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