Global longitudinal strain as a biomarker in diabetic cardiomyopathy. A comparative study with Gal-3 in patients with preserved ejection fraction

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A comparative study with Gal-3 in patients with preserved ejection fraction" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "278" "paginaFinal" => "285" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Ramiro Flores-Ramírez, José Ramón Azpiri-López, José Gerardo González-González, Alejandro Ordaz-Farías, Luis Eduardo González-Carrillo, Edgar Francisco Carrizales-Sepúlveda, Raymundo Vera-Pineda" "autores" => array:7 [ 0 => array:4 [ "nombre" => "Ramiro" "apellidos" => "Flores-Ramírez" "email" => array:1 [ 0 => "flores.ramiro@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "José Ramón" "apellidos" => "Azpiri-López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "José Gerardo" "apellidos" => "González-González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Alejandro" "apellidos" => "Ordaz-Farías" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Luis Eduardo" "apellidos" => "González-Carrillo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Edgar Francisco" "apellidos" => "Carrizales-Sepúlveda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Raymundo" "apellidos" => "Vera-Pineda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Cardiology Service and the Echocardiography Laboratory, Hospital Universitario Dr. Jose Eleuterio Gonzalez, Universidad Autónoma de Nuevo León, Monterrey, Mexico" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Endocrinology Service, Hospital Universitario Dr. Jose E. Gonzalez, Universidad Autónoma de Nuevo León, Monterrey, Mexico" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author. Tel.: +52 8116601001; fax: +52 8114928262." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Deformación longitudinal global como un biomarcador en miocardiopatía diabética. Estudio comparativo con galectina-3 en pacientes con fracción de eyección preservada" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1316 "Ancho" => 1652 "Tamanyo" => 84953 ] ] "descripcion" => array:1 [ "en" => "DmdEF (diabetics with mild depressed ejection fraction). DpEF (diabetics with preserved ejection fraction)." ] ] ] "textoCompleto" => "IntroductionDiabetic cardiomyopathy was first described by Rubler in 1972.<a class="elsevierStyleCrossRefs" href="#bib0125">1,2</a> The term describes several mechanisms involved in the pathogenesis of this entity including changes in myocardial structure and metabolism that are not directly attributed to other co-morbidities such as coronary artery disease (CAD) or hypertension. Left ventricular hypertrophy, myocardial lypotoxicity, increased oxidative stress, cell death from apoptosis, impaired contractile reserve, altered substrate utilization as free fatty acids (FFA), mitochondrial dysfunction and fibrosis are among the mechanisms involved with these changes in structure and metabolism contributing to the progression of heart failure.<a class="elsevierStyleCrossRef" href="#bib0130">2</a> In particular, fibrosis is one of the abnormalities that can be evaluated with the newer imaging techniques. Cardiac magnetic resonance (CMR) is the gold standard in the assessment of myocardial fibrosis given that T1 sequences separate normal from fibrotic tissue.<a class="elsevierStyleCrossRef" href="#bib0135">3</a> Nonetheless, CMR is not widely available, and it is time and cost consuming with longer and exhausting protocols. Speckle tracking echocardiography measurement of these parameters has been validated against magnetic resonance imaging.<a class="elsevierStyleCrossRefs" href="#bib0140">4,5</a> Global longitudinal strain (GLS) is the simplest deformation parameter and probably the closest to routine clinical application.<a class="elsevierStyleCrossRef" href="#bib0150">6</a> Quantitative assessment of myocardial function is now possible with speckle tracking echocardiography.<a class="elsevierStyleCrossRef" href="#bib0155">7</a>More than half of patients with heart failure have preserved ejection fraction (HFpEF).<a class="elsevierStyleCrossRef" href="#bib0160">8</a> Diagnosis and therapies are difficult because of a lack of specific biomarkers and imaging techniques. There is a need to anticipate the progression of heart failure in patients with diabetes and for that reason we propose a strategy of non-invasive analysis of inflammation-fibrosis LVD. Galectin-3 (Gal-3) has emerged as a new biomarker in heart failure and has a strong relationship with inflammation and fibrosis.<a class="elsevierStyleCrossRef" href="#bib0165">9</a> Galectin-3 is a β-galactoside-binding member of the lectin family in which 14 mammalian galectins have been identified. Galectin-3 is an ∼30kDa protein and contains a carbohydrate recognition binding domain (CRD) of 130 aminoacids that enables the specific binding of β-galactosides and is encoded on by a single gene, LGALSS3 located on chromosome14, locus q21-q22. Galectin-3 has recently been linked to HF development.<a class="elsevierStyleCrossRefs" href="#bib0170">10,11</a> We believe that Galectin-3 could detect early stages of left ventricular dysfunction (LVD) in diabetic patients with preserved ejection fraction. On the other hand, newer echocardiography techniques allow evaluating LVD before ejection fraction declines. This study aims to analyze the relation between a cardiac biomarker of fibrosis, Gal-3, and the patterns of GLS in asymptomatic patients with type 2 diabetes and preserved ejection fraction.MethodsParticipantsFrom April 1, 2015 to August 31, 2015 a total of 159 subjects from the endocrinology outpatient clinic were recruited. The study had ethics approval by our Institutional Review Board. Patients with type 2 diabetes and no history of cardiovascular disease were included. Thirty-one age- and sex-matched healthy volunteers were also studied. Each examination consisted of a clinical history and physical exam, anthropometry, blood samples and routine echocardiogram with strain measurements. Patients with a history of cardiovascular and renal disease, valvular heart disease, atrial fibrillation, angina or previous myocardial infarction were excluded. Two patients excluded had atrial fibrillation, one with chronic liver disease; two patients had myocardial infarction unknown to them and 9 had symptoms of angina; six had a history of stroke. Eighteen non-diabetic individuals in the control group were excluded because of depressed ejection fraction. A total of 121 participants were divided in 3 groups. Group 1: 14 patients with type 2 diabetes and mild depressed ejection fraction (mdEF); group 2: 76 patients with type 2 diabetes and preserved ejection fraction (pEF) and group 3: 31 age- and sex-matched controls without diabetes.BiomarkerBlood samples were collected after an overnight fast and immediately centrifuged and stored at −70°C until assayed. Plasma concentrations of Gal-3 were measured using an enzyme-linked immunosorbent assay with a sensitivity of 10pg/ml (Abcam Inc., Cambridge, MA), according to the manufacturer's instructions.EchocardiographyRoutine 2-dimensional and Doppler echocardiography was performed according to the American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines using a ViVid E9 echocardiogram with a 1.5–3.6MHz transducer (GE Vingmed, Horten, Norway). Two certified echocardiologists unaware of the clinical history and Gal-3 level acquired and evaluated all echocardiograms. Indexed ventricular mass was assessed in a linear fashion using the paraesternal long axis view. Left ventricular ejection fraction was calculated with the bi-plane Simpson's method. Preserved ejection fraction was defined as an ejection fraction (EF) above 52% in male subjects and 54% in female subjects; mildly depressed ejection fraction was defined as 41–51% in men and 41–53% in women as described in ASE/EACVI guidelines.<a class="elsevierStyleCrossRef" href="#bib0180">12</a> Pulsed-wave (PW) Doppler was performed in the apical 4-chamber view to obtain mitral inflow velocities to assess left ventricular (LV) filling. A 1-mm sample volume is then placed between the mitral leaflet tips during diastole. Diastolic function measurements include peak early filling (E-wave) and late diastolic filling (A-wave) velocities, the E/A ratio, and deceleration time. Pulsed wave tissue Doppler imaging (DTI) was performed in the 4CH apical view with sample volume positioned at 1cm within the septal insertion site of the mitral leaflet for E/e′. Diastolic dysfunction was defined with criteria described earlier.<a class="elsevierStyleCrossRef" href="#bib0185">13</a> Three cardiac cycles were recorded in 4, 2 and 3 chambers for the offline speckle tracking analyses of GLS. Offline analyses were performed in EchoPAC PC 113.0.X. (GE Vingmed Horten Norway). The complete region of interest (ROI) was defined at end-diastole as the endocardial border: the inner contour of the myocardium; epicardial border: the outer contour of the myocardium; and myocardial midline: the middle ROI axis defined in the middle between the inner and outer ROI contours.<a class="elsevierStyleCrossRef" href="#bib0190">14</a> Each of these contours can be either user-defined or generated automatically. In any case, these were generated automatically; our echocardiologists checked them and, if needed, edited the images manually taking care of defining the ROI to avoid pericardium inclusion.<a class="elsevierStyleCrossRef" href="#bib0155">7</a> Normal reference values of GLS were taken from the literature.<a class="elsevierStyleCrossRef" href="#bib0150">6</a> All individuals were in sinus rhythm at the time of imaging and had no significant cardiovascular abnormalities.ReproducibilityFor inter and intraobserver variability, GLS and EF were assessed in a subset of 45 subjects randomly selected from the study population and analyzed with Bland–Altman analysis and the Wilcoxon rank with no significant differences between observers. For biplane GLS (SD) interpreter 1, −19.75 (4.09) vs interpreter 2, −19.75 (4.72), Wilcoxon rank test .55 and for EF (SD) interpreter 1, 57 (9.64) vs interpreter 2, 57.5 (11.26) difference -0.5 (5.09) Wilcoxon rank test .60.Statistical analysisCategorical values were reported as frequencies. Quantitative variables were tested for normality with the Kolmogorov–Smirnov test. For variables with normal distribution mean±standard deviation (SD) was used. Difference in quantitative data between groups was analyzed using a one-way ANOVA test. When a significant difference was found (p<0.05), the Tukey test was used to determine which group was unequal from the others (p<0.05). The Gal-3 cutoff point was assessed using receiver operating characteristics (ROC curve) and the Youden index. Area under the curve (AUC) values >0.5 with a p<0.05 were considered statistically significant (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>All statistical data were analyzed with SPSS version 21.0 (IBM Corp., NY, USA).ResultsAll demographic results are described in (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). There were no differences between groups according to age, sex, body mass index and other cardio-metabolic parameters.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Based on updated echocardiographic guidelines,<a class="elsevierStyleCrossRef" href="#bib0180">12</a> we compare diabetic individuals with mdEF vs pEF vs controls (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Gal-3 was elevated in all individuals with diabetes compared to controls (3.46±1.36ng/ml vs 2.78±0.91ng/ml; p=0.003) with no difference between diabetic patients with mild depressed ejection fraction and preserved ejection fraction (3.76±1.12ng/ml vs 3.41±1.4ng/ml; p=0.603) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). All echocardiographic variables are described in (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Gal-3 was found to be higher in mdEF (2.78±0.9ng/ml vs 3.76±1.12ng/ml; p=0.009) and pEF subjects (2.78±0.9ng/ml vs 3.41±1.40ng/ml; p=0.058) compared to controls.To assess the effect of diabetes progression on left ventricular function, we divided our cohort in those who had less than 10 years since diagnosis and those with more than 10 years. Gal-3 levels were higher in patients with more than 10 years (p=0.011). There was no significant statistical difference regarding EF (p=0.286) and GLS (p=0.228). Diastolic function was more frequently altered in the group with more than 10 years (p=0.03) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). When we compare diabetic individuals did not found difference in baseline Gal-3 in diabetes with mdEF n=14 (3.76±1.12ng/ml) vs pEF n=76 (3.41±1.4ng/ml) p=0.60, but consistently LVD with GLS between these groups (−13.35±3.41 vs −19.46±3.26) p=0.001. Compared to controls, all individuals with diabetes had worst GLS (p=0.022). There was no difference in GLS in diabetic patients with pEF when compared to non-diabetic controls (p=0.70). Patients with mdEF had significantly lower GLS than controls (p<0.001) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Thirty per cent of those in the pEF group had impaired GLS values and 92.9% in the mdEF group. Both parameters move discretely in the desired direction, but with wide dispersion, without any correlation. Using 2 markers, Gal-3 (>2.71ng/ml) and GLS (<18%), we found a sensitivity of 0.85, a specificity of 0.81, a PPV of 0. 46 and a NPV of 0.97 for LVD (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>DiscussionLeft ventricular dysfunction (LVD) is now known to be a major co-morbidity in diabetes. Hypertension and DM are closely related and complicate each other. The activation of the rennin–angiotensin–aldosterone system causes insulin resistance.<a class="elsevierStyleCrossRefs" href="#bib0195">15,16</a> Cardiac remodeling occurs together with hypertension and DM.<a class="elsevierStyleCrossRef" href="#bib0205">17</a> Difficult exists in specifying the cause of cardiac remodeling in diabetes because of the lack of criteria and tools, including biomarkers and imaging techniques. Microvasculopathy is a primary feature in diabetic cardiac remodeling but no surrogate can directly monitor disease progression. Therefore there is an increasing interest in the link between DM and heart failure. Diabetic cardiomyopathy is a term assigned to those patients with cardiomyopathy without coronary artery disease and hypertension.<a class="elsevierStyleCrossRef" href="#bib0210">18</a> Multiple substrates are responsible for myocardial damage including fatty acid uptake, collagen metabolism, oxidation and fibrosis.<a class="elsevierStyleCrossRef" href="#bib0130">2</a> Because Gal-3 is a marker of inflammation and fibrosis<a class="elsevierStyleCrossRef" href="#bib0165">9</a> we aimed to correlate this biomarker with a non-invasive, easier and accessible tool in the evaluation of pre-clinical heart failure or incipient myocardial dysfunction in patients with diabetes.It is estimated than more than 50% of patients presenting with signs and symptoms of heart failure suffer from heart failure with preserved ejection fraction (HFpEF).<a class="elsevierStyleCrossRef" href="#bib0215">19</a> The vast majority of published articles on Gal-3 described patients with heart failure with reduced ejection fraction (HFrEF) not HFpEF.<a class="elsevierStyleCrossRef" href="#bib0165">9</a> Echocardiography is a non-invasive tool in the global evaluation of heart disease. Some of its features includes left ventricular ejection fraction (LVEF). LVEF has been demonstrated in patients with heart failure in different scenarios such as coronary artery disease, valvular heart disease and other cardiomyopathies. LVEF has been the fundamental tool for systolic function; nonetheless it is less sensitive for detecting early myocardial disease than newer techniques.<a class="elsevierStyleCrossRef" href="#bib0220">20</a> Asymptomatic myocardial dysfunction can occur in diabetic patients without CAD. LVEF could be normal but myocardial dysfunction in terms of abnormal deformation is not. GLS can detect myocardial abnormalities before EF declines.<a class="elsevierStyleCrossRef" href="#bib0220">20</a> The presence of LVD was defined in a large meta-analysis of strain. The mean GLS in normal subjects was −19.7%, with a lower 95% CI of −18.9%.<a class="elsevierStyleCrossRef" href="#bib0150">6</a> In a recent study, Holland et al. evaluated the 10-year outcomes in subclinical myocardial dysfunction evaluating GLS in a cohort of 249 type 2 diabetic patients with normal LVEF.<a class="elsevierStyleCrossRef" href="#bib0225">21</a> Holland found that almost half of patients (45%) had evidence of LVD detected by GLS in a median follow-up of 7.4±2.6 years. GLS was independently associated with the primary endpoint. Patients with LVD had a significantly worse outcome than those without. They concluded that subclinical LVD is common in asymptomatic patients with type 2 DM, that it was detectable by GLS imaging and is independently associated with adverse outcome.<a class="elsevierStyleCrossRef" href="#bib0225">21</a> In our study we found that GLS is depressed in all individuals with diabetes compared to controls (p=0.003) but there is no difference in GLS in diabetic patients with pEF when compared to controls (−19.4±3.2 vs −20±2.6; p=0.42) but Gal-3 was significantly elevated (p=0.008). Left ventricular dysfunction (GLS <−18) was found in 30.3% of pEF subjects. We assume at this point that diabetic individuals with pEF are in early phases of inflammation and extracellular matrix proliferation but these needs to be confirmed in a MRI study. Using 2 markers, Gal-3 (>2.71ng/ml) and GLS (<18%), we found a sensitivity of 0.85, a specificity of 0.81, a PPV of 0. 46 and a NPV of 0.97 for LVD.Only a few studies have described the levels and clinical correlation of Gal-3 and HFpEF. The COACH study de Boer et al. found, in a cohort of 592 patients admitted with acute heart failure, that 19.2% (114) of patients with HFpEF and Gal-3 levels where comparable between HFrEF and HFpEF (∼20ng/ml).<a class="elsevierStyleCrossRef" href="#bib0230">22</a> Our population was a non-Caucasian heart failure symptom-free cohort from the endocrinology outpatient clinic. Levels of Gal-3 were not highly elevated in this cohort compared to other studies (∼3.4pg/ml); in the fibrosis marker, Gal-3, and in the outcome in the general population, de Boer found a gender interaction, with female subjects having higher median Gal-3 levels 11.0ng/ml IQR (interquartile range 9.0–13.1ng/ml.) than men 10.7ng/ml IQR (8.9–12.8ng/ml) but they excluded non-Caucasian subjects.<a class="elsevierStyleCrossRef" href="#bib0235">23</a> In the epidemiological field Ho et al.<a class="elsevierStyleCrossRef" href="#bib0240">24</a> Investigated Gal-3 linked to the development of HF in the general population. Gal-3 concentrations were measured in 3353 participants from the Framingham Offspring Cohort and were associated independently with an increased risk for developing HF and mortality. Crude HF incidence rates were estimated by sex-specific Gal-3 quartile. Quartile 1: 3.9–11.1ng/ml, quartile 2: 11.1–13.1ng/ml, quartile 3: 13.1–15.4ng/ml and quartile 4: 16.8–51.1ng/ml. During a mean follow-up period of 11.2 years, 166 (5.1%) subjects developed HF. The heart failure incidence rate increased over Gal-3 quartiles, with rates of 2.8, 3.8, 5.2 and 12.4 events per 1000 persons-years in quartiles 1 through 4, respectively. Our cohort resembles quartile 1 of the Ho study. We believe that in diabetic patients adding GLS to standard echocardiograms is useful in the detection of early phases of LVD. The combination of Gal-3 and GLS has a high NPV of 0.94. At the same time our study demonstrates that Gal-3 was elevated in all diabetic individuals compared to controls (p=0.003). Gal-3 was found to be higher in patients with mdEF compared to pEF with diabetic subjects not reaching significance due to sample size (p=0.375). When compared to controls Gal-3 was found to be higher in pEF diabetic subjects (p=0.008).Study limitationsWe studied only one of the substrates of DCM. It would have been useful to compare GLS with cardiac magnetic resonance for detection of fibrosis; however, it was not available at our institution. Also, non-significant differences could be as a result of the sample size basically in the mdEF group. We did not studied the existence of ischemic heart disease even in those diabetic subjects with more than 10 years of diagnostic so these make harder to consider DCM by itself, an lastly GLS is not a surrogate of Gal-3.ConclusionsThis is a non-Caucasian study in a diabetic heart failure symptom free cohort. Global longitudinal strain is an easy and reproducible echocardiography tool in the evaluation and follow-up of DCM in diabetic subjects although is not a surrogate of Gal-3 because this biomarker is elevated in all diabetics. There still much to investigate in the physiopathology of DCM especially in asymptomatic patients with preserved ejection fraction. Including Gal-3 to standard echocardiography and GLS would be helpful in the early detection of LVD in DCM.Ethical responsibilitiesProtection of people and animalsThe authors state that the procedures conformed to the ethical standards of human experimentation committee responsible and according to the World Medical Association and the Declaration of Helsinki.Confidentiality of dataThe authors declare that they have followed the protocols of the workplace on the publication of patient data.Right to privacy and informed consentThe authors have obtained the informed consent of patients and/or subjects referred to in Article consent. This document is held by the corresponding author.FundingThis study has no funding.Conflict of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres933284" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 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" => "xpalclavsec907628" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres933283" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec907629" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Participants" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Biomarker" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Echocardiography" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Reproducibility" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Study limitations" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Conclusions" ] 10 => array:3 [ "identificador" => "sec0060" "titulo" => "Ethical responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Protection of people and animals" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "Right to privacy and informed consent" ] ] ] 11 => array:2 [ "identificador" => "sec0080" "titulo" => "Funding" ] 12 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 13 => array:2 [ "identificador" => "xack315047" "titulo" => "Acknowledgements" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-01-25" "fechaAceptado" => "2016-06-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec907628" "palabras" => array:4 [ 0 => "Galectin-3" 1 => "Global longitudinal strain" 2 => "Diabetic cardiomyopathy" 3 => "Mexico" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec907629" "palabras" => array:4 [ 0 => "Galectina-3" 1 => "Deformación longitudinal global" 2 => "Miocardiopatía diabética" 3 => "México" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectivesTo establish a relationship between global longitudinal strain (GLS) and Galectin-3 in pre-clinical heart failure in diabetic patients. Galectin-3 is a biomarker in heart failure with depressed ejection fraction (HFdEF). The hypothesis is presented that Galectin-3 is related to GLS and can detect left ventricular dysfunction in heart failure with preserved ejection fraction. MethodsGalectin-3 and GLS were measured in 121 asymptomatic individuals: 14 diabetics with mild depressed ejection fraction (mdEF) (LVEF 47.0±6.9); 76 diabetics with preserved ejection fraction (LVEF 61±5.5), and 31 controls (61.7±5.1). ResultsGalectin-3 was elevated in all diabetics vs controls (3.46±1.36 ng/ml vs 2.78±0.91 ng/ml; p=.003). It was also elevated in mdEF (3.76±1.12 ng/ml vs 2.78±0.9 ng/ml; p=.009) and pEF subjects (3.41±1.40 ng/ml vs 2.78±0.9 ng/ml; p=.058), respectively, vs controls. No difference in Gal-3 was found between diabetic groups (p=.603). Diabetics had lower GLS than controls (−18.5±3.9 vs −20±2.6; p=.022). Diabetics with mdEF had lower GLS than those with pEF (−13.3±3.41 vs −19±3.2; P<.001). There was no difference in GLS with pEF compared to controls (−19.4±3.2 vs −20±2.6; p=.70). ConclusionsGalectin-3 is elevated in diabetic patients with mdEF, and is associated with a diminished GLS. GLS could be an early marker of left ventricular dysfunction as well as evidence of diabetic cardiomyopathy." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivosEstablecer una asociación entre deformación longitudinal global (DLG) y galectina-3 en insuficiencia cardiaca preclínica en pacientes diabéticos.Galectina-3 es un biomarcador en insuficiencia cardiaca con fracción de eyección deprimida. Nuestra hipótesis es que la DLG y galectina-3 correlacionan y pueden detectar disfunción ventricular en insuficiencia cardiaca con FEVI preservada. MétodosSe midieron galectina-3 y DLG en 121 individuos asintomáticos: 14 diabéticos con FEVI deprimida leve (FEdl) (FEVI 47±6.9); 76 diabéticos con FEVI preservada (FEp) (FEVI 61±5.5) y 31 sujetos controles (FEVI 61.7±5.1). ResultadosGalectina-3 se encontró elevada en todos los diabéticos vs controles (3.46±1.36ng/ml vs 2.78±0.91ng/ml; p=0.003). Está elevada en sujetos con FEdl (3.76±1.12 vs 2.78±0.9 vs ng/ml p=0.009) y FEp (3.41±1.40 vs 2.78±0.9ng/ml p=0.058), respectivamente vs controles; no encontramos diferencia en galectina-3 en ambos grupos de diabéticos (p=0.603). Los diabéticos tienen menor DLG que los controles (−18.5±3.9 vs −20±2.6; p=0.022). Los diabéticos con FEdl tienen DLG más disminuida que aquellos con FEp (−13.3±3.41 vs −19±3.2; p<0.001). No existe diferencia en DLG con FEp y controles (−19.4±3.2 vs −20±2.6; p=0.70). ConclusionesGalectina-3 está elevada en diabéticos con FEdl y correlaciona DLG disminuida. DLG podría ser un marcador temprano de disfunción ventricular y evidencia en miocardiopatía diabética." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "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" => 1632 "Ancho" => 1656 "Tamanyo" => 74689 ] ] "descripcion" => array:1 [ "en" => "ROC curve for LVD (left ventricular dysfunction). Highest performance Gal-3 value was 2.71ng/ml with p=0.048, AUC: 0.663, sensitivity: 0.928, specificity: 0.381 and (NPV) negative predictive value: 0.96." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1316 "Ancho" => 1652 "Tamanyo" => 84953 ] ] "descripcion" => array:1 [ "en" => "DmdEF (diabetics with mild depressed ejection fraction). DpEF (diabetics with preserved ejection fraction)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1181 "Ancho" => 1639 "Tamanyo" => 74360 ] ] "descripcion" => array:1 [ "en" => "DmdEF (diabetics with mild depressed ejection fraction). DpEF (diabetics with preserved ejection fraction)." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1283 "Ancho" => 1616 "Tamanyo" => 62300 ] ] "descripcion" => array:1 [ "en" => "Sensitivity, specificity, PPV (positive predictive value) and NPV (negative predictive value). Using both parameters; Gal-3 at >2.71ng/ml and global longitudinal strain <18%." ] ] 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" => "Plus-minus values are means±SD. There were no significant between-group differences at baseline except for T2DM (type 2 diabetes mellitus). SBP: systolic blood pressure; DBP: diastolic blood pressure; BMI: body mass index." "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">T2DM with mdEF (n=14) \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">T2DM with pEF (n=76) \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">Non-diabetic controls (n=31) \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 value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age (yrs), mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55.42±8.51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55.25±10.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50.89±9.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.122 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Female, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (57.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46 (60.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 (64.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.880 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Smoking ever, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (28.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 (30.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 (45.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.158 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Dyslipidemia, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (71.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">41 (53.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.014 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hypertension, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (42.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 (52.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.106 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">T2DM, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 (0) \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">SBP (mmHg), mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">97.03±57.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">124.36±26.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">125.19±30.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.013 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">DBP (mmHg), mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59.64±34.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">73.71±15.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">74.87±17.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.034 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BMI, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">34.97±6.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30.79±5.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30.41±5.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.024 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1577232.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic characteristics of study group." ] ] 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" => "Plus-minus values are means±SD. There were significant differences in GLS (global longitudinal strain), biplane EF (ejection fraction) and diastolic dysfunction in diabetics vs controls." "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">T2DM with mdEF (n=14) \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">T2DM with pEF (n=76) \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">Non-diabetic controls (n=31) \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 value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Gal-3 (ng/ml), mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.76±1.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.41±1.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.78±9.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.026 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">GLS avg. (%), mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−13.35±3.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−19.46±3.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−20±2.68 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Biplane EF (%), mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47.07±6.97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61.81±5.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61.74±5.17 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Diastolic dysfunction, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 (84.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 (47.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (32.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.007 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1577231.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main findings between groups." ] ] 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" => "Plus-minus values are means±SD. BS: basal septal; MS: medium septal; AS: apical septal; BL: basal lateral; ML: medium lateral; AL: apical lateral; BI: basal inferior; MI: medium inferior; AI: apical inferior; BA: basal anterior; MA: medium anterior; AA: apical anterior; BP: basal posterior; MP: medium posterior; AP: apical posterior; BAS: basal antero-septal; MAS: medium antero-septal; AAS: apical antero-septal; GLS: global longitudinal strain; EF: ejection fraction." "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">T2DM with mdEF (n=14) \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">T2DM with pEF (n=76) \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">Non-diabetic controls (n=31) \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 value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3-Chamber GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−12.85±4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−19.6±4.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−20.83±3.38 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">4-Chamber GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−13.57±3.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−19±3.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−18.90±3.26 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2-Chamber GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−13.69±3.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−19.61±4.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−20.06±3.38 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Average GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−13.35±3.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−19.46±3.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−20±2.68 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BS GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−10.53±5.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−13.94±3.75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−13.96±2.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.009 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MS GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−14.92±3.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−18.63±3.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−18.80±2.88 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">AS GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−15.57±6.68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−24.56±5.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−24.00±5.56 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BL GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−12.38±5.43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−16.18±4.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−16.64±3.52 \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" title="table-entry " align="left" valign="top">ML GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−11.93±4.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−17.8±4.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−18.32±4.07 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">AL GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−12.23±7.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−22.39±6.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−21.64±6.64 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BI GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−11.38±7.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−16.39±3.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−18.06±3.18 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MI GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−15±5.65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−19.53±3.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−20.96±3.10 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">AI GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−16.07±8.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−24.75±6.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−24.80±5.35 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BA GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−10.61±5.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−16.22±4.94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−16.35±3.45 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MA GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−9.92±5.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−18.18±4.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−18.83±3.83 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">AA GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−13.3±6.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−22.93±7.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−22.16±6.43 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BP GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−9.92±8.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−16.63±4.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−17.38±4.24 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MP GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−11.92±6.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−18.78±4.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−20.09±3.32 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">AP GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−15.61±6.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−23.27±6.64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−24.48±4.21 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BAS GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−11.38±5.43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−15.85±3.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−17.51±3.84 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">MAS GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−12.3±6.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−19.36±4.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−20.67±4.15 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">AAS GLS, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−14±6.68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−23.75±7.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−24.90±5.14 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">E wave, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.79±0.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.78±0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.79±0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.974 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Deceleration time, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">148.42±67.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">189.21±53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">206.93±43.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">A wave velocity, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.84±0.027 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.75±0.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.65±0.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.016 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">E/A index, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.01±0.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.08±0.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.28±0.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.021 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">E/e′ index, mean SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.34±5.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.65±2.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.35±3.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Biplane EF, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47.07±6.97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61.81±5.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61.74±5.17 \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Diastolic dysfunction, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">11 (84.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 (47.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (32.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.007 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1577233.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Echocardiographic variables." ] ] ] "bibliografia" => array:2 [ "titulo" => 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"vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/14059940/0000008700000004/v1_201710301323/S1405994016300465/v1_201710301323/en/main.assets" "Apartado" => array:4 [ "identificador" => "14592" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Investigación clínica" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/14059940/0000008700000004/v1_201710301323/S1405994016300465/v1_201710301323/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1405994016300465?idApp=UINPBA00004N"]

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Clinical Research

Deformación longitudinal global como un biomarcador en miocardiopatía diabética. Estudio comparativo con galectina-3 en pacientes con fracción de eyección preservada

Ramiro Flores-Ramíreza,

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flores.ramiro@gmail.com

Corresponding author. Tel.: +52 8116601001; fax: +52 8114928262.

, José Ramón Azpiri-Lópeza, José Gerardo González-Gonzálezb, Alejandro Ordaz-Faríasa, Luis Eduardo González-Carrilloa, Edgar Francisco Carrizales-Sepúlvedaa, Raymundo Vera-Pinedaa

a Cardiology Service and the Echocardiography Laboratory, Hospital Universitario Dr. Jose Eleuterio Gonzalez, Universidad Autónoma de Nuevo León, Monterrey, Mexico

b Endocrinology Service, Hospital Universitario Dr. Jose E. Gonzalez, Universidad Autónoma de Nuevo León, Monterrey, Mexico

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            "entidad" => "Cardiology Service and the Echocardiography Laboratory&#44; Hospital Universitario Dr&#46; Jose Eleuterio Gonzalez&#44; Universidad Aut&#243;noma de Nuevo Le&#243;n&#44; Monterrey&#44; Mexico"
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        "titulo" => "Deformaci&#243;n longitudinal global como un biomarcador en miocardiopat&#237;a diab&#233;tica&#46; Estudio comparativo con galectina-3 en pacientes con fracci&#243;n de eyecci&#243;n preservada"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">DmdEF &#40;diabetics with mild depressed ejection fraction&#41;&#46; DpEF &#40;diabetics with preserved ejection fraction&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Diabetic cardiomyopathy was first described by Rubler in 1972&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">1&#44;2</span></a> The term describes several mechanisms involved in the pathogenesis of this entity including changes in myocardial structure and metabolism that are not directly attributed to other co-morbidities such as coronary artery disease &#40;CAD&#41; or hypertension&#46; Left ventricular hypertrophy&#44; myocardial lypotoxicity&#44; increased oxidative stress&#44; cell death from apoptosis&#44; impaired contractile reserve&#44; altered substrate utilization as free fatty acids &#40;FFA&#41;&#44; mitochondrial dysfunction and fibrosis are among the mechanisms involved with these changes in structure and metabolism contributing to the progression of heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a> In particular&#44; fibrosis is one of the abnormalities that can be evaluated with the newer imaging techniques&#46; Cardiac magnetic resonance &#40;CMR&#41; is the gold standard in the assessment of myocardial fibrosis given that T1 sequences separate normal from fibrotic tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a> Nonetheless&#44; CMR is not widely available&#44; and it is time and cost consuming with longer and exhausting protocols&#46; Speckle tracking echocardiography measurement of these parameters has been validated against magnetic resonance imaging&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">4&#44;5</span></a> Global longitudinal strain &#40;GLS&#41; is the simplest deformation parameter and probably the closest to routine clinical application&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> Quantitative assessment of myocardial function is now possible with speckle tracking echocardiography&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">More than half of patients with heart failure have preserved ejection fraction &#40;HFpEF&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a> Diagnosis and therapies are difficult because of a lack of specific biomarkers and imaging techniques&#46; There is a need to anticipate the progression of heart failure in patients with diabetes and for that reason we propose a strategy of non-invasive analysis of inflammation-fibrosis LVD&#46; Galectin-3 &#40;Gal-3&#41; has emerged as a new biomarker in heart failure and has a strong relationship with inflammation and fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a> Galectin-3 is a &#946;-galactoside-binding member of the lectin family in which 14 mammalian galectins have been identified&#46; Galectin-3 is an &#8764;30<span class="elsevierStyleHsp" style=""></span>kDa protein and contains a carbohydrate recognition binding domain &#40;CRD&#41; of 130 aminoacids that enables the specific binding of &#946;-galactosides and is encoded on by a single gene&#44; LGALSS3 located on chromosome14&#44; locus q21-q22&#46; Galectin-3 has recently been linked to HF development&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">10&#44;11</span></a> We believe that Galectin-3 could detect early stages of left ventricular dysfunction &#40;LVD&#41; in diabetic patients with preserved ejection fraction&#46; On the other hand&#44; newer echocardiography techniques allow evaluating LVD before ejection fraction declines&#46; This study aims to analyze the relation between a cardiac biomarker of fibrosis&#44; Gal-3&#44; and the patterns of GLS in asymptomatic patients with type 2 diabetes and preserved ejection fraction&#46;</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">Participants</span><p id="par0015" class="elsevierStylePara elsevierViewall">From April 1&#44; 2015 to August 31&#44; 2015 a total of 159 subjects from the endocrinology outpatient clinic were recruited&#46; The study had ethics approval by our Institutional Review Board&#46; Patients with type 2 diabetes and no history of cardiovascular disease were included&#46; Thirty-one age- and sex-matched healthy volunteers were also studied&#46; Each examination consisted of a clinical history and physical exam&#44; anthropometry&#44; blood samples and routine echocardiogram with strain measurements&#46; Patients with a history of cardiovascular and renal disease&#44; valvular heart disease&#44; atrial fibrillation&#44; angina or previous myocardial infarction were excluded&#46; Two patients excluded had atrial fibrillation&#44; one with chronic liver disease&#59; two patients had myocardial infarction unknown to them and 9 had symptoms of angina&#59; six had a history of stroke&#46; Eighteen non-diabetic individuals in the control group were excluded because of depressed ejection fraction&#46; A total of 121 participants were divided in 3 groups&#46; Group 1&#58; 14 patients with type 2 diabetes and mild depressed ejection fraction &#40;mdEF&#41;&#59; group 2&#58; 76 patients with type 2 diabetes and preserved ejection fraction &#40;pEF&#41; and group 3&#58; 31 age- and sex-matched controls without diabetes&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Biomarker</span><p id="par0020" class="elsevierStylePara elsevierViewall">Blood samples were collected after an overnight fast and immediately centrifuged and stored at &#8722;70<span class="elsevierStyleHsp" style=""></span>&#176;C until assayed&#46; Plasma concentrations of Gal-3 were measured using an enzyme-linked immunosorbent assay with a sensitivity of 10<span class="elsevierStyleHsp" style=""></span>pg&#47;ml &#40;Abcam Inc&#46;&#44; Cambridge&#44; MA&#41;&#44; according to the manufacturer&#39;s instructions&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Echocardiography</span><p id="par0025" class="elsevierStylePara elsevierViewall">Routine 2-dimensional and Doppler echocardiography was performed according to the American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines using a ViVid E9 echocardiogram with a 1&#46;5&#8211;3&#46;6<span class="elsevierStyleHsp" style=""></span>MHz transducer &#40;GE Vingmed&#44; Horten&#44; Norway&#41;&#46; Two certified echocardiologists unaware of the clinical history and Gal-3 level acquired and evaluated all echocardiograms&#46; Indexed ventricular mass was assessed in a linear fashion using the paraesternal long axis view&#46; Left ventricular ejection fraction was calculated with the bi-plane Simpson&#39;s method&#46; Preserved ejection fraction was defined as an ejection fraction &#40;EF&#41; above 52&#37; in male subjects and 54&#37; in female subjects&#59; mildly depressed ejection fraction was defined as 41&#8211;51&#37; in men and 41&#8211;53&#37; in women as described in ASE&#47;EACVI guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> Pulsed-wave &#40;PW&#41; Doppler was performed in the apical 4-chamber view to obtain mitral inflow velocities to assess left ventricular &#40;LV&#41; filling&#46; A 1-mm sample volume is then placed between the mitral leaflet tips during diastole&#46; Diastolic function measurements include peak early filling &#40;E-wave&#41; and late diastolic filling &#40;A-wave&#41; velocities&#44; the E&#47;A ratio&#44; and deceleration time&#46; Pulsed wave tissue Doppler imaging &#40;DTI&#41; was performed in the 4CH apical view with sample volume positioned at 1<span class="elsevierStyleHsp" style=""></span>cm within the septal insertion site of the mitral leaflet for E&#47;e&#8242;&#46; Diastolic dysfunction was defined with criteria described earlier&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> Three cardiac cycles were recorded in 4&#44; 2 and 3 chambers for the offline speckle tracking analyses of GLS&#46; Offline analyses were performed in EchoPAC PC 113&#46;0&#46;X&#46; &#40;GE Vingmed Horten Norway&#41;&#46; The complete region of interest &#40;ROI&#41; was defined at end-diastole as the endocardial border&#58; the inner contour of the myocardium&#59; epicardial border&#58; the outer contour of the myocardium&#59; and myocardial midline&#58; the middle ROI axis defined in the middle between the inner and outer ROI contours&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a> Each of these contours can be either user-defined or generated automatically&#46; In any case&#44; these were generated automatically&#59; our echocardiologists checked them and&#44; if needed&#44; edited the images manually taking care of defining the ROI to avoid pericardium inclusion&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a> Normal reference values of GLS were taken from the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> All individuals were in sinus rhythm at the time of imaging and had no significant cardiovascular abnormalities&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Reproducibility</span><p id="par0030" class="elsevierStylePara elsevierViewall">For inter and intraobserver variability&#44; GLS and EF were assessed in a subset of 45 subjects randomly selected from the study population and analyzed with Bland&#8211;Altman analysis and the Wilcoxon rank with no significant differences between observers&#46; For biplane GLS &#40;SD&#41; interpreter 1&#44; &#8722;19&#46;75 &#40;4&#46;09&#41; vs interpreter 2&#44; &#8722;19&#46;75 &#40;4&#46;72&#41;&#44; Wilcoxon rank test &#46;55 and for EF &#40;SD&#41; interpreter 1&#44; 57 &#40;9&#46;64&#41; vs interpreter 2&#44; 57&#46;5 &#40;11&#46;26&#41; difference -0&#46;5 &#40;5&#46;09&#41; Wilcoxon rank test &#46;60&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0035" class="elsevierStylePara elsevierViewall">Categorical values were reported as frequencies&#46; Quantitative variables were tested for normality with the Kolmogorov&#8211;Smirnov test&#46; For variables with normal distribution mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41; was used&#46; Difference in quantitative data between groups was analyzed using a one-way ANOVA test&#46; When a significant difference was found &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44; the Tukey test was used to determine which group was unequal from the others &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; The Gal-3 cutoff point was assessed using receiver operating characteristics &#40;ROC curve&#41; and the Youden index&#46; Area under the curve &#40;AUC&#41; values &#62;0&#46;5 with a <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 were considered statistically significant &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">All statistical data were analyzed with SPSS version 21&#46;0 &#40;IBM Corp&#46;&#44; NY&#44; USA&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">All demographic results are described in &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; There were no differences between groups according to age&#44; sex&#44; body mass index and other cardio-metabolic parameters&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Based on updated echocardiographic guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> we compare diabetic individuals with mdEF vs pEF vs controls &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Gal-3 was elevated in all individuals with diabetes compared to controls &#40;3&#46;46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;36<span class="elsevierStyleHsp" style=""></span>ng&#47;ml vs 2&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;91<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41; with no difference between diabetic patients with mild depressed ejection fraction and preserved ejection fraction &#40;3&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;12<span class="elsevierStyleHsp" style=""></span>ng&#47;ml vs 3&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;603&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; All echocardiographic variables are described in &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Gal-3 was found to be higher in mdEF &#40;2&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9<span class="elsevierStyleHsp" style=""></span>ng&#47;ml vs 3&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;12<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#41; and pEF subjects &#40;2&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9<span class="elsevierStyleHsp" style=""></span>ng&#47;ml vs 3&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;40<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;058&#41; compared to controls&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">To assess the effect of diabetes progression on left ventricular function&#44; we divided our cohort in those who had less than 10 years since diagnosis and those with more than 10 years&#46; Gal-3 levels were higher in patients with more than 10 years &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;011&#41;&#46; There was no significant statistical difference regarding EF &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;286&#41; and GLS &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;228&#41;&#46; Diastolic function was more frequently altered in the group with more than 10 years &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; When we compare diabetic individuals did not found difference in baseline Gal-3 in diabetes with mdEF <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14 &#40;3&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;12<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; vs pEF <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>76 &#40;3&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;60&#44; but consistently LVD with GLS between these groups &#40;&#8722;13&#46;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;41 vs &#8722;19&#46;46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;26&#41; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#46; Compared to controls&#44; all individuals with diabetes had worst GLS &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;022&#41;&#46; There was no difference in GLS in diabetic patients with pEF when compared to non-diabetic controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;70&#41;&#46; Patients with mdEF had significantly lower GLS than controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; Thirty per cent of those in the pEF group had impaired GLS values and 92&#46;9&#37; in the mdEF group&#46; Both parameters move discretely in the desired direction&#44; but with wide dispersion&#44; without any correlation&#46; Using 2 markers&#44; Gal-3 &#40;&#62;2&#46;71<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; and GLS &#40;&#60;18&#37;&#41;&#44; we found a sensitivity of 0&#46;85&#44; a specificity of 0&#46;81&#44; a PPV of 0&#46; 46 and a NPV of 0&#46;97 for LVD &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">Left ventricular dysfunction &#40;LVD&#41; is now known to be a major co-morbidity in diabetes&#46; Hypertension and DM are closely related and complicate each other&#46; The activation of the rennin&#8211;angiotensin&#8211;aldosterone system causes insulin resistance&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">15&#44;16</span></a> Cardiac remodeling occurs together with hypertension and DM&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a> Difficult exists in specifying the cause of cardiac remodeling in diabetes because of the lack of criteria and tools&#44; including biomarkers and imaging techniques&#46; Microvasculopathy is a primary feature in diabetic cardiac remodeling but no surrogate can directly monitor disease progression&#46; Therefore there is an increasing interest in the link between DM and heart failure&#46; Diabetic cardiomyopathy is a term assigned to those patients with cardiomyopathy without coronary artery disease and hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">18</span></a> Multiple substrates are responsible for myocardial damage including fatty acid uptake&#44; collagen metabolism&#44; oxidation and fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a> Because Gal-3 is a marker of inflammation and fibrosis<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a> we aimed to correlate this biomarker with a non-invasive&#44; easier and accessible tool in the evaluation of pre-clinical heart failure or incipient myocardial dysfunction in patients with diabetes&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">It is estimated than more than 50&#37; of patients presenting with signs and symptoms of heart failure suffer from heart failure with preserved ejection fraction &#40;HFpEF&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> The vast majority of published articles on Gal-3 described patients with heart failure with reduced ejection fraction &#40;HFrEF&#41; not HFpEF&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">9</span></a> Echocardiography is a non-invasive tool in the global evaluation of heart disease&#46; Some of its features includes left ventricular ejection fraction &#40;LVEF&#41;&#46; LVEF has been demonstrated in patients with heart failure in different scenarios such as coronary artery disease&#44; valvular heart disease and other cardiomyopathies&#46; LVEF has been the fundamental tool for systolic function&#59; nonetheless it is less sensitive for detecting early myocardial disease than newer techniques&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> Asymptomatic myocardial dysfunction can occur in diabetic patients without CAD&#46; LVEF could be normal but myocardial dysfunction in terms of abnormal deformation is not&#46; GLS can detect myocardial abnormalities before EF declines&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> The presence of LVD was defined in a large meta-analysis of strain&#46; The mean GLS in normal subjects was &#8722;19&#46;7&#37;&#44; with a lower 95&#37; CI of &#8722;18&#46;9&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> In a recent study&#44; Holland et al&#46; evaluated the 10-year outcomes in subclinical myocardial dysfunction evaluating GLS in a cohort of 249 type 2 diabetic patients with normal LVEF&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a> Holland found that almost half of patients &#40;45&#37;&#41; had evidence of LVD detected by GLS in a median follow-up of 7&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6 years&#46; GLS was independently associated with the primary endpoint&#46; Patients with LVD had a significantly worse outcome than those without&#46; They concluded that subclinical LVD is common in asymptomatic patients with type 2 DM&#44; that it was detectable by GLS imaging and is independently associated with adverse outcome&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a> In our study we found that GLS is depressed in all individuals with diabetes compared to controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41; but there is no difference in GLS in diabetic patients with pEF when compared to controls &#40;&#8722;19&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;2 vs &#8722;20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;42&#41; but Gal-3 was significantly elevated &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41;&#46; Left ventricular dysfunction &#40;GLS &#60;&#8722;18&#41; was found in 30&#46;3&#37; of pEF subjects&#46; We assume at this point that diabetic individuals with pEF are in early phases of inflammation and extracellular matrix proliferation but these needs to be confirmed in a MRI study&#46; Using 2 markers&#44; Gal-3 &#40;&#62;2&#46;71<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; and GLS &#40;&#60;18&#37;&#41;&#44; we found a sensitivity of 0&#46;85&#44; a specificity of 0&#46;81&#44; a PPV of 0&#46; 46 and a NPV of 0&#46;97 for LVD&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Only a few studies have described the levels and clinical correlation of Gal-3 and HFpEF&#46; The COACH study de Boer et al&#46; found&#44; in a cohort of 592 patients admitted with acute heart failure&#44; that 19&#46;2&#37; &#40;114&#41; of patients with HFpEF and Gal-3 levels where comparable between HFrEF and HFpEF &#40;&#8764;20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a> Our population was a non-Caucasian heart failure symptom-free cohort from the endocrinology outpatient clinic&#46; Levels of Gal-3 were not highly elevated in this cohort compared to other studies &#40;&#8764;3&#46;4<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41;&#59; in the fibrosis marker&#44; Gal-3&#44; and in the outcome in the general population&#44; de Boer found a gender interaction&#44; with female subjects having higher median Gal-3 levels 11&#46;0<span class="elsevierStyleHsp" style=""></span>ng&#47;ml IQR &#40;interquartile range 9&#46;0&#8211;13&#46;1<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46;&#41; than men 10&#46;7<span class="elsevierStyleHsp" style=""></span>ng&#47;ml IQR &#40;8&#46;9&#8211;12&#46;8<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41; but they excluded non-Caucasian subjects&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">23</span></a> In the epidemiological field Ho et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a> Investigated Gal-3 linked to the development of HF in the general population&#46; Gal-3 concentrations were measured in 3353 participants from the Framingham Offspring Cohort and were associated independently with an increased risk for developing HF and mortality&#46; Crude HF incidence rates were estimated by sex-specific Gal-3 quartile&#46; Quartile 1&#58; 3&#46;9&#8211;11&#46;1<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; quartile 2&#58; 11&#46;1&#8211;13&#46;1<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; quartile 3&#58; 13&#46;1&#8211;15&#46;4<span class="elsevierStyleHsp" style=""></span>ng&#47;ml and quartile 4&#58; 16&#46;8&#8211;51&#46;1<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; During a mean follow-up period of 11&#46;2 years&#44; 166 &#40;5&#46;1&#37;&#41; subjects developed HF&#46; The heart failure incidence rate increased over Gal-3 quartiles&#44; with rates of 2&#46;8&#44; 3&#46;8&#44; 5&#46;2 and 12&#46;4 events per 1000 persons-years in quartiles 1 through 4&#44; respectively&#46; Our cohort resembles quartile 1 of the Ho study&#46; We believe that in diabetic patients adding GLS to standard echocardiograms is useful in the detection of early phases of LVD&#46; The combination of Gal-3 and GLS has a high NPV of 0&#46;94&#46; At the same time our study demonstrates that Gal-3 was elevated in all diabetic individuals compared to controls &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#46; Gal-3 was found to be higher in patients with mdEF compared to pEF with diabetic subjects not reaching significance due to sample size &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;375&#41;&#46; When compared to controls Gal-3 was found to be higher in pEF diabetic subjects &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Study limitations</span><p id="par0080" class="elsevierStylePara elsevierViewall">We studied only one of the substrates of DCM&#46; It would have been useful to compare GLS with cardiac magnetic resonance for detection of fibrosis&#59; however&#44; it was not available at our institution&#46; Also&#44; non-significant differences could be as a result of the sample size basically in the mdEF group&#46; We did not studied the existence of ischemic heart disease even in those diabetic subjects with more than 10 years of diagnostic so these make harder to consider DCM by itself&#44; an lastly GLS is not a surrogate of Gal-3&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0085" class="elsevierStylePara elsevierViewall">This is a non-Caucasian study in a diabetic heart failure symptom free cohort&#46; Global longitudinal strain is an easy and reproducible echocardiography tool in the evaluation and follow-up of DCM in diabetic subjects although is not a surrogate of Gal-3 because this biomarker is elevated in all diabetics&#46; There still much to investigate in the physiopathology of DCM especially in asymptomatic patients with preserved ejection fraction&#46; Including Gal-3 to standard echocardiography and GLS would be helpful in the early detection of LVD in DCM&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Ethical responsibilities</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Protection of people and animals</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors state that the procedures conformed to the ethical standards of human experimentation committee responsible and according to the World Medical Association and the Declaration of Helsinki&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Confidentiality of data</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of the workplace on the publication of patient data&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Right to privacy and informed consent</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors have obtained the informed consent of patients and&#47;or subjects referred to in Article consent&#46; This document is held by the corresponding author&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Funding</span><p id="par0110" class="elsevierStylePara elsevierViewall">This study has no funding&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflict of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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    "fechaRecibido" => "2016-01-25"
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            2 => "Diabetic cardiomyopathy"
            3 => "Mexico"
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            0 => "Galectina-3"
            1 => "Deformaci&#243;n longitudinal global"
            2 => "Miocardiopat&#237;a diab&#233;tica"
            3 => "M&#233;xico"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">To establish a relationship between global longitudinal strain &#40;GLS&#41; and Galectin-3 in pre-clinical heart failure in diabetic patients&#46; Galectin-3 is a biomarker in heart failure with depressed ejection fraction &#40;HFdEF&#41;&#46; The hypothesis is presented that Galectin-3 is related to GLS and can detect left ventricular dysfunction in heart failure with preserved ejection fraction&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Galectin-3 and GLS were measured in 121 asymptomatic individuals&#58; 14 diabetics with mild depressed ejection fraction &#40;mdEF&#41; &#40;LVEF 47&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;9&#41;&#59; 76 diabetics with preserved ejection fraction &#40;LVEF 61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5&#41;&#44; and 31 controls &#40;61&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;1&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">Galectin-3 was elevated in all diabetics vs controls &#40;3&#46;46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;36 ng&#47;ml vs 2&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;91 ng&#47;ml&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;003&#41;&#46; It was also elevated in mdEF &#40;3&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;12 ng&#47;ml vs 2&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9 ng&#47;ml&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;009&#41; and pEF subjects &#40;3&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;40 ng&#47;ml vs 2&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9 ng&#47;ml&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;058&#41;&#44; respectively&#44; vs controls&#46; No difference in Gal-3 was found between diabetic groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;603&#41;&#46; Diabetics had lower GLS than controls &#40;&#8722;18&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;9 vs &#8722;20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;022&#41;&#46; Diabetics with mdEF had lower GLS than those with pEF &#40;&#8722;13&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;41 vs &#8722;19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;2&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; There was no difference in GLS with pEF compared to controls &#40;&#8722;19&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;2 vs &#8722;20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;70&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Galectin-3 is elevated in diabetic patients with mdEF&#44; and is associated with a diminished GLS&#46; GLS could be an early marker of left ventricular dysfunction as well as evidence of diabetic cardiomyopathy&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Establecer una asociaci&#243;n entre deformaci&#243;n longitudinal global &#40;DLG&#41; y galectina-3 en insuficiencia cardiaca precl&#237;nica en pacientes diab&#233;ticos&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Galectina-3 es un biomarcador en insuficiencia cardiaca con fracci&#243;n de eyecci&#243;n deprimida&#46; Nuestra hip&#243;tesis es que la DLG y galectina-3 correlacionan y pueden detectar disfunci&#243;n ventricular en insuficiencia cardiaca con FEVI preservada&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se midieron galectina-3 y DLG en 121 individuos asintom&#225;ticos&#58; 14 diab&#233;ticos con FEVI deprimida leve &#40;FEdl&#41; &#40;FEVI 47<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;9&#41;&#59; 76 diab&#233;ticos con FEVI preservada &#40;FEp&#41; &#40;FEVI 61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5&#41; y 31 sujetos controles &#40;FEVI 61&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;1&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Galectina-3 se encontr&#243; elevada en todos los diab&#233;ticos vs controles &#40;3&#46;46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;36<span class="elsevierStyleHsp" style=""></span>ng&#47;ml vs 2&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;91<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#46; Est&#225; elevada en sujetos con FEdl &#40;3&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;12 vs 2&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9 vs ng&#47;ml p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;009&#41; y FEp &#40;3&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;40 vs 2&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9<span class="elsevierStyleHsp" style=""></span>ng&#47;ml p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;058&#41;&#44; respectivamente vs controles&#59; no encontramos diferencia en galectina-3 en ambos grupos de diab&#233;ticos &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;603&#41;&#46; Los diab&#233;ticos tienen menor DLG que los controles &#40;&#8722;18&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;9 vs &#8722;20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;022&#41;&#46; Los diab&#233;ticos con FEdl tienen DLG m&#225;s disminuida que aquellos con FEp &#40;&#8722;13&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;41 vs &#8722;19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;2&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; No existe diferencia en DLG con FEp y controles &#40;&#8722;19&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;2 vs &#8722;20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;70&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Galectina-3 est&#225; elevada en diab&#233;ticos con FEdl y correlaciona DLG disminuida&#46; DLG podr&#237;a ser un marcador temprano de disfunci&#243;n ventricular y evidencia en miocardiopat&#237;a diab&#233;tica&#46;</p></span>"
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            "Tamanyo" => 74689
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">ROC curve for LVD &#40;left ventricular dysfunction&#41;&#46; Highest performance Gal-3 value was 2&#46;71<span class="elsevierStyleHsp" style=""></span>ng&#47;ml with <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;048&#44; AUC&#58; 0&#46;663&#44; sensitivity&#58; 0&#46;928&#44; specificity&#58; 0&#46;381 and &#40;NPV&#41; negative predictive value&#58; 0&#46;96&#46;</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" => 1316
            "Ancho" => 1652
            "Tamanyo" => 84953
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">DmdEF &#40;diabetics with mild depressed ejection fraction&#41;&#46; DpEF &#40;diabetics with preserved ejection fraction&#41;&#46;</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" => 1181
            "Ancho" => 1639
            "Tamanyo" => 74360
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">DmdEF &#40;diabetics with mild depressed ejection fraction&#41;&#46; DpEF &#40;diabetics with preserved ejection fraction&#41;&#46;</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" => 1283
            "Ancho" => 1616
            "Tamanyo" => 62300
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Sensitivity&#44; specificity&#44; PPV &#40;positive predictive value&#41; and NPV &#40;negative predictive value&#41;&#46; Using both parameters&#59; Gal-3 at &#62;2&#46;71<span class="elsevierStyleHsp" style=""></span>ng&#47;ml and global longitudinal strain &#60;18&#37;&#46;</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"
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        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Plus-minus values are means<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; There were no significant between-group differences at baseline except for T2DM &#40;type 2 diabetes mellitus&#41;&#46; SBP&#58; systolic blood pressure&#59; DBP&#58; diastolic blood pressure&#59; BMI&#58; body mass index&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">T2DM with mdEF &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41;&nbsp;\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">T2DM with pEF &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>76&#41;&nbsp;\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">Non-diabetic controls &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>31&#41;&nbsp;\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"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Age &#40;yrs&#41;&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55&#46;42<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55&#46;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&#46;89<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;122&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Female&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;57&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46 &#40;60&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20 &#40;64&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;880&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Smoking ever&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 &#40;28&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23 &#40;30&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;45&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;158&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Dyslipidemia&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;71&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">41 &#40;53&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Hypertension&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;42&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40 &#40;52&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">T2DM&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">76 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">SBP &#40;mmHg&#41;&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">97&#46;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>57&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">124&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">125&#46;19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>30&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">DBP &#40;mmHg&#41;&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59&#46;64<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>34&#46;54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;034&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">BMI&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">34&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&#46;79<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;024&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1577232.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Demographic characteristics of study group&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
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            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Plus-minus values are means<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; There were significant differences in GLS &#40;global longitudinal strain&#41;&#44; biplane EF &#40;ejection fraction&#41; and diastolic dysfunction in diabetics vs controls&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">T2DM with mdEF &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41;&nbsp;\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">T2DM with pEF &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>76&#41;&nbsp;\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">Non-diabetic controls &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>31&#41;&nbsp;\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"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Gal-3 &#40;ng&#47;ml&#41;&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;026&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">GLS avg&#46; &#40;&#37;&#41;&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;13&#46;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;19&#46;46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Biplane EF &#40;&#37;&#41;&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#46;81<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Diastolic dysfunction&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11 &#40;84&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35 &#40;47&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;32&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab1577231.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Main findings between groups&#46;</p>"
        ]
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        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
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        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Plus-minus values are means<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#46; BS&#58; basal septal&#59; MS&#58; medium septal&#59; AS&#58; apical septal&#59; BL&#58; basal lateral&#59; ML&#58; medium lateral&#59; AL&#58; apical lateral&#59; BI&#58; basal inferior&#59; MI&#58; medium inferior&#59; AI&#58; apical inferior&#59; BA&#58; basal anterior&#59; MA&#58; medium anterior&#59; AA&#58; apical anterior&#59; BP&#58; basal posterior&#59; MP&#58; medium posterior&#59; AP&#58; apical posterior&#59; BAS&#58; basal antero-septal&#59; MAS&#58; medium antero-septal&#59; AAS&#58; apical antero-septal&#59; GLS&#58; global longitudinal strain&#59; EF&#58; ejection fraction&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\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">T2DM with mdEF &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41;&nbsp;\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">T2DM with pEF &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>76&#41;&nbsp;\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">Non-diabetic controls &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>31&#41;&nbsp;\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"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">3-Chamber GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;12&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;19&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;20&#46;83<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">4-Chamber GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;13&#46;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;18&#46;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">2-Chamber GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;13&#46;69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;19&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;20&#46;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Average GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;13&#46;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;19&#46;46<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">BS GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;10&#46;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;13&#46;94<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;13&#46;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">MS GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;14&#46;92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;18&#46;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;18&#46;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">AS GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;15&#46;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;24&#46;56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;24&#46;00<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">BL GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;12&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;16&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;16&#46;64<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">ML GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;11&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;17&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;18&#46;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">AL GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;12&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;22&#46;39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;21&#46;64<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">BI GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;11&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;16&#46;39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;18&#46;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">MI GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;19&#46;53<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;20&#46;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">AI GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;16&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;24&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;24&#46;80<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">BA GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;10&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;16&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;16&#46;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">MA GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;9&#46;92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;18&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;18&#46;83<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">AA GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;13&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;22&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;22&#46;16<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">BP GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;9&#46;92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;16&#46;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;17&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">MP GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;11&#46;92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;18&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;20&#46;09<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">AP GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;15&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;23&#46;27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;24&#46;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">BAS GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;11&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;15&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;17&#46;51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">MAS GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;12&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;19&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;20&#46;67<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">AAS GLS&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;23&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;24&#46;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">E wave&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;79<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;79<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;974&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Deceleration time&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">148&#46;42<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>67&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">189&#46;21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">206&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>43&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;003&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;027&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">E&#47;e&#8242; index&#44; mean SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Biplane EF&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#46;81<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Diastolic dysfunction&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11 &#40;84&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35 &#40;47&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;32&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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        "texto" => "<p id="par0120" class="elsevierStylePara elsevierViewall">Authors would like to thank Neri A&#46; Alvarez MD for statistical analysis&#44; Gloria Jasso QFB for endocrinology lab analyses&#44; Rodolfo Flores-Alexander English language professor and Sergio Lozano M&#46;D&#46; for English translation advice&#46;</p>"
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Article information

ISSN: 14059940
Original language: English

DOI:10.1016/j.acmx.2016.06.002

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	4	0	4
2024 October	48	5	53
2024 September	45	10	55
2024 August	29	5	34
2024 July	52	5	57
2024 June	31	4	35
2024 May	43	5	48
2024 April	27	3	30
2024 March	70	12	82
2024 February	55	4	59
2024 January	81	8	89
2023 December	47	19	66
2023 November	51	4	55
2023 October	70	8	78
2023 September	64	7	71
2023 August	59	13	72
2023 July	64	15	79
2023 June	62	5	67
2023 May	56	8	64
2023 April	27	4	31
2023 March	19	8	27
2023 February	29	0	29
2023 January	28	2	30
2022 December	44	16	60
2022 November	31	13	44
2022 October	29	14	43
2022 September	31	12	43
2022 August	24	11	35
2022 July	28	16	44
2022 June	49	8	57
2022 May	56	7	63
2022 April	45	4	49
2022 March	61	10	71
2022 February	37	9	46
2022 January	17	10	27
2021 December	31	11	42
2021 November	29	14	43
2021 October	26	18	44
2021 September	27	15	42
2021 August	24	23	47
2021 July	20	21	41
2021 June	27	9	36
2021 May	44	11	55
2021 April	68	12	80
2021 March	202	11	213
2021 February	33	8	41
2021 January	83	8	91
2020 December	59	13	72
2020 November	26	13	39
2020 October	25	11	36
2020 September	38	13	51
2020 August	47	11	58
2020 July	30	19	49
2020 June	22	11	33
2020 May	36	7	43
2020 April	22	7	29
2020 March	42	10	52
2020 February	32	15	47
2020 January	40	12	52
2019 December	43	14	57
2019 November	36	9	45
2019 October	28	12	40
2019 September	41	8	49
2019 August	31	5	36
2019 July	33	18	51
2019 June	43	26	69
2019 May	68	29	97
2019 April	41	13	54
2019 March	12	9	21
2019 February	10	4	14
2019 January	5	12	17
2018 December	7	6	13
2018 November	10	7	17
2018 October	17	18	35
2018 September	33	8	41
2018 August	11	6	17
2018 July	21	4	25
2018 June	22	7	29
2018 May	39	8	47
2018 April	16	6	22
2018 March	17	7	24
2018 February	22	8	30
2018 January	22	8	30
2017 December	47	9	56
2017 November	55	4	59
2017 October	10	12	22
2017 September	4	17	21
2017 August	5	4	9
2017 July	4	8	12
2017 June	5	9	14
2017 May	10	8	18
2017 April	6	10	16
2017 March	10	70	80
2017 February	15	10	25
2017 January	1	3	4
2016 December	3	7	10
2016 November	5	13	18
2016 October	6	10	16
2016 September	9	8	17
2016 August	8	14	22
2016 July	3	28	31

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