Prevention of progressive heart failure
The present disclosure relates to methods for preventing progressive heart failure in subjects with persistent left ventricular (LV) dysfunction. Such methods may also be used for treating or preventing progressive heart failure in subjects with a proximal left anterior descending (LAD) lesion and persistent left ventricular dysfunction.
1. A method for reducing the risk of heart failure-related major adverse cardiac events (HF-MACE) in a human subject characterized by the following:
a) a left ventricular (LV) infarct, the size of which is greater than 18.5% of the left ventricle as measured by cardiovascular magnetic resonance imaging (cMR);
b) a proximal left anterior descending (LAD) arterial lesion;
c) a left ventricular end systolic volume (LVESV) of greater than 70 ml;
d) persistent left ventricular dysfunction; and
e) a left ventricular ejection fraction (LVEF) of less than 40%,
which comprises administering to the subject a population of mesenchymal lineage precursor or stem cells, progeny thereof, or a combination of any of the foregoing in an amount effective to (i) decrease the size of the subject's LV infarct and (ii) improve the subject's LV systolic function so as to thereby reduce the subject's risk of HF-MACE for a period of at least six months after the administration.
2. The method of claim 1 , wherein the effective amount of the population of mesenchymal lineage precursor or stem cells and/or progeny thereof is administered between 1 and 7 days post-myocardial infarction.
3. The method of claim 1 , wherein the subject has greater than 4× upper limit of normal creatine kinase-MB and/or troponin and/or myoglobin.
4. The method of claim 1 , wherein the subject has an infarct size greater than 30% of the left ventricle.
5. The method of claim 1 , wherein the population of mesenchymal lineage precursor or stem cells is enriched for STRO-1 + cells and/or progeny thereof.
6. The method of claim 1 , wherein the population of mesenchymal lineage precursor or stem cells is enriched for STRO-1 bright cells and/or progeny thereof.
7. The method of claim 1 , wherein the population of mesenchymal lineage precursor or stem cells and/or progeny thereof is administered systemically, intravenously or intranasally.
8. The method of claim 1 , comprising administering between 1.2×10 8 to 4×10 8 cells.
9. The method of claim 1 , wherein the population of mesenchymal lineage precursor or stem cells and/or progeny cells is autogeneic or allogeneic.
10. The method of claim 1 , wherein the population of mesenchymal lineage precursor or stem cells and/or progeny thereof has been culture expanded prior to administration.
11. The method of claim 1 , wherein the population of mesenchymal lineage precursor or stem cells and/or progeny cells thereof express tissue non-specific alkaline phosphatase (TNAP).
12. The method of claim 1 , wherein the population of mesenchymal lineage precursor or stem cells and/or progeny cells thereof express:
a) Angiopoietin-1 (Ang1) in an amount of at least 0.1 μg/10 6 cells; and/or
b) Vascular Endothelial Growth Factor (VEGF) in an amount less than 0.05 μg/10 6 cells.
13. The method of claim 1 , wherein the population of mesenchymal lineage precursor or stem cells and/or progeny cells thereof express Ang1:VEGF at a ratio of at least 2:1.
14. The method of claim 1 , wherein the population of mesenchymal lineage precursor or stem cells and/or of the progeny cells thereof is administered in the form of a composition comprising the mesenchymal lineage precursor or stem cells and/or the progeny cells thereof and a carrier and/or an excipient.
15. The method of claim 1 , wherein the subject's LV infarct size is decreased by 10%.
16. The method of claim 1 , wherein the subject's LV infarct size is decreased by 30%.