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

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Current Treatment Outcomes

Increased morbidity and mortality Decreased quality of life (Hagege, 2006)

Patients have less < 50 % survival rate after 5 yrs (Ichim, 2008)

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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

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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.