MD Conference Express AHA 2013 - (Page 16)
FEATURE
14
All-Cause Death (%)
Serelaxin: 42 deaths (7.3%)
10
n=580
n=581
6
4
p=0.002
-22.7%
n=9
-20
4
Months
p=0.039
-30.2%
n=6
12
Months
p=0.001
p=0.02
0
-10
-20
Change in MI Size (EED, g)
-10
10
MI Size (EED, g)
5
0
-5
-10
a
-15
c
b
-20
-25
-30
6 Months
12 Months
Allogeneic
MSCs
(n=14)
Autologous
MSCs
(n=13)
Overall
(n=27)
0
14
30
60
90
120
150
180 Days
580
581
567
573
559
563
547
555
535
546
523
542
514
536
444 Placebo
463 Serelaxin
Reproduced from Teerlink JR et al. Serelaxin, recombinant human relaxin-2, for treatment
of acute heart failure (RELAX-AHF): a randomised,placebo-controlled trial. Lancet
2013;381(9860):29-39. With permission from Elsevier.
Joshua Hare, MD, University of Miami, Miami, Florida,
USA, discussed regenerative medicine in HF. A major
regenerative approach to HF is cell therapy for ischemic
cardiomyopathy. In this method, mesenchymal stem cells
(MSCs) harvested from bone marrow aspirate are expanded
in culture. Some methods use cardiac stem cells (CSCs). It
is believed that MSCs cause the release of cytokines and
growth factors resulting in antifibrotic, immunomodulatory,
neoangiogenic, and proregenerative effects. The stem
cells can then be delivered to the heart via intravenous,
intracoronary, surgical, or transcatheter methods. For
example, one delivery method uses a specialized helical
needle for stability, has enhanced navigation, and uses
contrast imaging to guide delivery of stem cells.
In the SCIPIO, CADUCEUS, and POSEIDON trials,
patients that received stem cells as CSCs, cardiospheres, or
MSCs experienced a decrease in infarct scar size (Figure 4)
[Telukuntla KS et al. J Am Heart Assoc 2013]. In addition,
patients in the SCIPIO and POSEIDON trials reported an
improvement in quality of life. A decrease in sphericity
index in the POSEIDON trial suggests that MSCs can reverse
remodeling in patients with HF.
Lawrence S. Czer, MD, Cedars-Sinai Heart Institute,
Los Angeles, California, USA, presented information about
mechanical support in HF. Current mechanical support
includes extracorporeal membrane oxygenation (ECMO),
implantable mechanical circulatory support (MCS), and
the total artificial heart.
December 2013
CDC=cardiosphere-derived cells; EED=early enhancement defect; MI=myocardial infarction;
MSCs=mesenchymal stem cells.
Reproduced from Telekuntla KS et al. The Advancing Field of Cell-Based Therapy: Insights
and Lessons From Clinical Trials. J Am Heart Assoc 2013. With permission from Lippincott,
Williams and Wilkins.
No safety signal
2
16
-5
POSEIDON
C
Controls
CDC group
20
0
-15
30
HR, 0.63; 95% CI, 0.43 to 0.93; p=0.020
8
0
CADUCEUS
B
-30
Placebo: 65 deaths (11.3%)
12
SCIPIO
A
Difference in Scar Mass (g)
2. HF Figure 3.
FigureEffect ofEffect of Serelaxin Treatment on All-Cause Death in
Figure 3. 3. Serelaxin Treatment On All-Cause Death In Patients With HF.
Patients With Heart Failure
Figure 44. Effectofof Cell Therapy Event-Free Survival In HF.
2. HF Figure Figure 2. Effect NT-proBNP-Guided Therapy On on Infarct Scar Size
Change in Infarct Size
by Manual Delineation (g)
In an intention-to-treat population, treatment with
serelaxin resulted in significantly fewer cardiovascular deaths
(HR, 0.63; 95% CI, 0.41 to 0.96; p=0.028) and all-cause mortality
(HR, 0.63; 95% CI, 0.43 to 0.93; p=0.020; Figure 3) compared
with patients that received placebo over 180 days [Teerlink JR
et al. Lancet 2013]. Dr. Francis noted that the treatment of HF is
evolving slowly and is focused on systolic dysfunction instead
of HF with preserved ejection fraction (HFpEF).
ECMO is typically used in patients who require an
emergency option for biventricular support. In one study,
58% of patients that received ECMO therapy were alive at
hospital discharge and another study reported a survival
rate of 24% at 5 years. However, it is not widely available,
requires perfusion support, can be used for relatively
short duration, and its use has associated vascular access
complications. Implantable MCS devices are now smaller
and more durable with continuos axial and centrifugal flow
devices. In a prospective, noncontrolled trial, 281 patients
received an implantable MCS, which resulted in a survival
rate of 82% at 6 months and 73% at 12 months, as well as an
improvement in the 6-minute walk test at 6 months [Pagani
FD et al. J Am Coll Cardiol 2009].
An implantable, pulsatile, pneumatic pump, the total
artificial heart was approved by the United States Food
and Drug Administration in 2004. In a trial of 81 patients
with HF, patients who received the total artificial heart, 79%
survived until transplant compared with 46% of patients
that received medical therapy alone.
Dr. Czer pointed out that mechanical support is
effective as a bridge to transplant and 43% of all patients
that have received a transplant received MCS while waiting
for transplantation [Peura JL et al. Circulation 2012].
Typically, the 1-year survival rate of patients awaiting
heart transplant due to HF is 23%; however, MCS improves
survival, functionality, and quality of life in these patients.
Survival and quality of life have been improved in patients
with HF due to advances in CRT, pharmacologic therapy,
cell therapy, and mechanical support devices. Importantly,
tailoring therapy based on the presence of LBBB, QRS
duration, and elevated biomarkers appear to provide provide
further benefit. In addition, emerging therapies have the
potential to expand treatment choices for patients with HF.
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