Abstract
Background/Objectives: Troponin level elevation without an obstructive culprit lesion is caused by heterogenous entities. The effect of aging on this condition has been poorly investigated. Methods: After screening 24,775 patients between 2010 and 2021, this study included a total of 373 patients with elevated troponin levels without an obstructive culprit lesion or suspected myocardial infarction with non-obstructive coronary arteries (MINOCAs) categorized into four age groups containing 78 patients (<51 years), 72 patients (51–60 years), 81 patients (61–70 years), and 142 patients (>70 years). This study analyzed the baseline characteristics, the in-hospital complications, in-hospital mortality, and the long-term outcomes. Results: The older patients exhibited a higher rate of major adverse cardiovascular in-hospital events than those of the other age groups (15.4% in the <51-year-old group vs. 36.1% in the 51–60-year-old group vs. 33.3% in the 61–70-year-old group vs. 47.2% in the >70-year-old group; p < 0.001). However, the rate of non-sustained ventricular tachycardia (nsVT) was higher in the 51–60-year-old patients than those of the other age groups (5.6% in the 51–60-year-old group vs. 1.3% in the 61–70-year-old group vs. 0.7% in the >70-year-old group; p = 0.027). At the 11-year follow-up, cardiovascular mortality was higher among the older patients compared to that of the younger patients (3.9% in the 61–70-year-old group vs. 4.2% in the >70-year-old group, p = 0.042), while non-cardiovascular mortality was comparable between the age groups. Conclusions: The older patients with troponin level elevation without an obstructive culprit lesion experienced a higher incidence of major adverse cardiovascular events during hospitalization compared to that of the younger groups. Additionally, higher cardiovascular mortality rates were revealed in the older patients at a long-term follow-up.
Keywords: myocardial infarction, MINOCA, arrhythmias, atrial fibrillation, age, cardiovascular mortality
1. Introduction
Troponin level elevation without an obstructive culprit lesion is a common occurrence. This finding observed in 5–15% of patients who present with myocardial infarction (MI) [1,2]. The most frequent underlying causes of troponin level elevation without an obstructive culprit lesion appear to be coronary vasospasm, microvascular disease, coronary plaque dissection, coronary dissection, coronary thromboembolism, takotsubo cardiomyopathy, and myocarditis [2].
Whereas the treatment of MI with obstructive coronary disease by primary percutaneous coronary intervention (PCI) and novel thienopyridines has been well established, there are few randomized data on the effectiveness of preventive therapies in patients with troponin level elevation without an obstructive culprit lesion [3]. For this reason, identifying the underlying individual mechanisms to design patient-specific treatments is crucial in treating patients with troponin level elevation without an obstructive culprit lesion, ultimately resulting in optimized clinical outcomes. Choo et al. reported that treatment with renin–angiotensin system blockers and statins reduced the mortality in patients with troponin level elevation without an obstructive culprit lesion [4]. The SWEDEHEART trial showed lower rates of all-cause mortality, hospitalization for MI, ischemic stroke, and heart failure in patients with troponin level elevation without an obstructive culprit lesion treated with statins, an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), and a ß-blocker, but not in the patients treated with dual-antiplatelet agents [5]. However, the prognosis of this condition is not benign. Patients with troponin level elevation without obstructive coronary artery disease (CAD), as observed in the ACUITY trial, exhibited an increased risk of all cause-mortality compared to that of those with obstructive CAD at a one-year follow-up [6]. Furthermore, these patients experienced a higher incidence of heart failure (HF) comparable to that of individuals with obstructive CAD. Notably, HF in this population was predominantly characterized by preserved ejection fraction (HFpEF) [7].
Several data showed that age variation may impact the outcome of several cardiovascular diseases, e.g., HF [8]. In this regard, our aim was to provide a detailed description of demographic data, in-hospital complications, and clinical outcomes at long-term follow-up in patients with troponin level elevation without an obstructive culprit lesion grouped into different age groups.
2. Material and Methods
2.1. Study Population and Definition of Troponin Level Elevation Without Obstructive CAD
This is a monocentric, retrospective cohort study of consecutive patients admitted for troponin level elevation who underwent coronary angiography between 2010 and 2021 due to suspected acute coronary syndrome (ACS) [9]. Individuals were excluded if they met the criteria for obstructive CAD, or if their condition had a non-cardiac origin, such as stroke, pulmonary embolism, sepsis, acute respiratory distress syndrome, or end-stage renal failure [10]. Of the 24,775 patients screened, 373 patients with troponin level elevation without an obstructive culprit lesion or suspected myocardial infarction with non-obstructive coronary arteries (MINOCAs) were included in analysis. MINOCAs were defined in accordance with the 2023 ACS Guidelines of the European Society of Cardiology (ESC).
To meet the inclusion criteria, the patients first had to fulfill the modified criteria for acute MI according to the “Fourth Universal Definition of Myocardial Infarction” [11]. Additionally, there had to be clinical evidence of MI, as indicated by at least one of the following: symptoms of MI, new ischemic changes on an electrocardiogram, pathological Q waves, evidence of the new loss of a viable myocardium, new regional wall motion abnormalities suggestive of an ischemic cause, or evidence of coronary thrombus identified through angiography or autopsy. These patients were divided into four groups, younger (<51 years), early middle age (51–60 years), late middle age (61–70 years), and older (>70 years) (Figure 1). The data were collected using a specific database, including baseline characteristics, electrocardiographic data, malignant and supraventricular arrhythmias, medication given at admission and discharge, echocardiographic data at discharge, in-hospital complications, and in-hospital mortality. The clinical outcomes, including stroke, thromboembolic events, the recurrence of elevation troponin levels, cardiac arrest, percutaneous coronary intervention (PCI), and mortality due to cardiac or non-cardiac causes at a long-term follow-up, were gathered. This study was executed in compliance with the Declaration of Helsinki regarding investigations on human subjects, and this study protocol was approved by the Ethics Committee of the participating institutions.
Figure 1.
A flow-chart presenting the screened data and the patients included in the present study.
2.2. Definition of Troponin Level Elevation Without an Obstructive Culprit Lesion
Coronary angiography was performed by interventional cardiologists during admission for all the screened patients with elevated troponin levels and suspected ACS following the 2023 ACS guidelines. Obstructive CAD was defined as the presence of one or more coronary stenoses with a diameter reduction of ≥50%. Non-obstructive CAD was further classified based on the angiographic findings as stenoses <50%, or no angiographic evidence of coronary disease. Revascularization strategies were implemented in cases where a culprit lesion was identified or when the visually estimated diameter stenosis severity was ≥70% in non-left main coronary artery disease or ≥50% in left main coronary artery disease. These strategies were pursued when coronary artery bypass grafting (CABG) therapy was not preferred.
2.3. High-Sensitivity Troponin I
Regarding troponin analysis, high-sensitivity cardiac troponin I (hs-TnI) assays were used. The 99th percentile values were identified for all the patients using the results of measurements from a healthy reference population [12]. The first hs-Tn test was conducted upon admission, with the second test scheduled within the initial three hours, as recommended by the ESC [13,14].
2.4. Outcomes
We evaluated cardiovascular and non-cardiovascular mortality as the primary endpoints during the long-term follow-up. The in-hospital complications evaluated in this study included HF, cardiac arrest, left ventricular thrombus, pulmonary edema, cardiogenic shock, extracorporeal membrane oxygenation (ECMO), invasive ventilation, non-invasive ventilation, stroke, malignant cardiac arrhythmias, and supraventricular arrhythmias. The clinical outcomes at the long-term follow-up, including stroke, thromboembolic event, the recurrence of troponin level elevation, cardiac arrest, and PCI as the secondary endpoints, were also assessed. The mean duration of the long-term follow-up was 6.2 ± 3.1 years. Major adverse cardiovascular events were defined as a composite of cardiovascular death, myocardial infarction, or ischemic stroke.
2.5. Statical Analysis
Descriptive und comparative analyses were performed. Categorial variables are presented as numbers (frequency) and percentages. Continuous variables are presented as mean ± standard deviation (SD) if the distribution was normal, or the median (interquartile range) if not. Comparisons of the categorial variables were conducted with the Pearson chi-square test. For continuous variables, the Kruskal–Wallis test with Dunn’s multiple-comparison test were used. The comparative analysis of quantitative variables was presented using the Mann–Whitney U test for non-parametric variables and the t-student test for parametric variables, as verified by the Shapiro–Wilk test. All the tests were 2-sided, and a p value < 0.05 was considered statistically significant. SPSS version 26.0 (IBM Corp., Armonk, NY, USA) was used for statistical analyses.
3. Results
3.1. Baseline Characteristics According to Age
A total of 373 patients with troponin level elevation without an obstructive culprit lesion were included in this study, with a mean age of 63 ± 15.6 years old, and 49.6% were male. Out of the total sample, 78 (20.9%) were <51 years, 72 (19.3%) were aged from 51 to 60 years, 81 (21.7%) were aged from 61 to 70 years, and 142 (38%) were > 70 years old. Males were more prevalent among the patients < 51 years old (age < 51 years: 70.5%, 51–60 years: 58.3%, 61–70 years: 44.4%, and >70 years: 36.6%; p < 0.001). The baseline characteristics are presented in Table 1.
Table 1.
Baseline characteristics of 373 patients initially presenting elevated troponin levels with non-obstructive coronary artery disease presented according to age.
| Variables | All Patients n = 373 |
<51 n = 78 |
51–60 n = 72 |
61–70 n = 81 |
>70 n = 142 |
p Value |
|---|---|---|---|---|---|---|
| Age—years, mean ± SD | 63 ± 15.6 | 40 ± 9.3 | 56 ± 3 | 65 ± 3 | 78 ± 5 | <0.001 |
| Male—n (%) | 185 (49.6) | 55 (70.5) | 42 (58.3) | 36 (44.4) | 52 (36.6) | <0.001 |
| BMI—kg/m2, mean ± SD | 27.6 ± 5.6 | 27.8 ± 6 | 28.4 ± 6 | 27.3 ± 5 | 27.3 ± 5 | 0.502 |
| Duration of hospitalization—days, mean ± SD | 10 ± 8.5 | 8 ± 5 | 10.2 ± 8 | 11 ± 12 | 10.7 ± 8 | 0.060 |
| Symptoms—n (%) | ||||||
| Angina pectoris | 226 (61.6) | 55 (71.4) | 41 (58.6) | 49 (60.5) | 81 (58.3) | 0.252 |
| Dyspnea | 164 (44.4) | 18 (23.4) | 34 (47.2) | 39 (48.2) | 73 (52.5) | <0.001 |
| Palpations | 45 (12.3) | 12 (15.6) | 7 (10) | 9 (11.1) | 17 (12.2) | 0.750 |
| Clinic parameter, mean ± SD | ||||||
| Systolic BP, mmHg | 146.6 ± 64.4 | 137.1 ± 26 | 146.2 ± 31 | 154.3 ± 126 | 147 ± 26 | 0.553 |
| Diastolic BP, mmHg | 84.8 ± 18.1 | 58.7 ± 17 | 90.9 ± 24 | 81.4 ± 14 | 83.2 ± 17 | 0.026 |
| Heart rate, bpm | 89.8 ± 28.6 | 88.3 ± 24 | 93.8 ± 27 | 88.1 ± 33 | 89.6 ± 29 | 0.609 |
| ECG—n (%) | ||||||
| ST elevation | 55 (14.8) | 25 (32.1) | 7 (9.7) | 7 (8.6) | 16 (11.3) | <0.001 |
| Inversed T-Waves | 183 (49.2) | 27 (34.6) | 33 (45.8) | 44 (54.3) | 79 (56) | 0.015 |
| Medical history—n (%) | ||||||
| Current Smoking | 85 (23.1) | 31 (40.3) | 18 (25.4) | 25 (30.9) | 11 (7.9) | <0.001 |
| Obesity | 112 (30) | 23 (29.5) | 24 (34.3) | 25 (30.9) | 40 (28.2) | 0.887 |
| Arterial hypertension | 253 (68.2) | 33 (42.3) | 36 (51.4) | 66 (81.5) | 118 (83.1) | <0.001 |
| Dyslipidemia | 99 (26.6) | 16 (20.5) | 19 (26.8) | 22 (27.2) | 42 (29.6) | 0.547 |
| Diabetes Mellitus | 65 (17.5) | 8 (10.3) | 10 (14.1) | 13 (16.1) | 34 (23.9) | 0.054 |
| COPD | 47 (12.6) | 0 (0) | 8 (11.3) | 18 (22.2) | 21 (14.8) | <0.001 |
| Bronchial Asthma | 33 (8.9) | 7 (9) | 10 (14.1) | 5 (6.2) | 11 (7.7) | 0.344 |
| Malignancy | 47 (12.7) | 2 (2.6) | 2 (2.9) | 12 (15) | 31 (21.8) | <0.001 |
| Kidney disease | 53 (14.3) | 5 (6.4) | 5 (7) | 12 (14.8) | 31 (21.8) | 0.003 |
| Neurological disease | 90 (24.3) | 11 (14.1) | 12 (17.1) | 19 (23.5) | 48 (33.8) | 0.004 |
| Autoimmune disease | 17 (4.6) | 5 (6.4) | 2 (2.8) | 3 (3.7) | 7 (5) | 0.733 |
| Psychiatric disease | 39 (10.5) | 6 (7.7) | 10 (14.1) | 14 (17.3) | 9 (6.3) | 0.041 |
| Pacemaker | 14 (3.8) | 0 (0) | 1 (1.4) | 2 (2.5) | 11 (7.8) | 0.012 |
| History of Malignant cardiac arrhythmias *—n (%) | 8 (2.2) | 0 (0) | 0 (0) | 2 (2.5) | 6 (7.8) | 0.101 |
| Bradycardiac arrhythmias | 6 (1.6) | 0 (0) | 0 (0) | 1 (1.2) | 5 (3.6) | 0.123 |
| -AV block 2 Mobitz | 3 (0.8) | 0 (0) | 0 (0) | 1 (1.2) | 2 (1.4) | 0.567 |
| -AV block 3 | 3 (0.8) | 0 (0) | 0 (0) | 0 (0) | 3 (2.1) | 0.179 |
| -Asystole | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 |
| Ventricular arrhythmias | 1 (0.3) | 0 (0) | 0 (0) | 1 (1.2) | 0 (0) | 0.311 |
| -sustained | 1 (0.3) | 0 (0) | 0 (0) | 1 (1.2) | 0 (0) | 0.311 |
| -non-sustained | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 |
| -ventricular fibrillation | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 |
| Torsades de pointes | 1 (0.3) | 0 (0) | 0 (0) | 0 (0) | 1 (0.7) | 0.658 |
| Atrial fibrillation * | 57 (15.4) | 1 (1.3) | 6 (8.6) | 13 (16.1) | 37 (26.1) | <0.001 |
| Laboratory values, mean ± SD | ||||||
| Troponin (µg/L) | 2.1 ± 8.4 | 2.8 ± 5.8 | 2.7 ± 12.1 | 1.3 ± 7.3 | 1 ± 5 | 0.234 |
| Creatin Phosphokinase (U/L) | 288.6 ± 548.9 | 352.2 ± 407 | 427.4 ± 943 | 235.4 ± 340 | 215 ± 418 | 0.030 |
| BNP (pg/ml) | 433.5 ± 1004.5 | 175 ± 390 | 432 ± 1286 | 560 ± 987 | 514 ± 1070 | 0.181 |
| Creatinine (mg/dl) | 3.3 ± 30.9 | 0.9 ± 0.2 | 12.9 ± 70.6 | 1.1 ± 0.4 | 1.1 ± 0.4 | 0.040 |
| TSH (mU/l) | 2 ± 1.7 | 2 ± 1.2 | 2.3 ± 2.4 | 1.8 ± 1.8 | 1.9 ± 1.4 | 0.986 |
| fT3 (pmol/l) | 5.2 ± 1 | 5.5 ± 1 | 5.2 ± 1 | 5.2 ± 1.1 | 4.8 ± 0.9 | 0.861 |
| fT4 (ng/l) | 10.6 ± 2.8 | 10.2 ± 1.8 | 9.1 ± 1.5 | 10.6 ± 3.1 | 12 ± 3.3 | 0.941 |
| Echocardiography data, n (%) | ||||||
| LVEF %, (on admission), mean ± SD | 36.9 ± 25.7 | 46.7 ± 23 | 37.5 ± 25 | 34.4 ± 27 | 32.6 ± 25 | <0.001 |
| -LVEF > 50 % | 170 (66.9) | 52 (82.5) | 29 (60.4) | 35 (67.3) | 54 (59.3) | 0.016 |
| -LVEF 40–49 % | 31 (12.2) | 3 (4.8) | 9 (18.8) | 5 (9.6) | 14 (15.4) | 0.096 |
| -LVEF < 40 % | 52 (20.5) | 8 (12.7) | 10 (20.8) | 11 (21.2) | 23 (25.3) | 0.305 |
| Left ventricular hypertrophy | 103 (29.1) | 15 (32.5) | 20 (30.3) | 23 (29.5) | 45 (33.8) | 0.177 |
| Tricuspid valve regurgitation | 89 (24.2) | 7 (9) | 15 (21.4) | 21 (26.3) | 46 (32.9) | 0.001 |
| -mild | 63 (17.1) | 6 (7.7) | 11 (15.7) | 14 (17.5) | 32 (22.9) | 0.041 |
| -moderate | 23 (6.3) | 1 (1.3) | 4 (5.7) | 6 (7.5) | 12 (8.6) | 0.187 |
| -severe | 3 (0.8) | 0 (0) | 0 (0) | 1 (1.3) | 2 (1.4) | 0.564 |
| Mitral valve regurgitation | 106 (28.8) | 7 (9) | 16 (22.9) | 21 (26.3) | 62 (44.3) | <0.001 |
| -mild | 77 (20.9) | 6 (7.7) | 12 (17.1) | 17 (21.3) | 42 (29.8) | 0.001 |
| -moderate | 19 (5.2) | 1 (1.3) | 2 (2.9) | 3 (3.8) | 13 (9.2) | 0.041 |
| -severe | 10 (2.7) | 0 (0) | 2 (2.9) | 1 (1.3) | 7 (5) | 0.137 |
| Aortic valve regurgitation | 39 (10.6) | 0 (0) | 7 (10) | 3 (3.8) | 29 (20.7) | <0.001 |
| -mild | 31 (8.4) | 0 (0) | 5 (7.1) | 3 (3.8) | 23 (16.4) | <0.001 |
| -moderate | 4 (1.1) | 0 (0) | 2 (2.8) | 0 (0) | 2 (1.4) | 0.271 |
| -severe | 4 (1.1) | 0 (0) | 0 (0) | 0 (0) | 4 (2.9) | 0.086 |
| Drugs on admission, n (%) | ||||||
| ß-Blocker | 131 (35.2) | 8 (10.3) | 20 (28.2) | 32 (39.5) | 71 (50.7) | <0.001 |
| ACE inhibitor | 121 (32.6) | 14 (17.9) | 17 (23.9) | 35 (43.2) | 55 (39) | <0.001 |
| Sartans | 57 (15.3) | 4 (5.1) | 9 (12.7) | 11 (13.6) | 33 (23.6) | 0.003 |
| Ca-Blocker | 74 (19.9) | 6 (7.7) | 8 (11.3) | 16 (19.8) | 44 (31.4) | <0.001 |
| Diuretics | 101 (27.2) | 8 (10.3) | 14 (19.7) | 16 (19.8) | 63 (45) | <0.001 |
| Statin | 281 (76.8) | 78 (27.1) | 75 (25.2) | 61 (21.3) | 41 (18.1) | <0.001 |
| Anticoagulants ** | 58 (15.6) | 1 (1.3) | 2 (2.8) | 17 (21) | 38 (27.1) | <0.001 |
| Aspirin | 79 (21.2) | 7 (9) | 12 (16.9) | 23 (28.4) | 37 (26.4) | 0.006 |
| Clopidogrel | 18 (4.8) | 2 (2.6) | 2 (2.8) | 6 (7.4) | 8 (5.7) | 0.416 |
| Prasugrel | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 |
| Antiarrhythmics *** | 10 (2.7) | 0 (0) | 3 (4.2) | 3 (3.7) | 4 (2.9) | 0.375 |
p values for the comparison between groups of ages; SD, Standard deviation; BMI, body mass index; BP, blood pressure; ECG, Electrocardiogram; COPD, Chronic obstructive pulmonary disease; AV, atrioventricular; BNP, brain natriuretic Peptide; LV EF, Ejection fraction; ACE, Angiotensin-converting-enzyme; *, only one malignant cardiac/supraventricular arrhythmia is counted per patient (even if one patient has several arrhythmias at the same time); ** coumarin, heparin, selective factor 10-blocker, direct thrombin inhibitors; ***, Ivabradine, Flecainide, Sotalol, Dronedarone, Digitalis; Bold indicates significant value.
According to their medical history, the older patients had higher rates of arterial hypertension (42.3% in the <51-year-old group vs. 51.4% in 51–60-year-old group vs. 81.5% in the 61–70-year-olds vs. 83.1% in the >70 group; p < 0.001), malignancy (2.6% vs. 2.9% vs. 15% vs. 21.8%; p < 0.001), and kidney disease (6.4% vs. 7% vs. 14.8% vs. 21.8%; p = 0.003). The number of current smokers was higher in the <51-year-old group than those in the other groups (age < 51: 40.3% vs. age 51–60: 25.4% vs. age 61–70: 30.9% vs. age > 70: 7.9%; p < 0.001). The patients in the 51–60- and 61–70-year-old groups displayed psychiatric disorders more frequently than the other groups (7.7% vs. 14.1% vs. 17.3% vs. 6.3%; p = 0.045). The prevalence of atrial fibrillation (AF) on admission was higher in the >70-year-old group as compared to that of the other groups (1.3% vs. 8.6% vs. 16.1% vs. 26.1%; p < 0.001). The left ventricular ejection fraction (LVEF) was higher in the <51-year-old group as compared to those of the other groups (46.7% ± 23 vs. 37.5% ± 25 vs. 34.4% ± 27 vs. 32.6% ± 25; p < 0.001). The arrhythmias, the symptoms, the laboratory values, and the medication given on admission are presented in Table 1. The medication given at discharge is presented in Table 2.
Table 2.
Medication given at discharge.
| Variables | All Patients n = 373 |
<51 n = 78 |
51–60 n = 72 |
61–70 n = 81 |
>70 n = 142 |
p Value |
|---|---|---|---|---|---|---|
| ß-Blocker, n (%) | 270 (72.4) | 50 (64.1) | 54 (75) | 63 (77.8) | 103 (72.5) | 0.252 |
| ACE inhibitor, n (%) | 224 (60.1) | 46 (59) | 47 (65.3) | 51 (63) | 80 (56.3) | 0.584 |
| Sartans, n (%) | 62 (16.6) | 6 (7.7) | 10 (13.9) | 15 (18.5) | 31 (21.8) | 0.049 |
| Ca Blocker, n (%) | 100 (26.8) | 12 (15.4) | 15 (20.8) | 24 (29.6) | 49 (34.5) | 0.011 |
| Diuretics, n (%) | 166 (44.5) | 13 (16.7) | 29 (40.3) | 34 (42) | 90 (63.4) | <0.001 |
| Statin, n (%) | 206 (55.2) | 21 (26.9) | 32 (44.4) | 41 (50.6) | 73 (51.4) | <0.001 |
| Anticoagulants *, n (%) | 104 (27.9) | 3 (3.9) | 17 (23.6) | 25 (30.9) | 59 (41.5) | <0.001 |
| Aspirin, n (%) | 175 (46.9) | 27 (34.6) | 32 (44.4) | 46 (56.8) | 70 (49.3) | 0.038 |
| Clopidogrel, n (%) | 68 (18.2) | 14 (18) | 11 (15.3) | 20 (24.7) | 23 (16.2) | 0.381 |
| Prasugrel, n (%) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 |
| Antiarrhythmics **, n (%) | 26 (7) | 1 (1.3) | 7 (9.7) | 5 (6.2) | 13 (9.2) | 0.119 |
ACE, Angiotensin-converting-enzyme; * Coumarin, Heparin, selective factor 10-blocker, direct thrombin inhibitors; ** Ivabradine, Flecainide, Sotalol, Dronedarone, Digitalis; Bold indicates significant value.
3.2. In-Hospital Complications Presented According to Age
Major adverse cardiovascular events were associated with increased age (15.4% vs. 36.1% vs. 33.3% vs. 47.2%; p < 0.001). Interestingly, non-sustained ventricular arrhythmias (nsVTs) occurred more frequently in the 51–60-year-old group as compared to those in the other age groups (0% vs. 5.6% vs. 1.3% vs. 0.7; p = 0.027). Newly diagnosed AF was more prevalent in the >70 age group as compared to the rates in the other groups (3.8% vs. 6.9% vs. 7.4% vs. 20.4%; p < 0.001). The other cardiovascular in-hospital complications, including mortality, were similar in all the age groups (in-hospital mortality: none vs. 4.2% vs. 2.5% vs. 3.5%; p = 0.371) (Figure 2). Table 3 presents the in-hospital-complications according to age.
Figure 2.
In-hospital events related to age.
Table 3.
In-hospital complications presented according to age.
| Variables | All Patients n = 373 |
<51 n = 78 |
51–60 n = 72 |
61–70 n = 81 |
>70 n = 142 |
p Value |
|---|---|---|---|---|---|---|
| Adverse event, n (%) | 132 (35.5) | 12 (15.4) | 26 (36.1) | 27 (33.3) | 67 (47.2) | <0.001 |
| CPR | 7 (1.9) | 0 (0) | 3 (4.2) | 1 (1.2) | 3 (2.1) | 0.290 |
| Left ventricular thrombus | 3 (0.8) | 1 (1.3) | 1 (1.4) | 0 (0) | 1 (0.7) | 0.754 |
| Thromboembolic event | 3 (0.8) | 0 (0) | 0 (0) | 1 (1.2) | 2 (1.4) | 0.564 |
| Pulmonary edema | 9 (2.7) | 1 (1.3) | 2 (2.8) | 2 (2.5) | 4 (2.8) | 0.906 |
| Cardiogenic shock | 9 (2.7) | 1 (1.3) | 2 (2.8) | 2 (2.5) | 4 (2.8) | 0.906 |
| Invasive ventilation | 29 (7.8) | 4 (5.1) | 8 (11.1) | 6 (7.4) | 11 (7.8) | 0.597 |
| Non-invasive ventilation | 11 (3) | 0 (0) | 1 (1.4) | 4 (4.9) | 6 (4.3) | 0.180 |
| Stroke | 1 (0.3) | 0 (0) | 1 (1.4) | 0 (0) | 0 (0) | 0.243 |
| Malignant cardiac arrhythmias *, n (%) (on admission/in hospital) | 39 (10.5) | 8 (10.3) | 11 (15.3) | 5 (6.2) | 15 (10.6) | 0.339 |
| Bradycardiac arrhythmias | 13 (3.5) | 3 (3.8) | 1 (1.4) | 1 (1.2) | 8 (5.6) | 0.248 |
| -AV block 2 Mobitz | 3 (0.8) | 2 (2.6) | 0 (0) | 0 (0) | 1 (0.7) | 0.234 |
| -AV block 3 | 1 (0.3) | 0 (0) | 0 (0) | 0 (0) | 1 (0.7) | 0.655 |
| -Asystole | 10 (2.7) | 2 (2.6) | 1 (1.4) | 1 (1.2) | 6 (4.2) | 0.494 |
| Ventricular arrhythmias | 14 (3.8) | 2 (2.6) | 5 (6.9) | 4 (4.9) | 5 (3.5) | 0.438 |
| -sustained | 8 (2.2) | 2 (2.6) | 2 (2.8) | 0 (0) | 4 (2.8) | 0.524 |
| -non-sustained | 6 (1.6) | 0 (0) | 4 (5.6) | 1 (1.3) | 1 (0.7) | 0.027 |
| -ventricular fibrillation | 16 (4.3) | 3 (3.8) | 7 (9.7) | 3 (3.7) | 3 (2.1) | 0.075 |
| Torsades de pointes | 2 (0.5) | 0 (0) | 1 (1.4) | 0 (0) | 1 (0.7) | 0.598 |
| Supraventricular arrhythmias *, n (%) | 85 (22.8) | 3 (3.8) | 11 (15.3) | 19 (23.5) | 52 (36.6) | <0.001 |
| Atrial fibrillation | 77 (20.6) | 3 (3.8) | 8 (11.1) | 15 (18.5) | 51 (35.9) | <0.001 |
| -first appearance | 43 (11.5) | 3 (3.8) | 5 (6.9) | 6 (7.4) | 29 (20.4) | <0.001 |
| -recurrens | 34 (9.1) | 0 (0) | 3 (4.2) | 9 (11.1) | 22 (15.5) | <0.001 |
| Atrial flutter | 9 (2.4) | 0 (0) | 3 (4.2) | 4 (4.9) | 2 (1.4) | 0.129 |
| -first appereance | 9 (2.4) | 0 (0) | 3 (4.2) | 4 (4.9) | 2 (1.4) | 0.129 |
| -recurrens | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 |
| In-hospital death, n (%) | 10 (2.7) | 0 (0) | 3 (4.2) | 2 (2.5) | 5 (3.5) | 0.371 |
| Cardiac caused death | 6 (1.6) | 0 (0) | 2 (2.8) | 1 (1.3) | 3 (2.1) | 0.535 |
| Non-cardiac caused death | 4 (1.1) | 0 (0) | 1 (1.4) | 1 (1.3) | 2 (1.4) | 0.783 |
adverse event, major adverse cardiovascular events; CPR, cardiopulmonary resuscitation; AV, atrioventricular; *, only one malignant cardiac/supraventricular arrhythmia is counted per patient (even if one patient has several arrhythmias at the same time); Bold indicates significant values.
3.3. LVEF and Clinical Outcomes Presented According to Age at Long-Term Follow-Up
The LVEF at the follow-up was higher in the <51 age group than those in the other groups (58.1% ± 11 vs. 48.4% ± 17 vs. 41.3% ± 14 vs. 43.1% ± 12; p < 0.001) (Table 4). The rate of major adverse cardiovascular events at the long-term follow-up was higher in the >70 age group, without statistical significance (6.5% vs. 21.6% vs. 26.2% vs. 61.1%; p = 0.126). Cardiovascular mortality was more common in the patients >70 years of age (none in the <51- and 51–60-year-olds vs. 3.9% in the 61–70-year-olds vs. 4.2% in the >70-year-olds; p = 0.042). Non-cardiovascular mortality was more frequent in the patients aged 51–60 and >70 years, but without statistically significance (none in the <51-year-olds vs. 8.2% in the 51–60-year-olds vs. 3.9% in the 61–70-year-olds vs. 8.5% in the >70-year-olds; p = 0.075) (Figure 3). The clinical outcomes are presented in Table 5.
Table 4.
EF at follow-up and during in-hospital treatment.
| Variables | All Patients n = 373 |
<51 n = 78 |
51–60 n = 72 |
61–70 n = 82 |
>70 n = 142 |
p Value |
|---|---|---|---|---|---|---|
| FU EF (%), mean ± SD | 49 ± 14.7 | 58.1 ± 11 | 48.4 ± 17 | 42.3 ± 14 | 43.1 ± 12 | <0.001 |
| -LVEF ≥ 50 %, n (%) | 184 (49.3) | 33 (42.3) | 21 (30) | 15 (19.5) | 31 (23) | 0.005 |
| -LVEF 40-49 %, n (%) | 100 (27.8) | 3 (3.9) | 7 (10) | 5 (6.5) | 12 (8.9) | 0.457 |
| -LVEF < 40 %, n (%) | 27 (7.5) | 5 (6.4) | 10 (14.3) | 10 (13) | 25 (18.5) | 0.106 |
| Cardioversion, n (%) | 50 (13.9) | 5 (6.4) | 14 (19.4) | 17 (21.3) | 28 (19.7) | 0.042 |
| Pacemaker, n (%) | 64 (17.2) | 2 (2.6) | 8 (11.1) | 5 (6.2) | 9 (6.3) | 0.208 |
| LifeVest, n (%) | 24 (6.5) | 5 (6.4) | 4 (5.6) | 1 (1.2) | 2 (1.4) | 0.097 |
Figure 3.
Kaplan–Meier curve.
Table 5.
Clinical outcomes presented according to age at follow-up.
| All Patients n = 288 |
<51 n = 62 |
51–60 n = 51 |
61–70 n = 61 |
>70 n = 114 |
p Value |
|
|---|---|---|---|---|---|---|
| Adverse event, n (%) | 100 (34.8) | 4 (6.5) | 11 (21.6) | 16 (26.2) | 69 (61.1) | 0.126 |
| Stroke | 10 (4.2) | 2 (3.9) | 1 (2.1) | 1 (2) | 6 (6.8) | 0.797 |
| Thromboembolic event | 6 (2.5) | 2 (3.2) | 0 (0) | 1 (1.9) | 3 (4) | 0.385 |
| Recurrence of Troponin-positive with non-obstructive CAD | 3 (1.3) | 0 (0) | 1 (2.1) | 1 (1.9) | 1 (1.4) | 0.981 |
| Cardiac arrest | 4 (1.7) | 0 (0) | 1 (2.1) | 1 (1.9) | 2 (2.7) | 0.900 |
| Percutaneous coronary intervention | 17 (7.2) | 2 (3.2) | 3 (6.3) | 3 (5.7) | 9 (12.3) | 0.352 |
| Death, n (%) | 69 (24.1) | 0 (0) | 6 (11.8) | 12 (20) | 51 (45.1) | 0.067 |
| -cardiac caused death | 5 (2.1) | 0 (0) | 0 (0) | 2 (3.9) | 3 (4.2) | 0.042 |
| -non-cardiac caused death | 12 (5.1) | 0 (0) | 4 (8.2) | 2 (3.9) | 6 (8.5) | 0.075 |
Adverse event, major adverse cardiovascular events; CAD, coronary artery disease; Bold indicates significant values.
FU EF, follow up ejection fraction; LVEF, left ventricular ejection fraction; Bold indicates significant values.
4. Discussion
The main findings of this study are as follows: (1) The incidence of troponin level elevation without an obstructive culprit lesion was higher in the patients aged >70 years compared to those of the other age groups. (2) Adverse in-hospital events were more frequent in the older patients, but the in-hospital mortality rates were similar across the age groups. (3) At the long-term follow-up, cardiovascular mortality was higher in the group aged >70 years. (4) The overall all-cause mortality rate among all the patients over a decade was 24.1%.
Age impacts the outcome of cardiovascular diseases, such as atherosclerosis and arterial hypertension, and is a well-established risk factor for worse prognoses in these conditions [15]. Troponin level elevation without an obstructive culprit lesion presents an inherent challenge due to the numerous possible etiologies and pathogenic mechanisms. In this study, troponin level elevation without an obstructive culprit lesion was characterized by clinical evidence of MI with normal coronary arteries or stenosis <50%. However, coronary microvascular disease (CMD) plays a significant role in this condition [1]. In this context, the functional assessment of microcirculation represents a promising technique for evaluating patients with troponin level elevation, given the high prevalence of CMD and its significant clinical implications. This approach is likely to become more widely used in the future.
In our study, the incidence of troponin level elevation without an obstructive culprit lesion was notably high in the patients >70 years old. Among the patients <51 years old, males were more frequently affected; half of the total cohort consisted of females. One study corroborated our findings, showing a high prevalence of troponin level elevation without an obstructive culprit lesion in older patients, with female being the predominant sex [16]. Conversely, a systemic review reported that younger, predominantly female patients were more likely to experience troponin level elevation without an obstructive culprit lesion [17]. Another study highlighted that woman aged ≤70 years had worse prognoses, with significantly higher rates of major adverse cardiovascular events (MACEs) compared to men and women with MI and obstructive CAD [18]. This was attributed to distinct pathophysiological mechanisms affecting the long-term outcomes [18]. Additionally, the data from the VIRGO registry indicated that females had a fivefold higher risk of this developing syndrome compared to that of males [19].
Our data suggest that troponin level elevation without an obstructive culprit lesion becomes more prevalent with advancing age. Thus, a conservative approach avoiding invasive diagnostic measures may be appropriate in suspected cases of this syndrome. Furthermore, we observed a higher prevalence of psychiatric disorders in the 51–60 and 61–70 age groups. This is consistent with previous findings indicating that patients with troponin level elevation without an obstructive culprit lesion have a higher rate of psychiatric illness compared to those with obstructive CAD [20]. Psychiatric disorders have also been more frequently associated with takotsubo syndrome (TTS) [21]. Moreover, anxiety has been observed in patients with elevated troponin levels, which is linked to an increased risk of all-cause mortality [22]. In the 51–60 age group, the incidence of non-sustained ventricular tachycardia (nsVT) was higher compared to that in the other groups. This may be attributed to the higher prevalence of TTS and myocarditis in this age group [23,24]. Additionally, the patients in this group exhibited a reduced LVEF and elevated troponin levels, both of which are associated with an increased risk of ventricular arrhythmias. However, the data on troponin level elevation without an obstructive culprit lesion across different age groups remain limited.
Adverse events, including AF, were more frequent in the individuals >70 years. A meta-analysis reported that patients with troponin level elevation without an obstructive culprit lesion are at a high risk of having an MACE [25]. This increased risk may be due to undertreatment and the lack of personalized therapeutic options for these patients. Additionally, they often present with left ventricular dysfunction [26]. AF has also been identified as a risk factor for MACEs in patients with elevated troponin levels without an obstructive culprit lesion [27]. In our study, in-hospital mortality was comparable across all the age groups. However, unlike MI caused by obstructive CAD in older patients, troponin level elevation without obstructive CAD is associated with a higher risk of in-hospital mortality, as reported by Ishii et al. [28].
Our study revealed that the patients >70 years old exhibited a higher cardiovascular mortality rate during the long-term follow-up compared to those of the other age groups. Over a decade, the overall all-cause mortality rate among all the patients was 24.1%. This rate is higher compared to the previously reported data, such as in the VIRGO registry, which documented a 12-month mortality rate of 0.6% for patients with troponin level elevation without obstructive CAD. Similarly, a multicenter cohort study reported a 20% mortality rate at a 5-year follow-up, while a systematic meta-analysis estimated a mortality rate of 2% at 25 months [29,30]. Another meta-analysis reported a 4.7% mortality rate at 12 months [17]. In another study, approximately half of the patients with a history of troponin level elevation without an obstructive culprit lesion who experienced reinfarction showed evidence of atherosclerosis progression, often requiring revascularization. Furthermore, the recommended low-density-lipoprotein cholesterol (LDL-C) target levels were achieved in only a minority of these patients, suggesting that the cardiovascular disease risk in this population may be underestimated or insufficiently managed. It is important to note that our dataset spans a decade and provides a broader context for evaluating mortality trends. However, the patients >70 years old in our study exhibited a higher prevalence of cardiovascular comorbidities, including AF, and presented with a lower LVEF at admission compared to those of the other age groups. This indicates a more severe cardiovascular risk profile in the elderly population. Currently, data on the age-related trends in patients with elevated troponin levels without an obstructive culprit lesion extending beyond ten years remain scarce.
Summarizing, the prevalence of troponin level elevation without an obstructive culprit lesion was observed to be higher in the patients >70 years old compared to that in the other age groups. This group experienced more adverse events and had a higher cardiovascular mortality rate than those of the other patients. In this context, implementing advanced diagnostic approaches, such as cardiac magnetic resonance (CMR) imaging and the functional assessment of microcirculation, may be beneficial in selected cases, particularly at initial presentation with suspected non-obstructive coronary disease. However, the feasibility and clinical utility of such approaches require further investigation. The more refined stratification of patients with troponin level elevation without an obstructive culprit lesion may also help in tailoring treatment strategies. While age remains an important consideration in this population, additional studies are essential to better characterize and address their specific clinical needs.
5. Limitations
Several limitations of this study should be noted. This is a monocentric retrospective study. CMR imaging was not performed systematically on all the patients. Angiographic classification was assessed using visual evaluation. Intravascular imaging, which represents an important diagnostic tool, was not performed, including intravascular ultrasound (IVUS) or optical coherence tomography (OCT).
Author Contributions
Conceptualization, M.A., N.H., I.A., A.A. and I.E.-B.; methodology, D.M.; software, C.S., D.M. and I.E.-B.; validation, M.A., N.H., I.A. and A.A.; formal analysis, C.S. and D.M.; investigation, I.E.-B.; resources, A.M. and A.A.; data curation, C.S., D.M. and I.E.-B.; writing—original draft, M.A.; writing—review & editing, M.A., A.M., I.A. and I.E.-B.; visualization, I.E.-B.; supervision, A.M., N.H., I.A., A.A. and I.E.-B.; project administration, M.A., A.A. and I.E.-B.; funding acquisition, A.M. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Medical Faculty Ethics Committee at Ruhr University Bochum, approval number 22-7684, on the 16 October 2022.
Informed Consent Statement
Patient consent was waived due to the retrospective character of the study.
Data Availability Statement
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
Conflicts of Interest
The authors declare no conflicts of interest.
Funding Statement
This research received no external funding.
Footnotes
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References
- 1.Tamis-Holland J.E., Jneid H., Reynolds H.R., Agewall S., Brilakis E.S., Brown T.M., Lerman A., Cushman M., Kumbhani D.J., Arslanian-Engoren C., et al. Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association. Circulation. 2019;139:e891–e908. doi: 10.1161/CIR.0000000000000670. [DOI] [PubMed] [Google Scholar]
- 2.Scalone G., Niccoli G., Crea F. Editor’s Choice- Pathophysiology, diagnosis and management of MINOCA: An update. Eur. Heart J. Acute Cardiovasc. Care. 2019;8:54–62. doi: 10.1177/2048872618782414. [DOI] [PubMed] [Google Scholar]
- 3.Mukherjee D. Myocardial Infarction With Nonobstructive Coronary Arteries: A Call for Individualized Treatment. J. Am. Heart Assoc. 2019;8:e013361. doi: 10.1161/JAHA.119.013361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Choo E.H., Chang K., Lee K.Y., Lee D., Kim J.G., Ahn Y., Kim Y.J., Chae S.C., Cho M.C., Kim C.J., et al. Prognosis and Predictors of Mortality in Patients Suffering Myocardial Infarction With Non-Obstructive Coronary Arteries. J. Am. Heart Assoc. 2019;8:e011990. doi: 10.1161/JAHA.119.011990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Lindahl B., Baron T., Erlinge D., Hadziosmanovic N., Nordenskjold A., Gard A., Jernberg T. Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease. Circulation. 2017;135:1481–1489. doi: 10.1161/CIRCULATIONAHA.116.026336. [DOI] [PubMed] [Google Scholar]
- 6.Planer D., Mehran R., Ohman E.M., White H.D., Newman J.D., Xu K., Stone G.W. Prognosis of patients with non-ST-segment-elevation myocardial infarction and nonobstructive coronary artery disease: Propensity-matched analysis from the Acute Catheterization and Urgent Intervention Triage Strategy trial. Circ. Cardiovasc. Interv. 2014;7:285–293. doi: 10.1161/CIRCINTERVENTIONS.113.000606. [DOI] [PubMed] [Google Scholar]
- 7.Armillotta M., Amicone S., Bergamaschi L., Angeli F., Rinaldi A., Paolisso P., Stefanizzi A., Sansonetti A., Impellizzeri A., Bodega F., et al. Predictive value of Killip classification in MINOCA patients. Eur. J. Intern. Med. 2023;117:57–65. doi: 10.1016/j.ejim.2023.08.011. [DOI] [PubMed] [Google Scholar]
- 8.Abumayyaleh M., El-Battrawy I., Kummer M., Pilsinger C., Sattler K., Kuschyk J., Aweimer A., Mugge A., Borggrefe M., Akin I. Comparison of the prognosis and outcome of heart failure with reduced ejection fraction patients treated with sacubitril/valsartan according to age. Future Cardiol. 2021;17:1131–1142. doi: 10.2217/fca-2020-0213. [DOI] [PubMed] [Google Scholar]
- 9.Byrne R.A., Rossello X., Coughlan J.J., Barbato E., Berry C., Chieffo A., Claeys M.J., Dan G.A., Dweck M.R., Galbraith M., et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur. Heart J. 2023;44:3720–3826. doi: 10.1093/eurheartj/ehad191. [DOI] [PubMed] [Google Scholar]
- 10.Agewall S., Beltrame J.F., Reynolds H.R., Niessner A., Rosano G., Caforio A.L., De Caterina R., Zimarino M., Roffi M., Kjeldsen K., et al. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur. Heart J. 2017;38:143–153. doi: 10.1093/eurheartj/ehw149. [DOI] [PubMed] [Google Scholar]
- 11.Thygesen K., Alpert J.S., Jaffe A.S., Chaitman B.R., Bax J.J., Morrow D.A., White H.D., ESC Scientific Document Group Fourth universal definition of myocardial infarction (2018) Eur. Heart J. 2019;40:237–269. doi: 10.1093/eurheartj/ehy462. [DOI] [PubMed] [Google Scholar]
- 12.Sorensen N.A., Neumann J.T., Ojeda F., Giannitsis E., Spanuth E., Blankenberg S., Westermann D., Zeller T. Diagnostic Evaluation of a High-Sensitivity Troponin I Point-of-Care Assay. Clin. Chem. 2019;65:1592–1601. doi: 10.1373/clinchem.2019.307405. [DOI] [PubMed] [Google Scholar]
- 13.Wildi K., Nelles B., Twerenbold R., Rubini Gimenez M., Reichlin T., Singeisen H., Druey S., Haaf P., Sabti Z., Hillinger P., et al. Safety and efficacy of the 0 h/3 h protocol for rapid rule out of myocardial infarction. Am. Heart J. 2016;181:16–25. doi: 10.1016/j.ahj.2016.07.013. [DOI] [PubMed] [Google Scholar]
- 14.Collet J.P., Thiele H., Barbato E., Barthelemy O., Bauersachs J., Bhatt D.L., Dendale P., Dorobantu M., Edvardsen T., Folliguet T., et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur. Heart J. 2021;42:1289–1367. doi: 10.1093/eurheartj/ehaa575. [DOI] [PubMed] [Google Scholar]
- 15.Lakatta E.G. Age-associated cardiovascular changes in health: Impact on cardiovascular disease in older persons. Heart Fail. Rev. 2002;7:29–49. doi: 10.1023/A:1013797722156. [DOI] [PubMed] [Google Scholar]
- 16.Gabaldon-Perez A., Bonanad C., Garcia-Blas S., Marcos-Garces V., D’Gregorio J.G., Fernandez-Cisnal A., Valero E., Minana G., Merenciano-Gonzalez H., Mollar A., et al. Clinical Predictors and Prognosis of Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) without ST-Segment Elevation in Older Adults. J. Clin. Med. 2023;12:1181. doi: 10.3390/jcm12031181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Pasupathy S., Air T., Dreyer R.P., Tavella R., Beltrame J.F. Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries. Circulation. 2015;131:861–870. doi: 10.1161/CIRCULATIONAHA.114.011201. [DOI] [PubMed] [Google Scholar]
- 18.Canton L., Fedele D., Bergamaschi L., Foa A., Di Iuorio O., Tattilo F.P., Rinaldi A., Angeli F., Armillotta M., Sansonetti A., et al. Sex- and age-related differences in outcomes of patients with acute myocardial infarction: MINOCA vs. MIOCA. Eur. Heart J. Acute Cardiovasc. Care. 2023;12:604–614. doi: 10.1093/ehjacc/zuad059. [DOI] [PubMed] [Google Scholar]
- 19.Safdar B., Spatz E.S., Dreyer R.P., Beltrame J.F., Lichtman J.H., Spertus J.A., Reynolds H.R., Geda M., Bueno H., Dziura J.D., et al. Presentation, Clinical Profile, and Prognosis of Young Patients With Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): Results From the VIRGO Study. J. Am. Heart Assoc. 2018;7:e009174. doi: 10.1161/JAHA.118.009174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Pais J.L., Izquierdo Coronel B., Galan Gil D., Espinosa Pascual M.J., Martinez Peredo C.G., Awamleh Garcia P., Gorriz Magana J., Mata Caballero R., Fraile Sanz A., Muniz J., et al. Psycho-emotional disorders as incoming risk factors for myocardial infarction with non-obstructive coronary arteries. Cardiol. J. 2018;25:24–31. doi: 10.5603/CJ.a2017.0139. [DOI] [PubMed] [Google Scholar]
- 21.Lopez-Pais J., Izquierdo Coronel B., Raposeiras-Roubin S., Alvarez Rodriguez L., Vedia O., Almendro-Delia M., Sionis A., Martin-Garcia A.C., Uribarri A., Blanco E., et al. Differences Between Takotsubo and the Working Diagnosis of Myocardial Infarction With Nonobstructive Coronary Arteries. Front. Cardiovasc. Med. 2022;9:742010. doi: 10.3389/fcvm.2022.742010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.He C.J., Zhu C.Y., Han B., Hu H.Z., Wang S.J., Zhai C.L., Hu H.L. Association between anxiety and clinical outcomes in Chinese patients with myocardial infarction in the absence of obstructive coronary artery disease. Clin. Cardiol. 2020;43:659–665. doi: 10.1002/clc.23386. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Cammann V.L., Szawan K.A., Stahli B.E., Kato K., Budnik M., Wischnewsky M., Dreiding S., Levinson R.A., Di Vece D., Gili S., et al. Age-Related Variations in Takotsubo Syndrome. J. Am. Coll. Cardiol. 2020;75:1869–1877. doi: 10.1016/j.jacc.2020.02.057. [DOI] [PubMed] [Google Scholar]
- 24.Tornvall P., Gerbaud E., Behaghel A., Chopard R., Collste O., Laraudogoitia E., Leurent G., Meneveau N., Montaudon M., Perez-David E., et al. Myocarditis or “true” infarction by cardiac magnetic resonance in patients with a clinical diagnosis of myocardial infarction without obstructive coronary disease: A meta-analysis of individual patient data. Atherosclerosis. 2015;241:87–91. doi: 10.1016/j.atherosclerosis.2015.04.816. [DOI] [PubMed] [Google Scholar]
- 25.Pizzi C., Xhyheri B., Costa G.M., Faustino M., Flacco M.E., Gualano M.R., Fragassi G., Grigioni F., Manzoli L. Nonobstructive Versus Obstructive Coronary Artery Disease in Acute Coronary Syndrome: A Meta-Analysis. J. Am. Heart Assoc. 2016;5:e004185. doi: 10.1161/JAHA.116.004185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Almeida A.G. MINOCA and INOCA: Role in Heart Failure. Curr. Heart Fail. Rep. 2023;20:139–150. doi: 10.1007/s11897-023-00605-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Abdu F.A., Liu L., Mohammed A.Q., Luo Y., Xu S., Auckle R., Xu Y., Che W. Myocardial infarction with non-obstructive coronary arteries (MINOCA) in Chinese patients: Clinical features, treatment and 1 year follow-up. Int. J. Cardiol. 2019;287:27–31. doi: 10.1016/j.ijcard.2019.02.036. [DOI] [PubMed] [Google Scholar]
- 28.Ishii M., Kaikita K., Sakamoto K., Seki T., Kawakami K., Nakai M., Sumita Y., Nishimura K., Miyamoto Y., Noguchi T., et al. Characteristics and in-hospital mortality of patients with myocardial infarction in the absence of obstructive coronary artery disease in super-aging society. Int. J. Cardiol. 2020;301:108–113. doi: 10.1016/j.ijcard.2019.09.037. [DOI] [PubMed] [Google Scholar]
- 29.Quesada O., Yildiz M., Henry T.D., Okeson B.K., Chambers J., Shah A., Stanberry L., Volpenhein L., Aziz D., Lantz R., et al. Characteristics and Long-term Mortality in Patients with ST-Segment Elevation Myocardial Infarction with Non-Obstructive Coronary Arteries (STE-MINOCA): A High Risk Cohort. medRxiv. 2023 doi: 10.1101/2023.02.05.23285502. [DOI] [Google Scholar]
- 30.Pelliccia F., Pasceri V., Niccoli G., Tanzilli G., Speciale G., Gaudio C., Crea F., Camici P.G. Predictors of Mortality in Myocardial Infarction and Nonobstructed Coronary Arteries: A Systematic Review and Meta-Regression. Am. J. Med. 2020;133:73–83.e4. doi: 10.1016/j.amjmed.2019.05.048. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.