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despite well-defined selection criteria&#44; the CRT non-response rate&#44; which reaches 30-40&#37; in major trials&#44; still represents a major concern&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Different variables have been studied to determine markers that might predict CRT response&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">3&#8211;12</span></a> Echocardiographic measures of ventricular dyssynchrony&#44; for example&#44; cannot identify responders&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Identifying genuine predictors of CRT non-response remains a challenge&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Aim</span><p id="par0025" class="elsevierStylePara elsevierViewall">The study&#39;s main purpose was to assess the baseline variables that might significantly influence an echocardiographic response to CRT in HF&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">We performed a prospective&#44; single-center&#44; cohort study in a central hospital with a multidisciplinary program for HF and CRT&#44; between 2012 and 2014&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study population</span><p id="par0035" class="elsevierStylePara elsevierViewall">Patients were consecutively selected for CRT according to current guidelines<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a>&#58; New York Heart Association &#40;NYHA&#41; class II-IV&#44; LV ejection fraction &#40;LVEF&#41; &#60;35&#37; and QRS &#62;120 ms&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Inability to perform cardiopulmonary exercise testing &#40;CPET&#41; for any reason&#44; and therapeutic interventions such as exercise training that might confound the results&#44; were considered exclusion criteria&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study protocol</span><p id="par0045" class="elsevierStylePara elsevierViewall">Baseline clinical assessment and testing were performed before CRT device implantation&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">An outpatient visit and echocardiogram were scheduled at six months to assess clinical effects and LV reverse remodeling&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">A clinical response to CRT was defined as improvement of at least one NYHA functional class and an echocardiographic response as a minimum absolute increase of 5&#37; in LVEF&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Clinical and electrocardiographic parameters</span><p id="par0060" class="elsevierStylePara elsevierViewall">Age&#44; gender&#44; body mass index and HF etiology were recorded and cardiac rhythm&#44; heart rate &#40;HR&#41;&#44; QRS duration and morphology were determined on the electrocardiogram&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Blood collection and analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Blood samples were collected in a fasting state for assessment of complete blood count&#44; creatinine&#44; C-reactive protein and brain natriuretic peptide&#44; measured by standard techniques&#46; Creatinine clearance was calculated by the Cockcroft-Gault formula<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a>&#58;<elsevierMultimedia ident="eq0005"></elsevierMultimedia></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Cardiopulmonary exercise testing</span><p id="par0070" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing &#40;CPET&#41; was performed under medication using the modified Bruce protocol on a Mortara Multisyn EA 190 treadmill&#44; symptom-limited&#44; with breath-by-breath gas exchange measurements &#40;Innocor&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">CPET duration&#44; peak oxygen uptake &#40;peak VO<span class="elsevierStyleInf">2</span>&#41;&#44; percentage of maximum predicted oxygen uptake&#44; exercise ventilatory efficiency&#44; minute ventilation&#47;carbon dioxide production slope &#40;VE&#47;VCO<span class="elsevierStyleInf">2</span> slope&#41;&#44; anaerobic threshold&#44; peak HR&#44; baseline HR&#44; percentage of maximum predicted HR&#44; double product variation&#44; and difference between peak HR and heart rate recovery index &#40;HRRI&#41;&#44; defined as the difference between peak HR and HR at first minute of recovery&#44; were determined&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">24-h Holter study</span><p id="par0080" class="elsevierStylePara elsevierViewall">Twenty-four-hour Holter study &#40;Burdick Vision 5L Holter system&#41; included heart rate variation analysis for assessment of the autonomic nervous system&#46; From the time series of NN intervals&#44; a time domain measure&#44; the standard deviation of all N-N intervals &#40;SDNN&#41; was calculated over the 24-h recordings&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Endothelial function study</span><p id="par0085" class="elsevierStylePara elsevierViewall">Endothelial function was assessed by digital tonometry &#40;Itamar EndoPAT 2000&#41; to study arterial elasticity&#44; with calculation of the reactive hyperemia index &#40;RHI&#41; to determine peripheral arterial tone&#44; according to the EndoPAT protocol&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Echocardiographic study</span><p id="par0090" class="elsevierStylePara elsevierViewall">Transthoracic echocardiography&#44; including tissue Doppler imaging &#40;TDI&#41; and strain analysis &#40;GE Vivid 9&#41;&#44; was performed to assess LV end-diastolic and end-systolic volumes &#40;LVEDV and LVESV&#44; respectively&#41;&#44; LV mass &#40;LVM&#41;&#44; LVEF &#40;by Simpson&#39;s method&#41;&#44; global longitudinal strain &#40;GLS&#41;&#44; LV inflow E wave and A wave velocities &#40;E and A&#44; respectively&#41;&#44; E&#47;A ratio&#44; E&#47;mean e&#8217; wave ratio &#40;E&#47;e&#8217;&#41; on mitral annular TDI&#44; tricuspid annular plane systolic excursion &#40;TAPSE&#41;&#44; left and right atrial volumes &#40;LAV and RAV&#44; respectively&#41; and pulmonary artery systolic pressure &#40;PASP&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The study protocol was approved by the hospital&#39;s ethics committee and complies with the Declaration of Helsinki&#46; Written informed consent was obtained from all patients&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Statistical analysis</span><p id="par0100" class="elsevierStylePara elsevierViewall">An exploratory analysis was carried out for all variables&#46; Categorical data were presented as frequencies and percentages&#44; and continuous variables as means or medians and standard deviation or interquartile range &#40;25th-75th percentile&#41;&#44; as appropriate&#46; Chi-square&#44; Fisher&#39;s exact and non-parametric Mann-Whitney tests were used&#44; as appropriate&#46; Multivariate analysis was performed using logistic regression models&#59; all variables with a p-value &#60;0&#46;15 in univariate analysis were considered&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The Hosmer-Lemeshow goodness-of-fit test was used&#44; with a high p-value indicating that the model is well calibrated&#46; The Box-Tidwell transformation was used to test the assumption of linearity in the logit of continuous variables and 95&#37; confidence intervals &#40;CI&#41; were calculated as required&#46; The level of significance was considered to be &#945;&#61;0&#46;05&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">All data were analyzed using SPSS 22&#46;0 &#40;IBM SPSS Statistics for Windows&#44; Armonk&#44; NY&#58; IBM Corp&#46;&#41;&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Results</span><p id="par0115" class="elsevierStylePara elsevierViewall">Of the 116 consecutive patients referred for CRT&#44; 79 &#40;68&#46;4&#37; male&#44; 24&#37; with ischemic etiology&#41; were included in the study&#46; Four patients were lost to follow-up and 33 were excluded because they were referred for exercise training after CRT or refused to participate in the study&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Patients&#8217; baseline characteristics are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">At six months&#44; 54 patients &#40;68&#46;3&#37;&#41; were clinical responders and 51 &#40;64&#46;6&#37;&#41; were echocardiographic responders&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Of the 54 clinical responders&#44; 10 &#40;18&#46;5&#37;&#41; did not respond by echocardiographic criteria and of the 51 echocardiographic responders&#44; six &#40;11&#46;7&#37;&#41; did not improve clinically&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Seventy-seven patients &#40;97&#46;5&#37;&#41; had complete left bundle branch block &#40;LBBB&#41;&#44; 50 of them echocardiographic responders &#40;64&#37;&#41;&#46; Two patients had complete right bundle branch block &#40;RBBB&#41;&#44; one responding to CRT&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Univariate analysis results for baseline variables are summarized in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">Serum creatinine and TAPSE values were associated with echocardiographic response &#40;p&#61;0&#46;031 and p&#61;0&#46;045&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figures 1 and 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">On multivariate analysis only TAPSE was independently associated with echocardiographic response &#40;odds ratio 1&#46;13&#59; 95&#37; CI&#58; 1&#46;02-1&#46;26&#59; p&#61;0&#46;020&#41;&#46; TAPSE &#60;15 was associated with non-response &#40;p&#61;0&#46;0052&#41;&#46; Eight patients &#40;10&#37;&#41; had TAPSE &#60;14 mm&#44; seven of whom &#40;87&#46;5&#37;&#41; were non-responders&#46; There were no responders &#40;and two non-responders&#41; with TAPSE &#60;10 mm&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0155" class="elsevierStylePara elsevierViewall">There is considerable disagreement in the literature regarding the definition of a CRT responder&#44; as shown by Fornwalt et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">17</span></a> in a 26 CRT trials analysis&#44; in which the level of agreement between primary endpoints was poor&#44; with the proportion of patients defined as having a positive CRT response ranging from 32&#37; to 91&#37;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Clinical response by itself is non-specific&#44; largely subjective and too dependent on different variables&#46; On the other hand&#44; LVEF&#44; although influenced by preload&#44; afterload&#44; HR&#44; and mitral regurgitation&#44; is the most widely used echocardiographic parameter and an important index of LV function&#44; due to its clinical prognostic value&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">18</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">In our study&#44; echocardiographic response was defined as &#8805;5&#37; absolute improvement in LVEF&#44; in order to include the majority of responders&#46; Using a larger LVEF increase would restrict the range of responders&#44; improving response specificity&#44; but decreasing sensitivity&#46; There is still discussion concerning the best LVEF change to identify those who are really responding&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">17</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">We observed clinical response in 68&#46;3&#37; of patients and echocardiographic response in 64&#46;6&#37; &#40;non-response in 35&#46;4&#37;&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Demographic and clinical variables did not differ between responders and non-responders&#46; Other investigators also did not find gender or etiology&#44; adjusted to LV volumes&#44; to be independent predictors&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a> On the other hand&#44; sub-analyses of randomized clinical trials have suggested that CRT has greater beneficial effects on LV function and&#47;or prognosis in females<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">6&#44;9&#44;10&#44;19</span></a> and in nonischemic etiology&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">7&#44;11</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Of our patients&#44; 34&#37; were in atrial fibrillation&#44; the most common arrhythmia in HF and associated with worse prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">20</span></a> It is unclear if&#44; correcting for age and comorbidity&#44; the prognosis for patients in AF is in fact worse<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">21</span></a> or whether it is only a marker of more severe disease&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">We did not find a significant relation between QRS duration and response&#46; Previous randomized controlled trials did not clearly show QRS duration as a predictive factor&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">22&#8211;24</span></a> However&#44; in a recent meta-analysis including five randomized trials&#44; QRS duration was a powerful predictor of CRT effectiveness&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">25</span></a> Moreover&#44; a sub-analysis of the MADIT-CRT trial associated longer QRS &#40;&#62;150 ms&#41; with benefits of CRT in LV function&#44; morbidity and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">7</span></a> The REVERSE study confirmed the importance of QRS duration and LBBB pattern in CRT outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">26</span></a> With regard to our study&#44; the sample size&#44; the higher percentage of patients with nonischemic etiology and mean QRS &#62;150 ms influenced our results&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">In our population&#44; only two patients &#40;2&#46;5&#37;&#41; had RBBB and&#44; although these are generally not expected to benefit from CRT&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a> one was a responder&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The only laboratory parameter with statistical significance in univariate analysis was serum creatinine &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#44; although creatinine clearance<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a> showed no association with CRT response&#46; Although lower creatinine levels were seen in patients who responded to CRT &#40;p&#61;0&#46;045&#41;&#44; multivariate analysis did not demonstrate an independent association with response&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">In contrast to our results&#44; Fung et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">27</span></a> in a population with renal insufficiency&#44; showed that responders had worse baseline renal function&#46; In our study&#44; most patients had normal renal function or mild dysfunction &#40;34&#46;2&#37; and 36&#46;6&#37;&#44; respectively&#41;&#44; with only two patients &#40;0&#46;25&#37;&#41; having severe renal dysfunction as defined by the guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a> Different populations in the two studies may have contributed to the difference in results&#46; The relation of serum creatinine and creatinine clearance to response and outcome remains controversial&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">29</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">CPET&#44; Holter and peripheral arterial tonometry variables could not identify echocardiographic responders&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Non-responders had greater baseline LV volume&#44; LV mass and left atrial volume and lower LVEF and GLS&#44; although the differences did not reach statistical significance&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">In the literature&#44; there have sometimes been conflicting data on the impact of baseline LV dimensions on CRT response&#44; depending on study populations&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">3&#44;9&#44;10</span></a> Park et al&#46; demonstrated that baseline LV volume was a predictor of echocardiographic CRT response&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a> Rickard et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">3</span></a> showed that the smaller the LV size&#44; the greater the improvement in LVEF and all-cause mortality after CRT&#46; In contrast&#44; the MADIT-CRT trial<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a> showed that a larger LV was associated with echocardiographic response&#44; and a sub-analysis of PROSPECT<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">9</span></a> found no difference in responders&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Regarding the predictive value of baseline LVEF&#44; we found no relation with less severe patients&#44; unlike in the MADIT sub-analysis&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">30</span></a> in which patients with better LVEF had a greater response&#46; However&#44; because different inclusion criteria and definitions of CRT response were used&#44; direct comparisons of results are difficult or impossible&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">The right ventricle has always been considered the &#8216;poor relative&#8217; of the left ventricle&#44; although its importance in exercise tolerance and prognosis has been demonstrated&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">31</span></a> Because CRT was developed to improve LV synchronicity and function&#44; its effects on right ventricular &#40;RV&#41; function have not been fully examined&#44; although some studies have shown benefit&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">9&#44;32</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">An important issue concerns the potential role of baseline RV dysfunction in LV reverse remodeling after CRT&#46; In our study&#44; TAPSE &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>&#41;&#44; a marker of overall RV function<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">33</span></a> and an independent predictor of mortality in HF patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">34&#44;35</span></a> showed an association with echocardiographic response to CRT by multivariate analysis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>&#41;&#44; with responders having higher baseline TAPSE values&#46; RV dysfunction was present in 7&#37; of responders compared to 36&#37; of non-responders&#44; and TAPSE &#60;15 mm was statistically associated with non-response&#44; although TAPSE &#60;17 mm &#40;the cut-point for RV dysfunction in clinical practice&#41; showed no association&#46; There were no responders with TAPSE &#60;10 mm&#46; This means that only moderate or severe RV dysfunction was related to CRT non-response&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0235" class="elsevierStylePara elsevierViewall">Our results are in agreement with Capelli et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">36</span></a> who demonstrated that CRT induces both RV and LV reverse remodeling&#44; and is more effective in patients with higher TAPSE&#46; In addition&#44; Scuteri et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">32</span></a> concluded that low baseline TAPSE was associated with poor response and adverse prognosis&#44; while Sade et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">37</span></a> showed that preserved RV function is an independent predictor of long-term event-free survival after CRT&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">On the other hand&#44; a sub-analysis of the REVERSE study<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">38</span></a> demonstrated that while LV reverse remodeling was greater in patients with TAPSE &#62;14 mm&#44; the difference was not statistically significant&#46; Also&#44; in CARE-HF&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">39</span></a> patients with severely reduced TAPSE &#40;&#60;14 mm&#41; had a significantly lower response rate&#44; though this association was not strong enough to consider TAPSE an independent predictor&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Some of the uncertainty regarding whether TAPSE is an independent predictor of CRT response may result from differences in study populations and particularly in the criteria used to define CRT response&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">In conclusion&#44; in this advanced HF population&#44; TAPSE was the only independent predictor of CRT response regarding all the analyzed variables&#46; RV function clearly has a role in the selection of candidates for CRT&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Study limitations</span><p id="par0255" class="elsevierStylePara elsevierViewall">The study was performed in a single center&#44; and the sample size was moderate&#44; mostly of patients with non-ischemic etiology referred for CRT&#46; Follow-up duration was only six months&#44; even though a small percentage of patients can be late responders&#46; These results need to be reproduced in a larger study&#44; separating patients with ischemic and non-ischemic etiology&#44; with a longer follow-up period&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Ethical disclosures</span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Protection of human and animal subjects</span><p id="par0260" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association &#40;Declaration of Helsinki&#41;&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Confidentiality of data</span><p id="par0265" 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="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Right to privacy and informed consent</span><p id="par0270" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Funding</span><p id="par0275" class="elsevierStylePara elsevierViewall">This work was supported by research grant <span class="elsevierStyleGrantNumber" refid="gs1">PTDC&#47;DES&#47;120249&#47;2010</span> from the <span class="elsevierStyleGrantSponsor" id="gs1">Foundation for Science and Technology &#40;FCT&#41;</span>&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conflicts of interest</span><p id="par0280" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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              "titulo" => "Echocardiographic study"
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          "titulo" => "Results"
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          "titulo" => "Discussion"
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          "titulo" => "Study limitations"
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          "titulo" => "Ethical disclosures"
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              "titulo" => "Protection of human and animal subjects"
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              "titulo" => "Confidentiality of data"
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              "titulo" => "Right to privacy and informed consent"
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          "titulo" => "Funding"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-03-24"
    "fechaAceptado" => "2016-10-11"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec853565"
          "palabras" => array:4 [
            0 => "Chronic heart failure"
            1 => "Cardiac resynchronization therapy"
            2 => "Responder"
            3 => "Predictors"
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          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec853566"
          "palabras" => array:4 [
            0 => "Insufici&#234;ncia card&#237;aca cr&#243;nica"
            1 => "Terap&#234;utica de ressincroniza&#231;&#227;o card&#237;aca"
            2 => "Respondedor"
            3 => "Fatores preditivos"
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    "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">Cardiac resynchronization therapy &#40;CRT&#41; has modified the prognosis of chronic heart failure &#40;HF&#41; with left ventricular systolic dysfunction&#46; However&#44; 30&#37; of patients do not have a favorable response&#46; The big question is how to determine predictors of response&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Aims</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To identify baseline characteristics that might influence echocardiographic response to CRT&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods and Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We performed a prospective single-center hospital-based cohort study of consecutive HF patients selected to CRT &#40;NYHA class II-IV&#44; left ventricular ejection fraction &#40;LVEF&#41; &#60;35&#37; and QRS complex &#8805;120 ms&#41;&#46; Responders were defined as those with a &#8805;5&#37; absolute increase in LVEF at six months&#46; Clinical&#44; electrocardiographic&#44; laboratory&#44; echocardiographic&#44; autonomic&#44; endothelial and cardiopulmonary function parameters were assessed before CRT device implantation&#46; Logistic regression models were used&#46; Seventy-nine patients were included&#44; 54 male &#40;68&#46;4&#37;&#41;&#44; age 68&#46;1 years &#40;standard deviation 10&#46;2&#41;&#44; 19 with ischemic etiology &#40;24&#37;&#41;&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">At six months&#44; 51 patients &#40;64&#46;6&#37;&#41; were considered responders&#46; Although by univariate analysis baseline tricuspid annular plane systolic excursion &#40;TAPSE&#41; and serum creatinine were significantly different in responders&#44; on multivariate analysis only TAPSE was independently associated with response&#44; with higher values predicting a positive response to CRT &#40;OR&#61;1&#46;13&#59; 95&#37; CI&#58; 1&#46;02-1&#46;26&#59; p&#61;0&#46;020&#41;&#46; TAPSE &#8805;15 mm was strongly associated with response&#44; and TAPSE &#60;15 mm with non-response &#40;p&#61;0&#46;005&#41;&#46; Responders had no TAPSE values below 10 mm&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">From a range of clinical and technical baseline characteristics&#44; multivariate analysis only identified TAPSE as an independent predictor of CRT response&#44; with TAPSE &#60;15 mm associated with non-response&#46; This study highlights the importance of right ventricular dysfunction in CRT response&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">ClinicalTrials&#46;gov identifier&#58; <span class="elsevierStyleInterRef" id="intr0005" href="ctgov:NCT02413151">NCT02413151</span>&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
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            "titulo" => "Introduction"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Aims"
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      "pt" => array:3 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introdu&#231;&#227;o</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A terap&#234;utica de ressincroniza&#231;&#227;o card&#237;aca &#40;CRT&#41; modificou o progn&#243;stico da insufici&#234;ncia card&#237;aca &#40;HF&#41; com disfun&#231;&#227;o ventricular esquerda&#46; Contudo&#44; 30&#37; dos doentes n&#227;o s&#227;o respondedores&#46; A grande quest&#227;o est&#225; em identificar preditores de resposta&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Identificar caracter&#237;sticas basais que podem influenciar a resposta ecocardiogr&#225;fica &#224; CRT&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Metodologia e resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Estudo <span class="elsevierStyleItalic">cohort</span> prospetivo&#44; unic&#234;ntrico&#44; hospitalar&#44; de doentes consecutivos com HF selecionados para CRT &#40;classes II-IV NYHA&#44; fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda &#60;35&#37; e QRS&#8805;120 mseg&#41;&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Os respondedores foram definidos por aumento absoluto de fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda &#8805;5&#37; aos 6 meses&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Antes da implanta&#231;&#227;o do ressincronizador&#44; foram avaliados par&#226;metros cl&#237;nicos&#44; eletrocardiogr&#225;ficos&#44; laboratoriais&#44; ecocardiogr&#225;ficos&#44; auton&#243;micos&#44; endoteliais e funcionais cardiorrespirat&#243;rios&#46; Utilizaram-se modelos de regress&#227;o log&#237;stica&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Inclu&#237;ram-se 79 doentes&#44; 54 masculinos &#40;68&#44;4&#37;&#41;&#44; idade 68&#44;1 &#40;SD&#61;10&#44;2&#41; anos&#44; 19 isqu&#233;micos &#40;24&#37;&#41;&#46; Aos 6 meses&#44; consideraram-se respondedores 51 doentes &#40;64&#44;6&#37;&#41;&#46; Apesar de&#44; por an&#225;lise univari&#225;vel&#44; a excurs&#227;o sist&#243;lica do plano do anel tric&#250;spide &#40;TAPSE&#41; e a creatinina s&#233;rica serem significativamente diferentes nos respondedores&#44; em an&#225;lise multivari&#225;vel&#44; apenas TAPSE foi independentemente associada a resposta&#44; sendo valores superiores preditivos de resposta positiva &#224; CRT &#40;OR&#61;1&#44;13&#59; 95&#37; CI&#58; 1&#44;02-1&#44;26&#59; p&#61;0&#44;020&#41;&#46; A TAPSE&#8805;15 mm teve forte associa&#231;&#227;o com resposta&#44; enquanto TAPSE&#60;15 mm a n&#227;o resposta &#40;p&#61;0&#44;005&#41;&#46; Respondedores n&#227;o tiveram valores de TAPSE inferiores a 10 mm&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#227;o</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">De um conjunto de caracter&#237;sticas basais cl&#237;nicas e t&#233;cnicas&#44; a an&#225;lise multivari&#225;vel apenas identificou TAPSE como preditor independente de resposta a CRT&#44; associando TAPSE&#60;15 mm a n&#227;o resposta&#46; Este estudo destaca a import&#226;ncia da disfun&#231;&#227;o ventricular direita na resposta &#224; CRT&#46;</p><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">ClinicalTrials&#46;gov identifier&#58; NCT02413151&#46;</p></span>"
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Creatinine distribution according to echocardiographic response to cardiac resynchronization therapy&#46;</p>"
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          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">ACEIs&#47;ARBs&#58; angiotensin-converting enzyme inhibitors&#47;angiotensin receptor blockers&#59; AF&#58; atrial fibrillation&#59; BMI&#58; body mass index&#44; in kg&#47;m<span class="elsevierStyleSup">2</span>&#59; BNP&#58; B-type natriuretic peptide&#59; CrCl&#58; creatinine clearance &#40;Cockcroft-Gault formula&#41;&#59; CPET&#58; cardiopulmonary exercise testing&#59; CRP&#58; C-reactive protein&#59; GLS&#58; global longitudinal strain&#59; HR&#58; heart rate&#59; HRRI&#58; heart rate recovery index&#59; IQR&#58; interquartile range &#40;25th-75th percentile&#41;&#59; LAV&#58; left atrial volume&#59; LBBB&#58; left bundle branch block&#59; LVEF&#58; left ventricular ejection fraction&#59; LVEDV&#58; left ventricular end-diastolic volume&#59; LVESV&#58; left ventricular end-systolic volume&#59; LVM&#58; left ventricular mass&#59; NYHA&#58; New York Heart Association&#59; PASP&#58; pulmonary artery systolic pressure&#59; peak VO<span class="elsevierStyleInf">2</span>&#58; peak oxygen consumption&#59; RAV&#58; right atrial volume&#59; RBBB&#58; right bundle branch block&#59; SD&#58; standard deviation&#59; TAPSE&#58; tricuspid annular plane systolic excursion&#59; VE&#47;VCO<span class="elsevierStyleInf">2</span>&#58; minute ventilation&#47;carbon dioxide production&#46;</p>"
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                  <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">Variables&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">n&#61;79&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">Mean age&#44; years &#40;SD&#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">68&#46;1 &#40;10&#46;2&#41;&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">Female gender&#44; n &#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">25 &#40;31&#46;6&#41;&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">Mean BMI &#40;SD&#41; &#40;min-max&#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">27&#46;1 &#40;4&#46;1&#41; &#40;18&#46;0-36&#46;8&#41;&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">Ischemic etiology&#44; n &#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">19 &#40;24&#46;0&#41;&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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">NYHA class&#44; n &#40;&#37;&#41;</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>II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23 &#40;29&#46;1&#41;&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>III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">51 &#40;64&#46;5&#41;&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>IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;6&#46;3&#41;&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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Medication&#44; &#37;</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>Diuretics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">94&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>Beta-blockers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">89&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>ACEIs&#47;ARBs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90&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>Anticoagulants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73&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="2" 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="2" align="left" valign="top"><span class="elsevierStyleItalic">Rhythm&#44; n &#40;&#37;&#41;</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>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">49 &#40;62&#46;0&#41;&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>AF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27 &#40;34&#46;2&#41;&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>Pacing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;3&#46;8&#41;&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="2" 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">Median QRS interval&#44; ms &#40;IQR&#41; &#40;min-max&#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">140&#46;0 &#40;120&#46;0-160&#46;0&#41;&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="2" align="left" valign="top"><span class="elsevierStyleItalic">Conduction disturbance morphology&#44; n &#40;&#37;&#41;</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">77 &#40;97&#46;5&#37;&#41;&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>RBBB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;2&#46;5&#37;&#41;&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="2" 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">Mean resting HR&#44; bpm &#40;SD&#41; &#40;min-max&#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">79&#46;5 &#40;16&#46;5&#41; &#40;45&#46;0-126&#46;0&#41;&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">Mean hemoglobin&#44; g&#47;dl &#40;SD&#41; &#40;min-max&#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">13&#46;2 &#40;1&#46;6&#41; &#40;8&#46;7-16&#46;1&#41;&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">Median creatinine&#44; mg&#47;dl &#40;IQR&#41; &#40;min-max&#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">1&#46;0 &#40;0&#46;8-1&#46;3&#41; &#40;0&#46;6-2&#46;7&#41;&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="2" 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">Median CrCl&#44; ml&#47;min &#40;IQR&#41; &#40;min-max&#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">68&#46;5 &#40;53&#46;9-91&#46;5&#41; &#40;22&#46;7-146&#46;3&#41;&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>&#62;90&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27 &#40;34&#46;2&#41;&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>60-89&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29 &#40;36&#46;7&#41;&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>30-59&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21 &#40;26&#46;6&#41;&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>&#60;30&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;0&#46;25&#41;&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="2" 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">Median CRP &#40;mg&#47;dl&#41; &#40;IQR&#41; &#40;min-max&#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">2&#46;4 &#40;1&#46;3-6&#46;5&#41; &#40;0&#46;2-75&#46;4&#41;&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">Median BNP&#44; pg&#47;ml &#40;IQR&#41; &#40;min-max&#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">286&#46;0 &#40;132&#46;0-782&#46;0&#41; &#40;31&#46;0-2787&#46;0&#41;&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">HRRI&#44; bpm &#40;SD&#41; &#40;min-max&#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">15&#46;5 &#40;9&#46;0&#41; &#40;0&#46;0-37&#46;0&#41;&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">Mean CPET duration&#44; msec &#40;SD&#41; &#40;min-max&#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">381&#46;4 &#40;248&#46;4&#41; &#40;30&#46;0-947&#46;0&#41;&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">Mean peak VO</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#44; ml&#47;min&#47;kg &#40;SD&#41; &#40;min-max&#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">15&#46;1 &#40;5&#46;5&#41; &#40;5&#46;1-31&#46;6&#41;&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">Median VE&#47;VCO</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">slope &#40;IQR&#41; &#40;min-max&#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">37&#46;2 &#40;29&#46;8-46&#46;4&#41; &#40;21&#46;0-71&#46;0&#41;&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">Mean LVEF&#44; &#37; &#40;SD&#41; &#40;min-max&#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">26&#46;1 &#40;7&#46;0&#41; &#40;11&#46;0-34&#46;0&#41;&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">Mean LVESV&#44; ml &#40;SD&#41; &#40;min-max&#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">152&#46;8 &#40;63&#46;8&#41; &#40;91&#46;0-322&#46;0&#41;&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">Mean LVEDV&#44; ml &#40;SD&#41; &#40;min-max&#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">212&#46;2 &#40;68&#46;3&#41; &#40;116&#46;0-420&#46;0&#41;&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">E&#62;A&#44; n &#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">26&#47;49 &#40;53&#46;0&#41;&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">Mean E&#47;e&#8217; ratio &#40;SD&#41; &#40;min-max&#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">18&#46;8 &#40;9&#46;6&#41; &#40;4&#46;0-46&#46;0&#41;&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">Mean GLS&#44; &#37; &#40;SD&#41; &#40;min-max&#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">-6&#46;4 &#40;3&#46;4&#41; &#40;-18&#46;3-&#91;-1&#46;0&#93;&#41;&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">Mean LVM&#44; g &#40;SD&#41; &#40;min-max&#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">351&#46;5 &#40;114&#46;5&#41; &#40;129&#46;0-637&#46;0&#41;&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">Median LAV&#44; ml &#40;IQR&#41; &#40;min-max&#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">90&#46;0 &#40;48&#46;3-126&#46;5&#41; &#40;22&#46;0-222&#46;0&#41;&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">Median TAPSE&#44; mm &#40;IQR&#41; &#40;min-max&#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">19&#46;0 &#40;16&#46;0-25&#46;0&#41; &#40;5&#46;0-32&#46;0&#41;&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">Median RAV&#44; ml &#40;IQR&#41; &#40;min-max&#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">34&#46;0 &#40;20&#46;5-54&#46;5&#41; &#40;9&#46;0-254&#46;0&#41;&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">Mean PASP&#44; mmHg &#40;SD&#41; &#40;min-max&#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">40&#46;6 &#40;11&#46;7&#41; &#40;20&#46;0-71&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">ANS&#58; autonomic nervous system&#59; BMI&#58; body mass index&#44; in kg&#47;m<span class="elsevierStyleSup">2</span>&#59; BNP&#58; B-type natriuretic peptide&#59; CrCl&#58; creatinine clearance &#40;Cockcroft-Gault formula&#41;&#59; CPET&#58; cardiopulmonary exercise testing&#59; CRP&#58; C-reactive protein&#59; GLS&#58; global longitudinal strain&#59; HR&#58; heart rate&#59; HRRI&#58; heart rate recovery index&#59; IQR&#58; interquartile range &#40;25th-75th percentile&#41;&#59; LAV&#58; left atrial volume&#59; LVEF&#58; left ventricular ejection fraction&#59; LVEDV&#58; left ventricular end-diastolic volume&#59; LVESV&#58; left ventricular end-systolic volume&#59; LVM&#58; left ventricular mass&#59; PASP&#58; pulmonary artery systolic pressure&#59; peak VO<span class="elsevierStyleInf">2</span>&#58; peak oxygen consumption&#59; RAV&#58; right atrial volume&#59; RV&#58; right ventricular&#59; SD&#58; standard deviation&#59; TAPSE&#58; tricuspid annular plane systolic excursion&#59; VE&#47;VCO<span class="elsevierStyleInf">2</span>&#58; minute ventilation&#47;carbon dioxide production&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8805;5&#37; LVEF increase &#40;n&#61;51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#60;5&#37; LVEF increase &#40;n&#61;28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">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" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Clinical variables</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>Mean age&#44; years &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">68&#46;3 &#40;11&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&#46;7 &#40;8&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;571&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>Female gender&#44; n &#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">19 &#40;37&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;21&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;148&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 etiology&#44; n &#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">13 &#40;25&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;26&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;812&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>Mean BMI &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;1 &#40;4&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;0 &#40;4&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;975&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>Median QRS interval&#44; ms &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">135&#46;0 &#40;120&#46;0-160&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">145&#46;0 &#40;127&#46;5-152&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;865&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&#44; n &#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">34 &#40;66&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17 &#40;60&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;416&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>Mean resting HR&#44; bpm &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81&#46;5 &#40;15&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">75&#46;8 &#40;18&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;101&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="4" 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="4" align="left" valign="top"><span class="elsevierStyleItalic">Laboratory variables</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>Mean hemoglobin&#44; g&#47;dl &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;0 &#40;1&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;4 &#40;1&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;447&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>Median creatinine&#44; mg&#47;dl &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;9 &#40;0&#46;7-1&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;1 &#40;0&#46;9-1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;045&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>Median CrCl&#44; ml&#47;min &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">71&#46;6 &#40;55&#46;8-95&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65&#46;3 &#40;52&#46;1-76&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;191&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>Median CRP &#40;mg&#47;dl&#41; &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;3 &#40;1&#46;3-5&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;95 &#40;1&#46;4-9&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;216&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>Median BNP&#44; pg&#47;ml &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">284&#46;0 &#40;97&#46;5-936&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">324&#46;5 &#40;219&#46;5-537&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;673&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="4" 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="4" align="left" valign="top"><span class="elsevierStyleItalic">ANS function</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>Median SDNN &#40;P25-P75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">120&#46;0 &#40;83&#46;5-182&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">101&#46;0 &#40;74&#46;0-145&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;324&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>Mean HRRI&#44; bpm &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;5 &#40;8&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;5 &#40;9&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;721&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="4" 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="4" align="left" valign="top"><span class="elsevierStyleItalic">CPET variables</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>Mean peak VO<span class="elsevierStyleInf">2</span>&#44; ml&#47;min&#47;kg &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#46;7 &#40;5&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;9 &#40;5&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;387&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>Mean CPET duration&#44; msec &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">375&#46;4 &#40;253&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">393&#46;7 &#40;242&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;661&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>Median VE&#47;VCO<span class="elsevierStyleInf">2</span> slope &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#46;6 &#40;30&#46;1-44&#46;1&#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;4 &#40;28&#46;3-47&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;992&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="4" 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="4" align="left" valign="top"><span class="elsevierStyleItalic">Endothelial function</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>Median RHI &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;5 &#40;1&#46;3-1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;5 &#40;1&#46;3-1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;508&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="4" 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="4" align="left" valign="top"><span class="elsevierStyleItalic">LV function</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>Mean LVEF&#44; &#37; &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#46;1 &#40;7&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#46;9 &#40;6&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;930&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>Mean LVEDV&#44; ml &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">208&#46;6 &#40;72&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">218&#46;6 &#40;60&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;351&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>Mean LVESV&#44; ml &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">147&#46;2 &#40;67&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">162&#46;8 &#40;55&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;216&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>Mean LVM&#44; g &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">348&#46;9 &#40;123&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">357&#46;4 &#40;92&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;607&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>Mean GLS&#44; &#37; &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">-6&#46;7 &#40;3&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">-5&#46;9 &#40;2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;566&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>E&#62;A&#44; n &#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">16 &#40;48&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;58&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;488&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>Mean E&#47;e&#8217; ratio &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#46;6 &#40;10&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;0 &#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;513&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>Median LAV&#44; ml &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&#46;0 &#40;41&#46;0-123&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">101&#46;0 &#40;64&#46;0-140&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;172&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="4" 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="4" align="left" valign="top"><span class="elsevierStyleItalic">RV function</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>Median RAV&#44; ml &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&#46;0 &#40;21&#46;8-58&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&#46;0 &#40;19&#46;0-52&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;542&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>Median TAPSE&#44; mm &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#46;9 &#40;16&#46;7-26&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&#46;0 &#40;12&#46;8-20&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;031&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>TAPSE &#62;17 mm&#44; n &#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">31 &#40;60&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;42&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;119&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>TAPSE &#62;15 mm&#44; n &#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">47 &#40;92&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18 &#40;64&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;005&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>Mean PASP&#44; mmHg &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&#46;4 &#40;12&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#46;6 &#40;9&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;189&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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