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Autotransplantation of
Bone-Marrow Derived
Mesenchymal Stromal Cells
in Patients with Severe Ischemic Heart Failure
The MSC-HF Trial
Anders Bruun Mathiasen M.D.
Rigshospitalet, Copenhagen University Hospital
Copenhagen, Denmark
The MSC-HF trial
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•
•
•
•
•
Randomized Double Blind Placebo controlled
Phase 2
59 patients (2:1)
Severe Ischemic Heart Failure
Mesenchymal Stromal Cells
Intramyocardial injection (NOGA-XP™)
Inclusion Criteria
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•
•
•
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30-80 years
Chronic ischemic heart failure
LVEF < 45%
NYHA 2-3
No option for PCI or CABG
Maximum tolerable medication
Primary Endpoint
End systolic volume
– MRI or CT
– 60 patients (2:1)
– 10 mL difference (SD = 11.1)
– Power = 90%
Patient Recruitment
Signed consent (n=101)
38 excluded
36 did not meet inclusion criteria
1 consent withdrawn
1 dead
Bone marrow aspiration (n=63)
3 excluded
1 cells not expandable (MDS)
2 did no longer meet inclusion criteria
NOGA treatment initiated (n=60)
1 excluded
1 sustained VT during NOGA mapping
NOGA treatment completed (n=59)
Baseline Characteristics
Age (years)
Male
Years with IHD
LVEF (%)
NYHA Class II
NYHA Class III
Previous MI
Previous PCI
Previous CABG
ICD implant
CRT implant
Smoking current / former
IDDM / NIDDM
Antithrombotic agent
ACE or ARB
β-blocker
Calcium antagonist
Diuretic agent
Statins
Nitrate
MSC (n=39)
Placebo (n=20)
p
66.2 ± 7.7
35 (89.7)
12.9 ± 7.9
28.9 ± 9.1
10 (25.4)
29 (74.6)
34 (87.2)
27 (69.2)
26 (66.7)
19 (48.7)
11 (28.2)
6 (15.4) / 26 (66.7)
9 (23.1) / 6 (15.4)
39 (100.0)
34 (87.2)
34 (87.2)
11 (28.2)
31 (79.5)
35 (89.7)
23 (59.0)
64.2 ± 10.6
14 (70.0)
13.1 ± 8.5
26.3 ± 8.1
5 (25.0)
15 (75.0)
19 (95.0)
15 (75.0)
10 (50.0)
13 (65.0)
5 (25.0)
1 (5.0) / 15 (75.0)
2 (10.0) / 1 (5.0)
20 (100.00)
18 (90.0)
15 (75.0)
3 (15.0)
16 (80.0)
18 (90.0)
9 (45.0)
0.41
0.07
0.93
0.32
0.96
0.96
0.65
0.64
0.21
0.24
0.80
0.40 / 0.51
0.30 / 0.40
1.00
1.00
0.28
0.34
1.00
1.00
0.31
(%)
Treatment
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•
•
•
Bone marrow MSCs
Expansion for 6 - 8 weeks
77.5 million
Injected using NOGA-XP™
Follow-up overview
2:1 Randomization
MSC Treated (n=39)
Placebo treated (n=20)
1 Lost to follow-up (Stroke)
1 month follow-up (n=38)
1 month follow-up (n=20)
1 Excluded (CRT implantation)
3 month follow-up (n=38)
1 Excluded (CRT implantation)
6 month follow-up (n=37)
3 month follow-up (n=19)
1 Dead (Terminal heart failure)
6 month follow-up (n=18)
Safety
Serious Adverse Event
MSC (n=39)
Placebo (n=20)
p
0 (0.0)
0 (0.0)
2 (5.1)
5 (12.8)
0 (0.0)
0 (0.0)
1 (2.6)
1 (2.6)
1 (2.6)
1 (2.6)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
0 (0.0)
1 (5.0)
1 (5.0)
3 (15.0)
1 (5.0)
0 (0)
1 (5.0)
0 (0)
1 (5.0)
2 (10.0)
0 (0.0)
3 (15.0)
1 (5.0)
1 (5.0)
1.00
0.65
0.03
0.33
1.00
1.00
1.00
1.00
0.11
0.04
0.34
0.34
MI
PCI or CABG
Stroke or TCI
Heart failure worsening
Angina
Orthostatic syncope
Atrial fibrillation
VT/VF
ICD implantation
CRT implantation
Device related
Cancer
Pneumonia
Gallbladder infection
Observation for headache
(%)
Results I
End systolic volume
p = 0.001
ns
p = 0.001
∆ = 14.2 mL
End diastolic volume
ns
ns
p = 0.012
∆ = 5.8 mL
(Mean + SEM)
Results II
Ejection fraction
p < 0.0001
p < 0.0001
ns
∆ = 6.8 %
Stroke volume
p < 0.0001
p = 0.002
ns
∆ = 20.0 mL
(Mean + SEM)
Results III
End systolic myocardial mass
p < 0.0001
p < 0.0001
ns
∆ = 12.3 g
End diastolic myocardial mass
ns
ns
ns
∆ = 0.6 g
(Mean + SEM)
Results IV
Scar tissue mass
p = 0.017
ns
ns
∆ = 3.9 g
(Mean + SEM)
Results V
p < 0.0001
p = 0.001
p = 0.001
p = 0.0004
p < 0.0001
p = 0.003
m
p < 0.0001
ns
(Mean + SEM)
Post-hoc Power
55 patients (37 MSC : 18 placebo)
End systolic volume
– 14.2 mL difference (SD = 13.3 mL)
– Power = 95.4%
Ejection fraction
– 6.8 % difference (SD = 3.7 %)
– Power > 99.9%
Summary
MSC treatment in severe Heart Failure
• Treatment safe
• End systolic volume improved
• Ejection fraction and stroke volume
improved
• Myocardial mass increased
• Trend towards reduced scar tissue
• Fewer symptoms, better quality of life in
both groups