European Heart Journal (2018) 39, 1075–1077 EDITORIAL

doi:10.1093/eurheartj/ehy069

Reperfusion delay in patients with high-risk

ST-segment elevation myocardial infarction:
every minute counts, much more than suspected

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William Wijns1* and Christoph K. Naber2
1
The Lambe Institute for Translational Medicine and Curam, National University of Ireland Galway, and Saolta University Healthcare Group, Galway, Ireland; and 2Contilia Heart
and Vascular Centre, Department of Cardiology and Angiology, Elisabeth Krankenhaus Essen, Germany

Online publish-ahead-of-print 14 February 2018

This editorial refers to ‘Impact of treatment delay on mor-

.. within 24 h. The main reasons for exclusion were as follows: interhospital
..
tality in ST-segment elevation myocardial infarction (STEMI) .. transfer from a non-PCI centre (n = 3.025), self-transportation (n =
patients presenting with and without haemodynamic insta-
.. 2.077), and STEMI during hospital admission (n = 483). All patients with
..
bility: results from the German prospective, multicentre .. the following conditions were included: pre-hospital resuscitation for out
..
FITT-STEMI trial’†, by K.H. Scholz et al., on page 1065. .. of hospital cardiac arrest (OHCA = 9.5%), cardiogenic shock (CS =
.. 5.5%), and fibrinolysis (1.1%). Patients with brain damage were included,
..
Study director Karl H. Scholz, corresponding author Thomas Meyer, .. and global in-hospital mortality was 8%.
and their co-authors are publishing very important findings on the .. The external validity of the findings was verified with the use of inde-
..
impact of treatment delays on mortality in ST-segement elevation .. pendent surveys from insurance reimbursement files and German hos-
myocardial infarction (STEMI) patients treated with primary percuta- .. pital quality reports. Of note, this investigator group serves a
..
neous coronary intervention (PCI) in the environment of a fully .. population of 10 million (12% of the population of Germany), with cur-
developed Emergency Medical Service (EMS).1
.. rently 5.500 STEMI cases per year, consistent with the global incidence
..
The data have been collected in the context of the ongoing FITT- .. of hospital-treated STEMI cases in the entire country.
..
STEMI trial (NCT 00794001) in Germany, a prospective, observatio- .. Statistical analyses included logistic regression modelling to identify
nal, registry-based study involving a consortium of nearly 50 hospital .. predictors of in-hospital mortality with FMC to balloon time as the
..
systems committing to enrol prospectively all STEMI patients pre- .. independent variable, after adjustment for potential confounders.
senting within <24 h after onset of symptoms. The study started in ..
..
October 2007 and is planned to continue until December 2021 after ..
enrolment of 50 000þ patients. Key strategies for reducing door to
.. Main study findings
..
balloon (D2B) time2 and standard quality indicators3 were endorsed ..
by all participating hospitals. Phase I evaluates whether formal data
.. In patients treated within 60–180 min from FMC, there is a linear
.. relationship between mortality and treatment delay. Patients strati-
collection and regular feedback can improve first medical contact ..
.. fied by haemodynamic instability in four groups showed increasing
(FMC) to PCI treatment delays. Phase II investigates whether survival .. mortality rates (P < 0.0001): 3% in patients in a stable condition (n =
can be improved by behavioural changes triggered by quarterly feed- ..
.. 10.776), 16% after OHCA but in a stable condition (n = 369), 39% in
back data analysis with cardiology, emergency department, and EMS .. patients with CS (n = 699), and 45% in patients with OHCA and CS
staff. Outcome measures are the contact to balloon (C2B) time and ..
.. (n = 831). In the two patient groups with haemodynamic instability,
mortality at various time intervals up to 1 year (NCT 00794001). ..
.. there was a steep increase in mortality with prolonged treatment
.. delays, as shown in their figure 2.1 This strong association between
..
Present study population .. mortality and treatment delays can be summarized by a number of
.. memorable quotes (Table 1). Adjusted models show that treatment
..
As many as 12 675 patients with treatment delays of <360 min were .. delay remains a significant independent predictor of survival, after
included in the present analysis, out of all 20 130 patients presenting
.. accounting for clinical and procedural confounders, including disease

The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
†
doi:10.1093/eurheartj/ehy004.
* Corresponding author. The Lambe Institute for Translational Medicine, National University of Ireland Galway, University Road, Galway, Ireland. Tel: þ353 91 495 178,
Fax: þ353 91 494 509, Email: william.wyns@nuigalway.ie
Published on behalf of the European Society of Cardiology. All rights reserved. V
C The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
1076
..
Table 1 Impact of reperfusion delay in high-risk
.. use of balloon pump, extracorporeal membrane oxygenation
.. (ECMO), or assist devices.
STEMI patients: memorable quotes from the FITT-
STEMI trial
Mortality was 3.9% with C2B delay <_90 min vs. 12.2% with C2B delay
>90 min (P < 0.0001)
When patients with cardiogenic chock were treated <_90 min after
first medical contact, there was pronounced survival benefit: odds
ratio 0.49, 95% confidence interval 0.36–0.66 (P < 0.0001)
In cardiogenic shock patients, one additional life could be saved out
of five patients treated by reducing the C2B time to <_90 min
When patients with out of hospital cardiac arrest were treated <_90
min after first medical contact, there was pronounced survival
benefit: odds ratio 0.56, 95% confidence interval 0.38–0.82
(P = 0.0031)
In cardiogenic shock patients (no out of hospital cardiac arrest), every
10 min treatment delay results in 3.31 additional deaths per 100
PCI-treated patients
In cardiogenic shock patients with out of hospital cardiac arrest, every
10 min treatment delay results in 2.09 additional deaths per 100
PCI-treated patients
In out of hospital cardiac arrest patients (no cardiogenic shock), every
10 min treatment delay results in 1.34 additional deaths per 100
PCI-treated patients
In stable STEMI patients (no cardiogenic shock, no out of hospital car-
diac arrest), every 10 min treatment delay results in 0.34 additional
deaths per 100 PCI-treated patients
C2B, contact to balloon; PCI, percutaneous coronary intervention; STEMI,
ST-segment elevation myocardial infarction.
severity assessed by TIMI risk score. The particular importance of
implementing and monitoring best practices is nicely demonstrated
by the driver analysis reported in their table 21 showing that C2B
delays are shorter with pre-hospital ECG recording (– 5.4 min), pre-
announcement of patient arrival (–17.5 min), or direct transfer to the
catheterization laboratory (– 33.2 min). Of note, high-risk conditions
per se are associated with longer delays: þ 6.9 min in patients with CS
and þ 17.3 min in patients with OHCA, stressing the need for contin-
ued optimization of the care pathway in these subsets, representing
15% of all patients admitted with STEMI.
Study limitations
As mentioned by the authors, the main limitation of the study design
is the following: one cannot exclude that ‘late arrival of very sick
patients could be the consequence of their poor condition, rather
than the cause of increased mortality’. However, results of the
regression analyses and the fact that both C2B time and TIMI risk
score did confer independent prognostic significance are reassuring.
It should be mentioned that these results were obtained in the con-
text of a fully developed primary PCI (PPCI) programme engaging all
stakeholders. High performance EMS was available, with trained
physicians on board during transportation. The effect of a number of
additional confounders on individual outcomes cannot be measured,
such as the quality of resuscitation, the effect of hypothermia, or the
Editorial
..
.. The German prospective, multicentre FITT-STEMI trial is ongoing.
.. With increasing sample size, the investigators will be able to evaluate
..
.. whether feedback-driven quality control management of timely
.. reperfusion has a positive causal effect on survival. By comparing tem-
..
.. poral changes in outcomes, the relationship between gain in survival
.. and decreased C2B time will become assessable. Lastly, data on lon-
..
.. ger term mortality outcomes are eagerly awaited.
..
..
..
.. Study relevance
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..
..
.. The importance of this work cannot be overemphasized. The most
..
.. recent ESC Guidelines have insisted that the maximum expected
.. delay between FMC and PPCI should be considered as the essential
..
.. time target for clinical decision and the quality metric for care deliv-
.. ery, and not just the in-hospital D2B time.3 While the D2B time has
..
.. been used extensively as a quality measure of the in-hospital
.. processes, few data were available thus far on the components of
..
.. pre-hospital delay and their impact on outcomes. The current study
..
.. supports the recommendation to keep the FMC to treatment delay
.. as short as possible, in any case below 120 min. In addition, the study
..
.. by Scholz et al.1 provides, for the first time, impressive data on
.. the strong impact of C2B time on in-hospital mortality in patients
..
.. with CS and/or OHCA, and shows that 90 min should be the
.. appropriate time target in high-risk cases. Guideline implementation
..
.. programmes such as ‘Stent – Save a Life’ powered by the European
..
.. Association of Percutaneous Cardiovascular Interventions4 and the
.. PCR Interventional community worldwide (https://www.stentsavea
..
.. life.com/#) should follow the outstanding ‘best practice’ example
.. given by this consortium of hospital teams. The present work demon-
..
.. strates that time matters even more than we used to think, especially
.. in high-risk patients who still have poor outcomes, and that there are
..
.. ways to expedite the process. Simply offering PPCI and reperfusion
..
.. therapies is necessary, but not sufficient: the efficiency of the care
.. pathway in expediting each step of the process matters tremen-
..
.. dously, beyond what we suspected. The present data call for immedi-
.. ate action. D2B is part of the problem, but C2B is the main time
..
.. target. Reducing treatment delays as much as possible in all patients,
.. but especially in patients with CS and/or OHCA, should be our
..
.. immediate next objective.
..
.. Conflict of interest: The authors have no specific conflict of inter-
..
.. est in relation to this manuscript. Both W.W. and C.K.N. are mem-
.. bers of the Executive Committee of the ‘Stent – Save a Life’ initiative
..
.. (https://www.stentsavealife.com/#).
..
..
.. References
.. 1. Scholz KH, Maier SKG, Maier LS, Lengenfelder B, Jacobshagen C, Jung J,
..
.. Fleischmann C, Werner GS, Olbrich HG, Ott R, Mudra H, Seidl K, Schulze PC,
.. Weiss C, Haimerl J, Friede T, Meyer T. Impact of treatment delay on mortality in
.. ST-segment elevation myocardial infarction (STEMI) patients presenting with and
.. without haemodynamic instability: results from the German prospective, multi-
..
.. 2. centre FITT-STEMI trial. Eur Heart J 2018;39:1065–1074.
Bradley EH, Herrin J, Wang Y, Barton BA, Webster TR, Mattera JA, Roumanis SA,
..
.. Curtis JP, Nallamothu BK, Magid DJ, McNamara RL, Parkosewich J, Loeb JM,
.. Krumholz HM. Strategies for reducing the door-to-balloon time in acute myocar-
. dial infarction. N Engl J Med 2006;355:2308–2320.
Editorial 1077

3. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, .. Deleanu D, Dudek D, Erglis A, Gilard M, Goktekin O, Guagliumi G, Gudnason T,
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infarction in patients presenting with ST-segment elevation: The Task Force for the .. Sokolov M, Studencan M, Terzic I, Wahler S, Widimsky P; European Association
management of acute myocardial infarction in patients presenting with ST-segment .. for Percutaneous Cardiovascular Interventions. Reperfusion therapy for ST eleva-
elevation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:119–177. .. tion acute myocardial infarction 2010/2011: current status in 37 ESC countries.
4. Kristensen SD, Laut KG, Fajadet J, Kaifoszova Z, Kala P, Di Mario C, Wijns W, .. Eur Heart J 2014;35:1957–1970.
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..

Erratum doi:10.1093/eurheartj/ehx029

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Online publish-ahead-of-print 8 February 2017
....................................................................................................................................................
Erratum to: Increasing sex differences in the use of cardiac resynchronization therapy with or without implantable cardioverter-
defibrillator [Eur Heart J 2017; DOI: 10.1093/eurheartj/ehw598]
The publisher wishes to inform readers that an author affiliation was incorrect as first published. The affiliations should have been published
as follows:

Vicki A. Jackson5
Charlotta Lindvall6
5
Division of Palliative Care, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA;
6
Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston MA 02215, USA

The paper has now been corrected online.

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C The Author 2017. For permissions, please email: journals.permissions@oup.com.