Berry, Colin

McCartney, Peter J.

English

Enlighten: Publications

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Redefining successful primary PCI
Peter J. McCartney1,2 and Colin Berry1,2*
1British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, 126 University Place, University of Glasgow, Glasgow G12
8TA, UK; and 2West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, UK
Online publish-ahead-of-print 21 November 2018
This editorial refers to ‘Intramyocardial hemorrhage
and prognosis after ST-elevation myocardial infarction’ by
S.J. Reinstadler et al., pp. 138–146.
Restoration of coronary blood flow with primary percutaneous cor-
onary intervention (PCI) is an effective treatment for ST-segment ele-
vation myocardial infarction (STEMI), and primary PCI is the
evidence-based standard of care for STEMI patients presenting within
12 h of symptom onset.1 On the other hand, restoration of epicardial
blood flow results in reperfusion injury with failed myocardial perfu-
sion in approximately 50% of patients,2 typically in the context of a
successful primary PCI procedure. Procedure success defined as nor-
mal antegrade coronary blood flow is achieved in >95% of patients
during daily practice.3,4
Failed myocardial reperfusion is a complex, heterogeneous micro-
vascular problem. Several mechanisms have been implicated, includ-
ing intra-vascular problems, such as distal embolization of thrombus/
atheroma and extravascular problems, such as extrinsic microvascu-
lar compression due to intracellular (e.g. cardiomyocyte) and extra-
cellular oedema.5 Taken together, these pathologies manifest
clinically as microvascular obstruction (MVO).
Endothelial cells may be more resistant to ischaemia than the car-
diac myocte,6 but eventually sustained ischaemia leads to endothelial
dysfunction. Endothelial damage leads to impaired capillary integrity,
tissue oedema and extravasation of red bloods cells into the extracel-
lular space. Multiple studies have shown that MVO and intramyocar-
dial haemorrhage (IMH) are closely related. In general, IMH does not
occur in the absence of MVO but, on the other hand, MVO com-
monly occurs in the absence of IMH.2 The dynamic nature of MVO
supports the concept that it may be reversible and thus a therapeutic
target. On the other hand, IMH is a downstream pathological conse-
quence of irreversible microvascular damage.7 The occurrence of
IMH therefore represents failed myocardial reperfusion, and a failure
of the therapeutic strategy.
MVO is a predictor of poor outcome independent of infarct size.8
Patients with MVO are more likely to develop heart failure post-MI
with increased mortality. The prognostic significance of IMH has been
the subject of much debate. In a study of 286 patients presenting with
acute STEMI, we found that myocardial haemorrhage (identified by
T2* imaging) was more closely associated with all-cause death and
heart failure during 2.3 years follow-up when compared with MVO
alone.2
The pathophysiological mechanisms linking IMH with worse out-
comes independent of infarct size and MVO are incompletely under-
stood. Key to this may be persistent local tissue inflammation within
the infarct core in response to persistence of haemoglobin break-
down products and accumulation of deoxidized iron residues and tis-
sue fibrosis. These pathologies prevent the natural healing process
that otherwise would normally occur in reperfused myocardium in
the absence of MVO and IMH. Cigarette smoking and a history of
hypertension are risk factors for IMH. Carberry et al. demonstrated
that persistent iron affected one in five patients who survived through
to 6 months post-STEMI and was associated with adverse LV remod-
elling, worsening ejection fractions at 6 months. Systemic inflamma-
tion at baseline, reflected by the neutrophil count, was a univariable
associate of persistent iron at 6 months, and presenting heart rate
and a history of hypertension were multivariable associates.9
Additionally, iron deposition within the infarcted myocardium may
have deleterious effects on the electrical stability of the heart and so
may increase the likelihood of compromising ventricular arrhythmias
and sudden cardiac death post-MI.10
Cardiovascular magnetic resonance (CMR) is the only method
available to clinicians to detect this problem in vivo. T2* imaging is gen-
erally accepted as the reference method for the assessment of IMH
in STEMI patients,11 and T2* imaging is increasingly available as an op-
tion in standard CMR protocols. Blood degradation products such as
deoxyhaemoglobin exert a paramagnetic effect, reducing the T2* sig-
nal, represented by hypointense areas within the infarct core. Still,
local signal loss due to artefact can complicate the imaging read-out,
especially if supporting features such as reduced wall motion and in-
farction are absent.
Reinstadler et al.12 provide additional evidence for the clinical im-
portance of IMH characterized by T2* imaging post-STEMI. They
conducted a prospective multicentre study of 264 STEMI patients
presenting within 12 h of symptom onset undergoing primary PCI.
The primary endpoint was a composite of death, reinfarction, and
new congestive heart failure at 12 months. Sixty patients had IMH, of
these, 9 (15%) had major adverse cardiac events (MACE), whereas
The opinions expressed in this article are not necessarily those of the Editors of EHJCI, the European Heart Rhythm Association or the European Society of Cardiology.
* Corresponding author. Tel: þ44 0141 3303325; Fax: þ44 (0) 141 330 6794. E-mail: colin.berry@glasgow.ac.uk
VC The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestrict-
ed reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
European Heart Journal - Cardiovascular Imaging (2019) 20, 133–135 EDITORIAL
doi:10.1093/ehjci/jey159
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.
only 10 (4.9%) patients without IMH experienced a MACE. IMH was
independently associated with MACE, and IMH increased the prog-
nostic value of a model which included MVO. This study adds to the
previous work by Carrick et al.,2 reaffirming IMH as a determinative
pathological complication post-STEMI.
The study by Reinstadler et al.12 did have some limitations. The
number of MACE events (n= 19) was modest and in isolation the
results have qualified significance. On the other hand, these data are
consistent with other studies.2,13 Reinstadler et al. highlighted five
patients with IMH but no MVO which is not consistent with previous
studies. In a serial imaging time course sub-study of 30 patients, MVO
had resolved by day 10 in 44% of affected patients, with persistence
of IMH in 25% of these.2 One potential explanation is the differing
time-course of these pathologies with resolution of MVO in the pres-
ence of persistent IMH not disclosed by imaging at a single time-point
up to 7 days. Imaging artefact may also be relevant. A small amount of
MVO may not be visible within a zone of late gadolinium enhance-
ment imaging and T2* artefact occurs at a tissue–air interface such as
the infero-lateral wall of the left ventricle which may be mistaken for
haemorrhage.
Therefore, IMH represents a target for preventive therapy, how-
ever, aside from timely reperfusion, there are no specific treatments
for this problem. Favourable results in preclinical studies have not
translated when assessed in patients.14 Randomized controlled clinic-
al trials of novel therapeutic approaches designed to reduce the ex-
tent and severity of infarction, including novel cardioprotective
interventions such as intra-venous beta-blocker therapy before
reperfusion (EARLY-BAMI),15 intravenous inhibitors of
mitochondria-mediated reperfusion injury, i.e. cyclosporine
(CIRCUS),16 TRO40303 (MITOCARE),17 post-ischaemic condition-
ing (DANAMI-3 iPOST),18 and deferred stenting (DANAMI-3-
DEFER),19 have not proven beneficial and intra-coronary vasodilator
therapy with adenosine was actually harmful (REFLO-STEMI).20 A
post hoc analysis of the Phase 2 METOCARD-CNIC trial21 indicated
intravenous beta-blocker therapy might reduce the risk of MVO
through inhibition of neutrophil recruitment and platelet activation.
MVO is now identified as a therapeutic target in practice guidelines,22
but the gaps in evidence on the causes and treatment of IMH highlight
the need for more research.
We have recently conducted a Phase 2 clinical trial of low dose ad-
junctive intracoronary fibrinolysis with alteplase in reperfused STEMI
(ClinicalTrials.gov: NCT02257294). The clinical strategy involved
identifying patients in whom initial coronary angiography identified
occluded infarct-related artery and/or with a high thrombus burden.
These characteristics place the participants at an increased risk of
MVO. By targeting thrombus within the infarct-related artery and
microcirculation with fibrinolytic therapy the aim was to restore
microvascular blood flow at the earliest point after coronary reperfu-
sion. On the other hand, the intervention has the potential to pro-
mote bleeding within the infarct zone and systemically. The risk of
IMH was purposefully mitigated by selecting patients presenting with
a comparatively short ischaemic time (<6 h) in whom radial artery ac-
cess was used. The overall objective was to conduct a safety, efficacy
and mechanisms evaluation within the context of a trial that was suffi-
ciently large to give definitive results.
In conclusion, given that failed myocardial reperfusion occurs in
one in every two patients undergoing primary PCI for acute STEMI,
and IMH is an independent driver of prognosis, can primary PCI really
be considered successful when these eventualities routinely occur?
We think not. We propose that successful primary PCI is redefined
as restoration of normal coronary blood flow in the absence of MVO
and IMH. However, until specific evidence-based treatments for
MVO and IMH become available, routine imaging with CMR to assess
for these pathologies cannot be justified on economic grounds, and
clinicians should follow optimal guideline-directed management for
their post-MI patients.
Funding
This work was supported by the British Heart Foundation (BHF) Centre
of Research Excellence Award (RE/13/5/30177) and a research grant
from the National Institute of Health Research Efficacy and Mechanism
Evaluation Programme (12/170/45).
Conflict of interest:The University of Glasgow holds a research agree-
ment with Siemens Healthcare.
References
1. Huynh T, Perron S, O’Loughlin J, Joseph L, Labrecque M, Tu JV et al.
Comparison of primary percutaneous coronary intervention and fibrinolytic
therapy in ST-segment-elevation myocardial infarction: Bayesian hierarchical
meta-analyses of randomized controlled trials and observational studies.
Circulation 2009;119:3101–31.
2. Carrick D, Haig C, Ahmed N, McEntegart M, Petrie MC, Eteiba H et al.
Myocardial hemorrhage after acute reperfused ST-segment-elevation myocardial
infarction: relation to microvascular obstruction and prognostic significance. Circ
Cardiovasc Imaging 2016;9:e004148.
3. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous
thrombolytic therapy for acute myocardial infarction: a quantitative review of 23
randomised trials. Lancet 2003;361:13–20.
4. Carrick D, Haig C, Rauhalammi S, Ahmed N, Mordi I, McEntegart M et al.
Prognostic significance of infarct core pathology revealed by quantitative non-
contrast in comparison with contrast cardiac magnetic resonance imaging in
reperfused ST-elevation myocardial infarction survivors. Eur Heart J 2016;37:
1044–59.
5. Wu X, Mintz GS, Xu K, Lansky AJ, Witzenbichler B, Guagliumi G et al. The rela-
tionship between attenuated plaque identified by intravascular ultrasound and
no-reflow after stenting in acute myocardial infarction: the HORIZONS-AMI
(harmonizing outcomes with revascularization and stents in acute myocardial in-
farction) trial. JACC Cardiovasc Interv 2011;4:495–502.
6. Viehman GE, Ma XL, Lefer DJ, Lefer AM. Time course of endothelial dysfunction
and myocardial injury during coronary arterial occlusion. Am J Physiol 1991;261:
874–81.
7. Beek AM, Nijveldt R, van Rossum AC. Intramyocardial hemorrhage and micro-
vascular obstruction after primary percutaneous coronary intervention. Int J
Cardiovasc Imaging 2010;26:49–55.
8. Van Kranenburg M, Magro M, Thiele H, de Waha S, Eitel I, Cochet A et al.
Prognostic value of microvascular obstruction and infarct size, as measured by
CMR in STEMI patients. JACC Cardiovasc Imaging 2014;7:930–9.
9. Carberry J, Carrick D, Haig C, Ahmed N, Mordy I, McEntegart M et al. Persistent
iron within the infarct core after ST-segment elevation myocardial infarction:
implications for left ventricular remodeling and health outcomes. JACC Cardiovasc
Imaging 2017; doi:10.1016/j.jcmg.2017.08.027.
10. Mather AN, Fairbairn TA, Ball SG, Greenwood JP, Plein S. Reperfusion haemor-
rhage as determined by cardiovascular MRI is a predictor of adverse left ven-
tricular remodelling and markers of late arrhythmic risk. Heart 2011;97:453–9.
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..11. Kumar A, Green JD, Sykes JM, Ephrat P, Carson JJ, Mitchell AJ et al. Detection
and quantification of myocardial reperfusion hemorrhage using T2*-weighted
CMR. JACC Cardiovasc Imaging 2011;4:1274–83.
12. Reinstadler SJ, Stiermaier T, Reindl M, Feistritzer HJ, Fuernau G, Eitel C et al.
Intramyocardial hemorrhage and prognosis after ST-elevation myocardial infarc-
tion. Eur Heart J Cardiovasc Imaging 2019;20:138–46.
13. Eitel I, Kubusch K, Strohm O, Desch SD, Mikami Y, de Waha S et al. Prognostic
value and determinants of a hypointense infarct core in T2-weighted cardiac
magnetic resonance in acute reperfused ST-elevation-myocardial infarction. Circ
Cardiovasc Imaging 2011;4:354–62.
14. Hausenloy DJ, Botker HE, Engstrom T, Erlinge D, Heusch G, Ibanez B et al.
Targeting reperfusion injury in patients with ST-segment elevation myocardial in-
farction: trials and tribulations. Eur Heart J 2017;38:935–41.
15. Roolvink V, Ibanez B, Ottervanger JP, Pizarro G, van Royen N, Mateos A et al.
Early intravenous beta-blockers in patients with ST-segment elevation myocardial
infarction before primary percutaneous coronary intervention. J Am Coll Cardiol
2016;67:2705-15.
16. Cung TT, Morel O, Cayla G, Rioufol G, Garcia-Dorado D, Angoulvant D et al.
Cyclosporine before PCI in patients with acute myocardial infarction. N Engl J
Med 2015;373:1021-31.
17. Atar D, Arheden H, Berdeaux A, Bonnet JL, Carlsson M, Clemmensen P et al.
Effect of intravenous TRO40303 as an adjunct to primary percutaneous coron-
ary intervention for acute ST-elevation myocardial infarction: MITOCARE study
results. Eur Heart J 2015;36:112-9.
18. Engstrom T, Kelbaek H, Helqvist S, Hofsten DE, Klovgaard L, Clemmensen P
et al. Effect of ischemic postconditioning during primary percutaneous coronary
intervention for patients with ST-segment elevation myocardial infarction: a
randomized clinical trial. JAMA Cardiol 2017;2:490-7.
19. Kelbaek H, Hofsten DE, Kober L, Helqvist S, Klovgaard L, Holmvang L et al.
Deferred versus conventional stent implantation in patients with ST-segment ele-
vation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised
controlled trial. Lancet 2016;387:2199-206.
20. Nazir SA, McCann GP, Greenwood JP, Kunadian V, Khan JN, Mahmoud IZ et al.
Strategies to attenuate micro-vascular obstruction during P-PCI: the randomized
reperfusion facilitated by local adjunctive therapy in ST-elevation myocardial in-
farction trial. Eur Heart J 2016;37:1910-9.
21. Ibanez B, Macaya C, Sanchez-Brunete V, Pizarro G, Fernandez-Friera L,
Mateos A et al. Effect of early metoprolol on infarct size in ST-segment-eleva-
tion myocardial infarction patients undergoing primary percutaneous coron-
ary intervention: the effect of metoprolol in cardioprotection during an acute
myocardial infarction (METOCARD-CNIC) trial. Circulation 2013;128:
1495-503.
20. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H et al.
2017 ESC Guidelines for the management of acute myocardial infarction in
patients presenting with ST-segment elevation: the Task Force for the manage-
ment of acute myocardial infarction in patients presenting with ST-segment ele-
vation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:
119–77.
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Redefining successful primary PCI

Enlighten

......................................................................................................................Redefining successful primary PCIPeter J. McCartney1,2 and Colin Berry1,2*1British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, 126 University Place, University of Glasgow, Glasgow G128TA, UK; and 2West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Glasgow, UKOnline publish-ahead-of-print 21 November 2018This editorial refers to ‘Intramyocardial hemorrhageand prognosis after ST-elevation myocardial infarction’ byS.J. Reinstadler et al., pp. 138–146.Restoration of coronary blood flow with primary percutaneous cor-onary intervention (PCI) is an effective treatment for ST-segment ele-vation myocardial infarction (STEMI), and primary PCI is theevidence-based standard of care for STEMI patients presenting within12 h of symptom onset.1 On the other hand, restoration of epicardialblood flow results in reperfusion injury with failed myocardial perfu-sion in approximately 50% of patients,2 typically in the context of asuccessful primary PCI procedure. Procedure success defined as nor-mal antegrade coronary blood flow is achieved in >95% of patientsduring daily practice.3,4Failed myocardial reperfusion is a complex, heterogeneous micro-vascular problem. Several mechanisms have been implicated, includ-ing intra-vascular problems, such as distal embolization of thrombus/atheroma and extravascular problems, such as extrinsic microvascu-lar compression due to intracellular (e.g. cardiomyocyte) and extra-cellular oedema.5 Taken together, these pathologies manifestclinically as microvascular obstruction (MVO).Endothelial cells may be more resistant to ischaemia than the car-diac myocte,6 but eventually sustained ischaemia leads to endothelialdysfunction. Endothelial damage leads to impaired capillary integrity,tissue oedema and extravasation of red bloods cells into the extracel-lular space. Multiple studies have shown that MVO and intramyocar-dial haemorrhage (IMH) are closely related. In general, IMH does notoccur in the absence of MVO but, on the other hand, MVO com-monly occurs in the absence of IMH.2 The dynamic nature of MVOsupports the concept that it may be reversible and thus a therapeutictarget. On the other hand, IMH is a downstream pathological conse-quence of irreversible microvascular damage.7 The occurrence ofIMH therefore represents failed myocardial reperfusion, and a failureof the therapeutic strategy.MVO is a predictor of poor outcome independent of infarct size.8Patients with MVO are more likely to develop heart failure post-MIwith increased mortality. The prognostic significance of IMH has beenthe subject of much debate. In a study of 286 patients presenting withacute STEMI, we found that myocardial haemorrhage (identified byT2* imaging) was more closely associated with all-cause death andheart failure during 2.3 years follow-up when compared with MVOalone.2The pathophysiological mechanisms linking IMH with worse out-comes independent of infarct size and MVO are incompletely under-stood. Key to this may be persistent local tissue inflammation withinthe infarct core in response to persistence of haemoglobin break-down products and accumulation of deoxidized iron residues and tis-sue fibrosis. These pathologies prevent the natural healing processthat otherwise would normally occur in reperfused myocardium inthe absence of MVO and IMH. Cigarette smoking and a history ofhypertension are risk factors for IMH. Carberry et al. demonstratedthat persistent iron affected one in five patients who survived throughto 6 months post-STEMI and was associated with adverse LV remod-elling, worsening ejection fractions at 6 months. Systemic inflamma-tion at baseline, reflected by the neutrophil count, was a univariableassociate of persistent iron at 6 months, and presenting heart rateand a history of hypertension were multivariable associates.9Additionally, iron deposition within the infarcted myocardium mayhave deleterious effects on the electrical stability of the heart and somay increase the likelihood of compromising ventricular arrhythmiasand sudden cardiac death post-MI.10Cardiovascular magnetic resonance (CMR) is the only methodavailable to clinicians to detect this problem in vivo. T2* imaging is gen-erally accepted as the reference method for the assessment of IMHin STEMI patients,11 and T2* imaging is increasingly available as an op-tion in standard CMR protocols. Blood degradation products such asdeoxyhaemoglobin exert a paramagnetic effect, reducing the T2* sig-nal, represented by hypointense areas within the infarct core. Still,local signal loss due to artefact can complicate the imaging read-out,especially if supporting features such as reduced wall motion and in-farction are absent.Reinstadler et al.12 provide additional evidence for the clinical im-portance of IMH characterized by T2* imaging post-STEMI. Theyconducted a prospective multicentre study of 264 STEMI patientspresenting within 12 h of symptom onset undergoing primary PCI.The primary endpoint was a composite of death, reinfarction, andnew congestive heart failure at 12 months. Sixty patients had IMH, ofthese, 9 (15%) had major adverse cardiac events (MACE), whereasThe opinions expressed in this article are not necessarily those of the Editors of EHJCI, the European Heart Rhythm Association or the European Society of Cardiology.* Corresponding author. Tel: þ44 0141 3303325; Fax: þ44 (0) 141 330 6794. E-mail: colin.berry@glasgow.ac.ukVC The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestrict-ed reuse, distribution, and reproduction in any medium, provided the original work is properly cited.European Heart Journal - Cardiovascular Imaging (2019) 20, 133–135 EDITORIALdoi:10.1093/ehjci/jey159Downloaded from https://academic.oup.com/ehjcimaging/article-abstract/20/2/133/5197063 by University of Glasgow user on 07 August 2019.................................................................................................................................................................only 10 (4.9%) patients without IMH experienced a MACE. IMH wasindependently associated with MACE, and IMH increased the prog-nostic value of a model which included MVO. This study adds to theprevious work by Carrick et al.,2 reaffirming IMH as a determinativepathological complication post-STEMI.The study by Reinstadler et al.12 did have some limitations. Thenumber of MACE events (n= 19) was modest and in isolation theresults have qualified significance. On the other hand, these data areconsistent with other studies.2,13 Reinstadler et al. highlighted fivepatients with IMH but no MVO which is not consistent with previousstudies. In a serial imaging time course sub-study of 30 patients, MVOhad resolved by day 10 in 44% of affected patients, with persistenceof IMH in 25% of these.2 One potential explanation is the differingtime-course of these pathologies with resolution of MVO in the pres-ence of persistent IMH not disclosed by imaging at a single time-pointup to 7 days. Imaging artefact may also be relevant. A small amount ofMVO may not be visible within a zone of late gadolinium enhance-ment imaging and T2* artefact occurs at a tissue–air interface such asthe infero-lateral wall of the left ventricle which may be mistaken forhaemorrhage.Therefore, IMH represents a target for preventive therapy, how-ever, aside from timely reperfusion, there are no specific treatmentsfor this problem. Favourable results in preclinical studies have nottranslated when assessed in patients.14 Randomized controlled clinic-al trials of novel therapeutic approaches designed to reduce the ex-tent and severity of infarction, including novel cardioprotectiveinterventions such as intra-venous beta-blocker therapy beforereperfusion (EARLY-BAMI),15 intravenous inhibitors ofmitochondria-mediated reperfusion injury, i.e. cyclosporine(CIRCUS),16 TRO40303 (MITOCARE),17 post-ischaemic condition-ing (DANAMI-3 iPOST),18 and deferred stenting (DANAMI-3-DEFER),19 have not proven beneficial and intra-coronary vasodilatortherapy with adenosine was actually harmful (REFLO-STEMI).20 Apost hoc analysis of the Phase 2 METOCARD-CNIC trial21 indicatedintravenous beta-blocker therapy might reduce the risk of MVOthrough inhibition of neutrophil recruitment and platelet activation.MVO is now identified as a therapeutic target in practice guidelines,22but the gaps in evidence on the causes and treatment of IMH highlightthe need for more research.We have recently conducted a Phase 2 clinical trial of low dose ad-junctive intracoronary fibrinolysis with alteplase in reperfused STEMI(ClinicalTrials.gov: NCT02257294). The clinical strategy involvedidentifying patients in whom initial coronary angiography identifiedoccluded infarct-related artery and/or with a high thrombus burden.These characteristics place the participants at an increased risk ofMVO. By targeting thrombus within the infarct-related artery andmicrocirculation with fibrinolytic therapy the aim was to restoremicrovascular blood flow at the earliest point after coronary reperfu-sion. On the other hand, the intervention has the potential to pro-mote bleeding within the infarct zone and systemically. The risk ofIMH was purposefully mitigated by selecting patients presenting witha comparatively short ischaemic time (<6 h) in whom radial artery ac-cess was used. The overall objective was to conduct a safety, efficacyand mechanisms evaluation within the context of a trial that was suffi-ciently large to give definitive results.In conclusion, given that failed myocardial reperfusion occurs inone in every two patients undergoing primary PCI for acute STEMI,and IMH is an independent driver of prognosis, can primary PCI reallybe considered successful when these eventualities routinely occur?We think not. We propose that successful primary PCI is redefinedas restoration of normal coronary blood flow in the absence of MVOand IMH. However, until specific evidence-based treatments forMVO and IMH become available, routine imaging with CMR to assessfor these pathologies cannot be justified on economic grounds, andclinicians should follow optimal guideline-directed management fortheir post-MI patients.FundingThis work was supported by the British Heart Foundation (BHF) Centreof Research Excellence Award (RE/13/5/30177) and a research grantfrom the National Institute of Health Research Efficacy and MechanismEvaluation Programme (12/170/45).Conflict of interest:The University of Glasgow holds a research agree-ment with Siemens Healthcare.References1. Huynh T, Perron S, O’Loughlin J, Joseph L, Labrecque M, Tu JV et al.Comparison of primary percutaneous coronary intervention and fibrinolytictherapy in ST-segment-elevation myocardial infarction: Bayesian hierarchicalmeta-analyses of randomized controlled trials and observational studies.Circulation 2009;119:3101–31.2. Carrick D, Haig C, Ahmed N, McEntegart M, Petrie MC, Eteiba H et al.Myocardial hemorrhage after acute reperfused ST-segment-elevation myocardialinfarction: relation to microvascular obstruction and prognostic significance. CircCardiovasc Imaging 2016;9:e004148.3. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenousthrombolytic therapy for acute myocardial infarction: a quantitative review of 23randomised trials. Lancet 2003;361:13–20.4. Carrick D, Haig C, Rauhalammi S, Ahmed N, Mordi I, McEntegart M et al.Prognostic significance of infarct core pathology revealed by quantitative non-contrast in comparison with contrast cardiac magnetic resonance imaging inreperfused ST-elevation myocardial infarction survivors. Eur Heart J 2016;37:1044–59.5. Wu X, Mintz GS, Xu K, Lansky AJ, Witzenbichler B, Guagliumi G et al. The rela-tionship between attenuated plaque identified by intravascular ultrasound andno-reflow after stenting in acute myocardial infarction: the HORIZONS-AMI(harmonizing outcomes with revascularization and stents in acute myocardial in-farction) trial. JACC Cardiovasc Interv 2011;4:495–502.6. Viehman GE, Ma XL, Lefer DJ, Lefer AM. Time course of endothelial dysfunctionand myocardial injury during coronary arterial occlusion. Am J Physiol 1991;261:874–81.7. Beek AM, Nijveldt R, van Rossum AC. Intramyocardial hemorrhage and micro-vascular obstruction after primary percutaneous coronary intervention. Int JCardiovasc Imaging 2010;26:49–55.8. Van Kranenburg M, Magro M, Thiele H, de Waha S, Eitel I, Cochet A et al.Prognostic value of microvascular obstruction and infarct size, as measured byCMR in STEMI patients. JACC Cardiovasc Imaging 2014;7:930–9.9. Carberry J, Carrick D, Haig C, Ahmed N, Mordy I, McEntegart M et al. 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Redefining successful primary PCI

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