Search

We investigated the effects of cell therapy on local mechanical dyssynchrony (LMD) in patients with nonischemic dilated cardiomyopathy (NICM). We analyzed electromechanical data of 30 NICM patients undergoing CD34+ cell transplantation. All patients underwent bone marrow stimulation; CD34+ cells were collected by apheresis and injected transendocardially. At baseline and at 6 months after therapy, we performed electromechanical mapping and measured unipolar voltage (UV) and LMD at cell injection sites. LMD was defined as a temporal difference between global and segmental peak systolic displacement normalized to the average duration of the RR interval. Favorable clinical response was defined as increase in the left ventricular ejection fraction (LVEF) ≥5% between baseline and 6 months. Using paired electromechanical point-by-point analysis, we were able to identify 233 sites of CD34+ cell injections in 30 patients. We found no overall differences in local UV between baseline and 6 months (10.7 ± 4.1 mV vs 10.0 ± 3.6 mV, P = 0.42). In contrast, LMD decreased significantly (17 ± 17% at baseline vs 13 ± 12% at 6 months, P = 0.00007). Favorable clinical response at 6 months was found in 19 (63%) patients (group A), and 11 (37%) patients did not respond to cell therapy (group B). At baseline, the two groups did not differ in age, gender, LVEF, or N terminal-pro brain natriuretic peptide (NT-proBNP) levels. Similarly, we found no differences in baseline UV (9.5 ± 2.9 mV in group A vs 8.6 ± 2.4 mV in group B, P = 0.41) or LMD at cell injection sites (17 ± 19% vs 16 ± 14%, P = 0.64). In contrast, at 6 months, we found higher UV in group A (10.0 ± 3.1 mV vs 7.4 ± 1.9 mV in group B, P = 0.04). Furthermore, when compared with group B, patients in group A displayed a significantly lower LMD (11 ± 12% vs 16 ± 10%, P = 0.002). Thus, it appears that favorable clinical effects of cell therapy in NICM patients may be associated with a decrease of LMD at cell injection sites. [ABSTRACT FROM AUTHOR]

Non-ischemic dilated cardiomyopathy (NIDCM) constitutes one of the most common causes to non-ischemic heart failure. Despite treatment, the disease often progresses, causing severe morbidity and mortality, making novel treatment strategies necessary. Due to the regenerative actions of mesenchymal stem cells (MSCs), they have been proposed as a treatment for NIDCM. This systematic review aims to evaluate efficacy and mode of action (MoA) of MSC-based therapies in NIDCM. A systematic literature search was conducted in Medline (Pubmed) and Embase. A total of 27 studies were included (3 clinical trials and 24 preclinical studies). MSCs from different tissues and routes of delivery were reported, with bone marrow-derived MSCs and direct intramyocardial injections being the most frequent. All included clinical trials and 22 preclinical trials reported an improvement in cardiac function following MSC treatment. Furthermore, preclinical studies demonstrated alterations in tissue structure, gene, and protein expression patterns, primarily related to fibrosis and angiogenesis. Consequently, MSC treatment can improve cardiac function in NIDCM patients. The MoA underlying this effect involves anti-fibrosis, angiogenesis, immunomodulation, and anti-apoptosis, though these processes seem to be interdependent. These encouraging results calls for larger confirmatory clinical studies, as well as preclinical studies utilizing unbiased investigation of the potential MoA. [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]

Introduction: Although there is evidence of beneficial effects of CD34+ therapy in non-ischemic dilated cardiomyopathy (DCM), the individual patient response is highly variable. Hypothesis: We investigated the value of biomarkers of angiogenesis and endothelial dysfunction in predicting clinical response to transendocardial CD34+ cell transplantation in DCM patients. Methods: We enrolled 34 DCM patients (NYHA class III, LVEF<40%) in whom CD34+ cells were mobilized by G-CSF and collected via apheresis. Electromechanical mapping was performed to define areas of myocardial scar (unipolar voltage <8.3mV and local linear shortening <6%) and hibernation (unipolar voltage ≥8.3mV and local linear shortening <6%) and CD34+ cells were injected transendocardially in the hibernating areas. Patients were followed for 6 months and responders were defined as patients with LVEF increase of >5%. At the time of CD34+ cell transplantation we performed analysis of 27 biomarkers of angiogenesis and endothelial dysfunction. Results: Of 34 patients, 25 (74%) responded to CD34+ cell therapy (responders), and 9 (26%) were classified as non-responders. The groups did not differ in age (55±12 years in responders vs. 59±9 years in non-responders, P=0.43), gender (male: 88% vs. 78%, P=0.36) and baseline LVEF (31±9% vs. 33±7%, P=0.69). When compared to non-responders, responders had lower levels of NT-proBNP (1159±1043 ng/L in responders vs. 2667±2252 ng/L in non-responders, P=0.005), endocan (0.46±0.18 ng/mL vs. 0.62±0.21 ng/mL, P=0.04), thrombospondin-2 (13±5 ng/mL vs. 22±13 ng/mL, P=0.008), activin A (209±51 pg/mL vs. 299±62 pg/mL, P=0.002) and neuropilin-1 (175±35 ng/mL vs. 225±62 ng/mL, P=0.006). Interestingly, we found a significant correlation between these biomarkers and scar burden on electromechanical mapping (endocan: P=0.025, thrombospondin-2: P=0.01, activin A: P=0.015, neuropilin-1: P=0.018). Conclusion: Higher levels of endocan, thrombospondin-2, activin A and neuropilin-1 correlate with poor clinical response and higher scar burden in DCM patients undergoing transendocardial CD34+ cell transplantation. Thus, these biomarkers could represent a non-invasive tool for predicting response to CD34+ cell therapy. [ABSTRACT FROM AUTHOR]