New Horizons in Cardiogenic Shock - Timothy D. Henry, MD · New Horizons in Cardiogenic Shock Timothy D. Henry, MD Director of Cardiology Cedars-Sinai Heart Institute

New Horizons in Cardiogenic

Shock

Timothy D. Henry, MD

Director of Cardiology

Cedars-Sinai Heart Institute

High In-Hospital Mortality

During AMI Cardiogenic Shock3

1. Sandhu A, McCoy l, Negi S, et al. Use of Mechanical Circulatory Support in Patients Undergoing Percutaneous Coronary Intervention; Insights from the National Cardiovascular Data Registry.

Circulation, 2015;132:1243-1251

2. Acute Cardiac Assist Report, Health Research International – August 2015

3. Jeger, et al. Ann Intern Med. 2008

N = 23,696

74355

78954 78500 79823 80585

82626 86692

89923

2009 2010 2011 2012 2013 2014 2015 2016

US AMI/CGS cases per year1,2

AMI Shock Mortality Unchanged in > 20 years

Trial Follow-up n/N n/N Relative Risk Mortality

95% CI

Relative Risk

95% CI

Revascularization SHOCK 1 year 81/152 100/150 0.72 (0.54;0.95)

SMASH 30 days 22/32 18/23 0.87 (0.66;1.29)

Total 103/184 118/173 0.82 (0.69;0.97)

Early revascularization better Medical treatment better

Vasopressors SOAP-2 (CS subgroup) 28 days 64/145 50/135 0.75 (0.55;0.93)

Norepinephrine better Dopamine better

Inotropes Unverzagt et al. 30 days 5/16 10/16 0.33 (0.11;0.97)

Levosimendan better Control better

Glycoprotein IIb/IIIa inhibitors PRAGUE-18 In-hospital 15/40 13/40 1.15 (0.59;2.27)

Abciximab better Standard treatment better

NO synthase inhibitors TRIUMPH 30 days 97/201 76/180 1.14 (0.91;1.45)

SHOCK II 30 days 24/59 7/20 1.16 (0.59;2.69)

Cotter et al. 30 days 4/15 10/15 0.40 (0.13;1.05)

Total 125/275 93/215 1.05 (0.85;1.29)

NO synthase inhibition better Placebo better

IABP IABP-SHOCK I 30 days 7/19 6/21 1.28 (0.45;3.72)

IABP-SHOCK II 30 days 119/300 123/298 0.96 (0.79;1.17)

Total 126/319 129/319 0.98 (0.81;1.18)

IABP better Standard treatment better

LVAD Thiele et al. 30 days 9/21 9/20 0.95 (0.48;1.90)

Burkhoff et al. 30 days 9/19 5/14 1.33 (0.57;3.10)

ISAR-SHOCK 30 days 6/13 6/13 1.00 (0.44;2.29)

IMPRESS in Severe Shock 30 days 11/24 12/24 0.92 (0.51;1.66)

Total 35/77 32/71 1.01 (0.70;1.44)

LVAD better IABP better

3 0.5 1 2 0.75 1.5 2.5 0.25 0

Randomized Trials Cardiogenic Shock

Thiele et al. Eur Heart J 2015;36:1223-1230

Inotrope Harm in Cardiogenic Shock

1. Marked increase in MVO2 at a time of oxygen starvation.

2. Tachycardia increases MVO2 and decreases diastolic

interval.

3. Marked increase in LVEDP causes further decrease in

diastolic perfusion pressure and increased wall tension.

4. Tachycardia mediated apoptosis may decrease myocardial

recovery.

32%

54% 65% 65% 74%

0 1 2 3 4+

Mortality and Number of Inotropes from cVAD Registry1

P<0.001 (N=287)

Number of Inotropes/Pressors

1. Basir M, Schreiber T, Grines C, et al. Effect of Early Initiation of Mechanical Circulatory Support on Survival in Cardiogenic Shock. Am. J. of Cardiology, 2016

Increased Inotrope Exposure is associated

with Mortality in AMI/CGS

Samuels LE et al , J Card Surg. 1999

Mortality

6

12

21

36

57

89

49

33

55

13 14

0% to 10%

10% to 20%

20% to 30%

30% to 40%

40% to 50%

50% to 60%

60% to 70%

70% to 80%

80% to 90%

90% to 100%

Distribution of Survival to Explant at Impella Sites (379 sites supported >4 AMICS patients)

N=68 N=147 N=277 N=488 N=777 N=465 N=425 N=331 N=99 N=62

Survival

Total # of

Patients

SG USE ASSOCIATED WITH IMPROVED OUTCOMES

ABIOMED INTERNAL CLINICAL QUALITY DATA AMI/CGS APRIL 2015 – MARCH 2016

37% 38%

43% 45%

45%

46% 48%

47%

56%

53%

Swan

Hemodynamic Monitoring associated with

Improved Survival in AMI/CGS

68%

76%

No Hemodynamic Monitoring

Hemodynamic Monitoring

cVAD Registry2

49%

63%

No Hemodynamic Monitoring

Hemodynamic Monitoring

IQ Database1

N=516 N=634 N=5217 N=8767

P<0.0001

P=0.002

1. Abiomed Impella Quality (IQ) Database, US AMI/CGS Apr 2009– Jan 2017. Survival to Explant. Danvers, MA: Abiomed.

2. cVAD survival to explant 2009-2016

Key Issues

• Culprit-Shock

• Cardiac Arrest-Cardiogenic shock

interaction

• New AHA Scientific Statement-Shock

centers and Shock teams

• Refractory Shock

www.nejm.org

80.3%

19.7% Culprit only-PCI (n=4,857)

Multivessel-PCI (n=1,194)

Metaanalysis Mortality – Registry-Data:

de Waha et al. Eur Heart J Acute Cardiovasc Care. 2017; epub

Multivessel PCI in Cardiogenic Shock

Multivessel PCI in Cardiogenic Shock?

Metaanalysis Mortality – Registry-Data

de Waha et al. Eur Heart J Acute Cardiovasc Care. 2017; epub

Short-term follow-up

Events

75

81

13

19

20

40

158

406

Total

167

173

124

60

43

82

433

1082

MV-PCI

Events

119

201

56

68

42

95

737

1318

Total

284

562

386

278

156

254

2654

4574

C-PCI

1.07

1.31

0.72

1.29

1.73

1.30

1.31

1.26

[0.86-1.33]

[1.08-1.33]

[0.41-1.28]

[0.85-1.98]

[1.14-2.61]

[0.99-1.71]

[1.14-1.51]

[1.12-1.41]

RR 95%CI

IABP-SHOCK II

ALKK

KAMIR

Yang et al.

Cavender et al.

EHS-PCI

NCDR

Overall

Heterogeneity: τ2=0.007, I2=31.0%, p=0.19

Test for overall effect: p=0.001

Multivessel PCI better Culprit only PCI better

0.1 0.5 1 2 10 0.2 5

Multivessel PCI better Culprit only PCI better

IABP-SHOCK II

KAMIR

Yang et al.

Cavender et al.

Mylotte et al.

van der Schaaf et al.

SHOCK

Overall

Heterogeneity: τ2=0.043, I2=67.8%, p=0.005

Test for overall effect: p=0.77

Events

91

16

21

32

37

22

7

226

Total

167

124

60

43

66

37

9

506

MV-PCI

Events

149

69

85

101

82

66

26

578

Total

284

386

278

156

103

124

57

1387

C-PCI

1.04

0.72

1.14

1.15

0.70

1.12

1.71

1.03

[0.87-1.24]

[0.43-1.19]

[0.78-1.69]

[0.93-1.42]

[0.56-0.89]

[0.82-1.53]

[1.09-2.67]

[0.85-1.25]

RR 95%CI Long-term follow-up

0.1 0.5 1 2 10 0.2 5

Thiele et al. Am Heart J. 2016;172:160-169

Culprit lesion only PCI (with possible staged revascularization)

is superior to

immediate multivessel PCI

in multivessel coronary artery disease (≥2 mm in diameter, >70% stenosis incl. CTO)

patients with cardiogenic shock complicating acute myocardial

infarction.

Hypothesis

Statistical Methodology

Sample Size: Estimated 50% event rate in multivessel PCI versus 38% in culprit lesion only group for primary endpoint 1 interim analysis (50% of patients) 2-sided Chi2-test; power: 80%, alpha=0.048 for final analysis → 684 patients To compensate losses in follow-up → 706 patients

Primary Study Endpoint: 30-day all-cause mortality or renal replacement therapy

Secondary Study Endpoints: 30-day all-cause mortality

Renal failure with requirement of renal replacement therapy

Time to hemodynamic stabilization

Duration of catecholamine therapy

Serial creatinine-clearance

Length of ICU-stay

SAPS-II score

Requirement and length of mechanical ventilation

All-cause death within 6 and 12 months follow-up

Recurrent infarction within 30-days, 6 and 12 months follow-up

Death or recurrent infarction at 6 and 12 months follow-up

Rehospitalization for congestive heart failure within 30 days, 6-, and 12-months follow-up

Death/recurrent infarction/rehospitalization for congestive heart failure within 30 days, 6-, and 12-months follow-up

Need for repeat revascularization (PCI and/or CABG) within 30 days, 6-, and 12-months follow-up

Peak creatine kinase, creatine kinase-MB and troponin level during hospital stay

Thiele et al. Am Heart J. 2016;172:160-169

Study Flow Chart 1075 patients with acute myocardial infarction (STEMI and NSTEMI) and cardiogenic shock screened

369 excluded

706 randomized

355 randomized to immediate multivessel PCI

342 full informed consent 344 full informed consent

351 randomized to culprit lesion only PCI

301 culprit lesion only PCI

43 immediate multivessel PCI

60 staged PCI

1 staged CABG

13 urgent PCI



8 staged PCI

0 staged CABG

5 urgent PCI

344 with 30-day follow-up


1 lost to follow-up

344 primary endpoint analysis 341 primary endpoint analysis

344 full informed consent




60 staged PCI

1 staged CABG

13 urgent PCI






60 staged PCI

1 staged CABG

13 urgent PCI



344 primary endpoint analysis




60 staged PCI

1 staged CABG

13 urgent PCI





8 staged PCI

0 staged CABG

5 urgent PCI


1 lost to follow-up

341 primary endpoint analysis 344 primary endpoint analysis




60 staged PCI

1 staged CABG

13 urgent PCI


351 randomized to culprit lesion only PCI Allocation

Informed consent

Revascularization

Follow-up

Primary endpoint analysis

Baseline Characteristics Characteristic Culprit only PCI

(n=344)

Multivessel PCI

(n=342)

Age (years); median (IQR) 70 (60-78) 70 (60-77)

Male sex; n/total (%) 257/343 (74.9) 267/342 (78.1)

Prior myocardial infarction; n/total (%) 60/339 (17.7) 53/335 (15.8)

Prior PCI; n/total (%) 64/339 (18.9) 63/335 (18.8)

Prior coronary arterial bypass surgery; n/total (%) 20/341 (5.9) 13/337 (3.9)

Signs of impaired organ perfusion; n/total (%)

Altered mental status

Cold, clammy skin and extremities

Oliguria

Arterial lactate >2.0 mmol/l

237/341 (69.5)

233/338 (68.9)

80/334 (24.0)

216/334 (64.7)

224/341 (65.7)

236/335 (70.4)

93/326 (28.5)

224/330 (67.9)

Fibrinolysis <24 h before randomization; n/total (%) 19/341 (5.6) 15/341 (4.4)

Resuscitation before randomization; n/total (%) 177/341 (51.9) 189/342 (55.3)

ST-elevation myocardial infarction; n/total (%) 206/335 (61.5) 209/330 (63.3)

No. of diseased vessels; n/total (%)

1

2

3

3/343 (0.9)

122/343 (35.6)

218/343 (63.6)

2/342 (0.6)

124/342 (36.3)

216/342 (63.2)

Patients with at least one CTO; n/total (%) 77/344 (22.4) 82/342 (24.0)

Left ventricular ejection fraction (%); median (IQR) 33 (25-40) 30 (21-40)

Treatment

Characteristic Culprit only PCI

(n=344)

Multivessel PCI

(n=342) Femoral access; n/total (%) 287/343 (83.7) 277/342 (81.0) 0.36

Radial access; n/total (%) 61/343 (17.8) 66/342 (19.3) 0.61

Stent implanted in culprit lesion; n/total (%) 326/343 (95.0) 324/342 (94.7) 0.86

Drug-eluting stent in culprit lesion; n/total (%) 305/326 (93.6) 308/324 (95.1) 0.41

TIMI-flow III post PCI of culprit lesion; n/total (%) 289/342 (84.5) 293/338 (86.7) 0.46

Immediate PCI of non-culprit lesions; n/total (%) 43/344 (12.5) 310/342 (90.6) <0.001

Immediate complete revascularization; n/total (%) 26/344 (7.6) 277/342 (81.2) <0.001

Total amount of contrast agent (ml); median (IQR) 190 (140-250) 250 (200-350) <0.001

Staged PCI of non-culprit lesions; n/total (%) 60/344 (17.4) 8/341 (2.3) <0.001

Staged coronary artery bypass surgery; n/total (%) 1/344 (0.3) 0/341 >0.99

Mechanical circulatory support; n/total (%) 99/344 (28.8) 95/342 (27.8) 0.77

Intraaortic balloon pump; n/total (%) 25/99 (25.3) 26/95 (27.4) 0.74

Impella 2.5; n/total (%) 16/99 (16.2) 18/95 (18.9) 0.61

Impella CP; n/total (%) 30/99 (30.3) 18/95 (18.9) 0.07

TandemHeart; n/total (%) 2/99 (2.0) 0/95 0.50

ECMO; n/total (%) 18/99 (18.2) 27/95 (28.4) 0.09

Mild hypothermia; n/total (%) 111/344 (32.3) 118/340 (34.7) 0.50

Mechanical ventilation; n/total (%) 273/344 (79.4) 282/339 (83.2) 0.20

Duration of mechanical ventilation (days); median (IQR) 3 (1-7) 3 (1-7) 0.97

Duration of intensive care treatment (days); median (IQR) 5 (2-12) 5 (2-11) 0.61

Culprit lesion only PCI

Immediate multivessel PCI

344 219 207 198 192 189 184

341 199 172 162 156 153 152



0

10

20

30

40

50

60

0 5 10 15 20 25 30

Days after randomization



Relative risk 0.83; 95% confidence interval 0.71-0.96; P=0.01

All

-ca

us

e m

ort

ali

ty o

r

ren

al re

pla

ce

men

t th

era

py (

%)

344 219 207 198 192 189 184

341 199 172 162 156 153 152

Number at risk:

All

-ca

us

e m

ort

ali

ty o

r

ren

al re

pla

ce

men

t th

era

py (

%)

0

10

20

30

40

50

60

0 5 10 15 20 25 30



Primary Study Endpoint All-Cause Mortality or Renal Replacement Therapy

55.4%

Number at risk:

55.4%

45.9%

0

10

20

30

40

50

60

0 5 10 15 20 25 30

All

-ca

use

mo

rtali

ty (

%)



Relative risk 0.84; 95% confidence interval 0.72-0.98; P=0.03 0

10

20

30

40

50

60

0 5 10 15 20 25 30

All

-ca

use

mo

rtali

ty (

%)



All-Cause Mortality

344 237 226 211 203 198 193

341 229 197 179 170 166 165



Number at risk:

51.5%

344 237 226 211 203 198 193

341 229 197 179 170 166 165



Number at risk:

51.5%

43.3%

0

10

20

30

40

50

60

0 5 10 15 20 25 30

Ren

al re

pla

ce

me

nt

the

rap

y

(%)


0

10

20

30

40

50

60

0 5 10 15 20 25 30

Ren

al re

pla

ce

me

nt

the

rap

y

(%)




Relative risk 0.71; 95% confidence interval 0.49-1.03; P=0.07



344 219 207 198 192 189 184

341 199 172 162 156 153 152

Number at risk:



Renal Replacement Therapy

Number at risk:

Renal Replacement Therapy

11.6%

16.4%

0

1

2

3

4

5

6

7

8

9

Pre PCI 16h 32h Post PCI 24h 40h 48h

P=0.78* P=0.39* P=0.07* P=0.13* P=0.78* P=0.16* P=0.26*



8h

P=0.89*

Arterial Lactate

Art

erial la

cta

te (

mm

ol/l)

*No adjustment for multiple testing

0

20

40

60

80

100

120

Baseline Day 1 Day 2 Day 3 Day 4

P=0.87* P=0.56* P=0.12* P=0.04* P=0.04*

Estim

ate

d g

lom

eru

lar

filtra

tion

rate

(m

l/m

in)



Glomerular Filtration Rate

*No adjustment for multiple testing

Conclusions

In patients with multivessel coronary artery disease and

cardiogenic shock complicating acute myocardial infarction culprit

lesion only PCI with possible staged revascularization reduced the

composite of mortality or requirement for renal replacement therapy

at 30 days.

This effect in the primary outcome was mainly driven by a 30-day

mortality reduction.

This largest randomized European multicenter trial in cardiogenic

shock complicating myocardial infarction challenges current

guideline recommendations.

Key Issues

• Culprit-Shock


interaction




Cardiac Arrest

• Out-of-hospital cardiac arrest (OOHCA)

• 295,000 people annually in the US

• 7.9% median survival rate

• Anoxic encephalopathy and neurologic deficits

• Therapeutic hypothermia (TH) clinical trials

• ILCOR recommendation for TH after resuscitation

Lloyd-Jones D, Adams R, Carnethon M et al. Heart disease and stroke statistics-2009 update. Circulation 2009;119:e21-e181.

Interaction of Cardiac Arrest and

Cardiogenic Shock

Cardiogenic

Shock

(+)

Cardiogenic

Shock

(–) C

ard

iac

Arr

est

(+)

184 Patients

In-hospital

Mortality: 47.3%

1 – Year

Mortality: 51.6%

317 Patients

In-hospital

Mortality: 20.2%

1 – Year

Mortality: 22.7%

Card

iac

Arr

est

(–)

259 Patients

In-hospital

Mortality: 25.1%

1 – Year

Mortality: 33.6%

4157 Patients

In-hospital

Mortality: 1.7%

1 – Year

Mortality: 5.5%

OHCA survival to hospital

discharge by 5-year time periods

Comilla Sasson et al. Circ Cardiovasc Qual Outcomes. 2010;3:63-

81

Survival improves to 50-

60% with Favorable

neurological outcomes in

86% of survivors

With hypothermia and PCI!

Rab et al. JACC 2015;66:62-73

Early predictors of survival in OHCA

Florence Dumas et al. Circ Cardiovasc Interv. 2010;3:200-207

Key Issues

• Culprit-Shock


interaction




Circulation 2017

Detroit

Cardiogenic

Shock

Initiative

DETROIT CSI

DETROIT CSI PROTOCOL



Detroit Cardiogenic Shock Initiative

• Physicians from over 40

hospitals have contacted us

about joining Detroit CSI

• First site outside of Detroit

launched in August:

– Mercy Fitzgerald Hospital in

Philadelphia

• Similar to Detroit, regional

groups are forming to work

together on CGS

National Shock Initiative

0% 20% 40% 60% 80% 100%

National Outcomes Improving

Distribution of Impella Site Outcomes1

Survival to Explant

# of Sites

51% 62%

22% relative

improvement in

overall outcomes

since March, 2016

(p<0.0001)2

1. Data on file. Abiomed Impella Quality(IQ)Data, AMI/CGS Apr 2016 – Sept 2017. Danvers, MA: Abiomed.

2. 525 sites supporting >6 AMICS patients, 7,483 patients total since March 2016

https://www.henryford.com/national-csi

Key Issues

• Culprit-Shock


interaction




Early Transport to Cath Lab for ECMO

and Revasc in Refractory VF (?OHCA)

Early Transport to Cath Lab for

ECMO and Revascularization in

Refractory Ventricular Fibrillation

Out of Hospital

• VF/VT Initial rhythm

• DCCV x3 and 300mg Amiodarone without ROSC

• Time to CCL <30 min

Initial CCL

• ABG and lactate

• Stop if: ETCO2<10mmHg, PaO2<50mmHg or Lactate >18 mmol/L

• If ROSC, immediate Cor Angio +/- IABP.

• If no ROSC, ECLS , then Cor Angio +/- IABP.

• Continue ACLS/ECLS for 90 minutes/PCI; if no ROSC by 90 minutes, declared dead

Comparison Between the Refractory

VF/VT Protocol and the Historical

Comparison Group

Complication Rate

• 13% on ECMO had Vascular Complications

• 4 with significant retroperitoneal bleeding requiring transfusion

• 3 developed an ischemic leg after thrombosis of the distal perfusion cath

Documents

New Horizons in Cardiogenic Shock - Timothy D. Henry, MD · New Horizons in Cardiogenic Shock Timothy D. Henry, MD Director of Cardiology Cedars-Sinai Heart Institute