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" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 692 "Ancho" => 1800 "Tamanyo" => 111898 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Cardiac magnetic resonance.</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" => "xres572376" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec589457" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres572375" "titulo" => "Resumo" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec589456" "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" => "xpalclavsec589457" "palabras" => array:3 [ 0 => "Systemic sclerosis" 1 => "Cardiomyopathy" 2 => "Heart failure" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec589456" "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" => 780 "Ancho" => 1800 "Tamanyo" => 102502 ] ] "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" => 1138 "Ancho" => 2000 "Tamanyo" => 298420 ] ] "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" => 692 "Ancho" => 1800 "Tamanyo" => 111898 ] ] "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" => 809 "Ancho" => 1800 "Tamanyo" => 79663 ] ] "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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| 2024 Maio | 31 | 26 | 57 |
| 2024 Abril | 41 | 30 | 71 |
| 2024 Maro | 58 | 24 | 82 |
| 2024 Fevereiro | 47 | 34 | 81 |
| 2024 Janeiro | 31 | 33 | 64 |
| 2023 Dezembro | 37 | 26 | 63 |
| 2023 Novembro | 35 | 21 | 56 |
| 2023 Outubro | 33 | 15 | 48 |
| 2023 Setembro | 33 | 17 | 50 |
| 2023 Agosto | 35 | 21 | 56 |
| 2023 Julho | 33 | 11 | 44 |
| 2023 Junho | 43 | 14 | 57 |
| 2023 Maio | 52 | 23 | 75 |
| 2023 Abril | 28 | 3 | 31 |
| 2023 Maro | 51 | 29 | 80 |
| 2023 Fevereiro | 41 | 16 | 57 |
| 2023 Janeiro | 22 | 15 | 37 |
| 2022 Dezembro | 37 | 24 | 61 |
| 2022 Novembro | 44 | 29 | 73 |
| 2022 Outubro | 40 | 21 | 61 |
| 2022 Setembro | 17 | 25 | 42 |
| 2022 Agosto | 48 | 45 | 93 |
| 2022 Julho | 37 | 34 | 71 |
| 2022 Junho | 28 | 25 | 53 |
| 2022 Maio | 36 | 34 | 70 |
| 2022 Abril | 30 | 22 | 52 |
| 2022 Maro | 29 | 28 | 57 |
| 2022 Fevereiro | 31 | 19 | 50 |
| 2022 Janeiro | 25 | 25 | 50 |
| 2021 Dezembro | 38 | 30 | 68 |
| 2021 Novembro | 48 | 45 | 93 |
| 2021 Outubro | 32 | 46 | 78 |
| 2021 Setembro | 28 | 27 | 55 |
| 2021 Agosto | 36 | 26 | 62 |
| 2021 Julho | 34 | 22 | 56 |
| 2021 Junho | 19 | 21 | 40 |
| 2021 Maio | 23 | 25 | 48 |
| 2021 Abril | 46 | 36 | 82 |
| 2021 Maro | 50 | 13 | 63 |
| 2021 Fevereiro | 50 | 21 | 71 |
| 2021 Janeiro | 26 | 7 | 33 |
| 2020 Dezembro | 28 | 5 | 33 |
| 2020 Novembro | 43 | 18 | 61 |
| 2020 Outubro | 21 | 10 | 31 |
| 2020 Setembro | 69 | 19 | 88 |
| 2020 Agosto | 29 | 8 | 37 |
| 2020 Julho | 50 | 11 | 61 |
| 2020 Junho | 58 | 13 | 71 |
| 2020 Maio | 58 | 4 | 62 |
| 2020 Abril | 43 | 16 | 59 |
| 2020 Maro | 51 | 12 | 63 |
| 2020 Fevereiro | 95 | 14 | 109 |
| 2020 Janeiro | 33 | 6 | 39 |
| 2019 Dezembro | 52 | 12 | 64 |
| 2019 Novembro | 37 | 8 | 45 |
| 2019 Outubro | 52 | 9 | 61 |
| 2019 Setembro | 30 | 7 | 37 |
| 2019 Agosto | 46 | 10 | 56 |
| 2019 Julho | 44 | 10 | 54 |
| 2019 Junho | 49 | 19 | 68 |
| 2019 Maio | 48 | 6 | 54 |
| 2019 Abril | 37 | 11 | 48 |
| 2019 Maro | 115 | 12 | 127 |
| 2019 Fevereiro | 96 | 14 | 110 |
| 2019 Janeiro | 85 | 5 | 90 |
| 2018 Dezembro | 95 | 12 | 107 |
| 2018 Novembro | 163 | 11 | 174 |
| 2018 Outubro | 327 | 22 | 349 |
| 2018 Setembro | 73 | 11 | 84 |
| 2018 Agosto | 50 | 19 | 69 |
| 2018 Julho | 43 | 5 | 48 |
| 2018 Junho | 53 | 4 | 57 |
| 2018 Maio | 42 | 9 | 51 |
| 2018 Abril | 73 | 2 | 75 |
| 2018 Maro | 87 | 8 | 95 |
| 2018 Fevereiro | 19 | 2 | 21 |
| 2018 Janeiro | 30 | 2 | 32 |
| 2017 Dezembro | 77 | 11 | 88 |
| 2017 Novembro | 49 | 3 | 52 |
| 2017 Outubro | 36 | 11 | 47 |
| 2017 Setembro | 45 | 7 | 52 |
| 2017 Agosto | 40 | 14 | 54 |
| 2017 Julho | 29 | 7 | 36 |
| 2017 Junho | 40 | 9 | 49 |
| 2017 Maio | 49 | 9 | 58 |
| 2017 Abril | 33 | 6 | 39 |
| 2017 Maro | 28 | 3 | 31 |
| 2017 Fevereiro | 29 | 6 | 35 |
| 2017 Janeiro | 23 | 5 | 28 |
| 2016 Dezembro | 28 | 8 | 36 |
| 2016 Novembro | 30 | 10 | 40 |
| 2016 Outubro | 27 | 6 | 33 |
| 2016 Setembro | 12 | 8 | 20 |
| 2016 Agosto | 13 | 4 | 17 |
| 2016 Julho | 4 | 2 | 6 |
| 2016 Junho | 15 | 11 | 26 |
| 2016 Maio | 15 | 0 | 15 |
| 2016 Abril | 18 | 1 | 19 |
| 2016 Maro | 34 | 12 | 46 |
| 2016 Fevereiro | 24 | 20 | 44 |
| 2016 Janeiro | 27 | 13 | 40 |
| 2015 Dezembro | 30 | 15 | 45 |
| 2015 Novembro | 80 | 36 | 116 |
| 2015 Outubro | 110 | 69 | 179 |
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