Transendocardial CD34+ Cell Therapy Improves Local Mechanical Dyssynchrony in Patients With Nonischemic Dilated Cardiomyopathy.

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.

Improvement of arterial wall phenotype in subjects at moderate cardiovascular risk induced by very low-dose fluvastatin/valsartan combination: a pilot study.

BACKGROUND: The largest population that suffers from cardiovascular events are subjects at moderate cardiovascular risk. However, no effective and safe preventive treatment is available for this population. We investigated whether their arterial wall phenotype could be turned to a lower risk direction by low-dose fluvastatin/valsartan combination (low-flu/val). METHODS: Twenty males at moderate cardiovascular risk (as classified by SCORE) were blindly randomized into the intervention group (N.=10, low-flu/val: 10 mg/20 mg) or control group (N.=10, placebo). At inclusion and after 30 days of treatment, brachial flow-mediated dilatation (FMD), ß-stiffness coefficient, carotid pulse wave velocity (c-PWV), carotid-femoral PWV, Reactive Hyperemia Index, high-sensitivity C-reactive protein (hs-CRP), interleukin 6, vascular cell adhesion molecule 1, total antioxidant status and expression of several protective genes (SIRT1, mTOR, NF-κB1, NFE2L2, PRKAA1) were followed. RESULTS: Treatment resulted in improved FMD (from 3% to 4.2%, P=0.008), c-PWV (from 6.7 to 6.2 m/s, P=0.006), hs-CRP (from 5.39 to 3.35 mg/L, P=0.041) and SIRT1 expression (3.34-fold difference, P=0.047). No other vascular, inflammation and genetic parameters changed. The hs-CRP values after intervention correlated significantly with SIRT1 expression. The improved FMD persisted even 10 weeks after treatment discontinuation. The obtained changes were not followed by changes of lipids or blood pressure. Overall, the results revealed improvement in three different, although interrelated preventive arterial wall characteristics. CONCLUSIONS: This pilot study revealed that intervention with low-flu/val importantly shifts the arterial wall phenotype in a lower risk direction. This improvement could be interpolated into clinical benefits that remain to be further studied.