Myocardial Bridge and Atherosclerosis, an Intimal Relationship.

PURPOSE OF REVIEW: This review investigates the relationship between myocardial bridges (MBs), intimal thickening in coronary arteries, and Atherosclerotic cardiovascular disease. It focuses on the role of mechanical forces, such as circumferential strain, in arterial wall remodeling and aims to clarify how MBs affect coronary artery pathology. REVIEW FINDINGS: MBs have been identified as influential in modulating coronary artery intimal thickness, demonstrating a protective effect against thickening within the MB segment and an increase in thickness proximal to the MB. This is attributed to changes in mechanical stress and hemodynamics. Research involving arterial hypertension models and vein graft disease has underscored the importance of circumferential strain in vascular remodeling and intimal hyperplasia. Understanding the complex dynamics between MBs, mechanical strain, and vascular remodeling is crucial for advancing our knowledge of coronary artery disease mechanisms. This could lead to improved management strategies for cardiovascular diseases, highlighting the need for further research into MB-related vascular changes.

Dual guidewire balloon antegrade fenestration and re-entry technique for coronary chronic total occlusions percutaneous coronary interventions.

OBJECTIVES: To describe the experience of coronary chronic total occlusions (CTOs) percutaneous coronary interventions (PCI) using antegrade fenestration and re-entry (AFR) technique with a dedicated dual guidewire balloon (DGB). BACKGROUND: Antegrade dissection and re-entry (ADR) techniques has been emphasized in recent worldwide CTO consensus documents. We investigated the feasibility and safety of DGB as a dedicated device to perform guidewire-based AFR. METHODS AND RESULTS: Fourteen consecutive patients with complex CTO (J-CTO score: 3.1 ± 0.9) underwent DGB-AFR in the years 2020-2021. DGB-AFR consists in advancing the DGB over a guidewire that reached the vessel distal to the CTO in an extra plaque fashion, inflating/deflating the DGB to create fenestration between subintimal space and the true lumen and advancing a proximal re-entry guidewire through fenestration in the true lumen. DGB-AFR alone was successful in 10 of 14 (71%) cases, a rescue wire-based ADR was needed in two cases for re-entry into the true lumen with a total success rate in 12 of 14 (86%) cases. Among all DGB-AFR cases, four (28%) were performed as a first-line strategy while the remaining 10 (71%) cases were performed as a bail-out strategy after failure of other antegrade crossings for 30 min of procedural time. No DGB-related complications were observed. CONCLUSIONS: DGB-AFR is a user-friendly reliable strategy for the treatment of many CTO lesions. It can be used as bail-out after failure of conventional antegrade wiring techniques, achieving high procedural success rate and low occurrence of procedural adverse events.

Evaluation of remnant cholesterol levels and Monocyte-to-HDL-cholesterol ratio in South Asian patients with acute coronary syndrome.

BACKGROUND AND AIMS: In the present study, we aimed to compare the clinical and coronary angiography features between South Asian and Caucasian patients with Acute Coronary Syndrome (ACS). In particular, we focused our analysis on the evaluation of recent cardiovascular risk markers, such as remnant cholesterol, corresponding to all plasma cholesterol minus HDL-C (high-density lipoprotein cholesterol) and LDL-C (low-density lipoprotein cholesterol), and the Monocyte-to-HDL-cholesterol ratio. We also compared values of several lipoprotein ratios and the Platelet-to-lymphocyte ratio, accurate predictors of coronary events and coronary artery disease. METHODS AND RESULTS: We recruited 40 South Asian and 40 Caucasian patients admitted for ACS. Data were collected by consulting patients' medical records. We used Chi-square test and Student's t-test to analyse qualitative and quantitative variables, respectively. South Asian patients, compared to Caucasians, showed higher mean values of the parameters analysed: remnant cholesterol (32.6 ± 17 vs 26.5 ± 9.6), Monocyte-to-HDL-cholesterol ratio (26.4 ± 48.7 vs 16.5 ± 8.3), Platelet-to-lymphocyte ratio (124.7 ± 130.7 vs 120.5 ± 58.8). Moreover, higher mean values of several lipoprotein ratios were also found in South Asian patients compared to the control group. However, statistical significance was not reached for any of these differences observed. CONCLUSIONS: The evaluation of the parameters analysed in this study might provide accurate information regarding the cardio-metabolic risk in South Asian patients. However, further studies with larger samples are needed to obtain more significant results.

Correlation between longitudinal strain analysis and coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction.

OBJECTIVE: The aim of this study was to evaluate in patients with microvascular angina and heart failure with preserved ejection fraction, the speckle-tracking echocardiography, and longitudinal myocardial strain to evaluate the possible presence of alterations in heart failure with preserved ejection fraction patients compared with a control population. We also investigated the correlation between the longitudinal strain analysis and the TIMI frame count after coronary angiography. METHODS: Our study was performed on a population 41 patients with microvascular angina that underwent coronary angiography and speckle-tracking echocardiography. We divided the sample into two categories: patients with heart failure with preserved ejection fraction (n-21) and patients without heart failure with preserved ejection fraction (n-20). We calculated TIMI frame count indices for each patient based on angiographic images. RESULTS: Patients with heart failure with preserved ejection fraction had reduced global longitudinal strain values (-17.88) compared with the total control population, and this reduction was statistically significant (P = .028). This reduction was more marked in patients who had a significantly increased TIMI frame count. Therefore, a statistically significant correlation was observed between TIMI frame count and global longitudinal strain. CONCLUSION: Our results show that cardiac contractile mechanics are altered in patients with heart failure with preserved ejection fraction at a subclinical level hard to identifiable with conventional echocardiography. The dysfunction of the microcirculation and the consequent alteration of the TIMI frame count probably results in a reduction of myocardial performance.

Angiographic Evaluation of Coronary Microvascular Dysfunction in Patients with Heart Failure and Preserved Ejection Fraction.

BACKGROUND: The aim of this study was to evaluate myocardial perfusion and coronary blood flow through validated angiography indices to assess whether there is greater MVD in patients with microvascular angina and HFPEF compared to those who do not have. METHODS: Our study was performed on a population of 286 patients with stable angina that underwent coronary angiography and echocardiography. They showed epicardial coronary arteries free from stenosis. We divided the sample into two categories: patients with HFPEF and those without. We calculated indices for each patient based on angiographic images, including TFC, MBG, and TMBS. RESULTS: Our sample compared two groups: HFPEF (n = 155) and non-HFPEF (n = 135) patients. We showed that patients with HFPEF had a longest TFC of three major coronary arteries (TFC LAD 44.7 ± 12.5; TFC RCA 26.2 ± 6.9; TFC CX 27 ± 5.9) than non-HFPEF patients (TFC LAD 40.7 ± 11.6; TFC RCA 25 ± 6.3; TFC CX 21 ± 4.7). On the other hand, we found lower MBG on three coronary arteries (MBG LAD 2.1 ± 0.3; MBG RCA 2.1 ± 0.3; MBG CX 2.0 ± 0.32) in HFPEF than non-HFPEF patients (MBG LAD 2.6 ± 0.5; MBG RCA 2.2 ± 0.47; MBG CX 2.3 ± 0.4). CONCLUSION: Analysis of microcirculation through angiography indices in patients with and without HFPEF has led to assess that the HFPEF population has a greater involvement of microcirculation than patients without HFPEF.

Myocardical Infarction with Non-Obstructive Coronary Arteries (MINOCA): pathogenesis, diagnosis and treatment.

The term MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries) refers to myocardial infarction cases where coronary arteries exhibit less than 50 % stenosis. MINOCA encompasses a diverse range of pathologies with varying etiologies. Diagnosis involves meeting acute myocardial infarction criteria and excluding other causes (myocarditis, takotsubo syndrome). Clinical features often resemble those of traditional myocardial infarction, but MINOCA patients tend to be younger and more frequently female. Etiological investigations include coronary angiography, intracoronary imaging, and vasomotor function tests. Causes include plaque rupture, coronary dissection, vasospasm, microvascular dysfunction, thromboembolism. Prognosis varies, with some subsets at higher risk. Management involves a tailored approach addressing underlying causes, with emphasis on cardioprotective therapy, risk factor modification, and lifestyle interventions. Further research is needed to refine diagnostic strategies and optimize therapeutic approaches in MINOCA patients.

Cholesterol-Lowering Strategies for Cardiovascular Disease Prevention: The Importance of Intensive Treatment and the Simplification of Medical Therapy.

Cardiovascular diseases (CVDs) are a leading global cause of mortality and are primarily driven by atherosclerotic coronary artery disease. Their pathogenesis involves multi-factorial mechanisms, among which low-density lipoprotein (LDL) plays a causative role. Recent ESC/EAS guidelines advocate for a shift toward new risk estimation algorithms that better emphasize non-fatal cardiovascular events, lifetime risk prediction, and tailored pharmacological approaches, including statin + ezetimibe and triple therapy, in specific cases. Intensive lipid-lowering therapy has been shown to be pivotal, especially in post-acute coronary events. Intracoronary imaging has revealed insights into the composition of plaque and demonstrated the significant regression that can be achieved through the use of statins such as rosuvastatin and atorvastatin. The positive effects of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, particularly alirocumab and evolocumab, on plaque regression, have been demonstrated. Inclisiran, which targets PCSK9 gene expression, significantly reduces LDL cholesterol. The associated challenges include hesitancy to prescribe intensive regimens and limited treatment adherence, highlighting the need for pharmacological combinations to improve therapeutic outcomes.

Residual Cardiovascular Risk: Role of Remnants Cholesterol, Monocyte/HDL Ratio and Lipoprotein Ratios on Personalized Cardiovascular Prevention.

Cardiovascular diseases represent the leading cause of death in the world and are subject to limitations in prevention strategies despite the use of very effective drugs. The concept of residual risk (RR) is intrinsically related to that of global risk of which it represents a very significant percentage. In the cardiovascular field, the term RR refers to the probability of incurring a major cardiovascular event, despite adequate control of the risk factors present in the individual patient. A significant portion of the RR in the cardiovascular field results from the underestimation of additional risk factors not subjected to adequate intervention such as, for example, triglyceride levels in patients treated for the presence of hypertension and/or hypercholesterolemia. The control of the RR therefore appears as an essential condition for the effective reduction of the global risk profile and is based on an integrated intervention that combines all the different prevention strategies derived from the available evidence and capable of interacting on the basis of a strengthening reciprocal between lifestyle and pharmacological and nutraceutical intervention methods.

Global hemostasis assays in acute myeloid leukemia: results of an observational prospective study.

BACKGROUND: Acute myeloid leukemia (AML) is characterized by a complex spectrum of coagulopathy ranging from hemorrhagic to thrombotic symptoms. To date, platelet count (PLT) and conventional coagulation tests (CCTs) cannot predict hemorrhagic events and thrombotic risk. Thromboelastography (TEG) measures the viscoelastic properties of the clot, thus providing information on the entire process of blood coagulation. The primary aim of the study was to assess the hemostatic balance from AML diagnosis to the end of chemotherapy (CHT) by TEG. MATERIAL AND METHODS: Here we present the results of a prospective study enrolling newly diagnosed AML patients treated with chemotherapy. Patients had complete blood counts (CBCs), TEG and CCTs performed at three time points: 1) diagnosis (T0); 2) during the first cycle of CHT (T1); and 3) at the end of CHT (T2). An algorithm of TEG indirectly calculated thrombin generation (TG). Patients underwent daily follow-up for bleeding and thrombotic episodes up to the time of hospital discharge or death. RESULTS: Eighty consecutive patients were evaluated; forty were eligible for the study, and 21 completed the entire study. At T1, maximum amplitude (MA), TG and K-time were significantly shifted toward a hypocoagulability state compared to T0 (p<0.05), while a hypercoagulable state at T2 was shown by changes in α-angle, MA and TG values. Otherwise, there were no statistically significant differences in CCTs between the evaluated time points. DISCUSSION: Overall, TEG revealed complex and dynamic coagulation abnormalities in patients with AML according to both the course of disease and therapy. Further studies are needed to investigate more fully the role of TEG in defining the hemostatic profile in patients with AML.

Role of Lipoprotein Ratios and Remnant Cholesterol in Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA).

BACKGROUND: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical situation characterized by evidence of acute myocardial infarction (AMI)-according to the Fourth Universal Definition of Myocardial Infarction-with normal or near-normal coronary arteries on angiographic study (stenosis < 50%). This condition is extremely variable in etiology, pathogenic mechanisms, clinical manifestations, prognosis and consequently therapeutic approach. OBJECTIVE: The objective of the study was the evaluation of remnant cholesterol (RC), monocyte/high-density lipoprotein cholesterol ratio (MHR), platelet/lymphocyte ratio (PLR) and various lipoprotein ratios in patients with MINOCA in order to establish their validity as predictors of this event. MATERIALS AND METHODS: We included 114 patients hospitalized in the Intensive Coronary Care Unit (ICCU) and Hospital Wards of our Hospital Center from 2015 to 2019 who received a diagnosis of MINOCA compared to a control group of 110 patients without previous cardiovascular events. RC was calculated with the following formula: RC = total cholesterol (TC) - HDL-C - LDL-C. MHR was calculated by dividing the monocyte count in peripheral blood by high-density lipoprotein cholesterol (HDL-C) levels; PLR was obtained by dividing platelet count by lymphocyte count. We also calculated various lipoprotein ratios, like total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C), triglycerides/high-density lipoprotein cholesterol (TG/HDL-C), and non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol (non-HDL-C/HDL-C) ratios. RESULTS: The MINOCA group had higher mean levels of RC (21.3 ± 10.6 vs. 13.2 ± 7.7 mg/dL), MHR (23 ± 0.009 vs. 18.5± 8.3) and PLR (179.8 ± 246.1 vs. 135 ± 64.7) than the control group. Only the mean values of all calculated lipoprotein ratios were lower in MINOCA patients. Statistical significance was achieved only in the RC evaluation. CONCLUSIONS: Higher levels of RC and MHR were found in patients with MINOCA. We also observed higher levels of PLR than in the control group. Only various lipoprotein ratios were lower, but this could reflect the extreme heterogeneity underlying the pathogenic mechanisms of MINOCA. In patients who receive a diagnosis of MINOCA with a baseline alteration of the lipid profile and higher levels of cholesterol at admission as well, the evaluation of these parameters could play an important role, providing more detailed information about their cardiometabolic risk.

Uncommon Carotid Artery Stenting Complications: A Series by Images.

AIMS: To describe through emblematic images rare but clinically relevant carotid artery stenting complications that occurred at two high-volume centres for carotid artery stenting (CAS). BACKGROUND: CAS is an alternative to carotid endarterectomy (CEA) for the treatment of carotid artery stenosis in patients judged to be at high risk for CEA. CAS complications range between 1 and 9% and are higher in older patients complaining of neurological symptoms at the time of presentation. Besides periprocedural or early-after-procedure stroke, which remains the true Achilles' heel of CAS, other dramatic complications might compromise the clinical outcomes of this procedure. METHODS: Five infrequent complications, out of more than 1000 CAS performed in the years 2016-2021, have been described. RESULTS: Among CAS complications, acute carotid stent thrombosis, rescue retrieval of a disconnected distal cerebral embolic protection device, plaque prolapse after carotid stenting, cerebral hyperperfusion syndrome (CHS), and radial artery long sheath entrapment requiring surgical intervention were found to account for 0.3% of the total number of procedures performed by operators with high CAS volume. CONCLUSIONS: Unusual CAS complications may infrequently occur, even in hands of expert operators. To know how to deal with such complications might help interventionalists to improve CAS performance.

[Diagnosis of coronary microvascualar dysfunction in diabetic patients with cardiac syndrome X: comparison by current methods]. / Diagnosi di disfunzione del microcircolo coronarico in pazienti diabetici con sindrome X cardiaca: confronto tra le metodiche attualmente in uso.

The study population included 208 patients with chest pain and uninjured coronary arteries that we split into two populations: diabetics (72 patients) and non-diabetics (136 patients). We split patients with chest pain and uninjured coronary arteries that had a myocardial scintigraphy into two populations: patients with positive scintigraphy and negative. We calculated, on angiographic images of each patient, stored on suitable digital supports, Timi Frame Count (TFC), Myocardial Blush Grade (MBG) and Total Myocardial Blush Score (TMBS) using the protocol described by Gibson and Yusuf. On the basis of Yusuf's experience we imagined a new index: the Total Timi Frame Count as the sum of the three coronary Timi Frame Count. From our results we found a worse coronary microcirculation in diabetic patients with lower values of TFC, MBG and TMBS (p=0.02),compared with non- diabetics. New index TTFC is usually higher in diabetics than non-diabetic patients. Patients with positive scintigraphy had a worse TMBS than patients with a negative one, with a high statistical significance (p=0.003).We focused on the correlation between scintigraphy defect and angiography data in the arteries of ischemia relieved by nuclear imaging. The analysis showed that healthy vessels had a lower TFC than diseased vessels and therefore a better microcirculation with a high statistical significance (p=0.0001). According to the literature, diabetic population has a major microcirculation disease; moreover the study of microcirculation by coronary angiography and myocardial scintigraphy shows a good correlation between two methods.

[Dyslipidemia management with medical nutrition therapy: current status and perspectives]. / L'importanza del trattamento delle dislipidemie tramite la terapia medica nutrizionale: stato attuale e prospettive.

In Italy, patients with dyslipidemia account for 15-20% of the adult population with major healthcare and socio-economic impact. According to the ESC/EAS guidelines for the management of dyslipidemias, desirable cholesterol and triglyceride levels can be achieved with a synergy between drug treatment and adequate diet therapy. However, what diets should be adopted? In this review article, different types of dietary treatments are compared, with a special focus on diet education. The new scientific frontier of nutrigenetics is also discussed.

Coronary Artery Disease in South Asian Patients: Cardiovascular Risk Factors, Pathogenesis and Treatments.

In the last decades a significant increase of the migratory phenomenon from South Asian countries to the Western World has occurred for social, economic and geopolitical reasons. The aim of this review is to describe cardiovascular risk factors, pathogenesis and treatments of coronary artery disease in South Asian patients. It is well established that South Asian populations have a higher prevalence of coronary artery disease and premature onset of myocardial infarction episodes than other populations. This higher predisposition might be caused by genetic factors, common in both South Asian patients residing in their birth country and in those residing abroad, but it may also be due to the new spatial environment in which they live. It will be important to examine the leading cardiovascular risk factors determining increasing incidence of coronary artery disease in the South Asian population. These include: insulin resistance, hypertension, dyslipidaemia and abdominal obesity caused by a diet rich in refined carbohydrates and saturated fats. Furthermore, it is important to examine emerging cardiovascular risk factors strictly related to this particular ethnic group. The evidence of higher levels of prothrombotic and proinflammatory factors, for example lipoprotein(a) and proinflammatory adipokines, as well as the influence of air pollution and psychosocial stress, may have consequences on the risk, treatment and outcomes of the coronary artery disease in this population. Migrants from South Asia deserve to be addressed and framed with particular care in terms of cardiovascular risk and especially in the management of acute coronary events.

Longitudinal Strain Analysis and Correlation with TIMI Frame Count in Patients with Ischemia with No Obstructive Coronary Artery (INOCA) and Microvascular Angina (MVA).

Background: The aim of the study is to evaluate the subclinical alterations of cardiac mechanics detected using speckle-tracking echocardiography and compare these data with the coronary angiography indices used during coronary angiography in a population of patients diagnosed with ischemia with no obstructive coronary artery (INOCA) and microvascular angina (MVA). Methods: The study included 85 patients admitted to our center between November 2019 and January 2022 who were diagnosed with INOCA compared with a control group of 70 healthy patients. A collection of anamnestic data and a complete cardiovascular physical examination, and echocardiogram at rest with longitudinal strain were performed for all patients. Furthermore, the TIMI frame count (TFC) for the three coronary vessels was calculated according to Gibson's indications. All parameters were compared with a control population with similar characteristics. Results: Patients with INOCA compared to the control population showed statistically significant changes in the parameters assessed on the longitudinal strain analysis. In particular, patients with INOCA showed statistically significant changes in GLS (-16.71) compared to the control population (-19.64) (p = 0.003). In patients with INOCA, the total TIMI frame count (tTFC) correlated with the GLS value with a correlation coefficient of 0.418 (p = 0.021). Conclusions: In patients with angina, documented myocardial ischemia, the absence of angiographically significant stenosis (INOCA) and LVEF > 50%, the prevalence of microvascular dysfunction documented by TFC was extremely represented. A statistically significant reduction in GLS was observed in these patients. TFC and longitudinal strain, therefore, appear to be two reliable, sensitive and easily accessible methods for the study of alterations in coronary microcirculation and the characterization of patients with INOCA and microvascular angina.

Screening and Management of Coronary Artery Disease in Kidney Transplant Candidates.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD), especially in end-stage renal disease (ESRD) patients and during the first year after transplantation. For these reasons, and due to the shortage of organs available for transplant, it is of utmost importance to identify patients with a good life expectancy after transplant and minimize the transplant peri-operative risk. Various conditions, such as severe pulmonary diseases, recent myocardial infarction or stroke, and severe aorto-iliac atherosclerosis, need to be ruled out before adding a patient to the transplant waiting list. The effectiveness of systematic coronary artery disease (CAD) treatment before kidney transplant is still debated, and there is no universal screening protocol, not to mention that a nontailored screening could lead to unnecessary invasive procedures and delay or exclude some patients from transplantation. Despite the different clinical guidelines on CAD screening in kidney transplant candidates that exist, up to today, there is no worldwide universal protocol. This review summarizes the key points of cardiovascular risk assessment in renal transplant candidates and faces the role of noninvasive cardiovascular imaging tools and the impact of coronary revascularization versus best medical therapy before kidney transplant on a patient's cardiovascular outcome.

Outcomes of chronic total occlusion percutaneous coronary intervention from the RAIAN (RAjaie - Iran) registry.

OBJECTIVE: While most of the evidence in CTO interventions emerge from Western and Japanese studies, few data have been published up today from the Middle East. Objective of this study was to evaluate technical success rates and clinical outcomes of an Iranian population undergoing CTO PCI in a tertiary referral hospital. Moreover, we sought to evaluate the efficacy of our CTO teaching program. METHODS: This is a retrospective single-center cohort study including 790 patients who underwent CTO PCI performed by operators with different volumes of CTOs PCI performed per year. According to PCI result, all patients have been divided into successful (n = 555, 70.3 %) and unsuccessful (n = 235, 29.7 %) groups. Study endpoints were Major Adverse Cardiovascular Events and Health Status Improvement evaluated using the Seattle Angina Questionnaire at one year. RESULTS: A global success rate of 70 % for antegrade and 80 % for retrograde approach was shown despite the lack of some CTO-dedicated devices. During the enrollment period, the success rate increased significantly among operators with a lower number of CTO procedures per year. One-year MACE rate was similar in both successful and unsuccessful groups (13.5 % in successful and 10.6 % in unsuccessful group, p = 0.173). One year patients' health status improved significantly only in successful group. CONCLUSIONS: No significant differences of in-hospital and one-year MACE were found between the successful and unsuccessful groups. Angina symptoms and quality of life significantly improved after successful CTO PCI. The RAIAN registry confirmed the importance of operator expertise for CTO PCI success.

Classification, Diagnosis, and Treatment of Coronary Microvascular Dysfunction.

Coronary microvascular dysfunction represents a widespread disease which is highly disabling for the patient, who constantly presents angina [...].

Biomarkers of Coronary Microvascular Dysfunction in Patients With Microvascular Angina: A Narrative Review.

The current gold standard for diagnosis of coronary microvascular dysfunction (CMD) in the absence of myocardial diseases, whose clinical manifestation is microvascular angina (MVA), is reactivity testing using adenosine or acetylcholine during coronary angiography. This invasive test can be difficult to perform, expensive, and harmful. The identification of easily obtainable blood biomarkers which reflect the pathophysiology of CMD, characterized by high reliability, precision, accuracy, and accessibility may reduce risks and costs related to invasive procedures and even facilitate the screening and diagnosis of CMD. In this review, we summarized the results of several studies that have investigated the possible relationships between blood biomarkers involved with CMD and MVA. More specifically, we have divided the analyzed biomarkers into 3 different groups, according to the main mechanisms underlying CMD: biomarkers of "endothelial dysfunction," "vascular inflammation," and "oxidative stress." Finally, in the last section of the review, we consider mixed mechanisms and biomarkers which are not included in the 3 major categories mentioned above, but could be involved in the pathogenesis of CMD.

Coronary Arteries Aneurysms: A Case-Based Literature Review.

Coronary artery aneurysm (CAA) is an abnormal dilatation of a coronary artery segment; those coronary artery aneurysms that are very large in size are defined as giant. However, a standardized dimension cut-off to define giant CAAs is still missing. The reported prevalence of coronary aneurysms in the population who underwent coronary angiography ranges from 0.3% to 5%, and often CAAs are found in patient with aneurysms in other sites, such as the ascending or abdominal aorta. In half of the cases an atherosclerotic etiology could be recognized; often, CAA is found in the context of acute coronary syndrome. Seldomly, CAA is found at the autopsy of patients who died due to sudden cardiac death. Currently, very few data exist about CAA management and their prognostic relevance; moreover, CAA treatment is still not clearly codified, but rather case-based. Indeed, currently there are no published dedicated studies exploring the best medical therapy, i.e., with antiplatelets or anticoagulant agents rather than an interventional approach such as an endovascular or surgical technique. In this review, through two clinical cases, the current evidence regarding diagnostic tools and treatment options of CAAs will be described.