Investigation of autologous cell transplantation (ACT) for the treatment of damaged myocardium is still at its preliminary stages in human subjects. Research into basic scientific and procedural issues, as well as the conduction of clinical outcome studies to determine the safety and efficacy of the techniques, are still in their early development phase.

Investigational/Not Medically Necessary:

Autologous cell therapy, including, but not limited to, skeletal myoblasts, mesenchymal stem cells or hematopoietic stem cells, is considered investigational/not medically necessary as a treatment of damaged myocardium.

Infusion of growth factors (i.e., granulocyte colony stimulating factor [GCSF]) is considered investigational/not medically necessary as a technique to increase the numbers of circulating hematopoietic stem cells as treatment of damaged myocardium.
 

At this time, there is insufficient evidence to support the use of autologous cell transplantation or the infusion of growth factors as treatment of damaged myocardium.

From a basic science viewpoint, it must be shown that autologous cells, when transplanted into the heart, can 1) truly regenerate myocardium by incorporating themselves into the native tissue, surviving, differentiating, and ultimately electromechanically coupling to each other, or 2) serve as a trophic factor leading to survival of injured myocardial tissue and improved cardiac function through tissue preservation and ventricular remodeling. For example, preliminary studies have suggested that transplanted myoblasts are potentially arrhythmogenic. For this reason, 2 investigational device exemption (IDE) trials currently underway require that all patients receive a cardiac defibrillator in order to participate.  Additionally, patient selection criteria for this technology are still evolving, and 2 different patient groups are the focus of the two IDE trials underway.  One investigation involves patients who are in the immediate post-infarct period, where it is believed autologous cell transplant might function to alter the cardiac remodeling process. The other population under investigation is comprised of patients with congestive heart failure, where is hypothesized that ACT may function to stimulate myocardial regenesis.

There are also the practical issues of determining the optimal cell type, the timing of the transplantation post infarct and the method of delivery of transplanted cells (directly into myocardium, intracoronary artery or sinus, or intravenous). In addition, there are issues of harvesting the autologous cells. Hematopoietic stem cells, mesenchymal stem cells and skeletal myoblasts have been the focus of research. However, the ability to harvest hematopoietic stem cells and /or mesenchymal stem cells safely and efficiently with multiple bone core biopsies in the immediate post-infarct period in patients with large heart attacks is still questionable. Another option is the use of skeletal myoblasts.  One of the advantages of using skeletal myoblasts is their easy accessibility through a muscle biopsy.  However, the harvested tissue must undergo culture to expand the numbers of cells available for transplantation. In the IDE trials, skeletal biopsy must occur 3-4 weeks before the anticipated implantation, limiting their use in the immediate post-infarct period.  The immediate use of mesenchymal stem cells following myocardial infarction may also be limited due to the need to expand these cells in culture for days to weeks prior to their use.

At this time, the medical evidence supporting the use of ACT in the peri-infarct period is limited to only one randomized controlled study and a few case series with very small sample populations and very limited follow-up times.  The use of ACT in patients with congestive heart failure is limited to two small case series studies with non-randomized controls.  While there is some encouraging data, many questions are outstanding regarding the basic science of this technology as well as its clinical applications.  At this time we conclude that there is insufficient evidence to support the use of autologous cell transplantation.

Another method of ACT involves the infusion of growth factors, such as granulocyte colony stimulating factor (GCSF), with the intention of increasing the concentration of circulating hematopoietic stem cells as a treatment of damaged myocardium.  At this time there is great uncertainty from pre-clinical trials as to the efficacy of this strategy. There have been limited studies addressing this technique in clinical setting.  In a report of one small randomized controlled trial comparing the use of bone marrow transplant to GCSF infusion for the treatment patients with acute myocardial infarction who had undergone recent angioplasty and stenting, the researchers ended the trial early.  The authors reported that the GCSF group had a significantly higher rate of restenosis than the bone marrow group.  The current medical evidence is insufficient to allow any conclusions regarding the use of this treatment method.

Description of Coronary Heart Disease (CHD)

The American Heart Association reports an estimated 15,800,000 people in the US suffer from coronary heart disease (CHD). Of these, 7,900,000 people have had at least one myocardial infarction (MI, or heart attack) and 8,900,000 suffer angina. Coronary vascular disease (CVD) is the most common cause of death in the United State. Coronary artery or CHD occurs when the flow of blood through one or more of the coronary arteries becomes inadequate.  This results in oxygen deprivation in the heart muscle, and may eventually result in heart attack or even death (Rosamond, 2006).

Description of Congestive Heart Failure (CHF)

Congestive heart failure (CHF) is a progressive condition resulting from a declining ability of the left ventricle of the heart to fill with or to pump out blood.  According to the American Heart Association nearly 5.2 million Americans presently have CHF, and approximately 500,000 new cases are diagnosed yearly.  CHF results in about 300,000 deaths annually (Rosamond, 2006).

Description of Technology(s)

Autologous cell transplantation (ACT) for the treatment of damaged myocardium involves the transplantation of various types of cells into a damaged heart with the goal of replacing damaged heart muscle or to assist in the healing process. Various types of ACT have been researched to either stimulate regeneration of the heart muscle or modify ventricular remodeling post-infarct. For example, it is thought that after an MI an increased number of hematopoietic stem cells are released into the circulation and then engrafted into the heart. While these stem cells do not normally result in effective myocardial regeneration, it is theorized that enhancement of this process through a form of ACT, medical augmentation of stem cell production with granulocyte colony stimulating factor (GCSF) might result in improved cardiac regeneration or remodeling.

In humans, skeletal myoblasts, harvested from a muscle biopsy, or hematopoietic stem cells, harvested from the bone marrow or peripheral blood, or mesenchymal stem cells, harvested from the bone marrow have also been investigated as cell sources for ACT.  The harvested cells can be transplanted in a variety of ways, frequently as an adjunct to coronary artery bypass surgery; for example, either by injecting directly into the nonfunctional heart muscle, or injecting into a coronary artery or coronary sinus. Through the release of chemokines released by the heart circulating hematopoietic stem cells may have a natural homing ability to damaged myocardium.

At this time there have not been any U.S. Food and Drug Administration (FDA) approvals for any technologies associated with any ACT procedure for the treatment of damaged myocardium.  While FDA approval is not required in those situations in which autologous cells are processed on site with existing laboratory procedures and injected with existing catheter devices specialized technologies do require approval. There are currently 2 products under investigation for the treatment of damaged myocardium with ACT. MyoCell™ consists of patient autologous skeletal myoblasts that are expanded in a laboratory and supplied as a cell suspension for injection into the area of damaged myocardium.  In addition, implantation of Myocell™ may require the use of a unique catheter delivery system (MyoCath™) that is also under investigation for FDA approval. The manufacturer, BioHeart, Inc. (Ft. Lauderdale, FL) is currently conducting two Phase I Investigational New Device trials as part of the FDA approval process. The trials are focusing on patients with a previous myocardial infarction who undergo epicardial implantation of the cultured myoblasts at the time of coronary artery bypass grafting, or patients with a prior myocardial infarction and subsequent congestive heart failure who undergo subendocardial implantation using the MyoCath^TM device during a catheterization procedure. Also, all participants must receive implantation of a cardiac defibrillator, based on preliminary data suggesting that the implanted myoblasts may be arrhythmogenic (cause irregular heartbeats).

Proposed Benefits

The proposed benefits of ACT for the treatment of damaged myocardium are improved heart function, restored myocardial viability and potentially extended lifespan.

Possible Risks

At this time the risks of ACT for the treatment of damaged myocardium are unknown.  Insufficient data has been reported to allow a proper understanding of how this technology may affect patients either in the short or long term.  However, there are known risks related to the various methods utilized to harvest and transplant autologous cells, including pain, hemorrhage, cardiac arrest, and death.

Autologous cell therapy: a medical treatment involving the transplantation of various types of cells harvested from the patient and then returned to them in a unique manner; this treatment may involve one or several types of cells and has been proposed for a wide variety of conditions

Growth factors: a group of substances produced by the body that stimulates the survival, proliferation, differentiation and function of specific cells or tissues in the body; one example is granulocyte colony stimulating factor (GCSF), which stimulates the production of a certain type of white blood cell

Hematopoietic stem cells: a type of cell from which blood cells are created

Mesenchymal stem cells: a type of bone marrow derived cell from which muscles are created

Myocardium: the medical term for the heart muscle

Skeletal myoblasts: a type of cell from which skeletal muscle fibers are created

The following codes for treatments and procedures applicable to this policy are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the members contract benefits in effect at the time of service to determine coverage or non-coverage or these services as it applies to an individual member.

When services are Investigational/Not Medically Necessary:

For the following procedure and diagnosis codes, or when the code describes a procedure indicated in the Policy section as investigational/not medically necessary:

CPT

HCPCS

ICG-9 Procedure

ICD-9 Diagnoses

Peer Reviewed Publications:

1. Abbott JD, Giodano FJ. Stem cells and cardiovascular disease. J Nucl Cardiol. 2003; 10(4):403-412. 
2. Assmus B, Schachinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation. 2002; 106(24):3009-3017.
3. Forrester JS, Price MJ, Makkar RR. Stem cell repair of infarcted myocardium: an overview for clinicians. Circulation. 2003; 108(9):1139-1145.
4. Herreros J, Prosper F, Perez A, et al. Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction. Eur Heart J. 2003; 24(22):2012-2020. 
5. Kang HJ, Kim HS, Zhang SY, et al. Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet. 2004; 363(9411):751-756.
6. Kuethe F, Richartz BM, Kasper C, et al. Autologous intracoronary mononuclear bone marrow cell transplantation in chronic ischemic cardiomyopathy in humans. Int J Cardiol. 2005;100(3):485-491.
7. Lee MS, Makkar RR. Stem cell transplantation in myocardial infarction: a status report. Ann Intern Med. 2004; 140(9);729-737. 
8. Lunde K, Solheim S, Aakhus S, et al. Autologous stem cell transplantation in acute myocardial infarction: The ASTAMI randomized controlled trial. Intracoronary transplantation of autologous mononuclear bone marrow cells, study design and safety aspects. Scand Cardiovasc J. 2005 Jul;39(3):150-158.
9. Menasche P. Stem cells for clinical use in cardiovascular medicine: current limitations and future perspectives. Thromb Haemost. 2005; 94(4):697-701. 
10. Menasche P, Hagege AA, Scorsin M, et al. Myoblast transplantation for heart failure. Lancet. 2001; 357(9252):279-280.
11. Penn MS, Francis GS, Ellis SG, et al. Autologous cell transplantation for the treatment of damaged myocardium. Prog Cardiovasc Dis. 2002; 45(1):21-32. 
12. 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.
13. Pompilio G, Cannata A, Peccatori F, et al. Autologous peripheral blood stem cell transplantation for myocardial regeneration: a novel strategy for cell collection and surgical injection. Ann Thorac Surg. 2004; 78(5):1808-1812.
14. Rosamond W, Flegal K, Friday G, et al. Heart disease and stroke statistics-2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007; 115(5):e69-171. Available at: http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.106.179918. Accessed on January 5, 2007.
15. Schachinger V, Assmus B, Britten MB, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol. 2004; 44(8):1690-1699. 
16. Siminiak T, Kalawski R, Fiszer D, et al. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury: phase I clinical study with 12 months of follow-up. Am Heart J. 2004; 148(3):531-537.
17. Smits PC, van Geuns RJ, Poldermans D, et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J Am Coll Cardiol. 2003; 42(12):2063-2069.
18. Stamm C, Westphal B, Kleine HD. et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. 2003; 361(9351):45-46.
19. Strauer BE, Brehm M, Zeus T, et al. Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study. J Am Coll Cardiol. 2005; 46(9):1651-1658. 
20. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation. 2002; 106(15):1913-1938.
21. Tendera M, Wojakowski W. Clinical trials using autologous bone marrow and peripheral blood-derived progenitor cells in patients with acute myocardial infarction. Folia Histochem Cytobiol. 2005; 43(4):233-235. 
22. Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet. 2004; 364(9429):141-148.
23. Wojakowski W, Tendera M, Michalowsa A, et al. Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation. 2004; 110(20):3213-3220.
    

Government Agency, Medical Society, and Other Authoritative Publications:

1. Bioheart, Inc. MYOHEART™ (Myogenesis Heart Efficiency and Regeneration Trial). NCT00054678. Last updated on December 6, 2006. Available at:  http://www.clinicaltrials.gov/ct/show/NCT00054678?order=2. Accessed on January 18, 2007.

1. American Heart Association. Available at:  http://www.americanheart.org. Accessed on January 18, 2007.
2. National Heart, Lung, and Blood Institute. What Is Heart Failure? Available at:  http://www.nhlbi.nih.gov/health/dci/Diseases/Hf/HF_WhatIs.html. Accessed on January 18, 2007.
3. National Heart, Lung, and Blood Institute. What is Coronary Artery Disease? Available at:  http://www.nhlbi.nih.gov/health/dci/Diseases/Cad/CAD_WhatIs.html. Accessed on January 18, 2007.

Autologous Cell Therapy for the Treatment of Damaged Myocardium
Cellular Cardiomyoplasty
Heart - Autologous Cell Therapy for Damaged Myocardium
Myocardial Damage, Autologous Cell Transplantation for
Myocath™
Myocell™

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.
 

Federal and State law, as well as contract language, including definitions and specific contract provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The member's contract benefits in effect on the date that services are rendered must be used. Medical Policy, which addresses medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically.

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