Guest Post: This is a guest article by Clifford M. Thornton, a Certified Cardiovascular Technologist, experienced Echocardiographer Technician, and journalist in the cardiac and medical device fields. His articles have been published in Inventor’s Digest, Global Innovation Magazine, and Modern Health Talk. He is enthusiastic about progress with cardiac stem cell therapies and their role in heart failure treatment.
Intro to Cardiac Stem Cell Therapies
Human life is dependent upon the heart’s ability to pump forcefully and frequently enough. Most humans cannot live more than four minutes without a heartbeat or continuous blood-flow. At that time, brain cells begin to die because they lack adequately oxygenated blood-flow.
The human adult body requires, on average, 5.0 liters of re-circulated blood per minute. In the cardiology field, this metric is called the “Cardiac Output,” which is calculated as “Stroke Volume (SV)” x “Heart Rate (HR).” Another key metric is a patient’s “Ejection-Fraction (EF %)”. A patient’s EF tells a cardiologist and other physicians if his or her heart is functioning normally or “low normally”. It is a measurement of one’s heart contraction, with a normal EF range being 55-70%.
This number can also be combined with a patient’s heart rate to provide physicians with a baseline of a patient’s cardiac status. A normal range for an adult is 60-100 beats per minute and this can be significantly higher during a normal pregnancy.
Why Do Cardiac Metrics Matter?
For a cardiologist, cardiac metrics indicate if their services are required and allows them to sign-off on pre-operative cardiac clearances. For other physicians, it tells them if the organ which they specialize is being perfused adequately (for example, a nephrologist would be interested to know kidney perfusion). It can also indicate the degree to which decreased heart function may affect severity or spread of disease.
When the heart fails to contract forcefully enough and its performance decreases to the point where its ability to circulate blood adequately is compromised (the EF% falls below 40%), this is considered “heart failure.” The clinical parameters of heart failure are clearly defined by the New York Heart Association (NYHA), which places patients in NYHA Class III & IV into the heart failure category.
An echocardiogram (often called an “Echo”) as opposed to an Electrocardiogram (EKG or ECG), allows technicians and physicians to visualize the beating heart. Video clips of the heart contracting are digitally recorded and a patient’s EF and Cardiac Output (CO) can be measured with several diagnostic tools (Fractional Shortening via 2D or M-Mode measurements, Simpson’s Method via 2D and 3D Quantification) on a cardiovascular ultrasound system.
When an experienced echo tech or cardiologist views a failing heart, it is immediately apparent. Based on my experience reading echocardiograms, I can see that the heart walls or heart muscles (myocardium) are not contracting as vigorously as they should.
Lifestyle and Health Implications of Low Cardiac Function
For patients with a 5% EF range, any physical movement is extremely strenuous and they can go into cardiac arrest at any moment, which is why they are usually on cardiac telemetry in a hospital setting. Most likely, a patient with 5% EF range would be awaiting a heart transplant, unless there is a medical condition preventing them from being eligible.
Once a patient falls into the heart failure range, they will be lethargic and have severe limits on activities. Other clinical manifestations of heart failure can include peripheral edema (i.e. swelling in the feet, legs, ankles, or stomach), pulmonary edema, and shortness of breath. In many cases, this can lead to depression.
In evaluating the frequency of heart failure in the U.S, statistics from the U.S. Centers for Disease Control (CDC) find that approximately 5.7 million adults are afflicted with this condition. Additionally, care for congestive heart failure costs an estimated at $30.7B per year. Furthermore, mortality rates of patients suffering from heart failure indicate its clinical severity, with 1-in-5 patients with this condition dying within a year of receiving the diagnosis.
Treatment Options for Congestive Heart Failure (CHF)
A patient who is experiencing severe heart failure has limited treatment options, which are expensive, complicated, and have major lifestyle implications.
These limited options include:
- Pharmacological therapies
- Left-Ventricular Assist Device (LVAD) placement, a device used while awaiting a heart transplant
- Heart transplant – There are only ~2,000 harvested hearts available for transplant every year in the U.S. (and a heart transplanted may be rejected by the patient’s body)
Consequently, physicians need more effective weapons for treating heart failure in order to improve patients’ lives and reduce healthcare related costs. CHF patients have disproportionate hospital readmission rates when compared to other major diseases.
A Paradigm Shift – Cardiac Stem Cell Treatments
Enter in the growing field of cardiac stem cell treatments, which introduce fundamentally new treatment options for heart failure patients. In cardiac stem cell treatments, stem cells are taken from a patient’s bone marrow or fat tissue in a sterile surgical procedure and injected via a catheter-wire into infarcted or poorly contracting muscular segments of the heart’s main pumping chamber, the left ventricle (LV).
Over the course of a few months, the stem cells impact myocardial cells and begin to improve the contractility of the affected segments, most likely through paracrine signaling mechanisms and impacting the local microenvironment. This can bring a patient’s EF to low-normal or even normal levels. As a result, a patient can live a more normal life and return to many activities.
A very early clinical trial aimed at evaluating the potential and effectiveness of cardiac stem cell therapy in humans was conducted in 2006 utilizing a commercial product, VesCellTM. The parameters and results of this trial were documented in the American Heart Associations’ Circulation, “Abstract 3682: Treatment of Patients with Severe Angina Pectoris Using Intracoronarily Injected Autologous Blood-Borne Angiogenic Cell Precursors”. The subjects of this trial received an intracoronary injection of VesCellTM, an Autologous Angiogenic Cell Precursor (ACP) – based product.
The authors drew their conclusion regarding this study, “VesCell™ therapy for chronic stable angina seems to be safe and improves anginal symptoms at 3 and 6 months. Larger studies are being initiated to evaluate the benefit of VesCell™ for the treatment of this and additional severe heart diseases.” (Source: Tresukosol et al. Abstract 3682: Treatment of Patients with Severe Angina Pectoris Using Intracoronarily Injected Autologous Blood-Borne Angiogenic Cell Precursors. Circulation. October 31, 2006. Vol. 114, Issue Suppl 18. Link: http://circ.ahajournals.org/content/114/Suppl_18/II_786.4 )
Another early cardiac stem cell clinical trial was performed in 2009 by a Cedars-Sinai team based on technologies and discoveries made by Eduardo Marban, MD, PhD, and led by Raj Makkar, MD. In this study, they explored the safety of harvesting, expanding, and administering a patient’s cardiac stem cells to repair heart tissue injured by myocardial infarction.
Recently the American College of Cardiology (ACC) also announced results of a ground-breaking clinical study to evaluate the efficacy and effectiveness of cardiac stem cell treatment for heart failure patients. As stated by Timothy Henry, M.D., Director of Cardiology at Cedars-Sinai Heart Institute and one of the study’s lead authors, “This is the largest double-blind, placebo-controlled stem cell trial for treatment of heart failure to be presented…Based on these positive results, we are encouraged that this is an attractive potential therapy for patients with class III and class IV heart failure.”
Additionally, Dr. Charles Goldthwaite, Jr, published a whitepaper titled, “Mending a Broken Heart: Stem Cells and Cardiac Repair,” in which he draws the conclusion, “Given the worldwide prevalence of cardiac dysfunction and the limited availability of tissue for cardiac transplantation, stem cells could ultimately fulfill a large-scale unmet clinical need and improve the quality of life for millions of people with CVD. However, the use of these cells in this setting is currently in its infancy—much remains to be learned about the mechanisms by which stem cells repair and regenerate myocardium, the optimal cell types and modes of their delivery, and the safety issues that will accompany their use.”
Trend Toward Acceptance of Cardiac Stem Cell Therapies
Clearly, there is a trend toward acceptance of cardiac stem cell therapies as an emerging treatment option. Several world-renowned institutes are now conducting clinical studies involving cardiac stem cell treatment, as well as applying for intellectual property protection (patents) pertaining to the techniques required to administration the therapies.
The key questions at this point in time appear to be:
- What is the best technique or approach for cardiac stem cell therapy administration?
- How long will it take for treatments to get approved by the U.S. FDA and become available?
- How will treatments perform in terms of long-term outcomes for heart failure patients receiving the treatment?
- When cardiac stem and progenitor cells are administered, what mechanisms of action support repair?
An important whitepaper pertaining to cardiac stem cells is “Ischemic Cardiomyopathy Patients Treated with Autologous Angiogenic and Cardio-Regenerative Progenitor Cells,” written by Dr. Athina Kyritsis, et al. In it, the physicians describe their objective as investigating the “feasibility, safety, and clinical outcome of patients with Ischemic Cardiomyopathy treated with Autologous Angiogenic and Cardio-Regenerative Progenitor cells (ACP’s).”
The researchers state: “In numerous human trials there is evidence of improvement in the ejection fractions of Cardiomyopathy patients treated with ACP’s. Animal experiments, not only show improvement in cardiac function, but also engraftment and differentiation of ACP’s into cardiomyocytes, as well as neo-vascularization in infarcted myocardium. In our clinical experience the process has shown to be safe as well as effective.”
The authors also found that patients treated with this approach gained increases in cardiac ejection fraction from their starting measurements, with improvements in their cardiac ejection fraction of “21 points (75% increase) at rest and 28.5 points (80% increase) at stress.” As a result of these finding, the authors conclude, “ACP’s can improve the ejection fraction in patients with severely reduced cardiac function with benefits sustained to six months.”
What Does the Future Hold for Cardiac Stem Cell Therapies?
In the practice of medicine, the focus should be on delivering excellent care to patients. If there are cardiac stem cell treatments available, then regulatory obstacles should be removed when sufficient clinical trial evidence has been provided to indicate safety and efficacy.
Cardiologist Zannos Grekos, MD, a pioneer in cardiac stem cell therapy since 2006, points to the vastly untapped promise of related therapies, commenting “Those of us that have been involved with cardiac stem cell treatment for the last 10-plus years can see the incredible potential this approach has.”
As of 2017, the U.S. healthcare system is under enormous pressure to deliver affordable healthcare and to a growing population of patients, especially those who are fully or partially covered under Medicare or Medicaid (many have secondary coverage). Although we are in the infancy of its development, cardiac stem cell treatments represent a potentially powerful treatment alternative to patients with heart failure symptoms.
To learn more, view the resources below.
Additional Resources about Cardiac Stem Cell Therapies
1) REGENOCYTE – www.regenocyte.com
2) CLEVELAND CLINIC – Stem Cell Therapy for Heart Disease – my.clevelandclinic.org/health/articles/stem-cell-therapy-heart-disease
3) HARVARD STEM CELL INSTITUTE (HSCI) – hsci.harvard.edu/heart-disease-0
4) CEDARS-SINAI – Cardiac Stem Cell Treatment – www.cedars-sinai.edu/Patients/Programs-and-Services/Heart-Institute/Clinical-Trials/Cardiac-Stem-Cell-Research.aspx
5) JOHNS HOPKINS MEDICINE – Cardiac Stem Cell Treatments – http://www.hopkinsmedicine.org/stem_cell_research/cell_therapy/a_new_path_for_cardiac_stem_cells.html
About the Author: Clifford M. Thornton can be reached at phone at 267-524-7144 or by email at [email protected].