Tratamiento con células madres para el infarto de miocardio agudo
Appendices
Appendix 1. Search strategies 2007
CENTRAL (The Cochrane Library)
#1 STEM CELL TRANSPLANTATION single term (MeSH)
#2 PERIPHERAL BLOOD STEM CELL TRANSPLANTATION single term (MeSH)
#3 HEMATOPOIETIC STEM CELL TRANSPLANTATION single term (MeSH)
#4 HEMATOPOIETIC STEM CELL MOBILIZATION single term (MeSH)
#5 STEM CELLS single term (MeSH)
#6 HEMATOPOIETIC STEM CELLS explode all trees (MeSH)
#7 BONE MARROW CELLS single term (MeSH)
#8 haematopoietic OR hematopoietic OR haematopoetic OR hematopoetic OR haemopoietic OR haemopoietic OR marrow NEAR cell* OR stem cell* OR progenitor cell* OR precursor cell*
#9 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8
#10 MYOCARDIAL ISCHEMIA explode all trees (MeSH)
#11 myocardial NEAR infarct* OR myocardium NEAR infarct* OR subendocardial NEAR infarct* OR transmural NEAR infarct* OR cardiac NEAR infarct* OR cardial NEAR infarct* OR heart NEAR infarct* OR acute NEAR infarct*
#12 ischemi* NEAR myocard* OR ischemi* NEAR heart OR ischaemi* NEAR myocard* OR ischaemi* NEAR heart
#13 acute NEAR coronary OR occlusion* NEAR coronary OR disease* NEAR coronary
#14 unstable NEAR angina OR heart NEXT attack* OR AMI
#15 heart NEAR repair* OR heart NEAR reparation OR heart NEAR improve* OR heart NEAR regenerate* OR cardiac NEAR repair* OR cardiac NEAR reparation OR cardiac NEAR improve* OR cardiac NEAR regenerat* OR myocard* NEAR repair* OR myocard* NEAR reparation OR myocard* NEAR improve* OR myocard* NEAR regenerat*
#16 myoblast* NEAR transplantation OR myoblast* NEAR graft* OR myoblast* NEAR implant*
#17 #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16
#18 #9 AND #17
#19 cellular NEXT cardiomyoplasty or cardiomyocyte* NEAR transplantation* OR intramyocardial NEAR transplantation* OR transendocardial NEAR stem NEXT cell* OR intracoronary NEXT progenitor NEXT cell*
#20 #18 OR #19
MEDLINE (Dialog DataStar)
1. STEM‐CELL‐TRANSPLANTATION.DE.
2. PERIPHERAL‐BLOOD‐STEM‐CELL‐TRANSPLANTATION.DE.
3. HEMATOPOIETIC‐STEM‐CELL‐TRANSPLANTATION.DE.
4. HEMATOPOIETIC‐STEM‐CELL‐MOBILIZATION.DE.
5. STEM‐CELLS.DE.
6. HEMATOPOIETIC‐STEM‐CELLS#.DE.
7. BONE‐MARROW‐CELLS.DE.
8. (haematopoietic OR hematopoietic OR haematopoetic OR hematopoetic OR hemopoietic OR haemopoietic OR marrow NEAR cell$1 OR stem cell$1 OR progenitor cell$1 OR precursor cell$1).TI,AB.
9. 1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8
10. MYOCARDIAL‐ISCHEMIA#.DE.
11. (myocardial OR myocardium OR subendocardial OR transmural OR cardiac OR cardial OR heart OR acute) NEAR infarct$3
12. (ischemi$1 OR ischaemi$1) NEAR (myocardium OR myocardial OR heart)
13. (acute OR occlusion$1 OR disease$1) NEAR coronary
14. unstable NEAR angina OR heart NEXT attack$1 OR AMI
15. (heart or cardiac OR myocardium OR myocardial) NEAR (repair$3 OR reparation OR improve$1 OR regenerat$3)
16. (myoblast$1 NEAR (transplantation OR graft$3 OR implant$3)
17. 10 OR 11 OR 12 OR 13 OR 14 OR 15 OR 16
18. 9 AND 17
19. cellular ADJ cardiomyoplasty or cardiomyocyte$1 NEAR transplantation OR intramyocardial NEAR transplantation OR transendocardial NEAR stem ADJ cell$1 OR intracoronary ADJ progenitor ADJ cell$1
20. 18 OR 19
EMBASE (Dialog DataStar)
1. STEM‐CELL‐TRANSPLANTATION#.DE.
2. STEM‐CELL‐MOBILIZATION.DE.
3. STEM‐CELL.DE.
4. HEMATOPOIETIC‐STEM‐CELL.DE.
5. BONE‐MARROW‐CELL.DE.
6. (haematopoietic OR hematopoietic OR haematopoetic OR hematopoetic OR hemopoietic OR haemopoietic OR marrow NEAR cell$1 OR stem cell$1 OR progenitor cell$1 OR precursor cell$1).TI,AB.
7. 1 OR 2 OR 3 OR 4 OR 5 OR 6
8. HEART‐INFARCTION#.DE.
9. (myocardial OR myocardium OR subendocardial OR transmural OR cardiac OR cardial OR heart OR acute) NEAR infarct$3
10. (ischemi$1 OR ischaemi$1) NEAR (myocardium OR myocardial OR heart)
11. (acute OR occlusion$1 OR disease$1) NEAR coronary
12. unstable NEAR angina OR heart NEXT attack$1 OR AMI
13. (heart or cardiac OR myocardium OR myocardial) NEAR (repair$3 OR reparation OR improve$1 OR regenerat$3)
14. (myoblast$1 NEAR (transplantation OR graft$3 OR implant$3)
15. 8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14
16. 7 AND 15
17. cellular ADJ cardiomyoplasty or cardiomyocyte$1 NEAR transplantation OR intramyocardial NEAR transplantation OR transendocardial NEAR stem ADJ cell$1 OR intracoronary ADJ progenitor ADJ cell$1
18. 16 OR 17
CINAHL (Dialog DataStar)
1. HEMATOPOIETIC‐STEM‐CELL‐TRANSPLANTATION.DE.
2. STEM‐CELLS#.DE.
3. (haematopoietic OR hematopoietic OR haematopoetic OR hematopoetic OR hemopoietic OR haemopoietic OR marrow NEAR cell$1 OR stem cell$1 OR progenitor cell$1 OR precursor cell$1).TI,AB.
4. 1 OR 2 OR 3
5. MYOCARDIAL‐ISCHEMIA#.DE.
6. (myocardial OR myocardium OR subendocardial OR transmural OR cardiac OR cardial OR heart OR acute) NEAR infarct$3
7. (ischemi$1 OR ischaemi$1) NEAR (myocardium OR myocardial OR heart)
8. (acute OR occlusion$1 OR disease$1) NEAR coronary
9. unstable NEAR angina OR heart NEXT attack$1 OR AMI
10. (heart or cardiac OR myocardium OR myocardial) NEAR (repair$3 OR reparation OR improve$1 OR regenerat$3)
11. (myoblast$1 NEAR (transplantation OR graft$3 OR implant$3)
12. 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11
13. 4 AND 12
14. cellular ADJ cardiomyoplasty or cardiomyocyte$1 NEAR transplantation OR intramyocardial NEAR transplantation OR transendocardial NEAR stem ADJ cell$1 OR intracoronary ADJ progenitor ADJ cell$1
15. 13 OR 14
LILACS and INDMED
((marrow cell$ OR stem cell$ OR progenitor cell$ OR precursor cell$) AND (infarct$ OR coronar$ OR myocard$ OR heart attack$ OR heart failure OR cardiac$ OR cardiomyo$ OR intramyocardial$ OR ischemia))
KOREAMED
((marrow cell$ OR stem cell$ OR progenitor cell$ OR precursor cell$) AND (infarct$ OR coronar$ OR myocard$ OR heart attack$ OR heart failure OR cardiac$ OR cardiomyo$ OR intramyocardial$ OR ischemia))
mRCT
(("marrow cell%" OR "stem cell%" OR "progenitor cell%" or "precursor cell%") AND (infarct% OR coronar% OR myocard% OR "heart attack%" OR "heart failure" OR cardiac% OR cardiomyo% OR intramyocardial% OR ischemia))
Appendix 2. Search strategies 2011
CENTRAL (The Cochrane Library)
#1 STEM CELL TRANSPLANTATION single term (MeSH)
#2 PERIPHERAL BLOOD STEM CELL TRANSPLANTATION single term (MeSH)
#3 HEMATOPOIETIC STEM CELL TRANSPLANTATION single term (MeSH)
#4 HEMATOPOIETIC STEM CELL MOBILIZATION single term (MeSH)
#5 STEM CELLS single term (MeSH)
#6 HEMATOPOIETIC STEM CELLS explode all trees (MeSH)
#7 BONE MARROW CELLS single term (MeSH)
#8 haematopoietic OR hematopoietic OR haematopoetic OR hematopoetic OR haemopoietic OR haemopoietic OR (marrow NEAR/3 cell*) OR stem cell* OR progenitor cell* OR precursor cell* or cell* therap* or ((mesenchymal or stromal) AND marrow)
#9 (cell* NEAR/3 transplantation) OR (cell* NEAR/3 graft*) OR (cell* NEAR/3 implant*)
#10 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9
#11 MYOCARDIAL ISCHEMIA explode all trees (MeSH)
#12 myocardial NEAR/3 infarct* OR myocardium NEAR/3 infarct* OR subendocardial NEAR/3 infarct* OR transmural NEAR/3 infarct* OR cardiac NEAR/3 infarct* OR cardial NEAR/3 infarct* OR heart NEAR/3 infarct* OR acute NEAR/3 infarct*
#13 ischemi* NEAR/3 myocard* OR ischemi* NEAR/3 heart OR ischaemi* NEAR/3 myocard* OR ischaemi* NEAR/3 heart
#14 acute NEAR/3 coronary OR occlusion* NEAR/3 coronary OR disease* NEAR/3 coronary
#15 unstable NEAR/3 angina OR heart NEXT attack* OR AMI
#16 heart NEAR/3 repair* OR heart NEAR/3 reparation OR heart NEAR/3 improve* OR heart NEAR/3 regenerate* OR cardiac NEAR/3 repair* OR cardiac NEAR/3 reparation OR cardiac NEAR/3 improve* OR cardiac NEAR/3 regenerat* OR myocard* NEAR/3 repair* OR myocard* NEAR/3 reparation OR myocard* NEAR/3 improve* OR myocard* NEAR/3 regenerat*
#17 #11 OR #12 OR #13 OR #14 OR #15 OR #16
#18 #10 AND #17
#19 (cellular NEXT cardiomyoplasty) or (cardiomyocyte* NEAR/3 transplantation*) OR (intramyocardial NEAR/3 transplantation*) OR (transendocardial NEAR/3 stem NEXT cell*)
#20 (intracoronary NEAR/4 cell*) or (intracoronary NEAR/3 bone NEXT marrow) or (intracoronary NEAR/3 BMC*) or (intracoronary NEAR/3 infus*)
#21 #18 OR #19 OR #20
MEDLINE (Ovid)
1. exp STEM CELL TRANSPLANTATION/
2. exp STEM CELLS/
3. BONE MARROW TRANSPLANTATION/
4. BONE MARROW CELLS/
5. CELL TRANSPLANTATION/
6. (haematopoietic OR hematopoietic OR haematopoetic OR hematopoetic OR hemopoietic OR haemopoietic OR (marrow adj3 cell*) OR stem cell* OR progenitor cell* OR precursor cell* OR cell* therap* OR ((mesenchymal OR stromal) AND marrow).ti,ab.
7. (cell* adj3 (transplant* or graft* or implant*)).ti,ab
8. cell transplantation.jn. or cell stem cell.jn. or stem cell reviews.jn. or bone marrow transplantation.jn.
9. or/1‐8
10. exp MYOCARDIAL ISCHEMIA/
11. ((myocardial OR myocardium OR subendocardial OR transmural OR cardiac OR cardial OR heart OR acute) adj3 infarct*).ti,ab.
12. ((ischemi* OR ischaemi*) adj3 (myocardium OR myocardial OR heart)).ti,ab.
13. ((acute OR occlusion* OR disease*) adj3 coronary).ti,ab.
14. ((unstable adj3 angina) OR heart attack* OR AMI).ti,ab.
15. ((heart or cardiac OR myocardium OR myocardial) adj3 (repair* OR reparation OR improve* OR regenerat*)).ti,ab.
16. or/10‐15
17. 9 AND 16
18. (cellular cardiomyoplasty or (cardiomyocyte* adj3 transplant*) OR (intramyocardial* adj3 transplant*) OR (transendocardial* adj3 stem cell*)).ti,ab.
19. (intracoronary adj4 (cell* or BMC* or infus*)).ti,ab.
20. or/17‐19
21. RANDOMIZED CONTROLLED TRIAL.pt.
22. CONTROLLED CLINICAL TRIAL.pt.
23. exp CLINICAL TRIAL/
24. MULTICENTER STUDY.pt.
25. CLINICAL TRIALS AS TOPIC/
26. CLINICAL TRIALS PHASE III AS TOPIC/
27. CLINICAL TRIALS PHASE IV AS TOPIC/
28. exp CONTROLLED CLINICAL TRIALS AS TOPIC/
29. RANDOM ALLOCATION/
30. DOUBLE BLIND METHOD/
31. SINGLE BLIND METHOD/
32. CROSSOVER STUDIES/
33. PLACEBOS/
34. or/21‐33
35. (controlled adj3 (trial* or stud*)).ti,ab.
36. (blind* or mask*).ti,ab.
37. (placebo* or random* or factorial*).ti,ab.
38. (crossover or (cross adj over)).ti,ab.
39. aleatori*.ti,ab.
40. (treatment adj arm*).ti,ab.
41. ((phase adj iii) or (phase adj three) or (phase adj '3')).ti,ab.
42. (latin adj square).ti,ab.
43. or/35‐42
44. 34 or 43
45. ANIMALS/
46. HUMANS/
47. 45 and 46
48. 45 not 47
49. 44 not 48
50. 20 and 49
EMBASE (Ovid)
1. exp CELL THERAPY/
2. exp STEM CELL/
3. BONE MARROW CELL/
4. (haematopoietic OR hematopoietic OR haematopoetic OR hematopoetic OR hemopoietic OR haemopoietic OR (marrow adj3 cell*) OR stem cell* OR progenitor cell* OR precursor cell* OR cell* therap*).ti,ab.
5. ((mesenchymal OR stromal) AND marrow).ti,ab.
6. (cell* adj3 (transplant* or graft* or implant*)).ti,ab.
7. or/1‐6
8. exp HEART INFARCTION/
9. ((myocardial OR myocardium OR subendocardial OR transmural OR cardiac OR cardial OR heart OR acute) adj3 infarct*).ti,ab.
10. ((ischemi* OR ischaemi*) adj3 (myocardium OR myocardial OR heart)).ti,ab.
11. ((acute OR occlusion* OR disease*) adj3 coronary).ti,ab.
12. ((unstable adj3 angina) OR heart attack* OR AMI).ti,ab.
13. ((heart or cardiac OR myocardium OR myocardial) adj3 (repair* OR reparation OR improve* OR regenerat*)).ti,ab.
14. or/8‐13
15. 7 AND 14
16. (cellular cardiomyoplasty OR (cardiomyocyte* adj3 transplant*) OR (intramyocardial* adj3 transplant*) OR (transendocardial* adj3 stem cell*)).ti,ab.
17. (intracoronary adj4 (cell* OR BMC* OR infus*)).ti,ab.
18. or/15‐17
19. random*.ti,ab.
20. factorial*.ti,ab.
21. (crossover* OR cross over* OR cross‐over*).ti,ab.
22. placebo*.ti,ab.
23. (double* adj blind*).ti,ab.
24. (singl* adj blind*).ti,ab.
25. assign*.ti,ab.
26. allocat*.ti,ab.
27. volunteer*.ti,ab.
28. CROSSOVER PROCEDURE/
29. DOUBLE BLIND PROCEDURE/
30. RANDOMIZED CONTROLLED TRIAL/
31. SINGLE BLIND PROCEDURE/
32. or/19‐31
33. exp ANIMAL/
34. NONHUMAN/
35. exp ANIMAL EXPERIMENT/
36. or/33‐35
37. exp HUMAN/
38. 36 NOT 37
39. 32 NOT 38
40. 18 AND 39
CINAHL (NHS Evidence)
1. exp CELL TRANSPLANTATION/
2. exp STEM CELLS/
3. exp BONE MARROW TRANSPLANTATION/
4. (haematopoietic OR hematopoietic OR haematopoetic OR hematopoetic OR hemopoietic OR haemopoietic OR (marrow adj3 cell*) OR “stem cell*” OR “progenitor cell*” OR “precursor cell*” or “cell* therap*”).ti,ab
5. ((mesenchymal OR stromal) AND marrow).ti,ab
6. ((cell* adj3 transplant*) or (cell* adj3 graft*) or (cell* adj3 implant*)).ti,ab
7. 1 OR 2 OR 3 OR 4 OR 5 OR 6
8. exp MYOCARDIAL ISCHEMIA/
9. ((myocardial adj3 infarct*) OR (myocardium adj3 infarct*) OR (subendocardial adj3 infarct*) OR (transmural adj3 infarct*) OR (cardiac adj3 infarct*) OR (cardial adj3 infarct*) OR (heart adj3 infarct*) OR (acute adj3 infarct*).ti,ab
10. ((ischemi* adj3 myocardium) OR (ischemi* adj3 myocardial) OR (ischemi* adj3 heart)).ti,ab
11. ((ischaemi* adj3 myocardium) OR (ischaemi* adj3 myocardial) OR (ischaemi* adj3 heart)).ti,ab
12. ((acute adj3 coronary) OR (occlusion* adj3 coronary) OR (disease* adj3 coronary)).ti,ab
13. ((unstable adj3 angina) OR “heart attack*” OR AMI).ti,ab
14. ((heart adj3 repair*) or (cardiac adj3 repair*) OR (myocardium adj3 repair*) OR (myocardial* adj3 repair*)).ti,ab
15. ((heart adj3 reparation) or (cardiac adj3 reparation) OR (myocardium adj3 reparation) OR (myocardial* adj3 reparation)).ti,ab
16. ((heart adj3 improv*) or (cardiac adj3 improv*) OR (myocardium adj3 improv*) OR (myocardial* adj3 improv*)).ti,ab
17. ((heart adj3 regenerat*) or (cardiac adj3 regenerat*) OR (myocardium adj3 regenerat*) OR (myocardial* adj3 regenerat*)).ti,ab
18. 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17
19. 7 AND 18
20. (“cellular cardiomyoplasty” or (cardiomyocyte* adj3 transplant*) OR (intramyocardial* adj3 transplant*) OR (transendocardial* adj3 stem cell*)).ti,ab
21. ((intracoronary adj4 cell*) or (intracoronary adj3 BMC*) or (intracoronary adj3 infus*)).ti,ab
22. 19 or 20 or 21
23. "CLINICAL TRIAL".pt
24. ((controlled adj trial*) OR (clinical adj trial*)).ti,ab
25. ((singl* adj blind*) OR (doubl* adj blind*) OR (trebl* adj blind*) OR (singl* adj mask*) OR (doubl* adj mask*) OR (tripl* adj mask*)).ti,ab
randomi*.ti,ab
26. RANDOM ASSIGNMENT/
27. ("phase III" OR "phase 3" OR "phase three").ti,ab
28. (random* adj1 allocat*).ti,ab
29. (random* adj1 assign*).ti,ab
30. PLACEBOS/
31. 23 OR 24 OR 25 OR 26 OR 27 OR 28 OR 29 OR 30
32. 19 AND 31
PubMed (for e‐publications only)
(infarct[ti] OR infarction or coronary[ti] OR myocardial[ti] OR heart attack[ti] OR heart failure[ti] OR cardiac[ti] OR cardiomyopathy[ti] OR intramyocardial[ti] OR ischemi*[ti] OR ischaemi*[ti]) AND (marrow cell[ti] OR marrow cells[ti] OR stem cell[ti] OR stem cells[ti] OR progenitor cell[ti] OR progenitor cells[ti] OR precursor cell[ti] OR precursor cells[ti] OR cell therapy[ti] OR cellular therapy[ti] OR cell‐based therapy[ti] OR intracoronary cells[ti] or mononuclear cells[ti] OR mesenchymal cells[ti]) AND (publisher[sb] NOT pubstatusnihms)
LILACS and INDMED
(marrow cell$ OR stem cell$ OR progenitor cell$ OR precursor cell$ OR cell$ therap$ or mesenchymal cell$) AND (infarct$ OR coronar$ OR intracoronary OR myocard$ OR heart attack$ OR heart failure OR cardiac$ OR cardiomyo$ OR intramyocardial$ OR ischemi$)
KoreaMed, PakMediNet and the UKBTS/SRI Transfusion Evidence Library
(marrow cell* OR stem cell* OR progenitor cell* OR precursor cell* OR cell* therap* or mesenchymal cell*) AND (infarct* OR coronar* OR intracoronary OR myocard* OR heart attack* OR heart failure OR cardiac* OR cardiomyo* OR intramyocardial* OR ischemi*)
ClinicalTrials.gov
(myocardial infarction OR cardiomyopathy OR intramyocardial OR intracoronary OR myocardial ischemia) AND ("marrow cells" OR "stem cells" OR "cell therapy" OR "cellular therapy" OR "cell‐based therapy" OR "intracoronary cells" or "mononuclear cells")
ISRCTN Register
(stem cell OR stem cells OR marrow cell OR marrow cells OR progenitor cell or progenitor cells or precursor cell or precursor cells) AND (myocardial infarction OR infarct OR heart attack OR cardiomyopathy OR intramyocardial OR intracoronary OR ischemia OR ischaemia)
WHO International Clinical Trials Registry Platform (ICTRP)
(infarct AND cell* OR infarction AND cell* OR coronary AND cell* OR myocardial AND cell* OR heart attack AND cell* OR heart failure AND cell* OR cardiac AND cell* OR cardiomyopathy AND cell* OR intramyocardial AND cell* OR ischemia AND cell* OR ischemic AND cell* OR ischaemia AND cell* OR ischaemic AND cell*)
Appendix 3. Search strategies 2015
CENTRAL (The Cochrane Library)
#1 MeSH descriptor: [Stem Cell Transplantation] explode all trees
#2 MeSH descriptor: [Bone Marrow Cells] explode all trees
#3 MeSH descriptor: [Stem Cells] explode all trees
#4 MeSH descriptor: [Cell Transplantation] this term only
#5 MeSH descriptor: [Bone Marrow Transplantation] this term only
#6 MeSH descriptor: [Stromal Cells] explode all trees
#7 ((stem or haematopoietic or hematopoietic or haematopoetic or hematopoetic or hemopoietic or haemopoietic or progenitor or precursor or bone marrow or mononuclear or "adipose tissue" or mesenchymal or stromal or autologous or allogeneic or allogenic or ALDH* or C‐KIT*) next/2 cell*)
#8 "cell transplantation":so or "stem cell":so or "bone marrow transplantation":so
#9 (autologous next/3 transplant*) or "cell* therap*"
#10 ((cell* or myoblast*) near/3 (autologous or transplant* or autotransplant* or allotransplant* or graft* or implant*))
#11 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10
#12 MeSH descriptor: [Heart Diseases] explode all trees
#13 ((ischemi* or ischaemi* or nonischemi* or nonischaemi*) near/2 (myocardium or myocardial or cardiomyopath* or heart or coronary or cardiac or cardial or subendocardial))
#14 ((myocardial or myocardium or subendocardial or transmural or cardiac or cardial or coronary or heart) near/2 (failure* or decompensation or insufficien*))
#15 (IHD or CIHD or DCM or IDCM)
#16 ((myocardial near/3 dysfunction*) or stenocardia or angina*)
#17 ((end stage or endstage or dilated or idiopathic or congestive) near/2 cardiomyopath*)
#18 (arter* occlusion* or arter* disease* or arterioscleros* or atheroscleros*) near/2 coronary
#19 ((heart or cardiac or cardial or myocardium or myocardial) near/3 (repair* or reparation or improv* or regenerat*))
#20 (heart disease* or coronary disease* or cardiovascular disease*)
#21 ((end stage or endstage or dilated or idiopathic or congestive) near/2 cardiomyopath*)
#22 ((myocardial or myocardium or subendocardial or transmural or cardiac or cardial or coronary or heart or acute) near/3 (infarct* or postinfarct* or hypoxi* or anoxi*))
#23 heart attack* or coronary attack* or acute coronary syndrome* or AMI
#24 #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23
#25 #11 and #24
#26 cellular cardiomyoplast* or ((cardiomyocyte* or cardiac cell*) near/6 transplant*) or ((intramyocardial* or intracoronary or transendocardial* or transcoronary) near/6 (transplant* or stem or bone marrow or marrow cell* or BMC* or stromal or mesenchymal or progenitor cell* or precursor cell*))
#27 #25 or #26
MEDLINE (OvidSP)
1. exp STEM CELL TRANSPLANTATION/
2. BONE MARROW TRANSPLANTATION/
3. CELL TRANSPLANTATION/
4. exp STEM CELLS/
5. BONE MARROW CELLS/
6. exp STROMAL CELLS/
7. ((stem or haematopoietic or hematopoietic or haematopoetic or hematopoetic or hemopoietic or haemopoietic or progenitor or precursor or bone marrow or mononuclear or adipose tissue or mesenchymal or stromal or autologous or allogeneic or allogenic or ALDH* or C‐KIT*) adj2 cell*).ti,ab.
8. (cell transplantation or stem cell* or bone marrow transplantation).jn.
9. ((autologous adj3 transplant*) or cell* therap*).tw.
10. ((cell* or myoblast*) adj3 (autologous or transplant* or autotransplant* or allotransplant* or graft* or implant*)).ti,ab.
11. or/1‐10
12. exp HEART DISEASES/
13. ((ischemi* or ischaemi* or nonischemi* or nonischaemi*) adj2 (myocardium or myocardial or cardiomyopath* or heart or coronary or cardiac or cardial or subendocardial)).ti,ab.
14. ((myocardial or myocardium or subendocardial or transmural or cardiac or cardial or coronary or heart) adj2 (failure* or decompensation or insufficien*)).ti,ab.
15. (IHD or CIHD or DCM or IDCM).ti,ab.
16. ((myocardial adj3 dysfunction*) or stenocardia or angina*).ti,ab.
17. ((arter* occlusion* or arter* disease* or arterioscleros* or atheroscleros*) adj2 coronary).ti,ab.
18. (heart disease* or coronary disease* or cardiovascular disease*).ti,ab.
9. ((end stage or endstage or dilated or idiopathic or congestive) adj2 cardiomyopath*).ti,ab.
20. ((heart or cardiac or cardial or myocardium or myocardial) adj3 (repair* or reparation or improv* or regenerat*)).ti,ab.
21. ((myocardial or myocardium or subendocardial or transmural or cardiac or cardial or coronary or heart or acute) adj3 (infarct* or postinfarct* or hypoxi* or anoxi*)).ti,ab.
22. (heart attack* or coronary attack* or acute coronary syndrome* or AMI).ti,ab.
23. or/12‐22
24. 11 and 23
25. (cellular cardiomyoplast* or ((cardiomyocyte* or cardiac cell*) adj6 transplant*) or ((intramyocardial* or intracoronary or transendocardial* or transcoronary) adj6 (transplant* or stem or bone marrow or marrow cell* or BMC* or stromal or mesenchymal or progenitor cell* or precursor cell*))).mp.
26. 24 or 25
27. Meta‐Analysis.pt.
28. ((meta analy* or metaanaly*) and (trials or studies)).ab.
29. (meta analy* or metaanaly* or evidence‐based).ti.
30. ((systematic* or evidence‐based) adj2 (review* or overview*)).tw.
31. (cochrane or embase or cinahl or cinhal or lilacs or citation index or psyclit or psychlit or psycinfo or psychinfo or "web of science" or scopus).ab.
32. Cochrane Database of systematic reviews.jn.
33. ((literature or systematic* or comprehensive* or electronic*) adj2 search*).ab.
34. (additional adj (papers or articles or sources)).ab.
35. (bibliograph* or handsearch* or hand search* or manual* search* or searched or reference list*).ab.
36. (relevant adj (journals or articles)).ab.
37. or/27‐36
38. Review.pt.
39. RANDOMIZED CONTROLLED TRIALS AS TOPIC/
40. selection criteria.ab. or critical appraisal.ti.
41. (data adj (extraction or analys$)).ab.
42. RANDOMIZED CONTROLLED TRIALS/
43. or/39‐42
44. 38 and 43
45. 37 or 44
46. randomized controlled trial.pt.
47. controlled clinical trial.pt.
48. randomi*.tw.
49. (placebo or randomly or groups).ab.
50. clinical trials as topic.sh.
51. trial.ti.
52. or/46‐51
53. 45 or 52
54. (ANIMALS/ or exp ANIMAL EXPERIMENTATION/ or exp MODELS, ANIMAL/) not HUMANS/
55. (Comment or Editorial).pt.
56. 54 or 55
57. 53 not 56
58. 26 and 57
EMBASE (OvidSP)
1. exp STEM CELL TRANSPLANTATION/
2. exp BONE MARROW TRANSPLANTATION/
3. exp STEM CELL/
4. BONE MARROW CELL/
5. exp STROMA CELLS/
6. ((stem or haematopoietic or hematopoietic or haematopoetic or hematopoetic or hemopoietic or haemopoietic or progenitor or precursor or bone marrow or mononuclear or adipose tissue or mesenchymal or stromal or autologous or allogeneic or allogenic or ALDH* or C‐KIT*) adj2 cell*).ti,ab.
7. (cell transplantation or stem cell* or bone marrow transplantation).jn.
8. ((autologous adj3 transplant*) or cell* therap*).tw.
9. ((cell* or myoblast*) adj3 (autologous or transplant* or autotransplant* or allotransplant* or graft* or implant*)).ti,ab.
10. or/1‐9
11. exp ISCHEMIC HEART DISEASE/
12. exp HEART FAILURE/
13. exp MYOCARDIAL DISEASE/
14. ((ischemi* or ischaemi* or nonischemi* or nonischaemi*) adj2 (myocardium or myocardial or cardiomyopath* or heart or coronary or cardiac or cardial or subendocardial)).ti,ab.
15. ((myocardial or myocardium or subendocardial or transmural or cardiac or cardial or coronary or heart) adj2 (failure* or decompensation or insufficien*)).ti,ab.
16. (IHD or CIHD or DCM or IDCM).ti,ab.
17. ((myocardial adj3 dysfunction*) or stenocardia or angina*).ti,ab.
18. ((arter* occlusion* or arter* disease* or arterioscleros* or atheroscleros*) adj2 coronary).ti,ab.
19. (heart disease* or coronary disease* or cardiovascular disease*).ti,ab.
20. ((end stage or endstage or dilated or idiopathic or congestive) adj2 cardiomyopath*).ti,ab.
21. ((heart or cardiac or cardial or myocardium or myocardial) adj3 (repair* or reparation or improv* or regenerat*)).ti,ab.
22. ((myocardial or myocardium or subendocardial or transmural or cardiac or cardial or coronary or heart or acute) adj3 (infarct* or postinfarct* or hypoxi* or anoxi*)).ti,ab.
23. (heart attack* or coronary attack* or acute coronary syndrome* or AMI).ti,ab.
24. 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23
25. 10 and 24
26. (cellular cardiomyoplast* or ((cardiomyocyte* or cardiac cell*) adj6 transplant*) or ((intramyocardial* or intracoronary or transendocardial* or transcoronary) adj6 (transplant* or stem or bone marrow or marrow cell* or BMC* or stromal or mesenchymal or progenitor cell* or precursor cell*))).mp.
27. 25 or 26
28. Meta Analysis/
29. Systematic Review/
30. (meta analy* or metaanalys*).tw.
31. (systematic* adj2 (review* or overview* or search*)).tw.
32. (literature adj2 (review* or overview* or search*)).tw.
33. (cochrane or embase or cinahl or cinhal or lilacs or BIDS or science citation index or psyclit or psychlit or psycinfo or psychinfo or cancerlit).ti,ab.
34. (electronic* adj (sources or resources or databases)).ab.
35. (reference lists or bibliograph* or handsearch* or hand search* or (manual* adj1 search*)).ab.
36. (additional adj (papers or articles or sources)).ab.
37. (relevant adj (journals or articles)).ab.
38. (search term* or published articles or search strateg*).ab.
39. Review.pt. and (data extraction or selection criteria).ab.
40. or/28‐39
41. Controlled Clinical Trial/
42. Phase 3 Clinical Trial/
43. Phase 4 Clinical Trial/
44. Randomized Controlled Trial/
45. Randomization/
46. Single Blind Procedure/
47. Double Blind Procedure/
48. Crossover Procedure/
49. Placebo/
50. (randomized or randomised or RCT).tw.
51. (random* adj5 (allocat* or assign* or divid* or receiv*)).tw.
52. (single blind* or double blind* or treble blind* or triple blind*).tw.
53. (phase III or phase three or "phase 3").tw.
54. (crossover* or cross over* or cross‐over* or placebo*).tw.
55. Prospective Study/
56. or/41‐55
57. Case Study/
58. case report*.tw.
59. (note or editorial).pt.
60. or/57‐59
61. 56 not 60
62. 40 or 61
63. limit 62 to embase
64. 27 and 63
CINAHL (EBSCOHost)
S1 (MH "Cell Transplantation+")
S2 (MH "Stem Cells+")
S3 TI ( (stem or haematopoietic or hematopoietic or haematopoetic or hematopoetic or hemopoietic or haemopoietic or progenitor or precursor or bone marrow or mononuclear or adipose tissue or mesenchymal or stromal or autologous or allogeneic or allogenic or ALDH* or C‐KIT*) N2 cell* ) OR AB ( (stem or haematopoietic or hematopoietic or haematopoetic or hematopoetic or hemopoietic or haemopoietic or progenitor or precursor or bone marrow or mononuclear or adipose tissue or mesenchymal or stromal or autologous or allogeneic or allogenic or ALDH* or C‐KIT*) N2 cell)
S4 TX ( (autologous N3 transplant*) or cell* therap* )
S5 TI ( (cell* or myoblast*) N3 (autologous or transplant* or autotransplant* or allotransplant* or graft* or implant*) ) OR AB ( (cell* or myoblast*) N3 (autologous or transplant* or autotransplant* or allotransplant* or graft* or implant*) )
S6 S1 OR S2 OR S3 OR S4 OR S5
S7 (MH "Heart Diseases+")
S8 TI ( (myocardial or myocardium or subendocardial or transmural or cardiac or cardial or coronary or heart or acute) N3 (infarct* or postinfarct* or hypoxi* or anoxi*) ) OR AB ( (myocardial or myocardium or subendocardial or transmural or cardiac or cardial or coronary or heart or acute) N3 (infarct* or postinfarct* or hypoxi* or anoxi*) )
S9 TI ( ("heart disease*" or "coronary disease*" or IHD or CIHD or DCM or IDCM) ) AND AB ( ("heart disease*" or "coronary disease*" or IHD or CIHD or DCM or IDCM) )
S10 TI ( ((myocardial N3 dysfunction) OR angina OR stenocardia) ) OR AB ( ((myocardial N3 dysfunction) OR angina OR stenocardia) )
S11 TI ( ((ischemi* or ischaemi* or nonischemi* or nonischaemi*) N5 (myocardium or myocardial or heart or coronary or cardiac or cardial or subendocardial or cardiomyopath*)) ) OR AB ( ((ischemi* or ischaemi* or nonischemi* or nonischaemi*) N5 (myocardium or myocardial or heart or coronary or cardiac or cardial or subendocardial or cardiomyopath*)) )
S12 TI ( ((arter* occlusion* or arter* disease* or arterioscleros* or atheroscleros*) N2 coronary) ) OR AB ( ((arter* occlusion* or arter* disease* or arterioscleros* or atheroscleros*) N2 coronary) )
S13 TI ( ((myocardial or myocardium or subendocardial or transmural or cardiac or cardial or coronary or heart) N2 (failure* or decompensation or insufficien*)) ) OR AB ( ((myocardial or myocardium or subendocardial or transmural or cardiac or cardial or coronary or heart) N2 (failure* or decompensation or insufficien*)) )
S14 TI ( (end stage or endstage or dilated or idiopathic or congestive) N2 cardiomyopath* ) OR AB ( (end stage or endstage or dilated or idiopathic or congestive) N2 cardiomyopath* )
S15 TI ( (heart or cardiac or cardial or myocardium or myocardial) N3 (repair* or reparation or improv* or regenerat*) ) OR AB ( (heart or cardiac or cardial or myocardium or myocardial) N3 (repair* or reparation or improv* or regenerat*) )
S16 TI (heart attack* or coronary attack* or acute coronary syndrome* or AMI) OR AB (heart attack* or coronary attack* or acute coronary syndrome* or AMI)
S17 S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16
S18 S6 AND S17
S19 TI ( cellular cardiomyoplast* or ((cardiomyocyte* or cardiac cell*) N6 transplant*) or ((intramyocardial* or intracoronary or transendocardial* or transcoronary) N6 (transplant* or stem or bone marrow or marrow cell* or BMC* or stromal or mesenchymal or progenitor cell* or precursor cell*)) ) OR AB ( cellular cardiomyoplast* or ((cardiomyocyte* or cardiac cell*) N6 transplant*) or ((intramyocardial* or intracoronary or transendocardial* or transcoronary) N6 (transplant* or stem or bone marrow or marrow cell* or BMC* or stromal or mesenchymal or progenitor cell* or precursor cell*))
S20 S18 OR S19
S21 (MH CLINICAL TRIALS+)
S22 PT Clinical Trial
S23 TI ((controlled trial*) or (clinical trial*)) OR AB ((controlled trial*) or (clinical trial*))
S24 TI ((singl* blind*) OR (doubl* blind*) OR (trebl* blind*) OR (tripl* blind*) OR (singl* mask*) OR (doubl* mask*) OR (tripl* mask*)) OR AB ((singl* blind*) OR (doubl* blind*) OR (trebl* blind*) OR (tripl* blind*) OR (singl* mask*) OR (doubl* mask*) OR (tripl* mask*))
S25 TI randomi* OR AB randomi*
S26 MH RANDOM ASSIGNMENT
S27 TI ((phase three) or (phase III) or (phase three)) or AB ((phase three) or (phase III) or (phase three))
S28 ( TI (random* N2 (assign* or allocat*)) ) OR ( AB (random* N2 (assign* or allocat*)) )
S29 MH PLACEBOS
S30 TI placebo* OR AB placebo*
S31 MH QUANTITATIVE STUDIES
S32 S21 or S22 or S23 or S24 or S25 or S26 or S27 or S28 or S29 or S30 or S31
S33 S20 and S32
PubMed (for epublications)
#1 (stem[TI] OR haematopoietic[TI] OR hematopoietic[TI] OR haematopoetic[TI] OR hematopoetic[TI] OR hemopoietic[TI] OR haemopoietic[TI] OR progenitor[TI] OR precursor[TI] OR bone marrow[TI] OR mononuclear[TI] OR "adipose tissue"[TI] OR mesenchymal[TI] OR stromal[TI] OR autologous[TI] OR allogeneic[TI] OR allogenic[TI] OR ALDH*[TI] OR C‐KIT*[TI]) AND cell*[TI]
#2 cell transplantation[TA] OR stem cell*[TA] OR bone marrow transplant*[TA]
#3 "autologous transplant*"[TI] OR "cell therapy"[TI] OR "cell therapies"[TI] OR "cellular therapy"[TI]
#4 (cell[TI] OR cells[TI] OR cellular[TI] OR myoblast*[TI]) AND (transplant[TI] OR transplantation[TI] OR transplants[TI] OR transplanting[TI] OR transplanted[TI] OR autotransplant*[TI] or allotransplant*[TI] or graft*[TI] or implant[TI] OR implants[TI] OR implantation[TI] OR implanted[TI])
#5 #1 OR #2 OR #3 OR #4
#6 (ischemi*[TI] OR ischaemi*[TI] OR nonischemi*[TI] OR nonischaemi*) AND (myocardium[TI] OR myocardial[TI] OR cardiomyopath*[TI] OR heart[TI] OR coronary[TI] OR cardiac[TI] OR cardial[TI] OR subendocardial[TI])
#7 (myocardial[TI] OR myocardium[TI] OR subendocardial[TI] OR transmural[TI] OR cardiac[TI] OR cardial[TI] OR coronary[TI] OR heart) AND (failure*[TI] OR decompensation[TI] OR insufficien*[TI])
#8 "myocardial dysfunction*"[TI] OR stenocardia[TI] OR angina*[TI] OR IHD[TI] OR CIHD[TI] OR DCM[TI] OR IDCM[TI] OR "heart disease"[TI] OR "coronary disease"[TI] OR "coronary artery disease"[TI] OR "cardiovascular disease"[TI]
#9 ("arterial occlusion*"[TI] OR "arterial disease*"[TI] OR arterioscleros*[TI] OR atheroscleros*[TI]) AND coronary[TI]
#10 ("end stage"[TI] OR endstage[TI] OR dilated[TI] OR idiopathic[TI] OR congestive[TI]) AND cardiomyopath*[TI]
#11 (heart[TI] OR cardiac[TI] OR cardial[TI] OR myocardium[TI] OR myocardial[TI]) AND (repair*[TI] OR reparation[TI] OR improv*[TI] OR regenerat*[TI])
#12 (myocardial[TI] OR myocardium [TI] OR subendocardial [TI] OR transmural [TI] OR cardiac [TI] OR cardial [TI] OR coronary [TI] OR heart [TI] OR acute[TI]) AND (infarct* [TI] OR postinfarct* [TI] OR hypoxi* [TI] OR anoxi*)
#13 heart attack* [TI] OR coronary attack* [TI] OR acute coronary syndrome* [TI] OR AMI[TI]
#14 #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13
#15 #5 AND #14
#16 (cellular cardiomyoplast* OR ((cardiomyocyte* OR cardiac cell*) AND transplant*) OR ((intramyocardial* OR intracoronary OR transendocardial* OR transcoronary) AND (transplant* OR stem OR bone marrow OR marrow cell* OR BMC* OR stromal OR mesenchymal OR progenitor cell* OR precursor cell*)))
#17 #15 OR #16
#18 (random* OR blind* OR control group* OR placebo OR controlled trial OR controlled study OR trials OR systematic review OR meta‐analysis OR metaanalysis OR literature search OR medline OR cochrane OR embase) AND ((publisher[sb] OR inprocess[sb]) NOT pubstatusnihms)
#19 #17 AND #18
LILACS
(tw:((infarct OR infarction OR coronary OR myocardial OR heart OR cardiac OR cardiomyopathy OR myocardial OR subendocardial OR intramyocardial OR intracoronary OR ischemia OR ischemic OR nonischemic))) AND (tw:((bone marrow OR marrow cell OR marrow cells OR stem cell OR stem cells OR progenitor cells OR precursor cells OR cell therapy OR cellular therapy OR cell‐based therapy OR mononuclear cells OR mesenchymal cells OR stromal cells))) AND (instance:"regional") AND ( db:("LILACS") AND type_of_study:("clinical_trials"))
KoreaMed
Search lines were run separately, but presented this way for brevity:
(stem [ALL] OR marrow [ALL] OR mesenchymal[ALL] OR stromal[ALL]) AND (myocardial [ALL] OR heart[ALL] OR cardiac[ALL] OR coronary[ALL] OR cardiomyopathy[ALL]) AND "Randomized Controlled Trial" [PT]
IndMed
(bone marrow OR marrow cell OR marrow cells OR stem cell OR stem cells OR progenitor cell OR precursor cell OR cell therapy OR cellular therapy OR mesenchymal cells OR stromal cells) AND (infarct OR infarction OR coronary OR intracoronary OR myocardial OR heart OR cardiac OR congestive OR cardiomyopathy OR intramyocardial OR intramyocardial OR intracoronary OR ischemia OR ischemic OR ischaemia OR ischaemic OR nonischemic OR nonischaemic) AND (randomised OR randomly OR randomized OR blind OR blinded OR trial OR study OR control group)
PakMediNet
Combinations of the following free text terms were used:
stem cell, stem cells, bone marrow, marrow cells, progenitor cells, precursor cells, mesenchymal cells, stromal cells
AND
myocardial infarction, heart attack, cardiac ischemia, coronary ischemia, myocardial ischemia, cardiomyopathy, heart failure, cardiac failure, angina, coronary artery disease
Web of Science
Title: "cardiac failure" OR "heart attack" OR "heart failure" OR "coronary disease" OR "cardiovascular disease" OR "coronary artery" OR "coronary arterial" OR "myocardial infarction" OR cardiomyopathy OR "heart disease" OR "heart diseases" OR "cardiac insufficiency" OR AMI OR IHD OR CIHD OR DCM OR IDCM OR "myocardial dysfunction" OR stenocardia OR angina
AND
Title: "stem cell" OR "stem cells" OR "bone marrow" OR "marrow cells" OR "cellular therapy" OR "mesenchymal cells" OR "stromal cells" OR "cell transplant" OR "precursor cells" OR "progenitor cells" OR (c‐kit* NEAR/5 cells) OR HSCT OR SCT OR MSC OR MSCs OR BMT OR BMC OR BMAC OR BMCs OR HST OR HSTs
AND
Topic: randomised OR randomly OR randomized OR blind OR blinded OR trial OR study OR "control group" OR group
ClinicalTrials.gov
Search Terms: randomized OR randomised OR random OR randomly
Study Type: Intervention Studies
Condition: cardiac OR heart attack OR heart failure OR coronary OR myocardial OR cardiomyopathy OR heart disease OR angina
Intervention: stem cells OR bone marrow cells OR cellular therapy OR mesenchymal cells OR stromal cells OR cell transplant OR precursor cells OR progenitor cells OR HSCT OR SCT OR MSC OR MSCs OR BMT OR BMC OR BMAC OR BMCs OR HST OR HSTs
ISRCTN Register
(("marrow cell" OR "marrow cells" OR "stem cell" OR "stem cells" OR "progenitor cells" OR "precursor cells" OR "mesenchymal cells" OR "stromal cells") AND ("myocardial infarction" OR "heart attack" OR cardiomyopathy OR intramyocardial OR intracoronary))
OR
(("marrow cell" OR "marrow cells" OR "stem cell" OR "stem cells" OR "progenitor cells" OR "precursor cells" OR "mesenchymal cells" OR "stromal cells") AND ("cardiac ischemia" OR "coronary ischemia" OR "myocardial ischemia" OR "heart failure" OR "cardiac failure" OR congestive OR "coronary artery disease"))
OR
(("cell therapy" OR "cellular therapy") AND ("myocardial infarction" OR "heart attack" OR cardiomyopathy OR intramyocardial OR intracoronary OR "cardiac ischemia" OR "coronary ischemia" OR "myocardial ischemia" OR "heart failure" OR "cardiac failure" OR congestive OR "coronary artery disease" OR angina))
WHO ICTRP Portal
Intervention: stem cells OR bone marrow cells OR cellular therapy OR mesenchymal cells OR stromal cells OR cell transplant OR precursor cells OR progenitor cells OR HSCT OR SCT OR MSC OR MSCs OR BMT OR BMC OR BMAC OR BMCs OR HST OR HSTs
Condition: cardiac OR heart OR coronary OR myocardial OR angina
Recruitment Status: ALL
Study flow diagram.
Funnel plot of comparison: 1 Cells compared to no cells, outcome: 1.1 All‐cause mortality.
Trial sequential analysis of all‐cause mortality at long term follow‐up, assuming a long‐term mortality incidence rate of 6.1% in controls and a relative risk reduction of 35% in cell therapy patients
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 Cells compared to no cells, Outcome 1 All‐cause mortality.
Comparison 1 Cells compared to no cells, Outcome 2 Cardiovascular mortality.
Comparison 1 Cells compared to no cells, Outcome 3 Composite measure of death, reinfarction, re‐hospitalisation for heart failure.
Comparison 1 Cells compared to no cells, Outcome 4 Incidence of reinfarction.
Comparison 1 Cells compared to no cells, Outcome 5 Incidence of re‐hospitalisation for heart failure.
Comparison 1 Cells compared to no cells, Outcome 6 Incidence of target vessel revascularisation.
Comparison 1 Cells compared to no cells, Outcome 7 Incidence of arrhythmias.
Comparison 1 Cells compared to no cells, Outcome 8 Incidence of restenosis.
Comparison 1 Cells compared to no cells, Outcome 9 Quality of life measures.
Comparison 1 Cells compared to no cells, Outcome 10 NYHA classification.
Comparison 1 Cells compared to no cells, Outcome 11 Exercise tolerance.
Comparison 1 Cells compared to no cells, Outcome 12 Maximum VO2 (mL/kg/min).
Comparison 1 Cells compared to no cells, Outcome 13 VE/VCO2 slope.
Comparison 1 Cells compared to no cells, Outcome 14 Peak heart rate (bpm).
Comparison 1 Cells compared to no cells, Outcome 15 LVEF measured by MRI (<12 months).
Comparison 1 Cells compared to no cells, Outcome 16 LVEF measured by MRI (≥ 12 months).
Comparison 1 Cells compared to no cells, Outcome 17 LVEF measured by echocardiography (< 12 months).
Comparison 1 Cells compared to no cells, Outcome 18 LVEF measured by echocardiography (≥12 months).
Comparison 1 Cells compared to no cells, Outcome 19 LVEF measured by SPECT (< 12 months).
Comparison 1 Cells compared to no cells, Outcome 20 LVEF measured by SPECT (≥ 12 months).
Comparison 1 Cells compared to no cells, Outcome 21 LVEF measured by left ventricular angiography (< 12 months).
Comparison 1 Cells compared to no cells, Outcome 22 LVEF measured by left ventricular angiography (≥ 12 months).
Comparison 1 Cells compared to no cells, Outcome 23 LVEF measured by radionuclide ventriculography (RNV) (<12 months).
Comparison 1 Cells compared to no cells, Outcome 24 LVEF measured by radionuclide ventriculography (≥ 12 months).
Comparison 2 Sensitivity analysis ‐ route of cell delivery, Outcome 1 All‐cause mortality (< 12 months).
Comparison 3 Sensitivity analysis ‐ selection bias, Outcome 1 All‐cause mortality (< 12 months).
Comparison 4 Sensitivity analysis ‐ attrition bias, Outcome 1 All‐cause mortality (< 12 months).
Comparison 4 Sensitivity analysis ‐ attrition bias, Outcome 2 All‐cause mortality (≥ 12 months).
Comparison 4 Sensitivity analysis ‐ attrition bias, Outcome 3 Cardiovascular mortality (< 12 months).
Comparison 4 Sensitivity analysis ‐ attrition bias, Outcome 4 Cardiovascular mortality (≥ 12 months).
Comparison 5 Sensitivity analysis ‐ performance bias, Outcome 1 All‐cause mortality (< 12 months).
Comparison 5 Sensitivity analysis ‐ performance bias, Outcome 2 All‐cause mortality (≥ 12 months).
Comparison 6 Subgroup analysis ‐ baseline LVEF measured by MRI, Outcome 1 All‐cause mortality (< 12 months).
Comparison 6 Subgroup analysis ‐ baseline LVEF measured by MRI, Outcome 2 All‐cause mortality (≥ 12 months).
Comparison 6 Subgroup analysis ‐ baseline LVEF measured by MRI, Outcome 3 LVEF measured by MRI (< 12 months).
Comparison 6 Subgroup analysis ‐ baseline LVEF measured by MRI, Outcome 4 LVEF measured by MRI (≥ 12 months).
Comparison 7 Subgroup analysis ‐ cell type, Outcome 1 All‐cause mortality (< 12 months).
Comparison 7 Subgroup analysis ‐ cell type, Outcome 2 All‐cause mortality (≥ 12 months).
Comparison 8 Subgroup analysis ‐ dose of stem cells, Outcome 1 All‐cause mortality (< 12 months).
Comparison 8 Subgroup analysis ‐ dose of stem cells, Outcome 2 All‐cause mortality (≥ 12 months).
Comparison 8 Subgroup analysis ‐ dose of stem cells, Outcome 3 LVEF measured by MRI (< 12 months).
Comparison 8 Subgroup analysis ‐ dose of stem cells, Outcome 4 LVEF measured by MRI (≥ 12 months).
Comparison 8 Subgroup analysis ‐ dose of stem cells, Outcome 5 LVEF measured by left ventricular angiography (< 12 months).
Comparison 9 Subgroup analysis ‐ timing of cell administration, Outcome 1 All‐cause mortality (< 12 months).
Comparison 9 Subgroup analysis ‐ timing of cell administration, Outcome 2 All‐cause mortality (≥ 12 months).
Comparison 9 Subgroup analysis ‐ timing of cell administration, Outcome 3 LVEF measured by MRI (< 12 months).
Comparison 9 Subgroup analysis ‐ timing of cell administration, Outcome 4 LVEF measured by MRI (≥ 12 months).
Comparison 9 Subgroup analysis ‐ timing of cell administration, Outcome 5 LVEF measured by left ventricular angiography (< 12 months).
Comparison 10 Subgroup analysis ‐ heparinised cell solution, Outcome 1 All‐cause mortality (< 12 months).
Comparison 10 Subgroup analysis ‐ heparinised cell solution, Outcome 2 All‐cause mortality (≥ 12 months).
Comparison 10 Subgroup analysis ‐ heparinised cell solution, Outcome 3 LVEF measured by MRI (< 12 months).
Comparison 10 Subgroup analysis ‐ heparinised cell solution, Outcome 4 LVEF measured by MRI (≥ 12 months).
Comparison 10 Subgroup analysis ‐ heparinised cell solution, Outcome 5 LVEF measured by left ventricular angiography (< 12 months).
| Cells compared to no cells for acute myocardial infarction (AMI) | ||||||
| Patient or population: patients with AMI | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| No cells | Cells | |||||
| All‐cause mortality ‐ short‐term follow‐up (< 12 months) | Study population | RR 0.80 | 1365 | ⊕⊕⊕⊝ | Further research may change the estimate | |
| 28 per 1000 | 23 per 1000 | |||||
| All‐cause mortality ‐ long‐term follow‐up (≥ 12 months) | Study population | RR 0.93 | 996 | ⊕⊕⊕⊝ | Further research may change the estimate | |
| 70 per 1000 | 65 per 1000 | |||||
| Cardiovascular mortality ‐ short‐term follow‐up (< 12 months) | Study population | RR 0.72 | 290 | ⊕⊕⊕⊝ | Further research may change the estimate | |
| 54 per 1000 | 39 per 1000 | |||||
| Cardiovascular mortality ‐ long‐term follow‐up (≥ 12 months) | Study population | RR 1.04 | 527 | ⊕⊕⊕⊝ | Further research may change the estimate | |
| 72 per 1000 | 75 per 1000 | |||||
| Composite death, reinfarction and hospitalisation for heart failure ‐ short‐term follow‐up (< 12 months) | Study population | RR 0.36 | 379 | ⊕⊕⊕⊝ | Further research may change the estimate | |
| 66 per 1000 | 24 per 1000 | |||||
| Composite death, reinfarction and hospitalisation for heart failure ‐ long‐term follow‐up (≥ 12 months) | Study population | RR 0.63 | 497 | ⊕⊕⊕⊝ | Further research may change the estimate | |
| 140 per 1000 | 88 per 1000 | |||||
| *The assumed risk is based on the observed incidence across the pooled control groups. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Imprecision: information size criterion not met. Small size effect. | ||||||
| Study ID | Country of study | Patient population | Mean (SD) age of participants (years) | % Male | No. randomised participants receiving intervention | No. randomised participants receiving comparator | Mean duration of follow‐up |
| Brazil | STEMI with LVEF < 45%; successful PCI | n/r | n/r | 11 | 11 | 12 months | |
| China | STEMI; PCI within 12 hours, often with drug‐eluting stent implantation | BMMNC: 50.7 (SEM 1.1) | BMMNC: 95.1% | 41 | 45 | 48 months | |
| China | AMI; PCI within 12 hours, mostly with stent implantation | BMMNC: 58 (7.0) | BMMNC: 94% | 34 | 35 | 6 months | |
| Italy | Large anterior STEMI; PCI with bare metal stent implantation within 12 hours | CD133+: median 54 (range 47 to 60) | CD133+: 100% | 5 | 5 | 12 months | |
| China | Acute STEMI; PCI with stent implantation within 12 hours | BM‐MSC: 55.0 (SEM 1.6) | BM‐MSC: 100% | 21 | 22 | 24 months | |
| China | First STEMI within 24 hours; PCI with stent implantation | BMMNC: 58 (11) | BMMNC: 80% | 10 | 10 | 6 months | |
| Poland | First anterior AMI; PCI within 12 hours with bare metal stent implantation | BMMNC: 49.9 (8.4) | BMMNC: 87% | 31 | 14 | 12 months | |
| Hirsch 2011 | The Netherlands | First STEMI; PCI with stent implantation within 12 hours | BMMNC: 56 (9) | BMMNC: 84% | 69 | 65 | 60 months |
| China | AMI; PCI within 24 hours | BMMNC: 57.3 (10.1) | BMMNC: 65% | 20 | 20 | 6 months | |
| China | AMI; PCI within 24 hours with bare metal (35%) or drug‐eluting (65%) stent implantation | BMMNC: 54.8 (5.8) | BMMNC: 85% | 20 | 20 | 6 months | |
| Huikuri 2008 | Finland | STEMI; thrombolytic drugs initiated within 12 hours | BMMNC: 60 (10) | BMMNC: 90% | 40 | 40 | 6 months |
| Belgium | STEMI; PCI with bare metal stent implantation at median 3.7 hours (IQR 2.5 to 7.6) | BMMNC: 55.8 (11) | BMMNC: 82% | 33 | 34 | 4 months | |
| Iran | Anterior MI within 1 month with a history of anterior MI and LVEF < 35%; PCI | BMMNC: 48.0 (SEM 2.5) | BMMNC: 66% | n/r | n/r | 6 months | |
| China | AMI; thrombolytic drugs and PCI | BMMNC: 62.3 (7.7) | BMMNC: 71.4% | 14 | 12 | 12 months | |
| Russia | STEMI; PCI with bare metal stent implantation within 6.6 (4.9) hours and thrombolytic drugs | BMMNC: 55.2 (8.6) | BMMNC: 90% | 28 | 34 | 8.2 (0.72) years | |
| Lee 2014 | South Korea | STEMI within 24 hours enrolled < 72 hours after revascularisation by | BM‐MSC: 53.9 (10.5) | BM‐MSC: 90.0% | 40 | 40 | 6 months |
| Lunde 2006 | Norway | Anterior STEMI; PCI within 2 to 24 hours | BMMNC: 58.1 (8.5) | BMMNC: 84% | 50 | 51 | 36 months |
| Czech Republic | First STEMI; PCI with stent implantation within 12 hours or 3 days | BMMNC: 54 (SEM 2) | BMMNC: 90% (HD), 95% (LD) | n/r (a) | n/r (a) | 12 months | |
| Nogueira 2009 | Brazil | STEMI; thrombolytic drugs and PCI with stent implantation within 24 hours | BMMNC: 59.7 (14.3) (AG), 53.6 (8.3) (VG) | BMMNC: 71% (AG), 70% (VG) | 24 (14 AG, 10 VG) | 6 | 6 months |
| Czech Republic | First anterior STEMI and LVEF ≤ 50% | BMMNC: 61 (14) | BMMNC: 71% | 17 | 10 | 24 months | |
| Piepoli 2010 | Italy | Anterior STEMI; PCI with stent implantation within 2 to 6 hours | BMMNC: 63.1 (SEM 2.7) | BMMNC: 68.4% | 19 | 19 | 24 months |
| Poland | First anterior STEMI and LVEF < 40%; PCI within 12 hours | BMMNC: 59 (9) | BMMNC: 68% | 40 | 20 | 24 months | |
| Quyyumi 2011 | USA | Acute STEMI and LVEF ≤ 50% | CD34+: median 50.5 (IQR 45 ‐ 53) (HD), 63.0 (IQR 57 ‐ 66) (MD), 52.0 (IQR 51 ‐ 52) (LD) | CD34+: 100% (HD), 80% (MD), 80% (LD) | 16 (5 LD, 5 MD, 6 HD) | 15 | 12 months |
| Roncalli 2010 | France | Acute STEMI and LVEF ≤ 45%; PCI with bare metal stent implantation within 24 hours | BMMNC: 56 (12) | BMMNC: 80.8% | 52 | 49 | 12 months |
| China | AMI admitted within mean 12.1 (12.6) hours of onset; PCI | BMMNC: 61 (8) | BMMNC: 88.9 | 9 | 11 | 6 months | |
| Schachinger 2006 | Germany; Switzerland | Acute STEMI and visual estimated LVEF ≤ 45%; PCI with stent implantation at mean 7.5 (8.0) hours | BMMNC: 55 (11) | BMMNC: 82% | 101 | 103 | 60 months |
| Spain | Anterior STEMI within 12 hours; PCI (some with stent) or thrombolytics | BMMNC: 52 (12) | BMMNC: 80% | 10 | 10 | 3 months | |
| Sürder 2013 | Switzerland | Large STEMI with LVEF < 45%; thrombolytics and PCI with stent within 24 hours | BMMNC: median 55 (IQR 15) (E), 62 (IQR 15) (L) | BMMNC: 86.2% (E), 82.5 (L) | 133 (66 E, 67 L) | 67 | 12 months |
| Tendera 2009 | Poland | Anterior AMI and LVEF ≤ 40% | CD34/CXCR4+: median 58 BMMNC: median 55 | CD34/CXCR4+: 63.7% BMMNC: 70.6% | 160 (80 CD34/CXCR4+, 80 BMMNC) | 40 | 6 months |
| USA | First anterior STEMI; PCI mostly with drug‐eluting stent implantation | BMMNC: median 52.5 (IQR 43 ‐ 64) | BMMNC: 83.3% | 30 | 10 | 15 months | |
| Traverse 2011 | USA | STEMI with LVEF ≤ 45%; PCI with stent, mostly drug‐eluting, at median 3.4 (IQR 2.3 to 14.3) hours | BMMNC: 57.6 (11) | BMMNC: 79% | 59 | 29 | 6 months |
| Traverse 2012 | USA | Anterior STEMI with LVEF < 45%; PCI with stent, mostly drug‐eluting | BMMNC: 55.6 (10.8) (day 3)/58.2 (11.3) day 7) | BMMNC: 88.4% (day 3)/86.1% (day 7) | 43 (day 3) | 24 (day 3) | 12 months |
| Germany | Acute STEMI; PCI with stent implantation | BMMNC: 61 (15) | BMMNC: 67% | 42 | 20 | 12 months | |
| China | Acute STEMI; PCI predominantly with stent implantation within 8 hours | BM‐MSC: 58 (10.2) | BM‐MSC: 67.9% | 30 | 30 | 6 months | |
| Wohrle 2010 | Germany | AMI; PCI with stent, some drug eluting, within 6 to 48 hours | BMMNC: 61.0 (8.1) | BMMNC: 90% | 29 | 13 | 36 months |
| Wollert 2004 | Germany | STEMI within 5 days; PCI with bare metal stent implantation, some with thrombolytic drugs | BMMNC: 53.4 (14.8) | BMMNC: 67% | 33 | 32 | 60 months |
| China | AMI; undergoing elective PCI within 4 weeks of AMI | BM‐MSC: 60.4 (8.9) | BM‐MSC: 58.8% | 17 | 21 | 3 months | |
| China | STEMI within 1 week; PCI | BMMNC: 58.3 (9.5) | BMMNC: 89.1% | 92 | 92 | 30 months | |
| China | First anterior STEMI; PCI within 12 hours | BMMNC: 52.1 (6.3) (SD), 51.3 (7.4) (DD) | BMMNC: 83.3& (SD), 80.0% (DD) | 30 (15 SD, 15 DD) | 15 | 12 months | |
| China | AMI within 24 hours; thombolytic reperfusion | BM‐MSC: 60.5 | BM‐MSC: 71.4% | 7 | 16 | 8 weeks | |
| Russia | MI of the front wall; thrombolytic drugs and/or PCI with stent implantation | BMMNC: 48 (7) | BMMNC: 100% | 8 | 3 | 36 months | |
| STEMI, ST‐segment elevation myocardial infarction; AMI, acute myocardial infarction; PCI, percutaneous coronary intervention; LVEF, left ventricular ejection fraction; BMMNC, bone marrow mononuclear cells; BM‐MSC, bone marrow mesenchymal stem cells; SEM, standard error of the mean; SD, standard deviation; LD, low dose; MD, moderate dose; HD, high dose; AG, arterial group; VG, venous group; E, early cells; L, late cells; S, selected cells; U, unselected cells; SD, single dose; DD, double dose (a)Meluzin 2008: 73 participants were randomised in total ‐ the number randomised to each group was not reported. | |||||||
| Study ID | Time of cell administration | Intervention given by: | Route of cell administration | Intervention cell type | How are cells obtained? (*) | What were they re‐suspended in? | Dose administered? | Comparator arm (placebo or control) |
| 5 to 9 days after AMI | Cardiologist | Infusion into IRCA | BMMNC | n/r | n/r | 260 (160) million cells | Placebo (n/r) | |
| 7 days after PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised saline | 500 million cells | Placebo (heparinised saline) | |
| Mean 18.4 (0.5) days after PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised saline | 48,000 (60,000) million cells | Placebo (heparinised saline) | |
| Day 9 to 16 after PCI | Cardiologist | Infusion into IRCA | CD133‐positive cells | BM aspiration (**), immunomagnetic selection to isolate CD133‐positive cells | 0.9% saline solution and 10% human serum albumin | Median (range): 5.9 (4.9 to 13.5) million cells | No additional therapy (Control) | |
| Mean 17.1 (0.6) hours after PCI | Cardiologist | Infusion into IRCA | BM‐MSC | BM aspiration (**), culture for 14 days to select MSC | Heparinised saline | 3.08 (0.52) million cells | No additional therapy (Control) | |
| Within 15 hours of AMI | Cardiologist | Infusion into IRCA | BMMNC | n/r | n/r | 40 million cells | Placebo (n/r) | |
| 5 to 6 days after PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | X‐vivo 15 medium and 2% autologous plasma | 410 (180) million cells | No additional therapy (Control) | |
| Hirsch 2011 | 3 to 8 days after PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised saline and 4 % human serum albumin | 296 (164) million cells | No additional therapy (Control) |
| Within 2 hours of PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised saline | 180 (420) million cells | Placebo (heparinised saline) | |
| Within 2 hours of PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised saline | 120 (650) million cells | Placebo (heparinised saline) | |
| Huikuri 2008 | Mean 70 (36) hours after thombolysis | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised saline and 50% autologous serum | 402 (196) million cells | Placebo (heparinised saline and 50% autologous serum) |
| Within 20 hours of PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised saline and 5% autologous serum solution | 172 (72) million cells | Placebo (heparinised saline and 5% autologous serum) | |
| Within 1 month of AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | M199 medium containing VEGF, bFGF, IGF‐1 and 10% human serum | 2460 (SEM 840) million cells | No additional therapy (Control) | |
| At least 7 to 10 days after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised saline | 62.7 (17.5) million cells | No additional therapy (Control) | |
| 7 to 21 days after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | n/r | 88.5 (49.2) million cells | No additional therapy (Control) | |
| Lee 2014 | 25 (2.4) days after BM aspiration at 3.8 (1.5) days after admission | Cardiologist | Infusion into IRCA | BM‐MSC | BM aspiration (**), culture for 2 to 3 weeks to isolate MSC | n/r | 72 (9) million cells | No additional therapy (Control) |
| Lunde 2006 | 4 to 8 days after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised plasma | Median (interquartile range): 68 (54 to 130) million cells | No additional therapy (Control) |
| 5 to 9 days (mean 7 (0.3) days) after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | n/r | LD: 10 million cells (range: 9 to 20 million) HD: 100 million cells (90 to 200 million cells) | No additional therapy (Control) | |
| Nogueira 2009 | AG: 3 to 6 days (mean 5.5 (1.28) days) after PCI VG: 3 to 6 days (mean 6.1 (1.37) days) after PCI | Cardiologist | Infusion into IRCA (AG) or IRCV (VG) | BMMNC | BM aspiration (**) | Saline solution and 5% human serum albumin | 100 million cells | No additional therapy (Control) |
| 4 to 11 days (median 9 days) after PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | n/r | 2,640 million cells | No additional therapy (Control) | |
| Piepoli 2010 | 4 to 7 days after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Phosphate buffered saline ‐ EDTA and 5% human serum albumin | 249 million cells | No additional therapy (Control) |
| 3 to 11 days (mean 7 (2) days after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised saline | 144 (49) million cells | No additional therapy (Control) | |
| Quyyumi 2011 | LD: median 191.4 (IQR 167 to 201) hours, MD: 210.0 (IQR 194 to 210) hours, HD: 207.3 (IQR 191 to 215) hours after AMI | Cardiologist | Infusion into IRCA | CD34‐positive cells | BM aspiration (**), immunomagnetic selection to isolate CD34‐positive cells | Heparinised phosphate buffered saline, 40% autologous serum and 1% human serum albumin | LD: 4.8 (0.4) million cells MD: 9.9 (0.7) million cells HD: 14.3 (1.6) million cells | No additional therapy (Control) |
| Roncalli 2010 | At 7 to 10 days (mean 9 (SD 1.7)) days | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | 4% human serum albumin solution | 98.3 (8.7) million cells | No additional therapy (Control) |
| Within 2 hours of successful PTCA | Cardiologist | Infusion into IRCA | BMMNC | n/r | Diluted autologous serum | n/r | Placebo (diluted autologous serum) | |
| Schachinger 2006 | Within 5 days (mean 4.3 (1.3) days) of PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | X‐VIVO medium and 20% autologous serum | 236 (174) million cells | Placebo (X‐VIVO medium and 20% autologous serum) |
| 5 to 12 days (mean 7 (2) days) after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised saline | 900 (300) million | Placebo (heparinised saline) | |
| Sürder 2013 | 5 to 7 days (E) or 3 to 4 weeks (L) after PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Serum‐free medium and 20% of autologous serum | E: 159.7 (125.8) million cells L: 139.5 (120.5) million cells | No additional therapy (Control) |
| Tendera 2009 | Median 7 (IQR 3 to 12) days after PCI | Cardiologist | Infusion into IRCA | Selected cells (S): CD34/CXCR4‐ positive cells Unselected cells (U): BMMNC | BM aspiration (**). Selected cells: immunomagnetic selection to isolate CD34/CXCR4‐positive cells | Phosphate‐buffered saline | S: 1.9 million cells U: 178 million cells | No additional therapy (Control) |
| 3 to 10 days (median 4.5 (IQR 4 to 7) days) after PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | 0.9% saline solution and 5% human serum albumin | 100 million cells | Placebo (0.9% saline solution and 5% human serum albumin) | |
| Traverse 2011 | 2 to 3 weeks (median 17.5 (IQR 15.5 to 20.0) days) after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | 0.9% saline solution and 5% human serum albumin | 147 (17) million cells | Placebo (0.9% saline solution and 5% human serum albumin) |
| Traverse 2012 | 3 days or 7 days after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | 0.9% saline solution and 5% human serum albumin | 150 million cells | Placebo (0.9% saline solution and 5% human serum albumin) |
| 7 days after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | n/r | n/r | No additional therapy (control) | |
| 15 (1) days after PCI | Cardiologist | Infusion into IRCA | BM‐MSC | BM aspiration (**) and culture of MSC | Heparinised saline | 100 million cells | Placebo (heparinised saline) | |
| Wohrle 2010 | 5 to 7 days (median 6.1 (IQR 5.5 to 7.3) days) after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | 0.9% saline solution, 2% human serum albumin and 0.1% autologous erythrocytes | 381 (130) million cells | Placebo (0.9% saline solution, 2% human serum albumin and 0.1% autologous erythrocytes) |
| Wollert 2004 | 4.7 (1.3) days after PCI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised saline | 2460 (940) million cells | No additional therapy (Control) |
| Within 4 weeks of AMI | Cardiologist | Infusion into IRCA | BM‐MSC | BM aspiration (**) and culture of MSC | n/r | 460 (160) million cells | Placebo (heparinised saline) | |
| Within 7 days of AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Lymphocyte isolation medium | 210 (370) million cells | No additional therapy (control) | |
| SD: 3 to 7 days after PCI DD 3 to 7 days after PCI; second dose at 3 months | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Heparinised plasma | SD: 410 million cells DD: 190 (SE 120) million cells | Placebo (heparinised plasma) | |
| At day 14 | Cardiologist | Infusion into IRCA | BM‐MSC | BM aspiration (**), second centrifugation and culture of MSC | n/r | 75 million cells | No additional therapy (control) | |
| 14 to 19 days after AMI | Cardiologist | Infusion into IRCA | BMMNC | BM aspiration (**) | Autologous serum | 50 million cells | No additional therapy (control) | |
| AMI ‐ acute myocardial infarction, PCI ‐ percutaneous coronary intervention, BM ‐ bone marrow, PTCA ‐ percutaneous transluminal coronary angioplasty, IRCA ‐ infarct‐related coronary artery, IRCV ‐ infarct‐related coronary vein, BMMNC ‐ bone marrow mononuclear cells, BM‐MSC ‐ mesenchymal stem cells; LD ‐ low dose, MD ‐ moderate dose, HD ‐ high dose, AG ‐ arterial group, VG ‐ venous group, E ‐ early cells, L ‐ late cells, S ‐ selected cells, U ‐ unselected cells, SD ‐ single dose, DD ‐ double dose ** BM aspiration‐ bone marrow aspiration and isolation of bone marrow mononuclear cells by gradient centrifugation | ||||||||
| Study ID | Primary Outcomes | Secondary Outcomes | ||||||||||||||||||||||
| All‐cause mortality | Cardiovascular mortality | Composite MACE (a) | Reinfarction | Hospital readmission for HF | Target vessel revascularisation | Arrhythmias | Restenosis | NYHA class | Quality of life (QoL) | Exercise tolerance | LVEF (b) | |||||||||||||
| ST | LT | ST | LT | ST | LT | ST | LT | ST | LT | ST | LT | ST | LT | ST | LT | ST | LT | ST | LT | ST | LT | ST | LT | |
| PR* | PR* | PR* | PR* | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | FR | |
| PR* | FR | NR | NR | NR | NR | PR* | PR* | NR | NR | PR* | FR | NR | NR | PR* | FR | NR | NR | NR | NR | NR | NR | FR | FR | |
| PR* | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | PR* | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| PR* | PR* | NR | PR* | NR | NR | NR | NR | FR | PR | NR | NR | NR | FR | NR | NR | NR | NR | NR | NR | NR | PR | FR | FR | |
| FR | FR | FR | FR | NR | FR | FR | FR | NR | FR | NR | NR | PR* | PR* | NR | NR | NR | NR | NR | NR | NR | NR | FR | FR | |
| PR* | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | PR* | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| NR | FR | NR | NR | NR | NR | FR | NR | NR | NR | FR | NR | NR | NR | FR | NR | NR | NR | NR | NR | FR | FR | FR | FR | |
| PR* | FR | NR | NR | FR | FR | FR | FR | FR | FR | FR | FR | FR | FR | NR | NR | NR | FR | NR | NR | NR | NR | FR | FR | |
| PR* | NR | NR | NR | NR | NR | PR* | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| FR | NR | FR | NR | NR | NR | FR | NR | FR | NR | NR | NR | PR* | NR | PR | NR | NR | NR | NR | NR | FR | NR | FR | NR | |
| FR | NR | PR* | NR | NR | NR | NR | NR | NR | NR | PR* | NR | FR | NR | FR | NR | NR | NR | NR | NR | NR | NR | FR | FR | |
| PR* | NR | PR* | NR | NR | NR | PR* | NR | NR | NR | NR | NR | PR* | NR | PR* | NR | FR | NR | NR | NR | NR | NR | FR | NR | |
| NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | FR | FR | FR | NR | NR | FR | FR | |
| PR* | FR | PR* | FR | NR | NR | FR | FR | NR | NR | NR | NR | NR | NR | NR | NR | NR | PR | FR | NR | FR | NR | FR | NR | |
| PR* | NR | PR* | NR | NR | NR | FR | NR | NR | NR | PR* | NR | PR* | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| NR | FR | NR | NR | NR | NR | FR | FR | FR | FR | NR | FR | NR | FR | FR | NR | FR | NR | FR | NR | FR | NR | FR | FR | |
| PR* | PR* | PR* | PR* | NR | NR | FR | FR | FR | FR | NR | NR | PR* | NR | FR | PR | NR | NR | NR | NR | NR | NR | FR | FR | |
| FR | NR | PR* | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | PR | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| FR | FR | FR | FR | NR | FR | FR | FR | FR | FR | NR | NR | NR | PR* | NR | FR | NR | FR | NR | PR | NR | NR | FR | FR | |
| FR | FR | FR | FR | NR | NR | NR | NR | NR | NR | NR | NR | PR | NR | NR | FR | NR | NR | NR | NR | FR | PR | FR | FR | |
| FR | FR | FR | FR | NR | PR | FR | FR | NR | FR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | FR | |
| FR | FR | FR | FR | NR | NR | NR | NR | NR | FR | NR | FR | NR | PR* | NR | FR | NR | NR | NR | NR | NR | NR | FR | NR | |
| FR | PR | NR | NR | NR | NR | NR | NR | FR | NR | NR | NR | FR | NR | FR | NR | NR | NR | PR | PR | NR | NR | FR | PR | |
| NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| FR | FR | NR | FR | FR | FR | FR | FR | FR | FR | FR | FR | FR | FR | NR | NR | NR | NR | NR | NR | NR | NR | FR | FR | |
| PR* | NR | PR* | NR | NR | NR | PR* | NR | NR | NR | PR* | NR | PR* | NR | PR* | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| FR | PR | NR | NR | PR | PR | FR | NR | FR | NR | NR | NR | NR | NR | NR | NR | FR | NR | NR | NR | NR | NR | FR | FR | |
| FR | NR | NR | NR | NR | NR | FR | NR | NR | NR | FR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| PR* | NR | PR* | NR | NR | NR | NR | FR | NR | NR | NR | FR | NR | NR | NR | FR | NR | NR | NR | NR | NR | NR | FR | NR | |
| FR | NR | NR | NR | NR | NR | FR | NR | FR | NR | FR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| FR | FR | NR | NR | PR | PR | FR | FR | FR | FR | FR | FR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | FR | |
| PR* | NR | PR* | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | FR | NR | NR | NR | NR | FR | FR | |
| FR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| FR | NR | NR | NR | FR | FR | PR* | NR | FR | NR | PR* | NR | NR | NR | FR | NR | NR | NR | NR | NR | NR | NR | FR | FR | |
| PR* | FR | NR | FR | NR | FR | FR | FR | FR | FR | PR* | FR | NR | NR | FR | NR | NR | NR | NR | NR | NR | NR | FR | FR | |
| NR | NR | NR | NR | PR | NR | NR | NR | NR | NR | NR | NR | FR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | NR | |
| NR | PR* | NR | PR* | NR | NR | NR | FR | NR | NR | NR | NR | NR | NR | FR | FR | NR | NR | NR | NR | NR | NR | FR | NR | |
| PR* | PR* | PR* | PR* | NR | NR | FR | FR | NR | NR | NR | NR | PR | PR | NR | NR | NR | NR | NR | NR | NR | NR | FR | FR | |
| PR* | NR | PR* | NR | NR | NR | NR | NR | NR | NR | NR | NR | PR* | NR | NR | NR | PR | NR | PR | NR | NR | NR | FR | NR | |
| FR | FR | FR | FR | NR | NR | NR | FR | NR | NR | NR | NR | NR | FR | NR | NR | NR | NR | NR | NR | NR | NR | NR | FR | |
| Total (%) analysed (c) | 1365 (50.0) | 996 (36.5) | 290 (10.6) | 527 (19.3) | 379 (13.9) | 497 (18.2) | 1521 (55.7) | 1116 (40.8) | 1194 (43.7) | 825 (30.2) | 789 (28.9) | 758 (27.7) | 525 (19.2) | 457 (16.7) | 641 (23.5) | 395 (14.4) | 398 (14.6) | 237 (8.7) | 154 (5.6) | 26 (1.0) | 267 (9.8) | 45 (1.6) | 1135 (41.5)(d) | 727 (26.6)(d) |
| ST ‐ short‐term follow‐up (< 12 months) LT ‐ long‐term follow‐up (≥ 12 months) FR ‐ full reporting, outcome included in analysis PR ‐ partial reporting, insufficient information on outcome reported for inclusion in analysis * no incidence of outcome observed NR ‐ outcome not reported HF ‐ heart failure; NYHA ‐ New York Heart Association; LVEF ‐ left ventricular ejection fraction (a)Composite measure of mortality, reinfarction or rehospitalisation for heart failure. (b)LVEF measured by any method. (c)Total number of participants included in meta‐analysis of outcome (% of total number of participants from all included studies). (d)Total number analysed given for LVEF measured by magnetic resonance imaging. | ||||||||||||||||||||||||
| Study ID | Number of analysed participants | All‐cause mortality events | Cardiovascular mortality events | Reinfarction | Target vessel revascularisation | Composite MACE (death, reinfarction, rehospitalisation for HF) | |||||||||||
| Cells | No cells | Cells | No cells | Length of follow‐up | Cells | No cells | Length of follow‐up | Cells | No cells | Length of follow‐up | Cells | No cells | Length of follow‐up | Cells | No cells | Length of follow‐up | |
| 11 | 11 | 0 | 0 | 12 months | 0 | 0 | 12 months | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 41 | 45 | 0 | 1 | 48 months | NR | NR | ‐ | 0 | 0 | 48 months | 0 | 1 | 48 months | NR | NR | ‐ | |
| 34 | 35 | 0 | 0 | 6 months | 0 | 0 | 6 months | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 5 | 4 | 0 | 0 | 12 months | 0 | 0 | 12 months | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 21 | 21 | 1 | 0 | 24 months | 1 | 0 | 24 months | 1 | 0 | 24 months | NR | NR | ‐ | 2 | 1 | 24 months | |
| 10 | 10 | 0 | 0 | 6 months | 0 | 0 | 6 months | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 27 | 12 | 1 | 0 | 12 months | NR | NR | ‐ | 1 (a) | 1 (a) | 6 months | 3 (a) | 4 (a) | 6 months | NR | NR | ‐ | |
| 65 | 60 | 1 | 2 | 60 months | NR | NR | ‐ | 1 | 1 | 60 months | 20 | 14 | 60 months | 2 | 5 | 60 months | |
| 20 | 20 | 0 | 0 | 6 months | 0 | 0 | 6 months | 0 | 0 | 6 months | NR | NR | ‐ | NR | NR | ‐ | |
| 20 | 20 | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 40 | 40 | 0 | 1 | 6 months | 0 | 1 | 6 months | 0 | 2 | 6 months | NR | NR | ‐ | NR | NR | ‐ | |
| 33 | 34 | 1 | 0 | 4 months | 0 | 0 | 4 months | NR | NR | 4 months | NR | NR | ‐ | NR | NR | ‐ | |
| 16 | 16 | 0 | 0 | 6 months | 0 | 0 | 6 months | 0 | 0 | 6 months | NR | NR | ‐ | NR | NR | ‐ | |
| 14 | 12 | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 26 | 32 | 10 | 4 | 8.2 years | 8 | 2 | 8.2 years | 2 | 2 | 8.2 years | NR | NR | ‐ | NR | NR | ‐ | |
| 30 | 28 | 0 | 0 | 6 months | 0 | 0 | 6 months | 2 | 0 | 6 months | 0 | 0 | 6 months | NR | NR | ‐ | |
| 49 | 50 | 1 | 1 | 36 months | NR | NR | ‐ | 1 | 2 | 36 months | 12 | 9 | 36 months | NR | NR | ‐ | |
| 44 | 20 | 0 | 0 | 12 months | 0 | 0 | 12 months | 2 | 0 | 12 months | NR | NR | ‐ | NR | NR | ‐ | |
| 24 | 6 | 1 | 0 | 6 months | 0 | 0 | 6 months | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 17 | 10 | 3 | 0 | 24 months | 2 | 0 | 24 months | 1 | 1 | 24 months | NR | NR | ‐ | 6 | 5 | 24 months | |
| 19 | 19 | 2 | 4 | 12 months | 2 | 3 | 12 months | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 40 | 20 | 2 | 2 | 24 months | 2 | 2 | 24 months | 1 | 1 | 24 months | NR | NR | ‐ | NR (c) | NR (c) | ‐ | |
| 16 | 15 | 1 | 0 | 12 months | 1 | 0 | 12 months | NR | NR | ‐ | 2 | 1 | 12 months | NR | NR | ‐ | |
| 48 | 44 | 1 | 0 | 3 months | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 9 | 11 | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 100 (b) | 100 (b) | 7 | 15 | 60 months | 5 | 9 | 60 months | 5 (b) | 7 (b) | 24 months | 18 (b) | 28 (b) | 60 months | 4 | 15 | 24 months | |
| 10 | 10 | 0 | 0 | 3 months | 0 | 0 | 3 months | 0 | 0 | 3 months | 0 | 0 | 3 months | NR | NR | ‐ | |
| 115 | 60 | 2 | 0 | 4 months | 0 | 0 | 4 months | 1 | 1 | 4 months | NR | NR | ‐ | NR (d) | NR (d) | ‐ | |
| 160 | 40 | 2 | 1 | 6 months | NR | NR | 3 | 2 | 6 months | 25 | 7 | 6 months | NR | NR | ‐ | ||
| 30 | 10 | 0 | 0 | 15 months | 0 | 0 | 15 months | 0 | 1 | 15 months | 0 | 1 | 15 months | NR | NR | ‐ | |
| 58 | 29 | 0 | 1 | 6 months | NR | NR | ‐ | 1 | 0 | 6 months | 1 | 2 | 6 months | NR | NR | ‐ | |
| 79 | 41 | 1 | 0 | 12 months | NR | NR | ‐ | 2 | 3 | 12 months | 4 | 4 | 12 months | NR (e) | NR (e) | ‐ | |
| 42 | 20 | 0 | 0 | 6 months | 0 | 0 | 6 months | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 28 | 30 | 1 | 2 | 6 months | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 29 | 13 | 1 | 1 | 6 months | NR | NR | ‐ | 0 | 0 | 6 months | 0 | 0 | 6 months | 5 | 1 | 36 months | |
| 30 | 30 | 2 | 2 | 61 months | NR | NR | ‐ | 1 | 1 | 61 months | 6 | 4 | 61 months | 5 | 6 | 61 months | |
| 17 | 21 | NR | NR | 3 months | NR | NR | 3 months | NR | NR | 3 months | NR | NR | 3 months | NR (f) | NR (f) | 3 months | |
| 90 | 84 | 0 | 0 | 30 months | 0 | 0 | 30 months | 2 | 2 | 30 months | NR | NR | ‐ | NR | NR | ‐ | |
| 27 | 12 | 0 | 0 | 12 months | 0 | 0 | 12 months | 0 | 1 | 12 months | NR | NR | ‐ | NR | NR | ‐ | |
| 7 | 16 | 0 | 0 | 8 weeks | 0 | 0 | 8 weeks | NR | NR | ‐ | NR | NR | ‐ | NR | NR | ‐ | |
| 8 | 3 | 2 | 1 | 36 months * | 2 | 1 | 36 months * | 1 | 0 | 36 months | NR | NR | ‐ | NR | NR | ‐ | |
| (a)Grajek 2010: 31 BMMNC and 14 controls available for analysis at 6 months. (b)Schachinger 2006: 100 BMMNC and 101 controls analysed at 24 months; 3 patients (2 BMMNC and 1 control) only had mortality data at 60 months. (c)Plewka 2009: Composite death, MI, hospitalisation for HF, TVR: 9 BMMNC and 11 controls at 24 months. (d)Sürder 2013: Composite death, MI, revascularisation, hospitalisation for HF: 9 BMMNC and 8 controls at 12 months. (e)Traverse 2012: Composite death, MI, hospitalisation for HF, revascularisation, ICD, stroke: 18 BMMNC and 9 controls at 12 months. (f)Xiao 2012: Composite MACE (undefined): 3 BMMNC and 2 controls at 3 months. | |||||||||||||||||
| Study ID | Periprocedural adverse events |
| Not reported | |
| 1 x transient acute heart failure 7 days after cell transplantation | |
| Not reported | |
| No adverse events were reported until the end of hospitalisation | |
| 1 x death 3 days after cell transplantation due to suspected acute in‐stent thrombosis; 1 x serious complication of acute coronary occlusion during cell injection with subsequent recurrent MI | |
| No bleeding complications at BM puncture site and no angina aggravation, malignant diseases or substantial arrhythmias after PCI and BM transfer during hospitalisation in either treatment group | |
| Not reported | |
| No complications of cell harvesting. A CK or CK‐MB elevation between 1 and 2 times the ULN was detected in 4 patients and between 2 and 3 times the ULN in one patient. 1 x occluded infarct‐related artery (patient did not receive cell therapy as randomised). During cell catheterisation: 1 x coronary spasm, 1 x transient brachycardia and 1 x thrombus in the infarct related artery | |
| Not reported | |
| Not reported | |
| 3 x mild self terminating vasovagal reactions during BM aspiration; no other procedural complications relating to aspiration. Subacute stent thrombosis occurred in 4 patients (1 x cell therapy and 3 x placebo); 1 x cell therapy patient had 'no reflow' phenomenon after stenting of the infarcted artery | |
| 11 x treatment‐related tachycardia (supraventricular arrhythmia: 5 in the cell therapy group and 6 in the control group); 3 patients in the control group experienced non‐sustained ventricular tachycardia | |
| Not reported | |
| Not reported | |
| No complications of BM aspiration or cell infusion | |
| No serious inflammatory reactions or bleeding complications from BM aspiration. No (or mild) angina during balloon inflation. No serious procedural complications related to intracoronary administration of MSCs including ventricular arrhythmia, thrombus formation or dissection. Periprocedural MI occurred in 2 patients | |
| 2 x stent thrombosis in the acute phase in the cell therapy group (no cells administered as randomised); 1 x sustained ventricular tachycardia before cell administration; 1 x ventricular fibrillation at day 6, 24 hours after injection.1 x pulseless ventricular tachycardia in control patient ‐ converted to sinus rhythm by means of a precordial thump on day 2 | |
| 2 patients had fever and 1 patient had brachycardia, all within 20 hours prior to cells (these patients did not receive cell therapy as randomised). 3 x cell therapy‐related complications: 1 x intimal dissection during repeat balloon inflations at time of cell implantation, 1 x short‐lasting fever on day of scheduled transplantation, 1 x small thrombus in infarct‐related artery diagnosed immediately after cell transplantation. 2 x control patients had repeat MI 2 days after the hospital discharge due to in‐stent thrombosis | |
| Ck‐MB elevation (3 x normal value) in 3 patients in the arterial group and 1 patient in venous group. 1 x tortuous anterior interventricular vein (patient did not receive cell therapy as randomised). No new pericardial effusions | |
| 2 x serious complications (1 x stent thrombosis with reinfarction immediately after BM harvest, patient died 2 weeks later due to sepsis and acute respiratory distress syndrome; 1 x ventricular septal rupture before cell injection, patient died 3 months later from severe heart failure). | |
| All procedures well tolerated. No inflammatory reaction or abscess detected at the site of puncture after BM harvest. The invasive coronary catheterisation was associated with some mild angina during balloon inflations for cell infusions. No procedural complications during cardiac catheterisation related to cell injections (no ventricular arrhythmia, new thrombus formation or embolism after cell infusion or dissections due to balloon inflations) | |
| Not reported | |
| 1 high‐dose treatment group patient died soon after cell infusion from ventricular fibrillation attributed to recurrent MI from stent thrombosis preceding cell infusion. 1 x high‐dose treatment group patient with acute stent thrombosis before cell infusion (patient withdrawn from study). Cell therapy group: 1 x arrhythmia, 1 x chest pain, 3 x musculoskeletal pain, 2 x upper respiratory tract infection, 2 x rash, 3 x dyspnoea, 1 x fever. Control group: 1 x arrhythmia, 3 x musculoskeletal pain, 1 x upper respiratory tract infection, 1 x dyspnoea | |
| Cell therapy group: 1 x transient ischaemic attack and 1 x thrombopenia induced by GP2b3a inhibitor (both excluded before BM aspiration). Control group: 1 x steroids given for angioneurotic oedema; 1 x post‐MI ventricular septal defect (both withdrawn before day 7) | |
| Not reported | |
| No bleeding complications or haematoma formation at puncture site of BM aspiration. 1 x patient was excluded owing to fever and an increase in the level of C‐reactive protein. 1 x patient in placebo group had angiographic evidence of a thrombus in a non‐infarct‐related artery (placebo medium not infused). 2 x deaths, cause not reported (1 x cell therapy group and 1 x placebo) and 2 x reinfarction (cell therapy group) prior to discharge | |
| Not reported | |
| 1 death in cell therapy group prior to transplantation, cause of death not reported | |
| 1 patient developed arteriovenous fistula of the femoral artery after the procedure and required surgical treatment. No complications arising from BM cell transfer | |
| BM aspiration carried out without complications. No patient experienced a rise in troponin or procedure‐related complication following infusion | |
| No complications associated with BM aspiration. 2 x patients underwent additional stenting at time of cell infusion (1 x distal stent edge dissection related to primary PCI procedure; 1 x possible dissection related to stop‐flow procedure). 1 x postpartum spontaneous coronary dissection with diffuse thrombus throughout stented region of left anterior descending artery; 1 x presence of severe left main coronary stenosis identified before transfusion (this patient did not receive cell therapy as randomised). No patients experienced postprocedural increase in cardiac enzymes | |
| No complications associated with BM harvesting or intracoronary infusion. 1 x death in the BM cell therapy group due to subarachnoid haemorrhage prior to cell delivery | |
| No procedural or cell‐induced complications and no side effects in any patient | |
| Not reported | |
| Not reported | |
| No bleeding complications at BM harvest site. No increases in troponin T serum levels in any patients 24 hours after BM transfer | |
| Not reported | |
| 1 x temporary hypotension, 2 x brachycardia, 7 x new hyperuricaemia | |
| 1 x brachycardia with subsequent pacemaker implantation, 1 x fever (these patients did not receive cells as randomised) | |
| Not reported | |
| Not reported | |
| MI, acute myocardial infarction; PCI, percutaneous coronary intervention; BM, bone marrow; MSC, mesenchymal stem cells; ULN, upper limit of normal | |
| Study ID | No. analysed participants | Quality of life (QoL) assessment | Reported data (EP/MC/SR) | Performance assessment | Summary measures of performance | Reported data (EP/MC/SR) | Mean follow‐up | |
| Cells | No cells | |||||||
| 5 | 4 | n/r | n/r | Exercise stress test | Peak HR, peak MET, peak double product (SBPxHR), peak predicted HR | EP (median) | 12 months | |
| 31 | 14 | n/r | n/r | Cardiopulmonary exercise treadmill test (modified Bruce protocol) | METs, maximum VO2 , VE/VCO2 slope, RER, peak SBP, peak HR, VO2 anaerobic threshold, HR recovery | EP | 12 months | |
| 65 | 60 | n/r | n/r | NYHA class | EP | 60 months | ||
| 27 | 27 | n/r | n/r | Symptom‐limited maximal exercise test | METs, peak HR, T‐wave alternans | EP, MC | 6 months | |
| 16 | 16 | n/r | n/r | NYHA class | EP | 6 months | ||
| 14 | 12 | MLHFQ | EP | NYHA class | EP | 12 months | ||
| 16 (a) | 28 (a) | MLHFQ | EP | Six minute walk test; functional class (undefined) | Distance (metres) | EP | 6 months | |
| 50 (b) | 50 (b) | SF‐36 | EP, MC | Electrically braked bicycle ergometer; NYHA class | Time (min), maximum VO2 , VE/VCO2 slope etc., peak HR | EP, MC | 6 months | |
| 14 | 10 | SF‐36 | SR | NYHA class | EP | 24 months | ||
| 17 | 15 | n/r | n/r | Cardiopulmonary exercise treadmill test (modified Bruce protocol) | Exercise duration (min), maximum VO2 , VE/VCO2 slope | MC | 12 months | |
| 52 | 49 | MLHFQ | SR | n/r | 12 months | |||
| 117 | 61 | n/r | n/r | NYHA class | EP | 4 months | ||
| 42 | 20 | n/r | n/r | NYHA class | EP | 12 months | ||
| 7 | 16 | QoL (no details) | NYHA class | SR | 8 weeks | |||
| MLHFQ, Minnesota Living with Heart Failure Questionnaire; NYHA, New York Heart Association; SF‐36, Short‐Form 36 Quality of Life; MET, metabolic equivalent test (mL/kg/min); HR, heart rate (bpm); SBP, systolic blood pressure (mmHg); RER, respiratory exchange ratio; VE, minute ventilation; VO2, oxygen volume; VCO2, carbon dioxide volume; EP, endpoint; MC, mean change from baseline; SR, summary results; n/r, not reported. (a)Karpov 2005: QoL was measured in 37 participants (cells: 18 cells, no cells: 19) (b)Lunde 2006: QoL was measured in 46 BMMNC and 45 controls; exercise tolerance was measured in 49 BMMNC and 50 controls | ||||||||
| Study ID | No. randomised participants | No. analysed participants | Baseline LVEF | Mean follow‐up of LVEF | |||
| Cells | No cells | Cells | No cells | Cells | No cells | ||
| Measured by MRI | |||||||
| Hirsch 2011 (HEBE) | 69 | 65 | 59 | 52 | 43.7 (9.0)% | 42.4 (8.3)% | 24 months |
| 20 | 20 | 20 | 20 | 44.5 (7.1)% | 43.4 (6.7)% | 6 months | |
| 33 | 34 | 30 | 30 | 48.5 (7.2)% | 46.9 (8.2)% | 12 months | |
| Lunde 2006 (ASTAMI) | 50 | 51 | 44 | 44 | 54.8 (13.6)% | 53.6 (11.6)% | 36 months |
| Quyyumi 2011 (AMR‐1) | 16 | 15 | 11 | 10 | LD: 47.0 (13)% MD: 47.3 (11)% HD: 49.9 (7)% | 53.2(10)% | 6 months |
| Roncalli 2010 (BONAMI) | 52 | 49 | 47 | 43 | 37.0 (9.8)% | 38.7 (9.2)% | 3 months |
| Schachinger 2006 (REPAIR‐AMI) | 101 | 103 | 26 | 33 | 47.8 (6.2)% | 47.7 (6.2)% | 60 months (a) |
| Sürder 2013 (SWISS‐AMI) | 133 | 67 | 107 | 60 | E: 36.5 (9.9)% L: 36.3 (8.2)% | 40.0 (9.9)% | 4 months |
| Tendera 2009(REGENT) | 160 | 40 | 97 | 20 | S: 33.9 (8.6)% U: 35.6 (6.5)% | 38.9 (5.2)% | 6 months |
| 30 | 10 | 30 | 10 | 49 (9.5)% | 48.6 (8.5)% | 6 months | |
| Traverse 2011 (LATE‐TIME) | 59 | 29 | 55 | 26 | 48.7 (12)% | 45.3 (9.9)% | 6 months |
| Traverse 2012 (TIME) | 80 | 40 | 65 | 30 | 46.2 (9.6)% | 46.3 (8.5)% | 12 months |
| Wohrle 2010 (SCAMI) | 29 | 13 | 28 | 12 | 53.5 (9.3)% | 55.7 (9.4)% | 36 months |
| Wollert 2004 (BOOST) | 33 | 32 | 30 | 30 | 50 (10)% | 51.3 (9.3)% | 60 months |
| 30 | 15 | 27 | 11 | SD: 32.5 (3.6)% DD: 33.7 (4.7)% | 32.3 (2.0)% | 12 months | |
| 8 | 3 | 6 (b) | 1 (b) | 33.4 (3)% | 28 (4)% | 36 months (b) | |
| Measured by echocardiography | |||||||
| 11 | 11 | 11 | 11 | n/r | n/r | 12 months | |
| 41 | 45 | 41 | 45 | 41.3 (2.8)% | 40.7 (3.1)% | 48 months | |
| 5 | 5 | 5 | 4 | 44.6 (8.8)% | 43.2 (9.1)% | 12 months | |
| 21 | 22 | 19 | 20 | 50.8 (6.5)% | 51.4 (7.2)% | 24 months | |
| 10 | 10 | 10 | 10 | 53.8 (9.2)% | 58.2 (7.5)% | 6 months | |
| 31 | 14 | 27 | 12 | 50.3 (9.8)% | 50.8 (12)% | 12 months | |
| 20 | 20 | 20 | 20 | 48.5 (5.5)% | 48.2 (6.30% | 6 months | |
| Huikuri 2008 (FINCELL) | 40 | 40 | 39 | 38 | 56 (10)% | 57 (10)% | 6 months |
| 14 | 12 | 14 | 12 | 54.3 (5.5)% | 55.8 (5.9)% | 12 months | |
| 22 | 22 | 16 | 10 | 49.3 (11.1)% | 47.0 (7.5)% | 6 months | |
| Lee 2014 (SEED‐MSC) | 40 | 40 | 30 | 28 | 48.1 (8.0)% | 51.0 (9.2)% | 6 months |
| Lunde 2006 (ASTAMI) | 50 | 51 | 50 | 50 | 45.7 (9.4)% | 46.9 (8.6)% | 36 months |
| Nogueira 2009 (EMRTCC) | 24 | 6 | 22 | 6 | AG: 48.3 (10.4)% VG: 48.6 (7.1)% | 47.6 (14.3)% | 6 months |
| 17 | 10 | 14 | 10 | 39.2 (9.2)% | 39.4 (5.6)% | 24 months | |
| Piepoli 2010 (CARDIAC) | 19 | 19 | 17 | 15 | 38.4 (6.4)% | 38.9 (5.6)% | 24 months |
| 40 | 20 | 38 | 18 | 35 (6)% | 33 (7)% | 24 months | |
| Roncalli 2010 (BONAMI) | 52 | 49 | 47 | 43 | 38.1 (7.9)% | 39.8 (7.0)% | 12 months (c) |
| 9 | 11 | 9 | 11 | 53.4 (8.9)% | 53.5 (5.8)% | 6 months | |
| 17 | 21 | 17 | 21 | 35.6 (3.1)% | 35.7 (3.1)% | 3 months | |
| 7 | 16 | 7 | 16 | 37 (4.6)% | 38.6 (5.4)% | 8 weeks | |
| Measured by SPECT | |||||||
| 11 | 11 | 11 | 11 | n/r | n/r | 12 months | |
| 41 | 45 | 41 | 45 | 41.2 (3.1)% | 40.8 (3.3)% | 48 months | |
| Lee 2014 (SEED‐MSC) | 40 | 40 | 30 | 28 | 49.0 (11.7)% | 52.3 (9.3)% | 6 months |
| Lunde 2006 (ASTAMI) | 50 | 51 | 50 | 50 | 41.3 (10.4)% | 42.6 (11.7)% | 6 months |
| 44 | 22 | 40 | 20 | LD: 41 (2)% HD: 30 (2)% | 40 (2)% | 12 months | |
| Piepoli 2010 (CARDIAC) | 19 | 19 | 17 | 15 | 36.6 (8.2)% | 37.5 (8.9)% | 24 months |
| 40 | 20 | 26 | 10 | 41.2 (10.1)% | 40.0 (14.2)% | 6 months | |
| Measured by LV angiography | |||||||
| 34 | 35 | 34 | 35 | 49 (9)% | 48 (10)% | 6 months | |
| 20 | 20 | 20 | 20 | 56.7 (9.7)% | 57.3 (8.2)% | 6 months | |
| Huikuri 2008 (FINCELL) | 40 | 40 | 36 | 36 | 59 (11)% | 62 (12)% | 6 months |
| n/r | n/r | 16 | 16 | 33.37 (11.2)% | 29.0 (7.5)% | 6 months | |
| Schachinger 2006 (REPAIR‐AMI) | 101 | 103 | 95 | 92 | 48.3 (9.2)% | 46.9 (10.4)% | 4 months |
| 10 | 10 | 10 | 10 | 37 (5)% | 39 (6)% | 3 months | |
| 42 | 20 | 42 | 20 | 43 (10)% | 45 (10)% | 12 months | |
| 30 | 30 | 27 | 28 | 37.8 (6.3)% | 20.2 (2.5)% (d) | 6 months | |
| 92 | 92 | 90 | 84 | n/r | n/r | 6 months | |
| Measured by RNV | |||||||
| 31 | 14 | 27 | 12 | 45.4 (10.2)% | 42.7 (7.4)% | 12 months | |
| Nogueira 2009 (EMRTCC) | 24 | 6 | 22 | 6 | AG: 41.0 (10.3)% VG: 39.9 (7.4)% | 40.1 (12.4)% | 6 months |
| Roncalli 2010 (BONAMI) | 52 | 49 | 47 | 43 | 35.6 (7.0)% | 37.0 (6.7)% | 3 months |
| Measured by gated PET | |||||||
| 5 | 5 | 5 | 4 | 36.6 (5.4)% | 37.6 (7.0)% | 12 months | |
| n/r ‐ not reported LD ‐ low dose, MD ‐ moderate dose, HD ‐ high dose, AG ‐ arterial group, VG ‐ venous group, E ‐ early cells, L ‐ late cells, S ‐ selected cells, U ‐ unselected cells, SD ‐ single dose, DD ‐ double dose (a)Schachinger 2006: MRI was performed at five‐year follow‐up but summary results only were reported; 24‐month data are used in meta‐analysis. (b)Zhukova 2009: 24‐month data were used in the analysis as only one control was available at 36 months. (c)Roncalli 2010: echocardiography was performed at 12‐month follow‐up but summary results only were reported; three‐month data are used in meta‐analysis. (d)Wang 2014: the reported baseline LVEF value in the control group is assumed to be an error since the difference between values at baseline and endpoint (49.1%) is not significant. We have been unable to clarify the correct value with the study authors. | |||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 All‐cause mortality Show forest plot | 23 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1 Short‐term follow‐up (< 12 months) | 17 | 1365 | Risk Ratio (M‐H, Random, 95% CI) | 0.80 [0.43, 1.49] |
| 1.2 Long‐term follow‐up (≥ 12 months) | 14 | 996 | Risk Ratio (M‐H, Random, 95% CI) | 0.93 [0.58, 1.50] |
| 2 Cardiovascular mortality Show forest plot | 10 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1 Short‐term follow‐up (< 12 months) | 7 | 290 | Risk Ratio (M‐H, Random, 95% CI) | 0.72 [0.28, 1.82] |
| 2.2 Long‐term follow‐up (≥ 12 months) | 9 | 527 | Risk Ratio (M‐H, Random, 95% CI) | 1.04 [0.54, 1.99] |
| 3 Composite measure of death, reinfarction, re‐hospitalisation for heart failure Show forest plot | 6 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 3.1 Short‐term follow‐up (< 12 months) | 3 | 379 | Risk Ratio (M‐H, Random, 95% CI) | 0.36 [0.12, 1.14] |
| 3.2 Long‐term follow‐up (≥ 12 months) | 6 | 497 | Risk Ratio (M‐H, Random, 95% CI) | 0.63 [0.36, 1.10] |
| 4 Incidence of reinfarction Show forest plot | 20 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 4.1 Short‐term follow‐up (< 12 months) | 17 | 1521 | Risk Ratio (M‐H, Random, 95% CI) | 0.66 [0.33, 1.30] |
| 4.2 Long‐term follow‐up (≥ 12 months) | 14 | 1116 | Risk Ratio (M‐H, Random, 95% CI) | 0.64 [0.36, 1.12] |
| 5 Incidence of re‐hospitalisation for heart failure Show forest plot | 16 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 5.1 Short‐term follow‐up (< 12 months) | 13 | 1194 | Risk Ratio (M‐H, Random, 95% CI) | 0.81 [0.40, 1.62] |
| 5.2 Long‐term follow‐up (≥ 12 months) | 10 | 825 | Risk Ratio (M‐H, Random, 95% CI) | 0.55 [0.30, 1.00] |
| 6 Incidence of target vessel revascularisation Show forest plot | 11 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 6.1 Short‐term follow‐up (< 12 months) | 6 | 789 | Risk Ratio (M‐H, Random, 95% CI) | 0.70 [0.47, 1.06] |
| 6.2 Long‐term follow‐up (≥ 12 months) | 8 | 758 | Risk Ratio (M‐H, Random, 95% CI) | 0.96 [0.67, 1.37] |
| 7 Incidence of arrhythmias Show forest plot | 8 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 7.1 Short‐term follow‐up (< 12 months) | 5 | 525 | Risk Ratio (M‐H, Random, 95% CI) | 1.00 [0.51, 1.98] |
| 7.2 Long‐term follow‐up (≥ 12 months) | 5 | 457 | Risk Ratio (M‐H, Random, 95% CI) | 1.39 [0.58, 3.37] |
| 8 Incidence of restenosis Show forest plot | 13 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 8.1 Short‐term follow‐up (< 12 months) | 8 | 641 | Risk Ratio (M‐H, Random, 95% CI) | 0.95 [0.63, 1.43] |
| 8.2 Long‐term follow‐up (≥ 12 months) | 6 | 395 | Risk Ratio (M‐H, Random, 95% CI) | 0.58 [0.27, 1.25] |
| 9 Quality of life measures Show forest plot | 3 | Std. Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 9.1 Short‐term follow‐up (< 12 months) | 3 | 154 | Std. Mean Difference (IV, Random, 95% CI) | 0.58 [‐0.67, 1.83] |
| 9.2 Long‐term follow‐up (≥ 12 months) | 1 | 26 | Std. Mean Difference (IV, Random, 95% CI) | 3.23 [2.01, 4.46] |
| 10 NYHA classification Show forest plot | 7 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 10.1 Short‐term follow‐up (< 12 months) | 5 | 398 | Mean Difference (IV, Random, 95% CI) | ‐0.07 [‐0.24, 0.09] |
| 10.2 Long‐term follow‐up (≥ 12 months) | 4 | 237 | Mean Difference (IV, Random, 95% CI) | ‐0.23 [‐0.53, 0.07] |
| 11 Exercise tolerance Show forest plot | 5 | Std. Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 11.1 Short‐term follow‐up (< 12 months) | 5 | 267 | Std. Mean Difference (IV, Random, 95% CI) | 0.19 [‐0.06, 0.43] |
| 11.2 Long‐term follow‐up (≥ 12 months) | 1 | 45 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.05 [‐0.68, 0.58] |
| 12 Maximum VO2 (mL/kg/min) Show forest plot | 3 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 12.1 Short‐term follow‐up (< 12 months) | 3 | 175 | Mean Difference (IV, Random, 95% CI) | 1.15 [‐0.77, 3.07] |
| 12.2 Long‐term follow‐up (≥ 12 months) | 1 | 45 | Mean Difference (IV, Random, 95% CI) | 0.40 [‐3.76, 4.56] |
| 13 VE/VCO2 slope Show forest plot | 3 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 13.1 Short‐term follow‐up (< 12 months) | 3 | 174 | Mean Difference (IV, Random, 95% CI) | 0.28 [‐1.02, 1.57] |
| 13.2 Long‐term follow‐up (≥ 12 months) | 1 | 45 | Mean Difference (IV, Random, 95% CI) | 0.0 [‐3.07, 3.07] |
| 14 Peak heart rate (bpm) Show forest plot | 3 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 14.1 Short‐term follow‐up (< 12 months) | 3 | 198 | Mean Difference (IV, Random, 95% CI) | 0.55 [‐6.79, 7.89] |
| 14.2 Long‐term follow‐up (≥ 12 months) | 1 | 45 | Mean Difference (IV, Random, 95% CI) | ‐9.10 [‐20.59, 2.39] |
| 15 LVEF measured by MRI (<12 months) Show forest plot | 15 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 15.1 Mean change from baseline | 13 | 1057 | Mean Difference (IV, Random, 95% CI) | 0.43 [‐1.16, 2.03] |
| 15.2 Mean value at endpoint | 15 | 1125 | Mean Difference (IV, Random, 95% CI) | 0.81 [‐0.78, 2.41] |
| 15.3 Combined | 15 | 1135 | Mean Difference (IV, Random, 95% CI) | 1.05 [‐0.56, 2.67] |
| 16 LVEF measured by MRI (≥ 12 months) Show forest plot | 9 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 16.1 Mean change from baseline | 5 | 438 | Mean Difference (IV, Random, 95% CI) | 0.03 [‐1.72, 1.78] |
| 16.2 Mean value at endpoint | 8 | 551 | Mean Difference (IV, Random, 95% CI) | 1.40 [‐1.54, 4.34] |
| 16.3 Combined | 9 | 718 | Mean Difference (IV, Random, 95% CI) | 1.27 [‐1.14, 3.68] |
| 17 LVEF measured by echocardiography (< 12 months) Show forest plot | 20 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 17.1 Mean change from baseline | 6 | 372 | Mean Difference (IV, Random, 95% CI) | 2.72 [1.50, 3.95] |
| 17.2 Mean value at endpoint | 20 | 862 | Mean Difference (IV, Random, 95% CI) | 2.15 [0.89, 3.42] |
| 17.3 Combined | 20 | 862 | Mean Difference (IV, Random, 95% CI) | 2.31 [1.30, 3.33] |
| 18 LVEF measured by echocardiography (≥12 months) Show forest plot | 10 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 18.1 Mean change from baseline | 3 | 127 | Mean Difference (IV, Random, 95% CI) | 1.35 [‐2.25, 4.96] |
| 18.2 Mean value at endpoint | 9 | 377 | Mean Difference (IV, Random, 95% CI) | 2.87 [1.42, 4.31] |
| 18.3 Combined | 10 | 433 | Mean Difference (IV, Random, 95% CI) | 2.09 [0.74, 3.44] |
| 19 LVEF measured by SPECT (< 12 months) Show forest plot | 7 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 19.1 Mean change from baseline | 5 | 286 | Mean Difference (IV, Random, 95% CI) | 2.72 [0.23, 5.21] |
| 19.2 Mean value at endpoint | 6 | 375 | Mean Difference (IV, Random, 95% CI) | 2.19 [0.58, 3.81] |
| 19.3 Combined | 7 | 394 | Mean Difference (IV, Random, 95% CI) | 2.52 [0.59, 4.44] |
| 20 LVEF measured by SPECT (≥ 12 months) Show forest plot | 4 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 20.1 Mean change from baseline | 2 | 92 | Mean Difference (IV, Random, 95% CI) | 5.63 [1.77, 9.49] |
| 20.2 Mean value at endpoint | 3 | 181 | Mean Difference (IV, Random, 95% CI) | 3.46 [0.82, 6.11] |
| 20.3 Combined | 4 | 200 | Mean Difference (IV, Random, 95% CI) | 4.42 [2.68, 6.16] |
| 21 LVEF measured by left ventricular angiography (< 12 months) Show forest plot | 9 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 21.1 Mean change from baseline | 3 | 279 | Mean Difference (IV, Random, 95% CI) | 6.43 [0.60, 12.27] |
| 21.2 Mean value at endpoint | 9 | 711 | Mean Difference (IV, Random, 95% CI) | 4.94 [0.53, 9.35] |
| 21.3 Combined | 9 | 711 | Mean Difference (IV, Random, 95% CI) | 5.09 [0.95, 9.24] |
| 22 LVEF measured by left ventricular angiography (≥ 12 months) Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 22.1 Mean value at endpoint | 1 | 62 | Mean Difference (IV, Random, 95% CI) | 8.0 [4.27, 11.73] |
| 23 LVEF measured by radionuclide ventriculography (RNV) (<12 months) Show forest plot | 3 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 23.1 Mean change from baseline | 2 | 118 | Mean Difference (IV, Random, 95% CI) | 0.91 [‐3.11, 4.94] |
| 23.2 Mean value at endpoint | 3 | 157 | Mean Difference (IV, Random, 95% CI) | 1.08 [‐4.88, 7.04] |
| 23.3 Combined | 3 | 157 | Mean Difference (IV, Random, 95% CI) | 1.79 [‐1.86, 5.43] |
| 24 LVEF measured by radionuclide ventriculography (≥ 12 months) Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 24.1 Mean value at endpoint | 1 | 39 | Mean Difference (IV, Random, 95% CI) | 6.30 [‐1.03, 13.63] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 All‐cause mortality (< 12 months) Show forest plot | 16 | 1335 | Risk Ratio (M‐H, Random, 95% CI) | 0.80 [0.42, 1.51] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 All‐cause mortality (< 12 months) Show forest plot | 16 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1 Excluding studies with high risk of selection bias | 16 | 1307 | Risk Ratio (M‐H, Random, 95% CI) | 0.83 [0.43, 1.57] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 All‐cause mortality (< 12 months) Show forest plot | 13 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1 Excluding studies with a high or unclear risk of attrition bias | 13 | 899 | Risk Ratio (M‐H, Random, 95% CI) | 0.78 [0.38, 1.61] |
| 2 All‐cause mortality (≥ 12 months) Show forest plot | 11 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1 Excluding studies with a high or unclear risk of attrition bias | 11 | 847 | Risk Ratio (M‐H, Random, 95% CI) | 0.67 [0.38, 1.17] |
| 3 Cardiovascular mortality (< 12 months) Show forest plot | 5 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 3.1 Excluding studies with high or unclear risk of attrition bias | 5 | 199 | Risk Ratio (M‐H, Random, 95% CI) | 0.69 [0.22, 2.14] |
| 4 Cardiovascular mortality (≥ 12 months) Show forest plot | 6 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 4.1 Excluding studies with high or unclear risk of attrition bias | 6 | 378 | Risk Ratio (M‐H, Random, 95% CI) | 0.71 [0.34, 1.50] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 All‐cause mortality (< 12 months) Show forest plot | 8 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1 Excluding studies with a high risk of performance bias | 8 | 669 | Risk Ratio (M‐H, Random, 95% CI) | 0.60 [0.23, 1.56] |
| 2 All‐cause mortality (≥ 12 months) Show forest plot | 3 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1 Excluding studies with a high risk of performance bias | 3 | 406 | Risk Ratio (M‐H, Random, 95% CI) | 0.50 [0.22, 1.10] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 All‐cause mortality (< 12 months) Show forest plot | 10 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1 Baseline LVEF < 45% | 4 | 478 | Risk Ratio (M‐H, Random, 95% CI) | 0.77 [0.19, 3.16] |
| 1.2 Baseline LVEF ≥ 45% | 6 | 551 | Risk Ratio (M‐H, Random, 95% CI) | 0.98 [0.32, 2.98] |
| 2 All‐cause mortality (≥ 12 months) Show forest plot | 7 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1 Baseline LVEF < 45% | 2 | 136 | Risk Ratio (M‐H, Random, 95% CI) | 0.61 [0.13, 2.83] |
| 2.2 Baseline LVEF ≥ 45% | 5 | 510 | Risk Ratio (M‐H, Random, 95% CI) | 0.64 [0.31, 1.30] |
| 3 LVEF measured by MRI (< 12 months) Show forest plot | 15 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 3.1 Baseline LVEF < 45% | 6 | 579 | Mean Difference (IV, Random, 95% CI) | 2.28 [0.43, 4.13] |
| 3.2 Baseline LVEF ≥ 45% | 9 | 556 | Mean Difference (IV, Random, 95% CI) | ‐0.09 [‐2.42, 2.24] |
| 4 LVEF measured by MRI (≥ 12 months) Show forest plot | 9 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 4.1 Baseline LVEF < 45% | 4 | 326 | Mean Difference (IV, Random, 95% CI) | 3.93 [‐0.15, 8.02] |
| 4.2 Baseline LVEF ≥ 45% | 5 | 342 | Mean Difference (IV, Random, 95% CI) | ‐0.15 [‐2.34, 2.05] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 All‐cause mortality (< 12 months) Show forest plot | 17 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1 Mononuclear cells | 14 | 1153 | Risk Ratio (M‐H, Random, 95% CI) | 0.74 [0.38, 1.46] |
| 1.2 Mesenchymal stem cells | 2 | 101 | Risk Ratio (M‐H, Random, 95% CI) | 1.01 [0.15, 6.60] |
| 1.3 Haematopoietic progenitor cells | 2 | 151 | Risk Ratio (M‐H, Random, 95% CI) | 1.06 [0.13, 8.36] |
| 2 All‐cause mortality (≥ 12 months) Show forest plot | 14 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1 Mononuclear cells | 12 | 923 | Risk Ratio (M‐H, Random, 95% CI) | 0.88 [0.54, 1.43] |
| 2.2 Mesenchymal stem cells | 1 | 42 | Risk Ratio (M‐H, Random, 95% CI) | 3.0 [0.13, 69.70] |
| 2.3 Haematopoietic progenitor cells | 1 | 31 | Risk Ratio (M‐H, Random, 95% CI) | 2.82 [0.12, 64.39] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 All‐cause mortality (< 12 months) Show forest plot | 16 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1 ≤ 108 cells | 5 | 297 | Risk Ratio (M‐H, Random, 95% CI) | 1.03 [0.27, 3.96] |
| 1.2 > 108 and ≤ 109 cells | 12 | 1081 | Risk Ratio (M‐H, Random, 95% CI) | 0.66 [0.33, 1.34] |
| 2 All‐cause mortality (≥ 12 months) Show forest plot | 14 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1 ≤ 108 cells | 5 | 241 | Risk Ratio (M‐H, Random, 95% CI) | 2.20 [0.97, 4.95] |
| 2.2 > 108 and ≤ 109 cells | 7 | 668 | Risk Ratio (M‐H, Random, 95% CI) | 0.52 [0.28, 0.97] |
| 2.3 > 109 cells | 2 | 87 | Risk Ratio (M‐H, Random, 95% CI) | 1.56 [0.32, 7.55] |
| 3 LVEF measured by MRI (< 12 months) Show forest plot | 14 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 3.1 ≤ 108 cells | 4 | 270 | Mean Difference (IV, Random, 95% CI) | 0.00 [‐3.51, 3.52] |
| 3.2 > 108 and ≤ 109 cells | 11 | 825 | Mean Difference (IV, Random, 95% CI) | 1.08 [‐0.53, 2.69] |
| 4 LVEF measured by MRI (≥ 12 months) Show forest plot | 9 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 4.1 ≤ 108 cells | 2 | 98 | Mean Difference (IV, Random, 95% CI) | 3.60 [‐4.24, 11.44] |
| 4.2 > 108 and ≤ 109 cells | 7 | 570 | Mean Difference (IV, Random, 95% CI) | 1.48 [‐1.44, 4.40] |
| 5 LVEF measured by left ventricular angiography (< 12 months) Show forest plot | 8 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 5.1 > 108 and ≤ 109 cells | 6 | 548 | Mean Difference (IV, Random, 95% CI) | 2.26 [‐0.71, 5.23] |
| 5.2 > 109 cells | 2 | 101 | Mean Difference (IV, Random, 95% CI) | 11.64 [7.52, 15.75] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 All‐cause mortality (< 12 months) Show forest plot | 13 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1 ≤ 10 days since AMI | 10 | 839 | Risk Ratio (M‐H, Random, 95% CI) | 1.02 [0.45, 2.30] |
| 1.2 > 10 days since AMI | 3 | 156 | Risk Ratio (M‐H, Random, 95% CI) | 0.28 [0.06, 1.36] |
| 2 All‐cause mortality (≥ 12 months) Show forest plot | 10 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1 ≤ 10 days since AMI | 9 | 809 | Risk Ratio (M‐H, Random, 95% CI) | 0.61 [0.33, 1.11] |
| 2.2 > 10 days since AMI | 1 | 11 | Risk Ratio (M‐H, Random, 95% CI) | 0.75 [0.10, 5.54] |
| 3 LVEF measured by MRI (< 12 months) Show forest plot | 13 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 3.1 ≤ 10 days since AMI | 12 | 867 | Mean Difference (IV, Random, 95% CI) | 1.15 [‐0.66, 2.97] |
| 3.2 > 10 days since AMI | 2 | 190 | Mean Difference (IV, Random, 95% CI) | ‐0.71 [‐4.90, 3.48] |
| 4 LVEF measured by MRI (≥ 12 months) Show forest plot | 9 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 4.1 ≤ 10 days since AMI | 9 | 669 | Mean Difference (IV, Random, 95% CI) | 1.26 [‐1.20, 3.71] |
| 4.2 > 10 days since AMI | 1 | 109 | Mean Difference (IV, Random, 95% CI) | 1.17 [‐2.59, 4.93] |
| 5 LVEF measured by left ventricular angiography (< 12 months) Show forest plot | 8 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 5.1 ≤ 10 days since AMI | 5 | 535 | Mean Difference (IV, Random, 95% CI) | 2.20 [‐1.51, 5.91] |
| 5.2 > 10 days since AMI | 3 | 156 | Mean Difference (IV, Random, 95% CI) | 7.42 [‐1.83, 16.66] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 All‐cause mortality (< 12 months) Show forest plot | 16 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 1.1 Heparin | 6 | 339 | Risk Ratio (M‐H, Random, 95% CI) | 0.91 [0.31, 2.66] |
| 1.2 No heparin | 10 | 999 | Risk Ratio (M‐H, Random, 95% CI) | 0.66 [0.30, 1.45] |
| 2 All‐cause mortality (≥ 12 months) Show forest plot | 12 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
| 2.1 Heparin | 7 | 503 | Risk Ratio (M‐H, Random, 95% CI) | 0.83 [0.33, 2.10] |
| 2.2 No heparin | 5 | 408 | Risk Ratio (M‐H, Random, 95% CI) | 0.55 [0.28, 1.08] |
| 3 LVEF measured by MRI (< 12 months) Show forest plot | 15 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 3.1 Heparin | 7 | 434 | Mean Difference (IV, Random, 95% CI) | 1.99 [‐0.62, 4.59] |
| 3.2 No heparin | 8 | 701 | Mean Difference (IV, Random, 95% CI) | 0.25 [‐1.67, 2.17] |
| 4 LVEF measured by MRI (≥ 12 months) Show forest plot | 9 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 4.1 Heparin | 5 | 357 | Mean Difference (IV, Random, 95% CI) | 1.76 [‐1.93, 5.45] |
| 4.2 No heparin | 4 | 361 | Mean Difference (IV, Random, 95% CI) | 0.53 [‐2.14, 3.20] |
| 5 LVEF measured by left ventricular angiography (< 12 months) Show forest plot | 8 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 5.1 Heparin | 5 | 256 | Mean Difference (IV, Random, 95% CI) | 6.82 [0.25, 13.39] |
| 5.2 No heparin | 3 | 393 | Mean Difference (IV, Random, 95% CI) | 1.91 [‐3.46, 7.27] |
