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Classification of Myocardial Infarction: Frequency and Features of Type 2 Myocardial Infarction

      Abstract

      Background

      The classification of myocardial infarction into 5 types was introduced in 2007 as an important component of the universal definition. In contrast to the plaque rupture–related type 1 myocardial infarction, type 2 myocardial infarction is considered to be caused by an imbalance between demand and supply of oxygen in the myocardium. However, no specific criteria for type 2 myocardial infarction have been established.

      Methods

      We prospectively studied unselected hospital patients who had cardiac troponin I measured on clinical indication. The diagnosis and classification of myocardial infarction were established, and the frequency and features of type 2 myocardial infarction were investigated by use of novel developed criteria.

      Results

      From January 2010 to January 2011, a total of 7230 consecutive patients who had cardiac troponin I measured were evaluated, and 4499 patients qualified for inclusion. The diagnosis of myocardial infarction was established in 553 patients, of whom 386 (72%) had a type 1 myocardial infarction and 144 (26%) had a type 2 myocardial infarction. Patients in the group with type 2 myocardial infarction were older and more likely to be female, and had more comorbidities. The proportion of patients without significant coronary artery disease was higher in those with type 2 myocardial infarction (45%) than in those with type 1 myocardial infarction (12%) (P < .001). Tachyarrhythmias, anemia, and respiratory failure were the most prevalent mechanisms causing type 2 myocardial infarction.

      Conclusions

      In a cohort of patients with myocardial infarction who were admitted consecutively through 1 year, the category of type 2 myocardial infarction comprised one fourth when diagnosed by the use of newly developed criteria. Approximately half of patients with type 2 myocardial infarction had no significant coronary artery disease.

      Keywords

      The clinical classification of myocardial infarction into 5 types was introduced in 2007 as an important component of the universal definition.
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.
      Although the spontaneous type 1 myocardial infarction is related to a coronary plaque rupture, fissuring, or dissection with resulting intraluminal thrombosis, type 2 myocardial infarction is secondary to myocardial ischemia resulting from increased oxygen demand or decreased supply. Type 3 myocardial infarction is linked to unexpected cardiac death when cardiac biomarkers are unavailable, whereas types 4 and 5 myocardial infarction are procedure related.
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.
      The launch of this classification has raised clinical interest particularly in type 2 myocardial infarction. Several clinical conditions have been proposed as being the cause of type 2 myocardial infarction,
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.
      but so far no specific criteria have been proposed. The object of this study is to elucidate the frequency and characteristics of type 2 myocardial infarction in a prospective design when applying the novel developed clinical criteria.
      • In unselected hospital patients, one fourth of all myocardial infarctions are type 2.
      • The most frequent mechanisms causing type 2 myocardial infarction are anemia, respiratory failure, and tachyarrhythmias.
      • Approximately 50% of patients with type 2 myocardial infarction are found in other departments than cardiology.
      • Approximately 50% of patients with type 2 myocardial infarction have no significant coronary artery disease.

      Materials and Methods

      Study Design and Population

      The study comprises patients consecutively admitted to a 1000-bed university hospital, which serves as a tertiary referral center for a region with 1.2 million inhabitants and as a local hospital for a catchment area of 300,000 residents. The data is a part of the DEF-AMI Study (Consequences of the universal 2007 DEFinition of Acute Myocardial Infarction studied in a Danish consecutive hospital population). All admitted patients who had cardiac troponin I (cTnI) measured were traced through retrieval 3 times daily at the Department of  Clinical Biochemistry of the hospital. Within 24 hours after the first cTnI sampling, all patients had a supplementary history taken by dedicated study personnel paying special attention to symptoms on admission, clinical characteristics, and comorbidity. We only included comorbidity that could be validated by confirmation from the patient's medical records or the list of current medication. Exclusion criteria were residence outside the local catchment area, age <18 years, and a cTnI sample taken in an outpatient clinic.

      Biochemical Analysis

      The cTnI was analyzed on an Architect c16000 (Abbott Diagnostics, Abbott Park, Ill). This analysis has a detection limit of 0.01 μg/L, with an upper reference limit of the 99th percentile of 0.028 μg/L and a coefficient of variation <10% at 0.032 μg/L. Thus, a cTnI value >0.03 μg/L is considered the decision limit for the diagnosis of myocardial infarction.

      Imaging Data

      Information on echocardiographic examinations was retrieved from the hospital records. In addition, information on the results of in-hospital coronary angiography was collected from the Western Denmark Heart Registry.
      • Schmidt M.
      • Maeng M.
      • Jakobsen CJ.
      • et al.
      Existing data sources for clinical epidemiology: The Western Denmark Heart Registry.
      A significant coronary artery stenosis had to be ≥50% of the artery diameter. Patients were classified as having no significant coronary artery disease or 1-, 2-, or 3-vessel disease according to the number of major coronary arteries with significant stenoses. In the Western Denmark Heart Registry, significant left main stenoses are registered separately.

      Definition of Type 2 Myocardial Infarction

      In addition to the indicated diagnostic biomarker criteria we developed, partly on the basis of data from the literature,
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.
      • Dellinger R.P.
      • Levy M.M.
      • Carlet J.M.
      • et al.
      Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.
      • Celli B.R.
      • MacNee W.
      • Agusti A.
      • et al.
      Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.
      • Dickstein K.
      • Cohen-Solal A.
      • Filippatos G.
      • et al.
      ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart.
      • Nieminen M.S.
      • Harjola VP.
      Definition and epidemiology of acute heart failure syndromes.
      specific clinical standards for the definition of type 2 myocardial infarction, that is, conditions reflecting an imbalance between myocardial oxygen supply and demand. Conditions with decreased oxygen supply were:
      • Anemia defined as a hemoglobin concentration <5.5 mmol/L for men and <5.0 mmol/L for women;
      • Shock defined as systolic blood pressure <90 mm Hg together with signs of organ dysfunction (ie, metabolic acidosis, arterial oxygen tension <8 kPa, oliguria [diuresis <30 mL/h for at least 3 hours], or encephalopathy)
        • Dellinger R.P.
        • Levy M.M.
        • Carlet J.M.
        • et al.
        Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.
        • Celli B.R.
        • MacNee W.
        • Agusti A.
        • et al.
        Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.
        • Dickstein K.
        • Cohen-Solal A.
        • Filippatos G.
        • et al.
        ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart.
        ;
      • Bradyarrhythmia requiring medical treatment or cardiac pacing;
      • Coronary embolus in the presence of an increased risk of embolism (left heart endocarditis, intracardiac mural thrombus, documented venous thrombus, and a patent foramen ovale or atrial septum defect); or
      • Respiratory failure with an arterial oxygen tension <8 kPa and clinical signs of acute respiratory failure lasting ≥20 minutes.
        • Celli B.R.
        • MacNee W.
        • Agusti A.
        • et al.
        Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.
      Conditions with increased oxygen demand were:
      • Ventricular tachyarrhythmia lasting ≥20 minutes;
      • Supraventricular tachyarrhythmia lasting ≥20 minutes with a ventricular rate >150 beats/min;
      • Hypertensive pulmonary edema defined as the presence of a systolic blood pressure >160 mm Hg, signs of pulmonary edema, and a need for treatment with nitrates or diuretics
        • Nieminen M.S.
        • Harjola VP.
        Definition and epidemiology of acute heart failure syndromes.
        ; or
      • Arterial hypertension with a systolic blood pressure >160 mm Hg and concomitant left ventricular hypertrophy identified by echocardiography or electrocardiogram.
      The type of acute myocardial infarction also was categorized as ST-elevation myocardial infarction or non–ST-elevation myocardial infarction as defined in the universal definition.
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.
      Patients with new (or presumably new) left bundle branch block were designated as having an ST-elevation myocardial infarction. The remaining patients, including those with pacemaker rhythm and preexisting bundle branch block, were categorized as having non–ST-elevation myocardial infarction.

      Other Types of Myocardial Infarction

      Patients with type 3 myocardial infarction were not included in this study, because cardiac biomarkers per definition are unavailable in these patients.
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.
      Type 4a, 4b, and 5 myocardial infarctions were defined according to the universal definition.
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.

      Classification of Patients With Myocardial Necrosis but Without Myocardial Infarction

      Patients with cTnI values >0.03μg/L but without overt myocardial ischemia were classified into the following groups adapted from Thygesen et al
      • Thygesen K.
      • Mair J.
      • Katus H.
      • et al.
      Recommendations for the use of cardiac troponin measurement in acute cardiac care.
      :
      • cTnI elevation related to secondary ischemia (eg, hypertrophic cardiomyopathy, coronary vasculitis);
      • cTnI elevation not related to ischemia (eg, radiofrequency ablation, cardiac incision with surgery, chemotherapy);
      • cTnI elevation due to extracardiac conditions (eg, infection, stroke, renal failure);
      • cTnI elevation resulting from at least 2 cardiac or extracardiac conditions;
      • cTnI elevation of indeterminate origin.

      Classification of Patients Without Myocardial Necrosis

      Patients with cTnI ≤0.03 μg/L were classified as having unstable angina pectoris, prior or no prior ischemic heart disease. Unstable angina pectoris was defined as unstable chest discomfort (rest, new onset, or worsening of angina) or dynamic electrocardiographic changes indicative of ischemia.
      • Braunwald E.
      Unstable angina. A classification.
      Prior ischemic heart disease was defined as a documented medical history of such a diagnosis or current medical treatment for ischemic heart disease.

      Adjudicated Final Diagnosis

      Three experienced cardiologists (LS, TSP, HM) evaluated the conditions underlying the index event. The cardiac diagnoses were based on the source information provided by the supplementary history obtained, laboratory sheets, and patient records. The Task Force Co-Chairman (KT) of the universal definition was consulted in all cases of diagnostic ambiguity to reach consensus on the classification.
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.
      Patients with normal cTnI values were classified according to the 10th edition of International Classification of Diseases system provided at discharge.

      Statistical Analysis

      Continuous variables are presented as medians with interquartile range or as means (± standard deviation). Categoric variables are listed as numbers (%). The Mann-Whitney U test was used to calculate P values for continuous variables. Pearson chi-square test was used to compare categoric variables. For comparing larger contingency tables (r*c tables) the chi-square test also was used. Because less than 20% of the expected numbers are less than 5 and none are less than 1, the chi-square test is considered valid. P values less than .05 were considered to indicate statistical significance. All analyses were performed by the study group using STATA version 11 (StataCorp LP, College Station, Tex). The study complied with the Declaration of Helsinki and was approved by the Danish National Committee on Biomedical Research Ethics and the Danish Data Protection Agency.

      Results

      cTnI was measured in 7230 hospitalized patients admitted between January 6, 2010, and January 5, 2011. Approximately one third of patients did not meet the inclusion criteria. Thus, 4499 patients were enrolled, and of these 1961 had cTnI elevation above the 99th percentile upper reference limit. Figure 1 shows that 553 patients (12.3%) had myocardial infarction.
      Figure thumbnail gr1
      Figure 1Patient inclusion. AP = angina pectoris; CKMB = creatine kinase MB; cTnI = cardiac troponin I; GP = general practitioner; IHD = ischemic heart disease; MI = myocardial infarction.

      Classification According to the Universal Definition

      On the basis of the universal definition, 397 patients (71.8%) were classified as having type 1 myocardial infarction and 144 patients (26%) were classified as having type 2 myocardial infarction (Table 1). When compared with patients with type 1 myocardial infarction, patients with type 2 myocardial infarction were older and more likely female. Furthermore, the patients with type 2 myocardial infarction had more comorbidities (heart failure, renal failure, chronic obstructive pulmonary disease, and arrhythmias). Moreover, patients with type 2 myocardial infarction had significantly lower peak cTnI values and more non–ST-elevation myocardial infarction when compared with patients with type 1 myocardial infarction. The rate of coronary angiography was lower in type 2 myocardial infarction, and the pattern of coronary artery disease differed significantly with only approximately half of patients with type 2 myocardial infarction having significant coronary artery disease (Figure 2). Twelve patients (2.2%) had type 4a (n = 2), type 4b (n = 7), or type 5 myocardial infarction (n = 3).
      Table 1Baseline Characteristics of 397 Patients with Type 1 Myocardial Infarction and 144 Patients with Type 2 Myocardial Infarction
      CharacteristicsType 1 MI (N = 397)Type 2 MI (N = 144)P Value
      Age, y (± SD)71 (14)75 (11).010
      Male, no. (%)249 (62.7)76 (52.8).04
      Risk factors, no. (%)
       Diabetes52 (13.1)40 (27.9)<.001
       Hypercholesterolemia158 (39.8)60 (41.8).69
       Hypertension215 (54.2)81 (56.3).67
       Current smoker, no./total no. (%)129/342 (37.7)35/108 (32.4).07
       Family history, no./total no. (%)103/305 (33.8)14/74 (18.9).01
      Medical history, no. (%)
       Prior MI96 (24.2)39 (27.1).49
       Prior CABG37 (9.3)14 (9.7).89
       Prior percutaneous coronary intervention57 (14.4)25 (17.4).39
       Heart failure45 (11.3)34 (23.6)<.001
       Prior stroke54 (13.6)31 (21.5).03
       Peripheral arterial disease21 (5.3)18 (12.5).004
       Renal failure23 (5.8)20 (13.9).002
       Chronic obstructive pulmonary disease46 (11.6)36 (25.0)<.001
       Arrhythmia50 (12.6)34 (23.6).002
      Laboratory data, median/total no. (IQR)
       First troponin I, μg/L0.27 (0.06-1.48)0.20 (0.07-0.78).22
       Peak troponin I value, μg/L2.96 (0.44-15.85)1.09 (0.43-3.24)<.001
       Hemoglobin, mmol/L8.2/391 (7.4-8.9)7.7/138 (6.2-8.9)<.001
       Leukocytes, 10E9/L10.1/391 (7.7-12.8)11.6/142 (8.9-17.6)<.001
       Creatinine (enzymatic)-P, μmol/L84/394 (70-103)102/143 (76-141)<.001
       C-reactive protein, mg/L5/391 (2-18)21/134 (4-63)<.001
      Clinical findings, median/total no. (IQR)
       Systolic blood pressure, mm Hg146/395 (122-168)139/140 (106-167).01
       Diastolic blood pressure, mm Hg86/395 (73-101)77/140 (62-96)<.001
       Heart rate, beats/min80/393 (68-100)113/142 (90-131)<.001
      Ejection fraction, median/total no. (IQR)50/340 (40-55)40/107 (30-55)<.001
      ST-elevation MI, no. (%)130 (32.7)5 (3.4)<.001
      Non–ST-elevation MI, no. (%)267 (67.3)139 (96.6)<.001
      Coronary angiography, no. (%)281 (70.8)31 (21.5)<.001
      CABG = coronary artery bypass grafting; IQR = interquartile range; MI = myocardial infarction; SD = standard deviation.
      Figure thumbnail gr2
      Figure 2Results of coronary angiography. (A) Proportion of patients with type 1 versus type 2 myocardial infarction with or without significant coronary artery disease. (B) Patients are grouped according to the number of arteries with significant disease. Patients with left main disease are separately registered. One patient with type 1 myocardial infarction with left main disease had no other significant coronary lesions. The remaining 19 patients with left main disease had at least 1 more coronary vessel with significant coronary artery disease. MI = myocardial infarction.

      Mechanisms Underlying Type 2 Myocardial Infarction

      Figure 3 shows that anemia, tachyarrhythmias, and respiratory failure were the most prevalent conditions underlying type 2 myocardial infarction. If supraventricular and ventricular arrhythmias were added together, tachyarrhythmias played a role in 29.1% of type 2 myocardial infarctions. In 15 patients, at least 2 different mechanisms were involved.
      Figure thumbnail gr3
      Figure 3Mechanisms underlying myocardial oxygen demand/supply imbalance leading to type 2 myocardial infarction (n = 144).

      Patients Admitted to the Coronary Care Unit Versus Other Clinical Departments

      Almost half of patients with type 2 myocardial infarction were admitted to departments other than the coronary care unit (Table 2). These patients were a mean of 11 years older and comprised relatively more non–ST-elevation myocardial infarction cases than the coronary care unit grouping. Patients from other departments had more comorbidities. Of note, the index median cTnI value was significantly higher in patients with myocardial infarction outside the coronary care unit, but patients from the coronary care unit still exhibited significantly higher median peak cTnI concentrations (Table 2).
      Table 2Baseline Characteristics of 553 Patients with Myocardial Infarction Admitted to the Coronary Care Unit (n = 418) or to Other Clinical Departments (n = 135)
      CharacteristicsMI (N = 418) Coronary Care UnitMI (N = 135) Other DepartmentsP Value
      Age (y), mean (± SD)69 (13)80 (11)<.001
      Male, no. (%)276 (66.0)59 (43.7)<.001
      Risk factors, no. (%)
       Diabetes67 (16.0)30 (22.2).10
       Hypercholesterolemia177 (42.3)50 (37.0).28
       Hypertension226 (54.1)80 (59.3).29
       Current smoker, no./total no. (%)140/375 (37.3)29/87 (33.3).01
       Family history, no./total no. (%)109/346 (31.5)11/41 (26.8).54
      Medical history, no. (%)
       Prior MI105 (25.1)36 (26.7).72
       Prior CABG42 (10.1)11 (8.2).51
       Prior percutaneous coronary intervention71 (17.0)18 (13.3).32
       Heart failure56 (13.4)25 (18.5).14
       Prior stroke52 (12.4)34 (25.2)<.001
       Peripheral arterial disease25 (6.0)15 (11.1).05
       Renal failure25 (6.0)18 (13.3).006
       Chronic obstructive pulmonary disease37 (8.9)45 (33.3)<.001
       Arrhythmia53 (12.7)31 (23.0).004
      Laboratory data, median/total no. (IQR)
       First troponin I, μg/L0.20 (0.06-1.13)0.43 (0.11-1.35).003
       Peak troponin I, μg/L2.13 (0.42-13.02)1.38 (0.50-5.96)<.001
       Hemoglobin, mmol/L8.3/407 (7.5-8.9)7.5/130 (6.6-8.5)<.001
       Leukocytes, 10E9/L10.1/413 (7.7-12.5)12.9/131 (9.7-18.2)<.001
       Creatinine(enzymatic)-P, μmol/L85/416 (71-105)99/133 (77-135)<.001
       C-reactive protein, mg/L5/411 (2-14)47/125 (12-118)<.001
      Clinical findings, median/total no. (IQR)
       Systolic BP, mm Hg146/413 (120-168)135/132 (110-164).02
       Heart rate, beats/min82/414 (67-106)98/132 (80-117)<.001
       Ejection fraction, median/total no. (IQR)50/362 (40-55)45/96 (35-55).03
      Type of MI, no. (%)
       Type 1328 (78.5)69 (51.1)<.001
       Type 279 (18.9)65 (48.2)<.001
       Type 4a2 (0.5)0.42
       Type 4b7 (1.7)0.13
       Type 52 (0.5)1 (0.7).72
      ST-elevation MI, no./total no. (%)123/407 (30.2)12/134 (9.0)<.001
      Non–ST-elevation MI, no./total no. (%)284/407 (69.8)122/134 (91.0)<.001
      Coronary angiography, no./total no. (%)291/407 (71.5)21/134 (15.7)<.001
      BP = blood pressure; CABG = coronary artery bypass grafting; IQR = interquartile range; MI = myocardial infarction; SD = standard deviation.

      Discussion

      In this study, 4499 consecutive hospitalized patients with a suspected acute myocardial infarction were evaluated according to the principles of the universal definition and with particular emphasis on novel clinical standard criteria for the classification of type 2 myocardial infarction. Thus, 553 patients had acute myocardial infarction, of whom 26% were classified as having type 2 myocardial infarction. Approximately half of patients with type 2 myocardial infarction did not have significant coronary artery disease on coronary angiography.
      Few original studies addressing the frequency of type 2 myocardial infarction are available. However, in line with our results, Javed et al
      • Javed U.
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      • Ambrose J.
      • et al.
      Frequency of elevated troponin I and diagnosis of acute myocardial infarction.
      found a 29.6% frequency of type 2 myocardial infarction in a study of 216 patients. On the other hand, when Melberg et al
      • Melberg T.
      • Burman R.
      • Dickstein K.
      The impact of the 2007 ESC-ACC-AHA-WHF Universal definition on the incidence and classification of acute myocardial infarction: a retrospective cohort study.
      retrospectively reclassified 1093 patients with myocardial infarction, they found that only 1.6% had a type 2 myocardial infarction. Furthermore, in selected patients with acute coronary syndrome undergoing percutaneous coronary intervention, only 3.5% of the myocardial infarctions were classified as type 2.
      • Morrow D.
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      Effect of the novel thienopyridine prasugrel compared with clopidogrel on spontaneous and procedural myocardial infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38: an application of the classification system from the universal definition of myocardial infarction.
      • Bonaca M.P.
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      • Braunwald E.
      • et al.
      American College of Cardiology/American Heart Association/European Society of Cardiology/World Heart Federation universal definition of myocardial infarction classification system and the risk of cardiovascular death: observations from the TRITON-TIMI 38.
      Because of the lack of internationally accepted criteria for diagnosing type 2 myocardial infarction, we developed criteria to assess the imbalance between myocardial oxygen demand and oxygen supply including the clinical conditions proposed by the Task Force, for example, coronary artery spasm, coronary embolism, anemia, arrhythmias, hypertension, or hypotension.
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.
      However, many patients with pulmonary disease, anemia, septicemia, renal failure, stroke, tachycardia, or hypotension may have elevation of troponin values,
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.
      • Thygesen K.
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      • et al.
      Recommendations for the use of cardiac troponin measurement in acute cardiac care.
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      and in clinical practice it is often difficult to decide whether these elevations occur in an ischemic setting. Another challenge is to decide whether the patient has a type 1 or 2 myocardial infarction. According to the universal definition, a typical increasing or decreasing pattern in troponin values has to be present to fulfill the diagnosis of myocardial infarction.
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.
      By use of this crucial criterion and our prespecified type 2 myocardial infarction criteria, we found that anemia, supraventricular tachyarrhythmias, and respiratory failure were the 3 most prevalent mechanisms, each leading to 20% of type 2 myocardial infarctions (Figure 3). Anemia generally is present in 6% to 43% of patients with acute myocardial infarction depending on patient characteristics and the definition used.
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      Lower hemoglobin levels have consistently been associated with an adverse clinical outcome in the general population and in patients with cardiovascular disease.
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      The exact mechanism underlying the link between anemia and a poor prognosis is not clearly understood, but a number of physiologic adaptive processes aimed at maintaining adequate total oxygen delivery to the tissues may be relevant.
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      To avoid overestimation of the importance of anemia as the underlying type 2 myocardial infarction mechanism, we deliberately used a restrictive definition with hemoglobin cutoff limits lower than those of the World Health Organization definition
      Nutritional anaemias. Report of a WHO scientific group.
      and at the same time fulfilling the criteria of “severe anemia” proposed by other researchers.
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      Data on the importance of troponin elevation associated with supraventricular tachyarrhythmias are limited. In a recent retrospective study,
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      mild elevation of cTnI in patients with supraventricular tachycardia was found to be associated with greater than triple the risk of future cardiovascular events, including acute myocardial infarction. The exact mechanism for myocardial necrosis is unknown, but it is believed that there is an increase in oxygen consumption by the myocardium during a prolonged period of tachycardia and a reduction of the oxygen supply by a shortening of the diastole.
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      Causes of respiratory failure in our study included decompensated acute heart failure, severe pneumonia, and exacerbation of chronic obstructive pulmonary disease. Proposed underlying mechanisms in these patients are hypoxia causing imbalance between oxygen demand and delivery together with increased pressure in pulmonary circulation leading to increased right ventricle afterload that may promote cardiomyocyte damage or death.
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      • et al.
      Elevated high-sensitivity cardiac troponin T is associated with increased mortality after acute exacerbation of chronic obstructive pulmonary disease.
      In a recent prospective study of patients with acute exacerbation of chronic obstructive pulmonary disease, an association between arterial oxygen tension and highly sensitive cTnT was found in the univariable longitudinal analysis. Indeed, no significant association was demonstrated in the cross-sectional or multivariable analysis.
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      The authors concluded that their data did not support the theory that the elevated cTnT measurements could be explained as a type 2 myocardial infarction–mediated hypoxemia. However, patients with normal arterial oxygen tension in the emergency department may have received oxygen therapy in the ambulance and yet have had severe arterial hypoxemia before admission to the hospital, causing cTnT leakage from the cardiomyocytes.
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      Determinants of high-sensitivity cardiac troponin T during acute exacerbation of chronic obstructive pulmonary disease: a prospective cohort study.
      Of note, coronary artery spasm and coronary embolism were not identified as underlying mechanisms in any of the type 2 myocardial infarctions in our study, and their quantitative importance may be smaller than originally expected.
      Although patients with type 2 myocardial infarction had significantly lower peak cTnI values, our results showed that these patients had a lower left ventricular ejection fraction than their type 1 myocardial infarction counterparts. This may be partly explained by the higher rate of heart failure by history reported in patients with type 2 myocardial infarction (Table 1). Studies comparing angiographic data in types 1 and 2 myocardial infarction are limited. Ambrose et al
      • Ambrose J.
      • Loures-Vale A.
      • Javed U.
      • et al.
      Angiographic correlates in type 1 and 2 MI by the universal definition.
      recently reported on 224 patients with myocardial infarction who were selected because of the availability of an in-hospital angiogram and the diagnosis of a type 1 (n = 193) and type 2 myocardial infarction (n = 31). Nonobstructive coronary artery disease was present in 35.5% of patients with type 2 myocardial infarction versus 11.4% of patients with type 1 myocardial infarction.
      • Ambrose J.
      • Loures-Vale A.
      • Javed U.
      • et al.
      Angiographic correlates in type 1 and 2 MI by the universal definition.
      These observations are supported by our data. Thus, we found that 45.2% of patients with type 2 myocardial infarction and 11.7% of patients with type 1 myocardial infarction did not have significant coronary artery disease. Finally, 1-vessel disease—also in accordance with the findings by Ambrose et al
      • Ambrose J.
      • Loures-Vale A.
      • Javed U.
      • et al.
      Angiographic correlates in type 1 and 2 MI by the universal definition.
      —seems to be more than twice as prevalent in type 1 than in type 2 myocardial infarction (Figure 2).
      Our study design also allowed a comparison between patients admitted to the coronary care unit and patients admitted to other departments. Of note, the first cTnI value obtained was lower in patients in the coronary care unit than in other departments (Table 2). However, subsequent cTnI values were higher in patients in the coronary care unit. This observation is most likely due to differences in patient characteristics, clinical routines, and myocardial infarction types in the 2 settings. Thus, the time delay from symptom start to cTnI measurement in departments outside the coronary care unit is most likely longer because patients had more atypical symptoms and more comorbidity. Of interest, approximately half of patients with a type 2 myocardial infarction were admitted to other departments than the department of cardiology.

      Study Limitations

      First, a complete cardiac examination was not performed in every patient because diagnostic procedures, such as echocardiography and coronary angiography, were performed at the discretion of the treating physicians. Second, only 1 cTnI measurement is available in some patients. However, in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention, the diagnosis of a myocardial infarction will frequently be made despite the lack of serial cTnI measurements. Also, in most patients hospitalized more than 24 hours after the onset of symptoms, a single elevated cTnI value in an ischemic setting would be sufficient to meet the diagnostic myocardial infarction criteria.
      • Thygesen K.
      • Alpert J.S.
      • White H.D.
      Universal definition of myocardial infarction.
      Third, it should be noted that the proportion of type 4a myocardial infarction is surprisingly low, but according to the standards of the hospital, the cTnI is only measured after percutaneous coronary intervention in case of clinical symptoms of myocardial infarction. Last, the detailed type 2 myocardial infarction criteria proposed by our study group do not necessarily represent “the gold standard.” Indeed, we consider this work as a stepping stone in the development and adaption of a globally accepted definition of myocardial infarction.

      Conclusions

      This prospective study on the classification and features of patients with myocardial infarction defined according to the universal definition demonstrates that 26% of these patients had type 2 myocardial infarction when novel developed clinical criteria were used. Patients with type 2 myocardial infarction generally had more severe clinical characteristics than patients with type 1 myocardial infarction. Approximately half of patients with type 2 myocardial infarction had no significant coronary artery disease.

      Acknowledgments

      The authors thank Jens Lauritsen, MD, PhD, for taking care of the database.

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