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Global and regional patterns of longitudinal strain in screening for chemotherapy-induced cardiotoxicity
Importância da deformação longitudinal na deteção da cardiotoxicidade induzida por quimioterapia e na identificação de padrões específicos de afetação segmentar
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Observa‐se uma deterioração da deformação longitudinal global sob quimioterapia. O valor central representa o valor de GLS médio; as barras de erro representam o intervalo de confiança de 95% para o erro padrão. QT: quimioterapia.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Guilherme Portugal, Luísa Moura Branco, Ana Galrinho, Miguel Mota Carmo, Ana Teresa Timóteo, Joana Feliciano, João Abreu, Sónia Duarte Oliveira, Lurdes Batarda, Rui Cruz Ferreira" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Guilherme" "apellidos" => "Portugal" ] 1 => array:2 [ "nombre" => "Luísa" "apellidos" => "Moura Branco" ] 2 => array:2 [ "nombre" => "Ana" "apellidos" => "Galrinho" ] 3 => array:2 [ "nombre" => "Miguel" "apellidos" => "Mota Carmo" ] 4 => array:2 [ "nombre" => "Ana Teresa" "apellidos" => "Timóteo" ] 5 => array:2 [ "nombre" => "Joana" "apellidos" => "Feliciano" ] 6 => array:2 [ "nombre" => "João" "apellidos" => "Abreu" ] 7 => array:2 [ "nombre" => "Sónia" "apellidos" => "Duarte Oliveira" ] 8 => array:2 [ "nombre" => "Lurdes" "apellidos" => "Batarda" ] 9 => array:2 [ "nombre" => "Rui" "apellidos" => "Cruz Ferreira" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S217420491630229X" "doi" => "10.1016/j.repce.2016.06.009" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217420491630229X?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255116302165?idApp=UINPBA00004E" "url" => "/08702551/0000003600000001/v2_201701040047/S0870255116302165/v2_201701040047/pt/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S2174204916302306" "issn" => "21742049" "doi" => "10.1016/j.repce.2016.11.002" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "907" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2017;36:17-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2618 "formatos" => array:3 [ "EPUB" => 154 "HTML" => 2020 "PDF" => 444 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Subclinical cardiotoxicity in cancer therapy: The impact of early detection" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "17" "paginaFinal" => "19" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Cardiotoxicidade subclínica em oncologia: o impacto da deteção precoce" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana G. 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The central line represents mean GLS, and the error bars represent the 95% confidence interval for one standard deviation.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Anthracyclines, and more recently trastuzumab (a monoclonal antibody that interferes with the HER2 receptor), are routinely used in the treatment of breast cancer.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">1,2</span></a> However, it was soon recognized that these drugs can lead to left ventricular (LV) systolic dysfunction as assessed by LV ejection fraction (LVEF) and to heart failure.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">3–5</span></a> Chemotherapy-induced cardiotoxicity (CIC) is one of the main determinants of prognosis in breast cancer survivors,<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">6,7</span></a> but only a small subgroup of patients exposed to chemotherapy agents will develop CIC, which has a reported incidence of 3-12% for anthracycline therapy alone and up to 28% when combined with trastuzumab.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Effective strategies are therefore required for the screening and early detection of CIC, focusing particularly on a better understanding of the mechanisms responsible for deterioration of myocardial contractility.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Speckle tracking, now available in a range of echocardiographic systems, enables assessment of the different components of myocardial deformation – longitudinal, radial and circumferential strain. Decreased global longitudinal strain (GLS) in patients with preserved LVEF is associated with adverse cardiovascular events in a variety of clinical contexts.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this study was to analyze changes in myocardial contractility as assessed by regional and global longitudinal strain in patients undergoing chemotherapy for breast cancer. In addition, we sought to establish whether changes in myocardial contractility before a fall in LVEF could predict the development of CIC.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0025" class="elsevierStylePara elsevierViewall">This was a prospective observational study of patients with breast cancer undergoing chemotherapy with anthracyclines (≥240 mg/m<span class="elsevierStyleSup">2</span> of doxorubicin or equivalent), with or without adjuvant immunotherapy, between June 2011 and October 2015. All patients referred by the hospital's oncology department for echocardiographic assessment prior to beginning chemotherapy and monitored during treatment were included. Those with a personal history of heart disease or with significant findings on initial echocardiography (LVEF <53%, LV end-diastolic diameter >60 mm, LV wall thickness >12 mm, moderate or severe valve regurgitation, or congenital heart disease) were excluded. Demographic data, current anticancer therapy and echocardiographic parameters were recorded.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Echocardiographic acquisition and processing</span><p id="par0030" class="elsevierStylePara elsevierViewall">Initial and follow-up echocardiographic assessments were performed according to the clinical indications established by the oncologist. GE Vivid 9 or Vivid 7 ultrasound systems were used to acquire parasternal long- and short-axis views, as well as apical 4-, 2- and 3-chamber views. A subgroup of patients (n=99, 63.1%) also underwent tissue Doppler study. LVEF was calculated by Simpson's biplane method.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Longitudinal strain was analyzed off-line following acquisition of apical 3-, 2- and 4-chamber views, using a semi-automatic algorithm in the EchoPAC BT12 software, based on regional assessment of 18 segments, the mean of which was used to calculate GLS. Inter- and intra-observer variability in assessing longitudinal strain in patients treated with anthracyclines has been reported previously.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Definitions</span><p id="par0040" class="elsevierStylePara elsevierViewall">CIC was defined as LVEF <53% in accordance with the criteria of the 2014 expert consensus for multimodality imaging evaluation of adult patients undergoing chemotherapy of the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI).<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">11</span></a> GLS was defined as reduced (less negative) using the cutoff of -18% recommended by the ASE/EACVI for EchoPAC BT12 software.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Changes in LVEF and global and regional longitudinal strain were analyzed by comparing baseline with follow-up echocardiograms. When more than one follow-up echocardiogram had been performed, the values corresponding to the greatest variation in the study variables were used.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Logistic regression analysis was used to determine predictors of CIC, with the incidence of CIC during follow-up as the dependent variable and including demographic characteristics, baseline echocardiogram, anticancer therapy, and the presence or absence of impaired GLS during follow-up prior to the development of CIC as independent variables. Variables with values of p<0.05 on univariate analysis were included in the multivariate model.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Continuous variables with normal distribution were compared using the Student's t test, while categorical variables were compared using the chi-square test. A value of p<0.05 was considered statistically significant.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Population characteristics and echocardiographic follow-up</span><p id="par0060" class="elsevierStylePara elsevierViewall">A total of 165 women were assessed, seven of whom were excluded due to LV dysfunction on baseline echocardiography; the final study population thus comprised 158 patients. Mean follow-up was 5.4 months (1-48), with a total follow-up time of 71.1 person years. All patients had undergone at least two echocardiographic studies, with a mean of 3.6 exams at a mean interval of 107 days.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Mean age was 54.6±12.9 years; 33% of patients underwent immunotherapy and 16.5% received radiotherapy. Baseline echocardiographic variables are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. There were no deaths from cardiovascular cause.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Incidence of chemotherapy-induced cardiotoxicity during follow-up</span><p id="par0070" class="elsevierStylePara elsevierViewall">The incidence of CIC as defined above during follow-up in the study population was 18.9% (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>), and was higher in the subgroup with adjuvant trastuzumab therapy (38.1% vs. 11.7%, p=0.001).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Global longitudinal strain</span><p id="par0075" class="elsevierStylePara elsevierViewall">There was a significant worsening of GLS during follow-up, decreasing from a baseline value of -20.1±3.5% to -18.7±3.4% (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>, p=0.001 on the Student's t test), and was more marked among patients who developed CIC (-17.2±2.5%, p=0.02). Impaired myocardial contractility was observed in a significant proportion of the total study population, with 61.4% of patients (n=97) presenting GLS below the cutoff of -18%.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Of these 97 patients, 27 eventually developed CIC, while only three of the 61 patients with preserved GLS developed CIC (27.8% vs. 4.9%, p<0.001 on the chi-square test; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, <a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>). The mean period between evidence of worsening GLS and development of CIC was 101 days. Logistic regression analysis showed that worsening GLS was associated with a higher incidence of CIC (odds ratio [OR] 7.45, confidence interval [CI] 2.15-25.8, p=0.002); in multivariate analysis, the two independent variables associated with CIC were immunotherapy (OR 3.4, CI 1.21-8.2, p=0.018) and GLS below the cutoff of -18% (OR 4.88, CI 1.32-18.0, p=0.017) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Subgroup analysis excluding patients undergoing immunotherapy showed similar results for the risk of developing CIC in the presence of worsening GLS (OR 6.24, CI 1.32-29.3, p=0.020).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Regional longitudinal strain</span><p id="par0085" class="elsevierStylePara elsevierViewall">Overall, regional longitudinal strain was determined in 93.1% of the segments analyzed, with lower success rates in the laterobasal (86.1%) and posterobasal (81.4%) segments. Compared to baseline echocardiograms, exams performed during chemotherapy revealed impaired regional longitudinal strain in 10 out of 18 LV segments (<a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The main finding in this prospective study on echocardiographic assessment of longitudinal strain in breast cancer patients undergoing chemotherapy was an independent association between worsening GLS with preserved LVEF and the incidence of CIC. Patients with impaired GLS (below -18%) presented a high incidence of CIC (28.7%). Although preserved GLS did not preclude the development of CIC in our population, the finding does indicate a more favorable prognosis in terms of cardiovascular function, as these patients had a 4.9-fold lower probability of developing CIC.</p><p id="par0095" class="elsevierStylePara elsevierViewall">As far as the authors are aware, this is the largest study to date assessing longitudinal strain in CIC.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> Our patient population was similar to those assessed in previous studies of cardiotoxicity in breast cancer patients,<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">14,15</span></a> suggesting that our data could be used to identify patients at high risk of developing CIC.</p><p id="par0100" class="elsevierStylePara elsevierViewall">A worsening of GLS was observed during chemotherapy with anthracyclines, with most patients presenting at least one echocardiographic exam showing GLS below the normal limit. This suggests the presence of subclinical myocardial dysfunction, even in patients who do not go on to develop CIC, as reported in other studies using tissue Doppler.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">16,17</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Analysis of regional longitudinal strain appears feasible in this population, as it was successful in 93.1% of the segments assessed, a mean of 17 out of 18 segments per patient. Progressive worsening of regional strain was observed during chemotherapy, mainly involving the septal (6 out of 6) and anterior segments, sparing the posterior wall and most segments of the other walls. The preferential involvement of the septum has been reported previously in echocardiographic studies with visual assessment of regional wall motion,<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">18</span></a> as well as in cardiac magnetic resonance imaging.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">19</span></a> This finding is also in agreement with a previous study that reported decreased longitudinal strain in septal, anteroseptal, anterolateral and apical segments in 27 patients undergoing chemotherapy with anthracyclines.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> While it needs to be confirmed in further studies, recognition of this pattern of septal and anterior involvement may prove useful when screening for chemotherapy-related cardiotoxicity.</p><p id="par0110" class="elsevierStylePara elsevierViewall">The interest in longitudinal strain imaging and other techniques for the early detection of subclinical injury in this context is heightened by the fact that up to 58% of patients with CIC do not recover normal systolic function.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> Although multicenter studies<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">20,21</span></a> and a recent meta-analysis<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> support the use of speckle tracking echocardiography in screening for cardiotoxicity in patients treated with anthracyclines and trastuzumab, it is still not used routinely in clinical practice. The results of our study are in line with those of previous studies, and highlight the value of longitudinal strain for both assessment of subclinical cardiotoxicity and identification of patients at high risk of developing CIC.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The present study has certain limitations. The fact that the echocardiographic exams were performed based on clinical indication rather than at previously determined intervals may have led to gaps in the data. Mean follow-up was around six months, the usual period for echocardiographic monitoring during treatment with cardiotoxic drugs, but the duration of follow-up varied widely, ranging between one month and 48 months. For this reason, development of CIC at any point during follow-up was used as the event of interest, rather than at three or six months, since this is the relevant event in clinical practice, irrespective of the time elapsed between chemotherapy and CIC. Nevertheless, this approach may have led to underestimation of the incidence of CIC in patients with shorter follow-up in whom exposure to anthracyclines may not have reached a sufficiently high cumulative dose to cause LV dysfunction.</p><p id="par0120" class="elsevierStylePara elsevierViewall">A further limitation is the fact that a third of patients presented HER2-positive breast cancer and were under adjuvant therapy with trastuzumab, which means the results cannot be generalized to those under anthracycline therapy alone. However, subgroup analysis of those under anthracycline monotherapy revealed similar results to those of the total population. Finally, no information was available on any pharmacological treatment used to prevent or treat cardiotoxicity, and this should be borne in mind when interpreting the results.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conclusions</span><p id="par0125" class="elsevierStylePara elsevierViewall">Myocardial contractility, as assessed by GLS, worsened in most patients undergoing chemotherapy for breast cancer, with predominantly septal and anterior wall involvement. Impaired GLS in patients with preserved LVEF was independently associated with increased incidence of CIC, and can thus be considered an earlier predictor of cardiotoxicity than merely calculating LVEF, as usually recommended.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Ethical disclosures</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Protection of human and animal subjects</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Confidentiality of data</span><p id="par0135" 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="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Right to privacy and informed consent</span><p id="par0140" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicts of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres792102" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec790487" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres792101" "titulo" => "Resumo" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introdução e objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusões" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec790486" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Echocardiographic acquisition and processing" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Definitions" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Population characteristics and echocardiographic follow-up" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Incidence of chemotherapy-induced cardiotoxicity during follow-up" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Global longitudinal strain" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Regional longitudinal strain" ] ] ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusions" ] 9 => array:3 [ "identificador" => "sec0070" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0085" "titulo" => "Right to privacy and informed consent" ] ] ] 10 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflicts of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-02-10" "fechaAceptado" => "2016-06-22" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec790487" "palabras" => array:3 [ 0 => "Global longitudinal strain" 1 => "Cardiotoxicity" 2 => "Trastuzumab" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec790486" "palabras" => array:3 [ 0 => "Deformação longitudinal global" 1 => "Cardiotoxicidade" 2 => "Trastuzumab" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Serial echocardiographic assessment of left ventricular ejection fraction (LVEF) is the gold standard in screening for chemotherapy-induced cardiotoxicity (CIC). Measurement of myocardial deformation using speckle tracking enables more detailed assessment of myocardial contractility. The aim of this study was to determine the relationship between global and regional longitudinal strain and CIC.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This was a prospective study of 158 breast cancer patients undergoing chemotherapy with anthracyclines with or without adjuvant trastuzumab who underwent serial monitoring by transthoracic echocardiography with assessment of myocardial deformation. CIC was defined as a decrease in LVEF to <53%. Global longitudinal strain (GLS) was estimated using EchoPAC BT12 software on a GE Vivid E9 cardiac ultrasound system. Patients were classified according to the 2015 ASE/EACVI criteria as having impaired myocardial deformation when GLS was reduced (less negative), with a cutoff of -18%.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">During a mean follow-up of 5.4 months (1-48 months), the incidence of CIC was 18.9%. A decrease in GLS was observed during follow-up for the entire cohort (baseline GLS -20.1±3.5% vs. -18.7±3.4% at last follow-up assessment, p=0.001). A total of 97 patients (61.4%) were observed to have impaired myocardial deformation (GLS ≥18%) at some point during follow-up. This decrease was more significant in patients who eventually developed CIC (GLS -17.2±2.5%, p=0.02). On analysis of regional strain, impaired contractility was observed in the septal (6 out of 6) and anterior (2 out of 3) segments. Multivariate logistic regression showed that patients who developed impaired longitudinal strain had a 4.9-fold increased risk of developing CIC (odds ratio 4.88, confidence interval 1.32-18.0, p=0.017).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Worsening of myocardial deformation as assessed by speckle tracking is common in breast cancer patients undergoing chemotherapy, with predominantly septal and anterior wall involvement. Impaired myocardial deformation was independently associated with increased incidence of CIC.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introdução e objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A avaliação seriada da fração de ejeção ventricular esquerda (FEVE) é o padrão de referência na vigilância da cardiotoxicidade induzida por quimioterapia (CIT). A avaliação da deformação longitudinal com técnicas de <span class="elsevierStyleItalic">speckle tracking</span> permite uma avaliação mais detalhada da contractilidade miocárdica. O objetivo deste estudo foi avaliar a relação entre a deformação longitudinal global (GLS) e regional e a incidência de CIT.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Foram incluídos 158 pacientes num estudo prospetivo observacional de doentes com neoplasia da mama submetidos a quimioterapia com antraciclinas, com ou sem terapêutica adjuvante com trastuzumab. Foi efetuada uma monitorização ecocardiográfica seriada de parâmetros de função sistólica e diastólica, incluindo a avaliação da deformação miocárdica longitudinal bidimensional. A incidência de CIT foi definida como uma diminuição da FEVE para valor<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>53%, de acordo com o documento de consenso da Sociedade Europeia de Imagiologia Cardiovascular (EACVI). Os doentes foram classificados como tendo deterioração da contractilidade miocárdica para um valor de GLS menos negativo que -18%, de acordo com os critérios da EACVI.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Durante um período de seguimento médio de 5,4 meses (1-48 meses), a incidência de CIT foi de 18,9%. Na população global observou-se uma deterioração significativa do GLS durante o tratamento com quimioterapia (-20,1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3,5% <span class="elsevierStyleItalic">versus</span> 18,7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3,4%, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,001), com compromisso do GLS detetado durante em algum período do seguimento em 61,4% dos doentes. Esta deterioração foi mais marcada no subgrupo de doentes com CIT (GLS: -17,2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2,5%, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,02). Na análise regional da deformação longitudinal, verificou-se compromisso da contractilidade envolvendo preferencialmente os segmentos septais (seis em seis) e parede anterior (dois em três). Por regressão logística multivariada, o compromisso do GLS esteve independentemente associado ao desenvolvimento de CIT (<span class="elsevierStyleItalic">odds ratio</span> 4,88, IC 1,32-18,0, p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,017).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusões</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">O compromisso da deformação longitudinal é frequente em doentes submetidos a quimioterapia e mostrou um padrão de distribuição predominante a nível septal e anterior. A degradação da GLS foi um preditor independente de CIT.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introdução e objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusões" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Portugal G, Moura Branco L, Galrinho A, et al. Importância da deformação longitudinal na deteção da cardiotoxicidade induzida por quimioterapia e na identificação de padrões específicos de afetação segmentar. Rev Port Cardiol. 2017;36:9–15.</p>" ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1014 "Ancho" => 1549 "Tamanyo" => 39397 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curve of survival free of chemotherapy-induced cardiotoxicity.</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" => 1035 "Ancho" => 1500 "Tamanyo" => 75265 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Changes in global longitudinal strain (GLS) between baseline and follow-up echocardiograms for the total study population, showing worsening GLS during chemotherapy. The central line represents mean GLS, and the error bars represent the 95% confidence interval for one standard deviation.</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" => 1299 "Ancho" => 1556 "Tamanyo" => 83456 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Incidence of chemotherapy-induced cardiotoxicity (CIC) according to the presence of decreased global longitudinal strain (GLS), showing that patients with worsening GLS during follow-up had a significantly higher incidence of CIC. The error bars represent the 95% confidence interval calculated by the binomial test.</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" => 1319 "Ancho" => 1542 "Tamanyo" => 134052 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Worsening of regional longitudinal strain under chemotherapy with anthracyclines. The segments shown in green presented significant worsening of regional strain by the Student's t test.</p>" ] ] 4 => 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:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">LV: left ventricular; LVEF: left ventricular ejection fraction; SD: standard deviation.</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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years ± SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">54.6±12.9</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">158 (100)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chemotherapy with anthracyclines, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">158 (100)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Immunotherapy, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">52 (33)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Radiotherapy, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">26 (16.5)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Follow-up (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">5.4 (1-48)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Death from cancer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">4 (2.5)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Echocardiographic variables \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mean \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SD \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV end-diastolic diameter (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV end-systolic diameter (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fractional shortening (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVEF (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV end-diastolic volume (ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV end-systolic volume (ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Transmitral E-wave velocity (cm/s) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Transmitral A-wave velocity (cm/s) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">79.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">E/A ratio \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.33 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Septal S’ (cm/s) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.77 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lateral S’ (cm/s) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.45 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tricuspid S’ (cm/s) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">E/e’ ratio \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1324010.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics.</p>" ] ] 5 => 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" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">CIC: chemotherapy-induced cardiotoxicity.</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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Without CIC \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">With CIC \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preserved longitudinal strain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 (36.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (1.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61 (38.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Impaired longitudinal strain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 (44.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 (17.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 (61.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">128 (81.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 (18.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">158 (100) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1324009.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Development of chemotherapy-induced cardiotoxicity and impaired longitudinal strain during follow-up.</p>" ] ] 6 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">CI: confidence interval; CIC: chemotherapy-induced cardiotoxicity; GLS: global longitudinal strain; LVEF: left ventricular ejection fraction; OR: odds ratio.</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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Univariate analysis \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Multivariate analysis \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OR 1.01 (CI 0.95-1.05) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.832 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Trastuzumab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OR 4.33 (CI 1.87-10.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OR 3.14 (CI 1.21-8.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.018 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Radiotherapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OR 2.47 (CI 0.90-6.82) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.079 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">End-diastolic volume \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OR 0.99 (CI 0.97-1.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.665 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline LVEF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OR 0.01 (CI 0.00-8.96) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.186 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Development of impaired GLS (>-18%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OR 7.45 (CI 2.15-5.83) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">OR 4.88 (CI 1.32-8.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.017 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1324011.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Univariate and multivariate analysis of predictors of chemotherapy-induced cardiotoxicity.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib0110" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C. Tan" 1 => "H. Tasaka" 2 => "K.P. Yu" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "1967" "volumen" => "20" "paginaInicial" => "333" "paginaFinal" => "353" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4290058" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0115" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "L. Gianni" 1 => "U. Dafni" 2 => "R.D. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 2 | 6 |
| 2024 October | 40 | 32 | 72 |
| 2024 September | 51 | 28 | 79 |
| 2024 August | 43 | 24 | 67 |
| 2024 July | 40 | 26 | 66 |
| 2024 June | 32 | 21 | 53 |
| 2024 May | 42 | 23 | 65 |
| 2024 April | 35 | 28 | 63 |
| 2024 March | 33 | 18 | 51 |
| 2024 February | 31 | 27 | 58 |
| 2024 January | 22 | 22 | 44 |
| 2023 December | 25 | 26 | 51 |
| 2023 November | 37 | 24 | 61 |
| 2023 October | 30 | 17 | 47 |
| 2023 September | 24 | 20 | 44 |
| 2023 August | 23 | 25 | 48 |
| 2023 July | 20 | 9 | 29 |
| 2023 June | 24 | 9 | 33 |
| 2023 May | 44 | 25 | 69 |
| 2023 April | 26 | 5 | 31 |
| 2023 March | 33 | 26 | 59 |
| 2023 February | 35 | 14 | 49 |
| 2023 January | 28 | 20 | 48 |
| 2022 December | 41 | 25 | 66 |
| 2022 November | 72 | 26 | 98 |
| 2022 October | 35 | 26 | 61 |
| 2022 September | 38 | 27 | 65 |
| 2022 August | 44 | 35 | 79 |
| 2022 July | 44 | 30 | 74 |
| 2022 June | 34 | 34 | 68 |
| 2022 May | 25 | 31 | 56 |
| 2022 April | 27 | 24 | 51 |
| 2022 March | 33 | 33 | 66 |
| 2022 February | 28 | 31 | 59 |
| 2022 January | 39 | 16 | 55 |
| 2021 December | 19 | 32 | 51 |
| 2021 November | 43 | 41 | 84 |
| 2021 October | 55 | 51 | 106 |
| 2021 September | 33 | 27 | 60 |
| 2021 August | 63 | 30 | 93 |
| 2021 July | 41 | 26 | 67 |
| 2021 June | 49 | 22 | 71 |
| 2021 May | 40 | 35 | 75 |
| 2021 April | 86 | 37 | 123 |
| 2021 March | 60 | 24 | 84 |
| 2021 February | 78 | 19 | 97 |
| 2021 January | 58 | 16 | 74 |
| 2020 December | 65 | 14 | 79 |
| 2020 November | 69 | 19 | 88 |
| 2020 October | 41 | 14 | 55 |
| 2020 September | 93 | 9 | 102 |
| 2020 August | 42 | 13 | 55 |
| 2020 July | 74 | 18 | 92 |
| 2020 June | 79 | 17 | 96 |
| 2020 May | 58 | 15 | 73 |
| 2020 April | 65 | 22 | 87 |
| 2020 March | 189 | 9 | 198 |
| 2020 February | 168 | 35 | 203 |
| 2020 January | 80 | 9 | 89 |
| 2019 December | 49 | 5 | 54 |
| 2019 November | 53 | 9 | 62 |
| 2019 October | 79 | 5 | 84 |
| 2019 September | 83 | 15 | 98 |
| 2019 August | 61 | 8 | 69 |
| 2019 July | 65 | 13 | 78 |
| 2019 June | 48 | 13 | 61 |
| 2019 May | 52 | 11 | 63 |
| 2019 April | 22 | 16 | 38 |
| 2019 March | 118 | 15 | 133 |
| 2019 February | 95 | 15 | 110 |
| 2019 January | 81 | 11 | 92 |
| 2018 December | 107 | 11 | 118 |
| 2018 November | 131 | 11 | 142 |
| 2018 October | 192 | 26 | 218 |
| 2018 September | 47 | 18 | 65 |
| 2018 August | 39 | 15 | 54 |
| 2018 July | 34 | 7 | 41 |
| 2018 June | 56 | 11 | 67 |
| 2018 May | 50 | 18 | 68 |
| 2018 April | 72 | 15 | 87 |
| 2018 March | 61 | 6 | 67 |
| 2018 February | 27 | 6 | 33 |
| 2018 January | 37 | 8 | 45 |
| 2017 December | 55 | 10 | 65 |
| 2017 November | 59 | 14 | 73 |
| 2017 October | 47 | 15 | 62 |
| 2017 September | 41 | 22 | 63 |
| 2017 August | 52 | 19 | 71 |
| 2017 July | 43 | 9 | 52 |
| 2017 June | 45 | 20 | 65 |
| 2017 May | 52 | 21 | 73 |
| 2017 April | 28 | 12 | 40 |
| 2017 March | 39 | 20 | 59 |
| 2017 February | 82 | 36 | 118 |
| 2017 January | 79 | 48 | 127 |
| 2016 December | 5 | 4 | 9 |
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