Projects / Programmes
A PILOT TRIAL OF CELL THERAPY IN HEART FAILURE WITH PRESERVED
EJECTION FRACTION (CELLpEF)
| Code |
Science |
Field |
Subfield |
| 3.06.00 |
Medical sciences |
Cardiovascular system |
|
| Code |
Science |
Field |
| B530 |
Biomedical sciences |
Cardiovascular system |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
heart failure, stem cell therapy
Researchers (15)
Organisations (2)
Abstract
Background
Heart failure with preserved ejection fraction (HFpEF) is present in nearly half of the general heart failure population, but very few effective treatments for this condition are available. Our group has previously demonstrated that the disease progression in heart failure with reduced ejection fraction can be partially reversed by transendocardial application of autologous CD34+ cells. This approach was also associated with improvement in regional myocardial perfusion and diastolic parameters. Based on these results, the aim of the present project is to investigate the safety andefficacy of CD34+ cell therapy in HFpEF patients.
Objectives
The primary objective of the study is to investigate safety and efficacy of transendocardial CD34+ cell therapy in patients with HFpEF by evaluating changes in myocardial structure and function, myocardial perfusion and electrical activity, biomarkers of neurohormonal activation, patient exercise capacity and clinical outcome.
The secondary objective of the study is to better define the patophysiological background of HFpEF by use of multimodality imaging platform, which will include data from electro-anatomical mapping, cardiac magnetic resonance imaging, 2D and 3D echocardiography, and high resolution electrocardiography.
Methods
The study protocol will consist of a prospective, randomized double blind, placebo-controlled design. We will enroll 30 patients with HFpEF. After enrollment, all patients will receive 5-day stem cell mobilization with G-CSF. Thereafter, patients will be randomly allocated to either active (SC Group) or control group (Controls) in a 2:1 ratio. Patient inclusion criteria will consist of all of the following: age 18-80 years old, left ventricular ejection fraction)50%, evidence of diastolic dysfunction by echocardiography (E/e')15), symptoms of heart failure (NYHA functional class II or III), andNT-proBNP levels )300 pg/ml. Patient exclusion criteria will consist of any of the following: acute multi-organ failure, history of any malignant disease within 5 years or diminished functional capacity due to non-cardiac co-morbidities.
Patients in the SC Group will undergo apheresis; CD34+ cells will be collected with immunomagnetic selection, and delivered transendocardialy in the target areas defined by electroanatomical mapping. In the Controls, no apheresis or immunomagnetic selection of CD34+ cells will be performed; the patients will receive transendocardial injections of placebo using the same electroanatomical mapping protocol as in patients from the SC Group. Patients will be followed for 1 year. At baseline, at 6 months, and at 1 year we will perform comprehensive patient evaluation including clinical parameters, high-resolution electrocardiography, echocardiography and cardiac magnetic resonance imaging. All data on patient evaluation will be transferred to a secure central database. Imaging data will be analyzed in a blinded fashion at the independent multimodality-imaging center; laboratory and clinical data will be analyzed using an integration algorithm at the end of the follow-up period.
Expected Results
We expect that transendocardial CD34+ transplantation will be associated with improved heart diastolic function, improvement in exercise capacity, improved myocardial perfusion, decrease in NTproBNP, shortening of QRS complex duration, improved quality of life and decreased number of hospitalizations in patients with HFpEF. Thus, CD34+ cell transplantation could represent the first successful therapeutic approach in HFpEF to date and may significantly improve the outcome and quality of life in this patient population. Furthermore, imaging data generated by the unique multimodality platform may offer an additional insight into the patophysiology of this disease syndrome.
Significance for science
Heart failure remains a major growing public health problem. Although survival after diagnosis of heart failure has improved, overall mortality remains high: approximately 50% of people diagnosed with heart failure will die within 5 years. Despite recent advances in medical and device management of heart failure, a significant proportion of patients reach end-stage heart failure; for these patients, heart transplantation still remains the only treatment of choice.
Nearly one-half of patients with heart failure have preserved ejection fraction (HFpEF), and the prevalence appears to be rising. Patients with HFpEF experience similar patterns of morbidity and functional decline as do those with heart failure and reduced ejection fraction, but no effective treatments are available. The results of our previous clinical trials have demonstrated that CD34+ cell therapy may be associated with improved heart function, better exercise tolerance, and improved long-term survival in heart failure with reduced ejection fraction. Based on this experience, the aim of CELLpEF trial is to further expand the clinical potential of this therapeutic approach to patients with HFpEF.
We expect that transendocardial CD34+ transplantation will be associated with improved left ventricular function, improved quality of life, and decreased number of hospitalizations in patients with HFpEF. Thus, CD34+ cell transplantation could represent the first successful therapeutic approach in HFpEF to date and may significantly improve the outcome and quality of life in this patient population. Furthermore, imaging data generated by the unique multimodality platform may offer an additional insight into the patophysiology of the disease and offer a solid background for further studies in HFpEF patient population.
As demonstrated by epidemiological data and surveys, HFpEF affects the same proportion of male and female patients. Therefore, we expect that our trial will include a substantial proportion of female patient population. This will allow for direct correlation of effectiveness of stem cell therapy between male and female patients with HFpEF.
Significance for the country
Heart failure remains a major growing public health problem. Although survival after diagnosis of heart failure has improved, overall mortality remains high: approximately 50% of people diagnosed with heart failure will die within 5 years. Despite recent advances in medical and device management of heart failure, a significant proportion of patients reach end-stage heart failure; for these patients, heart transplantation still remains the only treatment of choice.
Nearly one-half of patients with heart failure have preserved ejection fraction (HFpEF), and the prevalence appears to be rising. Patients with HFpEF experience similar patterns of morbidity and functional decline as do those with heart failure and reduced ejection fraction, but no effective treatments are available. The results of our previous clinical trials have demonstrated that CD34+ cell therapy may be associated with improved heart function, better exercise tolerance, and improved long-term survival in heart failure with reduced ejection fraction. Based on this experience, the aim of CELLpEF trial is to further expand the clinical potential of this therapeutic approach to patients with HFpEF.
We expect that transendocardial CD34+ transplantation will be associated with improved left ventricular function, improved quality of life, and decreased number of hospitalizations in patients with HFpEF. Thus, CD34+ cell transplantation could represent the first successful therapeutic approach in HFpEF to date and may significantly improve the outcome and quality of life in this patient population. Furthermore, imaging data generated by the unique multimodality platform may offer an additional insight into the patophysiology of the disease and offer a solid background for further studies in HFpEF patient population.
As demonstrated by epidemiological data and surveys, HFpEF affects the same proportion of male and female patients. Therefore, we expect that our trial will include a substantial proportion of female patient population. This will allow for direct correlation of effectiveness of stem cell therapy between male and female patients with HFpEF.
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