Our group studies new ways to regenerate the heart, including cell-based therapies to boost our heart’s ability to repair itself. There have been numerous clinical trials using stem and progenitor cells to treat certain heart failure conditions, however with limited clinical outcome. We aim to improve cell-based treatments for heart failure, through high quality preclinical research, developing new technologies for use during surgical interventions and determining which cell types or factors are most effective for therapy.
Despite significant advances in disease and risk management, therapeutic drugs and surgical interventions, heart failure is still the number one cause of death, accounting for 31% of all deaths world-wide. We’re addressing these challenges in a number of ways.
A new paradigm for preclinical research
The precursor to human clinical trials is preclinical animal studies. We conducted meta-analyses on preclinical research reports to evaluate the quality of the studies. Our findings were disappointing and for many, call into question the leap to human clinical trials. Since then, we’ve created a website, www.preclinicaltrials.eu. Like the respected clinical trials registries (for example, www.clinicaltrialsregister.eu and www.clinicaltrials.gov), we propose to register all confirmatory preclinical animal studies. If reasonable safety and preclinical outcomes are observed, then the research may advance to clinical trials. Our position paper has just been published, launching this new paradigm of research, and scientific journals are considering incorporating this into their author guidelines. [Chamuleau, SAJ, et al; on behalf of the TACTICS group. Translational research in cardiovascular repair: A call for a paradigm shift. Circulation Research, Jan 2018]
New technology for cell therapy
An estimated 45% of patients who undergo stem cell therapy for heart failure do not respond to treatment simply because of inadequate transplantation technique using catheters for injection of cells into the heart. We’ve developed a new way that greatly improves visualization during the procedure, making placement more accurate and reducing procedure time by half. This has opened the field up to novel ways for targeted cardiac interventions.
Clinical trials to improve treatment outcome
The main challenge for heart repair is reversing the functional loss of heart muscle cells – the heart just doesn’t have the ability to do this by itself. We’re conducting several randomized, double-blind placebo-controlled clinical trials to determine which types of cells are best to improve clinical outcome for heart failure patients. [Clinical trials include: HEBE, LUMCU-HF, PRECISE, SCIENCE, AMICI, REPEAT, BAMI]
Finding answers to questions we face daily in the clinic
I still see patients on a daily basis, and as an investigator, am constantly looking for answers to basic clinical questions, particularly regarding imaging and valvular diseases. If there is no answer, we figure out how to provide one. For example, patients with prosthetic heart valves who are on anticoagulation medication (blood thinners to reduce the risk of stroke) often need to stop medication if they have to undergo surgery, even a dental operation. Physicians can bridge the patient by using heparin, of which there are two formulations: by iv injected into the arm that requires admission to the hospital ward; and by an injection just under the skin that can be done at home. The latter is for sure more practical, but no proof of superiority or equal performance is available. Now, in our large multicenter retrospective study, we’ve discovered that there is no difference, and that changed our daily routine practice. This is one way we’re re-defining medical care guidelines for questions we encounter every day.
- Steven Chamuleau, MD, PhD
- Mira van der Naald, MD
- Wouter Gathier, MD
- Thijs vd Broek
- Bas van Klarenbosh
- Steven Wenker
- Marijn Peters
- Einar Hart, MD
- Frebus van Slochteren, PhD
- Klaus Neef, PhD
Clinical Research Coördinator
- Ingrid Meijer – project management
- R&D Cardiology