This randomized pilot phase I trial studies the side effects of donor bone marrow derived mesenchymal stem cells in controlling heart failure in patients with cardiomyopathy caused by anthracyclines. Donor bone marrow derived mesenchymal stem cells may help to control symptoms of heart failure and improve heart function.

PRIMARY OBJECTIVE:

I. To demonstrate the safety of allogeneic human mesenchymal stem cells (hMSCs) administered by intravenous infusion and transendocardial injection in patients with left ventricular (LV) dysfunction and heart failure secondary to chemotherapy with anthracyclines.

SECONDARY OBJECTIVE:

I. To demonstrate the efficacy of allogeneic hMSCs administered by intravenous infusion and transendocardial injection in patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] < 40%) and heart failure secondary to treatment with anthracyclines.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive hMSCs intravenously (IV) over 10-20 minutes on days 1, 14, 21, and 28 and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive hMSCs transendocardially for a total of 15 injections and standard of care treatment for heart failure in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive standard of care treatment for heart failure.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

1. Patients with LVEF </= 40% documented from treatment with anthracyclines for any malignancy at any dose at any time without evidence of other causes of cardiomyopathy.
2. Age >/= 18 and </= 90 years of age. English and non-English speaking patients are eligible.
3. Documented NYHA class I, II and III.
4. For patients who have received trastuzumab: Persistent LV dysfunction must be present 90 days after discontinuation of trastuzumab.
5. Able to perform 6 minute walk test.
6. Been treated with appropriate maximal medical therapy for heart failure.
7. Patient or legally authorized representative able to sign informed consent.

Exclusion Criteria:

1. Evidence of Ischemic Heart Disease as determined by study cardiologist.
2. Significant Valvular Disease. (AS with AVA <1.5 and severe AR and MR)
3. History of Familial Cardiomyopathy.
4. Recent documented myocarditis within 2 months of enrollment.
5. History of Infiltrative cardiomyopathy or restrictive cardiomyopathy.
6. Presence of left ventricular thrombus as documented by echocardiography or left ventriculogram.
7. Liver function tests > 3 x upper limit of normal.
8. NYHA class IV heart failure.
9. Inotropic dependence.
10. Unstable or life-threatening arrhythmia.
11. For patients not on anticoagulants, INR>1.5
12. Mechanical or Bioprosthetic heart valve.
13. Cardiogenic shock.
14. Breastfeeding and/or pregnant women.
15. Autoimmune disorders on current immunosuppressive therapy.
16. Active infection not responding to appropriate therapy as determined by Study Chair.
17. Trastuzumab treatment within the last 3 months.
18. Automatic implantable cardioverter defibrillator (AICD) placement within the last 30 days.
19. AICD firing within the last 30 days.