Characterization of patients with myocardial infarction with non-obstructive coronary arteries – experience from the Croatian branch of the ISACS-CT Registry

    Authors

    • Ines Vinković — University Hospital Centre Zagreb, Zagreb, Croatia
    • Filip Lončarić — August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
    • Petra Mjehović — University Hospital Centre Zagreb, Zagreb, Croatia
    • Dorja Sabljak — University of Zagreb School of Medicine, Zagreb, CroatiaKEYWORDS: acute coronary syndrome, non-obstructive coronary disease.
    • Vedrana Vlahović — University of Zagreb School of Medicine, Zagreb, CroatiaKEYWORDS: acute coronary syndrome, non-obstructive coronary disease.
    • Grgur Salai — University of Zagreb School of Medicine, Zagreb, CroatiaKEYWORDS: acute coronary syndrome, non-obstructive coronary disease.
    • Klara Klarić — University of Zagreb School of Medicine, Zagreb, CroatiaKEYWORDS: acute coronary syndrome, non-obstructive coronary disease.
    • Toni Radić — University of Zagreb School of Medicine, Zagreb, CroatiaKEYWORDS: acute coronary syndrome, non-obstructive coronary disease.
    • Saša Pavasović — University Hospital Centre Zagreb, Zagreb, Croatia
    • Nina Jakuš — University Hospital Centre Zagreb, Zagreb, Croatia
    • Dora Fabijanović — University Hospital Centre Zagreb, Zagreb, Croatia
    • Ivo Planinc — University Hospital Centre Zagreb, Zagreb, Croatia
    • Maja Čikeš — University Hospital Centre Zagreb, Zagreb, Croatia
    • Davor Miličić — University Hospital Centre Zagreb, Zagreb, Croatia

    Abstract

    **Background and Aim**: There are still wide knowledge gaps in myocardial infarction with non-obstructive coronary arteries (MINOCA) - a heterogeneous entity seen in 1-10% of patients with acute coronary syndrome (ACS) (1). The aim is to determine characteristics of MINOCA in the Croatian branch of the ISACS-CT registry, and compare them to age- and gender-matched patients with unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI). **Patients and Methods**: The study included 2487 patients with ACS. MINOCA was defined by simultaneous cardiac troponin levels >0.014 ng/L, symptoms of ischemia or significant ST-T changes in the ECG, and an absence of coronary artery stenosis of ≥ 50% on angiography. Age and gender-matching was performed from the remaining cohort by randomly sampling patients from the UA, STEMI and NSTEMI subgroups, based on the mean age ± 5 years and the gender ratio of the MINOCA group. **Results**: MINOCA was seen in 2.5% (n=63) of the cohort, initially categorized as UA (37%), NSTEMI (48%) and STEMI (16%). Median age was 62 (53, 71) years, 56% male. After age- and gender-matching, there were 36 UA (10% of the UA cohort), 135 NSTEMI (15%) and 198 STEMI (16%) patients in the ACS control subgroups. MINOCA patients had a lower prevalence of diabetes, hypertension, dyslipidemia, chronic kidney disease and tobacco use as compared to UA and NSTEMI. MINOCA patients used less antiplatelets, beta-blockers and statins before hospitalization. MINOCA and STEMI subgroups had a high incidence of chest pain symptoms and a short time from symptom onset to hospitalization. In the first 24h of hospitalization, less MINOCA patients were treated with antiplatelets and statins, and at discharge, they were less frequently prescribed with antiplatelet drugs compared to UA and NSTEMI (**Table 1**). In-hospital mortality was low, with no deaths in MINOCA and UA patients, and 2 and 3 deaths in NSTEMI and STEMI, respectively. ### TABLE 1: Baseline characteristics and the comparison of patients with myocardial infarction with non-obstructive coronary arteries, unstable angina, ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction. | | **VARIABLES** | **MINOCA** **(n=63)** | **UA** **(n=36)** | **NSTEMI** **(n=135)** | **STEMI** **(n=198)** | **P-value** | **Misssing** | | --- | --- | --- | --- | --- | --- | --- | --- | | **ACS type** | UA | 37 | - | - | - | | 0 | | NSTEMI | 48 | - | - | - | | 0 | | | STEMI | 16 | - | - | - | | 0 | | | **General characteristics** | Age | 62 | 60 | 62 | 62 | 0.692 | 0 | | Male gender | 56 | 56 | 56 | 56 | 1 | 0 | | | BMI | 28.7 | 31.2 | 29.3 | 27.7 | **0.001** | 36 | | | Systolic blood pressure at admission | 145 | 150 | 140 | 140 | **0.003** | 20 | | | Family history of CAD | 27 | 31 | 31 | 26 | ns | 0 | | | Diabetes | 18 | 28 | 36 | 23 | **0.017** | 0 | | | Insulin therapy | 2 | 8 | 11 | 7 | 0.087 | 0 | | | Hypertension or on th | 77 | 92 | 82 | 76 | 0.118 | 1 | | | Smoking or ex-smoker | 36 | 56 | 42 | 62 | **<0.001** | 6 | | | Hypercholestroleamia or on therapy | 58 | 86 | 69 | 53 | **<0.001** | 5 | | | Angina classified by CCS | 7 | 13 | 14 | 5 | 0.057 | 13 | | | Unstable angina at rest | 8 | 49 | 11 | 2 | **<0.001** | 8 | | | Heart failure NYHA 2+ | 5 | 3 | 3 | 2 | 0.412 | 7 | | | COPD | 2 | 6 | 6 | 7 | 0.539 | 7 | | | Chronic kidney disease | 5 | 12 | 12 | 4 | **0.028** | 7 | | | **Theraphy before admission** | Aspirin | 35 | 43 | 32 | 18 | **0.002** | 6 | | Other antiplatlet therapy | 18 | 24 | 10 | 6 | **0.006** | 8 | | | ACEi | 49 | 57 | 47 | 40 | 0.249 | 6 | | | Beta-blockers | 44 | 49 | 41 | 22 | **<0.001** | 6 | | | Statins | 30 | 39 | 32 | 18 | **0.007** | 6 | | | **ACS presentation** | Two or more 20 mins chest pain episodes in the previous 24 hrs | 21 | 48 | 50 | 41 | **0.014** | 33 | | Onset <6 hours | 63 | 44 | 46 | 70 | **<0.001** | 3 | | | Chest pain | 97 | 92 | 90 | 98 | **0.004** | 1 | | | Abnormal ECG | 46 | 46 | 63 | 99 | **<0.001** | 1 | | | LBBB | 4 | 0 | 1 | 5 | 0.514 | 6 | | | ST elevation | 19 | 6 | 4 | 81 | **<0.001** | 0 | | | ST depression | 10 | 14 | 22 | 15 | 0.147 | 0 | | | Q wave | 5 | 11 | 8 | 15 | 0.074 | 0 | | | T wave inversion | 3 | 17 | 26 | 10 | **<0.001** | 0 | | | Initial descision for PCI treatment | 63 | 83 | 86 | 99 | **<0.001** | 0 | | | **Therapy at admission** | Nitrates | 45 | 57 | 47 | 34 | **0.021** | 10 | | Aspirin 24h | 100 | 100 | 96 | 96 | 0.394 | 2 | | | Clopidogrel | 71 | 86 | 90 | 69 | **<0.001** | 2 | | | Other antiplatelet therapy | 10 | 9 | 13 | 46 | **<0.001** | 3 | | | Statins 24 | 84 | 97 | 95 | 95 | **0.030** | 1 | | | ACEi 24h | 82 | 86 | 74 | 71 | 0.127 | 3 | | | Beta blockers 24h | 76 | 81 | 75 | 66 | 0.122 | 2 | | | GP IIb/IIIa | 3 | 12 | 10 | 50 | **<0.001** | 7 | | | | **VARIABLES** | **MINOCA** **(n=63)** | **UA** **(n=36)** | **NSTEMI** **(n=135)** | **STEMI** **(n=198)** | **P-value** | **Misssing** | | **Lab results** | Troponin T | 0.07 | 0.02 | 0.18 | 0.35 | **<0.001** | 15 | | Troponin T peak | 0.2 | 0.04 | 0.7 | 3.64 | **<0.001** | 25 | | | CRP | 2 | 38 | 30 | 25 | **0.001** | 35 | | | CRP-peak | 4 | 39 | 33 | 58 | **0.005** | 52 | | | Creatinemia | 90 | 88 | 90 | 80 | **0.024** | 5 | | | WBC | 7.5 | 8.9 | 9.0 | 11.3 | **<0.001** | 5 | | | Hemoglobin | 139 | 143 | 140 | 141 | 0.606 | 5 | | | Cholesterol | 4.7 | 5.1 | 5.2 | 5.0 | 0.419 | 15 | | | Tryglicerides | 1.28 | 1.61 | 1.63 | 1.40 | **0.001** | 15 | | | HDL-C | 1.3 | 1.17 | 1.10 | 1.17 | **0.003** | 15 | | | LDL-C | 2.87 | 3.68 | 3.71 | 3.68 | 0.322 | 15 | | | Kaliemia | 4.2 | 4.3 | 4.3 | 4.1 | **0.020** | 19 | | | Na | 140 | 140 | 140 | 139 | **<0.001** | 21 | | | CK peak | 207 | 161 | 165 | 1229 | **<0.001** | 42 | | | **Theraphy at discharge** | Aspirin at discharge | 94 | 100 | 97 | 96 | 0.446 | 0 | | Clopidogrel at discharge | 44 | 89 | 87 | 54 | **<0.001** | 0 | | | Other antiplatelet therapy at discharge | 0 | 8 | 8 | 47 | **<0.001** | 1 | | | Anticoagulants at discharge | 21 | 11 | 7 | 18 | **0.012** | 0 | | | ACEi at discharge | 81 | 81 | 81 | 81 | ns | 1 | | | Beta-blockers at discharge | 79 | 81 | 84 | 80 | 0.804 | 0 | | | Statins at discharge | 89 | 97 | 95 | 94 | 0.360 | 1 | | | Other lipid lowering drugs at discharge | 3 | 6 | 12 | 8 | 0.202 | 0 | | | Diuretics at discharge | 24 | 36 | 28 | 27 | 0.624 | 2 | | | Antiarrhythmics at discharge | 18 | 17 | 12 | 8 | 0.533 | 2 | | | Outcomes | Duration of hospitalisation | 4 (2, 5) | 3 (2, 5) | 4 (3, 7) | 5 (1, 7) | **0.005** | 0 | | EF at discharge | 55 | 60 | 55 | 50 | **<0.001** | 22 | | | Hospital mortality | 0 | 0 | 2 | 3 | 0.573 | 0 | | [†] MINOCA - Myocardial infarction with non-obstructive coronary arteries; UA - Unstable angina; STEMI - ST-segment elevation myocardial infarction; NSTEMI - Non-ST-segment elevation myocardial infarction; ACS - Acute coronary syndrome; BMI - Body mass index; CAD - Coronary artery disease; CCS - Canadian Cardiovascular Society; NYHA - New York Heart Association; COPD - Chronic obstructive pulmonary disease; ACEi - Angiotensin-converting-enzyme inhibitor; ECG – Electrocardiogram; LBBB - Left bundle branch block; GP IIb/IIIa - Glycoprotein IIb/IIIa; WBC - White blood cells; EF - Ejection fraction **Conclusion**: MINOCA patients are mainly categorized as UA and NSTEMI at presentation, but have less comorbidities, more pronounced symptoms of typical chest pain, a shorter time from symptoms to hospitalization, lower levels of statin and antiaggregation prescription at admission, and antiaggregation at discharge. In-hospital mortality confirms MINOCA as low risk, however, long-term registry follow-up is needed to learn about longer term outcomes.

    DOI

    https://doi.org/10.15836/ccar2019.217

    Literature

    1. Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, et al. WG on Cardiovascular Pharmacotherapy. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017 Jan 14;38(3):143–53. https://doi.org/10.1093/eurheartj/ehw149
    Cardiologia Croatica
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    Characterization of patients with myocardial infarction with non-obstructive coronary arteries – experience from the Croatian branch of the ISACS-CT Registry

    Extended Abstract
    Issue9-10
    Published
    Pages217-219
    PDF via DOIhttps://doi.org/10.15836/ccar2019.217

    Authors

    Ines Vinković*University Hospital Centre Zagreb, Zagreb, Croatia
    Filip LončarićAugust Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
    Petra MjehovićUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Dorja SabljakUniversity of Zagreb School of Medicine, Zagreb, CroatiaKEYWORDS: acute coronary syndrome, non-obstructive coronary disease.
    Vedrana VlahovićUniversity of Zagreb School of Medicine, Zagreb, CroatiaKEYWORDS: acute coronary syndrome, non-obstructive coronary disease.
    Grgur SalaiUniversity of Zagreb School of Medicine, Zagreb, CroatiaKEYWORDS: acute coronary syndrome, non-obstructive coronary disease.
    Klara KlarićUniversity of Zagreb School of Medicine, Zagreb, CroatiaKEYWORDS: acute coronary syndrome, non-obstructive coronary disease.
    Toni RadićUniversity of Zagreb School of Medicine, Zagreb, CroatiaKEYWORDS: acute coronary syndrome, non-obstructive coronary disease.
    Saša PavasovićUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Nina JakušUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Dora FabijanovićUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Ivo PlanincUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Maja ČikešUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Davor MiličićUniversity Hospital Centre Zagreb, Zagreb, Croatia

    *Correspondence email: iness.vinkovic@gmail.com

    Abstract

    **Background and Aim**: There are still wide knowledge gaps in myocardial infarction with non-obstructive coronary arteries (MINOCA) - a heterogeneous entity seen in 1-10% of patients with acute coronary syndrome (ACS) (1). The aim is to determine characteristics of MINOCA in the Croatian branch of the ISACS-CT registry, and compare them to age- and gender-matched patients with unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI). **Patients and Methods**: The study included 2487 patients with ACS. MINOCA was defined by simultaneous cardiac troponin levels >0.014 ng/L, symptoms of ischemia or significant ST-T changes in the ECG, and an absence of coronary artery stenosis of ≥ 50% on angiography. Age and gender-matching was performed from the remaining cohort by randomly sampling patients from the UA, STEMI and NSTEMI subgroups, based on the mean age ± 5 years and the gender ratio of the MINOCA group. **Results**: MINOCA was seen in 2.5% (n=63) of the cohort, initially categorized as UA (37%), NSTEMI (48%) and STEMI (16%). Median age was 62 (53, 71) years, 56% male. After age- and gender-matching, there were 36 UA (10% of the UA cohort), 135 NSTEMI (15%) and 198 STEMI (16%) patients in the ACS control subgroups. MINOCA patients had a lower prevalence of diabetes, hypertension, dyslipidemia, chronic kidney disease and tobacco use as compared to UA and NSTEMI. MINOCA patients used less antiplatelets, beta-blockers and statins before hospitalization. MINOCA and STEMI subgroups had a high incidence of chest pain symptoms and a short time from symptom onset to hospitalization. In the first 24h of hospitalization, less MINOCA patients were treated with antiplatelets and statins, and at discharge, they were less frequently prescribed with antiplatelet drugs compared to UA and NSTEMI (**Table 1**). In-hospital mortality was low, with no deaths in MINOCA and UA patients, and 2 and 3 deaths in NSTEMI and STEMI, respectively. ### TABLE 1: Baseline characteristics and the comparison of patients with myocardial infarction with non-obstructive coronary arteries, unstable angina, ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction. | | **VARIABLES** | **MINOCA** **(n=63)** | **UA** **(n=36)** | **NSTEMI** **(n=135)** | **STEMI** **(n=198)** | **P-value** | **Misssing** | | --- | --- | --- | --- | --- | --- | --- | --- | | **ACS type** | UA | 37 | - | - | - | | 0 | | NSTEMI | 48 | - | - | - | | 0 | | | STEMI | 16 | - | - | - | | 0 | | | **General characteristics** | Age | 62 | 60 | 62 | 62 | 0.692 | 0 | | Male gender | 56 | 56 | 56 | 56 | 1 | 0 | | | BMI | 28.7 | 31.2 | 29.3 | 27.7 | **0.001** | 36 | | | Systolic blood pressure at admission | 145 | 150 | 140 | 140 | **0.003** | 20 | | | Family history of CAD | 27 | 31 | 31 | 26 | ns | 0 | | | Diabetes | 18 | 28 | 36 | 23 | **0.017** | 0 | | | Insulin therapy | 2 | 8 | 11 | 7 | 0.087 | 0 | | | Hypertension or on th | 77 | 92 | 82 | 76 | 0.118 | 1 | | | Smoking or ex-smoker | 36 | 56 | 42 | 62 | **<0.001** | 6 | | | Hypercholestroleamia or on therapy | 58 | 86 | 69 | 53 | **<0.001** | 5 | | | Angina classified by CCS | 7 | 13 | 14 | 5 | 0.057 | 13 | | | Unstable angina at rest | 8 | 49 | 11 | 2 | **<0.001** | 8 | | | Heart failure NYHA 2+ | 5 | 3 | 3 | 2 | 0.412 | 7 | | | COPD | 2 | 6 | 6 | 7 | 0.539 | 7 | | | Chronic kidney disease | 5 | 12 | 12 | 4 | **0.028** | 7 | | | **Theraphy before admission** | Aspirin | 35 | 43 | 32 | 18 | **0.002** | 6 | | Other antiplatlet therapy | 18 | 24 | 10 | 6 | **0.006** | 8 | | | ACEi | 49 | 57 | 47 | 40 | 0.249 | 6 | | | Beta-blockers | 44 | 49 | 41 | 22 | **<0.001** | 6 | | | Statins | 30 | 39 | 32 | 18 | **0.007** | 6 | | | **ACS presentation** | Two or more 20 mins chest pain episodes in the previous 24 hrs | 21 | 48 | 50 | 41 | **0.014** | 33 | | Onset <6 hours | 63 | 44 | 46 | 70 | **<0.001** | 3 | | | Chest pain | 97 | 92 | 90 | 98 | **0.004** | 1 | | | Abnormal ECG | 46 | 46 | 63 | 99 | **<0.001** | 1 | | | LBBB | 4 | 0 | 1 | 5 | 0.514 | 6 | | | ST elevation | 19 | 6 | 4 | 81 | **<0.001** | 0 | | | ST depression | 10 | 14 | 22 | 15 | 0.147 | 0 | | | Q wave | 5 | 11 | 8 | 15 | 0.074 | 0 | | | T wave inversion | 3 | 17 | 26 | 10 | **<0.001** | 0 | | | Initial descision for PCI treatment | 63 | 83 | 86 | 99 | **<0.001** | 0 | | | **Therapy at admission** | Nitrates | 45 | 57 | 47 | 34 | **0.021** | 10 | | Aspirin 24h | 100 | 100 | 96 | 96 | 0.394 | 2 | | | Clopidogrel | 71 | 86 | 90 | 69 | **<0.001** | 2 | | | Other antiplatelet therapy | 10 | 9 | 13 | 46 | **<0.001** | 3 | | | Statins 24 | 84 | 97 | 95 | 95 | **0.030** | 1 | | | ACEi 24h | 82 | 86 | 74 | 71 | 0.127 | 3 | | | Beta blockers 24h | 76 | 81 | 75 | 66 | 0.122 | 2 | | | GP IIb/IIIa | 3 | 12 | 10 | 50 | **<0.001** | 7 | | | | **VARIABLES** | **MINOCA** **(n=63)** | **UA** **(n=36)** | **NSTEMI** **(n=135)** | **STEMI** **(n=198)** | **P-value** | **Misssing** | | **Lab results** | Troponin T | 0.07 | 0.02 | 0.18 | 0.35 | **<0.001** | 15 | | Troponin T peak | 0.2 | 0.04 | 0.7 | 3.64 | **<0.001** | 25 | | | CRP | 2 | 38 | 30 | 25 | **0.001** | 35 | | | CRP-peak | 4 | 39 | 33 | 58 | **0.005** | 52 | | | Creatinemia | 90 | 88 | 90 | 80 | **0.024** | 5 | | | WBC | 7.5 | 8.9 | 9.0 | 11.3 | **<0.001** | 5 | | | Hemoglobin | 139 | 143 | 140 | 141 | 0.606 | 5 | | | Cholesterol | 4.7 | 5.1 | 5.2 | 5.0 | 0.419 | 15 | | | Tryglicerides | 1.28 | 1.61 | 1.63 | 1.40 | **0.001** | 15 | | | HDL-C | 1.3 | 1.17 | 1.10 | 1.17 | **0.003** | 15 | | | LDL-C | 2.87 | 3.68 | 3.71 | 3.68 | 0.322 | 15 | | | Kaliemia | 4.2 | 4.3 | 4.3 | 4.1 | **0.020** | 19 | | | Na | 140 | 140 | 140 | 139 | **<0.001** | 21 | | | CK peak | 207 | 161 | 165 | 1229 | **<0.001** | 42 | | | **Theraphy at discharge** | Aspirin at discharge | 94 | 100 | 97 | 96 | 0.446 | 0 | | Clopidogrel at discharge | 44 | 89 | 87 | 54 | **<0.001** | 0 | | | Other antiplatelet therapy at discharge | 0 | 8 | 8 | 47 | **<0.001** | 1 | | | Anticoagulants at discharge | 21 | 11 | 7 | 18 | **0.012** | 0 | | | ACEi at discharge | 81 | 81 | 81 | 81 | ns | 1 | | | Beta-blockers at discharge | 79 | 81 | 84 | 80 | 0.804 | 0 | | | Statins at discharge | 89 | 97 | 95 | 94 | 0.360 | 1 | | | Other lipid lowering drugs at discharge | 3 | 6 | 12 | 8 | 0.202 | 0 | | | Diuretics at discharge | 24 | 36 | 28 | 27 | 0.624 | 2 | | | Antiarrhythmics at discharge | 18 | 17 | 12 | 8 | 0.533 | 2 | | | Outcomes | Duration of hospitalisation | 4 (2, 5) | 3 (2, 5) | 4 (3, 7) | 5 (1, 7) | **0.005** | 0 | | EF at discharge | 55 | 60 | 55 | 50 | **<0.001** | 22 | | | Hospital mortality | 0 | 0 | 2 | 3 | 0.573 | 0 | | [†] MINOCA - Myocardial infarction with non-obstructive coronary arteries; UA - Unstable angina; STEMI - ST-segment elevation myocardial infarction; NSTEMI - Non-ST-segment elevation myocardial infarction; ACS - Acute coronary syndrome; BMI - Body mass index; CAD - Coronary artery disease; CCS - Canadian Cardiovascular Society; NYHA - New York Heart Association; COPD - Chronic obstructive pulmonary disease; ACEi - Angiotensin-converting-enzyme inhibitor; ECG – Electrocardiogram; LBBB - Left bundle branch block; GP IIb/IIIa - Glycoprotein IIb/IIIa; WBC - White blood cells; EF - Ejection fraction **Conclusion**: MINOCA patients are mainly categorized as UA and NSTEMI at presentation, but have less comorbidities, more pronounced symptoms of typical chest pain, a shorter time from symptoms to hospitalization, lower levels of statin and antiaggregation prescription at admission, and antiaggregation at discharge. In-hospital mortality confirms MINOCA as low risk, however, long-term registry follow-up is needed to learn about longer term outcomes.

    Literature

    1. 1.
      Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, et al. WG on Cardiovascular Pharmacotherapy. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017 Jan 14;38(3):143–53.DOI