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EFFECTS OF CD34+ STEM CELL TRANSPLANTATION ON RIGHT VENTRICULAR FUNCTION IN PATIENTS WITH NONISCHEMIC DILATED CARDIOMYOPATHY

Sabina Frljak

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Abstract

ABSTRACT Aims. Contraction of interventricular septum (IVS) represents an important component of right ventricular (RV) function. We investigated the effects of transendocardial delivery of CD34+ cells into IVS on RV function in patients with non-ischemic dilated cardiomyopathy (DCM). Methods. We enrolled 80 patients with non-ischemic DCM, NYHA functional class 3 and LVEF<40%. At baseline, patients received granulocyte-colony stimulating factor; cells were collected by apheresis and immunomagnetic selection to yield a total dose of 80 million CD34+ cells. With the guidance of electroanatomical mapping cell suspension was injected transendocardialy in the areas of myocardial hibernation, defined as unipolar voltage ≥8.27 mV and linear shortening <6%. Each patient received 20 injections of 0.3 mL. Patients who received cell at least 1 cell injection in the IVS area were included in Group A (N=40), and patients without IVS cell injections were assigned to Group B (N=40). Patients from both groups were followed for 6 months and changes in RV function were assessed by tricuspid annular plane systolic excursion (TAPSE), peak systolic velocity of tricuspid annulus (St), and fractional area change (FAC). Results. At baseline, the groups did not differ in age (57±9 years in Group A vs. 55±10 years in Group B, P=0.48), gender (male: 87% vs. 80%, P=0.54), LVEF (30.3±8.2% vs. 31.7±6.8%, P=0.32), or NTproBNP (1219±1338 pg/ml vs. 1298±1359 pg/ml, P=0.79). Similarly, we found no inter-group difference in RV function (TAPSE: 1.82±0.40 cm vs. 1.86±0.52 cm, P=0.69; St: 10.3±2.2 cm/s vs. 10.6±3.2 cm/s, P=0.70; FAC: 30±6% vs. 31±9%, P=0.66). At 6 months, we found an overall improvement in all parameters of RV function (TAPSE: +0.31±0.12 cm, P=0.001; St: +1.0±1.2 cm/s; P=0.002; FAC: +8.9±2.9%, P=0.01). RV function improvement was more prominent in Group A (TAPSE: +0.43±0.64 cm, P=0.001; St: +1.5±2.4 cm/s; P=0.01; FAC: +9.9±2.1%, P=0.01) than in Group B (TAPSE: +0.18±0.14 cm, P=0.24; St: +0.4±1.1 cm/s; P=0.30; FAC: +8.7±3.1%, P=0.01). In both groups we found a significant correlation between TAPSE and IVS viability as measured by unipolar voltage (Pearson r=0.58, P<0.001). Conclusions. In non-ischemic DCM, RV function correlates with the viability of IVS. In these patients, cell therapy targeting IVS area appears to be associated with improvement of RV function.

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ABSTRACT Aims. Contraction of interventricular septum (IVS) represents an important component of right ventricular (RV) function. We investigated the effects of transendocardial delivery of CD34+ cells into IVS on RV function in patients with non-ischemic dilated cardiomyopathy (DCM). Methods. We enrolled 80 patients with non-ischemic DCM, NYHA functional class 3 and LVEF<40%. At baseline, patients received granulocyte-colony stimulating factor; cells were collected by apheresis and immunomagnetic selection to yield a total dose of 80 million CD34+ cells. With the guidance of electroanatomical mapping cell suspension was injected transendocardialy in the areas of myocardial hibernation, defined as unipolar voltage ≥8.27 mV and linear shortening <6%. Each patient received 20 injections of 0.3 mL. Patients who received cell at least 1 cell injection in the IVS area were included in Group A (N=40), and patients without IVS cell injections were assigned to Group B (N=40). Patients from both groups were followed for 6 months and changes in RV function were assessed by tricuspid annular plane systolic excursion (TAPSE), peak systolic velocity of tricuspid annulus (St), and fractional area change (FAC). Results. At baseline, the groups did not differ in age (57±9 years in Group A vs. 55±10 years in Group B, P=0.48), gender (male: 87% vs. 80%, P=0.54), LVEF (30.3±8.2% vs. 31.7±6.8%, P=0.32), or NTproBNP (1219±1338 pg/ml vs. 1298±1359 pg/ml, P=0.79). Similarly, we found no inter-group difference in RV function (TAPSE: 1.82±0.40 cm vs. 1.86±0.52 cm, P=0.69; St: 10.3±2.2 cm/s vs. 10.6±3.2 cm/s, P=0.70; FAC: 30±6% vs. 31±9%, P=0.66). At 6 months, we found an overall improvement in all parameters of RV function (TAPSE: +0.31±0.12 cm, P=0.001; St: +1.0±1.2 cm/s; P=0.002; FAC: +8.9±2.9%, P=0.01). RV function improvement was more prominent in Group A (TAPSE: +0.43±0.64 cm, P=0.001; St: +1.5±2.4 cm/s; P=0.01; FAC: +9.9±2.1%, P=0.01) than in Group B (TAPSE: +0.18±0.14 cm, P=0.24; St: +0.4±1.1 cm/s; P=0.30; FAC: +8.7±3.1%, P=0.01). In both groups we found a significant correlation between TAPSE and IVS viability as measured by unipolar voltage (Pearson r=0.58, P<0.001). Conclusions. In non-ischemic DCM, RV function correlates with the viability of IVS. In these patients, cell therapy targeting IVS area appears to be associated with improvement of RV function.

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Available abstract

ABSTRACT Aims. Contraction of interventricular septum (IVS) represents an important component of right ventricular (RV) function. We investigated the effects of transendocardial delivery of CD34+ cells into IVS on RV function in patients with non-ischemic dilated cardiomyopathy (DCM). Methods. We enrolled 80 patients with non-ischemic DCM, NYHA functional class 3 and LVEF<40%. At baseline, patients received granulocyte-colony stimulating factor; cells were collected by apheresis and immunomagnetic selection to yield a total dose of 80 million CD34+ cells. With the guidance of electroanatomical mapping cell suspension was injected transendocardialy in the areas of myocardial hibernation, defined as unipolar voltage ≥8.27 mV and linear shortening <6%. Each patient received 20 injections of 0.3 mL. Patients who received cell at least 1 cell injection in the IVS area were included in Group A (N=40), and patients without IVS cell injections were assigned to Group B (N=40). Patients from both groups were followed for 6 months and changes in RV function were assessed by tricuspid annular plane systolic excursion (TAPSE), peak systolic velocity of tricuspid annulus (St), and fractional area change (FAC). Results. At baseline, the groups did not differ in age (57±9 years in Group A vs. 55±10 years in Group B, P=0.48), gender (male: 87% vs. 80%, P=0.54), LVEF (30.3±8.2% vs. 31.7±6.8%, P=0.32), or NTproBNP (1219±1338 pg/ml vs. 1298±1359 pg/ml, P=0.79). Similarly, we found no inter-group difference in RV function (TAPSE: 1.82±0.40 cm vs. 1.86±0.52 cm, P=0.69; St: 10.3±2.2 cm/s vs. 10.6±3.2 cm/s, P=0.70; FAC: 30±6% vs. 31±9%, P=0.66). At 6 months, we found an overall improvement in all parameters of RV function (TAPSE: +0.31±0.12 cm, P=0.001; St: +1.0±1.2 cm/s; P=0.002; FAC: +8.9±2.9%, P=0.01). RV function improvement was more prominent in Group A (TAPSE: +0.43±0.64 cm, P=0.001; St: +1.5±2.4 cm/s; P=0.01; FAC: +9.9±2.1%, P=0.01) than in Group B (TAPSE: +0.18±0.14 cm, P=0.24; St: +0.4±1.1 cm/s; P=0.30; FAC: +8.7±3.1%, P=0.01). In both groups we found a significant correlation between TAPSE and IVS viability as measured by unipolar voltage (Pearson r=0.58, P<0.001). Conclusions. In non-ischemic DCM, RV function correlates with the viability of IVS. In these patients, cell therapy targeting IVS area appears to be associated with improvement of RV function.

Key concepts: Medicine, Interventricular septum, Cardiology, Ejection fraction, Dilated cardiomyopathy, Internal medicine, Transplantation, Ventricle

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EFFECTS OF CD34+ STEM CELL TRANSPLANTATION ON RIGHT VENTRICULAR FUNCTION IN PATIENTS WITH NONISCHEMIC DILATED CARDIOMYOPATHY — Research Paper | ScholarLens