***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background —This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility . Methods and Results —Twenty-one patients were enrolled in this prospect i ve , nonr and omized , open-label study ( first 14 patients , treatment ; last 7 patients , control ) . Baseline evaluations included complete clinical and laboratory evaluations , exercise stress ( ramp treadmill ) , 2D Doppler echocardiogram , single-photon emission computed tomography perfusion scan , and 24-hour Holter monitoring . Bone marrow mononuclear cells were harvested , isolated , washed , and resuspended in saline for injection by NOGA catheter ( 15 injections of 0.2 cc ) . Electromechanical mapping was used to identify viable myocardium ( unipolar voltage ≥6.9 mV ) for treatment . Treated and control patients underwent 2-month noninvasive follow-up , and treated patients alone underwent a 4-month invasive follow-up according to st and ard protocol s and with the same procedures used as at baseline . Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups ; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up , being relatively higher in control patients . At 2 months , there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups ( P = 0.02 ) on quantitative single-photon emission computed tomography analysis . At 4 months , there was improvement in ejection fraction from a baseline of 20 % to 29 % ( P = 0.003 ) and a reduction in end-systolic volume ( P = 0.03 ) in the treated patients . Electromechanical mapping revealed significant mechanical improvement of the injected segments ( P < 0.0005 ) at 4 months after treatment . Conclusions —Thus , the present study demonstrates the relative safety of intramyocardial injections of bone marrow – derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function Rationale : Ixmyelocel-T is associated with a wide range of biological activities relevant to tissue repair and regeneration . Objective : To evaluate the safety and efficacy of ixmyelocel-T in 2 prospect i ve r and omized phase 2A Trials administered via minithoracotomy or intramyocardial catheter injections in patients with dilated cardiomyopathy ( DCM ) stratified by ischemic or nonischemic status . Methods and Results : In IMPACT-DCM , patients were r and omized to either ixmyelocel-T or st and ard-of-care control in a 3:1 ratio ( n=39 ) ;  ixmyelocel-T was administered intramyocardially via minithoracotomy . In Catheter-DCM , patients were r and omized to either ixmyelocel-T or st and ard of care control  in a 2:1 ratio ( n=22 ) ;  ixmyelocel-T was administered intramyocardially using the NOGA Myostar catheter .  Only patients r and omized to ixmyelocel-T underwent bone marrow aspiration and injections . In the 2 studies , a total of 61 patients were r and omized , and 59 were treated or received st and ard of care . Fewer ischemic patients treated with ixmyelocel-T experienced a major adverse cardiovascular event during follow-up when compared with control patients . A similar benefit was not seen in the nonischemic patients . Heart failure exacerbation was the most common major adverse cardiovascular event . Ixmyelocel-T treatment was associated with improved New York Heart Association class , 6-minute walk distance , and Minnesota Living with Heart Failure Question naire scores in the ischemic population relative to control ; a similar trend was not observed in the nonischemic population . Conclusions : Intramyocardial injection with ixmyelocel-T reduces major adverse cardiovascular event and improves symptoms in patients with ischemic DCM but not in patients with nonischemic DCM AIMS Despite accumulated evidence that intracoronary bone marrow cell ( BMC ) therapy may be beneficial in acute myocardial infa rct ion , there are only limited data available on the effectiveness of BMC 's in chronic heart failure . The aim of this study was to quantitatively investigate ventricular haemodynamics , geometry , and contractility as well as the long-term clinical outcome of  BMC treated patients with reduced left ventricular ejection fraction ( LVEF ) due to chronic ischaemic cardiomyopathy . METHODS AND RESULTS Patients with chronic heart failure ( n = 391 LVEF < or=35 % ) due to ischaemic cardiomyopathy were enrolled in the present study . Of these , 191 patients ( mean NYHA class 3.22 ) underwent intracoronary BMC therapy . The control group ( mean NYHA class 3.06 ) consisted of 200 patients with comparable LVEF . Assessment s of haemodynamics at rest and exercise , quantitative ventriculography , spiroergometry , 24 h Holter ECG , late potentials , and heart rate variability were analysed . Over 3 months to 5 years after intracoronary BMC therapy there was a significant improvement in haemodynamics ( e.g. LVEF , cardiac index ) , exercise capacity , oxygen uptake , and LV contractility . Importantly , there was a significant decrease in long-term mortality in the BMC treated patients compared with the control group . CONCLUSION Intracoronary BMC therapy improves ventricular performance , quality of life and survival in patients with heart failure . These effects were present when BMC were administered in addition to st and ard therapeutic regimes . No side effects were observed OBJECTIVES This study sought to evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically oriented mesenchymal stem cell therapy and to probe for signs of efficacy in patients with chronic heart failure . BACKGROUND In pre- clinical heart failure models , cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodeling . METHODS The C-CURE ( Cardiopoietic stem Cell therapy in heart failURE ) trial , a prospect i ve , multicenter , r and omized trial , was conducted in patients with heart failure of ischemic origin who received st and ard of care or st and ard of care plus lineage-specified stem cells .  In the cell therapy arm , bone marrow was harvested and isolated mesenchymal stem cells were exposed to a cardiogenic cocktail . Derived cardiopoietic stem cells , meeting release criteria under Good Manufacturing Practice , were delivered by endomyocardial injections guided by left ventricular electromechanical mapping . Data acquisition and analysis were performed in blinded fashion . The primary endpoint was feasibility/safety at 2-year follow-up . Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy . RESULTS Mesenchymal stem cell cocktail-based priming was achieved for each patient with the dose attained in 75 % and delivery without complications in 100 % of cases . There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy .  Left ventricular ejection fraction was improved by cell therapy ( from 27.5 ± 1.0 % to 34.5 ± 1.1 % ) versus st and ard of care alone ( from 27.8 ± 2.0 % to 28.0 ± 1.8 % , p < 0.0001 ) and was associated with a reduction in left ventricular end-systolic volume ( -24.8 ± 3.0 ml vs. -8.8 ± 3.9 ml , p < 0.001 ) . Cell therapy also improved the 6-min walk distance ( + 62 ± 18 m vs. -15 ± 20 m , p < 0.01 ) and provided a superior composite clinical score encompassing cardiac parameters in t and em with New York Heart Association functional class , quality of life , physical performance , hospitalization , and event-free survival . CONCLUSIONS The C-CURE trial implements the paradigm of lineage guidance in cell therapy . Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure , meriting definitive clinical evaluation . ( C-Cure Clinical Trial ; NCT00810238 ) BACKGROUND Autologous adult stem cell transplantation has been touted as the latest tool in regenerative medical therapy . Its potential for use in cardiovascular disease has only recently been recognized . A r and omized study was conducted with a novel epicardial technique to deploy stem cells as an adjuvant to conventional revascularization therapy in patients with congestive heart failure . METHODS After institutional review board and government approval , adult autologous stem cell transplantation ( CD34 + ) was performed in patients with ischemic cardiomyopathy and an ejection fraction of less than 35 % who were scheduled for primary off-pump coronary artery bypass grafting . Preoperatively , the patients underwent echocardiography , stress thallium imaging single photon emission computed tomography , and cardiac catheterization to identify ischemic regions of the heart and to guide in the selection of stem cell injection sites . The patients were prospect ively r and omized before the operative therapy was performed . Patient follow-up was 1 , 3 , and 6 months with echocardiography , single photon emission computed tomography , and angiography . RESULTS There were 20 patients enrolled in the study . Ten patients had successful subepicardial transplantation of autologous stem cells into ischemic myocardium . The other 10 patients , the control group , only had off-pump coronary artery bypass grafting . There were 8 male and 2 female subjects in each group . The median number of grafts performed was 1 in both groups . On angiographic follow-up , all grafts were patent at 6 months . The ejection fractions of the off-pump coronary artery bypass grafting group versus the off-pump coronary artery bypass grafting plus stem cell transplantation group were as follows : preoperative , 30.7 % + /- 2.5 % versus 29.4 % + /- 3.6 % ; 1 month , 36.4 % + /- 2.6 % versus 42.1 % + /- 3.5 % ; 3 months , 36.5 % + /- 3.0 % versus 45.5 % + /- 2.2 % ; and 6 months , 37.2 % + /- 3.4 % versus 46.1 % + /- 1.9 % ( P < .001 ) . There were no perioperative arrhythmias or neurologic or ischemic myocardial events in either group . CONCLUSIONS Autologous stem cell transplantation led to significant improvement in cardiac function in patients undergoing off-pump coronary artery bypass grafting for ischemic cardiomyopathy . Further investigation is required to quantify the optimal timing and specific cellular effects of the therapy AIMS The SEISMIC study was an open-label , prospect i ve , r and omised study to assess the safety and feasibility of percutaneous myoblast implantation in heart failure patients with implanted cardioverter-defibrillators ( ICD ) . METHODS AND RESULTS Patients were r and omised 2:1 to autologous skeletal myoblast therapy vs. optimal medical treatment . The primary safety end-point was defined as the incidence of procedural and device related serious adverse events , whereas the efficacy endpoints were defined as the change in global LVEF by MUGA scan , change in NYHA classification of heart failure and in the distance achieved during a six-minute walk test ( 6MW ) at 6-month follow-up . Forty subjects were r and omised to the treatment arm ( n=26 ) , or to the control arm ( n=14 ) . There were 12 sustained arrhythmic events and one death after episodes of ventricular tachycardia ( VT ) in the treatment group and 14 events in the control group ( P = ns ) . At 6-month follow-up , 6MW distance improved by 60.3±54.1?meters in the treated group as compared to no improvement in the control group ( 0.4±185.7?meters ; P = ns ) . In the control group , 28.6 % experienced worsening of heart failure status ( 4/14 ) , while 14.3 % experienced an improvement in NYHA classification ( 2/14 ) . In the myoblast-treatment arm , one patient experienced a deterioration in NYHA classification ( 8.0 % ) , whereas five patients improved one or two classes ( 20.0 % ; P=0.06 ) . However , therapy did not improve global LVEF measured by MUGA at 6-month follow-up . CONCLUSIONS These data indicate that implantation of myoblasts in patients with HF  is feasible , appears to be safe and may provide symptomatic relief , though no significant effect was detected on global LVEF Background — In an open-label blinded study , we compared intracoronary and transendocardial CD34 + cell transplantation in patients with nonischemic dilated cardiomyopathy . Methods and Results — Of the 40 patients with dilated cardiomyopathy , 20 were r and omized to receive intracoronary injection  and 
    Output:
    
Left ventricular ejection fraction ( LVEF ) was improved in the majority of trials after therapy .
Cell delivery combined with coronary artery bypass grafting was associated with the greatest improvement in LVEF .
Left ventricular end-systolic volume ( or diameter ) , New York Heart Association functional classification , quality of life , and exercise capacity were also improved in most studies after cell therapy .
Most ICM trials demonstrated a significant improvement in perfusion defects , infa rct size , and myocardial viability .
Stem cells are a promising therapeutic modality for patients with heart failure due to ICM or NICM .