Post on 13-Apr-2017
Hypoperfusion
Adrian F. Hernandez, MD, MHS
Associate Director
Duke Clinical Research Institute
2015 Heart Failure
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DECLARATION OF INTEREST
• RESEARCH– AstraZeneca– BMS– GSK– Merck– Novartis
• Honorarium– AstraZeneca– GSK– Merck– Novartis
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Agenda
• Case Examples from the Duke Hospital
• Diagnostic Considerations
• Inotropic Options
• Mechanical Support
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Cases from the halls of Duke North 7300:Sick or Not Sick?
35 yo man with non-ischemic CM
• 3 weeks of worsening dyspnea, fatigue
• BP 90/50
• 75 yo female with long history of ischemic CM
• Progressive weight gain and edema
• BP 110/60
44
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Cases from the halls of Duke North 7300:Sick or Not Sick?
60 yo man with long history of HF
PE: JVP mildly elevated;
Cold, trace edema
• Labs:• BUN:70; • Creatinine: 2.1• AST 1500; ALT 1200• T.Bili 3.1
• 75 yo female with long history of HF, COPD
• PE: JVP elevatedMassive edema
• Labs:• BUN:70;• Creatinine: 2.1• AST 300; ALT 200• T.Bili 1.8
45
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Yes
Stevenson LW. Eur J Heart Failure 1999;1:251-257
NoWarm and Dry
PCW normal
CI normal
Cold and Wet
PCW elevated
CI decreased
Cold and Dry
PCW low/normal
CI decreased
Congestion at RestCongestion at Rest
LowLow
PerfusionPerfusion
at Restat Rest
No
Yes
Warm and Wet
PCW elevated
CI normal
Patient Patient Classification and Classification and TreatmentTreatment
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Mechanisms Leading to 2 Types ofCardiogenic Liver Injury
Samsky MD et al JACC 2013
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Biochemical Profile
Acute Cardiogenic Liver Injury• Rapid elevation of ALT/LDH 10-20
X normal • 1-3 days after hemodynamic
insult• Correction within 7-10 days after
hemodynamics normalize• ALT: LDH <1.5 characteristic of
acute cardiogenic liver injury• Prolonged PT/INR• Total bilirubin increase and
delayed c/w ALT, LDH, AST
Chronic Passive Congestion• LFTs commonly elevated
but small in magnitude• Often characterized as
cholestasis (increase alk phos, GGT, total bili)
Samsky MD et al JACC 2013
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Suspected Acute Heart Failure Algorithm
Authors/Task Force Members et al. Eur Heart J 2012;33:1787-1847
Shock:
Do something!
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Current Treatments of Acute Heart Failure
Diuretics
Reduce
fluid
volume
Vasodilators
Decrease
preload
and/or
afterload
Inotropes
Augment
contrac-
tility
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ResultsPlacebo Milrinone(n = 472) (n = 477) p-value
Primary Endpoint (Days of CV hospitalization within 60 days) Median days 7.0 6.0 Mean days ( sd) 12.5 14 12.3 14
Discharge to Day 60 Mean CV days 5.9 13 5.7 13 0.594
ACE-I at Target Dose (%) 48 hrs 35.8 40.5 0.140 Discharge 40.9 43.8 0.362
0.714
4 Cuffe MS et al. JAMA 2002
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Omecamtiv Mecarbil (OM) Selective Cardiac Myosin Activator
Malik FI, et al. Science 2011; 331:1439-43.
Mechanochemical Cycle of Myosin
Force production
4Om
ecam
tiv m
ecar
bil
Omecamtiv mecarbil increases the entry rate of myosin into the
tightly-bound, force-producing state with actin
“More hands pulling on the rope”
4Increases duration of systole
4Increases stroke volume
4No increase in myocyte calcium
4No change in dP/dtmax
4No increase in MVO2
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Time-dependent Elastance [E(t)]
0
0.5
1.0
0 0.1 0.2 0.3 0.4Time (sec)
Nor
mal
ized
E(t) Dobutamine
Baseline
TEmax
TEmin
0 0.1 0.2 0.3 0.4
Baseline
Omecamtiv mecarbil
TEmin
TEmax
Time (sec)
0
0.5
1.0
MVO2 Increased MVO2 UnchangedMalik FI, et al. Science 2011
Omecamtiv Mecarbil: Dog Heart Failure Model Increases the Duration but not the Velocity of Contraction
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Percutaneous Left Ventricular Support Devices
Werdan et al, EHJ 2014
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Physiological Effects of IABP
—Sheidt, NEJM 1973; Mueller, Circ 1972
Cardiac Index 40%(L/min/M2)
Arterial Lactate 42%(mmol/L)
Coronary 34%Blood Flow (M2/100g/min)
CardiacOutput 500 ml/min
Heart rate bts/min
Systolic BP 29 mmHg
Diastolic BP 30 mmHg
The Problem of Acute Cardiogenic Shock
New Engl J Med 2012;367:1287-96
IABP SHOCK II Trial
On the basis of the IABP-Shock II trial, we must move forward with the understanding that a cardiovascular condition with a 40% mortality at 30-days is unacceptable.
New Eng J Med 2012;367:1349-50
IABP SHOCK-2 Trial: Predictors of Mortality
Thiele et al, Lancet 2013
Univariate Multivariate
The two strongest predictors (age and prior stroke) cannot be modified by any acute intervention
The next three predictors (lactate, oliguria, and pH) suggest that the amount of LV support is important
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Impella Technology
2.5 – 12 Fr: 2.5 L/min
CP – 14 Fr: 3.5 L/Min
5.0 – 21 Fr: 5.0 L/Min
Cardiac Index
Car
diac
Inde
x(l/
min
/m2)
Wedge Pressure
01.61.82.02.22.42.6
OnImpella
PCW
P(m
mH
g)
020
24
28
22
26
30
PreImpella*
1.9±0.7
pH
pH L
evel
0
7.17.27.37.47.5
7.0
7.2±0.2
OnImpella
PreImpella
OnImpella
PreImpella
2.8±0.7
32±12
20±11
p=0.0001
P<0.0001p<0.0001
Mean Arterial Pressure
61±18
94±23p<0.0001
7.4±0.1
MA
P(m
mH
g)
05060708090
OnImpella
PreImpella*
100
USPella Registry: Hemodynamic and Metabolic Changes
O’Neill, TCT 2011
ISAR-SHOCK RANDOMIZED TRIAL
Impella
0.49
0.15
0.60
Primary Endpoint: Increase in Cardiac Index From Baseline
(measured after 30 min of support)
Car
diac
Inde
x (L
/min
/m2 )
IABP
P=0.02
0.45
0.30
0.75
00.11
1.10
0.200.25
1.25
Car
diac
Out
put (
L/m
in)
0.75
0.50
1.50
0
P<0.01
Seyfarth et al. JACC 2008;52:1584–8
Percutaneous VAD: TandemHeartCardiac Index
C. Venous Pressure
CVP
(mm
Hg)
0 91011121314
Serum Lactate
Seru
m L
acta
te(m
mol
/L)
02.83.23.64.04.44.6
15 4.8
01.4
1.8
2.2
1.6
2.0
2.4
Car
diac
Inde
x(l/
min
/m2)
IABP
1.51.7
PerVAD
1.7
2.3
Prep=0.4
n=20 n=21
Postp=0.005
IABP PerVAD
IABP
1312
PerVAD
1110
Prep=0.3
n=20 n=21
Postp=0.06
IABP PerVAD IABP
3.83.3
PerVAD
4.5
2.8
Prep=0.5
n=20 n=21
Postp=0.03
IABP PerVAD
Wedge Pressure
IABP
27
22
PerVAD
20
16
PCW
P(m
mH
g)
0
Prep=0.02
n=20 n=21
Postp=0.003
IABP PerVAD
16182022242628
Thiele and al. Eur. Heart Journal 2005:1276-83
Percutaneous VAD: TandemHeart30-day Mortality
010
30
50
20
40
60
30-d
ay M
orta
lity
(%)
IABP
45%
PerVAD
43%
p=0.8
9/20 9/21
Thiele et al. Eur. Heart Journal 2005:1276-83
Limb Ischemia
010
30
50
20
40
60
Lim
b Is
chem
ia (%
)
IABP
0%
PerVAD
33%
p=0.009
0/20 7/21
Transfusion
IABP
40%
PerVAD
90%p=0.002
8/20 19/21
DIC*
010
30
50
20
40
60
Lim
b Is
chem
ia (%
)
IABP
20%
PerVAD
62%p=0.001
4/20 13/210
40
60
80
50
70
90
Req
uire
d Tr
ansf
usio
n (%
)
100
§ Venous to arterial conduit with oxygenator
§ Can deliver 6 l/min CO§ Generally 18-21 Fr
venous and 14-16 Fr arterial catheters
§ No randomized trials§ Observational data
only
Percutaneous Cardiopulmonary Bypass (ECMO or CPS)
Lifebridge B2T Pump
Percutaneous Cardiopulmonary Bypass (ECMO or CPS) in Cardiogenic
Shock
§ 52 studies§ 533 patients§ Average 52% of
pts discharged alive (all studies)
§ Range of survival: 0-100%
Nichol et al, Rescuscitation 2006
Evidence of publication bias with most studies to the left of median