Case report
Systemic sclerosis: A rare cause of heart failure?
Esclerose sistémica: uma causa incomum de insuficiência cardíaca?
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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "617.e1" "paginaFinal" => "617.e5" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "María Cristina González-Cambeiro, Emad Abu-Assi, Rami Riziq-Yousef Abumuaileq, Sergio Raposeiras-Roubín, Pedro Rigueiro-Veloso, Alejandro Virgós-Lamela, Oscar Díaz-Castro, José Ramón González-Juanatey" "autores" => array:8 [ 0 => array:4 [ "nombre" => "María Cristina" "apellidos" => "González-Cambeiro" "email" => array:1 [ 0 => "cambe_cris@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Emad" "apellidos" => "Abu-Assi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Rami Riziq-Yousef" "apellidos" => "Abumuaileq" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Sergio" "apellidos" => "Raposeiras-Roubín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Pedro" "apellidos" => "Rigueiro-Veloso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Alejandro" "apellidos" => "Virgós-Lamela" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Oscar" "apellidos" => "Díaz-Castro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 7 => array:3 [ "nombre" => "José Ramón" "apellidos" => "González-Juanatey" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Cardiología y Unidad Coronaria, Hospital Clínico Universitario de Santiago de Compostela, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Cardiología y Unidad Coronaria, Complejo Hospitalario de Pontevedra, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Esclerose sistémica: uma causa incomum de insuficiência cardíaca?" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1301 "Ancho" => 3001 "Tamanyo" => 207783 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Chest radiograph.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Case report</span><p id="par0005" class="elsevierStylePara elsevierViewall">A 38-year-old woman without cardiovascular risk factors, diagnosed with SS one year previously, who had presented with simultaneous involvement of the skin and pleura and was under treatment with steroids and calcium channel blockers, was admitted to the emergency department because of progressive dyspnea at rest accompanied by orthopnea, abdominal distension, and lower limb edema for three weeks.</p><p id="par0010" class="elsevierStylePara elsevierViewall">On physical examination, her blood pressure was 117/81<span class="elsevierStyleHsp" style=""></span>mmHg and heart rate was 111<span class="elsevierStyleHsp" style=""></span>beats/min. The presence of microstomia, sclerodactyly, and diffuse cutaneous involvement were noted. Cardiac auscultation was normal without murmur or rub. Breath sounds were absent at the lung bases on both sides. Jugular venous engorgement at 45° was present, with positive hepatojugular reflux. Other physical signs were tender hepatomegaly with bilateral and symmetrical lower limb edema extending up to the knee joint.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The 12-lead electrocardiogram showed sinus tachycardia, incomplete right bundle branch block with left anterior hemiblock and first-degree atrioventricular block (PR interval 210<span class="elsevierStyleHsp" style=""></span>ms, QRS interval 111<span class="elsevierStyleHsp" style=""></span>ms).</p><p id="par0020" class="elsevierStylePara elsevierViewall">Baseline arterial blood gas analysis showed hypoxemia as the only abnormality.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Blood tests revealed microcytic anemia (hemoglobin 9.9<span class="elsevierStyleHsp" style=""></span>g/dl, mean corpuscular volume 69.0<span class="elsevierStyleHsp" style=""></span>fl) and slight abnormalities in coagulation parameters (INR 1.5) without renal dysfunction.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The chest X-ray showed findings consistent with pleural effusion, mainly at the right base (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Transthoracic echocardiography showed mild left ventricular (LV) dilation (end-diastolic diameter [EDD] 55<span class="elsevierStyleHsp" style=""></span>mm, end-systolic diameter 49<span class="elsevierStyleHsp" style=""></span>mm), normal LV thickness, asynchronous LV wall motion, LV ejection fraction 37% by the Teichholz method, LV diastolic dysfunction (restrictive pattern), right ventricular (RV) dilation (EDD 48<span class="elsevierStyleHsp" style=""></span>mm in 4-chamber apical view) and impaired RV systolic function (tricuspid annular plane systolic excursion 9<span class="elsevierStyleHsp" style=""></span>mm), without evidence of significant pulmonary hypertension (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">During her hospital stay the patient received conventional heart failure therapy, with a favorable response. Pro-BNP levels were found to be high (8191.0<span class="elsevierStyleHsp" style=""></span>pg/ml).</p><p id="par0045" class="elsevierStylePara elsevierViewall">Cardiac magnetic resonance imaging (MRI) showed a slightly dilated LV with severe LV systolic dysfunction (LV ejection fraction 21%), together with anterolateral subendocardial delayed enhancement, possibly due to fibrosis, and slight RV dilatation (EDD 50<span class="elsevierStyleHsp" style=""></span>mm) with severe systolic dysfunction (<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Diagnostic workup was completed with cardiac catheterization, which showed no significant coronary artery stenosis or signs of significant pulmonary hypertension (peak pulmonary artery systolic pressure 30<span class="elsevierStyleHsp" style=""></span>mmHg, mean 17<span class="elsevierStyleHsp" style=""></span>mmHg, and pulmonary capillary wedge pressure 15<span class="elsevierStyleHsp" style=""></span>mmHg) (<a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The patient was eventually discharged, clinically stable, with a diagnosis of congestive heart failure and biventricular systolic dysfunction in the context of cardiomyopathy, possibly related to SS. This diagnosis was made on the basis of the absence of other potential causes (coronary disease, hypertension, or family history of heart disease), since a definitive diagnosis based on histological criteria was not available.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and angiotensin receptor blockers (ARBs) were added to her routine SS treatment.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">SS, also called systemic scleroderma, is a chronic disease in which there may be multisystem manifestations, as can be seen in the case presented. There is still debate concerning the role of myocardial fibrosis as a causative mechanism of heart failure. Current hypotheses include arteriolar endothelial injury resulting in fibrosis and vessel obliteration. One theory is that necrotic cardiomyocytes induce recruitment of fibroblasts and their differentiation into myofibroblasts. According to another theory, evolution of the disease with permanent arteriolar wall damage will result in irreversible myocardial ischemia and fibrosis (“coronary Raynaud's phenomenon”).<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The natural history of SS is highly variable. Depending on the extent of skin involvement, SS is divided into two forms (limited and diffuse), with considerable clinical and prognostic differences. Cardiac dysfunction may be induced by various pathways, which may be either primary or secondary to lung damage (pulmonary hypertension) or through renal involvement. Both are frequent situations in these patients.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In the last two decades, several authors have studied the prevalence of heart disease in SS.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">4,5</span></a> Follansbee et al.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a> found a higher frequency of cardiac damage in diffuse forms. More recently, Tzelepis et al.,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> using cardiac MRI in a mixed SS population, found no differences in degree of myocardial fibrosis. Delayed enhancement on cardiac MRI (indicative of fibrosis) was detected in 60% of these patients. In the present case, a large area of subendocardial delayed enhancement was detected. Steen et al.,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a> in a series of 953 patients, reported cardiac symptoms in 15%. Mortality due to cardiovascular causes was 20%, most of which were recorded in the first five years of follow-up. In a cohort of 1012 patients,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> 35% reported cardiac symptoms, 70% of deaths were related to cardiopulmonary disease while isolated heart involvement accounted for 36% of deaths. In a large international meta-analysis<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">10</span></a> renal, cardiac, and pulmonary involvement were described as important prognostic factors, and heart disease was present in 10% of patients (8–28% depending on the series).</p><p id="par0080" class="elsevierStylePara elsevierViewall">The prevalence of angiographically documented coronary artery disease was reported to be similar to that in the general population (approximately 22%). Acute myocardial infarction is rare, with a rate of 1.09%.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a> Nevertheless, subclinical atherosclerosis has recently been detected by multidetector computed tomography in most of these patients.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">12</span></a> Moreover, coronary reserve flow studies in SS have revealed a surprisingly reduced vasodilation capacity, a phenomenon that could be explained by abnormalities in small arteries.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">13</span></a> In the case of our patient, the coronary arteries were found to be normal, as expected in a healthy young person.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Myocardial fibrosis can lead to systolic dysfunction and heart failure in the course of the disease. However, according to data from a large registry, the prevalence of LV systolic dysfunction by Doppler echocardiography appears to be low (1.4%).<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">14</span></a> Doppler echocardiography may underestimate specific findings compared with other measuring methods. In a recent study<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">15</span></a> assessing LVEF by strain rate and tissue Doppler imaging, hypocontractility was frequently detected, although LVEF appeared normal by conventional Doppler. In addition to primary involvement, there are other causes of LV systolic dysfunction, such as acute myocarditis, microvascular coronary artery disease and hypertension. Acute myocarditis was reported in the early disease stages in patients with active peripheral myopathy.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> In these subjects, the clinical course can be devastating because of severe heart failure. LV diastolic dysfunction as a cause of heart failure is very common in SS, with a prevalence ranging from 27 to 60% depending on the method used to estimate it. A lower prevalence has been observed in patients under treatment with ACE inhibitors and ARBs.</p><p id="par0090" class="elsevierStylePara elsevierViewall">RV involvement is less frequent, and is usually secondary to pulmonary hypertension. Bewley et al.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> described a rare case of SS with isolated RV dysfunction due to primary involvement. In a later study, subclinical RV systolic dysfunction was found to be more prevalent than previously thought, which become clear after using newer diagnostic modalities such as cardiac MRI, speckle-tracking-derived strain and strain rate analysis. In the present case, biventricular systolic dysfunction was found on both Doppler echocardiography and cardiac MRI.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Pericardial involvement can present in different forms, ranging from acute or chronic fibrinous pericarditis or pericardial adhesions, to effusion and pericardial tamponade. Early studies based on macroscopic observation estimated the prevalence of this involvement to be between 33% and 72%, while symptoms were less common. On histological analysis chronic pericarditis was observed in 77.5% of these individuals.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Tachyarrhythmias and conduction defects are also usually present.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a> Premature ventricular complex is the most described abnormality, with strong associations with mortality, sudden death and cardiopulmonary disease. The prevalence of supraventricular arrhythmias is around 25%. Ventricular arrhythmias have been documented in a small percentage of patients. A higher incidence of sudden death was reported in patients with myocardial and skeletal muscle abnormalities. In a prospective study, 32% had abnormal baseline electrocardiogram, left bundle branch block (16%) and first-degree atrioventricular block (8%) being the most common abnormalities.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Cardiac involvement in previously diagnosed SS patients is confirmed by standard diagnostic techniques (electrocardiography, echocardiography, cardiac catheterization, cardiac MRI). Myocardial biopsy is not commonly used.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Clinical management is controversial because of the lack of randomized clinical trials, and management is generally palliative.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1–3</span></a> In heart failure cases, ACE inhibitors and ARBs appear to be associated with some benefits, because of their vasodilator effects. Antiarrhythmic drugs are the mainstay therapy for SS-related arrhythmias. Beta-blockers and amiodarone are usually contraindicated in SS patients, because of Raynaud's phenomenon and risk of pulmonary fibrosis, respectively. Calcium channel blockers such as verapamil are the drug of first choice in supraventricular arrhythmias in patients with preserved ejection fraction, while amlodipine can be used in cases of Raynaud's phenomenon. Electrophysiological study and radiofrequency ablation are indicated in sustained ventricular arrhythmias recurring despite medical treatment. Implantable cardioverter-defibrillators should be used in life-threatening arrhythmias. Pacemaker implantation is the only treatment in cases of severe conduction impairment. Moreover, in severe refractory cases, and in the absence of contraindications, cardiac transplantation should be considered.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Ethical disclosures</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Protection of human and animal subjects</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Confidentiality of data</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Right to privacy and informed consent</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflicts of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres817829" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec814940" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres817828" "titulo" => "Resumo" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec814941" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Case report" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Right to privacy and informed consent" ] ] ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflicts of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-08-13" "fechaAceptado" => "2015-02-25" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec814940" "palabras" => array:3 [ 0 => "Systemic sclerosis" 1 => "Cardiomyopathy" 2 => "Heart failure" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec814941" "palabras" => array:3 [ 0 => "Esclerose sistémica" 1 => "Cardiomiopatia" 2 => "Insuficiência cardíaca" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systemic sclerosis (SS) is a chronic disease in which there may be multisystem involvement. It is rare (estimated prevalence: 0.5–2/10<span class="elsevierStyleHsp" style=""></span>000) with high morbidity and mortality, and there is as yet no curative treatment.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We report the case of a young woman newly diagnosed with SS, in whom decompensated heart failure was the main manifestation.</p></span>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A esclerose sistémica (ES) é uma doença crónica com possível apresentação multi-sistémica. É considerada uma doença rara (prevalência estimada: 0.5-2/10,000) com alta morbilidade e mortalidade para a qual não há cura hoje em dia.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Relatamos o caso de uma jovem mulher, recém diagnosticada de ES por afetação pleural e cutânea, com insuficiência cardíaca global no momento da consulta.</p></span>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1301 "Ancho" => 3001 "Tamanyo" => 207783 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Chest radiograph.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1897 "Ancho" => 3334 "Tamanyo" => 601248 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Transthoracic echocardiography.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1154 "Ancho" => 3000 "Tamanyo" => 180608 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Cardiac magnetic resonance.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1350 "Ancho" => 3003 "Tamanyo" => 150419 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Cardiac catheterization.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:19 [ 0 => array:3 [ "identificador" => "bib0105" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The heart in systemic sclerosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "V. 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| Year/Month | Html | Total | |
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| 2024 November | 7 | 3 | 10 |
| 2024 October | 61 | 21 | 82 |
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| 2022 November | 65 | 23 | 88 |
| 2022 October | 68 | 23 | 91 |
| 2022 September | 61 | 16 | 77 |
| 2022 August | 46 | 32 | 78 |
| 2022 July | 57 | 49 | 106 |
| 2022 June | 62 | 19 | 81 |
| 2022 May | 49 | 36 | 85 |
| 2022 April | 62 | 28 | 90 |
| 2022 March | 47 | 32 | 79 |
| 2022 February | 55 | 22 | 77 |
| 2022 January | 69 | 24 | 93 |
| 2021 December | 30 | 33 | 63 |
| 2021 November | 84 | 41 | 125 |
| 2021 October | 72 | 50 | 122 |
| 2021 September | 57 | 33 | 90 |
| 2021 August | 63 | 48 | 111 |
| 2021 July | 57 | 26 | 83 |
| 2021 June | 39 | 28 | 67 |
| 2021 May | 44 | 41 | 85 |
| 2021 April | 161 | 79 | 240 |
| 2021 March | 79 | 19 | 98 |
| 2021 February | 73 | 22 | 95 |
| 2021 January | 51 | 14 | 65 |
| 2020 December | 66 | 14 | 80 |
| 2020 November | 67 | 17 | 84 |
| 2020 October | 37 | 17 | 54 |
| 2020 September | 56 | 17 | 73 |
| 2020 August | 29 | 11 | 40 |
| 2020 July | 56 | 11 | 67 |
| 2020 June | 37 | 8 | 45 |
| 2020 May | 58 | 2 | 60 |
| 2020 April | 80 | 11 | 91 |
| 2020 March | 62 | 12 | 74 |
| 2020 February | 147 | 17 | 164 |
| 2020 January | 38 | 8 | 46 |
| 2019 December | 48 | 7 | 55 |
| 2019 November | 46 | 6 | 52 |
| 2019 October | 38 | 8 | 46 |
| 2019 September | 33 | 11 | 44 |
| 2019 August | 36 | 12 | 48 |
| 2019 July | 34 | 10 | 44 |
| 2019 June | 36 | 16 | 52 |
| 2019 May | 42 | 7 | 49 |
| 2019 April | 23 | 14 | 37 |
| 2019 March | 86 | 11 | 97 |
| 2019 February | 96 | 12 | 108 |
| 2019 January | 75 | 10 | 85 |
| 2018 December | 69 | 11 | 80 |
| 2018 November | 155 | 15 | 170 |
| 2018 October | 324 | 18 | 342 |
| 2018 September | 94 | 14 | 108 |
| 2018 August | 76 | 5 | 81 |
| 2018 July | 30 | 3 | 33 |
| 2018 June | 36 | 9 | 45 |
| 2018 May | 77 | 12 | 89 |
| 2018 April | 56 | 15 | 71 |
| 2018 March | 94 | 3 | 97 |
| 2018 February | 31 | 7 | 38 |
| 2018 January | 70 | 5 | 75 |
| 2017 December | 61 | 15 | 76 |
| 2017 November | 23 | 11 | 34 |
| 2017 October | 25 | 8 | 33 |
| 2017 September | 22 | 10 | 32 |
| 2017 August | 24 | 9 | 33 |
| 2017 July | 18 | 9 | 27 |
| 2017 June | 17 | 7 | 24 |
| 2017 May | 25 | 10 | 35 |
| 2017 April | 21 | 1 | 22 |
| 2017 March | 27 | 7 | 34 |
| 2017 February | 34 | 9 | 43 |
| 2017 January | 34 | 3 | 37 |
| 2016 December | 30 | 8 | 38 |
| 2016 November | 24 | 2 | 26 |
| 2016 October | 33 | 5 | 38 |
| 2016 September | 10 | 5 | 15 |
| 2016 August | 21 | 1 | 22 |
| 2016 July | 16 | 11 | 27 |
| 2016 June | 9 | 2 | 11 |
| 2016 May | 14 | 3 | 17 |
| 2016 April | 29 | 17 | 46 |
| 2016 March | 21 | 15 | 36 |
| 2016 February | 28 | 15 | 43 |
| 2016 January | 22 | 13 | 35 |
| 2015 December | 21 | 8 | 29 |
| 2015 November | 26 | 13 | 39 |
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