EDITORIAL

Myocardial Infarction With Nonobstructive

Coronary Arteries (MINOCA)
The Past, Present, and Future Management

Article, see p 1481 Sivabaskari Pasupathy,

BSc(Hons), PhD

M
yocardial infarction with nonobstructive coronary arteries (MINOCA) is clini- Rosanna Tavella,
cally defined by the presence of the universal acute myocardial infarction BSc(Hons), PhD
(AMI) criteria, absence of obstructive coronary artery disease (≥50% steno- John F. Beltrame, BSc,
sis), and no overt cause for the clinical presentation at the time of angiography (eg, BMBS, PhD
classic features for takotsubo cardiomyopathy).1 With the more frequent contempo-
rary use of coronary angiography in AMI, clinicians have been regularly confronted
with this puzzling problem and seeking guidance in its management. An article by
Lindahl et al2 in this issue of Circulation represents a major step forward in MINOCA
and thereby warrants taking stock of the past, present, and future management
strategies of this intriguing condition.
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THE PAST
The pioneering early angiography studies of DeWood et al demonstrated that ST-seg-
ment–elevation myocardial infarction was often associated with an occluded epicar-
dial artery, but this occurred less frequently in non–ST-segment–elevation myocardial
infarction, although in both conditions obstructive coronary artery disease was evi-
dent in >95% of patients.3 These findings underscored the importance of the underly-
ing atherothrombotic process and provided the impetus for major advances in AMI
management over the next 35 years. However, when angiography failed to reveal the
presence of obstructive atheroma or thrombosis in patients with clinical criteria for
ST-segment–elevation myocardial infarction, some clinicians labeled these patients
The opinions expressed in this
as having a false-positive ST-segment–elevation myocardial infarction diagnosis.4 article are not necessarily those
Such a label implies that an AMI has not occurred (despite the clinical presentation) of the editors or of the American
and therefore no further diagnostic investigation or cardiac therapy is required. Heart Association.
To avoid such diagnostic complacency, the diagnosis of MINOCA was coined5 Correspondence to: John F.
with an emphasis on investigating these patients to identify the underlying cause Beltrame, BSc, BMBS, PhD,
of their AMI presentation. Providing a label for this clinical syndrome was the first Discipline of Medicine, The Queen
key step in improving the management of these patients because MINOCA was Elizabeth Hospital, University of
Adelaide, 28 Woodville Road,
promoted as a working diagnosis that necessitated the identification of an underly-
Woodville South, Adelaide, South
ing cause, much the same as a diagnosis of heart failure or anemia requires such Australia, Australia 5011. E-mail
action.3 This was further emphasized in the first position statement on this disorder,1 john.beltrame@adelaide.edu.au
although it has yet to be incorporated into AMI guidelines.
Key Words: Editorials ◼ coronary
angiography ◼ coronary artery
disease ◼ myocardial infarction ◼
THE PRESENT myocardial ischemia ◼ secondary
With the concept of MINOCA established, the next key step in its management prevention angiography
was to identify the potential underlying causes and optimal diagnostic pathway © 2017 American Heart
in evaluating these patients. Potential underlying mechanisms include coronary Association, Inc.

1490 April 18, 2017 Circulation. 2017;135:1490–1493. DOI: 10.1161/CIRCULATIONAHA.117.027666


causes such as coronary spasm, coronary microvas-
cular dysfunction, plaque disruption, spontaneous
coronary thrombosis/emboli, and coronary dissec-
tion; myocardial disorders, including myocarditis, ta-
kotsubo cardiomyopathy, and other cardiomyopathies;
and noncardiac causes, for example, pulmonary em-
bolism. Multiple diagnostic pathways have been pro-
posed to evaluate patients with MINOCA,1,6,7 with early
cardiac magnetic resonance imaging (CMRI) being a
central investigation in most pathways because of its
ability to detect common causes.8 Indeed, recent re-
ports claimed that CMRI identifies the underlying cause
in as many as 87% of patients with MINOCA.9 Other
investigations include provocative spasm testing,
screening for thrombophilia disorders, and intravascu-
lar ultrasound1; however, routine screening for pulmo-
nary embolism with computed tomographic pulmonary
angiography is of very limited value.10
Contemporary research studies of MINOCA have
evaluated the prognosis of these patients, reporting a
12-month all-cause mortality of 4.7% (95% confidence
interval, 2.6–6.9),3 with comparative studies consistent-
ly demonstrating a better prognosis than for those who
experience AMI associated with obstructive coronary ar-
tery disease.3,11 Moreover, Kang et al12 confirmed that
12-month major adverse cardiac events (MACE; death
and myocardial infarction) in patients with MINOCA were
comparable to patients with AMI associated with single-
or double-vessel coronary artery disease. In addition to
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these MACE outcomes, Grodzinsky et al13 demonstrated
that 25% of patients with MINOCA continued to experi-
ence angina 12 months after AMI, which is equivalent to
the rate in those with AMI associated with obstructive
coronary artery disease.
Considering the guarded prognosis of patients with
MINOCA, the next beckoning question is, What therapies
should be recommended? Currently, there are no ran-
domized trials addressing this question. However, the
article by Lindahl et al12 published in this issue of Circu-
lation provides the first insight into potential long-term
medical therapy in the management of MINOCA. Using
the strength of the internationally acclaimed SWEDE-
HEART Registry (Swedish Web-System for Enhancement
and Development of Evidence-Based Care in Heart Dis-
ease Evaluated According to Recommended Therapy),
the authors have garnered a large cohort of consecu-
tive patients with MINOCA (n=9466) and used a strati-
fied propensity score analysis approach to examine the
effect of 4 conventional postinfarct therapies (statins,
angiotensin-converting enzyme inhibitors/angiotensin
receptor blockers, β-blockers, and dual antiplatelet ther-
apy) on long-term MACE (defined as all-cause mortality,
AMI hospitalization, ischemic stroke, and heart failure). A
secondary objective was to examine the impact of these
therapies on bleeding events. The key study findings in-
clude (1) a reduced hazard ratio of MACE with the use
Circulation. 2017;135:1490–1493. DOI: 10.1161/CIRCULATIONAHA.117.027666
MINOCA: The Past, Present, and Future Management
of statins (hazard ratio=0.77; 95% confidence interval,
0.68–0.87) or angiotensin-converting enzyme inhibitors/
angiotensin receptor blockers (hazard ratio=0.82; 95%
confidence interval, 0.73–0.93) with a trend observed in
β-blocker therapy (hazard ratio=0.86; 95% confidence
interval, 0.74–1.01) and (2) no associated benefit with
the use of dual antiplatelet therapy but a trend toward an
increased bleeding rate.
Although a nonrandomized study with important limita-
tions (see below), this study is a game changer because
for the first time there are data (rather than opinion) on
potential beneficial therapies to reduce MACE in patients
EDITORIAL
with MINOCA. Accordingly, clinicians can no longer dis-
miss patients with MINOCA as having false-positive AMIs
but need to consider the potential benefit of statins and
angiotensin-converting enzyme inhibitors/angiotensin re-
ceptor blockers in these patients. Hence, the study is a
major step forward in the recognition and management
of MINOCA.
As indicated by the authors, important limitations in
this retrospective cohort study are the heterogeneous
nature of MINOCA and that no investigations to identify
the underlying causes were routinely performed in this
cohort. Although clinically overt causes were excluded
because study inclusion was based on discharge di-
agnosis, less conspicuous presentations may have
been overlooked. For example, in a meta-analysis of
5 studies involving 556 patients with MINOCA, Tornvall
et al14 demonstrated that 33% had CMRI evidence of
myocarditis despite fulfilling the diagnostic criteria for
AMI. Hence, in the above analysis, up to one third of the
patients treated with statin or angiotensin-converting
enzyme inhibitors/angiotensin receptor blockers may
have had myocarditis, for which the benefits of these
therapies are unclear. If CMRI were performed on all pa-
tients and the therapies were targeted to those patients
with MINOCA with evidence of true myocardial infarc-
tion, perhaps the observed benefits would have been
even greater.
THE FUTURE
The Lindahl et al12 study has provided direction for the
next key step in the management of MINOCA, namely
a multicenter randomized controlled trial confirming the
benefits of these conventional therapies on MACE. With
a prospectively designed trial, there is an opportunity
for a more targeted therapeutic approach by identify-
ing the underlying cause with screening investigations.
Confirmation of the above findings would mandate the
evaluation of patients with MINOCA and the initiation of
secondary prevention therapies. This would not only be
paradigm shifting in relation to the treatment of MINOCA
but also provoke a re-evaluation of the mechanisms for
these beneficial agents in the context of minimal or no
atherosclerotic disease.
April 18, 2017 1491
 Pasupathy et al
This trial design also highlights an evolving problem in
MINOCA publications relating to the generic and specific
uses of the term. In the position paper,1 the term MI-
NOCA is used in an all-encompassing context to include
all patients fulfilling the universal criteria for AMI with-
out obstructive coronary artery disease and no clinically
overt cause for the presentation at the time of coronary
angiography. As described above, this should initiate fur-
ther investigation such as CMRI to identify the underlying
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cause. However, the term MINOCA is also being used in
a more specific context to exclusively describe patients
with evidence of ischemia-related myocardial necrosis
(as the name implies). This dual interpretation of the MI-
NOCA term will cause confusion in the future, especially
if specific therapies are identified for ischemic-related
MINOCA. Thus, a revision of the nomenclature is war-
ranted, and perhaps the generic form of the term should
be replaced with a broader label (eg, troponin-positive
nonobstructive coronary arteries [TP-NOCA]) that encom-
passes patients with coronary disorders resulting in isch-
emic necrosis (ie, MINOCA), as well as structural myo-
cardial disorders and noncardiac disorders11 (Figure).
Future position papers should address this important is-
sue in this rapidly evolving field.
DISCLOSURES
None.
AFFILIATIONS
From Discipline of Medicine, University of Adelaide, Australia
(S.P., R.T., J.F.B.); Cardiology Department, Central Adelaide
Local Health Network, Adelaide, Australia (S.P., R.T., J.F.B.);
and Cardiology Department, Lyell McEwin Hospital, Adelaide,
Australia (J.F.B.).
1492 April 18, 2017
Figure.  Troponin-positive nonob-
structive coronary arteries.
MINOCA indicates myocardial infarction
with nonobstructive coronary arteries.
FOOTNOTES
Circulation is available at http://circ.ahajournals.org.
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