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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 discusses management of heart failure in the 21st century, including successes, failures, new treatments, and telecardiology.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EHeart Failure\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EMichel Komajda, MD, Piti\u00e9-Salp\u011btri\u00e8re Hospital, Paris, France, discussed management of heart failure (HF) in the 21\u003Csup\u003Est\u003C\/sup\u003E century, including successes, failures, new treatments, and telecardiology.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ESuccesses and Failures\u003C\/h2\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EImprovements in HF management can be attributed to the advent of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers. Currently, all major guidelines recommend the combination of ACE inhibitors (or angiotensin II receptor blockers [ARBs]) and beta-blockers for reducing morbidity and mortality in patients with chronic HF and low ejection fraction (EF) levels. The magnitude of success was demonstrated by the reduction in mortality rates from 15.7% in 1991 in SOLVD-T [SOLVD Investigators. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 1991] to 6.1% in 2003 in CHARM-Added [McMurray JJ et al. \u003Cem\u003ELancet\u003C\/em\u003E 2003] with the use of ACE inhibitors, beta-blockers, and ARBs. The annual incidence of first hospitalization for HF has also decreased. The European Society of Cardiology (ESC) registry for HF (n=3226) reported prescription rates of ACE inhibitors\/ARBs and beta-blockers close to 90%, with aldosterone blockers at 43%. There is room for improvement, however, with all-cause mortality rates and all-cause mortality\/HF hospitalization rates of 6.8% and 17.2% in chronic HF and 16.8% and 35.1% in acute HF, respectively (ESC registry).\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003ETwo recent trials have shown positive results in chronic HF:\u003C\/p\u003E\n         \u003Col class=\u0022list-ord \u0022 id=\u0022list-1\u0022\u003E\u003Cli id=\u0022list-item-1\u0022\u003E\n               \u003Cp id=\u0022p-5\u0022\u003EThe SHIFT trial, which studied patients with chronic HF, low EF levels, and increased heart rate, showed that cardiovascular (CV) death or HF hospitalization was significantly reduced by 18% with the selective sinus-node inhibitor ivabradine versus placebo (HR, 0.82; p\u0026lt;0.0001). Hospitalization for worsening HF was reduced by 26% (HR, 0.74; 0.66 to 0.83; p\u0026lt;0.0001) [Swedberg K et al. \u003Cem\u003ELancet\u003C\/em\u003E 2010]. Other studies of ivabradine demonstrated significantly improved quality of life [Ekman I et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2011] and left ventricular end systolic volume index and left ventricular EF (LVEF) [Tardif JC et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2011].\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-2\u0022\u003E\n               \u003Cp id=\u0022p-6\u0022\u003EThe EMPHASIS trial of eplerenone (n=2737) was stopped prematurely because of the overwhelming benefit of eplerenone versus placebo in reducing CV death or HF hospitalization (18.3% vs 25.9%; HR, 0.63; 95% CI, 0.54 to 0.74; p \u0026lt;0.001) [Zannad F et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011].\u003C\/p\u003E\n            \u003C\/li\u003E\u003C\/ol\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EMuch has been learned about implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT). The SCD-HeFT trial demonstrated a significant reduction in mortality with ICDs versus placebo (p=0.007) and amiodarone (amiodarone vs placebo; p=0.53) [Bardy GH et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2005]. Two pivotal trials reported a significant benefit with CRT versus medical therapy in event-free survival (EFS; CV death or hospitalization). EFS was improved in the COMPANION trial [Bristow MR et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2004] with CRT-defibrillators (CRT-D; p\u0026lt;0.001) and CRT-pacemakers (CRT-P; p=0.002) and in the CARE-HF study [Cleland JG et al. \u003Cem\u003EN Eng J Med\u003C\/em\u003E 2005], with CRT-P (p\u0026lt;0.001). Failures concern acute or acutely decompensated HF, and HF with preserved EF. Not all acute HF trials have shown positive results. The ESSENTIAL trial of low-dose enoximone [Metra MM et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2009], the SURVIVE and REVIVE trials of levosimendan [Mebazza A et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2009], and the EVEREST trial of tolvaptan [Udelson JE et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2008] all had negative results. The PROTECT trial found no benefit with the adenosine antagonist rolofylline versus placebo [Voors AA et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2011]. Likewise, nesiritide was not superior to placebo with respect to 30-day death\/HF rehospitalization, 30-day death, or HF rehospitalization (p=0.31).\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EThe second major failure is in HF with preserved EF (HF-PEF), which represents 33% to 50% of all HF patients. Two key trials in this population failed to show a benefit in death or HF hospitalization with treatment: the CHARM-Preserved trial of candesartan versus placebo (HR, 0.92; p=0.221) [MacDonald MR et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2008] and the PEP-CHF trial of perindopril versus placebo (HR, 0.92; p=0.545) [Cleland JG et al. \u003Cem\u003EEur Heart J\u003C\/em\u003E 2006]. The I-PRESERVE trial found no benefit with the renin-angiotensin-aldosterone system blocker irbesartan versus placebo in death or hospitalization (HR, 0.95; p=0.35) [McMurray JJ et al. \u003Cem\u003EJ Heart Fail\u003C\/em\u003E 2007]. A meta-analysis of trials in patients with HF-PEF found that none of the treatments studied has a proven benefit in these patients (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Holland DJ et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2011]. The ongoing TOPCAT trial [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00094302\u0026amp;atom=%2Fspmdc%2F12%2F3%2F4.atom\u0022\u003ENCT00094302\u003C\/a\u003E] is investigating the potential benefit of a treatment with an aldosterone antagonist in this condition.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/3\/4\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Treatment Effect on Mortality.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-841660762\u0022 data-figure-caption=\u0022Treatment Effect on Mortality.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/3\/4\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/3\/4\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/12\/3\/4\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13988\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\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003ETreatment Effect on Mortality.\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced with permission from the American College of Cardiology. Effects of Treatment on Exercise Tolerance, Cardiac Function, and Mortality in Heart Failure With Preserved Ejection Fraction. Holland DJ et al. \u003Cem\u003EJ Am Coll of Cardiol\u003C\/em\u003E 2011;57(16):1676\u20131686.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ENew Drugs\u003C\/h2\u003E\n         \u003Cp id=\u0022p-10\u0022\u003ENew drugs being investigated for HF include renin inhibitors, such as aliskiren, inotropes, vasodilators\/GMPc modulators, chimeric natriuretic peptides (NPs), neutral endopeptidase (NEP) inhibitors, and sinus-node inhibitors. The ATMOSPHERE trial [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00853658\u0026amp;atom=%2Fspmdc%2F12%2F3%2F4.atom\u0022\u003ENCT00853658\u003C\/a\u003E] is comparing treatment with aliskiren versus enalapril in 2162 patients. The PARADIGM-HF study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01035255\u0026amp;atom=%2Fspmdc%2F12%2F3%2F4.atom\u0022\u003ENCT01035255\u003C\/a\u003E] is investigating LCZ696, a molecular complex of the ARB valsartan, and the NEP inhibitor AHU 377, in 7980 patients. The new vasodilator relaxin acts through nitric oxide and cyclic GMP effectors and has anti-inflammatory, anti-ischemic, anti-apoptotic, and antifibrotic properties. Results of proof-of-concept studies will determine if this drug has a place in the management of acute HF. Studies are also ongoing with the chimeric natriuretic peptide CD-NP.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EPreliminary results of the HORIZON-HF [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00616161\u0026amp;atom=%2Fspmdc%2F12%2F3%2F4.atom\u0022\u003ENCT00616161\u003C\/a\u003E] trial show that the new calcium-cycling modulator istaroxime produced a rapid and sustained dose-dependent significant decrease in pulmonary capillary wedge pressure that was maintained at 6 hours. A proof-of-concept study of the direct myosin activator, omecamtiv mecarbil, showed improvement in heart function indices.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ENew Devices\u003C\/h2\u003E\n         \u003Cp id=\u0022p-12\u0022\u003ETwo trends in the use of devices for hemodynamic support are emerging: 1) the move toward using them as destination therapy rather than a bridge to transplantation, and 2) the development of new indications for CRT based on results from 2 studies. The REVERSE trial analyzed the percentage of mild to moderate HF patients with improved\/unchanged or worsened condition with the CRT turned on or off [Daubert C et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2009]. At 24 months, 81% of patients in the CRT ON group were improved\/unchanged versus 66% in the CRT OFF group (p=0.01). Left ventricular end-systolic volume index was also significantly improved in the CRT ON group (69.7 mL\/m\u003Csup\u003E2\u003C\/sup\u003E) versus the CRT OFF group (94.5 mL\/m\u003Csup\u003E2\u003C\/sup\u003E; p\u0026lt;0.0001). The RAFT trial compared ICD versus ICD-CRT in patients with mild to moderate HF (n=1798) [Tang AS et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2010]. Patients with ICD-CRT had significantly better all-cause mortality or HF hospitalization rates versus those with an ICD alone (HR, 0.56; p\u0026lt;0.001).\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-4\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EOther Approaches\u003C\/h2\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EOther approaches in HF management include cell therapy using cardiac skeletal muscle myoblast injections, embryonic or bone marrow stem cells, and gene therapy. The AGENT-HF trial is investigating gene therapy with percutaneous intracoronary infusion of SERCA2a, which has decreased expression in HF. Several preclinical studies indicate that restoring SERCA2a levels improves cardiac function. The CUPID trial [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00454818\u0026amp;atom=%2Fspmdc%2F12%2F3%2F4.atom\u0022\u003ENCT00454818\u003C\/a\u003E] in the United States is evaluating SERCA2a in HF.\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003EThe HF-ACTION trial investigated the effects of exercise training in patients with HF. Patients who received exercise training versus usual care had significantly decreased rates of CV death or HF hospitalization (adjusted HR, 0.85; 95% CI, 0.74 to 0.99; p=0.03) [O\u0027Connor CM et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2009].\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003ETelemonitoring allows physicians to remotely monitor parameters usually evaluated in an office visit, including a patient\u0027s weight and blood pressure. This technology alerts physicians to any significant variations in patients\u0027 parameters, and this approach might benefit patients with CHF.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2012 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\/12\/3\/4.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_figures.js?nzndtd\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_openurl.js?nzndtd\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}