Review article
Cardiac resynchronization therapy in patients with atrial fibrillation: A meta-analysis
Terapêutica de ressincronização cardíaca em doentes com fibrilhação auricular: uma metanálise
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CABG: coronary artery bypass grafting; PCI: percutaneous coronary intervention; STEMI: 90% or more patients with diagnosis of ST-segment elevation myocardial infarction or Q-wave myocardial infarction; NSTE-ACS: 90% or more patients with diagnosis of non-ST-segment elevation ACS; mixed ACS: mixture of patients with several types of ACS.</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">* If a study provided data on treatment with both reperfusion and revascularization, it contributed to both groups. 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AF: atrial fibrillation; M-H: Mantel-Haenszel; SR: sinus rhythm.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Atrial fibrillation (AF) is the most common arrhythmia in patients with heart failure (HF) and is associated with increased mortality and morbidity.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> About 20% of patients treated with cardiac resynchronization therapy (CRT) are in AF.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Despite the high prevalence of AF in patients with HF and the fact that many meet the criteria for CRT, randomized controlled trials have excluded these patients in most cases.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Thus, the effect of this therapy in patients with AF is still controversial.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Notwithstanding this controversy, according to the American Heart Association, American College of Cardiology and Heart Rhythm Society guidelines, CRT is a class IIa recommendation (level of evidence B) for patients with AF, left ventricular ejection fraction (LVEF) ≤35% and ventricular dyssynchrony, since a high percentage of biventricular capture can be ensured. Atrioventricular (AV) nodal ablation should be performed in cases of incomplete biventricular capture.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">AV nodal ablation offers the most effective method for rate control in AF patients, by creating a complete heart block and regularizing cardiac rhythm through permanent pacing. This approach enables complete biventricular pacing.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Nevertheless, the importance of AV nodal ablation (compared to pharmacologic therapy) in achieving an optimized response to CRT in AF patients remains unclear.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The meta-analyses published by Upadhyay et al. in 2008<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and by Wilton et al. in 2011<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> suggested significant differences in outcomes between patients in SR and those in AF, highlighting the need for further research.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of this meta-analysis was to investigate the effects of CRT in patients with AF compared with patients in SR, and to evaluate the effect of AV nodal ablation in the former group. To the best of our knowledge, this is the most recent and up-to-date meta-analysis on this subject.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Search strategy</span><p id="par0030" class="elsevierStylePara elsevierViewall">Searches were conducted in the electronic databases PubMed, B-On, and Cochrane Central Register of Controlled Trials, and included the following terms: “atrial fibrillation”, “heart failure”, “congestive heart failure”, “congestive cardiac failure”, “chronic heart failure”, “chronic cardiac failure”, “resynchronization therapy”, “cardiac resynchronization therapy”, “cardiac resynchronization”, “heart resynchronization”, “artificial biventricular pacemaker”, “biventricular pacemaker”, “biventricular pacing”, “biv”, “dual-chamber pacing”, “dual-chamber pacemaker”, “atrioventricular nodal ablation”, “atrioventricular junction ablation”, “ablation pacing”, “ablation techniques”, “ablation”, “AV nodal ablation”, “AVJ ablation”.</p><p id="par0035" class="elsevierStylePara elsevierViewall">We considered studies in humans, published and unpublished, written in English or Portuguese, up to November 2012. In addition, we performed a manual search of abstracts in journals and conferences and in reference lists of selected articles.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Inclusion criteria</span><p id="par0040" class="elsevierStylePara elsevierViewall">We included studies that met all of the following criteria: randomized controlled trials or cohort studies; individuals with a diagnosis of HF in NYHA class II–IV with LVEF ≤35%, in AF or SR; comparison between patients in AF and SR; implantation of cardiac resynchronization devices; study of all-cause mortality, cardiovascular mortality, non-responders to therapy and follow-up ≥6 months.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Data extraction</span><p id="par0045" class="elsevierStylePara elsevierViewall">From each study, the following data were extracted and analyzed: characteristics of the study population, study design, methodological criteria, interventions, outcomes of interest and results. All text, tables and figures were reviewed for data extraction.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The primary endpoint was all-cause mortality. The secondary endpoints included cardiovascular mortality and non-response to CRT. If the investigators reported endpoints at two different follow-up times, endpoints for the longest available duration of follow-up were used.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Quality assessment</span><p id="par0055" class="elsevierStylePara elsevierViewall">Assessment of studies’ quality and eligibility and their selection were performed independently by two investigators. Studies that did not meet the inclusion criteria were excluded from the meta-analysis. Disagreements were resolved by consensus. We included articles by the same author(s) if they had different samples or analyzed different outcomes.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The quality of included studies was assessed using a checklist developed by the reviewers. This instrument analyzed a series of items involving methodology, participants, interventions and outcomes, designed to minimize bias.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">The statistical analysis was performed with Review Manager (RevMan) statistical software, version 5.1.</p><p id="par0070" class="elsevierStylePara elsevierViewall">For dichotomous clinical outcomes, overall estimation of the treatment effect was performed with the Peto statistical method, through a random effects model. Odds ratios (OR) and corresponding 95% confidence intervals were calculated, and the Z-test was used to determine the statistical significance of the estimated overall effect. Statistical heterogeneity was quantified using Cochran's chi-square test. The I<span class="elsevierStyleSup">2</span> statistic was also calculated to assess the inter-study consistency of the results. An I<span class="elsevierStyleSup">2</span> of 25%, 50% and 75% indicates low, moderate or high heterogeneity, respectively. Sensitivity analysis was performed to identify reasons for heterogeneity. Different strategies included changing criteria for inclusion of studies according to their methodological characteristics; exclusion of studies that showed some ambiguity in their inclusion criteria; exclusion of unpublished studies; and re-evaluation of the data using different statistical methods, such as calculation of risk ratios (RR) instead of OR, calculated by both fixed and random effect models. These multivariate analyses were performed to determine whether modification of some criteria would be sufficient to change the combined result and thus assess the degree of confidence of the results of the meta-analysis.</p><p id="par0075" class="elsevierStylePara elsevierViewall">A funnel plot was used to assess publication bias. This analysis identifies inter-study asymmetries that should be explored. In the absence of bias, dispersion of the points of the plot is similar to a symmetric pyramid. The presence of asymmetry in the graph suggests the existence of publication bias.</p><p id="par0080" class="elsevierStylePara elsevierViewall">A p-value of <0.05 was adopted as the criterion for statistical significance.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Search results</span><p id="par0085" class="elsevierStylePara elsevierViewall">The search retrieved 470 potentially relevant articles. The first stage of selection, based on titles, excluded 365 articles. Of the 105 studies considered, 75 were excluded after examination of the abstract. The full text of the remaining 30 publications was examined in more detail. Finally, 19 articles were included in our meta-analysis (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Description of included studies</span><p id="par0090" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the characteristics of the included articles, which involved a total of 5325 patients (1399 with AF and 3925 in SR). Mean age was 67.7 years in the AF patients and 66.2 years in the SR patients. Comparing patients with and without AF, the proportion of males was 81.3% vs. 75.1%, ischemic cardiomyopathy was present in 40.6% vs. 45.5%, LVEF was 24.5% vs. 24.3%, and QRS duration was 171.8 ms vs. 167.9 ms, respectively. Most participants reported symptoms of advanced HF (NYHA functional class III and IV). Length of follow-up ranged from 6 to 34 months.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Diuretics were prescribed in 90% vs. 85% of patients, beta-blockers in 66% vs. 70%, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in 94% vs. 90%, amiodarone in 35% vs. 22% and digitalis in 56% vs. 39% in the AF and SR groups, respectively.</p><p id="par0100" class="elsevierStylePara elsevierViewall">There were statistically significant differences in baseline characteristics between patients with AF and SR in most studies included.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">All-cause mortality</span><p id="par0105" class="elsevierStylePara elsevierViewall">When the results of the 11 randomized trials were pooled, the odds ratio for overall mortality was 1.69 (95% confidence interval [CI]: 1.20–2.37; p=0.002), meaning a 69% higher probability of death in patients with AF compared with patients in SR. We found statistical evidence of moderate heterogeneity (I<span class="elsevierStyleSup">2</span>=54%; p=0.02) (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">We explored potential causes of heterogeneity between studies through sensitivity analyses. After exclusion of an unpublished study (Nascimento C, Pereira T, Providência R, Rodrigues P), there was no change in the pooled estimate using a random effects model (OR: 1.74; 95% CI: 1.18–2.57; p=0.005; I<span class="elsevierStyleSup">2</span>=59%). The inclusion of six studies in which no individuals underwent AV nodal ablation resulted in a total effect of 1.58 (95% CI: 0.97–2.56; p=0.06), with heterogeneity of 47%, compared to an OR of 1.87 (95% CI: 1.08–3.23; p=0.02) and heterogeneity of 68% in the other five studies.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Excluding studies that included patients in NYHA class II, the increase in all-cause mortality in AF patients was even more pronounced (OR: 2.14; 95% CI: 1.47–3.09; p<0.0001; I<span class="elsevierStyleSup">2</span>=32%). In the sensitivity analysis that included only cohort studies, a similar increase in all-cause mortality was observed (OR: 1.76; 95% CI: 1.22–2.54; p=0.003; I<span class="elsevierStyleSup">2</span>=58%).</p><p id="par0120" class="elsevierStylePara elsevierViewall">In order to explore statistical heterogeneity and investigate potential publication bias, a funnel plot was constructed, which revealed qualitative evidence of asymmetry in the distribution of the estimated effects in several studies. The analysis of all-cause mortality was redone excluding studies with greater dispersion. This produced an OR of 1.38 (95% CI: 1.07–1.78), a statistically significant difference (p=0.01), and a decrease in heterogeneity (I<span class="elsevierStyleSup">2</span>=20%).</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Cardiovascular mortality</span><p id="par0125" class="elsevierStylePara elsevierViewall">Pooled analysis of six studies comparing cardiovascular mortality in patients with AF and SR after treatment with CRT showed no statistically significant differences between groups (OR: 1.36; 95% CI: 0.92–2.01; p=0.12), although there was a trend in favor of the SR group. There was mild heterogeneity (I<span class="elsevierStyleSup">2</span>=33%; p=0.19) (<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Non-response to cardiac resynchronization therapy</span><p id="par0130" class="elsevierStylePara elsevierViewall">Response to CRT was defined as improvement of one NYHA functional class after six months,<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> decrease in left ventricular end-systolic volume (LVESV) of 10% or 15% measured by cardiac ultrasound,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,11–13</span></a> or improvement in absolute LVEF of ≥5% after three months.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In studies by Tolosana et al.,<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,15</span></a> clinical responders were defined as those with an increase of ≥10% in the 6-minute walk test 12 months after implantation or improvement of at least one NYHA functional class. Echocardiographic responders were defined as patients who had a ≥10% reduction in LVESV.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Other trials used a definition of CRT response that required both objective symptomatic improvement in quality of life and a ≥15% reduction in LVESV.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,13</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">The rate of non-response to CRT was significantly higher in individuals with AF (OR=1.41, 95% CI: 1.15–1.73, p=0.001). No statistical heterogeneity was found (I<span class="elsevierStyleSup">2</span>=0%) (<a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a>). The overall mean proportion of responders was 65% in those with AF and 71% in those in SR. Excluding the three studies that included patients with paroxysmal AF gave similar results (OR=1.56, 95% CI: 1.23–1.99, p=0.0002, I<span class="elsevierStyleSup">2</span>=0%).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">The role of atrioventricular nodal ablation</span><p id="par0140" class="elsevierStylePara elsevierViewall">We identified two studies that evaluated the impact of ablation on all-cause mortality in AF patients. In these studies, mortality was 58% (OR=0.42) lower in the group who underwent AV nodal ablation. Pooled analysis of three studies showed that cardiovascular mortality was 61% (OR=0.39) lower in this group than in those who did not undergo AV nodal ablation. In both analyses, the overall effect was statistically significant (p=0.008 and p=0.005, respectively), with no evidence of heterogeneity between studies (I<span class="elsevierStyleSup">2</span>=0%) (<a class="elsevierStyleCrossRef" href="#fig0025">Figure 5</a>).</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">In four studies analyzed, the likelihood of non-response to CRT was 69% lower in patients treated by ablation (OR: 0.31; 95% CI: 0.10–0.97; p=0.04; I<span class="elsevierStyleSup">2</span>=72%). There was moderate inconsistency, which means the results should be treated with caution.</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0150" class="elsevierStylePara elsevierViewall">This meta-analysis suggests that AF, compared to SR, is associated with increased all-cause mortality in patients undergoing CRT. This finding was particularly robust when re-evaluated in sensitivity analyses performed to explore heterogeneity. Furthermore, although cardiovascular mortality was not significantly different between groups, there was a trend in favor of SR, and the large standard deviation in some studies may have reduced the statistical significance of their results. Therefore, we cannot exclude small differences in cardiovascular mortality between patients with AF and SR. Finally, our meta-analysis suggests that AV nodal ablation decreases all-cause and cardiovascular mortality in AF patients. To the best of our knowledge, this is the most recent and up-to-date meta-analysis on this subject, which increases its clinical applicability.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Our findings are consistent with those of other studies.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,14,16,17</span></a> In a systematic review and meta-analysis of 23 studies, Wilton et al. suggested that AF was associated with a weaker clinical response to CRT and an increased risk of death from any cause.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> By contrast, Molhoek et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and Delnoy et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> found no differences in survival between subjects with AF and SR. Some investigators have suggested that digoxin and amiodarone may increase morbidity and mortality in patients with HF.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19–21</span></a> Some studies included in this meta-analysis showed significant differences in medication between the AF and SR groups, with more patients in the former treated with these drugs. This difference may have contributed to a worsening of all-cause mortality in these patients.</p><p id="par0160" class="elsevierStylePara elsevierViewall">The Resynchronization for Ambulatory Heart Failure Trial (RAFT) randomized patients to an implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy with defibrillator (CRT-D) in patients with permanent AF and found no differences in cardiovascular mortality, heart failure hospitalization, 6-minute walk test or rate of perioperative complications.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Our meta-analysis contradicts these findings to some extent, as a clear benefit from CRT was shown in the AF group.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Patients with AF had a higher rate of lack of response to CRT. The rates of non-response in the two groups were similar to those of previous studies,<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,11,23,24</span></a> despite the fact that the definition of response to CRT differs widely in the literature.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> In their 2011 meta-analysis of 23 studies, Wilton et al. reported higher rates of non-response to CRT in patients with AF and a clinical benefit from AV nodal ablation in this group,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> which is corroborated by our findings. In fact, our meta-analysis strongly suggests the ablation procedure may be associated with increased survival and response rate to CRT in subjects with AF.</p><p id="par0170" class="elsevierStylePara elsevierViewall">Considering that AF in patients with HF is associated with worse prognosis and higher mortality,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> a higher adverse event rate and a lower probability of response to CRT would be expected in these patients. In this context, the benefits found in patients with this arrhythmia, although less than those reported in patients in SR, are clinically significant and may be proportional; in other words, CRT could have the same impact in patients in SR and AF when adjusted for the overall greater comorbidity and frailty of the latter group. On the other hand, the possibility that AF impacts directly on the outcome of CRT should be considered, as AF has already been unequivocally demonstrated to predict mortality in patients with structural cardiac abnormalities and HF.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,27–30</span></a> Our results suggest that CRT benefits patients with AF, even if less than those in SR.</p><p id="par0175" class="elsevierStylePara elsevierViewall">AF can directly impair the function of CRT devices by reducing biventricular capture, due to loss of AV synchrony and rapid and irregular ventricular rate, which has been associated with adverse outcomes.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31,32</span></a> Therefore, AV junction ablation may be of particular value, as it ensures adequate biventricular pacing in patients with AF. Nevertheless, potential benefits must be balanced against the risks associated with pacemaker dependency. Observational studies have investigated the effects of AV nodal ablation in patients with HF and AF treated with CRT and demonstrated benefits in left ventricular systolic function, NYHA class, mitral regurgitation and exercise capacity.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10,33–38</span></a> A study by Brignole et al. included 186 patients randomized to CRT or conventional right ventricular (RV) pacing following AV junction ablation. These investigators proposed that CRT is superior to RV apical pacing in reducing the clinical manifestations of HF in patients with AF, providing further evidence that CRT is effective in patients with AF, especially if AV junction ablation is performed concurrently.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> Gasparini et al. found that patients with AF who underwent AV nodal ablation showed significant improvement in LVEF, NYHA class and exercise capacity, a better response to CRT and faster reverse remodeling. All-cause mortality was significantly lower in patients with AV nodal ablation compared with those treated pharmacologically. These data, together with the findings of our meta-analysis, suggest that patients with AF can benefit from ablation and pacing.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,40</span></a> AV nodal ablation ensures 100% capture and heart rate control, which are difficult to achieve with pharmacological treatment, overcoming the deleterious effects of rapid and irregular ventricular rate and competitive pacing.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> In fact, in the 2013 ACCF/HRS/AHA/ASE/HFSA/SCAI/SCCT/SCMR Appropriate Use Criteria, CRT was deemed appropriate to use in any situation where >40% RV pacing is anticipated, such as after AV junction ablation.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> Moreover, AV nodal ablation enables discontinuation of drugs such as digoxin and amiodarone, which can have a positive impact on mortality and morbidity in patients with HF, as mentioned above.</p><p id="par0180" class="elsevierStylePara elsevierViewall">Notwithstanding such considerations, some authors have found that prognosis and symptomatic benefits are similar between patients with and without AV nodal ablation,<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,19,43,44</span></a> adding to the controversy surrounding the subject. In a study by Himmel et al., no significant differences were found in functional status, LVEF or left ventricular end-diastolic dimensions between patients with and without AV nodal ablation. This suggests that AV nodal ablation might not be strictly required in all patients with permanent AF and biventricular pacemaker.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">A meta-analysis with similar objectives to ours was previously published,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> but ours also reported cardiovascular mortality in patients with AF and SR, as well as comparing mortality in AF patients who did or did not undergo AV nodal ablation.</p><p id="par0190" class="elsevierStylePara elsevierViewall">In conclusion, the current meta-analysis confirms that CRT should not be ruled out in AF patients as it can have a positive impact on their clinical outcomes, especially when combined with AV nodal ablation.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Study limitations</span><p id="par0195" class="elsevierStylePara elsevierViewall">Our study has several limitations. First, this meta-analysis included mainly observational studies, some with small sample sizes, rather than randomized controlled trials. Thus, we cannot exclude confounding factors as an alternative explanation for our results. Significant differences in baseline characteristics were noted between AF and SR patients in a number of studies. The conclusions of this analysis are limited by the available data. Another possible limitation of our study is the influence of publication bias. However, we included articles with several study designs, as well as abstracts and unpublished studies, so as to reduce the risk of publication bias and improve the sensitivity and power of the meta-analysis.</p><p id="par0200" class="elsevierStylePara elsevierViewall">Significant heterogeneity was present in several analyses and was an important limitation. We applied sensitivity analysis to explore the reasons for heterogeneity.</p><p id="par0205" class="elsevierStylePara elsevierViewall">Further limitations were: differences in total number of patients in each group, with fewer subjects in AF; small numbers of patients who underwent AV nodal ablation; differences in duration of follow-up; inclusion of individuals in paroxysmal, persistent and permanent AF; and the lack of a uniform definition of response to CRT. Finally, the lack of information regarding programming of resynchronization devices and left ventricular lead position may have impaired the homogeneity of the samples.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conclusions</span><p id="par0210" class="elsevierStylePara elsevierViewall">Patients with HF and AF benefit from CRT, although less than patients in SR. However, the former group is at increased risk of all-cause mortality and shows a higher non-response rate to CRT. AV nodal ablation is associated with a reduction in all-cause and cardiovascular mortality and non-response rate. Therefore, it seems reasonable to consider AV nodal ablation in patients with AF, although the exact extent of the benefits, and the long-term safety of this approach, still remain to be determined. Large randomized trials are needed to confirm our findings.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Ethical disclosures</span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Protection of human and animal subjects</span><p id="par0215" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Confidentiality of data</span><p id="par0220" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Right to privacy and informed consent</span><p id="par0225" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Conflicts of interest</span><p id="par0230" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:2 [ "identificador" => "xres389804" "titulo" => array:5 [ 0 => "Abstract" 1 => "Background and Objective" 2 => "Methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec368079" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres389803" "titulo" => array:5 [ 0 => "Resumo" 1 => "Introdução e objetivos" 2 => "Métodos" 3 => "Resultados" 4 => "Conclusões" ] ] 3 => array:2 [ "identificador" => "xpalclavsec368078" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Search strategy" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Inclusion criteria" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Data extraction" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Quality assessment" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Search results" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Description of included studies" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "All-cause mortality" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Cardiovascular mortality" ] 4 => array:2 [ "identificador" => "sec0065" "titulo" => "Non-response to cardiac resynchronization therapy" ] 5 => array:2 [ "identificador" => "sec0070" "titulo" => "The role of atrioventricular nodal ablation" ] ] ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Study limitations" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Conclusions" ] 10 => array:3 [ "identificador" => "sec0090" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0095" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0100" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0105" "titulo" => "Right to privacy and informed consent" ] ] ] 11 => array:2 [ "identificador" => "sec0110" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-05-20" "fechaAceptado" => "2014-05-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec368079" "palabras" => array:4 [ 0 => "Atrial fibrillation" 1 => "Cardiac resynchronization therapy" 2 => "Atrioventricular nodal ablation" 3 => "Meta-analysis" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec368078" "palabras" => array:4 [ 0 => "Fibrilhação auricular" 1 => "Terapêutica de ressincronização cardíaca" 2 => "Ablação auriculoventricular" 3 => "Metanálise" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background and Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To combine the results of the best scientific evidence in order to compare the effects of cardiac resynchronization therapy (CRT) in heart failure patients with atrial fibrillation (AF) and in sinus rhythm (SR) and to determine the effect of atrioventricular nodal ablation in AF patients.</p> <span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The electronic databases PubMed, B-On and Cochrane CENTRAL were searched, and manual searches were performed, for randomized controlled trials and cohort studies up to November 2012. The endpoints analyzed were all-cause and cardiovascular mortality and response to CRT.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We included 19 studies involving 5324 patients: 1399 in AF and 3925 in SR. All-cause mortality was more likely in patients with AF compared to patients in SR (OR<span class="elsevierStyleMonospace">=</span>1.69; 95% CI: 1.20–2.37; p<span class="elsevierStyleMonospace">=</span>0.002). There were no statistically significant differences in cardiovascular mortality (OR<span class="elsevierStyleMonospace">=</span>1.36; 95% CI: 0.92–2.01; p<span class="elsevierStyleMonospace">=</span>0.12). AF was associated with an increased likelihood of lack of response to CRT (OR<span class="elsevierStyleMonospace">=</span>1.41; 95% CI: 1.15–1.73; p<span class="elsevierStyleMonospace">=</span>0.001). Among subjects with AF, ablation of the atrioventricular node was associated with a reduction in all-cause mortality (OR<span class="elsevierStyleMonospace">=</span>0.42; 95% CI: 0.22–0.80; p<span class="elsevierStyleMonospace">=</span>0.008), cardiovascular death (OR<span class="elsevierStyleMonospace">=</span>0.39; 95% CI: 0.20–0.75; p<span class="elsevierStyleMonospace">=</span>0.005) and the number of non-responders to CRT (OR<span class="elsevierStyleMonospace">=</span>0.30; 95% CI: 0.10–0.90; p<span class="elsevierStyleMonospace">=</span>0.03).</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The presence of AF is associated with increased likelihood of all-cause death and non-response to CRT, compared to patients in SR. However, many patients with AF benefit from CRT. Atrioventricular nodal ablation appears to increase the benefits of CRT in patients with AF.</p>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Introdução e objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Combinar os resultados da melhor evidência científica de forma a comparar os efeitos da terapêutica de ressincronização cardíaca (TRC) em doentes com insuficiência cardíaca em fibrilhação auricular (FA) e em ritmo sinusal (RS) e determinar a influência da ablação auriculoventricular (AV) no grupo de doentes em FA.</p> <span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A pesquisa realizou-se nas bases de dados eletrónicas da PubMed, B-On e CENTRAL e de forma manual, incluindo ensaios clínicos controlados aleatorizados e estudos de coorte até novembro de 2012. Analisou-se a mortalidade total e cardiovascular e a resposta à TRC.</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Foram incluídos 19 estudos que envolveram 5324 pacientes: 1399 em FA e 3925 em RS. O grupo com doentes em FA apresenta maior risco de mortalidade total, comparativamente ao grupo de doentes em RS (OR<span class="elsevierStyleMonospace">=</span>1,69; IC 1,20–2,37, p<span class="elsevierStyleMonospace">=</span>0,002). Não foram verificadas diferenças estatisticamente significativas quanto à mortalidade cardiovascular (OR<span class="elsevierStyleMonospace">=</span>1,36, IC 0,92–2,01, p<span class="elsevierStyleMonospace">=</span>0,12). A não resposta à TRC foi maior no grupo em FA (OR<span class="elsevierStyleMonospace">=</span>1,41; IC 1,15–1,73; p<span class="elsevierStyleMonospace">=</span>0,001). Entre os indivíduos em FA, a ablação do nódulo auriculoventricular foi associada à redução da mortalidade total (OR<span class="elsevierStyleMonospace">=</span>0,42; IC 0,22–0,80; p<span class="elsevierStyleMonospace">=</span>0,008), mortalidade cardiovascular (OR<span class="elsevierStyleMonospace">=</span>0,39; IC 0,20–0,75; p<span class="elsevierStyleMonospace">=</span>0,005) e número de não respondedores à TRC (OR<span class="elsevierStyleMonospace">=</span>0,30; IC 0,10–0,90; p<span class="elsevierStyleMonospace">=</span>0,03).</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusões</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A presença de FA está associada a maior probabilidade de morte por todas as causas e de não resposta à TRC, comparativamente aos doentes em RS. Contudo, um número significativo de doentes em FA beneficia da TRC. A ablação AV parece aumentar os benefícios da TRC nos doentes com FA.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1475 "Ancho" => 1654 "Tamanyo" => 239753 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flow diagram of article selection. SR: sinus rhythm.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1053 "Ancho" => 2668 "Tamanyo" => 320025 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Forest plot comparing all-cause mortality in patients with atrial fibrillation and sinus rhythm. AF: atrial fibrillation; M-H: Mantel-Haenszel; SR: sinus rhythm.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 798 "Ancho" => 2668 "Tamanyo" => 224035 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular mortality for patients with atrial fibrillation versus sinus rhythm. AF: atrial fibrillation; M-H: Mantel-Haenszel; SR: sinus rhythm.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 993 "Ancho" => 2668 "Tamanyo" => 294421 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Meta-analysis of the odds ratios of non-response to cardiac resynchronization therapy in patients with atrial fibrillation and sinus rhythm. AF: atrial fibrillation; M-H: Mantel-Haenszel; SR: sinus rhythm.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1365 "Ancho" => 2668 "Tamanyo" => 338896 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Meta-analysis comparing all-cause mortality (A) and cardiovascular mortality (B) in patients with atrial fibrillation who did or did not undergo atrioventricular nodal ablation. ABL: atrioventricular nodal ablation; AF: atrial fibrillation; NABL: no atrioventricular nodal ablation (pharmacological therapy); SR: sinus rhythm.</p>" ] ] 5 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Data expressed as mean ± SD. AF: atrial fibrillation; CRT-D: cardiac resynchronization therapy with defibrillator; Prosp: prospective; RCT: randomized controlled trial; Retrosp: retrospective; SR: sinus rhythm.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Type \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Patients (n)</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Age (years)</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Men (%)</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Follow-up (months)</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">CRT-D (n)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">AF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">SR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">AF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">SR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">AF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">SR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">AF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">SR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">AF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">SR \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leclercq at al.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68±6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67±8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Linde et al.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RCT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63±10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Molhoek et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63±10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68±8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gasparini et al.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">162 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">511 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66±8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63±10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">299 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Delnoy et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">167 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73±8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Buck et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63±11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62±12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ferreira et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66±10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gasparini et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">243 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63±10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Khadjooi et al.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">209 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72±10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68±11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tolosana et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">126 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69±7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">215 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Schütte et al.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kim et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Wo et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68±13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66±14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Luedorff et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">139 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">445 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71±7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Wilton et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68±7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69±12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tolosana et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Retrosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">156 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">68±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">136 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Himmel et al.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prosp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">230 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69±9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70±8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab600498.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the included studies.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:45 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2010 Focused Update of ESC Guidelines on device therapy in heart failure: an update of the 2008 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007 ESC guidelines for cardiac and resynchronization therapy. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 4 | 9 |
| 2024 October | 39 | 24 | 63 |
| 2024 September | 42 | 23 | 65 |
| 2024 August | 48 | 24 | 72 |
| 2024 July | 35 | 30 | 65 |
| 2024 June | 42 | 18 | 60 |
| 2024 May | 41 | 29 | 70 |
| 2024 April | 26 | 26 | 52 |
| 2024 March | 26 | 21 | 47 |
| 2024 February | 28 | 25 | 53 |
| 2024 January | 29 | 15 | 44 |
| 2023 December | 26 | 25 | 51 |
| 2023 November | 27 | 16 | 43 |
| 2023 October | 18 | 20 | 38 |
| 2023 September | 16 | 14 | 30 |
| 2023 August | 26 | 18 | 44 |
| 2023 July | 23 | 10 | 33 |
| 2023 June | 24 | 6 | 30 |
| 2023 May | 38 | 29 | 67 |
| 2023 April | 19 | 3 | 22 |
| 2023 March | 32 | 31 | 63 |
| 2023 February | 31 | 20 | 51 |
| 2023 January | 25 | 19 | 44 |
| 2022 December | 39 | 20 | 59 |
| 2022 November | 41 | 26 | 67 |
| 2022 October | 42 | 21 | 63 |
| 2022 September | 25 | 37 | 62 |
| 2022 August | 20 | 23 | 43 |
| 2022 July | 27 | 43 | 70 |
| 2022 June | 21 | 21 | 42 |
| 2022 May | 27 | 29 | 56 |
| 2022 April | 31 | 44 | 75 |
| 2022 March | 34 | 36 | 70 |
| 2022 February | 26 | 27 | 53 |
| 2022 January | 29 | 28 | 57 |
| 2021 December | 30 | 31 | 61 |
| 2021 November | 33 | 31 | 64 |
| 2021 October | 43 | 35 | 78 |
| 2021 September | 30 | 30 | 60 |
| 2021 August | 28 | 26 | 54 |
| 2021 July | 24 | 23 | 47 |
| 2021 June | 20 | 19 | 39 |
| 2021 May | 36 | 27 | 63 |
| 2021 April | 50 | 38 | 88 |
| 2021 March | 49 | 13 | 62 |
| 2021 February | 43 | 13 | 56 |
| 2021 January | 25 | 12 | 37 |
| 2020 December | 27 | 6 | 33 |
| 2020 November | 34 | 14 | 48 |
| 2020 October | 26 | 8 | 34 |
| 2020 September | 29 | 4 | 33 |
| 2020 August | 22 | 6 | 28 |
| 2020 July | 45 | 7 | 52 |
| 2020 June | 36 | 6 | 42 |
| 2020 May | 34 | 1 | 35 |
| 2020 April | 28 | 5 | 33 |
| 2020 March | 44 | 8 | 52 |
| 2020 February | 81 | 24 | 105 |
| 2020 January | 38 | 10 | 48 |
| 2019 December | 23 | 4 | 27 |
| 2019 November | 33 | 8 | 41 |
| 2019 October | 43 | 7 | 50 |
| 2019 September | 24 | 7 | 31 |
| 2019 August | 20 | 9 | 29 |
| 2019 July | 26 | 10 | 36 |
| 2019 June | 34 | 12 | 46 |
| 2019 May | 31 | 7 | 38 |
| 2019 April | 28 | 14 | 42 |
| 2019 March | 28 | 11 | 39 |
| 2019 February | 37 | 10 | 47 |
| 2019 January | 29 | 13 | 42 |
| 2018 December | 52 | 10 | 62 |
| 2018 November | 93 | 12 | 105 |
| 2018 October | 311 | 11 | 322 |
| 2018 September | 34 | 8 | 42 |
| 2018 August | 25 | 5 | 30 |
| 2018 July | 16 | 5 | 21 |
| 2018 June | 29 | 4 | 33 |
| 2018 May | 29 | 7 | 36 |
| 2018 April | 18 | 4 | 22 |
| 2018 March | 42 | 9 | 51 |
| 2018 February | 24 | 3 | 27 |
| 2018 January | 20 | 13 | 33 |
| 2017 December | 30 | 5 | 35 |
| 2017 November | 36 | 15 | 51 |
| 2017 October | 28 | 10 | 38 |
| 2017 September | 32 | 13 | 45 |
| 2017 August | 33 | 11 | 44 |
| 2017 July | 13 | 16 | 29 |
| 2017 June | 39 | 10 | 49 |
| 2017 May | 35 | 14 | 49 |
| 2017 April | 17 | 6 | 23 |
| 2017 March | 24 | 15 | 39 |
| 2017 February | 50 | 3 | 53 |
| 2017 January | 43 | 4 | 47 |
| 2016 December | 50 | 8 | 58 |
| 2016 November | 32 | 13 | 45 |
| 2016 October | 27 | 13 | 40 |
| 2016 September | 42 | 4 | 46 |
| 2016 August | 14 | 1 | 15 |
| 2016 July | 20 | 8 | 28 |
| 2016 June | 8 | 17 | 25 |
| 2016 May | 15 | 4 | 19 |
| 2016 April | 19 | 14 | 33 |
| 2016 March | 23 | 20 | 43 |
| 2016 February | 31 | 27 | 58 |
| 2016 January | 19 | 25 | 44 |
| 2015 December | 21 | 17 | 38 |
| 2015 November | 25 | 15 | 40 |
| 2015 October | 23 | 20 | 43 |
| 2015 September | 26 | 19 | 45 |
| 2015 August | 29 | 2 | 31 |
| 2015 July | 24 | 5 | 29 |
| 2015 June | 9 | 5 | 14 |
| 2015 May | 17 | 2 | 19 |
| 2015 April | 23 | 8 | 31 |
| 2015 March | 13 | 4 | 17 |
| 2015 February | 36 | 9 | 45 |
| 2015 January | 39 | 12 | 51 |
| 2014 December | 26 | 6 | 32 |
Show all
