Search

Introduction: Previous studies have demonstrated that cell therapy may improve diastolic parameters in heart failure. Hypothesis: We sought to investigate the effects of transendocardial CD34+ cell therapy in patients with heart failure with preserved ejection fraction (HFpEF). Methods: In a pilot study we enrolled 14 patients with HFpEF (LVEF>50%, E/e'>15, NYHA III, NTproBNP levels >300 pg/ml). All patients received granulocyte-colony stimulating factor (G-CSF; 10 mcg/kg, 5 days); CD34+ cells were collected by apheresis. We performed electroanatomical mapping of the left ventricle and assessed local diastolic function by measuring local ventricular relaxation times at each of the sampling points. CD34+ cells were then injected transendocardially in the areas of diastolic dysfunction. Each patient received a dose of 80 million CD34+ cells divided into 20 injections. Results: Our study cohort included 9 male and 5 female patients aged 57±9 years, with LVEF of 56.9±6.6%, creatinine of 85±28 μmol/L, and bilirubin of 12.7±4.7 μmol/L. In all patients, electroanatomical mapping consisting of at least 150 sampling points was performed without any adverse events enabling us to adequately measure local diastolic function and identify target areas for cell delivery. At 1 year after cell delivery we found a significant improvement in left ventricular filling pressures as measured by E/e' (from 17.2±6.8 to 12.7±6.1, P=0.03), a decrease in NTproBNP (from 1137±792 pg/ml to 843±710 pg/ml, P=0.03), and a trend of improvement in global systolic strain (from -11.2±1.6% to -12.9±3.7%, P=0.16). Notably, we found a significant improvement of local systolic strain in myocardial segments that were targeted with stem cell injections (-3.4±4.2%, P=0.001). Conclusions: In patients with HFpEF, transendocardial CD34+ cell transplantation is feasible and safe, and appears to be associated with improved diastolic function and decrease in NTproBNP at 1 year after therapy. [ABSTRACT FROM AUTHOR]

Introduction: End-diastolic volume (EDV) between 200 and 370 mL has been associated with favorable clinical response to cell therapy in ischemic heart failure. Hypothesis: We sought to investigate the effects of EDV, a marker of disease severity, on the response to cell therapy in patients with nonischemic dilated cardiomyopathy (DCM). Methods: Five-year registry data from 134 consecutive patients with DCM (LVEF<40%, NHYA III) who underwent CD34+ cell transplantation was analyzed. All patients received granulocyte-colony stimulating factor (G-CSF; 10 mcg/kg, 5 days); CD34+ cells were collected by apheresis and delivered by transendocardial injection in areas of electromechanical missmatch. Patients with baseline EDV<200 mL were included in Group A (N=72), patients with EDV 200-370 mL were included in Group B (N=54); patients with EDV>370 mL were excluded (N=7). Favorable clinical response was defined by improved LVEF≥5% at 1 year post-cell therapy. Results: At baseline, Groups A and B did not differ in age (52±11 years in Group A vs. 53±10 years in Group B, P=0.95), sex (male: 79% vs. 83%, P=0.55), creatinine (1.07±0.28 mg/dL vs. 1.03±0.21 mg/dL, P=0.21), bilirubin (0.98±0.55 mg/dL vs. 1.00±0.51 mg/dL, P=0.58), or NTproBNP levels (1454±1658 pg/mL vs. 1589±1338 pg/mL, P=0.80). Baseline LVEF was higher in Group A (32.8±8.7%) than in Group B (30.2±8.7%, P=0.03). During follow-up, there were 4 deaths in Group A (6%), and 2 in Group B (4%, P=0.63); heart transplantation was performed in 4 patients from Group A (6%) and in 5 patients in Group B (9%, P=0.42). Favorable clinical response was found in 31/72 patients (43%) in Group A vs. 35/54 (65%) in Group B (P=0.016). Furthermore, EDV significantly decreased at 1 year in Group B (-56±30 mL, P=0.003), but not in Group A (+12±97 mL, P=0.13). On multivariate analysis, baseline EDV was an independent correlate of 1-year clinical outcome (P=0.02). Conclusions: EDV predicted clinical outcome following transendocardial CD34+ cell therapy in a nonischemic DCM patient population, informing target individuals with the highest likelihood of regenerative response. [ABSTRACT FROM AUTHOR]