Channalging Cases in AHF Hypoperfusion

Hypoperfusion

Adrian F. Hernandez, MD, MHS

Associate Director

Duke Clinical Research Institute

2015 Heart Failure

4All Rights Reserved, Duke Medicine 2007

DECLARATION OF INTEREST

• RESEARCH– AstraZeneca– BMS– GSK– Merck– Novartis

• Honorarium– AstraZeneca– GSK– Merck– Novartis


Agenda

• Case Examples from the Duke Hospital

• Diagnostic Considerations

• Inotropic Options

• Mechanical Support

All Rights Reserved, Duke Medicine 2007

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


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


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


Mechanisms Leading to 2 Types ofCardiogenic Liver Injury

Samsky MD et al JACC 2013


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


Suspected Acute Heart Failure Algorithm

Authors/Task Force Members et al. Eur Heart J 2012;33:1787-1847

Shock:

Do something!


Current Treatments of Acute Heart Failure

Diuretics

Reduce

fluid

volume

Vasodilators

Decrease

preload

and/or

afterload

Inotropes

Augment

contrac-

tility


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


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


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


Percutaneous Left Ventricular Support Devices

Werdan et al, EHJ 2014


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


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

Tandem Heart

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

Abrams, et al, JACC 2014

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


Conclusions

• Hypoperfusion in acute heart failure is a major challenge:– Diagnosis may be complex

• Inotrope treatment to ‘rescue’ the patient

• Mechanical circulatory support evolving– Technology improvement– Challenges for evidence-based medicine

Channalging Cases in AHF Hypoperfusion

Healthcare

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