Time to left ventricular reverse remodeling after cardiac resynchronization therapy: Better late than never | Revista Portuguesa de Cardiologia (English edition)

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array:1 [ "pt" => array:1 [ "titulo" => "Tempo para a remodelagem inversa do ventrículo esquerdo: mais vale tarde do que nunca" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1157 "Ancho" => 1515 "Tamanyo" => 109649 ] ] "descripcion" => array:1 [ "en" => "Clinical outcomes during follow-up. LVRR: left ventricular reverse remodeling." ] ] ] "textoCompleto" => "IntroductionCardiac resynchronization therapy (CRT) has become an effective non-pharmacological treatment for patients with impaired left ventricular ejection fraction (LVEF), prolonged QRS duration and New York Heart Association (NYHA) functional class ≥III symptoms of heart failure (HF) despite optimal medical therapy. Large multicenter clinical trials have shown that CRT can mitigate HF symptoms, improve exercise capacity and quality of life, reduce the incidence of hospitalizations due to HF and decrease mortality.<a class="elsevierStyleCrossRefs" href="#bib0155">1–4</a> Most of these benefits are thought to be related to left ventricular (LV) reverse remodeling (LVRR), a response characterized by a reduction in LV end-diastolic (LVEDD) and end-systolic (LVESD) dimensions and volumes and improvement of LV ejection fraction (LVEF).<a class="elsevierStyleCrossRefs" href="#bib0175">5–7</a> The time course of this phenomenon remains poorly characterized. It has been suggested that the structural and functional changes associated with LVRR occur early after CRT and are more pronounced before the six-month landmark, a time by which the extent of reverse remodeling has been shown to predict long-term prognosis in these patients.<a class="elsevierStyleCrossRefs" href="#bib0180">6–9</a> Nevertheless, a variable proportion of eligible patients fail to respond initially but appear to develop LVRR after six months following CRT implantation. This population with late LVRR, who are not included in the already known proportion (around 30%) of non-responders to CRT, correspond to a different spectrum of individuals that, to the best of our knowledge, has never been directly analyzed in a prospective study. To overcome this limitation, the present study characterizes the timing of LVRR occurrence and assesses the long-term echocardiographic and clinical evolution of patients with LVRR occurring >6 months after CRT implantation. We also sought to identify potentially related clinical characteristics that might predict a late response to CRT.MethodsThis is a single-center analysis of patients who underwent successful CRT device implantation. A total of 127 consecutive CRT recipients were included and patient data were prospectively collected in the information system of our cardiology department and analyzed. Patients were selected for CRT if they met currently recommended criteria: (1) LVEF <35%; (2) symptoms of HF, defined as NYHA class II–IV despite optimal medical therapy; and (3) QRS duration ≥120 ms. Patients were classified as ischemic in the presence of significant coronary artery disease (>50% stenosis of two or more epicardial vessels or >50% left main or proximal left anterior descending coronary artery stenosis on coronary angiography and/or a history of previous myocardial infarction or revascularization). Other patients were classified as non-ischemic. All leads were placed transvenously via the subclavian and cephalic route using fluoroscopy. The right ventricular lead was positioned in the apex or mid septum. The LV lead was placed with an over-the-wire system in the posterolateral or lateral tributary vein of the coronary sinus depending on the ability to cannulate the veins, pacing threshold, or diaphragmatic stimulation. The standard settings included an atrioventricular (AV) delay of 100 ms (sensed) and 130 ms (paced), with DDD or DDDR mode and standard lower (50 beats/min) and upper (120–130 beats/min) pacing rates. Extensive demographic and clinical data, including death, NYHA class and hospitalization for worsening HF or CRT dysfunction, were collected from medical records. Transthoracic two-dimensional echocardiographic information was assessed at baseline, six months after CRT device implantation and thereafter once a year until the end of follow-up. In this study, LVRR was defined as an increase >10% in LVEF over baseline, combined with a >10% reduction in LVEDD and LVESD. Echocardiographic cardiac structure and function were assessed using a commercially available ultrasound system (Vivid 7 and Vivid E9; GE Vingmed Ultrasound, Horten, Norway) equipped with a 3.5-MHz transducer. LVESD, LVEDD and LVEF were determined according to standard techniques and digitally stored for offline analysis in cine-loop format. Interventricular mechanical delay was calculated by pulmonary and aortic pulsed Doppler measurement of the difference in time from QRS onset to onset of flow in the pulmonary and aortic outflow tracts, respectively. LV intraventricular dyssynchrony was assessed offline using a previously validated software package (EchoPAC PC-2D strain; GE Healthcare, USA). The cohort was divided according to the time course of LVRR response into three groups: Group A, presence of LVRR after >6 months (late LVRR); Group B, with LVRR before 6 months (early LVRR); and Group C, without LVRR during follow-up (no LVRR). Follow-up data were obtained by review of medical records, outpatient clinical visits, and telephone contact. Ethical and hospital permission were obtained from the appropriate local authorities.Statistical analysisSPSS version 21 software (SPSS Inc., Chicago, Illinois) was used for computation. Data are expressed as means ± standard deviation for continuous variables and as frequencies and percentages for categorical variables. Data distribution was tested for normality using the Kolmogorov–Smirnov or Shapiro–Wilk test as appropriate. Missing patient-level covariates were assumed to be missing and no imputation was performed. Baseline characteristics and outcomes were compared using the chi-square test or Fisher's exact test, when appropriate, for categorical variables and the Student's t test or the Mann–Whitney test for continuous variables. Univariate and multivariate logistic regression analysis was used to examine for potential predictors of a delayed LVRR response. A value of p<0.05 was considered statistically significant.ResultsPatient baseline characteristicsOverall, the study population consisted of 127 consecutive patients who underwent successful CRT implantation (aged 63.9±10.7 years, 74.8% male). The mean follow-up was 48±36 months (median 37 months). Baseline patient characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The majority of the cohort (60.6%) had non-ischemic cardiomyopathy.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Regarding differences between groups, late LVRR patients were older than those in Groups B and C (70 years vs. 62.2 years vs. 63.3 years, respectively, p=0.026) and fewer were in NYHA class ≥III (78.9% vs. 96.6% vs. 92%, respectively, p<0.021). Group B, with an early favorable CRT response, were younger than those in Groups A and C (62.24 years vs. 70 years vs. 63 years, respectively, p=0.026), less often had ischemic etiology (13.8% vs. 42.1% vs. 44%, respectively, p<0.001), included more patients with left bundle branch block (LBBB) (92.6 vs. 76.5 vs. 76, respectively, p=0.038) and showed more LV dyssynchrony (240±129.5 vs. 202±115.5 vs. 168±128.6, respectively, p=0.049) as evaluated by the Pitzalis method. Group C, the non-responders, had more patients with ischemic etiology than Groups A and B (44 vs. 13.8 vs. 42.1, respectively, p<0.001), and had greater LVEDD (77±9.02 vs. 74±9.38 vs. 72±22 mm, respectively, p=0.048) and less previous LV dyssynchrony (168±128.6 vs. 202±115.5 vs. 240±129.5 ms, respectively, p=0.049), as assessed by the Pitzalis method. No statistically significant differences were detected in other electrocardiographic or echocardiographic parameters.Echocardiographic and clinical changes after cardiac resynchronization therapyComparison between groups of echocardiographic data from the last evaluation during follow-up is displayed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. After CRT implantation, LVRR occurred in 77 (60.6%) patients. The time course of LVRR was different within this population, with 19 patients having late LVRR (Group A), and 58 patients having evidence of early LVRR (Group B). A significant difference was noticed between groups in terms of the extent of LVRR response. At the last echocardiographic evaluation, compared to Groups A and C, Group B presented lower LVEDD (66±12.33 vs. 68±10.05 vs. 77±11.12 mm, respectively, p<0.001), lower LVESD (49±12.9 vs. 53±11.8 vs. 63±11.0 mm, respectively, p<0.001), higher LVEF (43±9.4 vs. 41±7.73 vs. 27±6.3%, respectively, p=<0.001) and smaller left atrial diameter (44±9.3 vs. 54±10.0 vs. 50±11.2, respectively, p<0.001).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Regarding clinical outcomes, during the mean follow-up of 48±36 months, both groups A and B presented better clinical status than Group C (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). The clinical response to CRT, defined as a sustained improvement in NYHA functional class, was more evident in group B than in groups A and C (94.8% vs. 68.4% vs. 38.3%, respectively, p<0.001). Group B subjects were also less often hospitalized for worsening of HF symptoms (12.1% vs. 31.6% vs. 57.1%, respectively, p<0.001). Group C showed higher cardiac mortality compared to Groups A and B (28.6% vs. 5.6% vs. 7.3%, respectively, p=0.010).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Predictors of late left ventricular reverse remodelingIn order to identify characteristics that might have an impact on the time course of LVRR after CRT, a logistic regression analysis was performed to predict a late LVRR response (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Ischemic etiology (odds ratio [OR] 0.044; p=0.013) and NYHA functional class ≤II (OR 0.056; p=0.063) were the baseline variables with the highest predictive value for a late LVRR response to CRT.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>DiscussionThe major findings of the present study, which focused on the impact of the time course of LVRR after CRT, are as follows: first, the majority of patients (60.6%) presented evidence of LVRR during long-term follow-up; second, 14.9% showed LVRR only six months after CRT; third, late LVRR patients were older and more often had ischemic etiology, and fewer were in NYHA class ≥III; fourth, late LVRR was significantly associated with better clinical and echocardiographic outcomes than no LVRR, although with a suboptimal response compared with the early LVRR population; and finally, ischemic etiology and NYHA functional class ≤II were independent predictors of late LVRR.Several studies have addressed the favorable impact of CRT in mid- and long-term follow-up, which usually occurs in the first six months after implantation.<a class="elsevierStyleCrossRefs" href="#bib0200">10–15</a> The underlying mechanism responsible for this early improvement seems to be the LVRR response initiated soon after biventricular pacing.<a class="elsevierStyleCrossRefs" href="#bib0175">5–7</a> Van de Veire et al., analyzing 49 patients scheduled for CRT, documented a decrease of ≥15% in LV end-diastolic volume in 47% of patients in the first 48 hours after device implantation.<a class="elsevierStyleCrossRef" href="#bib0225">15</a> Nina et al., in a review of 222 consecutive patients with HF implanted with a CRT system, reported a significant increase in LVEF and a decrease in LV end-diastolic volume (LVESV) acutely after implantation followed by an additional improvement in these parameters at six-month follow-up.<a class="elsevierStyleCrossRef" href="#bib0230">16</a> Wang et al., in a study of 30 patients scheduled for CRT, revealed a decrease of ≥15% in LVESV before six months in 60% of the population.<a class="elsevierStyleCrossRef" href="#bib0235">17</a> Also, Sanderson et al., in a report of 30 patients scheduled for CRT, revealed an increase of ≥15% in LVESV at three months after implantation in 56.7% of the population.<a class="elsevierStyleCrossRef" href="#bib0240">18</a> However, to the best of our knowledge, no reports have focused on LVRR documented only after six months. There are no studies demonstrating differences in the long-term prognosis of this group compared with early reverse remodeling. Pires et al., in a related study of 313 HF patients from the MIRACLE-ICD trial, compared early (1–3 months) and late (six months) clinical response after CRT and correlated it with the presence or absence of LVRR, but no significant difference was found.<a class="elsevierStyleCrossRef" href="#bib0245">19</a>Despite being a recognized therapy with a favorable influence on NYHA functional class, quality-of-life scores, rehospitalizations and cardiac death, there are a significant proportion of patients, estimated at 30%, who are considered clinical non-responders to CRT.<a class="elsevierStyleCrossRefs" href="#bib0250">20–22</a> This population has been extensively studied in previous reports and many factors have been proposed as potential contributors to a lack of response. In this study we found that a delayed reverse remodeling response after six months shares some of the variables that are present in non-responders.Patients with an LVRR response, in fact, also had less conventional electrical dyssynchrony (i.e. shorter QRS interval), even though not statistically significant, and less severe mechanical dyssynchrony evaluated by echocardiography at baseline. Although the PROSPECT trial showed modest sensitivity and specificity of echocardiographic parameters of dyssynchrony,<a class="elsevierStyleCrossRef" href="#bib0265">23</a> subanalysis including 286 patients from the original PROSPECT cohort that focused on three simple preprocedural measures of dyssynchrony reported a strong association of their parameters with more extensive reverse remodeling at 6-month follow-up.<a class="elsevierStyleCrossRef" href="#bib0270">24</a> LBBB is clearly more evident in early LVRR patients.<a class="elsevierStyleCrossRefs" href="#bib0275">25,26</a> In our study, Groups B and C had a higher incidence of ischemic etiology. Several previous studies have shown less clinical and LV function improvement in ischemic patients, probably due to the presence of myocardial scar tissue in the vicinity of the pacing lead, limiting the extent of LVRR regardless of the extent of baseline dyssynchrony.<a class="elsevierStyleCrossRefs" href="#bib0250">20–22</a> Pressure and volume overload associated with LV involvement typical of HF patients leads to gradual fibrosis, left atrial (LA) enlargement and subsequently mitral regurgitation. In this report, as stated in other studies, an increased in LA size was also correlated with late or no remodeling.<a class="elsevierStyleCrossRefs" href="#bib0285">27,28</a>Those who responded early with reverse remodeling were more symptomatic and also had higher LV systolic and diastolic dimensions at baseline, suggesting that sicker patients have more to benefit from CRT. There are other factors that could help to explain the difference in LVRR. Identification and treatment of reversible causes in the first six months after CRT, such as AV and VV delays and suboptimal HF therapy, could transform a late into an early response. Furthermore, factors such as the position of the LV lead, optimization of device programming and the presence of rhythm abnormalities could be related to a delayed response, but were not analyzed in this report.Regarding clinical outcomes during follow-up, the achievement of LVRR, regardless of duration of CRT, was followed by symptomatic and prognostic improvement as demonstrated by a sustained decrease in NYHA functional class, fewer hospitalizations due to HF worsening and less cardiac deaths compared to non-responders. Potential underlying factors could be the restoration of inter- and intraventricular synchrony and improvements in contractility and hemodynamics. These results are in line with previously described long-term positive outcomes of reverse remodeling obtained by CRT.<a class="elsevierStyleCrossRefs" href="#bib0175">5–7</a> However, analyzing early and late LVRR responses, it is clear that clinical benefits are more pronounced in the early group. This could be explained, in part, by the less intense LVRR response achieved in Group A, with a smaller impact on LV dimensions and LVEF compared with Group B. Nevertheless, long-term outcomes of late LVRR patients are significantly better than non-responders.The mechanism of a delayed response to CRT is complex and probably multifactorial, with no conclusive explanation currently available. Proper selection of a suitable subset of patients is mandatory, since it appears that sicker HF patients may respond better to CRT. According to our findings, ischemic etiology and NYHA functional classLimitationsThe present study had some limitations. First, it was a single-center retrospective cohort, albeit representative of real-world clinical practice. Second, the definition of LVRR, also used in previous studies,<a class="elsevierStyleCrossRef" href="#bib0300">30</a> required a cut-off of 10% reduction in LV dimensions and an increase of 10% in LVEF. Other studies were stricter and used a 15% threshold.<a class="elsevierStyleCrossRefs" href="#bib0295">29,30</a> Third, clinical response was based only on improvement in NYHA class and did not include assessment of functional capacity or quality of life scores. Fourth, echocardiographic parameters depend on the operator and there will always be a degree of intra- and interobserver variability. Fifth, other parameters such as position of LV lead, device programming, presence of rhythm abnormalities and levels of brain natriuretic peptide (BNP) were incomplete and thus were not considered for the present study. Finally, because of the modest number of patients studied, the current findings regarding late LVRR predictors need confirmation in large-scale prospective studies.ConclusionsOur data confirm, like other reports, that CRT is associated with favorable clinical and echocardiographic responses during long-term follow-up. This study is the first of this kind to analyze the time course of LVRR and to characterize the impact of a delayed reverse remodeling response in long-term follow-up. Late LVRR is significantly associated with better clinical and echocardiographic outcomes than no LVRR, although with a suboptimal response compared to the early LVRR population. Improvement in HF symptoms and survival after CRT are proportional to the timing and extent of LVRR response. Among all baseline parameters studied, ischemic etiology and NYHA functional class ≤II were identified as predictors of late LVRR. Better selection of suitable patients may potentially improve the rate of early CRT responders.Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this study.Confidentiality of dataThe authors declare that they have followed the protocols of their work center on the publication of patient data.Right to privacy and informed consentThe authors declare that no patient data appear in this article.Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres617670" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec631880" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres617671" "titulo" => "Resumo" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introdução" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusões" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec631879" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Patient baseline characteristics" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Echocardiographic and clinical changes after cardiac resynchronization therapy" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Predictors of late left ventricular reverse remodeling" ] ] ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Limitations" ] 10 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusions" ] 11 => array:3 [ "identificador" => "sec0055" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Right to privacy and informed consent" ] ] ] 12 => array:2 [ "identificador" => "sec0075" "titulo" => "Conflicts of interest" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-08-03" "fechaAceptado" => "2015-11-22" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec631880" "palabras" => array:3 [ 0 => "Cardiac resynchronization therapy" 1 => "Left ventricular reverse remodeling" 2 => "Time course" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec631879" "palabras" => array:3 [ 0 => "Terapêutica de ressincronização cardíaca" 1 => "Remodelagem inversa do ventrículo esquerdo" 2 => "Evolução temporal" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionLeft ventricular reverse remodeling (LVRR), defined as reduction of end-diastolic and end-systolic dimensions and improvement of ejection fraction, is associated with the prognostic implications of cardiac resynchronization therapy (CRT). The time course of LVRR remains poorly characterized. Nevertheless, it has been suggested that it occurs ≤6 months after CRT. ObjectiveTo characterize the long-term echocardiographic and clinical evolution of patients with LVRR occurring >6 months after CRT and to identify predictors of a delayed LVRR response. MethodsA total of 127 consecutive patients after successful CRT implantation were divided into three groups according to LVRR response: Group A, 19 patients (15%) with LVRR after >6 months (late LVRR); Group B, 58 patients (46%) with LVRR before 6 months (early LVRR); and Group C, 50 patients (39%) without LVRR during follow-up (no LVRR). ResultsThe late LVRR group was older, more often had ischemic etiology and fewer patients were in NYHA class ≤II. Overall, group A presented LVRR between group B and C. This was also the case with the percentage of clinical response (68.4% vs. 94.8% vs. 38.3%, respectively, p<0.001), and hospital readmissions due to decompensated heart failure (31.6% vs. 12.1% vs. 57.1%, respectively, p<0.001). Ischemic etiology (OR 0.044; p=0.013) and NYHA functional class ConclusionsLate LVRR has better clinical and echocardiographic outcomes than no LVRR, although with a suboptimal response compared to the early LVRR population. Ischemic etiology and NYHA functional class" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "IntroduçãoA remodelagem inversa do ventrículo esquerdo (RIVE), definida pela redução das dimensões telediastólicas e telessistólicas e pela melhoria da fração de ejeção, tem sido associada às implicações prognósticas da terapia de ressincronização cardíaca (TRC). A evolução temporal da RIVE permanece um processo pouco caracterizado. No entanto, tem sido sugerido que ocorrerá num período ≤6 meses após TRC. ObjetivosCaracterizar a longo prazo a evolução ecocardiográfica e clínica dos pacientes (P) com evidência de RIVE, num período >6 meses após TRC, e identificar preditores de uma resposta de RIVE tardia. MétodosCento e vinte e sete P consecutivos, após implantação bem-sucedida de TRC, foram divididos em três grupos, de acordo com a resposta de RIVE: grupo A, 19P (15%) com RIVE após seis meses (RIVE tardia); grupo B, 58P (46%) com RIVE antes dos seis meses (RIVE precoce) e grupo C, 50P (39%) sem RIVE durante o follow-up (sem RIVE). ResultadosO grupo da RIVE tardia era mais velho, tinha mais etiologia isquémica e menos P em classe NYHA≥III. Globalmente, o grupo A apresentou um grau de RIVE entre os grupos B e C. O mesmo ocorreu em relação ao grau da resposta clínica (68,4 versus 94,8 versus 38,3%, respetivamente, p<0,001) e às readmissões hospitalares por descompensação da insuficiência cardíaca (31,6 versus 12,1 versus 57,1%, respetivamente, p<0,001). A etiologia isquémica (OR 0,044; p=0,013) e a classe funcional ConclusõesA RIVE tardia tem uma melhor resposta clínica e ecocardiográfica do que a ausência de RIVE, embora com uma resposta subótima, quando comparada com a população com RIVE precoce. A etiologia isquémica e uma classe NYHA" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introdução" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusões" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1157 "Ancho" => 1515 "Tamanyo" => 109649 ] ] "descripcion" => array:1 [ "en" => "Clinical outcomes during follow-up. LVRR: left ventricular reverse remodeling." ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "IVMD: interventricular mechanical delay; LAD: left atrial diameter; LBBB: left bundle branch block; LVEDD: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; LVESD: left ventricular end-systolic diameter; LVlat-IVS: left ventricular lateral wall to interventricular septum; LVRR: left ventricular reverse remodeling; NYHA: New York Heart Association; Pitzalis: LV dyssynchrony by the Pitzalis method. A mixed etiology was defined as the presence of both ischemic and non-ischemic causes." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline \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">All patients n=127 \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">Late LVRR n=19 \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">Early LVRR n=58 \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">No LVRR n=50 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">63.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70±10.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62.2±11.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">63.3±8.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.026 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">74.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">73.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">69.0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">82.0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Etiology (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ischemic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42.1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.8% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Non-ischemic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31.6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77.6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mixed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.041 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="6" align="left" valign="top">Baseline ECG</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LBBB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">79.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92.6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.038 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">QRS (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">170.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">164±26.78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">176.29±29.75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">164.85±31.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sinus rhythm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">66.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">57.9% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">74.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59.6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NYHA class ≥III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">78.9% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">96.6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.021 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVESD (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70±10.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62±11.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">63±8.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVEDD (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">74.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">74±9.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72±22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77±9.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.048 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LAD (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50±10.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46±9.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50±12.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVEF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24.8% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26.3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25.8% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pitzalis (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">210.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">202±115.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">240±129.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">168±128.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.049 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVMD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47±28.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">51±27.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37±30.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVlat-IVS delay (ms) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">134.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">130±113.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">119±92.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">135±95.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1010912.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Baseline clinical and echocardiographic characteristics." ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "LAD: left atrial diameter; LVEDD: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; LVESD: left ventricular end-systolic diameter; LVRR: left ventricular reverse remodeling." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Follow-up \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">All patients n=127 \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">Late LVRR n=19 \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">Early LVRR n=58 \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">No LVRR n=50 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVESD (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53.53±13.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53±11.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49±12.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63±11.04 \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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVEDD (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69.31±12.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">68±10.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66±12.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">77±11.12 \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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LAD (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.38±10.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54±10.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44±9.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50±11.22 \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 " colspan="6" align="char" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVEF (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.48±11.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41±7.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43±9.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27±6.32 \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></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1010910.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Echocardiographic characteristics at follow-up." ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "OR: odds ratio; NYHA: New York Heart Association." "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">OR \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Etiology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.044 \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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NYHA class \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.056 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.063 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1010911.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Multivariate baseline predictors of late reverse remodeling response." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relationship between acute improvement in left ventricular function to 6-month outcomes after cardiac resynchronization therapy in patients with chronic heart failure" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "L.A. 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Original Article

Time to left ventricular reverse remodeling after cardiac resynchronization therapy: Better late than never

Tempo para a remodelagem inversa do ventrículo esquerdo: mais vale tarde do que nunca

André Viveiros Monteiro

Corresponding author

andreviveirosmonteiro@gmail.com

Corresponding author.

, Mário Martins Oliveira, Pedro Silva Cunha, Manuel Nogueira da Silva, Joana Feliciano, Luísa Branco, Pedro Rio, Ricardo Pimenta, Ana Sofia Delgado, Rui Cruz Ferreira

Serviço de Cardiologia do Hospital de Santa Marta – Centro Hospitalar de Lisboa Central, Lisboa, Portugal

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cardiac resynchronization therapy &#40;CRT&#41; has become an effective non-pharmacological treatment for patients with impaired left ventricular ejection fraction &#40;LVEF&#41;&#44; prolonged QRS duration and New York Heart Association &#40;NYHA&#41; functional class &#8805;III symptoms of heart failure &#40;HF&#41; despite optimal medical therapy&#46; Large multicenter clinical trials have shown that CRT can mitigate HF symptoms&#44; improve exercise capacity and quality of life&#44; reduce the incidence of hospitalizations due to HF and decrease mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#8211;4</span></a> Most of these benefits are thought to be related to left ventricular &#40;LV&#41; reverse remodeling &#40;LVRR&#41;&#44; a response characterized by a reduction in LV end-diastolic &#40;LVEDD&#41; and end-systolic &#40;LVESD&#41; dimensions and volumes and improvement of LV ejection fraction &#40;LVEF&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#8211;7</span></a> The time course of this phenomenon remains poorly characterized&#46; It has been suggested that the structural and functional changes associated with LVRR occur early after CRT and are more pronounced before the six-month landmark&#44; a time by which the extent of reverse remodeling has been shown to predict long-term prognosis in these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#8211;9</span></a> Nevertheless&#44; a variable proportion of eligible patients fail to respond initially but appear to develop LVRR after six months following CRT implantation&#46; This population with late LVRR&#44; who are not included in the already known proportion &#40;around 30&#37;&#41; of non-responders to CRT&#44; correspond to a different spectrum of individuals that&#44; to the best of our knowledge&#44; has never been directly analyzed in a prospective study&#46; To overcome this limitation&#44; the present study characterizes the timing of LVRR occurrence and assesses the long-term echocardiographic and clinical evolution of patients with LVRR occurring &#62;6 months after CRT implantation&#46; We also sought to identify potentially related clinical characteristics that might predict a late response to CRT&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">This is a single-center analysis of patients who underwent successful CRT device implantation&#46; A total of 127 consecutive CRT recipients were included and patient data were prospectively collected in the information system of our cardiology department and analyzed&#46; Patients were selected for CRT if they met currently recommended criteria&#58; &#40;1&#41; LVEF &#60;35&#37;&#59; &#40;2&#41; symptoms of HF&#44; defined as NYHA class II&#8211;IV despite optimal medical therapy&#59; and &#40;3&#41; QRS duration &#8805;120 ms&#46; Patients were classified as ischemic in the presence of significant coronary artery disease &#40;&#62;50&#37; stenosis of two or more epicardial vessels or &#62;50&#37; left main or proximal left anterior descending coronary artery stenosis on coronary angiography and&#47;or a history of previous myocardial infarction or revascularization&#41;&#46; Other patients were classified as non-ischemic&#46; All leads were placed transvenously via the subclavian and cephalic route using fluoroscopy&#46; The right ventricular lead was positioned in the apex or mid septum&#46; The LV lead was placed with an over-the-wire system in the posterolateral or lateral tributary vein of the coronary sinus depending on the ability to cannulate the veins&#44; pacing threshold&#44; or diaphragmatic stimulation&#46; The standard settings included an atrioventricular &#40;AV&#41; delay of 100 ms &#40;sensed&#41; and 130 ms &#40;paced&#41;&#44; with DDD or DDDR mode and standard lower &#40;50 beats&#47;min&#41; and upper &#40;120&#8211;130 beats&#47;min&#41; pacing rates&#46; Extensive demographic and clinical data&#44; including death&#44; NYHA class and hospitalization for worsening HF or CRT dysfunction&#44; were collected from medical records&#46; Transthoracic two-dimensional echocardiographic information was assessed at baseline&#44; six months after CRT device implantation and thereafter once a year until the end of follow-up&#46; In this study&#44; LVRR was defined as an increase &#62;10&#37; in LVEF over baseline&#44; combined with a &#62;10&#37; reduction in LVEDD and LVESD&#46; Echocardiographic cardiac structure and function were assessed using a commercially available ultrasound system &#40;Vivid 7 and Vivid E9&#59; GE Vingmed Ultrasound&#44; Horten&#44; Norway&#41; equipped with a 3&#46;5-MHz transducer&#46; LVESD&#44; LVEDD and LVEF were determined according to standard techniques and digitally stored for offline analysis in cine-loop format&#46; Interventricular mechanical delay was calculated by pulmonary and aortic pulsed Doppler measurement of the difference in time from QRS onset to onset of flow in the pulmonary and aortic outflow tracts&#44; respectively&#46; LV intraventricular dyssynchrony was assessed offline using a previously validated software package &#40;EchoPAC PC-2D strain&#59; GE Healthcare&#44; USA&#41;&#46; The cohort was divided according to the time course of LVRR response into three groups&#58; Group A&#44; presence of LVRR after &#62;6 months &#40;late LVRR&#41;&#59; Group B&#44; with LVRR before 6 months &#40;early LVRR&#41;&#59; and Group C&#44; without LVRR during follow-up &#40;no LVRR&#41;&#46; Follow-up data were obtained by review of medical records&#44; outpatient clinical visits&#44; and telephone contact&#46; Ethical and hospital permission were obtained from the appropriate local authorities&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0015" class="elsevierStylePara elsevierViewall">SPSS version 21 software &#40;SPSS Inc&#46;&#44; Chicago&#44; Illinois&#41; was used for computation&#46; Data are expressed as means &#177; standard deviation for continuous variables and as frequencies and percentages for categorical variables&#46; Data distribution was tested for normality using the Kolmogorov&#8211;Smirnov or Shapiro&#8211;Wilk test as appropriate&#46; Missing patient-level covariates were assumed to be missing and no imputation was performed&#46; Baseline characteristics and outcomes were compared using the chi-square test or Fisher&#39;s exact test&#44; when appropriate&#44; for categorical variables and the Student&#39;s t test or the Mann&#8211;Whitney test for continuous variables&#46; Univariate and multivariate logistic regression analysis was used to examine for potential predictors of a delayed LVRR response&#46; A value of p&#60;0&#46;05 was considered statistically significant&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Patient baseline characteristics</span><p id="par0020" class="elsevierStylePara elsevierViewall">Overall&#44; the study population consisted of 127 consecutive patients who underwent successful CRT implantation &#40;aged 63&#46;9&#177;10&#46;7 years&#44; 74&#46;8&#37; male&#41;&#46; The mean follow-up was 48&#177;36 months &#40;median 37 months&#41;&#46; Baseline patient characteristics are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The majority of the cohort &#40;60&#46;6&#37;&#41; had non-ischemic cardiomyopathy&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Regarding differences between groups&#44; late LVRR patients were older than those in Groups B and C &#40;70 years vs<span class="elsevierStyleItalic">&#46;</span> 62&#46;2 years vs<span class="elsevierStyleItalic">&#46;</span> 63&#46;3 years&#44; respectively&#44; p&#61;0&#46;026&#41; and fewer were in NYHA class &#8805;III &#40;78&#46;9&#37; vs<span class="elsevierStyleItalic">&#46;</span> 96&#46;6&#37; vs<span class="elsevierStyleItalic">&#46;</span> 92&#37;&#44; respectively&#44; p&#60;0&#46;021&#41;&#46; Group B&#44; with an early favorable CRT response&#44; were younger than those in Groups A and C &#40;62&#46;24 years vs<span class="elsevierStyleItalic">&#46;</span> 70 years vs<span class="elsevierStyleItalic">&#46;</span> 63 years&#44; respectively&#44; p&#61;0&#46;026&#41;&#44; less often had ischemic etiology &#40;13&#46;8&#37; vs<span class="elsevierStyleItalic">&#46;</span> 42&#46;1&#37; vs<span class="elsevierStyleItalic">&#46;</span> 44&#37;&#44; respectively&#44; p&#60;0&#46;001&#41;&#44; included more patients with left bundle branch block &#40;LBBB&#41; &#40;92&#46;6 vs<span class="elsevierStyleItalic">&#46;</span> 76&#46;5 vs<span class="elsevierStyleItalic">&#46;</span> 76&#44; respectively&#44; p&#61;0&#46;038&#41; and showed more LV dyssynchrony &#40;240&#177;129&#46;5 vs<span class="elsevierStyleItalic">&#46;</span> 202&#177;115&#46;5 vs<span class="elsevierStyleItalic">&#46;</span> 168&#177;128&#46;6&#44; respectively&#44; p&#61;0&#46;049&#41; as evaluated by the Pitzalis method&#46; Group C&#44; the non-responders&#44; had more patients with ischemic etiology than Groups A and B &#40;44 vs<span class="elsevierStyleItalic">&#46;</span> 13&#46;8 vs<span class="elsevierStyleItalic">&#46;</span> 42&#46;1&#44; respectively&#44; p&#60;0&#46;001&#41;&#44; and had greater LVEDD &#40;77&#177;9&#46;02 vs<span class="elsevierStyleItalic">&#46;</span> 74&#177;9&#46;38 vs<span class="elsevierStyleItalic">&#46;</span> 72&#177;22 mm&#44; respectively&#44; p&#61;0&#46;048&#41; and less previous LV dyssynchrony &#40;168&#177;128&#46;6 vs<span class="elsevierStyleItalic">&#46;</span> 202&#177;115&#46;5 vs<span class="elsevierStyleItalic">&#46;</span> 240&#177;129&#46;5 ms&#44; respectively&#44; p&#61;0&#46;049&#41;&#44; as assessed by the Pitzalis method&#46; No statistically significant differences were detected in other electrocardiographic or echocardiographic parameters&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Echocardiographic and clinical changes after cardiac resynchronization therapy</span><p id="par0030" class="elsevierStylePara elsevierViewall">Comparison between groups of echocardiographic data from the last evaluation during follow-up is displayed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; After CRT implantation&#44; LVRR occurred in 77 &#40;60&#46;6&#37;&#41; patients&#46; The time course of LVRR was different within this population&#44; with 19 patients having late LVRR &#40;Group A&#41;&#44; and 58 patients having evidence of early LVRR &#40;Group B&#41;&#46; A significant difference was noticed between groups in terms of the extent of LVRR response&#46; At the last echocardiographic evaluation&#44; compared to Groups A and C&#44; Group B presented lower LVEDD &#40;66&#177;12&#46;33 vs<span class="elsevierStyleItalic">&#46;</span> 68&#177;10&#46;05 vs<span class="elsevierStyleItalic">&#46;</span> 77&#177;11&#46;12 mm&#44; respectively&#44; p&#60;0&#46;001&#41;&#44; lower LVESD &#40;49&#177;12&#46;9 vs<span class="elsevierStyleItalic">&#46;</span> 53&#177;11&#46;8 vs<span class="elsevierStyleItalic">&#46;</span> 63&#177;11&#46;0 mm&#44; respectively&#44; p&#60;0&#46;001&#41;&#44; higher LVEF &#40;43&#177;9&#46;4 vs<span class="elsevierStyleItalic">&#46;</span> 41&#177;7&#46;73 vs<span class="elsevierStyleItalic">&#46;</span> 27&#177;6&#46;3&#37;&#44; respectively&#44; p&#61;&#60;0&#46;001&#41; and smaller left atrial diameter &#40;44&#177;9&#46;3 vs<span class="elsevierStyleItalic">&#46;</span> 54&#177;10&#46;0 vs<span class="elsevierStyleItalic">&#46;</span> 50&#177;11&#46;2&#44; respectively&#44; p&#60;0&#46;001&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Regarding clinical outcomes&#44; during the mean follow-up of 48&#177;36 months&#44; both groups A and B presented better clinical status than Group C &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46; The clinical response to CRT&#44; defined as a sustained improvement in NYHA functional class&#44; was more evident in group B than in groups A and C &#40;94&#46;8&#37; vs<span class="elsevierStyleItalic">&#46;</span> 68&#46;4&#37; vs<span class="elsevierStyleItalic">&#46;</span> 38&#46;3&#37;&#44; respectively&#44; p&#60;0&#46;001&#41;&#46; Group B subjects were also less often hospitalized for worsening of HF symptoms &#40;12&#46;1&#37; vs<span class="elsevierStyleItalic">&#46;</span> 31&#46;6&#37; vs<span class="elsevierStyleItalic">&#46;</span> 57&#46;1&#37;&#44; respectively&#44; p&#60;0&#46;001&#41;&#46; Group C showed higher cardiac mortality compared to Groups A and B &#40;28&#46;6&#37; vs<span class="elsevierStyleItalic">&#46;</span> 5&#46;6&#37; vs<span class="elsevierStyleItalic">&#46;</span> 7&#46;3&#37;&#44; respectively&#44; p&#61;0&#46;010&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Predictors of late left ventricular reverse remodeling</span><p id="par0040" class="elsevierStylePara elsevierViewall">In order to identify characteristics that might have an impact on the time course of LVRR after CRT&#44; a logistic regression analysis was performed to predict a late LVRR response &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Ischemic etiology &#40;odds ratio &#91;OR&#93; 0&#46;044&#59; p&#61;0&#46;013&#41; and NYHA functional class &#8804;II &#40;OR 0&#46;056&#59; p&#61;0&#46;063&#41; were the baseline variables with the highest predictive value for a late LVRR response to CRT&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0045" class="elsevierStylePara elsevierViewall">The major findings of the present study&#44; which focused on the impact of the time course of LVRR after CRT&#44; are as follows&#58; first&#44; the majority of patients &#40;60&#46;6&#37;&#41; presented evidence of LVRR during long-term follow-up&#59; second&#44; 14&#46;9&#37; showed LVRR only six months after CRT&#59; third&#44; late LVRR patients were older and more often had ischemic etiology&#44; and fewer were in NYHA class &#8805;III&#59; fourth&#44; late LVRR was significantly associated with better clinical and echocardiographic outcomes than no LVRR&#44; although with a suboptimal response compared with the early LVRR population&#59; and finally&#44; ischemic etiology and NYHA functional class &#8804;II were independent predictors of late LVRR&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Several studies have addressed the favorable impact of CRT in mid- and long-term follow-up&#44; which usually occurs in the first six months after implantation&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">10&#8211;15</span></a> The underlying mechanism responsible for this early improvement seems to be the LVRR response initiated soon after biventricular pacing&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#8211;7</span></a> Van de Veire et al&#46;&#44; analyzing 49 patients scheduled for CRT&#44; documented a decrease of &#8805;15&#37; in LV end-diastolic volume in 47&#37; of patients in the first 48 hours after device implantation&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> Nina et al&#46;&#44; in a review of 222 consecutive patients with HF implanted with a CRT system&#44; reported a significant increase in LVEF and a decrease in LV end-diastolic volume &#40;LVESV&#41; acutely after implantation followed by an additional improvement in these parameters at six-month follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> Wang et al&#46;&#44; in a study of 30 patients scheduled for CRT&#44; revealed a decrease of &#8805;15&#37; in LVESV before six months in 60&#37; of the population&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> Also&#44; Sanderson et al&#46;&#44; in a report of 30 patients scheduled for CRT&#44; revealed an increase of &#8805;15&#37; in LVESV at three months after implantation in 56&#46;7&#37; of the population&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> However&#44; to the best of our knowledge&#44; no reports have focused on LVRR documented only after six months&#46; There are no studies demonstrating differences in the long-term prognosis of this group compared with early reverse remodeling&#46; Pires et al&#46;&#44; in a related study of 313 HF patients from the MIRACLE-ICD trial&#44; compared early &#40;1&#8211;3 months&#41; and late &#40;six months&#41; clinical response after CRT and correlated it with the presence or absence of LVRR&#44; but no significant difference was found&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Despite being a recognized therapy with a favorable influence on NYHA functional class&#44; quality-of-life scores&#44; rehospitalizations and cardiac death&#44; there are a significant proportion of patients&#44; estimated at 30&#37;&#44; who are considered clinical non-responders to CRT&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">20&#8211;22</span></a> This population has been extensively studied in previous reports and many factors have been proposed as potential contributors to a lack of response&#46; In this study we found that a delayed reverse remodeling response after six months shares some of the variables that are present in non-responders&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Patients with an LVRR response&#44; in fact&#44; also had less conventional electrical dyssynchrony &#40;i&#46;e&#46; shorter QRS interval&#41;&#44; even though not statistically significant&#44; and less severe mechanical dyssynchrony evaluated by echocardiography at baseline&#46; Although the PROSPECT trial showed modest sensitivity and specificity of echocardiographic parameters of dyssynchrony&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> subanalysis including 286 patients from the original PROSPECT cohort that focused on three simple preprocedural measures of dyssynchrony reported a strong association of their parameters with more extensive reverse remodeling at 6-month follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> LBBB is clearly more evident in early LVRR patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">25&#44;26</span></a> In our study&#44; Groups B and C had a higher incidence of ischemic etiology&#46; Several previous studies have shown less clinical and LV function improvement in ischemic patients&#44; probably due to the presence of myocardial scar tissue in the vicinity of the pacing lead&#44; limiting the extent of LVRR regardless of the extent of baseline dyssynchrony&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">20&#8211;22</span></a> Pressure and volume overload associated with LV involvement typical of HF patients leads to gradual fibrosis&#44; left atrial &#40;LA&#41; enlargement and subsequently mitral regurgitation&#46; In this report&#44; as stated in other studies&#44; an increased in LA size was also correlated with late or no remodeling&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">27&#44;28</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Those who responded early with reverse remodeling were more symptomatic and also had higher LV systolic and diastolic dimensions at baseline&#44; suggesting that sicker patients have more to benefit from CRT&#46; There are other factors that could help to explain the difference in LVRR&#46; Identification and treatment of reversible causes in the first six months after CRT&#44; such as AV and VV delays and suboptimal HF therapy&#44; could transform a late into an early response&#46; Furthermore&#44; factors such as the position of the LV lead&#44; optimization of device programming and the presence of rhythm abnormalities could be related to a delayed response&#44; but were not analyzed in this report&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Regarding clinical outcomes during follow-up&#44; the achievement of LVRR&#44; regardless of duration of CRT&#44; was followed by symptomatic and prognostic improvement as demonstrated by a sustained decrease in NYHA functional class&#44; fewer hospitalizations due to HF worsening and less cardiac deaths compared to non-responders&#46; Potential underlying factors could be the restoration of inter- and intraventricular synchrony and improvements in contractility and hemodynamics&#46; These results are in line with previously described long-term positive outcomes of reverse remodeling obtained by CRT&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">5&#8211;7</span></a> However&#44; analyzing early and late LVRR responses&#44; it is clear that clinical benefits are more pronounced in the early group&#46; This could be explained&#44; in part&#44; by the less intense LVRR response achieved in Group A&#44; with a smaller impact on LV dimensions and LVEF compared with Group B&#46; Nevertheless&#44; long-term outcomes of late LVRR patients are significantly better than non-responders&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The mechanism of a delayed response to CRT is complex and probably multifactorial&#44; with no conclusive explanation currently available&#46; Proper selection of a suitable subset of patients is mandatory&#44; since it appears that sicker HF patients may respond better to CRT&#46; According to our findings&#44; ischemic etiology and NYHA functional class</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Limitations</span><p id="par0080" class="elsevierStylePara elsevierViewall">The present study had some limitations&#46; First&#44; it was a single-center retrospective cohort&#44; albeit representative of real-world clinical practice&#46; Second&#44; the definition of LVRR&#44; also used in previous studies&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> required a cut-off of 10&#37; reduction in LV dimensions and an increase of 10&#37; in LVEF&#46; Other studies were stricter and used a 15&#37; threshold&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">29&#44;30</span></a> Third&#44; clinical response was based only on improvement in NYHA class and did not include assessment of functional capacity or quality of life scores&#46; Fourth&#44; echocardiographic parameters depend on the operator and there will always be a degree of intra- and interobserver variability&#46; Fifth&#44; other parameters such as position of LV lead&#44; device programming&#44; presence of rhythm abnormalities and levels of brain natriuretic peptide &#40;BNP&#41; were incomplete and thus were not considered for the present study&#46; Finally&#44; because of the modest number of patients studied&#44; the current findings regarding late LVRR predictors need confirmation in large-scale prospective studies&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusions</span><p id="par0085" class="elsevierStylePara elsevierViewall">Our data confirm&#44; like other reports&#44; that CRT is associated with favorable clinical and echocardiographic responses during long-term follow-up&#46; This study is the first of this kind to analyze the time course of LVRR and to characterize the impact of a delayed reverse remodeling response in long-term follow-up&#46; Late LVRR is significantly associated with better clinical and echocardiographic outcomes than no LVRR&#44; although with a suboptimal response compared to the early LVRR population&#46; Improvement in HF symptoms and survival after CRT are proportional to the timing and extent of LVRR response&#46; Among all baseline parameters studied&#44; ischemic etiology and NYHA functional class &#8804;II were identified as predictors of late LVRR&#46; Better selection of suitable patients may potentially improve the rate of early CRT responders&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ethical disclosures</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Protection of human and animal subjects</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Confidentiality of data</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Right to privacy and informed consent</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "identificador" => "sec0045"
          "titulo" => "Limitations"
        ]
        10 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Conclusions"
        ]
        11 => array:3 [
          "identificador" => "sec0055"
          "titulo" => "Ethical disclosures"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Protection of human and animal subjects"
            ]
            1 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Confidentiality of data"
            ]
            2 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Right to privacy and informed consent"
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        12 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Conflicts of interest"
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        13 => array:1 [
          "titulo" => "References"
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      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2015-08-03"
    "fechaAceptado" => "2015-11-22"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec631880"
          "palabras" => array:3 [
            0 => "Cardiac resynchronization therapy"
            1 => "Left ventricular reverse remodeling"
            2 => "Time course"
          ]
        ]
      ]
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec631879"
          "palabras" => array:3 [
            0 => "Terap&#234;utica de ressincroniza&#231;&#227;o card&#237;aca"
            1 => "Remodelagem inversa do ventr&#237;culo esquerdo"
            2 => "Evolu&#231;&#227;o temporal"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Left ventricular reverse remodeling &#40;LVRR&#41;&#44; defined as reduction of end-diastolic and end-systolic dimensions and improvement of ejection fraction&#44; is associated with the prognostic implications of cardiac resynchronization therapy &#40;CRT&#41;&#46; The time course of LVRR remains poorly characterized&#46; Nevertheless&#44; it has been suggested that it occurs &#8804;6 months after CRT&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To characterize the long-term echocardiographic and clinical evolution of patients with LVRR occurring &#62;6 months after CRT and to identify predictors of a delayed LVRR response&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 127 consecutive patients after successful CRT implantation were divided into three groups according to LVRR response&#58; Group A&#44; 19 patients &#40;15&#37;&#41; with LVRR after &#62;6 months &#40;late LVRR&#41;&#59; Group B&#44; 58 patients &#40;46&#37;&#41; with LVRR before 6 months &#40;early LVRR&#41;&#59; and Group C&#44; 50 patients &#40;39&#37;&#41; without LVRR during follow-up &#40;no LVRR&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The late LVRR group was older&#44; more often had ischemic etiology and fewer patients were in NYHA class &#8804;II&#46; Overall&#44; group A presented LVRR between group B and C&#46; This was also the case with the percentage of clinical response &#40;68&#46;4&#37; vs<span class="elsevierStyleItalic">&#46;</span> 94&#46;8&#37; vs<span class="elsevierStyleItalic">&#46;</span> 38&#46;3&#37;&#44; respectively&#44; p&#60;0&#46;001&#41;&#44; and hospital readmissions due to decompensated heart failure &#40;31&#46;6&#37; vs<span class="elsevierStyleItalic">&#46;</span> 12&#46;1&#37; vs<span class="elsevierStyleItalic">&#46;</span> 57&#46;1&#37;&#44; respectively&#44; p&#60;0&#46;001&#41;&#46; Ischemic etiology &#40;OR 0&#46;044&#59; p&#61;0&#46;013&#41; and NYHA functional class</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Late LVRR has better clinical and echocardiographic outcomes than no LVRR&#44; although with a suboptimal response compared to the early LVRR population&#46; Ischemic etiology and NYHA functional class</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objective"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "pt" => array:3 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introdu&#231;&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A remodelagem inversa do ventr&#237;culo esquerdo &#40;RIVE&#41;&#44; definida pela redu&#231;&#227;o das dimens&#245;es telediast&#243;licas e telessist&#243;licas e pela melhoria da fra&#231;&#227;o de eje&#231;&#227;o&#44; tem sido associada &#224;s implica&#231;&#245;es progn&#243;sticas da terapia de ressincroniza&#231;&#227;o card&#237;aca &#40;TRC&#41;&#46; A evolu&#231;&#227;o temporal da RIVE permanece um processo pouco caracterizado&#46; No entanto&#44; tem sido sugerido que ocorrer&#225; num per&#237;odo &#8804;6 meses ap&#243;s TRC&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Caracterizar a longo prazo a evolu&#231;&#227;o ecocardiogr&#225;fica e cl&#237;nica dos pacientes &#40;P&#41; com evid&#234;ncia de RIVE&#44; num per&#237;odo &#62;6 meses ap&#243;s TRC&#44; e identificar preditores de uma resposta de RIVE tardia&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Cento e vinte e sete P consecutivos&#44; ap&#243;s implanta&#231;&#227;o bem-sucedida de TRC&#44; foram divididos em tr&#234;s grupos&#44; de acordo com a resposta de RIVE&#58; grupo A&#44; 19P &#40;15&#37;&#41; com RIVE ap&#243;s seis meses &#40;RIVE tardia&#41;&#59; grupo B&#44; 58P &#40;46&#37;&#41; com RIVE antes dos seis meses &#40;RIVE precoce&#41; e grupo C&#44; 50P &#40;39&#37;&#41; sem RIVE durante o <span class="elsevierStyleItalic">follow-up</span> &#40;sem RIVE&#41;&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">O grupo da RIVE tardia era mais velho&#44; tinha mais etiologia isqu&#233;mica e menos P em classe NYHA&#8805;III&#46; Globalmente&#44; o grupo A apresentou um grau de RIVE entre os grupos B e C&#46; O mesmo ocorreu em rela&#231;&#227;o ao grau da resposta cl&#237;nica &#40;68&#44;4 <span class="elsevierStyleItalic">versus</span> 94&#44;8 <span class="elsevierStyleItalic">versus</span> 38&#44;3&#37;&#44; respetivamente&#44; p&#60;0&#44;001&#41; e &#224;s readmiss&#245;es hospitalares por descompensa&#231;&#227;o da insufici&#234;ncia card&#237;aca &#40;31&#44;6 <span class="elsevierStyleItalic">versus</span> 12&#44;1 <span class="elsevierStyleItalic">versus</span> 57&#44;1&#37;&#44; respetivamente&#44; p&#60;0&#44;001&#41;&#46; A etiologia isqu&#233;mica &#40;OR 0&#44;044&#59; p&#61;0&#44;013&#41; e a classe funcional</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclus&#245;es</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">A RIVE tardia tem uma melhor resposta cl&#237;nica e ecocardiogr&#225;fica do que a aus&#234;ncia de RIVE&#44; embora com uma resposta sub&#243;tima&#44; quando comparada com a popula&#231;&#227;o com RIVE precoce&#46; A etiologia isqu&#233;mica e uma classe NYHA</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Introdu&#231;&#227;o"
          ]
          1 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Objetivos"
          ]
          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "M&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0050"
            "titulo" => "Conclus&#245;es"
          ]
        ]
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1157
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Clinical outcomes during follow-up&#46; LVRR&#58; left ventricular reverse remodeling&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">IVMD&#58; interventricular mechanical delay&#59; LAD&#58; left atrial diameter&#59; LBBB&#58; left bundle branch block&#59; LVEDD&#58; left ventricular end-diastolic diameter&#59; LVEF&#58; left ventricular ejection fraction&#59; LVESD&#58; left ventricular end-systolic diameter&#59; LV<span class="elsevierStyleInf">lat</span>-IVS&#58; left ventricular lateral wall to interventricular septum&#59; LVRR&#58; left ventricular reverse remodeling&#59; NYHA&#58; New York Heart Association&#59; Pitzalis&#58; LV dyssynchrony by the Pitzalis method&#46; A mixed etiology was defined as the presence of both ischemic and non-ischemic causes&#46;</p>"
          "tablatextoimagen" => array:1 [
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                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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline&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">All patients<br>n&#61;127&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">Late LVRR<br>n&#61;19&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">Early LVRR<br>n&#61;58&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">No LVRR<br>n&#61;50&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">p&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&#177;10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62&#46;2&#177;11&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63&#46;3&#177;8&#46;9&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;026&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Male &#40;&#37;&#41;</span>&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;8&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;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">69&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">82&#46;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Etiology &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ischemic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42&#46;1&#37;&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;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" 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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Non-ischemic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">77&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" 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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mixed&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;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21&#46;1&#37;&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;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;0&#37;&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;041&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleItalic">Baseline ECG</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>LBBB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">79&#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">76&#46;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">92&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">76&#37;&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;038&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>QRS &#40;ms&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">170&#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">164&#177;26&#46;78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">176&#46;29&#177;29&#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">164&#46;85&#177;31&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sinus rhythm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">66&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">57&#46;9&#37;&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;5&#37;&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;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>NYHA class &#8805;III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">92&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">78&#46;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">96&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">92&#37;&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;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>LVESD &#40;mm&#41;&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;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&#177;10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">62&#177;11&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63&#177;8&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>LVEDD &#40;mm&#41;&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;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74&#177;9&#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">72&#177;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">77&#177;9&#46;0&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;048&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">47&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&#177;10&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46&#177;9&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&#177;12&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>LVEF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#46;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#46;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pitzalis &#40;ms&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">210&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">202&#177;115&#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">240&#177;129&#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">168&#177;128&#46;6&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;049&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">47&#177;28&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">51&#177;27&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37&#177;30&#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">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>LV<span class="elsevierStyleInf">lat</span>-IVS delay &#40;ms&#41;&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">130&#177;113&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">119&#177;92&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">135&#177;95&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">LAD&#58; left atrial diameter&#59; LVEDD&#58; left ventricular end-diastolic diameter&#59; LVEF&#58; left ventricular ejection fraction&#59; LVESD&#58; left ventricular end-systolic diameter&#59; LVRR&#58; left ventricular reverse remodeling&#46;</p>"
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">All patients<br>n&#61;127&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVESD &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&#46;53&#177;13&#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">53&#177;11&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&#177;12&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&#177;11&#46;04&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVEDD &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">69&#46;31&#177;12&#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">68&#177;10&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66&#177;12&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77&#177;11&#46;12&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
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&#46;38&#177;10&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54&#177;10&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&#177;9&#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">50&#177;11&#46;22&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  " colspan="6" align="char" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVEF &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&#46;48&#177;11&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&#177;7&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&#177;9&#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">27&#177;6&#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></tbody></table>
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Echocardiographic characteristics at follow-up&#46;</p>"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">OR&#58; odds ratio&#59; NYHA&#58; New York Heart Association&#46;</p>"
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                  \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
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Etiology&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;044&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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NYHA class&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;056&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;063&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab1010911.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Multivariate baseline predictors of late reverse remodeling response&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:30 [
            0 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relationship between acute improvement in left ventricular function to 6-month outcomes after cardiac resynchronization therapy in patients with chronic heart failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "L&#46;A&#46; Pires"
                            1 => "S&#46; Ghio"
                            2 => "E&#46;S&#46; Chung"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1751-7133.2010.00207.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Congest Heart Fail"
                        "fecha" => "2011"
                        "volumen" => "17"
                        "paginaInicial" => "65"
                        "paginaFinal" => "70"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21449994"
                            "web" => "Medline"
                          ]
                        ]
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                    ]
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                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "S&#46; Cazeau"
                            1 => "C&#46; Leclercq"
                            2 => "T&#46; Lavergne"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM200103223441202"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2001"
                        "volumen" => "344"
                        "paginaInicial" => "873"
                        "paginaFinal" => "880"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11259720"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of cardiac resynchronization on morbidity and mortality in heart failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46;G&#46; Cleland"
                            1 => "J&#46;C&#46; Daubert"
                            2 => "E&#46; Erdmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa050496"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2005"
                        "volumen" => "352"
                        "paginaInicial" => "1539"
                        "paginaFinal" => "1549"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15753115"
                            "web" => "Medline"
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                    ]
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            ]
            3 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure&#58; the MIRACLE ICD trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "J&#46;B&#46; Young"
                            1 => "W&#46;T&#46; Abraham"
                            2 => "A&#46;L&#46; Smith"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.289.20.2685"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2003"
                        "volumen" => "289"
                        "paginaInicial" => "2685"
                        "paginaFinal" => "2694"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12771115"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "5"
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                0 => array:2 [
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Article information

ISSN: 21742049
Original language: English

DOI:10.1016/j.repce.2015.11.014

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Year/Month	Html	Pdf	Total

2024 November	4	3	7
2024 October	49	27	76
2024 September	49	23	72
2024 August	44	23	67
2024 July	32	26	58
2024 June	38	15	53
2024 May	30	25	55
2024 April	34	25	59
2024 March	59	27	86
2024 February	39	38	77
2024 January	23	36	59
2023 December	34	35	69
2023 November	29	22	51
2023 October	21	13	34
2023 September	23	20	43
2023 August	26	11	37
2023 July	27	23	50
2023 June	20	11	31
2023 May	36	16	52
2023 April	21	4	25
2023 March	22	26	48
2023 February	24	22	46
2023 January	17	16	33
2022 December	27	31	58
2022 November	24	29	53
2022 October	23	14	37
2022 September	21	38	59
2022 August	24	26	50
2022 July	54	36	90
2022 June	39	26	65
2022 May	66	39	105
2022 April	32	28	60
2022 March	30	32	62
2022 February	31	27	58
2022 January	31	29	60
2021 December	37	26	63
2021 November	46	34	80
2021 October	66	36	102
2021 September	32	23	55
2021 August	63	29	92
2021 July	37	28	65
2021 June	30	9	39
2021 May	29	34	63
2021 April	59	23	82
2021 March	64	18	82
2021 February	56	29	85
2021 January	49	21	70
2020 December	43	17	60
2020 November	53	13	66
2020 October	25	14	39
2020 September	53	8	61
2020 August	25	6	31
2020 July	50	11	61
2020 June	46	14	60
2020 May	44	9	53
2020 April	36	21	57
2020 March	47	14	61
2020 February	113	26	139
2020 January	33	6	39
2019 December	45	8	53
2019 November	28	12	40
2019 October	38	6	44
2019 September	33	11	44
2019 August	20	10	30
2019 July	32	8	40
2019 June	28	11	39
2019 May	32	13	45
2019 April	32	14	46
2019 March	34	13	47
2019 February	42	15	57
2019 January	16	9	25
2018 December	40	10	50
2018 November	143	8	151
2018 October	329	15	344
2018 September	59	13	72
2018 August	91	8	99
2018 July	20	7	27
2018 June	27	7	34
2018 May	28	14	42
2018 April	37	6	43
2018 March	38	8	46
2018 February	28	6	34
2018 January	24	10	34
2017 December	51	16	67
2017 November	46	7	53
2017 October	36	14	50
2017 September	48	19	67
2017 August	39	9	48
2017 July	17	12	29
2017 June	34	14	48
2017 May	31	8	39
2017 April	19	5	24
2017 March	29	36	65
2017 February	35	6	41
2017 January	31	9	40
2016 December	26	14	40
2016 November	19	4	23
2016 October	22	6	28
2016 September	14	9	23
2016 August	6	0	6
2016 July	18	10	28
2016 June	5	19	24
2016 May	13	13	26
2016 April	14	1	15
2016 March	21	12	33

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