***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: Dyssynchronous myocardial motion aggravates cardiac pump function .  Cardiac resynchronization using pacing devices is a st and ard-of-care in the management of heart failure . Post-infa rct ion , however , scar tissue formation impedes the efficacy of device-based therapy . The present study tests a regenerative approach aim ed at targeting the origin of abnormal motion to prevent dyssynchronous organ failure . Induced pluripotent stem ( iPS ) cells harbour a reparative potential , and were here bioengineered from somatic fibroblasts reprogrammed with the stemness factors OCT3/4 , SOX2 , KLF4 , and c-MYC . In a murine infa rct ion model , within 30 min of coronary ligation , iPS cells were delivered to mapped infa rct ed areas . Focal deformation and dysfunction underlying progressive heart failure was resolved prospect ively using speckle-tracking imaging . Tracked at high temporal and spatial resolution , regional iPS cell transplantation restored , within 10 days post-infa rct ion , the contractility of targeted infa rct ed foci and nullified conduction delay in adjacent non-infa rct ed regions . Local iPS cell therapy , but not delivery of parental fibroblasts or vehicle , prevented or normalized abnormal strain patterns correcting the decrease in peak strain , disparity of time-to-peak strain , and pathological systolic stretch . Focal benefit of iPS cell intervention translated into improved left ventricular conduction and contractility , reduced scar , and reversal of structural remodelling , protecting from organ decompensation . Thus , in ischaemic cardiomyopathy , targeted iPS cell transplantation synchronized failing ventricles , offering a regenerative strategy to achieve biological resynchronization Background . Magnetic resonance imaging ( MRI ) strain analysis is a sensitive method to assess myocardial function . Our objective was to define the feasibility of MRI circumferential strain ( ε cc ) analysis in assessing subtle changes in myocardial function following stem cell therapy . Methods and Results . Patients in the Amorcyte Phase I trial were r and omly assigned to treatment with either autologous bone-marrow-derived stem cells infused into the infa rct -related artery 5 to 11 days following primary PCI or control . MRI studies were obtained at baseline , 3 , and 6 months . ε cc was measured in the short axis views at the base , mid and apical slices of the left ventricle ( LV ) for each patient ( 13 treatments and 10 controls ) . Mid-anterior LV ε cc improved between baseline −18.5 ± 8.6 and 3 months −22.6 ± 7.0 , P = 0.03 . There were no significant changes in ε cc at 3 months and 6 months compared to baseline for other segments . There was excellent intraobserver and interobserver agreement for basal and mid circumferential strain . Conclusion . MRI segmental strain analysis is feasible in assessment of regional myocardial function following cell therapy with excellent intra- and inter-observer variability 's . Using this method , a modest interval change in segmental ε cc was detected in treatment group Background —The present sub study of a recently published r and omized trial aim ed to investigate the effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia . Methods and Results —In a total of 50 patients , diastolic function was evaluated before and 3 months after bone marrow cell injection using st and ard echocardiography and strain analysis . In addition , MRI-derived transmitral flow measurements were obtained in a subset of 36 patients . Left ventricular ejection fraction increased from 50±5 % to 54±7 % in the bone marrow cell group , which was a significant improvement as compared with the placebo group ( 52±5 % versus 51±7 % , P=0.001 ) . Filling pressure estimate E/E′ ratio improved from 14±5 at baseline to 12±4 at 3 months in the bone marrow cell group , whereas no improvement was observed in the placebo group ( 13±4 versus 13±5 ) . The improvement in E/E′ ratio was significantly larger in the bone marrow cell group ( P=0.008 ) . Furthermore , the E/A peak flow ratio as assessed by MRI showed a significant increase in the bone marrow cell group as compared with the placebo group ( + 0.16±0.25 versus −0.04±0.21 , P=0.01 ) , which was mainly related to an increase in the early ( E ) peak flow rate in the bone marrow cell group ( from 407±96 mL/s to 468±110 mL/s , P=0.009 as compared with the placebo group ) . Conclusions —The current study demonstrates that intramyocardial bone marrow cell injection is associated with a beneficial effect on myocardial relaxation and filling pressures in patients with chronic myocardial ischemia . Clinical Trial Registration —URL : http://www.trialregister.nl . Unique identifier : NTR400/IS RCT N58194927 Rationale : Transcatheter , intramyocardial injections of bone marrow – derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy . Objective : We used cardiac MRI ( CMR ) in patients with left ventricular ( LV ) dysfunction related to remote myocardial infa rct ion ( MI ) to test the hypothesis that bone marrow progenitor cell injection causes functional recovery of scarred myocardium and reverse remodeling . Methods and Results : Eight patients ( aged 57.2±13.3 years ) received transendocardial , intramyocardial injection of autologous bone marrow progenitor cells ( mononuclear or mesenchymal stem cells ) in LV scar and border zone . All patients tolerated the procedure with no serious adverse events . CMR at 1 year demonstrated a decrease in end diastolic volume ( 208.7±20.4 versus 167.4±7.32 mL ; P=0.03 ) , a trend toward decreased end systolic volume ( 142.4±16.5 versus 107.6±7.4 mL ; P=0.06 ) , decreased infa rct size ( P<0.05 ) , and improved regional LV function by peak Eulerian circumferential strain in the treated infa rct zone ( −8.1±1.0 versus −11.4±1.3 ; P=0.04 ) . Improvements in regional function were evident at 3 months , whereas the changes in chamber dimensions were not significant until 6 months . Improved regional function in the infa rct zone strongly correlated with reduction of end diastolic volume ( r2=0.69 , P=0.04 ) and end systolic volume ( r2=0.83 , P=0.01 ) . Conclusions : These data suggest that transcatheter , intramyocardial injections of autologous bone marrow progenitor cells  improve regional contractility of a chronic myocardial scar , and these changes predict subsequent reverse remodeling . The findings support the potential clinical benefits of this new treatment strategy and ongoing r and omized clinical trials Background —Experimental data suggest that bone marrow – derived cells may contribute to the healing of myocardial infa rct ion ( MI ) . For this reason , we analyzed 10 patients who were treated by intracoronary transplantation of autologous , mononuclear bone marrow cells ( BMC s ) in addition to st and ard therapy after MI . Methods and Results —After st and ard therapy for acute MI , 10 patients were transplanted with autologous mononuclear BMC s via a balloon catheter placed into the infa rct -related artery during balloon dilatation ( percutaneous transluminal coronary angioplasty ) .  Another 10 patients with acute MI were treated by  st and ard therapy alone . After 3 months of follow-up , the infa rct region ( determined by left ventriculography ) had decreased significantly within the cell therapy group ( from 30±13 to 12±7 % , P = 0.005 ) and was also significantly smaller compared with the st and ard therapy group ( P = 0.04 ) . Likewise , infa rct ion wall movement velocity increased significantly only in the cell therapy group ( from 2.0±1.1 to 4.0±2.6 cm/s , P = 0.028 ) . Further cardiac examinations ( dobutamine stress echocardiography , radionuclide ventriculography , and catheterization of the right heart ) were performed for the cell therapy group and showed significant improvement in stroke volume index , left ventricular end-systolic volume and contractility ( ratio of systolic pressure and end-systolic volume ) , and myocardial perfusion of the infa rct region . Conclusions —These results demonstrate for the first time that selective intracoronary transplantation of autologous , mononuclear BMC s is safe and seems to be effective under clinical conditions . The marked therapeutic effect may be attributed to BMC -associated myocardial regeneration and neovascularization Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more To investigate the effect of intracoronary injection of autologous mononuclear bone marrow stem cells ( BMSCs ) in patients with ST-elevation myocardial infa rct ion ( STEMI ) on left ventricular ( LV ) systolic and diastolic function using st and ard echocardiography and 2-dimensional systolic strain . A total of 60 patients with first anterior wall STEMI and LV ejection fraction of < 40 % , treated with successful primary percutaneous coronary intervention were r and omly assigned to the treatment group ( BMSC group ) or the control group in a 2:1 ratio . Transcatheter intracoronary injection of BMSCs into the infa rct -related artery was performed 7 days after STEMI . St and ard echocardiography and speckle tracking analysis was performed at baseline and 6 months after STEMI . No differences were found in the baseline echocardiographic parameters of LV systolic and diastolic dysfunction -- the LV ejection fraction was 35 + /- 6 % in the BMSC group , similar to that in the control group ( 33 + /- 7 % , p = 0.42 ) . After 6 months , the absolute change in the LV ejection fraction was significantly greater in the BMSC group than in the control group ( 10 + /- 9 % versus 5 + /- 8 % , p = 0.04 ) . Significant improvement was seen in 2-dimensional systolic strain in all segments ( 12 + /- 4 vs 14 + /- 4 ; p = 0.0009 ) and in the infa rct ed area ( 5 + /- 2 vs 6 + /- 2 ; p = 0.0038 ) only in the BMSC group . Of the diastolic function parameters , we observed improvement in the early filling propagation velocity ( 30 + /- 8 cm/s vs 37 + /- 13 cm/s ; p = 0.0008 ) , early diastolic velocity - E ' ( 4.5 + /- 1.5 vs 5.0 + /- 1.3 , p = 0.02 ) , and the E/E ' ratio ( 17 + /- 7 vs 14 + /- 5 ; p = 0.03 ) in the BMSC group . In conclusion , intracoronary injection of unselected BMSCs in patients with STEMI improved both LV systolic and diastolic function at 6 months of follow-up OBJECTIVES Cell loss during cardiac injection and hostility of the host-tissue microenvironment have the potential to diminish the overall effect of stem cell therapy . The purpose s of this study were to evaluate the effect of a hypoxic preconditioning of mesenchymal stromal cells ( MSC ) , to determine its safety and effectiveness , and to improve the efficacy of cell therapy using MSC in the setting of chronic myocardial ischaemia in swine . METHODS Myocardial ischaemia was induced by an ameroid constrictor . Human MSC were cultured under normoxic ( 20 % O2 ) or hypoxic conditions ( 1.5 % O2 ) before transplantation . One month after ischaemia , pigs were r and omly assigned to saline injection ( sham ) , and 1 × 10(6)/kg normoxic or hypoxic MSC transplantation into the ischaemic inferior-lateral zone . RESULTS Twenty-seven pigs were operated on and the mortality rate was 33.3 % . The remaining 18 animals were r and omly assigned to sham ( n = 4 ) , normoxic ( n = 8) or hypoxic MSC ( n = 6 ) treatment . Global systolic ( left ventricle ejection fraction , P = 0.04 ) and diastolic ( E/Ea , P = 0.008 ) functions were increased in the hypoxic group compared with other groups . The peak of 2-dimensional longitudinal strain was less altered in the hypoxic group compared with other groups ( P < 0.001 ) . Haemodynamic data showed that dP/dT max was improved in the hypoxic group compared with the other group ( P < 0.01 ) . Capillary density was increased in the hypoxic group ( P = 0.001 ) . MSC density was significantly higher in the ischaemic zone 
    Output:
    
Hence ,  deformation imaging  seems at least equal , and perhaps superior , to LVEF measurement in the assessment of cardiac regenerative therapy .