Online Data Supplement

Title: The ENCOURAGE mortality-risk score and

analysis of long-term outcomes after VA-ECMO for acute

myocardial infarction with cardiogenic shock

Grégoire Muller, MD; Erwan Flecher, MD, PhD; Guillaume Lebreton, MD, PhD;

Charles-Edouard Luyt, MD, PhD; Jean-Louis Trouillet, MD; Nicolas Bréchot, MD,

PhD; Matthieu Schmidt, MD, PhD; Ciro Mastroianni, MD, PhD; Jean Chastre, MD;

Pascal Leprince, MD, PhD; Amedeo Anselmi, MD and Alain Combes, MD, PhD*

From the Medical–Surgical Intensive Care Unit (G.M., C.-E.L., J.-L.T, N.B., J.C., A.C.), and

Cardiac Surgery Department (G.L., C.M., P.L.), INSERM UMRS 1166 iCAN, Institute of

Cardiometabolism and Nutrition, Hôpital de la Pitié–Salpêtrière, Assistance Publique–

Hôpitaux de Paris, Université Pierre et Marie Curie, Paris 6, 47, bd de l’Hôpital, 75651 Paris

Cedex 13, France. Thoracic and Cardio-Vascular Surgery Department (E.F., A.A.), Centre

Cardio-Pneumologique, Hôpital Universitaire Pontchaillou, 2, rue Henri-Le-Guilloux, 35000

Rennes, France.

*Corresponding author. Tel: +331.42.16.38.16; Fax: +33 1.42.16.38.17;

e-mail: alain.combes@aphp.fr

Methods

Data collected at intensive care unit (ICU) admission

The following information was recorded retrospectively: age; sex; height, weight and body

mass index; underlying comorbidities; Simplified Acute Physiology Score II (SAPSII);[1]

Sepsis-related Organ Failure Assessment (SOFA) score [2]; mobile extracorporeal membrane

oxygenation (ECMO)-team patient retrieval; pre-venoarterial (VA)-ECMO cardiac arrest;

pre-ECMO EKG; pre-ECMO thrombolysis for acute myocardial infarction (AMI); AMI

location; ICU admission- and percutaneous coronary intervention (PCI)-to-ECMO–

implantation times; ECMO initiation under cardiopulmonary resuscitation (CPR); use of

intra-aortic balloon pump (IABP); pre-ECMO mechanical ventilation (MV); PCI attempts

and successes, numbers of coronary vessels dilated and stents implanted; Glasgow Coma

Score (GCS), the last value recorded when the patient was assessable (before intubation or

when the patient was still awake); hemodynamic variables pre- and post-ECMO initiation;

blood-gas analyses; serum lactate, hemoglobin, bicarbonate, creatininemia and troponin Ic

levels; platelet and leukocyte counts; and prothrombin activity.

ECMO implantation and management

The detailed surgical procedure for femorofemoral VA-ECMO placement was described

previously [3-6]. Briefly, all procedures were performed by trained cardiovascular surgeons

at the bedside because of patients’ hemodynamic instability. Femoral vessels were cannulated

after limited cut-down using the Seldinger technique and an additional 7–10 Fr catheter was

systematically inserted distally into the femoral artery to prevent severe leg ischemia. For

highly unstable patients diagnosed with refractory cardiogenic shock at other hospitals, our

institution’s Mobile Circulatory Assistance Unit traveled rapidly to primary-care hospitals

with a portable ECMO system, installed the device before refractory multiorgan failure or

cardiac arrest took hold and then transported the patient to our tertiary-care ICUs [7]. The

detailed management of VA-ECMO–treated patients was described previously [3-5]. Briefly,

pump speed was adjusted to obtain a blood flow of 3.5–5 L/min. Intravenous unfractionated

heparin was given to maintain the activated partial thromboplastin time at 1.5–2-times

normal. ECMO-associated complications were carefully monitored: cannulation-related

injuries, like leg ischemia, femoral hemorrhage due to arterial laceration, cannula insertion-

site infection, hemolysis or other technical problems. Patients classified as developing

pulmonary edema under ECMO were those with overt pulmonary edema, defined as marked

progression of alveolar consolidation on chest X-ray after ECMO initiation or expelling

abundant pink frothy sputum through the intubation tube. When a pulsatile arterial waveform

was maintained for at least 24 hours, an ECMO-weaning trial was undertaken, as previously

described [3].

Health-related quality of life (HRQOL) and psychological assessment

During a telephone interview, in September 2013, after the purpose and objectives of the

study were explained, survivors self-assessed their HRQOL psychological status by

completing the French version of the Medical Outcome Study Short-Form 36 (SF-36)

questionnaire [8-10]. This standardized, widely used questionnaire has been validated for the

French population [8]. Its 36 items combined evaluate eight domains (physical functioning,

role-physical, bodily pain, general health, vitality, social functioning, role-emotional and

mental health). The aggregate physical and mental component scores were then computed as

recommended [8]. Our patients’ mean SF-36 levels were compared with those obtained for

French age- and sex-matched controls with no adverse health conditions (or minor, non-acute

conditions) [8], 424 AMI survivors evaluated 4 years post-event [11], 1-year survivors after

non-ST–segment elevation acute coronary syndromes included in the early interventional

strategy of the Randomized Intervention Trial of unstable Angina-3 (RITA-3) [12],

venovenous (VV)-ECMO–treated severe acute respiratory distress (ARDS) survivors [10]

and ECMO-rescued severe myocarditis patients [5].

Anxiety and depression symptoms were also analyzed, using the Hospital Anxiety and

Depression (HAD) Scale [13], which contains 14 questions: seven to assess anxiety and

seven for depression (respectively, HAD-A/-D), using a four-point Likert scale (range, 0–3)

giving a possible score of 0 (none) to 21 (severe) for each subscale. Subscale scores ≥8/21

indicated clinically significant anxiety or depression symptoms, whereas subscale scores of

≥11/21 suggested severe psychological distress [13]. Our patients’ scores were compared to

those of VV-ECMO–treated severe ARDS survivors [10], VA-ECMO–rescued severe

myocarditis patients[5] and 335 post-AMI patients [14]. Finally, post-traumatic stress

disorder (PTSD)-related symptoms were assessed with the Impact of Event Scale (IES) [15],

consisting of 15 questions divided into two subscales: intrusion (seven items) and avoidance

(eight items). The total score ranges from 0 (no symptoms) to 75 (severe symptoms). In

agreement with previous reports, patients with a total IES score ≥30/75 points were

considered at high risk for PTSD [5]. Our patients’ IES scores were compared with those of

VV-ECMO–treated severe ARDS survivors [10], VA-ECMO–rescued severe myocarditis

patients [5], 268 car-accident survivors[16] and survivors of acute coronary syndromes [17].

Ethics

In accordance with the ethical standards of our hospitals’ institutional review boards

(Committees for the Protection of Human Subjects), informed consent for demographic,

physiological and hospital-outcome data analyses was not obtained because this observational

study did not modify existing diagnostic or therapeutic strategies. Survivors gave oral consent

to participate in the telephone interview, conducted by the same investigator, who asked the

questionnaire questions in the same order. The protocol for long-term evaluation with

quality-of-life questionnaires was submitted to CPP Ile de France II under the title

“Evaluation à long terme des séquelles fonctionnelles des survivants après un séjour en

réanimation”.

References

1. Le Gall JR, Lemeshow S, Saulnier F, (1993) A new Simplified Acute Physiology

Score (SAPS II) based on a European/North American multicenter study. JAMA 270:

2957-2963

2. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart

CK, Suter PM, Thijs LG, (1996) The SOFA (Sepsis-related Organ Failure

Assessment) score to describe organ dysfunction/failure. On behalf of the Working

Group on Sepsis-Related Problems of the European Society of Intensive Care

Medicine. Intensive Care Med 22: 707-710

3. Aissaoui N, Luyt CE, Leprince P, Trouillet JL, Leger P, Pavie A, Diebold B, Chastre

J, Combes A, (2011) Predictors of successful extracorporeal membrane oxygenation

(ECMO) weaning after assistance for refractory cardiogenic shock. Intensive Care

Med 37: 1738-1745

4. Combes A, Leprince P, Luyt CE, Bonnet N, Trouillet JL, Leger P, Pavie A, Chastre J,

(2008) Outcomes and long-term quality-of-life of patients supported by

extracorporeal membrane oxygenation for refractory cardiogenic shock. Crit Care

Med 36: 1404-1411

5. Mirabel M, Luyt CE, Leprince P, Trouillet JL, Leger P, Pavie A, Chastre J, Combes

A, (2011) Outcomes, long-term quality of life, and psychologic assessment of

fulminant myocarditis patients rescued by mechanical circulatory support. Crit Care

Med 39: 1029-1035

6. Schmidt M, Brechot N, Hariri S, Guiguet M, Luyt CE, Makri R, Leprince P, Trouillet

JL, Pavie A, Chastre J, Combes A, (2012) Nosocomial infections in adult cardiogenic

shock patients supported by venoarterial extracorporeal membrane oxygenation. Clin

Infect Dis 55: 1633-1641

7. Beurtheret S, Mordant P, Paoletti X, Marijon E, Celermajer DS, Leger P, Pavie A,

Combes A, Leprince P, (2013) Emergency circulatory support in refractory

cardiogenic shock patients in remote institutions: a pilot study (the cardiac-RESCUE

program). Eur Heart J 34: 112-120

8. Leplege A, Ecosse E, Verdier A, Perneger TV, (1998) The French SF-36 Health

Survey: translation, cultural adaptation and preliminary psychometric evaluation. J

Clin Epidemiol 51: 1013-1023

9. Trouillet JL, Luyt CE, Guiguet M, Ouattara A, Vaissier E, Makri R, Nieszkowska A,

Leprince P, Pavie A, Chastre J, Combes A, (2011) Early percutaneous tracheotomy

versus prolonged intubation of mechanically ventilated patients after cardiac surgery:

a randomized trial. Ann Intern Med 154: 373-383

10. Schmidt M, Zogheib E, Roze H, Repesse X, Lebreton G, Luyt CE, Trouillet JL,

Brechot N, Nieszkowska A, Dupont H, Ouattara A, Leprince P, Chastre J, Combes A,

(2013) The PRESERVE mortality risk score and analysis of long-term outcomes after

extracorporeal membrane oxygenation for severe acute respiratory distress syndrome.

Intensive Care Med 39: 1704-1713

11. Brown N, Melville M, Gray D, Young T, Munro J, Skene AM, Hampton JR, (1999)

Quality of life four years after acute myocardial infarction: short form 36 scores

compared with a normal population. Heart 81: 352-358

12. Kim J, Henderson RA, Pocock SJ, Clayton T, Sculpher MJ, Fox KA, (2005) Health-

related quality of life after interventional or conservative strategy in patients with

unstable angina or non-ST-segment elevation myocardial infarction: one-year results

of the third Randomized Intervention Trial of unstable Angina (RITA-3). J Am Coll

Cardiol 45: 221-228

13. Zigmond AS, Snaith RP, (1983) The hospital anxiety and depression scale. Acta

Psychiatr Scand 67: 361-370

14. Martin CR, Lewin RJ, Thompson DR, (2003) A confirmatory factor analysis of the

Hospital Anxiety and Depression Scale in coronary care patients following acute

myocardial infarction. Psychiatry research 120: 85-94

15. Horowitz M, Wilner N, Alvarez W, (1979) Impact of Event Scale: a measure of

subjective stress. Psychosom Med 41: 209-218

16. Ameratunga S, Tin Tin S, Coverdale J, Connor J, Norton R, (2009) Posttraumatic

stress among hospitalized and nonhospitalized survivors of serious car crashes: a

population-based study. Psychiatr Serv 60: 402-404

17. Edmondson D, Richardson S, Falzon L, Davidson KW, Mills MA, Neria Y, (2012)

Posttraumatic stress disorder prevalence and risk of recurrence in acute coronary

syndrome patients: a meta-analytic review. PLoS One 7: e38915

18. Schmidt M, Burrell A, Roberts L, Bailey M, Sheldrake J, Rycus PT, Hodgson C,

Scheinkestel C, Cooper DJ, Thiagarajan RR, Brodie D, Pellegrino V, Pilcher D,

(2015) Predicting survival after ECMO for refractory cardiogenic shock: the survival

after veno-arterial-ECMO (SAVE)-score. Eur Heart J 36: 2246-2256

19. Cheng JM, Helming AM, van Vark LC, Kardys I, Den Uil CA, Jewbali LS, van

Geuns RJ, Zijlstra F, van Domburg RT, Boersma E, Akkerhuis KM, (2015) A simple

risk chart for initial risk assessment of 30-day mortality in patients with cardiogenic

shock from ST-elevation myocardial infarction. European heart journal Acute

cardiovascular care, in press

20. Sleeper LA, Reynolds HR, White HD, Webb JG, Dzavik V, Hochman JS, (2010) A

severity scoring system for risk assessment of patients with cardiogenic shock: a

report from the SHOCK Trial and Registry. Am Heart J 160: 443-450

21. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van De

Werf F, Avezum A, Goodman SG, Flather MD, Fox KA, (2003) Predictors of hospital

mortality in the global registry of acute coronary events. Arch Intern Med 163: 2345-

2353

22. Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, Richardt G,

Hennersdorf M, Empen K, Fuernau G, Desch S, Eitel I, Hambrecht R, Fuhrmann J,

Bohm M, Ebelt H, Schneider S, Schuler G, Werdan K, (2012) Intraaortic balloon

support for myocardial infarction with cardiogenic shock. N Engl J Med 367: 1287-

1296

Table S1. Patients’ characteristics at ECMO initiation according to ICU-survival status

Characteristic All patients

(n = 138)

Survivors

(n = 65)

Non-survivors

(n = 73)

P-

value

Height, cm 175 (167–180) 175 (169–180) 173 (165–178) 0.27

Weight, kg 80 (70–89) 80 (70–84) 80 (70–90) 0.57

Body mass index, kg/m2 26 (24–29) 25 (24–28) 26 (24–30) 0.06

Co-morbidity

Diabetes 23 (17) 10 (15) 13 (18) 0.68

Active smoking 59 (43) 33 (51) 26 (36) 0.08

Dyslipidemia 38 (28) 17 (26) 21 (29) 0.70

Hypertension 38 (28) 19 (29) 19 (26) 0.71

Ischemic cardiomyopathy 17 (12) 8 (12) 9 (12) 0.99

Peripheral arterial disease 10 (7) 4 (6) 6 (8) 0.61

SOFA score 11 (8–15) 10 (7–12) 13 (9–16) 0.001

Respiratory SOFA 2 (1–3) 2 (1–3) 3 (1–3) 0.54

Liver SOFA 0 (0–1) 0 (0–1) 0 (0–1) 0.69

Platelet SOFA 1 (0–2) 1 (0–1) 1 (0–2) 0.90

Glasgow SOFA 3 (1–4) 2 (1–4) 4 (1–4) 0.003

Renal SOFA 2 (0–4) 1 (0–3) 2 (1–4) <0.001

Pre-ECMO EKG

STEMI 123 (89) 60 (92) 63 (86)

Non-STEMI 10 (7) 4 (6) 5 (7)

LBBB 5 (4) 1 (2) 4 (5)

Pre-ECMO LVEF 20 (15–25) 20 (15–25) 20 (15–25) 0.99

Door-to-balloon time, min 200 (120–360) 180 (120–293) 240 (130–360) 0.17

Patients with attempted PCI 112 (81) 54 (83) 58 (80) 0.59

Pre-PCI TIMI 0 (0–0) 0 (0–0) 0 (0–1) 0.92

Patients with successful PTCA 99 (72) 48 (74) 51 (70) 0.60

Number of vessels dilated 1 (1–2) 1 (1–1) 1 (1–2) 0.53

Number of stents implanted 1 (0–2) 1 (1–2) 1 (0–2) 0.97

Post-PCI TIMI 3 (1–3) 3 (1–3) 3 (2–3) 0.94

ECMO pre-PCI 14 (10) 8 (12) 6 (8) 0.46

ECMO to PCI, hours 2 (1–6) 1 (1–5) 4 (1–24) 0.99

ECMO post-PCI 124 (90) 57 (88) 67 (92) 0.66

PCI to ECMO, hours 12 (4–24) 11 (3–24) 12 (5–24) 0.88

IABP associated with ECMO 96 (70) 46 (71) 50 (69) 0.77

Pre-ECMO IABP 76 (55) 37 (57) 39 (53) 0.91

Antegrade limb perfusion 132 (96) 64 (98) 68 (93) 0.92

Pre-ECMO hemodynamic parametersa

SAP, mmHg 84 (70–100) 88 (69–100) 83 (74–100) 0.70

DAP, mmHg 54 (40–60) 60 (44–65) 50 (40–60) 0.45

MAP, mmHg 64 (53–73) 67 (54–75) 63 (51–75) 0.72

Pulse pressure, mmHg 32 (20–40) 31 (20–40) 32 (20–45) 0.32

Heart rate, /min 100 (80–120) 103 (87–120) 100 (67–120) 0.30

Post-ECMO hemodynamic parameters

SAP, mmHg 110 (91–128) 112 (95–128) 109 (90–129) 0.53

DAP, mmHg 67 (55–82) 66 (55–81) 67 (56–82) 0.86

MAP, mmHg 83 (71–96) 81 (74–101) 85 (67–94) 0.66

Pulse pressure, mmHg 38 (24–57) 41 (26–57) 35 (23–55) 0.27

Heart rate, /min 94 (79–109) 89 (79–105) 96 (80–112) 0.30

Respiratory rate, /min 16 (14–21) 16 (14–22) 17 (13–20) 0.83

Inotropic scoreb 52 (26–145) 34 (14–65) 78 (33–200) 0.001

Biological parameters

pH 7.32 (7.22–7.45) 7.39 (7.29–7.47) 7.27 (7.15–7. 42) <0.001

HCO3–, mmol/L 18 (13–23) 21 (16–24) 16 (11–21) <0.001

Arterial lactate, mmol/L 4.1 (2.1–8.2) 2.8 (1.7–6.1) 6.0 (3.0–11.0) <0.001

Bilirubin, mmol/L 14 (9–25) 15 (9–22) 14 (8–25) 0.69

Prothrombin activity, % 57 (40–69) 61 (50–79) 48 (32–64) <0.001

Creatininemia, µmol/L 148 (100–237) 118 (87–199) 165 (126–248) 0.002

Hemoglobin, g/dL 10.2 (8.7–12.2) 10.2 (9.0–12.2) 10.2 (8.6–12.2) 0.72

Hematocrit, % 0.31 (0.28–0.39) 0.31 (0.28–0.38) 0.32 (0.28–0.40) 0.78

Platelet, G/L 166 (103–244) 159 (112–245) 170 (101–242) 0.54

Troponin Ic, µg/L 45 (10–188) 31 (4–104) 67 (19–294) 0.02

Values are expressed as medians (25th to 75th percentile). STEMI, ST-elevation myocardial

infarction; non-STEMI, non-ST-elevation myocardial infarction; LBBB, left bundle-branch

block; LVEF, left ventricle ejection fraction; TIMI, thrombolysis in myocardial infarction;

PTCA, percutaneous transluminal coronary angioplasty; SAP, DAP and MAP, systolic,

diastolic and mean arterial blood pressure, respectively.

aValues were obtained for 76/138 patients (33 survivors and 43 non-survivors).

bInotropic score, expressed in µg/kg/min, was calculated as follows: 100 epinephrine + 100

norepinephrine + dobutamine.

Table S2. ENCOURAGE (PrEdictioN of Cardiogenic shock OUtcome foR AMI patients

salvaGed by VA-ECMO) mortality-risk score generation: transformation of continuous

variables into categorical variables

Variable Quartile

(25th, 50th, 75th percentiles) 1 2 3 4

Age (46, 55, 63) 56 50 50 32

Body mass index (24, 26, 29) 60 50 38 38

SAPSII (48, 66, 82) 72 39 54 28

Glasgow Coma Score (3, 6, 14) 36 45 64 49

Creatininemia (100, 148, 237) 74 43 32 40

Lactate (2.1, 4.1, 8.2) 77 51 45 21

Prothrombin activity (40, 57, 69) 26 41 52 71

Troponin Ic (10, 45, 188) 56 54 48 36

Inotropic score (25, 50, 145) 36 50 66 73

Door to balloon time (120, 200, 360) 45 51 66 61

Median values were chosen for body mass index, SAPSII, Glasgow Coma Score, troponin Ic

and creatininemia. Because mortality for age was similar for quartiles 2 and 3 but much

higher for quartile 4, we reanalyzed quartile-3 mortality and determined that the breakpoint

was 60. Similarly, the breakpoint was 50 for prothrombin activity. Lactate was

trichotomized because mortality was comparable for quartiles 2 and 3 but markedly different

for quartiles 1 and 4. For practical purposes, values were rounded to the nearest integer.

Table S3. Univariable and multivariable analyses of factors associated with in-ICU death

Factor Univariable analysis Multivariable analysis

OR (95% CI) P-value OR (95% CI) P-value

Age >60 years 1.86 (0.903.84) 0.093 2.63 (1.016.85) 0.048

Female 1.80 (0.764.25) 0.179 4.35 (1.2914.72) 0.018

Body mass index >25 kg/m² 2.24 (1.124.48) 0.020 3.10 (1.217.92) 0.018

Active smoker 0.54 (0.271.08) 0.082

SAPSII >65 1.75 (0.893.44) 0.106

Glasgow Coma Score <6 1.97 (1.003.91) 0.054 3.09 (1.198.05) 0.021

Creatininemia >150 mol/L 2.45 (1.234.87) 0.011 2.60 (1.056.49) 0.040

Serum lactate

<2 mmol/L 1 1

2–8 mmol/L 6.80 (2.1321.65) 0.001 4.71 (1.3117.01) 0.020

>8 mmol/L 22.18 (5.7685.44) <0.001 8.71 (1.7643.10) 0.004

Inotropic score >50 3.85 (1.82–8.16) 0.001Door to balloon time >200 min 2.27 (0.95–5.42) 0.065Prothrombin activity <50% 3.85 (1.82–8.16) 0.001 2.80 (1.017.77) 0.049Troponin Ic >45 µg/L 2.93 (1.004.07) 0.047

OR, odds ratio.

The SOFA score was not included in the model. Only renal (creatininemia) and neurological

(Glasgow Coma Score) SOFA subscores were included.

Mobile ECMO retrieval, Pre-ECMO cardiac arrest, ECMO under CPR, AMI location, IABP

associated with ECMO and Post-PCI TIMI were forced into the final multivariable model

although not P values for the difference between survivors and non-survivors was >0.20.

None of these factors were retained in the final multivariable model. Arterial HCO3– and pH

were not included since they were collinear to arterial lactate.

Table S4. Spearman rank correlation matrix for the prediction scoring systems

ENCOURAGE SAVE SAPSII SOFA CHENG SLEEPER GRACE

ENCOURAGE 1.000

SAVE [18] -0.660 1.000

SAPSII [1] 0.495 -0.520 1.000

SOFA [2] 0.413 -0.573 0.660 1.000

CHENG [19] 0.648 -0.524 0.263 0.173 1.000

SLEEPER [20] 0.575 -0.636 0.631 0.695 0.365 1.000

GRACE [21] 0.331 -0.535 0.246 0.199 0.361 0.319 1.000

Table S5. Long-term outcome variables and comparisons of scores according to the median

duration of follow-up

Outcome variable All followed Follow-up duration P- value

patients

(n = 41)

<945 days

(n = 21)

≥945 days

(n = 20)

SF-36 domains

Physical Functioning 75 (54–90) 65 (45–81) 80 (68–95) 0.03

Role-Physical 75 (25–100) 75 (25–100) 100 (63–100) 0.03

Bodily Pain 100 (67–100) 100 (67–100) 100 (64–100) 0.84

General Health 58 (46–75) 58 (38–75) 56 (50–73) 0.68

Vitality 50 (44–76) 50 (40–71) 65 (55–80) 0.10

Social Functioning 88 (50–100) 63 (34–100) 100 (75–100) 0.01

Role-Emotional 100 (33–100) 100 (25–100) 100 (50–100) 0.27

Mental Health 76 (59–80) 72 (44–82) 76 (64–78) 0.66

SF-36 Physical Component Score 50 (42–53) 44 (40–52) 50 (46–54) 0.16

SF-36 Mental Component Score 50 (39–56) 47 (34–55) 53 (49–56) 0.16

HAD Scale 9 (7–14) 10 (6–17) 9 (8–12) 0.54

HAD-A Subscale 5 (4–9) 5 (3–10) 6 (4–9) 0.81

HAD-A ≥8 14 (34) 7 (33) 7 (35) 0.99

HAD-D Subscale 3 (3–7) 5 (3–10) 3 (2–4) 0.21

HAD-D ≥8 8 (20) 7 (33) 1 (5) 0.04

IES 5 (0–16) 7 (2–21) 3 (0–13) 0.11

IES ≥30 2 (5) 2 (10) 0 0.16

NYHA class 2 (1–2) 2 (1–3) 1 (1–2) 0.07

Values are medians (25th to 75th percentile) or n (%). SF-36, Short-Form 36 questionnaire; HAD-A/-D, Hospital Anxiety and Depression Scale-Anxiety/-Depression; IES, Impact of Event Scale; NYHA, New York Heart Association.

Table S6. Comparison of ENCOURAGE and IABP-SHOCK[22] populations

Characteristic ENCOURAGE

(n = 138)

IABP-SHOCK

(n = 600)

Age, years 55 70

Men 110 (80) 413 (69)

SAPSII 66 52

Arterial lactate, mmol/L 4.1 4.1

LVEF, % 20 35

Pre-ECMO cardiac arrest 79 (57) 270 (45)

Catecholamines used 138 (100) 538 (90)

On mechanical ventilation 134 (97) 492 (82)

Renal replacement therapy 63 (46) 109 (18)

Post-PCI hemodynamics

SAP, mmHg 84 102

DAP, mmHg 54 57

MAP, mmHg 64 73

Heart rate, /min 100 90

Values are medians or n (%).

SAPS, Simplified Acute Physiology Score; LVEF, left ventricle ejection fraction; PCI,

percutaneous coronary intervention; SAP, DAP, MAP, systolic, diastolic and mean arterial

blood pressure, respectively.

Figure Legends

Figure S1. Study flow chart for survivors. LVAD, left ventricular assist device; BiVAD, bi-

ventricular assist device; MOF, multiorgan failure.

Figure S2. Study flow chart for non-survivors. LVAD, left ventricular assist device;

BiVAD, bi-ventricular assist device; MOF, multiorgan failure. Of the 67 patients who died

while still on mechanical assistance, 61 had refractory multiple organ failure. Early death

related to initial refractory shock (within the first 7 days of ECMO) occurred in 38 patients.

Eleven and twelve patients died after 8-14 and 15-28 days of ECMO support, respectively.

Causes of multiple organ failure in these patients were 5 septic shock due to nosocomial

pneumonia, 5 post-operative shock, 2 hemorrhagic shock and 11 non-specific shock.

Figure S3. KaplanMeier estimates of cumulative probabilities of 180-day survival for

patients with the indicated pre-ECMO ENCOURAGE-score classes.

Figure S4. Comparison of median SF-36 scores of 41 of our ECMO-treated AMI survivors

after median follow-up of 32 months post-ECMO initiation and their 41 age- and sex-

matched controls [8], 424 AMI survivors evaluated 4 years post-event [11], 1-year survivors

after non-ST–segment elevation acute coronary syndromes included in the early

interventional strategy of the Randomized Intervention Trial of unstable Angina-3 (RITA-3)

[12], venovenous-ECMO–treated severe ARDS survivors [10] or ECMO-rescued severe

myocarditis patients [5]. PF, physical functioning; RP, role-physical; BP, body pain; GH,

general health; VT, vitality; SF, social functioning; RE, role-emotional; MH, mental health.

Figure S5. A, Mean percentages of our ECMO-treated ARDS survivors (evaluated after

median follow-up of 17 months post-ICU discharge) with clinically significant anxiety and/or

depression (Hospital Anxiety and Depression [HAD-A/D] subscale scores ≥8/21) compared

to those of VV-ECMO–treated severe ARDS survivors,[10] VA-ECMO–rescued severe

myocarditis patients [5] and 335 AMI patients [14]. B, Mean percentages of our ECMO-

treated ARDS survivors at risk of developing PTSD compared to those of VV-ECMO–treated

severe ARDS survivors [10], VA-ECMO–rescued severe myocarditis patients [5], 268 car-

accident survivors [16] and survivors of acute coronary syndromes (ACS) [17].

Figure S1.

Figure S2

Figure S3

0.0

0.2

0.4

0.6

0.8

1.0

0

Cum

ulati

ve P

roba

bilit

yof

Sur

viva

l

0.0

0 20 40 60 80 100 120 140 160 180Days after ECMO Initiation

P<0.001, log-rank test

ENCOURAGE 0–12

ENCOURAGE 13–18

ENCOURAGE ≥28

ENCOURAGE 19–22

ENCOURAGE 23–27

Number at risk

26 24 23 23 22 22

27 18 17 17 17 17

26 14 12 11 9 8

29 8 7 5 5 3

30 8 7 5 5 3

Figure S4

0

20

40

60

80

100

PF

RP

BP

GH

VT

SF

RE

MH

Controls, (20)

VA-ECMO ENCOURAGE

ECMO PRESERVE ARDS, (22)

Myocarditis & ECMO, (5)

Myocardial Infarction, (33)

NonSTEMI RITA-3, (34)

Figure S5

AMI survivors (14)ECMO PRESERVE ARDS (10)

Myocarditis & ECMO (5)

VA-ECMO ENCOURAGE

10

20

30

40

50

HAD-A HAD-D

Scor

e ≥8 (

%)

A

B

ACS survivors (17)ECMO PRESERVE ARDS (10)

Myocarditis & ECMO (5)

Car-accident survivors (16)

10

20

30

40

Impact of Event Scale

Scor

e ≥30

(%)

VA-ECMO ENCOURAGE