The FOCUS-CCTRN Trial – Transendocardial Delivery of Bone Marrow Stem Cells Improves Heart Function in Heart Attack Patients

Mayo Clinic researchers have completes a Phase II clinical study that demonstrates that bone marrow stem cells can fix a sick heart. They discovered that stem cells derived the bone marrow of heart patients, when isolated and injected into their hearts, improved heart function. These researchers also found that particular types of the stem cells seemed to be responsible for the largest patient improvement, and, therefore, warrant further study.

This clinical study is an extension of earlier work in Brazil that treated a small number of patients with fewer stem cells (Perin EC, Dohmann HF, Borojevic R, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation. 2003;107(18):2294-2302.). The earlier study treated 21 patients, seven of whom received placebo treatments and fourteen others who received injections of bone marrow stem cells into the walls of their hearts.  In this study, a total of 92 (82 men; average age: 63 years) were randomly assigned to the placebo or experimental groups (n=61 in Bone Marrow Cell transplant group and n=31 in the placebo group).  This patient group suffered from coronary artery disease or LV dysfunction, and limiting heart failure or angina.  These patients had weakened hearts as a result of previous heart attacks.

These 92 patients received either a placebo (sterile saline bereft of any cells) or 100 million bone marrow-derived stem cells that were extracted from the patient’s hips. In all cases the treatment consisted of a one-time injection into the wall of the heart.  This injection procedure actually consisted of 15 small injections in stem cells into regions of the ventricle wall that were known to consist of live cells as demonstrated by previous “electromechanical mapping” studies of the heart (see Willerson JT, Perin EC, Ellis SG, et al. Intramyocardial injection of autologous bone marrow mononuclear
cells for patients with chronic ischemic heart disease and left ventricular dysfunction (First Mononuclear Cells injected in the US [FOCUS]). Am Heart J. 2010;160(2):215-223
for a description of this mapping).  The injections were made performed with a NOGA catheter.  This clinical trial is the first clinical to use such a large a dose of stem cells.

NOGA Catheter

The significance of using these patient’s own bone marrow stem cells is not lost on cardiologists, since previous reports have shown that bone marrow from patients with chronic heart conditions or who have suffered heart attacks show diminished stem cell populations and activities (see Heeschen C, Lehmann R, Honold J, et al. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation. 2004;109(13):1615-1622 & Kissel CK, Lehmann R, Assmus B, et al. Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure. J Am Coll Cardiol. 2007;49(24):2341-2349).  If higher doses of stem cells can still help improve the function of such heart patients, then perhaps such a protocol would be helpful for them.

Mayo Clinic cardiologist Robert Simari, who was part of this study, said “We found that the bone marrow cells did not have a significant impact on the original end points that we chose, which involved reversibility of a lack of blood supply to the heart, the volume of the left ventricle of the heart at the end of a contraction, and maximal oxygen consumption derived through a treadmill test.” Simari is chairman of the Cardiovascular Cell Therapy Research Network (CCTRN), which is a network of five academic centers and associated satellite sites that conducted the study. The CCTRN is supported by the National Heart, Lung, and Blood Institute, which also funded the study.

Simari described the results of this study: “But interestingly, we did find that the very simple measure of ejection fraction was improved in the group that received the cells compared to the placebo group by 2.7 percent.” Ejection fraction refers to the average percentage of blood pumped from the left ventricle each time the heart pumps.  You can listen to Simari discuss this clinical trial here.

Emerson Perin, and James Willerson of the Texas Heart Institute, who were the principal investigators in this study, noted that although 2.7 percent does not seem like a large number, it does represent a statistically significant increase and this means an improvement in heart function for chronic heart failure patients who have no other options.

Dr. Perin noted, “This was a pretty sick population. They had already had heart attacks, undergone bypass surgery, and had stents placed. However, they weren’t at the level of needing a heart transplant yet. In some patients, particularly those who were younger or whose bone marrows were enriched in certain stem cell populations had even greater improvements in their ejection fractions.”

The study participants had an average age of 63 years old, but this study showed that those patients who are younger than the average participant age improved more than the average. In these patients, the ejection fraction improved by 4.7 percent. The variable that seemed to predict whether or not the patient would benefit from this procedure was the quality of their bone marrow stem cells.  Detailed examinations of bone marrow stem cell populations from each patient showed that younger patients who showed greater improvements have large quantities of CD34+- and CD133+-type stem cells in their bone marrow isolates.  Stem cells with these particular markers tend to produce blood vessels and making more blood vessels, increases the flow of oxygen and nutrients to the heart muscle.  This spares the damaged heart muscle from experiencing more damage and shores the existing heart muscle to improve its function.

Dr. Simari concluded, “This tells us that the approach we used to deliver the stems cells was safe. It also suggests new directions for the next series of clinical trials, including the type of patients, endpoints to study and types of cells to deliver.”

Dick Cheney’s Heart Transplant

Because people have asked me to comment on the Dick Cheney heart transplant, I thought I would make one entry about it. Readers of this blog will recognize that I have very conservative leanings when it comes to subjects such as politics and health care. Also, the organ transplant waiting lists are local and federal. The decision to put someone on the organ recipient list is a decision that is between the patient and their physicians. I do not think the government has any right to intercede in the decision because it is a private decision. The shortage of organs can be addressed in other ways, but it seems to me that rationing by the government is simply wrong and contrary to the founding principles of our constitutional republic.

Having said all that, Cheney waited 20 months to receive his heart, and he was given no special treatment. You can argue that a younger person should have received this heart, but why? Cheney waited his turn. His age was, in his doctor’s opinion, not an important factor. Therefore, we should go with his doctor and not some bureaucrat.

Nevertheless, the best story on this comes from the inimitable Wesley Smith.  Read his view here.  It says it all.