1. Cardiac Stem Cell Therapy for the Treatment of Heart Failure
Brandy Weller

2. PICO Question
Patient: Adult patients aged 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 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?

3. 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

4. Heart Failure (Ze-Wei, 2007)
Irrespective of etiology classified by
Cardiac hypertrophy
Insufficient vascularization
Loss of cardiomyoctes
Reduced contractility

5. Diastolic Heart Failure Systolic Heart Failure
Preserved EF
Elevated filling pressure
Systolic Heart Failure
Reduced EF less than 55 %

6. Heart Failure Left sided heart failure Right 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)

7. Heart Failure: (Gajos, 2008)

8. Current Treatment Beta-Blockers ACE-Inhibitors ARB Diuretic
Cardiac Glycosides
(digoxin)
Heart Transplantation

9. Current Treatment Outcomes
Increased morbidity and mortality
Decreased quality of life (Hagege, 2006)
Patients have less < 50 % survival rate after 5 yrs (Ichim, 2008)

10. 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)

11. Stem Cells (Wollert, 2005)

12. 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

13. 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
No controls in this study

14. 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%

15. Stem Cell Therapy (Ichim, 2007, Angelini, 2005)
Improved EF
Immediate vs. long term
Reduction in angina
Improved quality of life
In a review study:

16. 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

17. 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

18. Future Research Methodology of Transplantation During CABG
Intravenous infusion
Transendocardial injection
Transepicardial injection
Transcoronary vein injection
Direct injection into the ventricular wall
Vary in concentration delivered, efficacy, and localization

19. 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

20. 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,
Barbash, IM., Leor, J. (2006). Myocardial regeneration by adult stem cells. Israeli Medical Association Journal. 8,
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):
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),
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: CD
Wollert, KC, Drexler, H. (2005) Clinical applications of stem cells for the heart. Circulation Research. 96,
Ze-Wei, T., Long-gui, LI. (2007). Cell therapy in congestive heart failure. Journal of Zehjang University Science B. 8 (9),