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The Prevention and Treatment of Atherosclerosis

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 46109

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Guest Editor
Department of Interventional Cardiology, Institute of Cardiology, The John Paul II Hospital, Jagiellonian University Medical College, 80 Prądnicka St, 31-202 Krakow, Poland
Interests: cardiovascular disease; inflammatory cytokines and microRNAs in atherosclerosis and aortic valve stenosis; athero-sclerosis prevention and treatment; interventions on carotid and renal arteries; renovascular disease; monitoring of ath-erosclerosis progression; carotid intima-media; arterial stiffness; vascular age
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Special Issue Information

Dear Colleagues,

This special issue of Journal of Clinical Medicine ‘The Prevention and Treatment of Atherosclerosis’ will walk the Readers across novel diagnostic achievements in atherosclerosis and contemporary actions towards optimizing therapy.

Everything begins with diagnosis. Correct and timely, optimally providing additional information on the risk associated with findings, diagnosis enables introduction of prevention and cure. Thus, accurate diagnostic tools and tests are of utmost importance. Contemporary research on microparticles, non-coding RNAs, proteomic characterization, …, offers detailed molecular characteristics of athero-thrombosis.

In the field of atherosclerosis, prevention is equally important as treatment. The impact of eating habits in prophylaxis of many pathologies, including cardiovascular disease has been documented. Nutraceutical products, smoking cessation, physical activity, and many others they all have impact on atherosclerosis retention.

Then new pharmacological agents. Managing hypercholesterolemia with protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, shown great potential in efficient lipid lowering to achieve low-density lipoprotein-cholesterol (LDL-C) treatment goals, as well as reduction in cardiovascular mortality and morbidity. Some new noninsulin glucose-lowering drugs show improvement of cardiovascular outcomes in diabetic patients.

However, therapeutic goals accomplishment requires supervision.  Arising number of data support that cardiovascular risk prediction can be improved with imaging modalities displaying atheroma: carotid plaque ultrasonography, coronary calcium score, intravascular ultrasonography, and optical coherent tomography or many others.

As atherosclerosis is a progressive disease, it comes the time for more radical management, including endovascular and surgical intervention. Both safety, and procedure optimization guarantee good outcome. There is field for new stent and equipment technologies, new surgical and endovascular techniques, supervision of endovascular procedures with IVUS, OCT, functional flow assessment or cell therapy.

From diagnosis to risk stratification, elaborated prevention models, finally to modern and optimized therapeutic intervention.

We welcome the submission of original research and review articles on the following topics:

  • Molecular triggers of atherosclerosis
  • Achieving goals in cardiovascular risk factors prevention and treatment
  • Cardiovascular risk stratification and algorithms
  • Imaging tools to control atherosclerosis reduction and progression
  • Optimizing treatment for occlusive atherosclerotic lesions in coronary and extra coronary territories

Prof. Dr. Anna Kabłak-Ziembicka
Guest Editor

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Keywords

  • Atherosclerosis
  • Cardiovascular risk
  • Diagnosis and prevention
  • Cell biology
  • Proteomic
  • Pharmacological and non-pharmacological prevention
  • Monitoring of goals
  • Optimizing therapy
  • Carotid intima-media
  • Optical coherence tomography
  • IVUS
  • Coronary
  • Carotid and peripheral interventions

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Published Papers (11 papers)

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Editorial

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3 pages, 184 KiB  
Editorial
Special Issue “The Prevention and Treatment of Atherosclerosis”
by Anna Kabłak-Ziembicka
J. Clin. Med. 2022, 11(4), 1023; https://doi.org/10.3390/jcm11041023 - 16 Feb 2022
Viewed by 1887
Abstract
This editorial summarizes the 10 scientific papers that contributed to the Special Issue of the Journal of Clinical Medicine: ‘The Prevention and Treatment of Atherosclerosis’ [...] Full article
(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)

Research

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11 pages, 277 KiB  
Article
Small Differences in Vitamin D Levels between Male Cardiac Patients in Different Stages of Coronary Artery Disease
by Ewelina A. Dziedzic, William B. Grant, Izabela Sowińska, Marek Dąbrowski and Piotr Jankowski
J. Clin. Med. 2022, 11(3), 779; https://doi.org/10.3390/jcm11030779 - 31 Jan 2022
Cited by 4 | Viewed by 2489
Abstract
Cardiovascular diseases are the main cause of mortality in males older than 65 years of age. The prevalent vitamin D deficiency in the worldwide population may have multiple effects on the cardiovascular system. This study sought to determine the association between serum levels [...] Read more.
Cardiovascular diseases are the main cause of mortality in males older than 65 years of age. The prevalent vitamin D deficiency in the worldwide population may have multiple effects on the cardiovascular system. This study sought to determine the association between serum levels of 25-hydroxyvitamin D (25(OH)D) and the stage of coronary artery disease (CAD) in Polish male subjects. Additionally, subjects with a history of myocardial infarction (MI) were analyzed for potential differences in 25(OH)D levels in comparison with those diagnosed with stable CAD. The study was conducted prospectively in a group of 669 male patients subjected to coronarography examination. CAD stage was defined using the Coronary Artery Surgery Study Score. Patients without significant coronary lesions had significantly higher 25(OH)D levels than patients with single-, double-, or triple-vessel disease (median, 17 vs. 15 ng/mL; p < 0.01). Significantly lower levels of 25(OH)D were apparent when MI was identified as the cause of the then-current hospitalization in comparison with stable CAD, as well as in patients with a history of MI; all of these cases had lower levels of 25(OH)D in comparison with patients with no such history. Male patients with single-, double-, or triple-vessel CAD, acute coronary syndrome, or a history of MI presented lower serum 25(OH)D. Full article
(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)
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13 pages, 464 KiB  
Article
Management of High-Risk Atherosclerotic Patients by Statins May Be Supported by Logistic Model of Intima-Media Thickening
by Dorota Formanowicz, Jacek B. Krawczyk, Bartłomiej Perek, Dawid Lipski and Andrzej Tykarski
J. Clin. Med. 2021, 10(13), 2876; https://doi.org/10.3390/jcm10132876 - 29 Jun 2021
Cited by 7 | Viewed by 2111
Abstract
While the use of statins in treating patients with atherosclerosis is an undisputed success, the questions regarding an optimal starting time for treatment and its strength remain open. We proposed in our earlier paper published in Int. J. Mol. Sci. (2019, 20) that [...] Read more.
While the use of statins in treating patients with atherosclerosis is an undisputed success, the questions regarding an optimal starting time for treatment and its strength remain open. We proposed in our earlier paper published in Int. J. Mol. Sci. (2019, 20) that the growth of intima-media thickness of the carotid artery follows an S-shape (i.e., logistic) curve. In our subsequent paper in PLoS ONE (2020, 15), we incorporated this feature into a logistic control-theoretic model of atherosclerosis progression and showed that some combinations of patient age and intima-media thickness are better suited than others to start treatment. In this study, we perform a new and comprehensive calibration of our logistic model using a recent clinical database. This allows us to propose a procedure for inferring an optimal age to start statin treatment for a particular group of patients. We argue that a decrease in the slope of the IMT logistic growth curve, induced by statin treatment, is most efficient where the curve is at its steepest, whereby the efficiency means lowering the future IMT levels. Using the procedure on an aggregate group of severely sick men, 38 years of age is observed to correlate with the steepest point of the logistic curve, and, thus, it is the preferred time to start statin treatment. We believe that detecting the logistic curve’s steepest fragment and commencing statin administration on that fragment are courses of action that agree with clinician intuition and may support decision-making processes. Full article
(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)
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10 pages, 1108 KiB  
Article
Importance of Increased Arterial Resistance in Risk Prediction in Patients with Cardiovascular Risk Factors and Degenerative Aortic Stenosis
by Jakub Baran, Paweł Kleczyński, Łukasz Niewiara, Jakub Podolec, Rafał Badacz, Andrzej Gackowski, Piotr Pieniążek, Jacek Legutko, Krzysztof Żmudka, Tadeusz Przewłocki and Anna Kabłak-Ziembicka
J. Clin. Med. 2021, 10(10), 2109; https://doi.org/10.3390/jcm10102109 - 13 May 2021
Cited by 10 | Viewed by 2476
Abstract
Background: Cardiovascular disease is a leading cause of heart failure (HF) and major adverse cardiac and cerebral events (MACCE). Objective: To evaluate impact of vascular resistance on HF and MACCE incidence in subjects with cardiovascular risk factors (CRF) and degenerative aortic valve stenosis [...] Read more.
Background: Cardiovascular disease is a leading cause of heart failure (HF) and major adverse cardiac and cerebral events (MACCE). Objective: To evaluate impact of vascular resistance on HF and MACCE incidence in subjects with cardiovascular risk factors (CRF) and degenerative aortic valve stenosis (DAS). Methods: From January 2016 to December 2018, in 404 patients with cardiovascular disease, including 267 patients with moderate-to-severe DAS and 137 patients with CRF, mean values of resistive index (RI) and pulsatile index (PI) were obtained from carotid and vertebral arteries. Patients were followed-up for 2.5 years, for primary outcome of HF and MACCE episodes. Results: RI and PI values in patients with DAS compared to CRF were significantly higher, with optimal cut-offs discriminating arterial resistance of ≥0.7 for RI (sensitivity: 80.5%, specificity: 78.8%) and ≥1.3 for PI (sensitivity: 81.3%, specificity: 79.6%). Age, female gender, diabetes, and DAS were all independently associated with increased resistance. During the follow-up period, 68 (16.8%) episodes of HF-MACCE occurred. High RI (odds ratio 1.25, 95% CI 1.13–1.37) and PI (odds ratio 1.21, 95% CI 1.10–1.34) were associated with risk of HF-MACCE. Conclusions: An accurate assessment of vascular resistance may be used for HF-MACCE risk stratification in patients with DAS. Full article
(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)
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10 pages, 1154 KiB  
Article
Increased Circulating Malondialdehyde-Modified Low-Density Lipoprotein Level Is Associated with High-Risk Plaque in Coronary Computed Tomography Angiography in Patients Receiving Statin Therapy
by Keishi Ichikawa, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki and Hiroshi Ito
J. Clin. Med. 2021, 10(7), 1480; https://doi.org/10.3390/jcm10071480 - 2 Apr 2021
Cited by 10 | Viewed by 2391
Abstract
Objective: To evaluate the association of serum malondialdehyde low-density lipoprotein (MDA-LDL), an oxidatively modified LDL, with the prevalence of high-risk plaques (HRP) determined with coronary computed tomography angiography (CTA) in statin-treated patients. Methods: This study was a single-center retrospective cohort comprising 268 patients [...] Read more.
Objective: To evaluate the association of serum malondialdehyde low-density lipoprotein (MDA-LDL), an oxidatively modified LDL, with the prevalence of high-risk plaques (HRP) determined with coronary computed tomography angiography (CTA) in statin-treated patients. Methods: This study was a single-center retrospective cohort comprising 268 patients (mean age 67 years, 58% men) with statin therapy and who underwent coronary CTA for suspected stable coronary artery disease. Patients were classified into two groups according to median MDA-LDL level or median LDL-C level. Coronary CTA-verified HRP was defined when two or more characteristics, including positive remodeling, low-density plaques, and spotty calcification, were present. Results: Patients with HRP had higher MDA-LDL (p = 0.011), but not LDL-C (p = 0.867) than those without HRP. High MDA-LDL was independently associated with HRP (odds ratio 1.883, 95% confidential interval 1.082–3.279) after adjustment for traditional risk factors. Regarding incremental value of MDA-LDL for predicting CTA-verified HRP, addition of serum MDA-LDL levels to the baseline model significantly increased global chi-square score from 26.1 to 32.8 (p = 0.010). Conclusions: A high serum MDA-LDL level is an independent predictor of CTA-verified HRP, which can lead to cardiovascular events in statin-treated patients. Full article
(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)
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12 pages, 512 KiB  
Article
The Relationship between Cardiovascular Risk Scores and Several Markers of Subclinical Atherosclerosis in an Asymptomatic Population
by Ovidiu Mitu, Adrian Crisan, Simon Redwood, Ioan-Elian Cazacu-Davidescu, Ivona Mitu, Irina-Iuliana Costache, Viviana Onofrei, Radu-Stefan Miftode, Alexandru-Dan Costache, Cristian Mihai Stefan Haba and Florin Mitu
J. Clin. Med. 2021, 10(5), 955; https://doi.org/10.3390/jcm10050955 - 1 Mar 2021
Cited by 17 | Viewed by 2437
Abstract
Background: The current cardiovascular disease (CVD) primary prevention guidelines prioritize risk stratification by using clinical risk scores. However, subclinical atherosclerosis may rest long term undetected. This study aimed to evaluate multiple subclinical atherosclerosis parameters in relation to several CV risk scores in asymptomatic [...] Read more.
Background: The current cardiovascular disease (CVD) primary prevention guidelines prioritize risk stratification by using clinical risk scores. However, subclinical atherosclerosis may rest long term undetected. This study aimed to evaluate multiple subclinical atherosclerosis parameters in relation to several CV risk scores in asymptomatic individuals. Methods: A cross-sectional, single-center study included 120 asymptomatic CVD subjects. Four CVD risk scores were computed: SCORE, Framingham, QRISK, and PROCAM. Subclinical atherosclerosis has been determined by carotid intima-media thickness (cIMT), pulse wave velocity (PWV), aortic and brachial augmentation indexes (AIXAo, respectively AIXbr), aortic systolic blood pressure (SBPao), and ankle-brachial index (ABI). Results: The mean age was 52.01 ± 10.73 years. For cIMT—SCORE was more sensitive; for PWV—Framingham score was more sensitive; for AIXbr—QRISK and PROCAM were more sensitive while for AIXao—QRISK presented better results. As for SBPao—SCORE presented more sensitive results. However, ABI did not correlate with any CVD risk score. Conclusions: All four CV risk scores are associated with markers of subclinical atherosclerosis in asymptomatic population, except for ABI, with specific particularities for each CVD risk score. Moreover, we propose specific cut-off values of CV risk scores that may indicate the need for subclinical atherosclerosis assessment. Full article
(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)
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13 pages, 988 KiB  
Article
Cigarette Smoking, miR-27b Downregulation, and Peripheral Artery Disease: Insights into the Mechanisms of Smoking Toxicity
by Tiago Pereira-da-Silva, Patrícia Napoleão, Marina C. Costa, André F. Gabriel, Mafalda Selas, Filipa Silva, Francisco J. Enguita, Rui Cruz Ferreira and Miguel Mota Carmo
J. Clin. Med. 2021, 10(4), 890; https://doi.org/10.3390/jcm10040890 - 22 Feb 2021
Cited by 14 | Viewed by 2983
Abstract
Cigarette smoking is a risk factor for the development of peripheral artery disease (PAD), although the proatherosclerotic mediators of cigarette smoking are not entirely known. We explored whether circulating microRNAs (miRNAs) are dysregulated in cigarette smokers and associated with the presence of PAD. [...] Read more.
Cigarette smoking is a risk factor for the development of peripheral artery disease (PAD), although the proatherosclerotic mediators of cigarette smoking are not entirely known. We explored whether circulating microRNAs (miRNAs) are dysregulated in cigarette smokers and associated with the presence of PAD. Ninety-four participants were recruited, including 58 individuals without and 36 with PAD, 51 never smokers, 28 prior smokers, and 15 active smokers. The relative expression of six circulating miRNAs with distinct biological roles (miR-21, miR-27b, miR-29a, miR-126, miR-146, and miR-218) was assessed. Cigarette smoking was associated with the presence of PAD in multivariate analysis. Active smokers, but not prior smokers, presented miR-27b downregulation and higher leukocyte, neutrophil, and lymphocyte counts; miR-27b expression levels were independently associated with active smoking. Considering the metabolic and/or inflammatory abnormalities induced by cigarette smoking, miR-27b was independently associated with the presence of PAD and downregulated in patients with more extensive PAD. In conclusion, the atheroprotective miR-27b was downregulated in active smokers, but not in prior smokers, and miR-27b expression was independently associated with the presence of PAD. These unreported data suggest that the proatherogenic properties of cigarette smoking are mediated by a downregulation of miR-27b, which may be attenuated by smoking cessation. Full article
(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)
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11 pages, 791 KiB  
Article
Improving Familial Hypercholesterolemia Index Case Detection: Sequential Active Screening from Centralized Analytical Data
by Fernando Sabatel-Pérez, Joaquín Sánchez-Prieto, Víctor Manuel Becerra-Muñoz, Juan Horacio Alonso-Briales, Pedro Mata and Luis Rodríguez-Padial
J. Clin. Med. 2021, 10(4), 749; https://doi.org/10.3390/jcm10040749 - 13 Feb 2021
Cited by 7 | Viewed by 2887
Abstract
The majority of familial hypercholesterolemia index cases (FH-IC) remain underdiagnosed and undertreated because there are no well-defined strategies for the universal detection of FH. The aim of this study was to evaluate the diagnostic yield of an active screening for FH-IC based on [...] Read more.
The majority of familial hypercholesterolemia index cases (FH-IC) remain underdiagnosed and undertreated because there are no well-defined strategies for the universal detection of FH. The aim of this study was to evaluate the diagnostic yield of an active screening for FH-IC based on centralized analytical data. From 2016 to 2019, a clinical screening of FH was performed on 469 subjects with severe hypercholesterolemia (low-density lipoprotein cholesterol ≥220 mg/dL), applying the Dutch Lipid Clinic Network (DLCN) criteria. All patients with a DLCN ≥ 6 were genetically tested, as were 10 patients with a DLCN of 3–5 points to compare the diagnostic yield between the two groups. FH was genetically confirmed in 57 of the 84 patients with DLCN ≥ 6, with a genetic diagnosis rate of 67.9% and an overall prevalence of 12.2% (95% confidence interval: 9.3% to 15.5%). Before inclusion in the study, only 36.8% (n = 21) of the patients with the FH mutation had been clinically diagnosed with FH; after genetic screening, FH detection increased 2.3-fold (p < 0.001). The sequential, active screening strategy for FH-IC increases the diagnostic yield for FH with a rational use of the available resources, which may facilitate the implementation of FH universal and family-based cascade screening strategies. Full article
(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)
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Review

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25 pages, 1296 KiB  
Review
Clinical Significance of Carotid Intima-Media Complex and Carotid Plaque Assessment by Ultrasound for the Prediction of Adverse Cardiovascular Events in Primary and Secondary Care Patients
by Anna Kabłak-Ziembicka and Tadeusz Przewłocki
J. Clin. Med. 2021, 10(20), 4628; https://doi.org/10.3390/jcm10204628 - 9 Oct 2021
Cited by 38 | Viewed by 10647
Abstract
Recently published recommendations from the American Society of Echocardiography on ‘Carotid Arterial Plaque Assessment by Ultrasound for the Characterization of Atherosclerosis and Evaluation of Cardiovascular Risk’ provoked discussion once more on the potential clinical applications of carotid intima-media complex thickness (CIMT) and carotid [...] Read more.
Recently published recommendations from the American Society of Echocardiography on ‘Carotid Arterial Plaque Assessment by Ultrasound for the Characterization of Atherosclerosis and Evaluation of Cardiovascular Risk’ provoked discussion once more on the potential clinical applications of carotid intima-media complex thickness (CIMT) and carotid plaque assessment in the context of cardiovascular risk in both primary and secondary care patients. This review paper addresses key issues and milestones regarding indications, assessment, technical aspects, recommendations, and interpretations of CIMT and carotid plaque findings. We discuss lacks of evidence, limitations, and possible future directions. Full article
(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)
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15 pages, 1210 KiB  
Review
Fibrin Clot Properties in Atherosclerotic Vascular Disease: From Pathophysiology to Clinical Outcomes
by Michał Ząbczyk, Joanna Natorska and Anetta Undas
J. Clin. Med. 2021, 10(13), 2999; https://doi.org/10.3390/jcm10132999 - 5 Jul 2021
Cited by 32 | Viewed by 9034
Abstract
Fibrin is a major component of thrombi formed on the surface of atherosclerotic plaques. Fibrin accumulation as a consequence of local blood coagulation activation takes place inside atherosclerotic lesions and contributes to their growth. The imbalance between thrombin-mediated fibrin formation and fibrin degradation [...] Read more.
Fibrin is a major component of thrombi formed on the surface of atherosclerotic plaques. Fibrin accumulation as a consequence of local blood coagulation activation takes place inside atherosclerotic lesions and contributes to their growth. The imbalance between thrombin-mediated fibrin formation and fibrin degradation might enhance atherosclerosis in relation to inflammatory states reflected by increased fibrinogen concentrations, the key determinant of fibrin characteristics. There are large interindividual differences in fibrin clot structure and function measured in plasma-based assays and in purified fibrinogen-based systems. Several observational studies have demonstrated that subjects who tend to generate denser fibrin networks displaying impaired clot lysis are at an increased risk of developing advanced atherosclerosis and arterial thromboembolic events. Moreover, the majority of cardiovascular risk factors are also associated with unfavorably altered fibrin clot properties, with their improvement following effective therapy, in particular with aspirin, statins, and anticoagulant agents. The prothrombotic fibrin clot phenotype has been reported to have a predictive value in terms of myocardial infarction, ischemic stroke, and acute limb ischemia. This review article summarizes available data on the association of fibrin clot characteristics with atherosclerotic vascular disease and its potential practical implications. Full article
(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)
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10 pages, 4113 KiB  
Review
OCT Findings in MINOCA
by Krzysztof Bryniarski, Pawel Gasior, Jacek Legutko, Dawid Makowicz, Anna Kedziora, Piotr Szolc, Leszek Bryniarski, Pawel Kleczynski and Ik-Kyung Jang
J. Clin. Med. 2021, 10(13), 2759; https://doi.org/10.3390/jcm10132759 - 23 Jun 2021
Cited by 12 | Viewed by 3502
Abstract
Myocardial infarction with non-obstructive coronary artery disease (MINOCA) is a working diagnosis for patients presenting with acute myocardial infarction without obstructive coronary artery disease on coronary angiography. It is a heterogenous entity with a number of possible etiologies that can be determined through [...] Read more.
Myocardial infarction with non-obstructive coronary artery disease (MINOCA) is a working diagnosis for patients presenting with acute myocardial infarction without obstructive coronary artery disease on coronary angiography. It is a heterogenous entity with a number of possible etiologies that can be determined through the use of appropriate diagnostic algorithms. Common causes of a MINOCA may include plaque disruption, spontaneous coronary artery dissection, coronary artery spasm, and coronary thromboembolism. Optical coherence tomography (OCT) is an intravascular imaging modality which allows the differentiation of coronary tissue morphological characteristics including the identification of thin cap fibroatheroma and the differentiation between plaque rupture or erosion, due to its high resolution. In this narrative review we will discuss the role of OCT in patients presenting with MINOCA. In this group of patients OCT has been shown to reveal abnormal findings in almost half of the cases. Moreover, combining OCT with cardiac magnetic resonance (CMR) was shown to allow the identification of most of the underlying mechanisms of MINOCA. Hence, it is recommended that both OCT and CMR can be used in patients with a working diagnosis of MINOCA. Well-designed prospective studies are needed in order to gain a better understanding of this condition and to provide optimal management while reducing morbidity and mortality in that subset patients. Full article
(This article belongs to the Special Issue The Prevention and Treatment of Atherosclerosis)
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