scholarly journals Correlation between Therapeutic Efficacy of CD34+ Cell Treatment and Directed In Vivo Angiogenesis in Patients with End-Stage Diffuse Coronary Artery Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Tien-Hung Huang ◽  
Cheuk-Kwan Sun ◽  
Yi-Ling Chen ◽  
Pei-Hsun Sung ◽  
Chi-Hsiang Chu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Therapeutic Efficacy ◽  
Peripheral Blood Mononuclear ◽  
Angiogenesis Assay ◽  
Diffuse Coronary Artery Disease ◽  
Significant Difference ◽  
Artery Disease ◽  
End Stage

Background. This study was aimed at testing the association between the therapeutic efficacy of CD34+ cell treatment in patients with end-stage diffuse coronary artery disease as reflected in angiographic grading and results of directed in vivo angiogenesis assay (DIVAA) on their isolated peripheral blood mononuclear cell- (PBMC-) derived endothelial progenitor cells (EPCs). Methods. Angiographic grades (0: <5%; 1: 5–35%; 2: 35–75%; 3: >75%) which presented the improvement of vessel density pre- and post-CD34+ treatment were given to 30 patients with end-stage diffuse coronary artery disease having received CD34+ cell treatment. The patients were categorized into low-score group (angiographic grade 0 or 1, n=12) and high-score group (angiographic grade 2 or 3, n=18). The percentages of circulating EPCs with KDR+/CD34+/CD45−, CD133+/CD34+/CD45−, and CD34+ were determined in each patient using flow cytometry. PBMC-derived EPCs from all patients were subjected to DIVAA through a 14-day implantation in nude mice. The DIVAA ratio (i.e., mean fluorescent units in angioreactors with EPCs/mean fluorescent units in angioreactors without EPCs) was obtained for each animal with implanted EPCs from each patient. Results and Conclusions. The number of EPCs showed no significant difference among the two groups. The DIVAA ratio in the high-score group was significantly higher than that in the low-score group (p=0.0178). Logistic regression revealed a significant association between the DIVAA ratio and angiographic grading (OR 3.12, 95% CI: 1.14–8.55, p=0.027). The area under the ROC curve (AUC) was 0.8519 (p=0.0013). We proposed that DIVAA may be a reliable tool for assessing coronary vascularization after CD34+ cell treatment.

scholarly journals Baseline Factors Identified For Prediction of Good Responders in Patients With End-Stage Diffuse Coronary Artery Disease Undergoing Intracoronary CD34+ Cell Therapy

2020 ◽  
Author(s):  
Pei-Hsun Sung ◽  
Hsin-Ju Chiang ◽  
Yi-Chen Li ◽  
John Y Chiang ◽  
Chi-Hsiang Chu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Coronary Artery ◽  
Cell Therapy ◽  
Phase I ◽  
Diastolic Dysfunction ◽  
Diffuse Coronary Artery Disease ◽  
Artery Disease ◽  
End Stage

Abstract Background: Treating patients with end-stage diffuse coronary artery disease (EnD-CAD) unsuitable for coronary intervention remains a clinical challenge. They usually express refractory angina and have high risk for mortality. Although growing data have indicated cell therapy is an alternative solution to medical or invasive therapy, there are still lacking useful markers to predict whether heart function will improve in the EnD-CAD patients who underwent circulatory-derived CD34+ cell therapy. By utilizing the baseline variables and results from our previous phase I/II clinical trials, the aim of this study tried to elucidate the variables predictive of the “good response” to CD34+ cell therapy.Methods: This retrospective study included 38 patients in the phase I clinical trial (2011-2014), and 30 patients in the phase II clinical trial (2013-2017). These patients were categorized into “good responders” and “non-responders” according to their 1-year improvement of LVEF ≥7.0% or <7.0% after intracoronary CD34+ cell therapy. Univariate and multivariate logistic regression model was performed to identify potential independent predictors of good responder to cell therapy, followed by Hosmer–Lemeshow (H-L) test for goodness of fit and prediction power.Results: Among baseline data, multivariate analysis demonstrated that history of former smoker was independently predictive of good responders (p=0.006). On the other hand, male gender, the baseline Canadian Cardiovascular Society angina score ≥3 and grades of LV diastolic dysfunction ≥2 were significantly negative predictors of good responders (all p<0.01). After administration of subcutaneous granulocyte-colony stimulating factor (G-CSF), a higher post-G-CSF neutrophil count in addition to the above four baseline variables played crucial roles in early prediction of good response to CD34+ cell therapy for EnD-CAD (all p<0.03). The H-L test displayed a good prediction power with sensitivity 83.3%, specificity 85.3% and accuracy 84.4%. Conclusions: Using the results of our phase I/II clinical trials, previous smoking habit, female sex, lower grades of angina score and diastolic dysfunction were identified to be independently predictive of “good response” to CD34+ cell therapy in the patients with EnD-CAD.Trial registration: This is a retrospective analysis based on the phase I (ISRCTN72853206) and II (ISRCTN26002902) clinical trials

scholarly journals Baseline factors identified for prediction of good responders in patients with end-stage diffuse coronary artery disease undergoing intracoronary CD34+ cell therapy

2020 ◽  
Author(s):  
Pei-Hsun Sung ◽  
Hsin-Ju Chiang ◽  
Yi-Chen Li ◽  
John Y Chiang ◽  
Chi-Hsiang Chu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Coronary Artery ◽  
Cell Therapy ◽  
Phase I ◽  
Diastolic Dysfunction ◽  
Diffuse Coronary Artery Disease ◽  
Artery Disease ◽  
End Stage

Abstract Background: Treating patients with end-stage diffuse coronary artery disease (EnD-CAD) unsuitable for coronary intervention remains a clinical challenge. They usually express refractory angina and have high risk for mortality. Although growing data have indicated cell therapy is an alternative solution to medical or invasive therapy, there are still lacking useful markers to predict whether heart function will improve in the EnD-CAD patients who underwent circulatory-derived CD34+ cell therapy. By utilizing the baseline variables and results from our previous phase I/II clinical trials, the aim of this study tried to elucidate the variables predictive of the “good response” to CD34+ cell therapy.Methods: This retrospective study included 38 patients in the phase I clinical trial (2011-2014), and 30 patients in the phase II clinical trial (2013-2017). These patients were categorized into “good responders” and “non-responders” according to their 1-year improvement of LVEF ≥7.0% or <7.0% after intracoronary CD34+ cell therapy. Univariate and multivariate logistic regression models were performed to identify potential independent predictors of good responder to cell therapy, followed by Hosmer–Lemeshow (H-L) test for goodness of fit and prediction power.Results: Among baseline data, multivariate analysis demonstrated that history of former smoker was independently predictive of good responders (p=0.006). On the other hand, male gender, the baseline Canadian Cardiovascular Society angina score ≥3 and grades of LV diastolic dysfunction ≥2 were significantly negative predictors of good responders (all p<0.01). After administration of subcutaneous granulocyte-colony stimulating factor (G-CSF), a higher post-G-CSF neutrophil count in addition to the above four baseline variables also played crucial roles in early prediction of good response to CD34+ cell therapy for EnD-CAD (all p<0.03). The H-L test displayed a good prediction power with sensitivity 83.3%, specificity 85.3% and accuracy 84.4%. Conclusions: Using the results of our phase I/II clinical trials, previous smoking habit, female sex, lower grades of angina score and diastolic dysfunction were identified to be independently predictive of “good response” to CD34+ cell therapy in the patients with EnD-CAD.Trial registration: This is a retrospective analysis based on the phase I (ISRCTN72853206) and II (ISRCTN26002902) clinical trials

Markers of Hemostatic Activation in Affected Coronary Arteries during Angioplasty

1994 ◽  
Vol 72 (05) ◽  
pp. 672-675 ◽  
Author(s):  
Nicolas W Shammas ◽  
Michael J Cunningham ◽  
Richard M Pomearntz ◽  
Charles W Francis
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Venous Blood ◽  
Balloon Inflation ◽  
Blood Samples ◽  
Hemostatic System ◽  
Significant Difference ◽  
Hemostatic Markers ◽  
Artery Disease ◽  
High Doses

SummaryTo characterize the extent of early activation of the hemostatic system following angioplasty, we obtained blood samples from the involved coronary artery of 11 stable angina patients during the procedure and measured sensitive markers of thrombin formation (fibrino-peptide A, prothrombin fragment 1.2, and soluble fibrin) and of platelet activation ((3-thromboglobulin). Levels of hemostatic markers in venous blood obtained from 14 young individuals with low pretest probability for coronary artery disease were not significantly different from levels in venous blood or intracoronary samples obtained prior to angioplasty. Also, there was no translesional (proximal and distal to the lesion) gradient in any of the hemostatic markers before or after angioplasty in samples obtained between 18 and 21 min from the onset of the first balloon inflation. Furthermore, no significant difference was noted between angioplasty and postangioplasty intracoronary concentrations. We conclude that intracoronary hemostatic activation does not occur in the majority of patients during and immediately following coronary angioplasty when high doses of heparin and aspirin are administered.

The Effect of Antiplatelet Drugs on Plasma Betathromboglobulin in Coronary Artery Disease

1979 ◽  
Author(s):  
P Han ◽  
A Turpie ◽  
E Genton ◽  
M Gent
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Crossover Trial ◽  
Specific Protein ◽  
Antiplatelet Drugs ◽  
Significant Difference ◽  
Pre Treatment ◽  
Artery Disease ◽  
Therapeutic Doses ◽  
Granule Release

Platelets play a role in the development and complications of coronary artery disease (CAD) and a number of abnormalities of platelet function which can be corrected by antiplatelet drugs have been described. Betathromboglobulin (BTG), a platelet-specific protein which is released from α-granules during platelet activation is significantly elevated in patients with angiographically demonstrated CAD (51.0 ± 31.0 ng/ml., n = 50) compared to normal (28.0 ± 8.0 ng/ml., n = 70) p < 0.001. The effect of sulphinpyrazone (800 mg.) or aspirin (1200 mg.)/dipyridamole (200 mg.) on plasma BTG in CAD was studied in a blind prospective crossover trial in 25 patients. Mean BTG concentration pre-treatment was 52.3 ng/ml. and after 1 month’s treatment with placebo, sulphinpyrazone or aspirin/dipyridamole mean plasma BTG concentrations were 53.5, 49.6 and 56.7 ng/ml. respectively. Analysis of variance showed no significant difference between the means (p > 0.1) . This study confirms increased plasma BTG concentrations in patients with CAD and indicates that therapeutic doses of these antiplatelet drugs do not significantly effect the BTG level and thus appear not to prevent α-granule release in CAD.

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