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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThis article presents the results of a pooled analysis that addressed several questions concerning worsening heart failure (HF). The meta-analysis was based on patient-level data (n=3733) from 4 studies: the RELAX-AHF [Relaxin for the Treatment of Acute Heart Failure; Teerlink JR et al. \u003Cem\u003ELancet\u003C\/em\u003E 2013], the Pre-RELAX-AHF [Teerlink JR et al. \u003Cem\u003ELancet\u003C\/em\u003E 2009], the PROTECT pilot study [Pro-BNP Outpatient Tailored Chronic Heart Failure Therapy; Cotter G et al. \u003Cem\u003EJ Cardiac Fail\u003C\/em\u003E 2008], and PROTECT [Massie BM et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHeart Failure\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology \u0026amp; Cardiovascular Medicine\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHeart Failure\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EBeth A. Davison, PhD, Momentum Research, Inc., Durham, North Carolina, USA, presented the results of a pooled analysis that addressed several questions concerning worsening heart failure (HF). The authors attempted to better understand which baseline characteristics are associated with the occurrence of worsening HF among those hospitalized for acute heart failure (AHF). Worsening HF was defined as worsening signs and symptoms of HF during an admission for AHF requiring rescue therapy with intravenous (IV) medications or mechanical support. In addition, the researchers sought to describe the relationship between worsening HF and adverse outcomes, the mechanism by which worsening HF results in poor outcomes, and whether worsening HF treated with therapies other than IV loop diuretics confers a different risk from worsening HF treated with IV loop diuretics alone.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EThe meta-analysis was based on patient-level data (n=3733) from 4 studies: the RELAX-AHF [Relaxin for the Treatment of Acute Heart Failure; Teerlink JR et al. \u003Cem\u003ELancet\u003C\/em\u003E 2013], the Pre-RELAX-AHF [Teerlink JR et al. \u003Cem\u003ELancet\u003C\/em\u003E 2009], the PROTECT pilot study [Pro-BNP Outpatient Tailored Chronic Heart Failure Therapy; Cotter G et al. \u003Cem\u003EJ Cardiac Fail\u003C\/em\u003E 2008], and PROTECT [Massie BM et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010]. The authors created multivariable models of worsening HF (through 5 days after baseline) and other outcomes developed in the pooled database. Associations of worsening HF with downstream clinical outcomes were estimated, with adjustment for covariates found in the models to be associated with these outcomes. Estimates were stratified by study. Differences in the patient populations were minor and reflected mainly the differences in eligibility criteria. Subjects in the 2 PROTECT studies had lower systolic blood pressure, a slightly higher proportion of patients with a recent history of HF, and somewhat worse renal function compared with those in the 2 RELAX studies. Approximately 12% of patients (range, 9.5% to 14.5%) overall had worsening HF through Day 5; the length of stay was about 10 days; and an average of 18% of patients (range, 9.8% to 24.3%) experienced cardiovascular death or HF or renal failure rehospitalizations through Day 60. Approximately 14% of patients (range, 9.3% to 18.6%) died by Day 180. Clinical outcomes in the 4 studies are summarized in \u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E.\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/14346\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/14346\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14346\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EClinical Outcomes\u003Csup\u003E\u003Csup\u003Ea\u003C\/sup\u003E\u003C\/sup\u003E\n            \u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EThe strongest multivariable predictor of death or worsening HF through Day 5 was increased blood urea nitrogen, followed by an increase in respiratory rate per 1 breath\/minute, a decrease in hematocrit rate per 1%, and a decrease in systolic blood pressure. The C-statistic of the model was 0.6739, which indicated a modest ability to discriminate between patients with and without worsening HF.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EWorsening HF by Day 5 was associated with a longer length of initial hospital stay (combined adjusted mean difference, 5.20 days; 95% CI, 4.56 to 5.84 days; p\u0026lt;0.0001) and with an increased risk of HF or renal failure readmission or cardiovascular death by Day 60 (combined adjusted HR, 1.64; 95% CI 1.34\u20132.01; p\u0026lt;0.0001). The risk of death by 180 days was also higher for those with worsening HF by Day 5 (adjusted HR, 1.93; 95% CI, 1.55 to 2.41; p\u0026lt;0.0001).\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EWorsening HF treated with IV loop diuretics alone is associated with increased risk of 180-day mortality (adjusted HR, 1.80; 95% CI, 1.36 to 2.36; p\u0026lt;0.0001). Worsening HF requiring IV inotropes or mechanical therapy was also associated with increased risk of 180-day mortality (adjusted HR, 3.03; 95% CI, 2.11 to 4.36; p\u0026lt;0.0001). Changes in markers of renal or hepatic impairment, lower cholesterol\/albumin, or HF signs and symptoms explained little of the association of worsening HF with future clinical outcomes.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EThe associations and outcomes of worsening HF are more pronounced in the early weeks and months after the event and do not seem to be explained by the baseline characteristics of the patients in the studies analyzed. Worsening HF may be driven by a yet unknown pathophysiologic mechanism that conveys an independent risk for adverse outcomes in AHF.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/12\/17.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzp5pe\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzp5pe\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}