- Email: [email protected]
The Many Faces of Type 2 Myocardial Infarction∗
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
VOL. 70, NO. 13, 2017
ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jacc.2017.07.784
EDITORIAL COMMENT
The Many Faces of Type 2 Myocardial Infarction* James L. Januzzi, MD,a Yader Sandoval, MDb
C
linicians have long recognized that acute
mortality after type 2 MI is similar to type 1 MI, or
myocardial infarction (MI) can occur in the
even higher.
absence of atherothrombosis (1). The Uni-
versal Definition of MI Global Taskforce introduced
SEE PAGE 1558
a classification system in 2007 (and reaffirmed in
In this issue of the Journal, the APACE (Advanta-
2012) that defined type 2 MI (following standard diag-
geous Predictors of Acute Coronary Syndrome Evalu-
nostic criteria) as MI occurring due to an imbalance in
ation) investigators offer their insights on type 2 MI
myocardial oxygen supply and/or demand not caused
based on a secondary analysis involving patients with
by atherosclerotic plaque disruption (2,3) (Table 1).
acute chest pain (16). In this analysis, the diagnosis of
Nevertheless, ambiguity remains regarding how to
type 2 MI was considered using 2 methods: 1 required
diagnose type 2 MI and how to distinguish it from both
presence of coronary artery disease (CAD) and the
type 1 MI and myocardial injury (4,5). For example,
other did not. This was based on a presumption by the
because those with type 2 MI are less likely to have chest
authors that in the 2007 definition, CAD was required
pain, studies focusing on patients with chest discomfort
to diagnose type 2 MI (2), whereas in the 2012 version,
have a higher prevalence of type 1 MI, whereas in
type 2 MI CAD was not required (3). Scrutiny of the 2
studies of hospitalized patients with another medical
documents, however, could argue against this inter-
illness, type 2 MI predominates. Patients with type 2 MI
pretation (Table 1). This issue notwithstanding, the
presenting with acute chest pain differ from the more
work by the APACE Investigators reveals the hetero-
heterogeneous and medically complex cohort of
geneity of type 2 MI: their main findings were: 1) the
patients having type 2 MI in the context of another acute
incidence of type 2 MI increased when CAD was not
illness, who may have multiple identifiable triggers
required to make the diagnosis; and 2) outcomes in
leading to imbalances in myocardial oxygen supply and
those with type 2 MI without CAD had a more benign
demand; venue, context, and mechanism all matter
course, with a 90-day cardiovascular death rate of 0%.
when classifying type 2 MI (Figure 1).
There are caveats regarding the present study.
Regardless of the heterogeneity observed across
First, the design of the APACE study—enrollment of
type 2 MI studies, the diagnosis is frequent and far
patients presenting to the emergency department
from benign (Table 2) (6–22). Some studies show that
with chest discomfort—undoubtedly resulted in a different population than that encountered in other studies of type 2 MI; the latter group is often more
*Editorials published in the Journal of the American College of Cardiology
medically complex and presents with another acute
reflect the views of the authors and do not necessarily represent the
illness that requires hospitalization. Second, it is not
views of JACC or the American College of Cardiology. From the aDivision of Cardiology, Massachusetts General Hospital and Cardiometabolic Trials, Baim Institute for Clinical Research, Boston,
clear that all patients in this analysis “without CAD” actually had normal coronary arteries or normal
Massachusetts; and the Department of Cardiovascular Medicine, Mayo
coronary vascular function, because a normal stress
Clinic, Rochester, Minnesota. Dr. Januzzi has received grants from Roche
test (used as a surrogate test for CAD) cannot exclude
Diagnostics, Siemens, Singulex, Abbott, and Prevencio; served as a
the presence of underlying CAD. Because patients
b
consultant for Roche Diagnostics, Abbott, and Critical Diagnostics; and has served on the endpoint committee for Boehringer Ingelheim, Pfizer,
with type 2 MI often do not undergo coronary
Abbvie, and Janssen. Dr. Sandoval has reported that he has no relation-
evaluation, with a reported range of 7% to 50% of
ships relevant to the contents of this paper to disclose.
patients with type 2 MI referred for angiography,
1570
Januzzi and Sandoval
JACC VOL. 70, NO. 13, 2017 SEPTEMBER 26, 2017:1569–72
Type 2 Myocardial Infarction
most judged to have at least 30% obstruction of 1
T A B L E 1 2007 and 2012 Universal Definition of MI Consensus
coronary vessel (10).
Document Statements Regarding Type 2 MI
It is interesting that patients in this analysis with Year 2007
Year 2012
MI secondary to ischemia due to either increased oxygen demand or decreased supply
MI secondary to an ischemic imbalance. Diagnosed in instances of myocardial injury with necrosis where a condition other than CAD contributes to an imbalance between myocardial oxygen consumption supply and/or demand
Examples: coronary artery spasm, coronary embolism, anemia, arrhythmias, hypertension, or hypotension
type 2 MI without CAD had lower mortality risk over a very short term of follow-up; analyses from the SWEDEHEART (Swedish MI Registry) do support that MI outcomes may differ based on the presence or absence of CAD (23). Based on the low short-term mortality for patients with type 2 MI without CAD, the APACE Investigators argue that assigning a diag-
Examples: coronary endothelial dysfunction, coronary artery spasm, coronary embolism, tachyarrhythmias/ bradyarrhythmias, anemia, respiratory failure, hypotension, and hypertension with or without left ventricular hypertrophy.
nosis of “MI” for such patients may be misleading. Although it is likely that patients with type 2 MI without CAD have lower risk, does short-term death alone matter when informing future MI classification systems? Contrary to establishing a more restrictive definition of MI requiring CAD, we would emphasize
Data from the 2007 and 2012 universal definition of MI consensus document statements (2,3).
that certain groups of patients, in particular women,
CAD ¼ coronary artery disease; MI ¼ myocardial infarction.
can indeed present with MI in the absence of obstructive atherosclerotic CAD, and even with normal coronaries (24,25). Patients with spontaneous coronary
the prevalence of CAD in those having type 2 MI has
artery dissection present unequivocally with acute MI
been difficult to ascertain, with studies reporting CAD
in the absence of CAD, yet numerous series show a low
rates ranging from 28% to 78% (4). In 1 study, patients
mortality, some reporting a death rate of 0% at short-
with subsequent type 2 MI indeed did have CAD, with
term follow-up (26). Should we label such patients as
F I G U R E 1 A Proposed Framework for Type 2 MI
Emergency department
Inpatient wards
Post-operative setting
Intensive care unit
Main reason leading to clinical presentation (e.g.: chest pain) Context Secondary to another illness or process Coronary spasm Type 2 myocardial infarction
Pure supply reduction
Coronary embolism
Not due to obstructive CAD
Coronary endothelial dysfunction Spontaneous coronary artery dissection
Mechanisms Increased demand Supply-demand imbalance
Tachyarrhythmias
If concomitant CAD:
Severe hypertension Bradyarrhythmias
Follow CAD guidelines, risk reduction strategies.
Severe hypoxia Reduced supply Severe anemia Severe hypotension
If no concomitant CAD: Treat/control trigger.
The venue, context, and mechanism of type 2 MI should be considered when classifying the diagnosis and considering therapy. CAD ¼ coronary artery disease; MI ¼ myocardial infarction.
Januzzi and Sandoval
JACC VOL. 70, NO. 13, 2017 SEPTEMBER 26, 2017:1569–72
Type 2 Myocardial Infarction
T A B L E 2 Mortality for Type 2 MI in Selected Studies
First Author (Ref. #)
Number of Type 2 MIs
Mortality
Comments
Saaby et al. (6) Sarkisian et al. (7)
119
Index hospitalization: 19% 30 days: 24% 1 yr: 44% 2.1 yrs: 49% 3.2 yrs: 63%
Unselected hospital patients with cTnI measured on clinical indication. Used strict criteria to adjudicate type 2 MI.
Sandoval et al. (8)
140
180 days: 13% 2 yrs: 22%
U.S. patients presenting to the emergency department undergoing cTnI measurements on clinical indication.
Sandoval et al. (9)
190
180 days: 11%
U.S. patients presenting to the emergency department undergoing cTnI measurements on clinical indication.
Gaggin et al. (10)
152
All cause death, 4 years: 56% Cardiovascular death, 4 years: 42%
Consecutive patients undergoing coronary and peripheral angiography followed for subsequent events, including type 2 MI
Bonaca et al. (11)
42
Cardiovascular death at 180 days: 7%
Post-hoc analysis of acute coronary syndrome randomized controlled trial.
Shah et al. (12) Chapman et al. (13)
429
1 yr: 31% 5 yrs: 60%
Consecutive patients to regional cardiac center with cTnI $50 ng/l irrespective of clinical presentation. Included all patients in whom cTn was measured as part of routine clinical care whether or not they presented with suspected acute coronary syndrome.
Meigher et al. (14)
452
Index hospitalization: 11%
U.S. patients presenting to the emergency department with increased cTn.
1-yr mortality: 25%
Consecutive patients with acute MI admitted to a cardiac or medical intensive care.
60 days: CV death 2.7%, all-cause: 8% 90 days: CV death 3.7%, all-cause: 9.8% 120 days: CV death 3.7%, all-cause 9.8%
Patients presenting to the emergency department with typical angina pectoris or other thoracic sensations at rest or minor exertion that are suspected to be caused by myocardial ischemia.
Baron et al. (15) Nestelberger et al. (16)
1,403 240
Javed et al. (17)
64
Index hospitalization: 14%
All adult hospitalized patients who had an abnormal cTn.
ski et al. (18) Szyman
58
30 days: 5.2% 180 days: 6.9%
Consecutive patients presenting to the emergency department with an initial diagnosis of acute coronary syndrome.
Smilowitz et al. (19)
146
Index hospitalization: CV death 2%, all-cause 11.6% 30 days: CV death 4.1%, all-cause 15.1% 1.8 yrs: CV death 5.5%, all-cause 30.8%
Patients admitted to a Veterans Affairs tertiary hospital with a rise and fall in cTn.
Stein et al. (20)
127
Index hospitalization: 12% 30 days: 14% 1 yr: 24%
All intensive ICCU and cardiology wards in all public hospitals in Israel on patients admitted with a diagnosis of acute coronary syndrome.
Cediel et al. (21)
194
2 yrs: 40%
Patients who were admitted at the emergency department in whom at least one cTn was obtained. Used strict criteria to adjudicate type 2 MI.
El-Haddad et al. (22)
295
Index hospitalization: 28%
Hospitalized patients with an increased cTn.
cTn ¼ cardiac troponin; cTnI ¼ cardiac troponin I; CV ¼ cardiovascular; ICCU ¼ intensive cardiac care unit; MI ¼ myocardial infarction.
not having MI based on their low mortality rates?
Although the discovery made by Dr. Hammer led to
Although we agree in principle that type 2 MI without
numerous efforts that improved our understanding
CAD likely has a more benign course, we do not support
and improved outcomes for patients with MI, the case
reconsideration of their diagnosis—this should be
was not due to CAD, but rather a case involving an
considered just one of many causes of type 2 MI, and
aortic valve vegetation with an attached thrombus
one with a possibly less malignant outcome.
that obstructed the coronary artery (29), a condition
Recognizing that type 2 MI reflects a diagnosis
we would refer to as today as type 2 MI. For over
with heterogeneous causes, we propose investigating
a century, our attention has been largely placed
type 2 MI using a phenotype-specific approach;
on atherothrombotic causes of type 1 MI. Moving
this framework is similar to that of another hetero-
forward, a similar urgency should be applied to
geneous diagnosis: heart failure with preserved
understanding classification and management of the
ejection fraction (27). Only with a clear understanding
many faces of type 2 MI.
of the spectrum of type 2 MI can we approach the development of treatment options for this frequently
ADDRESS FOR CORRESPONDENCE: Dr. James L.
encountered and often deleterious condition.
Januzzi, Jr., Division of Cardiology, Massachusetts
The first reported case of coronary thrombosis was published in 1878 by Dr. Adam Hammer (28).
General Hospital, Yawkey 5984, Boston, Massachusetts 02114. E-mail: [email protected].
1571
1572
Januzzi and Sandoval
JACC VOL. 70, NO. 13, 2017 SEPTEMBER 26, 2017:1569–72
Type 2 Myocardial Infarction
REFERENCES 1. Friedberg CK, Horn H. Acute myocardial infarction not due to coronary artery occlusion. JAMA 1939;112:1675–9. 2. Thygesen K, Alpert JS, White HD, for the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. University definition of myocardial infarction. J Am Coll Cardiol 2007; 27:2173–95. 3. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012;60:1581–98. 4. Sandoval Y, Thygesen K. Myocardial infarction type 2 and myocardial injury. Clin Chem 2017;63: 101–7. 5. Sandoval Y, Smith SW, Thordsen SE, Apple FS. Supply/demand type 2 myocardial infarction: should we be paying more attention? J Am Coll Cardiol 2014;63:2079–87. 6. Saaby L, Poulsen TS, Diederichsen AC, et al. Mortality rate in type 2 myocardial infarction: observations from an unselected hospital cohort. Am J Med 2014;127:295–302.
Heart Federation universal definition of myocardial infarction classification system and the risk of cardiovascular death: observations from the TRITON-TIMI 38 trial (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38). Circulation 2012;125:577–83. 12. Shah AS, McAllister DA, Mills R, et al. Sensitive troponin assay and the classification of myocardial infarction. Am J Med 2015;128:493–501. 13. Chapman AR, Shah AS, Anand A, et al. Long term outcomes of patients with type 2 myocardial infarction or myocardial injury. Heart 2016;102:A80. 14. Meigher S, Thode HC, Peacock WF, Bock JL, Gruberg L, Singer AJ. Causes of elevated cardiac troponins in the emergency department and their associated mortality. Acad Emerg Med 2016;23: 1267–73. 15. Baron T, Hambraeus K, Sundström J, Erlinge D, Jernberg T, Lindahl B, for the TOTAL-AMI Study Group. Type 2 myocardial infarction in clinical practice. Heart 2015;101:101–6.
characteristics and outcomes of patients with myocardial infarction, myocardial injury, and nonelevated troponins. Am J Med 2016;129:446.e5–21.
16. Nestelberger T, Boeddinghaus J, Badertscher P, et al. Effect of definition on incidence and prognosis of type 2 myocardial infarction. J Am Coll Cardiol 2017;70:1558–68.
8. Sandoval Y, Smith SW, Sexter A, et al. Type 1 and 2 myocardial infarction and myocardial injury: clinical transition to high-sensitivity cardiac troponin I. Am J Med 2017 July 21 [E-pub ahead of print].
17. Javed U, Aftab W, Ambrose JA, et al. Frequency of elevated troponin I and diagnosis of acute myocardial infarction. Am J Cardiol 2009; 104:9–13.
9. Sandoval Y, Thordsen SE, Smith SW, et al. Cardiac troponin changes to distinguish type 1 and
ski FM, Karpin ski G, Płatek AE, et al. 18. Szyman Clinical characteristics, aetiology, and occurrence of type 2 myocardial infarction. Kardiol Pol 2014; 72:339–44.
7. Sarkisian L, Saaby L, Poulsen TS, et al. Clinical
type 2 myocardial infarction and 180-day mortality risk. Eur Heart J Acute Cardiovasc Care 2014;3: 317–25. 10. Gaggin HK, Liu Y, Lyass A, et al. Incident type 2 myocardial infarction in a cohort of patients undergoing coronary or peripheral arterial angiography. Circulation 2017;135:116–27. 11. Bonaca MP, Wiviott SD, Braunwald E, et al. American College of Cardiology/American Heart Association/European Society of Cardiology/World
19. Smilowitz NR, Subramanyam P, Gianos E, Reynolds HR, Shah B, Sedlis SP. Treatment and outcomes of type 2 myocardial infarction and myocardial injury compared with type 1 myocardial infarction. Coron Artery Dis 2017 Jul 25 [E-pub ahead of print]. 20. Stein GY, Herscovici G, Korenfeld R, et al. Type-II myocardial infarction—patient characteristics,
management and outcomes. PLoS One 2014;9: e84285. 21. Cediel G, Gonzalez-Del-Hoyo M, Carrasquer A, Sanchez R, Boqué C, Bardají A. Outcomes with type 2 myocardial infarction compared with nonischaemic myocardial injury. Heart 2017;103: 616–22. 22. El-Haddad H, Robinson E, Swett K, Wells GL. Prognostic implications of type 2 myocardial infarctions. World J Cardiovasc Dis 2012;2: 237–41. 23. Baron T, Hambraeus K, Sundström J, et al. Impact of long-term mortality of presence of obstructive coronary artery disease and classification of myocardial infarction. Am J Med 2016; 129:398–406. 24. Pasupathy S, Tavella R, Beltrame JF. Myocardial infarction with nonobstructive coronary arteries (MINOCA): the past, present and future management. Circulation 2017;135: 1490–3. 25. Reynolds HR, Srichai MB, Iqbal SN, et al. Mechanisms of myocardial infarction in women without angiographically obstructive coronary artery disease. Circulation 2011;124:1414–25. 26. Saw J, Mancini GB, Humphries KH. Contemporary review on spontaneous coronary artery dissection. J Am Coll Cardiol 2016;68:297–312. 27. Shah SJ, Kitzman DW, Borlaug BA, et al. Phenotype-specific treatment of heart failure with preserved ejection fraction: a multiorgan roadmap. Circulation 2016;134:73–90. 28. Hammer A. Ein Fall von thrombostischem Vershlüsse einer der Kranzarterien des Herzens. Wien Med Wchnschr 1878;28:97–102. 29. Fye WB. The delayed diagnosis of myocardial infarction: it took half a century! Circulation 1985; 72:262–71.
KEY WORDS diagnosis, high-sensitivity cardiac troponin, type 2 myocardial infarction
VOL. 70, NO. 13, 2017
ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jacc.2017.07.784
EDITORIAL COMMENT
The Many Faces of Type 2 Myocardial Infarction* James L. Januzzi, MD,a Yader Sandoval, MDb
C
linicians have long recognized that acute
mortality after type 2 MI is similar to type 1 MI, or
myocardial infarction (MI) can occur in the
even higher.
absence of atherothrombosis (1). The Uni-
versal Definition of MI Global Taskforce introduced
SEE PAGE 1558
a classification system in 2007 (and reaffirmed in
In this issue of the Journal, the APACE (Advanta-
2012) that defined type 2 MI (following standard diag-
geous Predictors of Acute Coronary Syndrome Evalu-
nostic criteria) as MI occurring due to an imbalance in
ation) investigators offer their insights on type 2 MI
myocardial oxygen supply and/or demand not caused
based on a secondary analysis involving patients with
by atherosclerotic plaque disruption (2,3) (Table 1).
acute chest pain (16). In this analysis, the diagnosis of
Nevertheless, ambiguity remains regarding how to
type 2 MI was considered using 2 methods: 1 required
diagnose type 2 MI and how to distinguish it from both
presence of coronary artery disease (CAD) and the
type 1 MI and myocardial injury (4,5). For example,
other did not. This was based on a presumption by the
because those with type 2 MI are less likely to have chest
authors that in the 2007 definition, CAD was required
pain, studies focusing on patients with chest discomfort
to diagnose type 2 MI (2), whereas in the 2012 version,
have a higher prevalence of type 1 MI, whereas in
type 2 MI CAD was not required (3). Scrutiny of the 2
studies of hospitalized patients with another medical
documents, however, could argue against this inter-
illness, type 2 MI predominates. Patients with type 2 MI
pretation (Table 1). This issue notwithstanding, the
presenting with acute chest pain differ from the more
work by the APACE Investigators reveals the hetero-
heterogeneous and medically complex cohort of
geneity of type 2 MI: their main findings were: 1) the
patients having type 2 MI in the context of another acute
incidence of type 2 MI increased when CAD was not
illness, who may have multiple identifiable triggers
required to make the diagnosis; and 2) outcomes in
leading to imbalances in myocardial oxygen supply and
those with type 2 MI without CAD had a more benign
demand; venue, context, and mechanism all matter
course, with a 90-day cardiovascular death rate of 0%.
when classifying type 2 MI (Figure 1).
There are caveats regarding the present study.
Regardless of the heterogeneity observed across
First, the design of the APACE study—enrollment of
type 2 MI studies, the diagnosis is frequent and far
patients presenting to the emergency department
from benign (Table 2) (6–22). Some studies show that
with chest discomfort—undoubtedly resulted in a different population than that encountered in other studies of type 2 MI; the latter group is often more
*Editorials published in the Journal of the American College of Cardiology
medically complex and presents with another acute
reflect the views of the authors and do not necessarily represent the
illness that requires hospitalization. Second, it is not
views of JACC or the American College of Cardiology. From the aDivision of Cardiology, Massachusetts General Hospital and Cardiometabolic Trials, Baim Institute for Clinical Research, Boston,
clear that all patients in this analysis “without CAD” actually had normal coronary arteries or normal
Massachusetts; and the Department of Cardiovascular Medicine, Mayo
coronary vascular function, because a normal stress
Clinic, Rochester, Minnesota. Dr. Januzzi has received grants from Roche
test (used as a surrogate test for CAD) cannot exclude
Diagnostics, Siemens, Singulex, Abbott, and Prevencio; served as a
the presence of underlying CAD. Because patients
b
consultant for Roche Diagnostics, Abbott, and Critical Diagnostics; and has served on the endpoint committee for Boehringer Ingelheim, Pfizer,
with type 2 MI often do not undergo coronary
Abbvie, and Janssen. Dr. Sandoval has reported that he has no relation-
evaluation, with a reported range of 7% to 50% of
ships relevant to the contents of this paper to disclose.
patients with type 2 MI referred for angiography,
1570
Januzzi and Sandoval
JACC VOL. 70, NO. 13, 2017 SEPTEMBER 26, 2017:1569–72
Type 2 Myocardial Infarction
most judged to have at least 30% obstruction of 1
T A B L E 1 2007 and 2012 Universal Definition of MI Consensus
coronary vessel (10).
Document Statements Regarding Type 2 MI
It is interesting that patients in this analysis with Year 2007
Year 2012
MI secondary to ischemia due to either increased oxygen demand or decreased supply
MI secondary to an ischemic imbalance. Diagnosed in instances of myocardial injury with necrosis where a condition other than CAD contributes to an imbalance between myocardial oxygen consumption supply and/or demand
Examples: coronary artery spasm, coronary embolism, anemia, arrhythmias, hypertension, or hypotension
type 2 MI without CAD had lower mortality risk over a very short term of follow-up; analyses from the SWEDEHEART (Swedish MI Registry) do support that MI outcomes may differ based on the presence or absence of CAD (23). Based on the low short-term mortality for patients with type 2 MI without CAD, the APACE Investigators argue that assigning a diag-
Examples: coronary endothelial dysfunction, coronary artery spasm, coronary embolism, tachyarrhythmias/ bradyarrhythmias, anemia, respiratory failure, hypotension, and hypertension with or without left ventricular hypertrophy.
nosis of “MI” for such patients may be misleading. Although it is likely that patients with type 2 MI without CAD have lower risk, does short-term death alone matter when informing future MI classification systems? Contrary to establishing a more restrictive definition of MI requiring CAD, we would emphasize
Data from the 2007 and 2012 universal definition of MI consensus document statements (2,3).
that certain groups of patients, in particular women,
CAD ¼ coronary artery disease; MI ¼ myocardial infarction.
can indeed present with MI in the absence of obstructive atherosclerotic CAD, and even with normal coronaries (24,25). Patients with spontaneous coronary
the prevalence of CAD in those having type 2 MI has
artery dissection present unequivocally with acute MI
been difficult to ascertain, with studies reporting CAD
in the absence of CAD, yet numerous series show a low
rates ranging from 28% to 78% (4). In 1 study, patients
mortality, some reporting a death rate of 0% at short-
with subsequent type 2 MI indeed did have CAD, with
term follow-up (26). Should we label such patients as
F I G U R E 1 A Proposed Framework for Type 2 MI
Emergency department
Inpatient wards
Post-operative setting
Intensive care unit
Main reason leading to clinical presentation (e.g.: chest pain) Context Secondary to another illness or process Coronary spasm Type 2 myocardial infarction
Pure supply reduction
Coronary embolism
Not due to obstructive CAD
Coronary endothelial dysfunction Spontaneous coronary artery dissection
Mechanisms Increased demand Supply-demand imbalance
Tachyarrhythmias
If concomitant CAD:
Severe hypertension Bradyarrhythmias
Follow CAD guidelines, risk reduction strategies.
Severe hypoxia Reduced supply Severe anemia Severe hypotension
If no concomitant CAD: Treat/control trigger.
The venue, context, and mechanism of type 2 MI should be considered when classifying the diagnosis and considering therapy. CAD ¼ coronary artery disease; MI ¼ myocardial infarction.
Januzzi and Sandoval
JACC VOL. 70, NO. 13, 2017 SEPTEMBER 26, 2017:1569–72
Type 2 Myocardial Infarction
T A B L E 2 Mortality for Type 2 MI in Selected Studies
First Author (Ref. #)
Number of Type 2 MIs
Mortality
Comments
Saaby et al. (6) Sarkisian et al. (7)
119
Index hospitalization: 19% 30 days: 24% 1 yr: 44% 2.1 yrs: 49% 3.2 yrs: 63%
Unselected hospital patients with cTnI measured on clinical indication. Used strict criteria to adjudicate type 2 MI.
Sandoval et al. (8)
140
180 days: 13% 2 yrs: 22%
U.S. patients presenting to the emergency department undergoing cTnI measurements on clinical indication.
Sandoval et al. (9)
190
180 days: 11%
U.S. patients presenting to the emergency department undergoing cTnI measurements on clinical indication.
Gaggin et al. (10)
152
All cause death, 4 years: 56% Cardiovascular death, 4 years: 42%
Consecutive patients undergoing coronary and peripheral angiography followed for subsequent events, including type 2 MI
Bonaca et al. (11)
42
Cardiovascular death at 180 days: 7%
Post-hoc analysis of acute coronary syndrome randomized controlled trial.
Shah et al. (12) Chapman et al. (13)
429
1 yr: 31% 5 yrs: 60%
Consecutive patients to regional cardiac center with cTnI $50 ng/l irrespective of clinical presentation. Included all patients in whom cTn was measured as part of routine clinical care whether or not they presented with suspected acute coronary syndrome.
Meigher et al. (14)
452
Index hospitalization: 11%
U.S. patients presenting to the emergency department with increased cTn.
1-yr mortality: 25%
Consecutive patients with acute MI admitted to a cardiac or medical intensive care.
60 days: CV death 2.7%, all-cause: 8% 90 days: CV death 3.7%, all-cause: 9.8% 120 days: CV death 3.7%, all-cause 9.8%
Patients presenting to the emergency department with typical angina pectoris or other thoracic sensations at rest or minor exertion that are suspected to be caused by myocardial ischemia.
Baron et al. (15) Nestelberger et al. (16)
1,403 240
Javed et al. (17)
64
Index hospitalization: 14%
All adult hospitalized patients who had an abnormal cTn.
ski et al. (18) Szyman
58
30 days: 5.2% 180 days: 6.9%
Consecutive patients presenting to the emergency department with an initial diagnosis of acute coronary syndrome.
Smilowitz et al. (19)
146
Index hospitalization: CV death 2%, all-cause 11.6% 30 days: CV death 4.1%, all-cause 15.1% 1.8 yrs: CV death 5.5%, all-cause 30.8%
Patients admitted to a Veterans Affairs tertiary hospital with a rise and fall in cTn.
Stein et al. (20)
127
Index hospitalization: 12% 30 days: 14% 1 yr: 24%
All intensive ICCU and cardiology wards in all public hospitals in Israel on patients admitted with a diagnosis of acute coronary syndrome.
Cediel et al. (21)
194
2 yrs: 40%
Patients who were admitted at the emergency department in whom at least one cTn was obtained. Used strict criteria to adjudicate type 2 MI.
El-Haddad et al. (22)
295
Index hospitalization: 28%
Hospitalized patients with an increased cTn.
cTn ¼ cardiac troponin; cTnI ¼ cardiac troponin I; CV ¼ cardiovascular; ICCU ¼ intensive cardiac care unit; MI ¼ myocardial infarction.
not having MI based on their low mortality rates?
Although the discovery made by Dr. Hammer led to
Although we agree in principle that type 2 MI without
numerous efforts that improved our understanding
CAD likely has a more benign course, we do not support
and improved outcomes for patients with MI, the case
reconsideration of their diagnosis—this should be
was not due to CAD, but rather a case involving an
considered just one of many causes of type 2 MI, and
aortic valve vegetation with an attached thrombus
one with a possibly less malignant outcome.
that obstructed the coronary artery (29), a condition
Recognizing that type 2 MI reflects a diagnosis
we would refer to as today as type 2 MI. For over
with heterogeneous causes, we propose investigating
a century, our attention has been largely placed
type 2 MI using a phenotype-specific approach;
on atherothrombotic causes of type 1 MI. Moving
this framework is similar to that of another hetero-
forward, a similar urgency should be applied to
geneous diagnosis: heart failure with preserved
understanding classification and management of the
ejection fraction (27). Only with a clear understanding
many faces of type 2 MI.
of the spectrum of type 2 MI can we approach the development of treatment options for this frequently
ADDRESS FOR CORRESPONDENCE: Dr. James L.
encountered and often deleterious condition.
Januzzi, Jr., Division of Cardiology, Massachusetts
The first reported case of coronary thrombosis was published in 1878 by Dr. Adam Hammer (28).
General Hospital, Yawkey 5984, Boston, Massachusetts 02114. E-mail: [email protected].
1571
1572
Januzzi and Sandoval
JACC VOL. 70, NO. 13, 2017 SEPTEMBER 26, 2017:1569–72
Type 2 Myocardial Infarction
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KEY WORDS diagnosis, high-sensitivity cardiac troponin, type 2 myocardial infarction