candidates for a myocardial study with CMR&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">We found no correlation between the cardiac findings and any clinical characteristic&#46; Cardiac involvement in SSc has been related to the presence of anti-scl70 antibodies&#44; the diffuse skin subtype&#44; and the severity of the skin involvement&#46; Although none of these characteristics predominated in our series&#44; we still found a high prevalence of cardiac alterations&#44; further enhancing the importance of performing an active screening for cardiac involvement in all patients&#44; regardless of their phenotype&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">The lack of correlation in our results between CSA according to different diagnostic methods&#44; as well as between CSA and the echocardiographic findings&#44; suggests that it is not possible to predict the presence of CSA using a single diagnostic technique and reinforces the importance of performing a complete cardiac evaluation with at least EKG&#44; TDE and Holter in these patients&#46; Although asymptomatic and with no history of heart diseases or risk factors&#44; to rule out silent cardiac involvement&#46; In addition&#44; the absence of clinical parameters that associate with cardiac findings makes it impossible to distinguish who will develop a cardiac manifestation&#44; so the screening should be performed routinely as we already do with PAH or DILD screenings&#46; Rises in serologic biomarkers could be an add-on reason to perform the heart disease assessment&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">This study has several limitations&#46; First of all&#44; not having performed a CMR as of the diagnostic procedures&#44; which is currently considered the gold standard for studying SSc heart involvement&#46; CMR seem to be a faster&#44; noninvasive tool to determine subclinical myocardiocal involvement in SSc by detecting right and left systolic and diastolic volumes and right and LVEF&#44; being its sensitivity higher compared to ecochardiography&#46; In relation to the detection of arrhythmias&#44; CMR allows the identification of myocardial edema and fibrosis&#44; being myocardial fibrosis the most common substrate for re-entrant arrhythmias&#46; CMR can thus potentially translate the Holter findings to distinguishable structural myocardial abnormalities functioning as arrhythmogenic foci&#44; as myocardial fibrosis identified by CMR is the most common arrhythmogenic substrate&#46; Some CMR parameters as the T2 ratio and the percentage of late gadolinium enhancement have been associated to life-threatening ventricular rhythm disturbances in SSc patients<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a>&#44; which allow doctors to diminish the uncertainty of other diagnostic methods like the Holter which can depend on presenting the rhythm disturbance at the time of the test&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Other limitations of our study include the relatively small sample size&#44; due to strict inclusion criteria&#59; we could only analyze the impact of treatments as two general groups &#40;immunosuppressants yes&#47;no&#44; vasodilator drugs yes&#47;no&#41;&#44; due to the sample size and the high variability in treatments taken&#46; The definition of major and minor EKG abnormalities given by the Minnesota Code could be limitative&#44; since there are other alterations &#40;AVBs&#44; QRS duration in LBBB&#44; etc&#46;&#41; that could also have an important impact on prognosis&#46; Troponin T and NT-proBNP are non-specific biomarkers&#44; especially out of a specific clinical context&#46; We did not measure any SSc activity indexes to investigate whether left ventricular dysfunction and&#47;or arrhythmias were associated to disease activity&#46; Holter monitoring was only performed during a 24-h period&#59; if longer monitoring had been done&#44; the diagnostic yield would have been greater&#44; due to the fact that there is a day-to-day variability in the frequency of premature atrial contractions and ventricular contraction&#46; Finally&#44; we did not use a control group to evaluate if the recorded arrhythmias are specific for the 36 selected patients or can be found also in the general SSc population or even in another age-matched population without SSc&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0240" class="elsevierStylePara elsevierViewall">We found a high prevalence of left ventricular dysfunction and arrhythmias&#44; even in a cohort of SSc selected patients&#44; without symptoms or heart disease&#44; CVRF or PAH&#46; We evidenced an up to 10 times higher prevalence of LVSD than that previously reported&#44; probably due to the use of GLS&#44; which reinforces the importance of incorporating GLS measurements in the routine echocardiographic study of these patients&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">According to our results&#44; both TnTc and NT-proBNP could be used routinely as markers in the study of LVDD&#44; and TnTc also as a minimally invasive and highly available biomarker in the detection of CSA in populations similar to ours&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">The absence of correlation between left ventricular dysfunction and CSA&#44; as well as the presence of a normal atrial and ventricular diameter in all patients&#44; indicate that the arrhythmias could be due&#44; not only to a supposed structural alteration of the myocardium&#44; but also to an independent and early cardiac involvement related to SSc being probably arrhythmogenic per se&#46; Those patients with LVSD and elevation of NT-proBNP could present an increased risk of CSA&#44; so they would be eligible for a complete cardiac study to early detection of arrhythmias&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">The lack of correlation between CSA according to different diagnostic methods or with any echocardiographic findings&#44; suggests that it is not possible to predict the presence of CSA using a single diagnostic technique and reinforces the importance of performing a complete cardiac evaluation in these patients to rule out silent cardiac involvement&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">One-sentence summary</span><p id="par0260" class="elsevierStylePara elsevierViewall">The novelty of this article lies on the study of arrhythmias and left ventricular dysfunction in patients with systemic sclerosis without other cardiac risk factors apart from the disease itself&#44; and on the analysis of the relationship between both entities and with other characteristics of the patients and the disease&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Ethical considerations</span><p id="par0265" class="elsevierStylePara elsevierViewall">All patients signed the informed consent form&#46; The protocol for our study was consistent with the provisions of the Declaration of Helsinki and was approved by the ethics committee of the Hospital del Mar &#40;CEIm-PSMAR&#41;&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Data availability statement</span><p id="par0270" class="elsevierStylePara elsevierViewall">The data underlying this article are available in the article and in its online supplementary material&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Funding</span><p id="par0275" class="elsevierStylePara elsevierViewall">The research leading to these results has not received any funding&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conflict of interest</span><p id="par0280" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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              "titulo" => "Assessment of skin involvement"
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              "titulo" => "Evaluation of left ventricular cardiac dysfunction"
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              "titulo" => "24-h Holter electrocardiogram monitoring and study of cardiac dysautonomia"
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              "titulo" => "Peripheral blood biomarkers analysis"
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              "titulo" => "Study of cardiac dysautonomia through heart rate variability"
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              "titulo" => "Analysis of peripheral blood biomarkers"
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              "titulo" => "Other univariate associations"
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            0 => "Systemic sclerosis"
            1 => "Scleroderma"
            2 => "Arrhythmias"
            3 => "Left ventricular dysfunction"
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            0 => "Esclerosis sist&#233;mica"
            1 => "Esclerodermia"
            2 => "Arritmias"
            3 => "Disfunci&#243;n ventricular izquierda"
            4 => "Disautonom&#237;a"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and aims</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cardiac involvement in systemic sclerosis &#40;SS&#41; is frequently silent and a major cause of mortality in these patients&#46; This work aims to study the prevalence and associations of left ventricular dysfunction &#40;LVD&#41; and arrhythmias in SS&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods and results</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Prospective study of SS patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>36&#41;&#44; excluding those with symptoms of &#40;or&#41; cardiac disease&#44; pulmonary arterial hypertension or cardiovascular risk factors &#40;CVRF&#41;&#46; A clinical&#44; analytical&#44; electrocardiogram &#40;EKG&#41;&#44; Holter&#44; and echocardiogram with global longitudinal strain &#40;GLS&#41; assessment were performed&#46; Arrhythmias were classified into clinically significant arrhythmias &#40;CSA&#41; and non-significant&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Twenty-eight percent had left ventricular diastolic dysfunction &#40;LVDD&#41;&#44; 22&#37; LV systolic dysfunction &#40;LVSD&#41; according to the GLS&#44; 11&#46;1&#37; both&#44; and 16&#46;7&#37; cardiac dysautonomia&#46; Fifty percent presented alterations by EKG &#40;44&#37; CSA&#41;&#44; 55&#46;6&#37; by Holter &#40;75&#37; CSA&#41; and 8&#46;3&#37; CSA by both&#46; An association was found between the elevation of troponin T &#40;TnTc&#41; and CSA and between the elevation of both NT-proBNP and TnTc with LVDD&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We found a higher prevalence of LVSD than in the literature&#44; detected by GLS and being 10 times higher than that detected by LVEF&#44; which justifies the need to incorporate this technique in the routine evaluation of these patients&#46; The association of TnTc and NT-proBNP with LVDD suggests that they can be used as minimally invasive biomarkers of this affectation&#46; The absence of correlation between LVD and CSA indicates that the arrhythmias could be due&#44; not only to a supposed structural alteration of the myocardium&#44; but to an independent and early cardiac involvement&#44; which should be actively investigated even in asymptomatic patients without CVRF&#46;</p></span>"
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        "resumen" => "<span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Introducci&#243;n y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La afectaci&#243;n cardiaca en la esclerosis sist&#233;mica &#40;ES&#41; es frecuentemente asintom&#225;tica y se asocia con una mortalidad importante&#46; Este trabajo tiene como objetivo estudiar la prevalencia y las asociaciones de la disfunci&#243;n ventricular izquierda &#40;DVI&#41; y las arritmias en la ES&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">M&#233;todos y resultados</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo de pacientes con ES &#40;n &#61; 36&#41;&#44; excluyendo aquellos con s&#237;ntomas o enfermedad cardiaca&#44; hipertensi&#243;n arterial pulmonar o factores de riesgo cardiovascular &#40;FRCV&#41;&#46; Se les realiz&#243; una evaluaci&#243;n cl&#237;nica&#44; anal&#237;tica&#44; con electrocardiograma &#40;ECG&#41;&#44; Holter y ecocardiograma con <span class="elsevierStyleItalic">strain</span> longitudinal global &#40;SLG&#41;&#46; Las arritmias se clasificaron en arritmias cl&#237;nicamente significativas &#40;ACS&#41; y no significativas&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De los pacientes estudiados&#44; 27&#44;8&#37; presentaba disfunci&#243;n diast&#243;lica del ventr&#237;culo izquierdo &#40;DDVI&#41;&#44; 22&#37; disfunci&#243;n sist&#243;lica del VI &#40;DSVI&#41; seg&#250;n el SLG&#44; 11&#44;1&#37; ambas y 16&#44;7&#37; disautonom&#237;a cardiaca&#59; 50&#37; present&#243; alteraciones por ECG &#40;44&#37; ACS&#41;&#44; 55&#44;6&#37; por Holter &#40;75&#37; ACS&#41; y 8&#44;3&#37; ACS por ambos&#46; Se encontr&#243; una asociaci&#243;n entre la elevaci&#243;n de troponina T &#40;TnTc&#41; y ACS y entre la elevaci&#243;n NT-proBNP y TnTc con la DDVI&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Encontramos una prevalencia de DSVI mayor que en la literatura&#44; detectada por SLG y siendo 10 veces superior a la detectada por FEVI&#44; lo que justifica la necesidad de incorporar esta t&#233;cnica en la evaluaci&#243;n rutinaria de estos pacientes&#46; La asociaci&#243;n de TnTc y NT-proBNP con DDVI sugiere que pueden ser utilizados como biomarcadores m&#237;nimamente invasivos de esta afectaci&#243;n&#46; La ausencia de correlaci&#243;n entre DVI y ACS indica que las arritmias podr&#237;an deberse&#44; no solo a una supuesta alteraci&#243;n estructural del miocardio&#44; sino a un compromiso cardiaco independiente y temprano&#44; que debe investigarse activamente incluso en pacientes asintom&#225;ticos sin FRCV&#46;</p></span>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Algorithm that shows patient selection and the examinations performed&#46; SSc&#58; systemic sclerosis&#59; DILD&#44; diffuse interstitial lung disease&#59; PFT&#58; pulmonary function tests&#59; HRCT&#58; high-resolution computed tomography&#59; LVSD&#58; left ventricular systolic dysfunction&#59; LVEF&#58; left ventricular ejection fraction&#59; PAH&#58; pulmonary hypertension&#59; mPAP&#58; mean pulmonary artery pressure&#59; CVRF&#58; cardiovascular risk factors&#59; DM&#58; diabetes mellitus&#59; DLP&#58; dyslipidaemia&#59; AHT&#58; arterial hypertension&#59; CKD&#58; chronic kidney disease&#59; GFR&#58; glomerular filtration rate&#59; mRSS&#58; modified Rodnan skin score&#59; EKG&#58; electrocardiogram&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">AHT&#58; arterial hypertension&#59; dSS&#58; diffuse systemic sclerosis&#59; lSS&#58; limited systemic sclerosis&#59; DLco&#58; diffusing capacity for carbon monoxide&#59; FVC&#58; forced vital capacity&#59; SD&#58; standard deviation&#59; pro-BNP&#58; N-terminal brain natriuretic peptide&#59; TnTc&#58; cardiac troponin T&#59; PIIINP&#58; procollagen type III aminoterminal propeptide&#59; ACE inhibitors&#58; angiotensin converting enzyme inhibitors&#46; Y&#58; years&#59; ACE&#58; angiotensin-converting enzyme&#46;</p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Qualitative variables are expressed with absolute numbers and percentages and quantitative ones with means<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>History of prostaglandin treatment&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Bosentan&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">None of the 3 treatments above</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="7" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Cardiovascular risk factors</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Active smokers&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Elevated cholesterol level<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Elevated blood pressure<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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>Obesity &#40;BMI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">4 &#40;22&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;17&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;25&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;15&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5 &#40;31&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">TAPSE&#58; Tricuspid Annular Plane Systolic Excursion&#59; <span class="elsevierStyleItalic">E</span> wave&#58; peak velocity blood flow from left ventricular relaxation in early diastole&#59; <span class="elsevierStyleItalic">A</span> wave&#58; peak velocity flow in late diastole caused by atrial contraction&#59; <span class="elsevierStyleItalic">E</span>&#47;<span class="elsevierStyleItalic">A</span>&#58; ratio between <span class="elsevierStyleItalic">E</span> and <span class="elsevierStyleItalic">A</span> waves&#59; <span class="elsevierStyleItalic">E</span>&#47;<span class="elsevierStyleItalic">E</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">a</span></span>&#58; the relation between transmitral peak <span class="elsevierStyleItalic">E</span>-wave velocity and peak early diastolic velocity&#59; LEVF&#58; left ventricle ejection fraction measured by Simpson&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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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" scope="col" style="border-bottom: 2px solid black">Means<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>Standard deviation&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
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                  \t\t\t\t">Left atrium area &#40;cm<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">13&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></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 atrium area &#40;cm<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">10&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#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">Right ventricle area &#40;mm&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#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">TAPSE &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">24&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">E</span> wave&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&#46;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;1&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"><span class="elsevierStyleItalic">A</span> wave&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#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"><span class="elsevierStyleItalic">EA</span> wave&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">13&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">E</span>&#47;<span class="elsevierStyleItalic">A</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">E</span>&#47;<span class="elsevierStyleItalic">E</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">a</span></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="char" valign="\n
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                  \t\t\t\t">7&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#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">Mitral deceleration time&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">182&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>46&#46;7&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">LVEF &#40;Simpson&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;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">Global longitudinal strain&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Echocardiogram findings&#46;</p>"
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          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">LBBB&#58; left bundle branch block&#59; RBBB&#58; right bundle branch block&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of alteration&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Number of patients&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">Major&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">Complete LBBB<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">Minor&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">Abnormal QRS prolongation in the precordial&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nonspecific changes in ST&#47;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="char" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Incomplete LBBB<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&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="char" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Incomplete RBBB<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&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="char" 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">Other&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">Minimal prolongation of the QT segment&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Indicates that they are considered clinically significant arrhythmias&#46;</p>"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">EKG abnormalities &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>18&#41;&#46;</p>"
        ]
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      4 => array:8 [
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        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
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        "tabla" => array:2 [
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of alteration&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">Subtype&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></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">Supraventricular extrasystoles&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">Infrequent&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Frequent<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&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="char" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mono or polymorphic&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="char" 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">Nonsustained supraventricular tachycardia<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&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">Ventricular extrasystoles&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">Benign&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="char" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Not benign<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&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="char" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doublets&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Two morphologies&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="char" 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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Accelerated idioventricular rhythm&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">1st degree atrioventricular block<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">Sinus tachycardia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" 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></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Indicates that they are considered clinically significant arrhythmias&#46;</p>"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Types of electrocardiographic abnormalities detected by the 24-h Holter &#40;<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41;&#46;</p>"
        ]
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        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">CSA Holter&#58; clinically significant arrhythmias by Holter&#59; SDNN&#58; standard deviation of all RR sinus normal intervals &#40;NN&#41; in milliseconds&#59; pro-BNP&#58; N-terminal brain natriuretic peptide&#59; LVDD&#58; left ventricle diastolic dysfunction&#59; LVSD&#58; left ventricular systolic dysfunction&#59; ref&#46; v&#46;&#58; reference value&#46;</p><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">p</span>-Value is significant if &#60;0&#46;05 &#40;bold&#41;&#46; Underlined <span class="elsevierStyleItalic">p</span>-values indicate marginally significant associations between 0&#46;05 and 0&#46;1&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">CSA EKG&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">CSA Holter&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">CSA EKG and Holter&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">CSA EKG or Holter&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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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" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-Value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-Value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-Value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-Value&nbsp;\t\t\t\t\t\t\n
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                  \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">Modified Rodnan skin score &#8805;15&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;720&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;650&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;686&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;940&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">Digital ulcers&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;486&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;166&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;116&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;279&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">SDNN alteration&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;720&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;174&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;418&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;549&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">Pro-BNP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>125<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;511&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;324&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;324&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;332&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">Troponin T<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>14<span class="elsevierStyleHsp" style=""></span>ng&#47;L&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;245&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">0&#46;056</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#46;008</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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;189&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">LVDD&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;842&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;166&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;822&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;279&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">LVSD&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;239&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;278&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;629&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;720&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">LVSD<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>LVDD&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;887&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;720&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;201&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;813&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">NT-proBNP<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>LVDD&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;653&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;355&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;526&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;346&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">NT-proBNP<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>LVSD&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;898&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;278&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;309&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">0&#46;085</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">Collagen degradation products<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>ref v&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;628&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;892&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;614&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;810&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3174396.png"
              ]
            ]
          ]
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