# Long-term outcome in early survivors of cardiogenic shock at the acute stage of myocardial infarction: a landmark analysis from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) Registry

Nadia Aissaoui, Etienne Puymirat, Tabassome Simon, Eric Bonnefoy-Cudraz, Denis Angoulvant, Francois Schiele, Hakim Benamer, Philippe Quandalle, Fabrice Prunier, Eric Durand, et al.

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Nadia Aissaoui, Etienne Puymirat, Tabassome Simon, Eric Bonnefoy-Cudraz, Denis Angoulvant, et al. Long-term outcome in early survivors of cardiogenic shock at the acute stage of myocardial infarction: a landmark analysis from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) Registry. Critical Care, 2014, 18 (5), pp.516. 10.1186/s13054-014-0516-y. hal-01313020

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# Long-term outcome in early survivors of cardiogenic shock at the acute stage of myocardial infarction: a landmark analysis from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) Registry

Nadia Aissaoui¹,<fnref n="2" />, Etienne Puymirat¹,<fnref n="2" />,³, Tabassome Simon⁴,⁵,⁶, Eric Bonnefoy-Cudraz⁷, Denis Angoulvant⁸, Francois Schiele⁹, Hakim Benamer¹⁰, Philippe Quandalle¹¹, Fabrice Prunier¹², Eric Durand¹³, Laurence Berard⁴, Didier Blanchard¹⁴ and Nicolas Danchin¹,<fnref n="2" />*

**Abstract**

**Introduction:** There are little data about patients with cardiogenic shock (CS) who survive the early phase of acute myocardial infarction (AMI). The aim of this study was to assess long-term (5-year) mortality among early survivors of AMI, according to the presence of CS at the acute stage.

**Methods:** We analyzed 5-year follow-up data from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2005 registry, a nationwide French survey including consecutive patients admitted for ST or non-ST-elevation AMI at the end of 2005 in 223 institutions.

**Results:** Of 3670 patients enrolled, shock occurred in 224 (6.1%), and 3411 survived beyond 30 days or hospital discharge, including 99 (2.9%) with shock. Early survivors with CS had a more severe clinical profile, more frequent concomitant in-hospital complications, and were less often managed invasively than those without CS. Five-year survival was 59% in patients with, versus 76% in those without shock (adjusted hazard ratio (HR) = 1.72 [1.24-2.38], P = 0.001). The excess of death associated with CS, however, was observed only during the first year (one-year survival: 77% vs 93%, adjusted HR: 2.87 [1.85 to 4.46] P <0.001), while survival from one to 5 years was similar (76% vs 82%, adjusted HR: 1.06 [0.64 to 1.74]). Propensity score-matched analyses yielded similar results.

**Conclusions:** In patients surviving the early phase of AMI, CS at the initial stage carries an increased risk of death up to one year after the acute event. Beyond one year, however, mortality is similar to that of patients without shock.

**Trial registration:** ClinicalTrials.gov number, NCT00673036, Registered May 5, 2008.

**Introduction**

Despite considerable progress in the management of patients admitted for acute myocardial infarction (AMI), cardiogenic shock (CS) remains a major complication [1,2]. In-hospital mortality has declined due to early revascularization and improved overall management, however,

early mortality rates remain high; only about 50% of AMI patients developing CS are alive at one month [1-4].

Little data exist on the long-term outcomes of patients surviving the acute phase of CS following AMI [4-6]. Most studies report that patients with CS have an increased risk of death up to one year after the acute event. Beyond 1 year, mortality seems to be similar to that of patients without CS. However, most of these studies were performed in the 1990s., Marked reductions in AMI mortality have recently been reported, including among patients with CS [4-6].

<footnote>* Correspondence: nicoals.danchin@egp.aphp.fr
¹Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France</footnote>

<footnote n="2">²Faculty of Medicine, University Paris Descartes, Paris, France
Full list of author information is available at the end of the article</footnote>
The French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST MI) 2005 registry is a prospective, nationwide, observational study conducted at the end of 2005 in a large number of the French hospitals treating AMI patients [7,8]. It allows evaluation of the long-term outcome in acute ST-elevation and non-ST-elevation myocardial infarction patients with and without CS. The aim of the present study was to analyse long-term outcomes of early survivors of the acute phase, according to the presence of CS at the acute stage.

## Materials and methods

### Study population

The methods of the FAST-MI 2005 registry have been described in detail elsewhere [7,8]. Briefly, the primary objectives were to evaluate myocardial infarction (MI) management in real-life practice and to assess short- and long-term outcomes of patients admitted to ICUs for MI. Patients were consecutively recruited from ICU departments over a period of 1 month (October to November 2005), with a 1-month extension for patients with known diabetes mellitus. Participation in the study was offered to all French institutions, university teaching hospitals, general and regional hospitals, and private clinics with ICUs authorized to receive acute coronary syndromes (ACS). In each centre, a physician was in charge of the registry and provided a full list of all patients admitted to the unit. The number of participating centres was 223, representing 60% of all centres taking care of AMI patients in France at that time.

Inclusion criteria were (1) men or women, over 18 years old; (2) patients admitted within 48 h after symptom onset in an ICU for an AMI characterized by increased troponin or creatine kinase-MB associated with at least one of the following elements: symptoms compatible with myocardial ischaemia, appearance of pathologic Q-waves, or ST-T changes compatible with myocardial ischaemia (ST-segment elevation or depression, T-wave inversion); and (3) consent to take part in the study. Patients who died very soon after admission and for whom cardiac markers were not measured were included if they had compatible signs or symptoms associated with typical ST-segment changes. Exclusion criteria were (1) refusal to participate; (2) patients with MI who were admitted more than 48 h after symptom onset; (3) patients with iatrogenic MI, defined as MI occurring within 48 h of a therapeutic procedure (bypass surgery, coronary angio-plasty, or any other medical or surgical intervention); (4) ACS diagnosis invalidated in favour of another diagnosis; and (5) patients with unstable angina and no increase in cardiac biomarkers.

CS was defined as systolic blood pressure <90 mm Hg for ≥1 h not responsive to fluid administration alone, thought to be secondary to cardiac dysfunction, and

associated with signs of hypoperfusion or cardiac index ≤2.2 l/min/mm2 and pulmonary capillary wedge pressure >18 mm Hg [9,10].

All patients provided informed consent for their participation in the registry. The protocol was reviewed by the Committee for the Protection of Human Subjects in Biomedical Research of St Antoine University Hospital and the data file of the study was declared to and authorized by the French data protection committee (Commission Nationale Informatique et Liberté). Participating physicians were asked not change their usual therapeutic approach for the purpose of the survey. All the authors vouch for the fidelity of the study to the trial protocol, which is available at ClinicalTrials.gov number, NCT00673036 (Registered 5 May 2008).

Overall, 3,670 patients were included in the survey. Among them, 224 (6.1%) developed shock: 259 patients died in hospital or during the first 30 days following admission, and 3,411 patients survived the early phase (patients surviving the initial hospital stay and alive at 30 days) and were included in the present study.

### Data collection

Baseline characteristics, namely demographics (age, gender), risk factors (hypertension, body mass index >30 kg/m², diabetes, current smoking, hyperlipidaemia, family history), medical history (previous AMI, previous percutaneous coronary intervention (PCI), previous coronary artery bypass grafting, previous stroke, previous heart failure, prior peripheral arterial disease, previous chronic renal failure, previous chronic obstructive pulmonary disease and previous cancer), and previous medications (antiplatelet agents, statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB)s, beta-blockers and insulin) were collected prospectively and stored electronically as previously described.

Clinical presentation, and glycaemia at the time of admission were also collected and the last value of left ventricular ejection fraction (LVEF) during the hospital stay was recorded. We also recorded the use of cardiac procedures, in-hospital complications (re-infarction, stroke, major bleeding, the need for transfusion, ventricular fibrillation, new atrial fibrillation and second-and third-degree atrio-ventricular (AV) block) and medications (antiplatelet agents, diuretics, beta-blockers, ACE-inhibitors and lipid-lowering agents) used in the first 48 h and at hospital discharge in early CS survivors.

### Outcome

Mortality was assessed at 1 and 5 years both in patients with and without CS, who were discharged alive and were alive at one month (early survivors). Follow up was centralised at the French Society of Cardiology and dedicated research technicians contacted both physicians and patients
themselves, after checking patients' vital status in munici-
pal registries. Causes of death were obtained by direct
contact with patients' physicians or families, and from
the national causes of death registry. Two cardiologists,
unaware of patients' hospital course, adjudicated causes
of death as cardiovascular, non-cardiovascular, or un-
known. The rate of patients lost to follow up was 0.3% at
1 year, 2% at 3 years and 5% at 5 years.

**Statistical analysis**

Statistical analysis was performed using IBM SPSS 20.0 (IBM SPSS, Inc., Armonk, NY, USA) and NCSS 9.0.7 (NCSS, LLC, Kaysville, UT, USA). For quantitative variables, mean and standard deviations were calculated. Discrete variables are presented as percentages. Comparisons were performed with the chi-square or Fisher's exact test for discrete variables and with the unpaired t-test, or Wilcoxon sign-rank tests for continuous variables. Odds ratios (OR) or hazard ratios (HR) are presented with the 95% CI. Five-year mortality rates were calculated using the Kaplan-Meier method and comparisons were made using log-rank tests.

Because coronary artery disease remains unstable for
several months after an acute coronary syndrome, and
potent antithrombotic medications, such as dual anti-
platelet therapy, are recommended for 1 year following
AMI, we selected the 1-year time point for performing
landmark analyses: the analyses were performed with
1-year survival as the dependent variable in the popu-
lation of early survivors, and 5-year survival as the
dependent variable in the population of patients alive at
one year [11].

Correlates of 5-year mortality were determined using a
multivariate Cox backward analysis. The cumulative haz-
ard functions for each covariable were computed to assess
proportionality, and colinearity was verified by calculating
variance inflation factors. Shock was analysed as a time-
dependent variable, with the time-point set at 12 months
from the acute episode. Variables included in the final
multivariate models were selected ad hoc, based upon
their physiological relevance and potential to be associated
with outcomes; thus, we included variables likely to influ-
ence outcome negatively (age, history of heart failure, his-
tory of diabetes, history of prior AMI, history of stroke,
history of peripheral artery disease, anemia on admission)
or positively (history of hypertension, current smoking,
revascularisation by percutaneous coronary intervention
or surgery, early use of low molecular weight heparin,
glycoprotein IIB-IIIa inhibitors, and discharge medica-
tions: aspirin, clopidogrel, statins, ACE-inhibitors, ARBs,
beta-blockers) as well as sex, type and region of institu-
tion, and type of MI (segment-elevation myocardial infarc-
tion (STEMI) versus non-segment-elevation myocardial
infarction (NSTEMI).

In addition, to assess the potential role of CS on late
mortality, we calculated propensity scores for having
presented CS, using logistic regression analysis 1) in
patients alive at hospital discharge and at 30 days, and 2)
in patients who were alive at one year (c-statistic = 0.76
for both propensity scores). Cohorts with and without
CS were constituted, matched on the propensity scores
(3-to-1 matching: population of early survivors, 94 pa-
tients with CS, 282 patients without CS; population of
1-year survivors, 73 patients with CS, 217 patients with-
out CS), and their outcomes were compared using log-
rank tests. For calculating the propensity scores, we
used baseline characteristics, early management including
revascularisation procedures and antithrombotic medica-
tions, in-hospital complications (re-infarction and major
bleeding) and discharge medications. LVEF and medi-
cations indicated for heart failure (renin angiotensin aldos-
terone inhibitors and beta-blockers) were not included in
the model to avoid over-adjustment. For all analyses, a
P-value <0.05 was considered significant.

**Results**

Baseline characteristics of all 30-day survivors

Among the 3,411 early survivors, 99 (2.9%) had developed CS at the acute stage. Patients with CS were significantly older and had more comorbid conditions (Table 1). Clinical presentation at admission of patients with CS was more severe, and they had developed more complications during hospitalization. The use of revascularization procedures was comparable in the two groups.

Five-year survival

Five-year survival was 59% in early survivors with CS,
compared with 76% in early survivors without shock
(P <0.001) (Figure 1).

Landmark analyses in the overall population

One-year survival was 93% in early survivors without CS and 77% in patients with CS. Cause of death analysis showed that cardiovascular death was as frequent in CS patients (65.2%) as in non-CS patients (66.3%). Five-year survival was 76% in the 76 CS patients surviving at one year, versus 82% in the 3,072 non-CS patients surviving at one year (an additional table shows this in more detail; see Additional file 1). Beyond 1 year, there was a non-significant trend towards increased cardiovascular mortality in CS patients (55.6% versus 36.3%), but with fewer deaths of unknown cause (22.2% versus 31.1%).

In the time-dependent Cox multivariate model, CS
was independently associated with increased hazard for
death at 12 months (HR: 2.87, 95% CI: 1.85, 4.46, P <0.001),
but carried no increased risk from 1 year to 5 years
(HR 1.06, 95% CI: 0.64, 1.74).
<table><caption>**Table 1** Baseline characteristics of patients surviving at 30 days and hospital discharge according to presence of cardiogenic shock at the acute stage</caption><thead><tr><th></th><th>No shock (n = 3,312)</th><th>Shock (n = 99)</th><th>P-value</th></tr></thead><tbody><tr><td>Age, years, mean ± SD</td><td>66 ± 14</td><td>70 ± 13</td><td>&lt;0.001</td></tr><tr><td>Sex, female, n (%)</td><td>1014 (30.6)</td><td>37 (37.4)</td><td>0.43</td></tr><tr><td>Body mass index, Kg/m², mean ± SD</td><td>27.2 ± 4.7</td><td>26.5 ± 4.9</td><td>0.15</td></tr><tr><td><strong>Risk factors, n (%)</strong></td><td></td><td></td><td></td></tr><tr><td>Hypertension</td><td>1949 (58.8)</td><td>62 (62.6)</td><td>0.45</td></tr><tr><td>Diabetes mellitus</td><td>1166 (35.2)</td><td>37 (37.4)</td><td>0.65</td></tr><tr><td>Current smoking</td><td>990 (29.9)</td><td>27 (27.3)</td><td>0.59</td></tr><tr><td>Hypercholesterolemia</td><td>1622 (49.0)</td><td>44 (44.4)</td><td>0.37</td></tr><tr><td>Family history of coronary artery disease</td><td>796 (24.0)</td><td>11 (11.1)</td><td>0.003</td></tr><tr><td><strong>Previous medical history, n (%)</strong></td><td></td><td></td><td></td></tr><tr><td>Myocardial infarction</td><td>591 (17.8)</td><td>23 (23.2)</td><td>0.17</td></tr><tr><td>Percutaneous coronary intervention</td><td>472 (14.3)</td><td>13 (13.1)</td><td>0.75</td></tr><tr><td>Coronary artery bypass graft</td><td>186 (5.6)</td><td>8 (8.1)</td><td>0.30</td></tr><tr><td>Stroke</td><td>168 (5.1)</td><td>5 (5.1)</td><td>0.99</td></tr><tr><td>Peripheral arterial disease</td><td>316 (9.6)</td><td>17 (17.2)</td><td>0.01</td></tr><tr><td>Heart failure</td><td>172 (5.2)</td><td>9 (9.1)</td><td>0.09</td></tr><tr><td>Chronic kidney disease</td><td>172 (5.2)</td><td>6 (6.1)</td><td>0.71</td></tr><tr><td>Chronic obstructive pulmonary disease</td><td>141 (4.3)</td><td>9 (9.1)</td><td>0.02</td></tr><tr><td>Cancer</td><td>218 (6.6)</td><td>4 (4.0)</td><td>0.31</td></tr><tr><td><strong>Previous medications, n (%)</strong></td><td></td><td></td><td></td></tr><tr><td>Antiplatelet agents</td><td>1058 (31.9)</td><td>35 (35.4)</td><td>0.47</td></tr><tr><td>Statins</td><td>930 (28.1)</td><td>32 (32.4)</td><td>0.35</td></tr><tr><td>Angiotensin-converting enzyme inhibitor</td><td>640 (19.3)</td><td>33 (33.3)</td><td>0.001</td></tr><tr><td>Angiotensin receptor blockers</td><td>515 (15.5)</td><td>13 (13.1)</td><td>0.52</td></tr><tr><td>Beta-blockers</td><td>828 (25.0)</td><td>28 (28.3)</td><td>0.46</td></tr><tr><td>Insulin</td><td>335 (10.1)</td><td>13 (13.1)</td><td>0.33</td></tr><tr><td><strong>Current episode, n (%)</strong></td><td></td><td></td><td></td></tr><tr><td>Typical chest pain</td><td>2538 (79.0)<br>(n = 3213)</td><td>58 (65.2)<br>(n = 89)</td><td>0.002</td></tr><tr><td>Resuscitated cardiac arrest</td><td>31 (0.9)</td><td>10 (10.1)</td><td>&lt;0.001</td></tr><tr><td>Segment-elevation myocardial infarction</td><td>1688 (50.9)</td><td>54 (54.5)</td><td>0.47</td></tr><tr><td>Anaemia on admission</td><td>689 (21.5) (n = 3202)</td><td>35 (36.8) (n = 95)</td><td>&lt;0.001</td></tr><tr><td>Admission glycaemia, mg/dl, mean ± SD</td><td>156 ± 77</td><td>203 ± 109</td><td>&lt;0.001</td></tr><tr><td>Left ventricular ejection fraction, %, mean ± SD</td><td>53 ± 13</td><td>42 ± 16</td><td>&lt;0.001</td></tr><tr><td><strong>Medications within the first 48 h, n (%)</strong></td><td></td><td></td><td></td></tr><tr><td>Low molecular-weight heparin</td><td>2159 (65.1)</td><td>45 (45.5)</td><td>&lt;0.001</td></tr><tr><td>Clopidogrel</td><td>2882 (86.9)</td><td>81 (81.8)</td><td>0.14</td></tr><tr><td>GP IIb-IIIa inhibitors</td><td>1236 (37.3)</td><td>35 (35.4)</td><td>0.69</td></tr><tr><td><strong>Procedures during hospital stay, n (%)</strong></td><td></td><td></td><td></td></tr><tr><td>Coronary angiography</td><td>2898 (87.4)</td><td>79 (79.8)</td><td>0.03</td></tr><tr><td>Percutaneous coronary intervention</td><td>2186 (65.9)</td><td>60 (60.9)</td><td>0.27</td></tr><tr><td>Coronary artery bypass graft</td><td>140 (4.2)</td><td>4 (4.0)</td><td>0.93</td></tr></tbody></table>
<table><caption>**Table 1** Baseline characteristics of patients surviving at 30 days and hospital discharge according to presence of cardiogenic shock at the acute stage (Continued)</caption><thead><tr><th></th><th></th><th></th><th></th></tr></thead><tbody><tr><td colspan="4"><strong>In-hospital complications, n (%)</strong></td></tr><tr><td>Re-infarction</td><td>51 (1.5)</td><td>3 (3.0)</td><td>0.24</td></tr><tr><td>Stroke</td><td>19 (0.6)</td><td>4 (4.0)</td><td>&lt;0.001</td></tr><tr><td>Major bleeding</td><td>54 (1.6)</td><td>7 (7.1)</td><td>&lt;0.001</td></tr><tr><td>Transfusion</td><td>119 (3.6)</td><td>13 (13.1)</td><td>&lt;0.001</td></tr><tr><td>Ventricular fibrillation</td><td>44 (1.3)</td><td>12 (12.1)</td><td>&lt;0.001</td></tr><tr><td>Atrial fibrillation, new</td><td>150 (4.5)</td><td>25 (25.3)</td><td>&lt;0.001</td></tr><tr><td>Atrio-ventricular block</td><td>39 (1.2)</td><td>4 (4.0)</td><td>0.01</td></tr><tr><td colspan="4"><strong>Medications at discharge, n (%)</strong></td></tr><tr><td>Aspirin</td><td>3039 (92.3)</td><td>88 (90.7)</td><td>0.58</td></tr><tr><td>Clopidogrel</td><td>2662 (81.0)</td><td>78 (7906)</td><td>0.73</td></tr><tr><td>Statins</td><td>2760 (84.4)</td><td>70 (72.9)</td><td>0.002</td></tr><tr><td>Beta-blockers</td><td>2566 (78.7)</td><td>62 (65.3)</td><td>0.002</td></tr><tr><td>Angiotensin-converting enzyme inhibitors</td><td>2030 (62.9)</td><td>66 (68.8)</td><td>0.24</td></tr><tr><td>Angiotensin receptor blockers</td><td>270 (8.6)</td><td>4 (4.3)</td><td>0.15</td></tr><tr><td>Aldosterone receptor blockers</td><td>153 (4.9)</td><td>17 (18.3)</td><td>&lt;0.001</td></tr><tr><td>Loop diuretics</td><td>613 (19.7)</td><td>53 (57.6)</td><td>&lt;0.001</td></tr><tr><td>Digoxin</td><td>17 (0.5)</td><td>0</td><td>0.48</td></tr><tr><td>Nitrates</td><td>581 (18.6)</td><td>25 (27.2)</td><td>0.04</td></tr><tr><td>Amiodarone</td><td>232 (7.0)</td><td>24 (24.2)</td><td>&lt;0.001</td></tr></tbody></table>

## Propensity-score-matched population

Separate analyses on propensity-score-matched populations confirmed these data: 1-year mortality in propensity-score-matched cohorts of early survivors was significantly higher in those with CS at the acute stage (HR: 2.49, 95% CI: 1.43, 4.33, *P* = 0.001) (Figure 2 and Additional file 2 show this in more detail).

In contrast, 5-year mortality in propensity-score-matched cohorts of 1-year survivors was similar in patients with CS at the acute stage (25%) and in those without (23%) (HR: 1.11, 95% CI: 0.65, 1.91, *P* = 0.69) (Figure 3 and Additional file 3 show this in more detail). In this population, similar characteristics were correlated with long-term survival in patients with or without CS (see Additional file 4).

<figure><img src="image_2.png" /><figcaption>**Figure 1** Five-year survival in patients surviving at 30 days and hospital discharge according to the cardiogenic shock status. HR, hazard ratio.</figcaption></figure>
<figure><img src="image_3.png" /><figcaption>**Figure 2** Landmark analysis: 1-year survival in propensity-score-matched cohorts of early survivors.</figcaption></figure>

## Predictors of 1-year death in early survivors with shock

Using Cox multivariate analysis in the population of patients with CS, most prognostic factors for death at 1 year were un-modifiable (older age, diabetes mellitus, history of chronic kidney disease); likewise, patients with STEMI had a markedly increased risk, compared with NSTEMI patients (HR: 4.31; 95% CI 1.38, 13.44). When STEMI patients were categorised according to use of reperfusion therapy at the acute stage, and compared with NSTEMI patients, lack of reperfusion in STEMI patients was related to poorer survival (HR: 6.44, 95% CI: 1.91, 21.7 versus NSTEMI), while only a trend persisted

for STEMI patients with reperfusion therapy (HR: 2.87, 95% CI: 0.69, 11.9 versus NSTEMI). None of the discharge medications were associated with improved survival, although non-significant trends were observed for statins (HR: 0.43, 95% CI: 0.10, 1.75) and clopidogrel (HR: 0.37, 95% CI: 0.08, 1.60).

## Predictors of 5-year death in 1-year survivors with shock

In 1-year survivors who had CS at the acute stage, both older age, and previous history of coronary artery disease were associated with lower survival rate. Revascularisation procedures during the initial hospital stay were

<figure><img src="image_4.png" /><figcaption>**Figure 3** Landmark analysis: from one year to five years. Five-year survival in propensity-score-matched cohorts of patients surviving at one year. HR, hazard ratio.</figcaption></figure>
associated with lower 5-year mortality (HR: 0.12, 95% CI: 0.03, 0.42).

Discussion

The main finding of the present study in a contemporary
real-world population of AMI patients, is that early
survivors of CS still have higher mortality at 1 year, com-
pared with early survivors without CS. Beyond 1 year,
however, mortality up to 5 years becomes comparable
between patients with or without CS at the acute stage,
although the former have a more severe clinical profile.
Mortality is higher in STEMI patients with CS than in
NSTEMI patients with CS, and early revascularization is
associated with better long-term survival.

Most data available on the long-term outcome of CS
patients surviving the early phase of AMI were obtained
before major changes in AMI treatment were widely
implemented [3-5]. They are derived from populations
selected for inclusion into randomized trials, or less fre-
quently from real-life populations. Patient inclusion was
usually before the year 2000, at a time when outcomes
were notably poorer than nowadays [12].

Despite improved early management, early mortality
in CS patients remains considerably higher than that of
patients without CS [2,13]. In prior studies the reported
overall long-term survival of CS patients surviving the
early period varies widely from 12% to 73% at 5 years
[4-6,14,15]. In the large GUSTO-1 population of STEMI
patients [5], mortality at 11 years in early survivors was
45% in patients with CS, compared with 31% in patients
without CS. Patients included in the trial were relatively
young and had to fulfill the trial inclusion criteria, which
included early presentation after symptom onset, and all
received intravenous fibrinolytic therapy. Our patients
were enrolled in 2005, and more than 80% of patients
underwent myocardial revascularization. This clearly
differentiates our study, which is therefore clinically
relevant in the current era.

To the best of our knowledge, there has been only one
recent report on a large contemporary series of patients
with long-term follow up after CS [16]. The data, gath-
ered from the CRUSADE registry cross-linked with the
Medicare administrative database, were limited to older
(≥65 years) patients and only included NSTEMI patients.
Four-year survival in CS early survivors was 48%, com-
pared with 56.5% in non-CS survivors. Another novelty
of our study is that both STEMI and NSTEMI patients
were included.

In this population, 5-year survival of CS patients alive
after the acute phase was 59%. Improvements in primary
angioplasty and adjunctive pharmacotherapy are likely to
explain higher survival rates [4,5] in recent series. Of
note, a majority of our patients had undergone myocar-
dial revascularization during the initial hospital stay and

early revascularization was associated with better long-
term survival. In the SHOCK trial, early revascularization
significantly reduced 6-year mortality in early survivors by
41% (absolute risk reduction: 18%) [4]. Our study un-
derlines the potential interest of performing immediate
coronary reperfusion in CS, as it is also associated with
improved long-term survival. In this regard, developing
networks for the management of AMI patients, particu-
larly for the most severely affected patients, seems import-
ant to improve both early and long-term outcomes.

A consistent finding in all studies, including ours, is
similar mortality beyond 1 year in patients with or with-
out CS, regardless of the period studied or the inclusion
of STEMI or NSTEMI patients. The GUSTO-1 study
confirmed similar long-term survival between CS and
non-CS patients who were alive at 1 year. In the much
more recent CRUSADE registry in NSTEMI patients
65 years of age or older, no difference was observed
between patients with or without CS, once they had
survived the first months following the acute episode
[16]. The reasons for late survival becoming similar are
unclear, especially when considering the difference in
LVEF between patients who have developed CS and
those who have not. Mechanisms leading to CS include
left ventricular dysfunction, systemic inflammatory re-
sponse, activation of complement, release of cytokines,
and expression of inducible nitric oxide synthase [4,14,17].
The recent IABP SHOCK II trial confirmed the presence
of a high degree of inflammatory response in CS patients,
irrespective of the management strategy, and that CS
could be present even in the absence of profound LV
dysfunction (median LVEF 35%) [17]. The resolution of
severe ischaemia and/or neurohormonal abnormalities
may explain the potential reversibility of shock [4,14].
Also, the increasing use of medications such as beta-
blockers, ACE-inhibitors, ARBs or aldosterone blockers in
patients with CS during the hospital admission may have
participated in their improved long-term survival; of note,
the percentage of patients with CS receiving beta-blockers
increased from 68% at discharge to 81% at one year, and
the percentage of patients receiving either ACE-inhibitors
or ARBs marginally increased from 78% to 81%.

Strengths and limitations

Our study has the usual limitation of observational data.
Namely, no causality can be inferred from the associations
we observed. In addition, the sample size of patients with
CS was small, and subgroup analyses were therefore un-
realistic. We excluded patients admitted more than 48 h
after symptoms onset. These patients could have devel-
oped CS. Likewise, we were not able to assess the poten-
tial effect of implantable cardioverter defibrillators or of
cardiac resynchronization therapy, as very few patients
were implanted during the initial hospital stay (one in the
CS group and six in the patients without CS). Conversely, our population was extremely well-characterized and reflected a real-world population. Also, it included both STEMI and NSTEMI patients and the rate of patients lost to follow up was low.

## Conclusion

The long-term outcome for early survivors of CS is worse than that of patients without CS. Patients who survive the first year after the acute event, however, have a 5-year survival rate similar to that of non-CS patients. This divergence between early, semi-early, and long-term outcomes has remained consistent since the late 1980s and underlines the importance of improving short-term outcome by the early detection and management of CS, including early myocardial revascularisation.

## Key messages

* Early survivors of CS still have a higher mortality at 1 year, compared with early survivors without CS

* Beyond 1 year, however, mortality up to 5 years becomes comparable between patients with or without CS at the acute stage, although the former have a more severe initial profile

* Mortality is higher in STEMI patients with CS than in NSTEMI patients with CS

* Early revascularization is associated with better long-term survival in CS patients following acute myocardial infarction

## Additional files

Additional file 1: Baseline, in-hospital and 1-year characteristics of the patients alive at one year.

Additional file 2: Propensity-score-matched cohorts of patients alive at hospital discharge and 30 days.

Additional file 3: Propensity-score-matched cohorts of patients alive at one year.

Additional file 4: Characteristics of patients in the propensity-score-matched cohorts of 1-year survivors according to survival status at 5 years.

## Abbreviations

ACE: angiotensin-converting enzyme; AMI: acute myocardial infarction; ARB: angiotensin-receptor blocker; AV: atrio-ventricular; CS: cardiogenic shock; FAST-MI: French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction; LVEF: left ventricular ejection fraction; MI: myocardial infarction; NSTEMI: non-segment-elevation myocardial infarction; STEMI: segment-elevation myocardial infarction.

## Competing interests

N Aissaoui, none; E Puymirat, none; T Simon, research grants: Astra-Zeneca, Daiichi-Sankyo, Eli-Lilly, Glaxo-Smith-Kline, MSD, Novartis, Pfizer, sanofi-aventis, and Servier and speaker and consulting fees: AstraZeneca, Bayer-Schering, Eli-Lilly, and Sanofi-Aventis; E Bonnefoy, significant research grants: Astra-Zeneca, Daiichi-Sankyo, Gambro; D Angoulvant, research grants: Eli-Lilly, Abbott and speaker and consulting fees: Astra Zeneca, Eli-Lilly, Novartis, Bayer, MSD, Amgen, Pfizer; F Schiele, none; H Benamer, none; P Quandalle,

none; F Prunier, Servier, significant research grant; E Durand, none; L Berard, none; D Blanchard, none; N Danchin, Servier, significant, research grant; Pfizer, significant, research grant; Sanofi-Aventis, significant, research grant.

## Authors' contributions

NA conceived the study, drafted the manuscript, wrote the manuscript and revised the manuscript. EP helped to draft the manuscript and perform statistical analysis and helped to revise the manuscript. TS helped in acquisition of data, drafting the manuscript and statistical analysis. EBC helped in acquisition of data, and helped to conceive the study and correct the manuscript. DA helped in acquisition of data, interpretation of data and correction of the manuscript. FS participated in the design of the study, performed the statistical analysis and helped to revise the manuscript. HB helped in acquisition of data, interpretation of data, and drafting and revising the manuscript. PQ helped in acquisition of data, drafting the manuscript and performing the revision. FP helped in acquisition of data, drafting the manuscript and statistical analysis. ED helped in acquisition of data and revised it critically for important intellectual content. LB helped in acquisition of data, drafting the manuscript and statistical analysis. DB helped in acquisition and interpretation of data and revised it critically for important intellectual content. ND conceived of the study, performed the statistical analysis and the interpretation of data, and corrected the manuscript. All authors read the manuscript and gave final approval of the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

## Acknowledgements

We are indebted to all patients having accepted to participate in the surveys, and to all participating physicians. The FAST-MI 2005 registry is a registry of the French Society of Cardiology, funded by unrestricted grants from Pfizer and Servier, and an additional grant from the Caisse Nationale d'Assurance Maladie. Special thanks to ICTA contract research organisation (Fontaine-lès-Dijon, France), and the devoted personnel of the URCEST (Assistance Publique des Hôpitaux de Paris and University Paris 6) and INSERM U 558 (Toulouse). Special thanks to Vincent Bataille, for his careful data management, to Benoit Pace (Société Française de Cardiologie) for his invaluable assistance in designing the electronic CRF, and to Geneviève Mulak (Société Française de Cardiologie) and Elodie Drouet, who supervised the patients' follow-up.

## Author details

¹Department of Cardiology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France. ²Faculty of Medicine, University Paris Descartes, Paris, France. ³INSERM U970, Paris Cardiovascular Research Center PARCC, Paris, France. ⁴Assistance Publique-Hôpitaux de Paris, CHU St Antoine, Paris, France. ⁵INSERM U-698, Paris, France. ⁶UPMC, Paris 06, Paris, France. ⁷Intensive Cardiac Care Unit Hôpital Cardio-pneumologique, Lyon, France. ⁸Department of Cardiology CHRU de Tours and EA 4245 Faculty of Medicine, University François Rabelais, Tours, France. ⁹CHU Besançon, Besançon, France. ¹⁰Hôpital Privé Jacques Cartier, Massy, France. ¹¹Hôpital Victor Provo, Roubaix, France. ¹²Department of Cardiology, CHU Angers, and I'UNAM Université, Laboratoire Cardioprotection Remodelage et Thrombose, Angers, France. ¹³CHU de Rouen, Rouen, France. ¹⁴Clinique St Gatien, Tours, France.

Received: 25 April 2014 Accepted: 28 August 2014

Published online: 19 September 2014

## References

1. Babaev A, Frederick PD, Pasta DJ, Every N, Sichrovsky T, Hochman JS, for the NRMI Investigators: *Trends in management and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock*. JAMA 2005, **294**:448–454.

2. Aissaoui N, Puymirat E, Tabone X, Charbonnier B, Schiele F, Lefèvre T, Durand E, Blanchard D, Simon T, Cambou JP, Danchin N: *Improved outcome of cardiogenic shock at the acute stage of myocardial infarction: a report from the USIK 1995, USIC 2000, and FAST-MI French nationwide registries*. *Eur Heart J* 2012, **33**:2535–2543.

3. Goldberg RJ, Spencer FA, Gore JM, Lessard D, Yarzebski J: *Thirty-year trends (1975 to 2005) in the magnitude of, management of, and hospital death rates associated with cardiogenic shock in patients with acute*
myocardial infarction: a population-based perspective. *Circulation* 2009, **119**:1211–1219.

4. Hochman JS, Sleeper LA, Webb JG, Dzavik V, Buller CE, Aylward P, Col J, White HD, SHOCK Investigators: Early revascularization and long-term survival in cardiogenic shock complicating acute myocardial infarction. *JAMA* 2006, **295**:2511–2515.

5. Singh M, White J, Hasdai D, Hodgson PK, Berger PB, Topol EJ, Calif RM, Holmes DR Jr: Long-term outcome and its predictors among patients with ST-segment elevation myocardial infarction complicated by shock: insights from the GUSTO-I trial. *J Am Coll Cardiol* 2007, **50**:1752–1758.

6. Tedesco JV, Williams BA, Wright RS, Reeder GS, Dvorak D, Kopecky SL, Miller WL, Coronary Care Unit Group: Baseline comorbidities and treatment strategy in elderly patients are associated with outcome of cardiogenic shock in a community-based population. *Am Heart J* 2003, **146**:472–478.

7. Cambou JP, Simon T, Mulak G, Bataille V, Danchin N: The French registry of Acute ST elevation or non-ST-elevation Myocardial Infarction (FAST-MI): study design and baseline characteristics. *Arch Mal Coeur Vaiss* 2007, **100**:524–534.

8. Danchin N, Coste P, Ferrières J, Steg PG, Cottin Y, Blanchard D, Belle L, Ritz B, Kirkorian G, Angioi M, Sans P, Charbonnier B, Eltchaninoff H, Guéret P, Khalife K, Asseman P, Puel J, Goldstein P, Cambou JP, Simon T, FAST-MI Investigators: Comparison of thrombolysis followed by broad use of percutaneous coronary intervention with primary percutaneous coronary intervention for ST-segment-elevation acute myocardial infarction: data from the french registry on acute ST-elevation myocardial infarction (FAST-MI). *Circulation* 2008, **118**:268–276.

9. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK, for the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. *Circulation* 2004, **110**:588–636.

10. Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, Filippatos G, Fox K, Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M, ESC Committee for Practice Guidelines (CPG), Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, et al: Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. *Eur Heart J* 2008, **29**:909–945.

11. Dafni U: Landmark analysis at the 25-year landmark point. *Circ Cardiovasc Qual Outcomes* 2011, **4**:363–371.

12. Puymirat E, Simon T, Steg PG, Schiele F, Guéret P, Blanchard D, Khalife K, Goldstein P, Cattan S, Vaur L, Cambou JP, Ferrières J, Danchin N, USIK USIC 2000 Investigators; FAST MI Investigators: Association of changes in clinical characteristics and management with improvement in survival among patients with ST-elevation myocardial infarction. *JAMA* 2012, **308**:998–1006.

13. Jeger RV, Radovanovic D, Hunziker PR, Pfisterer ME, Stauffer JC, Erne P, Urban P, AMIS Plus Registry Investigators: Ten-year trends in the incidence and treatment of cardiogenic shock. *Ann Intern Med* 2008, **149**:618–626.

14. Hochman JS: Cardiogenic shock complicating acute myocardial infarction: expanding the paradigm. *Circulation* 2003, **107**:2998–3002.

15. Lindholm MG, Køber L, Boesgaard S, Torp-Pedersen C, Aldershvile J, Trandolapril Cardiac Evaluation study group: Cardiogenic shock complicating acute myocardial infarction; prognostic impact of early and late shock development. *Eur Heart J* 2003, **24**:258–265.

16. Bagai A, Chen AY, Wang TY, Alexander KP, Thomas L, Ohman EM, Hochman JS, Peterson ED, Roe MT: Long-term outcomes among older patients with non-ST-segment elevation myocardial infarction complicated by cardiogenic shock. *Am Heart J* 2013, **166**:298–305.

17. 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, Böhm M, Ebelt H, Schneider S, Schuler G, Werdan K, IABP-SHOCK II Trial Investigators: Intraaortic balloon support for myocardial infarction with cardiogenic shock. *N Engl J Med* 2012, **367**:1287–1296.

doi:10.1186/s13054-014-0516-y

Cite this article as: Aissaoui et al.: Long-term outcome in early survivors of cardiogenic shock at the acute stage of myocardial infarction: a landmark analysis from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) Registry. *Critical Care* 2014 **18**:516.

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