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Cardiac Stem Cell Therapy for the Treatment of Heart Failure
Brandy Weller
PICO Question Patient: Adult patients aged 18-75 with heart
failure defined as an ejection fraction of less than 50%
Interventions: Stem cell therapy Comparison: Medical management Outcome: Reduced morbidity/mortality and
improved ejection fraction Question: In adult patients aged 18-75 with heart
failure defined as an ejection fraction of less than 50% does stem cell therapy reduce morbidity/mortality, and improve ejection fraction when compared to medical management?
Heart Failure(www.MDconsult.com)
Affects nearly 5 million Americans currently, > 500,000 new cases diagnosed each year
Most common inpatient diagnosis in the US for patients > 65 years of age
Affects 2% of the population in developing nations
12-15 million office visits per year More common in men before age 75,
after equally affects both genders
Heart Failure (Ze-Wei, 2007)
Irrespective of etiology classified by Cardiac hypertrophy Insufficient vascularization Loss of cardiomyoctes
Reduced contractility
Systolic Heart Failure Reduced EF less
than 55 %
Diastolic Heart Failure Preserved EF Elevated filling
pressure
www.med.uc.edu/kranias/heart_failure.htm
Heart Failure Left sided heart
failure Ischemic heart
disease HTN Arrhythmias Valvular disease
(AS, AI, MI) Cardiomyopathy Volume Over
loaded
Right sided heart failure Left sided heart
failure COPD PE Pulmonary HTN Valvular disease
(MS)
Heart Failure:(Gajos, 2008)
Current Treatment
Beta-Blockers ACE-Inhibitors ARB Diuretic Cardiac Glycosides
(digoxin) Heart Transplantation
www.googleimages.com
Current Treatment Outcomes
Increased morbidity and mortality Decreased quality of life (Hagege, 2006)
Patients have less < 50 % survival rate after 5 yrs (Ichim, 2008)
http://kidneyinthenews.files.wordpress.com/2007/10/pills1.jpg
Cardiac Myocytes
Believed to be terminally differentiated
Angiogenesis/arteriogenesis Collateral circulation in long standing
ischemia Provides hypothesis that in-situ
cardiac stem cells exist (Wollert, 2005)
Stem Cells(Wollert, 2005)
Stem Cell Therapy(Martin-Rendon, 2008; Zei-Wei, 2007; Angelini, 2005, Wollert, 2005) Initial research in mice with
ischemic heart failure Cardiac myocte repair Increased EF Decreased mortality
Pigs with chronic ischemia Increased collateral blood flow Increased regional contractility
www.googleimages.com
Stem Cell Therapy(Martin-Rendon, 2008 ; Angelini, 2005, Barbash, 2006)
By 2004 > 150 humans underwent stem cell therapy
Observational studies No controls Reduction in scar tissue after MI Revascularization Reversed ischemia (75% improvement) Increased ejection fraction
N=8 avg increase 8.7% in <1 yr
Stem Cell Therapy(Zei-Wei, 2007)
Randomized Control study N=60 5% improvement in EF at 6 months No significant improvement over
controls at one year. Greatest improvement seen with
baseline EF less than 48%
Stem Cell Therapy(Ichim, 2007, Angelini, 2005)
Improved EF Immediate vs. long term
Reduction in angina Improved quality of life
Conclusion
Limited research appears to offer hope
More effective than medical management alone
5-10 % improvement in EF can drastically improve quality of life Increased exercise capacity Decreased morbidity/mortality
Future Research(Barbash, 2006)
Type of Donor source Bone Marrow In-situ cardiac stem
cells Skeletal myoblasts Placental/
mesenchymal cord blood
Endothelial progenitor cells
Adult stem cells Located in body
tissues Reservoir for damaged
and aging cells Restricted
differentiation Embryonic stem cells
Controversial Versatile Difficult to control &
tend to form tumors
Future Research
Methodology of Transplantation During CABG Intravenous infusion Transendocardial injection Transepicardial injection Transcoronary vein injection Direct injection into the ventricular
wall
Application With future research confirming
efficacy An adjunct to medical management
Reduction in infarcted tissue (Wollert, 2005)
Not generally achieved with medical management alone
Potential to reduce demand for heart transplantation
Patients with inoperable CAD
References Angelini, P., Markwald, RR. (2005). Stem cell treatment of the heart. A review of its
current status on the brink of clinical experimentation. Texas Heart Institute Journal. 32, 479-488.
Barbash, IM., Leor, J. (2006). Myocardial regeneration by adult stem cells. Israeli Medical Association Journal. 8, 283-187.
Hagege, AA., Marolleau J., Vilquin, J., Alheritiere, A., Peyrard, S., Duboc, D., Abergel, E., Messas, E., Mosseaux, E., Schwartz, K., Desnos, M., Menasche, P., (2006). Skeletal myoblast transplantation in ischemic heart failure. Long-term follow-up of the first phase I cohort of patients. Circulation. 114 (supplement I): 108-113.
Ichim, TE., Solano, F., Brenes, R., Eduardo, G., Chang, J., Chan, K., Riordan, NH. (2007). Placental mesenchymal and cord blood stem cell therapy for dilated cardiomyopathy. Reproductive BioMedicine. 16 (6), 898-905.
Martin-Rendon, E., Brunskill, S., Doree, C., Watt, S., Mathur, A., Stanworth, S. (2008). Stem cell treatment for acute myocardial infarction. Cochrane Database System Review, 4: CD006536.
Wollert, KC, Drexler, H. (2005) Clinical applications of stem cells for the heart. Circulation Research. 96, 151-163.
Ze-Wei, T., Long-gui, LI. (2007). Cell therapy in congestive heart failure. Journal of Zehjang University Science B. 8 (9), 647-660.