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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\u003EThe last 3 decades have seen major advances in cardiovascular medicine and surgery. Unfortunately, the results of efforts to improve outcomes in patients with heart failure (HF) are mixed. Although patients with chronic HF with reduced ejection fraction (HFrEF) have benefited in terms of survival and quality of life from neurohormonal blockers and devices, there has been no improvement in the management of patients with HF with preserved EF, and little improvement in patients presenting with acute HF. This article summarizes the progress that has been made in the treatment of HF in six areas: biomarkers, microRNAs, calcium cycling, gene therapy, cell therapy, and left ventricular assist devices.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHeart Failure\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EHeart Failure\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ECardiology\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe last 3 decades have seen major advances in cardiovascular medicine and surgery. Unfortunately, the results of efforts to improve outcomes in patients with heart failure (HF) are mixed. Although patients with chronic HF with reduced ejection fraction (HFrEF) have benefited in terms of survival and quality of life from neurohormonal blockers and devices, there has been no improvement in the management of patients with HF with preserved EF (HFpHF), and little improvement in patients presenting with acute HF. During the inaugural Braunwald Lecture, Eugene Braunwald, MD, Harvard Medical School, Brigham and Women\u0027s Hospital Boston, Massachusetts, USA, summarized the progress that has been made in the treatment of HF. He focused on six areas: biomarkers, microRNAs (miRNAs), calcium cycling, gene therapy, cell therapy, and left ventricular assist devices (LVADs).\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EBIOMARKERS\u003C\/h2\u003E\n         \u003Cp id=\u0022p-3\u0022\u003ECurrently available biomarkers for HF reflect seven biological processes that are independently associated with negative outcome (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Braunwald E. \u003Cem\u003EJACC Heart Fail\u003C\/em\u003E 2013]. Several multimarker scoring systems have been developed to predict outcomes in different populations such as chronic HFrEF [Ky B et al. \u003Cem\u003ECirc Heart Fail\u003C\/em\u003E 2012], HFpEF [Zile MR et al. \u003Cem\u003ECirc Heart Fail\u003C\/em\u003E 2011] and patients without HF [Wang TJ et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2012]. Although the clinical utility of biomarker-guided therapy has been controversial, a recent meta-analysis (2700 patients; 12 trials) reported a significant (p=0.005) 26% mortality reduction among HF patients when natriuretic peptide-guided therapy was added to optimized medical therapy [Savarese G et al. \u003Cem\u003EPLoS One\u003C\/em\u003E 2013].\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\/14\/4\/10\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Biomarker Profile of Heart Failure\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1230053913\u0022 data-figure-caption=\u0022Biomarker Profile of Heart Failure\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\/14\/4\/10\/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\/14\/4\/10\/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\/14\/4\/10\/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\/15799\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-4\u0022 class=\u0022first-child\u0022\u003EBiomarker Profile of Heart Failure\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced from Braunwald E. State-of-the-Art Paper: Heart Failure. \u003Cem\u003EJACC: Heart Failure\u003C\/em\u003E 2013;1(1)1\u201320. With permission from Elsevier.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EDr. Braunwald sees multiple applications for biomarkers in HF including diagnosis, prognosis, risk assessment, as therapeutic targets, and potentially, as part of personalized therapy.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EMICRORNAS\u003C\/h2\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EMiRNAs are short noncoding RNAs, which are present in all forms of life. More than 1600 have been isolated in humans. In HF, they have been shown to be associated with the development of hypertrophy (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) [Matkovich SJ et al. \u003Cem\u003ECirc Res\u003C\/em\u003E 2012]. In the future they may have a role as biomarkers for HF [Tijsen AJ et al. \u003Cem\u003ECirc Res\u003C\/em\u003E 2010], or as targets for the development of novel therapies [Kr\u00fctzfeldt J et al. \u003Cem\u003ENature\u003C\/em\u003E 2005; Wahlquist C et al. \u003Cem\u003ENature\u003C\/em\u003E 2014].\u003C\/p\u003E\n         \u003Cdiv id=\u0022F2\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\/14\/4\/10\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Expression of MiR-499 in Humans\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1230053913\u0022 data-figure-caption=\u0022Expression of MiR-499 in Humans\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/4\/10\/F2.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\/14\/4\/10\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\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\/14\/4\/10\/F2.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\/15801\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 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EExpression of MiR-499 in Humans\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EHF=heart failure; LVAD=left ventricular assist devices.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EReproduced from Matkovich SJ et al. Direct and indirect involvement of microRNA-499 in clinical and experimental cardiomyopathy. \u003Cem\u003ECirc Res\u003C\/em\u003E 2012 Aug 17;111(5):521\u201331. With permission from Lippincott Williams and Wilkins.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EDr. Braunwald believes that of all the new HF research areas, miRNAs hold the most promise by helping to improve our understanding of HF and its diagnosis, and ultimately in developing new therapies in antagonists to miRNAs (antagomirs).\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ECALCIUM CYCLING\u003C\/h2\u003E\n         \u003Cp id=\u0022p-9\u0022\u003ECalcium cycling (CA\u003Csup\u003E2+\u003C\/sup\u003E cycling) is critical to normal cardiac contraction and relaxation. Disturbances in this process such as calcium leakage, insufficient release of calcium, or calcium overload are important factors in the development of HF [Luo M, Anderson ME. \u003Cem\u003ECirc Res\u003C\/em\u003E 2013]. Medications that improve myocardial contractility and ventricular dysfunction hold promise for patients with HF. In a Phase 2 randomized, placebo-controlled clinical trial, the cardiac myosin activator, omecamtiv mecarbil, was shown to improve cardiac function in patients with HFrEF by increasing the sensitivity of cardiac myocytes to calcium (\u003Ca id=\u0022xref-fig-3-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFigure 3\u003C\/a\u003E) [Cleland JG et al. \u003Cem\u003ELancet\u003C\/em\u003E 2011]. Omecamtiv mecarbil is in Phase 3 trials.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F3\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\/14\/4\/10\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Cardiac Myosin Activation in Patients With HFrEF\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1230053913\u0022 data-figure-caption=\u0022Cardiac Myosin Activation in Patients With HFrEF\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 3.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/4\/10\/F3.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\/14\/4\/10\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 3.\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\/14\/4\/10\/F3.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\/15803\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 3.\u003C\/span\u003E \n               \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003ECardiac Myosin Activation in Patients With HFrEF\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-4\u0022\u003EHFrEF=heart failure with reduced ejection fraction; LVEDV=left ventricular end-diastolic volume; LVESV=left ventricular end-systolic volume; SET= systolic ejection time; SV=systolic volume.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-5\u0022\u003EReproduced from Cleland 1G et al. The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. \u003Cem\u003ELancet\u003C\/em\u003E 2011; 378(9792):676\u2013683. With permission from Elsevier.\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-4\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EGENE THERAPY\u003C\/h2\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EDespite difficult beginnings, much progress has been made with gene therapy in patients with HF over the last few years. Investigators have successfully introduced the SERCA2a gene into SERCA2a-ablated mice as well as in rat, pig, and sheep models of LV overload, and into isolated cardiomyocytes obtained from patients with HFrEF [Hajjar R et al. \u003Cem\u003EJ Clin Invest\u003C\/em\u003E 2013].\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EGene therapy using adeno-associated virus type 1\/sarcoplasmic reticulum Ca(2+)-ATPase was studied in the Phase 2 Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease trial [CUPID; Jessup M et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2011]. The treatment was well tolerated and led to improvements in clinical outcomes, symptoms, functional status, biomarkers, and cardiac structure. Gene expression persisted up to 31 months, with clinical benefits lasting up to 3 years [Zsebo K et al. \u003Cem\u003ECirc Res\u003C\/em\u003E 2014]. Other potential gene targets include phospholamban and S100A1.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-5\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ECELL THERAPY\u003C\/h2\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EOne of the most challenging approaches to the treatment of HF is cell therapy. In addition to autologous cardiac cells, a broad range of other cell sources have been studied including bone marrow cells (BMCs), skeletal myoblasts, adipose-derived stem cells, hematopoietic stem cells, mesenchymal stem cells, and blood-derived endothelial progenitor cells. After cell implantation, myocardial repair is accomplished by activation of endogenous progenitor cells, inhibition of apoptosis, extracellular matrix remodeling, or the promotion of neovascularization [Sanganalmath SK, Bolli R. \u003Cem\u003ECirc Res\u003C\/em\u003E 2013].\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003ECell therapy was studied in the Intracoronary Progenitor Cells in Acute Myocardial Infarction trial [REPAIR-AMI], which enrolled 204 patients with left ventricular dysfunction (LVD) or HF post-myocardial infarction (MI). Patients receiving intracoronary BMC had significant improvement in both EF (p=0.009) and wall thickening (p\u0026lt;0.001) compared with those receiving placebo at 2 years [Assmus B et al. \u003Cem\u003ECirc HF\u003C\/em\u003E 2010]. Results of a meta-analysis of adult BMC therapy (50 studies; 2625 patients, most with LVD or HF post MI), indicated that BMC transplantation significantly improved survival, LV function, infarct size, and LV remodeling in patients with ischemic heart disease compared with standard therapy [Jeevanantham V et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2012].\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EIn a Phase I study, carried out in patients with post-Mi HF who were enrolled into the Cardiosphere-Derived Autologous Stem Cells to Reverse Ventricular Dysfunction trial [CADUCEUS; Malliaras K et al. \u003Cem\u003EJ Am Coll Cardiol\u003C\/em\u003E 2014] and received autologous cardiac-derived cells (n=17) were noted to have a marked reduction in scar size, increased circumferential strain, and greater LV wall thickening of the infarcted section than in patients receiving placebo.\u003C\/p\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EThe first relatively large scale trial (n=3000) of cell therapy, the Effect of Intracoronary Reinfusion of Bone Marrow-Derived Mononuclear Cells (BM-MNC) on All-Cause Mortality in Acute Myocardial Infarction [BAMI; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01569178\u0026amp;atom=%2Fspmdc%2F14%2F4%2F10.atom\u0022\u003ENCT01569178\u003C\/a\u003E], is ongoing in 11 European countries. The objective of this Phase 3 trial, which is being conducted in patients who have a reduced LVEF (\u226445%) following an AMI, is to demonstrate that BMC therapy is safe and reduces all-cause mortality compared with controls who are receiving optimal medical care.\u003C\/p\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EDr. Braunwald believes that cell therapy will play a role in the war against HF, but not alone. He sees this therapy being most useful when used in combination with LVADs.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-6\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ELEFT VENTRICULAR ASSIST DEVICES\u003C\/h2\u003E\n         \u003Cp id=\u0022p-18\u0022\u003ENewer continuous flow LVADs are smaller, have no mechanical bearings, and can generate outputs as high as 10 L\/minute [Aaronson KD et al. \u003Cem\u003ECirculation\u003C\/em\u003E 2012]. Although originally used as a bridge to transplant, there has been a steady increase in the use of LVADs as destination therapy. Survival rates with continuous flow devices are better than with the pulsatile devices [Kirklin JK et al. \u003Cem\u003EJ Heart Lung Transplant\u003C\/em\u003E 2013] but complications of prolonged LVAD use, such as infection and bleeding, remain a challenge.\u003C\/p\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EThere is good news, however, in that reverse remodeling of the heart with continuous use of LVADs has been reported. There are reductions in circulating neurohormones and regression of cardiomyocyte hypertrophy, increases in myocardial contractility and in the density of beta adrenergic receptors, as well as improvements in CA\u003Csup\u003E2+\u003C\/sup\u003E cycling [Ambardekar AV, Buttrick PM. \u003Cem\u003ECirc Heart Fail\u003C\/em\u003E 2011]. These reports have led to attempts to wean patients from their assist devices. In one observational study, long-term survival in these patients who were able to be weaned off of a LVAD was similar when compared with patients who underwent heart transplant (\u003Ca id=\u0022xref-fig-4-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F4\u0022\u003EFigure 4\u003C\/a\u003E) [Birks EJ et al. \u003Cem\u003EJ Thorac Cardiovasc Surg\u003C\/em\u003E 2012]\u003C\/p\u003E\n         \u003Cdiv id=\u0022F4\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\/14\/4\/10\/F4.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Survival: Post Explantation\/Transplantation\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1230053913\u0022 data-figure-caption=\u0022Survival: Post Explantation\/Transplantation\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 4.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/4\/10\/F4.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\/14\/4\/10\/F4.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 4.\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\/14\/4\/10\/F4.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\/15805\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 4.\u003C\/span\u003E \n               \u003Cp id=\u0022p-20\u0022 class=\u0022first-child\u0022\u003ESurvival: Post Explantation\/Transplantation\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-6\u0022\u003EBTR=bridge to recovery; BTT=bridge to transplant.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-7\u0022\u003EReproduced from Birks EJ et al. Long-term outcomes of patients bridged to recovery versus patients bridged to transplantation. \u003Cem\u003EJ Thorac Cardiovasc Surg\u003C\/em\u003E 2012; 144(1):190\u2013196. With permission from Elsevier.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-21\u0022\u003EWe have not yet seen remission of HF in patients with chronic ischemic cardiomyopathy, however. To achieve this Dr. Braunwald suggests considering earlier intervention (perhaps at Stage III) with LVAD in these patients and eliminating the use of transcutaneous lines to reduce infection.\u003C\/p\u003E\n         \u003Cp id=\u0022p-22\u0022\u003EIn conclusion, Dr. Braunwald is optimistic that novel therapies offer the potential for progress in the war on HF.\u003C\/p\u003E\n      \u003C\/div\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\/4\/10.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?nzpb9d\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?nzpb9d\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}