European Heart Journal (2015) 36, 2348–2355
doi:10.1093/eurheartj/ehv217
Ischaemic stroke and ST-segment elevation
myocardial infarction: fast-track single-stop
approach
Peter Lanzer 1* and Petr Widimský 2
1
Division of Cardiovascular Disease, Center of Internal Medicine, Health Center Bitterfeld-Wolfen gGmbH, Friedrich-Ludwig-Jahn Strasse 2, Bitterfeld-Wolfen 06749, Germany; and
2
Department of Cardiology, University Hospital Kralovske Vinohrady and the Third Faculty of Medicine, Charles University, Šrobárova 50, 100 34 Prague 10, Czech Republic
Received 12 February 2015; revised 22 April 2015; accepted 4 May 2015; online publish-ahead-of-print 2 June 2015
Introduction
Acute ischaemic stroke (AIS) is a devastating disease associated with
high morbidity and mortality, ranking 2nd single most common
cause of death in Europe1 and 4th cause of death in the USA.2 Based
on the 2014 American Heart Association statistic, 795 000 US
Americans experienced a stroke annually, 87% related to ischaemic,
and 10% to haemorrhagic events with 3% related to sub-arachnoidal
bleeding.2 According to the current guidelines, systemic fibrinolysis
is reserved for patients treated within 3 h after the onset of ischae-
mic symptoms (recommendation I/A) or within 3 – 4.5 h after the
onset of ischaemic symptoms (recommendation I/B). Intra-arterial
fibrinolysis is recommended for patients who are not candidates
for systemic fibrinolysis within 6 h after the onset of ischaemic
symptoms (recommendation I/B). Mechanical thrombectomy is
reserved for patients who have contraindications for systemic fibrin-
olysis (recommendation IIa/C) or as a rescue procedure in patients
with large-artery occlusion who have not responded to intravenous
fibrinolysis (recommendation IIb/B). The usefulness of (primary)
intracranial angioplasty and/or stenting is considered ‘not well estab-
lished’, and if these techniques are employed they should be used in
context of clinical trials (IIb/C); however, these 2013 guidelines lag
behind the current evidence (see below).3
Utilization of revascularization therapy in patients with AIS is low;
, 5% of all patients admitted with AIS receive systemic fibrinolysis
and the use of catheter-based therapy is even less.4 In contrast,
according to the guidelines the vast majority of patients with ST-
segment elevation myocardial infarction (STEMI) receive primary
percutaneous coronary intervention (PCI) ‘defined as percutaneous
catheter intervention in the setting of STEMI, without previous
fibrinolysis’ as a first-line treatment ‘provided it can be performed
in a timely manner in high volume PCI centers with experienced
operators and 24-hour, 7-day catheterization laboratory activa-
tion’,5 conditioned on availability of PCI centers.
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.
* Corresponding author. Tel: +49 3493 312301, Fax: +49 3493 312304, Email: planzer@gzbiwo.de
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: journals.permissions@oup.com.
CURRENT OPINION
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Here, we briefly compare the interventional approach to AIS and
STEMI and suggest a novel fast-track approach to AIS management.
Ischaemia and reperfusion tissue
damage and salvage
The degree and extent of the ischaemic and reperfusion tissue injury
of an organ depends on factors such as the duration of ischaemia,
metabolic rate, status of collaterals, and preconditioning.6 Based
on experimental evidence largely obtained in rodents in brain tissue,
three critical levels of cerebral blood flow (CBF) reduction have
been defined; first, ca. 70 – 80% of normal CBF, corresponding to
50 –55 mL/100 g/min inhibition of protein synthesis occurs; second,
ca. 50% of normal CBF, corresponding to ca. 35 mL/100 g/min, lactic
acidosis, and cytotoxic oedema develop; third critical, ca. 30% of
normal CBF, corresponding to ca. 20 mL/100 g/min, depletion of
adenosine-tri-phosphate, and breakdown of metabolism and func-
tions occur. With reperfusion, the initial transient hyperperfusion
is followed by prolonged hypoperfusion partly due to the no-reflow
phenomenon. The ischaemia-reperfusion state is accompanied
by progressive microvascular-cellular damage. Based on the degree
of CBF reduction the necrotic core (CBF ,10 mL/100 g/min;
irreversible brain tissue damage) and ischaemic penumbra (CBF .
20 mL/100 g/min; functional reversible brain tissue damage) can
be differentiated (for review, see Ref. 7). The current perfusion
computed tomography (CT) allows reliable distinction between
penumbra and ischemic core.8
The penumbra represents tissue at risk susceptible to the dynam-
ic ischaemia-reperfusion injury (IRI); the key determinant of the
width of the therapeutic window. Ischaemia-reperfusion injury is
typically associated with transient hyperperfusion, no-reflow, loss
of autoregulation, disruption of the blood – brain barrier (BBB),
formation of cytotoxic (intracellular) and vasogenic (extracellular)
parenchymal oedema and risk of haemorrhagic transformation
Ischaemic stroke and STEMI
Figure 1 Summary of trials. Shown is the primary outcome – the score on the modified Rankin scale at 90 days following the treatment in
three trials MR CLEAN, EXTEND-1A, ESCAPE.49 – 51
and other phenomena, all related to the activation of the complex
biological cascades (for review, see Ref. 9). Thus, while the ischae-
mic penumbra corresponds to the maximum potentially salvageable
brain tissue at a given point of time (moving target of interventions)
the maximum tissue salvage is rarely achieved due to progressive
character of IRI, and in case of intervention the risk of procedure-
related injury. In addition, the ultimate tissue salvage shall depend on
modifying individual factors; foremost individually highly variable
availability and efficacy of primary and secondary collaterals,10,11 but
also reactivity of brain tissue’s neuro-immune-endocrine systems,
pre-strokes status, ischaemic preconditioning, and topography of the
lesion.12,13
Necrotic core and ischaemic penumbra in AIS correspond to myo-
cardial necrosis and myocardium at risk in STEMI patients. Experimental
data obtained in dogs suggested that myocardium subjected to coron-
ary blood flow (CoBF) reduction even down to ca. 30 mL/100 g/min
(normal CoBF ca. 110 mL/100 g/min) may be salvageable. Following
complete sudden occlusion of a coronary artery irreversible myo-
cardial ischaemic injury develops within 20 min in the inner layer of
the myocardium and proceeds in a wave-like fashion towards the
epicardium to be completed within up to 3 – 4 h. Brief periods of
myocardial ischaemia may be associated with prolonged dysfunc-
tional yet reversible states such as stunning and hibernation. Simi-
lar to AIS salvage of the myocardium at risk in STEMI is limited due
to IRI and risk of procedure-related factors (for review, see Refs.
14,15).
Although both, AIS and STEMI, are caused by sudden complete
arterial blockage important differences exist. First, AIS are mostly
caused by distal emboli16 while STEMIs are typically caused by local
thrombi,17 the former with highly different material composition18,19
affecting the site and distribution of embolization20 and possible dif-
ferences in the fibrinolytic and mechanical properties, not yet studied.
Second, damage to BBB is far more detrimental, particularly due to
the formation of vasogenic parenchymal oedema and risk of intra-
parenchymal haemorrhage 21,22 compared with the frequently
less deleterious endothelial myocardial damage.23 Third, the col-
lateral networks of the brain are more efficient compared with
those of the myocardium.24 – 27 Fourth, in the brain the topography
and the size of the ischaemic lesion determine the outcome and
prognosis (for review see Ref. 28) while in the myocardium largely
the size alone is decisive determinant of prognosis in STEMI pa-
tients. 29,30 For the outcome of interventional treatment
2349
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particularly in AIS patients, the presence of the individual modify-
ing factors (see above) appears also critical.
Reperfusion interventions
In patients with AIS systemic fibrinolysis was firmly established based
on the National Institute of Neurological Disorders and Stroke
(NINDS)31 and the European Cooperative Acute Stroke Study (ECASS)
trials32 in mid-1990th after initially promising,33 yet later rather dis-
appointing results.34 – 36 Despite benefits intra-arterial fibrinolysis 37,38
has remained second-line treatment based on current guidelines.3
To achieve mechanical revascularization initially balloon angio-
plasty39 and stenting40 were employed. Subsequently, intracranial
blood clot removal have been marketed41 and tested in clinical trials
with positive42 – 45 and negative46 – 48 results. However, in recent
carefully designed randomized trials clear benefits of mechanical
thrombectomy over standard care have been demonstrated
(Figure 1).49 – 51 Figure 2A – C provides an example of a successful
revascularization of the right middle cerebral artery using the
stent-retriever technology.
In patients with STEMI systemic fibrinolysis was introduced in
1970th52 and in 1980th firmly clinically established following a series
of successful early trials.53,54 Although proven effective55,56 intra-
coronary fibrinolysis has been subsequently largely abandoned
because cumbersome without offering clear benefits over the sys-
temic application. Following introduction for emergency cases57,58
balloon angioplasty has proven superior to systemic fibrinolysis in
numerous randomized trials59 – 61 only to be later replaced by stent-
ing.62 – 64 Nevertheless, scientific discussions regarding the optimum
interventional strategy in acute STEMI settings concerning issues
such as timing of stenting65 and use of thrombus aspiration66 are still
ongoing. Figure 3 demonstrates the timeline of interventional
therapy in AIS and STEMI settings.
Technical aspects
The need of embolus retrieval in AIS settings makes the use of
dedicated devices such as the clot retrieval stents (see Appendix)
mandatory. Retrievable stents are delivered via micro-catheters fre-
quently requiring co-axial support catheters for safe delivery.
Balloon dilatation or stenting are usually not required. To restore
patency several thrombectomy passages are usually needed. The
main technical challenges consist in dealing with tortuosities and
2350 P. Lanzer and P. Widimský

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Figure 2 (A – C) An 83 old female presenting in the hospital with a severe right hemispheric syndrome (NIHSS: 20), 1 h: 15 min after the onset of
symptoms. Following the exclusion of cerebral haemorrhage on native cerebral computed tomography the cerebral x-ray angiography was per-
formed showing occlusion of proximal middle cerebral artery (MCA) (M1-segment) (A). Employing a stent retriever (arrow) deployed via micro-
catheter and 8 F sheath, the embolus was removed (B) and antegrade blood flow (TICI III) with a complete reperfusion of the MCA territory was
achieved (C). (Courtesy Albrecht Bormann, MD, Altenburg).

complex lesions such as long dissections, tandems, and complex
carotid-T lesions. In some cases, general anaesthesia (GA) may
be needed. Acute stroke intervention without GA has two
main advantages: (i) short door-to-groin puncture time (GA
causes usually 20 – 60 min delays) and (ii) possibly also better
outcomes (due to shorter delays and avoidance of GA risks).
Patients undergoing mechanical thrombectomy should receive
systemic fibrinolysis prior to the intervention based on current
guidelines (3).
In STEMI cases conventional instrumentation including
over-the-wire balloon catheters or micro-catheters, dilatation
balloon and stent are employed. The use of adjunct pharmaco-
logical agents, 67 thrombus aspiration catheters, 66 covered
stents 68 or thrombo-embolic protection umbrellas 69 remains
optional. While potentially beneficial 70,71 residual role of sys-
temic fibrinolytic treatment concerns patients in whom PCI
cannot be delivered within 90 – 120 min based on current
guidelines. 5
Metrics
To assure the quality of the catheter-based treatments standard
of therapy have been developed for both, AIS72 and STEMI,5,73
settings. Thrombolysis in cerebral infarction flow grades IIb/III and
thrombolysis in myocardial infarction flow grades, respectively,
represent the targets in AIS74 – 76 and STEMI interventions.77,78
The AIS and STEMI interventions are usually performed by
neuro-interventional radiologists and interventional cardiologists,
respectively. While the training requirements for AIS treatments
have not yet been internationally established, for STEMI treatments
they have been defined.79,80
Rationale for the streamlined
fast-track single-stop approach
Rationale for the streamlined fast-track single-stop approach is
based on five main precepts. First, recent evidence suggests better
clinical outcome in AIS patients treated by mechanical thrombec-
tomy compared with the current approach.49 – 51 This advantage
should be further explored and exploited. Second, duration of
ischemia represents the key determinant of the severity of the
resulting IRI and the opportunity of the therapeutic window. 81
The symptom onset-to-revascularization time and even more press-
ingly the door-to-revascularization time must be dramatically
reduced. Third, new data confirms the critical importance of individ-
ual factors, predominantly the status of the collateral networks,
significantly modifying the viability of brain tissue.10,11 Therefore,
determination of the therapeutic window should be based on indi-
vidual criteria including the status of collaterals. Fourth, broad inter-
ventional expertise within the cardiology community is available,
and could be activated, provided an extensive dedicated training
build upon the existing procedural skills developed in carotid artery
stenting.82 Fifth, logistics and regional catheterization laboratory
networks providing 24/7 services are available83 and could be
potentially modified to accommodate a second tier.
Opportunities to meet
Based on experience, the onset of ‘symptoms-to-door time’ accounts
for ca. 40% and the ‘door-to-revascularization time’ accounts for ca.
60% of the entire time span, i.e. ‘symptom-to-revascularization time’.
In the latter, the time required for diagnostics accounts for ca. 40%
and that for therapy ca. 60%. To shorten the ‘symptoms-to-door
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Ischaemic stroke and STEMI 2351
Figure 3 Timeline, interventional Therapy in STEMI and ischemic stroke patients, 1976– 2015 (see also references).
2352
time’ community alert and public awareness must be improved. To
shorten the ‘door-to-revascularization time’, diagnostics and therapy
can be merged, operators and interdisciplinary teams can be trained,
and continuous quality control and strict logistics concerning all
professionals involved can be introduced and maintained.
With the emergence of the new imaging technology employing
rotational angiography allowing CT-like 3D-image reconstruction
comparable information with conventional CT may be acquired in
a single step process including high-resolution cerebral angiograms.
In addition, while imaging is taking place in the angiography suite, the
operator may proceed with mechanical thrombectomy with no
further delay. More specifically, during a single/double 2008 rotation
800 images are acquired. The raw digital data set with a spatial
resolution of 0.103 mm3/voxel (down to 0.01 mm3/voxel) and
grey scale resolution of 5 HU (down to 3HU) is reconstructed using
a dedicated cone-beam reconstruction algorithm to generate high-
resolution images of the brain parenchyma and brain vessels.
Depending on the analytical software tools anatomic or functional
perfusion images can be calculated allowing CT-like definition of
ischaemic and/or haemorrhagic brain tissues, cerebral perfusion,
and cerebral extra- and intracranial (lepto-meningeal) collaterals.
Image acquisition and image reconstruction time for the entire
data set are 12 – 20 and 30 s, respectively. On-site imaging
with immediate interventional option should clearly reduce the
‘door-to-groin puncture time’. In addition, and equally importantly,
the suitability of individual patients and individual target sites and
target lesions for the interventional approach can be determined
in real-time on-site.
The ‘groin puncture-to-revascularization time’ can be shortened
by improving the devices and by dedicated training of the operators.
Technological progress depends on industrial efforts and is to be
expected. Dedicated curriculum to train operators to perform
intracranial interventions limited to the treatments of AIS would
need to be discussed in interdisciplinary forum and based on con-
sensus developed and established. According to the anecdotal
evidence from the UK between April 2013 and March 2014, a total
of 295 procedures in a 21 hospitals were registered.84 This low
number of procedures would prevent adequate training of sufficient
number of operators regardless of specific background. Data from
interventional cardiology provide unequivocal evidence for signifi-
cant relationship between procedural volumes performed by indi-
vidual operators and by their institutions.85 Because intracranial
interventions belong arguably to the most advanced and technically
demanding catheter-based cardiovascular interventions only expert
Appendix Marketed and CE-certified stent-retrievers for mechanical intracranial thrombectomy
Product Manufacturer
...............................................................................................................................................................................
Trevo ProVue Stryker Neurovascular, Fremont, U.S.A.
pREset/pREset Phenox, Bochum, Germany
LITE
SolitaireTM FR/ Covidien, Mansfield U.S.A. (since January
SolitaireTM 2 2015 Medtronic, Minneapolis, U.S.A.)
P. Lanzer and P. Widimský
operators regardless of specific training background shall receive
procedural privileges.
Increasing availability of hybrid-theaters86 designed for interdis-
ciplinary use of cardiovascular specialists, frequently equipped
with the rotational angiography, represent the ideal hosting environ-
ment for interventional management of stroke patients. Single-stop
diagnostic and, when indicated, interventional therapy represents
the most advanced workflow to date. The current practice
of interdisciplinary collaboration exemplified by heart teams5
provides promising guide to form teams of AIS experts.
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Open issues
Comprehensive management of patients with AIS requires 24/7
availability of interdisciplinary teams of specialists with complemen-
tary expertise. The required core expertise includes neurologists,
neuro-radiologists, interventionists, anaesthesiologists, intensive
care specialists, and neuro-surgeons. Development of functioning
interdisciplinary teams shall be one of the key determinants of
success of the streamlined fast-track single-stop strategy and
sensible approach to deal with upcoming, potentially controversial
issues shall be required.
Streamlined fast-track single-stop approach established within the
framework of comprehensive stroke management and care shall
require 24/7 availability of interdisciplinary teams, increased utilization
of interventional procedures, greater need for post-procedural inten-
sive and post-stroke care. Cost calculation shall become critical issue
to assure long-term costs of this new kind of AIS treatment.
Finally, to improve outcomes better understanding of the patho-
physiology and the time-course of IRI shall be required not as an end
to itself but mainly to improve selection criteria for interventional
therapy and to assess the procedural risk of individual patients.
Summary
Current management of patients with AIS relies primarily on con-
servative approach. Suggested streamlined fast-track single-stop
approach should expedite the workflow and improve clinical
outcomes. Given the broadly available interventional cardiology
expertise cardiologist should play an active and sensible role in
the development of new interventional concepts of care of patients
with acute ischaemic stroke.
CE certificate Main features
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September 9, 2009/ Self-expanding, non-detachable, nitinol, closed cell, open slit
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Ischaemic stroke and STEMI
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