Technical solutions to improve cardiac regenerative therapy (CART)

Introduction to CArdiac Regenerative Therapy (CART)
Cardiovascular disease is the leading cause of death and disability, claiming an estimated annual 17.3 million lives worldwide. Ischemic heart disease, which includes myocardial infarction, angina pectoris and chronic heart failure, is the main contributor to cardiovascular morbidity and mortality. Up to 74% of myocardial infarctions lead to heart failure, with a 5-year-mortality of more than 60% in the affected population and an average survival rate of less than 1.7 years after diagnosis.

Over the past decade, cardiac regenerative therapy has emerged as a promising therapeutic strategy for ischemic heart disease. Novel regenerative therapies involve stem cells and second generation products can also include biologicals or small molecule drugs which in some cases can be formulated with biomaterials.

Despite the excitement surrounding cardiac regenerative therapy, many challenges still remain. These include selection of the appropriate cell type, appropriate dose and timing of therapy, and efficient and standardized delivery methods.

Optimal targeting of CArdiac Regenerative Therapy
Injecting therapeutics into the beating heart is a difficult and currently inefficient procedure. With the most advanced catheters, which deliver the cells directly in the heart tissue, higher delivery efficiencies may be reached. It is vital that a high proportion of the therapeutic dosage is delivered to a location close to the ischemic area where oxygen and nutrients are available to support the survival of injected cells. This area is defined as the infarct border zone, and accurate targeting of therapeutics precisely to this border zone is essential for effective repair or support of the ischemic heart.

Moreover, certain areas of the myocardium, in particular the transmurally infarcted areas, or areas where the myocardium is very thin need to be avoided at all cost since puncturing of these areas (danger zones) can lead to serious injury for the patients.

Currently there is no gold standard for the determination and targeting of the border zone for the injections, and cardiologists worldwide rely on their own experience and judgment. To optimize cardiac regenerative therapy, CART-Tech is developing a new image-guided delivery technology which provides real-time visualization of the border zone of the infarcted area, and the danger zones during catheter based intramyocardial injection procedures. Hereby injections can be performed on the optimal location and dangerous areas can be avoided. This is an important step to increase the efficacy and safety of cardiac regenerative therapy.

Catheterisation lab, Department of Cardiology,
Utrecht Universty Medical Center