The CADUCEUS clinical trial, which stands for CArdiosphere-Derived aUtologous stem CElls, to reverse ventricUlar dySfunction) was the brainchild of Cedar-Sinai cardiologist Eduardo Marbán and his colleagues.
This CADUCEUS trial used a heart-specific stem cell called CDCs or cardiosphere-derived cells to treat patients who had recently suffered a heart attack. CDCs are extracted from the patient’s own heart and they can be grown in culture, expanded, and then implanted back into the patient’s heart. The initial assessments of those patients who had received the stem cell treatments was published in 2012 in the Journal Lancet (R.R. Makkar, R.R. Smith, K. Cheng et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet, 379 (2012), pp. 895–904). The initial assessments of these patients showed shrinkage of their heart scars. However, these patients showed regional improvements in heart function but no significant differences in global heart function. Despite these caveats, the initial results were hopeful.
Now the one-year follow-up of these patients has been published in the Journal of the American College of Cardiology. The results of this examination are even more exciting.
CDCs were extracted from patients by means of heart biopsies of the inner part of the heart muscle (myocardium). After the cells were grown in culture to larger numbers, they were reintroduced to the hearts of the patients by means of “stop-flow” technique. This procedure utilizes the same technology as stents in that an over-the-wire balloon angioplasty catheter that was positioned in the blood vessels on the heart that were blocked. The figure below shows the cultured cardiospheres.
The initial assessment of these patients showed shrinkage of the heart scar and regional improvements in heart function. However in the one-year follow-up the scar showed even more drastic shrinkage (-11.9 grams or -11.1% of the left ventricle). Also, several of the indicators of global heart function showed substantial improvements (end-diastolic volume – -12.7 mls and end-systolic volume – -13.2 mls).
When it come to the all-important ejection fraction, which is the percentage of blood pumped from the left ventricle, the results are a little more complicated. When the ejection factions of each patient was compared with the size of their heart scars, there was a tight correlation between the increase in ejection fraction and the shrinkage of the heart scar. See the figure below for a scatter plot of ejection fraction versus heart scar size.
Other observations included safety assessments. When the number of adverse events between the control group and CDC-receiving group were measured, there were no differences between the two groups. The patients in the CDC-receiving group were more likely to be hospitalized and had transient cases of fast heartbeats, and there was also one death in this group. However the incidence of these events were not statistically different from the control group.
From these assessments, it is clear that the CDC treatments are safe, and decreased the scar size and regional function of infarcted heart muscle. From these results, the researchers state that “These findings motivate the further exploration of CDCs in future clinical studies.