Advancing the access to cardiovascular diagnosis and treatment among women with cardiovascular disease: a joint British Cardiovascular Societies' consensus document.

Despite significant progress in cardiovascular pharmacotherapy and interventional strategies, cardiovascular disease (CVD), in particular ischaemic heart disease, remains the leading cause of morbidity and mortality among women in the UK and worldwide. Women are underdiagnosed, undertreated and under-represented in clinical trials directed at management strategies for CVD, making their results less applicable to this subset. Women have additional sex-specific risk factors that put them at higher risk of future cardiovascular events. Psychosocial risk factors, socioeconomic deprivation and environmental factors have an augmented impact on women's cardiovascular health, highlighting the need for a holistic approach to care that considers risk factors specifically related to female biology alongside the traditional risk factors. Importantly, in the UK, even in the context of a National Health Service, there exist significant regional variations in age-standardised mortality rates among patients with CVD. Given most CVDs are preventable, concerted efforts are necessary to address the unmet needs and ensure parity of care for women with CVD. The present consensus document, put together by the British Cardiovascular Society (BCS)'s affiliated societies, specifically portrays the current status on the sex-related differences in the diagnosis and treatment of each of the major CVD areas and proposes strategies to overcome the barriers in accessing diagnoses and treatments among women. This document aims at raising awareness of the scale of the current problem and hopes to stimulate a multifaceted approach to address sex disparities and enable future comprehensive sex- and gender-based research through collaboration across different affiliated societies within the BCS.

Novel diagnostic approaches and management of coronary microvascular dysfunction.

The mechanism underlying ischaemic heart disease (IHD) has been primarily attributed to obstructive coronary artery disease (CAD). However, non-obstructive coronary arteries are identified in >50% of patients undergoing elective coronary angiography, recently leading to growing interest in the investigation and management of angina/ischaemia with non-obstructive coronary arteries (ANOCA/INOCA). INOCA is an umbrella term encompassing a multiple spectrum of possible pathogenetic entities, including coronary vasomotor disorders which consist of two major endotypes: coronary microvascular dysfunction (CMD) and vasospastic angina. Both conditions can coexist and be associated with concomitant obstructive CAD. Particularly, CMD refers to myocardial ischaemia due to reduced vasodilatory capacity of coronary microcirculation secondary to structural remodelling or impaired resting microvascular tone (functional) or a combination of both. CMD is not a benign condition and is more prevalent in women presenting with chronic coronary syndrome compared to men. In this setting, an impaired coronary flow reserve has been associated with increased risk of major adverse cardiovascular events. ANOCA/INOCA patients also experience impaired quality of life and associated increased healthcare costs. Therefore, research in this scenario has led to better definition, classification, and prognostic stratification based on the underlying pathophysiological mechanisms. The development and validation of non-invasive imaging modalities, invasive coronary vasomotor function testing and angiography-derived indices provide a comprehensive characterisation of CMD. The present narrative review aims to summarise current data relating to the diagnostic approach to CMD and provides details on the sequence that therapeutic management should follow.

Coronary Artery Plaque Phenotype and 5-Year Clinical Outcomes in Older Patients with Non-ST Elevation Acute Coronary Syndrome.

Background: Lesions with thin-cap fibroatheroma (TCFA), small luminal area and large plaque burden (PB) have been considered at high risk of cardiovascular events. Older patients were not represented in studies which demonstrated correlation between clinical outcome and plaque characteristics. This study aims to investigate the prognostic role of high-risk plaque characteristics and long-term outcome in older patients presenting with non-ST elevation acute coronary syndrome (NSTEACS). Methods: This study recruited older patients aged ≥ 75 years with NSTEACS undergoing virtual-histology intravascular ultrasound (VH-IVUS) imaging from the Improve Clinical Outcomes in high-risk patieNts with acute coronary syndrome (ICON-1). Primary endpoint was the composite of major adverse cardiovascular events (MACE) consisting of all-cause mortality, myocardial infarction (MI), and any revascularisation. Every component of MACE and target vessel failure (TVF) including MI and any revascularisation were considered as secondary endpoints. Results: Eighty-six patients with 225 vessels undergoing VH-IVUS at baseline completed 5-year clinical follow-up. Patients with minimal lumen area (MLA) ≤ 4 mm 2 demonstrated increased risk of MACE (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.00-5.59, p = 0.048) with a worse event-free survival (Log Rank 4.17, p = 0.041) than patients with MLA > 4 mm 2 . Patients with combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% showed high risk of MI (HR 5.23, 95% CI 1.05-25.9, p = 0.043). Lesions with MLA ≤ 4 mm 2 had 6-fold risk of TVF (HR 6.16, 95% CI 1.24-30.5, p = 0.026). Conclusions: Small luminal area appears as the major prognostic factor in older patients with NSTEACS at long-term follow-up. Combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% was associated with high risk of MI. Clinical Trial Registration: NCT01933581.

The association of inflammatory biomarkers and long-term clinical outcomes in older adults with non-ST elevation acute coronary syndrome.

BACKGROUND: The prognostic significance of inflammatory markers on the long-term risk of major adverse cardiovascular and cerebrovascular events (MACCE) in older NSTEACS patients remains unclear. METHODS: NSTEACS patients aged 75 and older were recruited to the multicentre cohort study Improve Cardiovascular Outcomes in High-Risk PatieNts with Acute Coronary Syndrome (ICON1). Inflammatory markers including interleukin-6 (IL-6), myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), fibrinogen and tumor necrosis factor-alpha (TNF-α) were collected at baseline. Primary outcome was MACCE consisting of all-cause mortality, reinfarction, stroke/transient ischaemic attack, urgent revascularization, and significant bleeding at 5-year follow-up. RESULTS: There were 230 patients with baseline IL-6 (median age 80.9 [interquartile range (IQR):78.2-83.9] years). High IL-6 was not associated with MACCE, but it was independently associated with all-cause mortality (adjusted hazard ratio [aHR]: 2.26 [95% Confidence Interval (CI):1.34-3.82]; P = 0.002). For patients with hsCRP (n = 260, median age 80.9 [IQR:77.9-84.1] years), higher levels were significantly associated with increased risk of MACCE (aHR:1.77 [95% CI:1.26-2.49], P = 0.001). In the cohort with MPO (230 patients, median age 80.9 [IQR:78.2-83.9] years), lower MPO was independently associated with the risk of MACCE (aHR: 0.67 [95%CI:0.46-0.96]; P = 0.029). There was no prognostic significance with fibrinogen and TNF-α. CONCLUSION: Among older NSTEACS patients, elevated IL-6 and hsCRP were associated with increased risk of all-cause mortality and MACCE, respectively. Low MPO levels were associated with higher MACCE. Further studies are required to determine how these biomarkers should influence treatment strategy in this understudied subset. CLINICAL TRIAL REGISTRATION: NCT01933581.

Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction and High Bleeding Risk: A Randomized Clinical Trial.

Importance: Patients with high bleeding risk (HBR) have a poor prognosis, and it is not known if they may benefit from complete revascularization after myocardial infarction (MI). Objective: To investigate the benefit of physiology-guided complete revascularization vs a culprit-only strategy in patients with HBR, MI, and multivessel disease. Design, Setting, and Participants: This was a prespecified analysis of the Functional Assessment in Elderly MI Patients With Multivessel Disease (FIRE) randomized clinical trial data. FIRE was an investigator-initiated, open-label, multicenter trial. Patients 75 years or older with MI and multivessel disease were enrolled at 34 European centers from July 2019 through October 2021. Physiology treatment was performed either by angiography- or wire-based assessment. Patients were divided into HBR or non-HBR categories in accordance with the Academic Research Consortium HBR document. Interventions: Patients were randomized to either physiology-guided complete revascularization or culprit-only strategy. Main Outcomes and Measures: The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. Secondary outcomes included a composite of cardiovascular death or MI and Bleeding Academic Research Consortium (BARC) types 3 to 5. Results: Among 1445 patients (mean [SD] age, 81 [5] years; 917 male [63%]), 1025 (71%) met HBR criteria. Patients with HBR were at higher risk for the primary end point (hazard ratio [HR], 2.01; 95% CI, 1.47-2.76), cardiovascular death or MI (HR, 1.89; 95% CI, 1.26-2.83), and BARC types 3 to 5 (HR, 3.28; 95% CI, 1.40-7.64). The primary end point was significantly reduced with physiology-guided complete revascularization as compared with culprit-only strategy in patients with HBR (HR, 0.73; 95% CI, 0.55-0.96). No indication of interaction was noted between revascularization strategy and HBR status for primary and secondary end points. Conclusions and Relevance: HBR status is prevalent among older patients with MI, significantly increasing the likelihood of adverse events. Physiology-guided complete revascularization emerges as an effective strategy, in comparison with culprit-only revascularization, for mitigating ischemic adverse events, including cardiovascular death and MI. Trial Registration: ClinicalTrials.gov Identifier: NCT03772743.

Non-invasive vascular measures as prognostic predictors for older patients with non-ST elevation acute coronary syndrome.

BACKGROUND: Adverse cardiac events are common in older patients with non-ST elevation acute coronary syndrome (NSTEACS), yet prognostic predictors are still lacking. This study investigated the long-term prognostic significance of non-invasive measures including endothelial function, carotid intima-media thickness (CIMT), and vascular stiffness in older NSTEACS patients referred for invasive treatment. METHODS: NSTEACS patients aged 75 years and older recruited to a multicentre cohort study (NCT01933581) were assessed for baseline endothelial function using endoPAT logarithm of reactive hyperemia index (LnRHI), CIMT using B-mode ultrasound, and vascular stiffness using carotid-femoral pulse wave velocity (cfPWV). Long-term outcomes included major adverse cardiovascular events (MACE), a composite of death, reinfarction, urgent revascularization, stroke/transient ischemic attack, and significant bleeding. RESULTS: Recruitment resulted in 214 patients assessed for LnRHI, 190 patients assessed for CIMT and 245 patients assessed for cfPWV. For LnRHI group (median follow-up 4.73 years [IQR: 1.41-5.00]), Cox regression analysis revealed a trend towards increased risk of MACE (HR: 1.24 [95% CI: 0.80-1.93]; P  = 0.328) and mortality (HR: 1.49 [95% CI: 0.86-2.59]; P  = 0.157), but no significance was reached. No difference for other components of MACE was found. For CIMT group (median follow up 4.74 years [IQR: 1.55-5.00]), no statistically significant difference in MACE was found (HR: 0.92 [95% CI: 0.53-1.59]; P  = 0.754). Similarly, for cfPWV group (median follow-up 4.96 years [IQR: 1.55-5.00]), results did not support prognostic significance (for MACE, HR: 0.95 [95% CI: 0.65-1.39]; P  = 0.794). CONCLUSION: Endothelial function, CIMT and vascular stiffness were proven unsuitable as strong prognostic predictors in older patients with NSTEACS. CLINICAL TRIAL REGISTRATION: NCT01933581.

Vasospastic angina: a review on diagnostic approach and management.

Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels responsible for an inadequate supply of blood and oxygen. Coronary artery spasm is a heterogeneous phenomenon that can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction (MI). VSA was originally described as Prinzmetal angina or variant angina, classically presenting at rest, unlike most cases of angina (though in some patients, vasospasm may be triggered by exertion, emotional, mental or physical stress), and associated with transient electrocardiographic changes (transient ST-segment elevation, depression and/or T-wave changes). Ischaemia with non-obstructive coronary arteries (INOCA) is not a benign condition, as patients are at elevated risk of cardiovascular events including acute coronary syndrome, hospitalization due to heart failure, stroke and repeat cardiovascular procedures. INOCA patients also experience impaired quality of life and associated increased healthcare costs. VSA, an endotype of INOCA, is associated with major adverse events, including sudden cardiac death, acute MI and syncope, necessitating the study of the most effective treatment options currently available. The present literature review aims to summarize current data relating to the diagnosis and management of VSA and provide details on the sequence that treatment should follow.

Diagnosis and treatment of epicardial coronary artery spasmVasospastic angina (VSA) refers to chest pain experienced as a consequence of a sudden narrowing of the epicardial coronary arteries. VSA can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction. Reduced blood and oxygen supply in patients with non-obstructive coronary arteries is not a benign condition, as patients are at elevated risk of adverse cardiovascular events. These patients also experience impaired quality of life and associated increased healthcare costs. This review aims to summarise current data relating to the diagnosis of VSA and provides details on treatment strategies.

Coronary Physiology Guidance vs Conventional Angiography for Optimization of Percutaneous Coronary Intervention: The AQVA-II Trial.

BACKGROUND: The debate surrounding the efficacy of coronary physiological guidance compared with conventional angiography in achieving optimal post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) values persists. OBJECTIVES: The primary aim of this study was to demonstrate the superiority of physiology-guided PCI, using either angiography or microcatheter-derived FFR, over conventional angiography-based PCI in complex high-risk indicated procedures (CHIPs). The secondary aim was to establish the noninferiority of angiography-derived FFR guidance compared with microcatheter-derived FFR guidance. METHODS: Patients with obstructive coronary lesions and meeting CHIP criteria were randomized 2:1 to receive undergo physiology- or angiography-based PCI. Those assigned to the former were randomly allocated to angiography- or microcatheter-derived FFR guidance. CHIP criteria were long lesion (>28 mm), tandem lesions, severe calcifications, severe tortuosity, true bifurcation, in-stent restenosis, and left main stem disease. The primary outcome was invasive post-PCI FFR value. The optimal post-PCI FFR value was defined as >0.86. RESULTS: A total of 305 patients (331 study vessels) were enrolled in the study (101 undergoing conventional angiography-based PCI and 204 physiology-based PCI). Optimal post-PCI FFR values were more frequent in the physiology-based PCI group compared with the conventional angiography-based PCI group (77% vs 54%; absolute difference 23%, relative difference 30%; P < 0.0001). The occurrence of the primary outcome did not differ between the 2 physiology-based PCI subgroups, demonstrating the noninferiority of angiography- vs microcatheter-derived FFR (P < 0.01). CONCLUSIONS: In CHIP patients, procedural planning and guidance on the basis of physiology (through either angiography- or microcatheter-derived FFR) are superior to conventional angiography for achieving optimal post-PCI FFR values. (Physiology Optimized Versus Angio-Guided PCI [AQVA-II]; NCT05658952).

The role of physiology in the contemporary management of coronary artery disease.

Coronary physiology assessment, including epicardial and microvascular investigations, is a fundamental tool in the contemporary management of patients with coronary artery disease. Coronary revascularisation guided by functional evaluation has demonstrated superiority over angiography-only-guided treatment. In patients with chronic coronary syndrome, revascularisation did not demonstrate prognostic advantage in terms of mortality over optimal medical therapy (OMT). However, revascularisation of coronary stenosis, which induces myocardial ischaemia, has demonstrated better outcome than OMT alone. Pressure wire (PW) or angiography-based longitudinal coronary physiology provides a point-by-point analysis of the vessel to detect the atherosclerotic pattern of coronary disease. A careful evaluation of this disease pattern allows clinicians to choose the appropriate management strategy.Patients with diffuse disease showed a twofold risk of residual angina after percutaneous coronary intervention (PCI) than those with focal disease. Therefore, OMT alone or coronary artery bypass graft might be considered over PCI. In addition, the post-PCI physiological assessment aims to optimise the result revealing residual myocardial ischaemia. Improvement in post-PCI PW or angiography-based functional indices has been associated with better quality of life and reduced risk of cardiac events and residual angina. Therefore, the information obtained from coronary physiology allows for an optimised treatment strategy, which ultimately leads to improve patient's prognosis and quality of life. This review provides an overview of the latest available evidence in the literature regarding the use of functional assessment of epicardial coronary stenosis in different settings in the contemporary patient-tailored management of coronary disease.

Cognitive impairment and outcomes in older adults with non-ST-elevation acute coronary syndrome.

OBJECTIVE: This study aimed to explore the prognostic impact of cognitive impairment on the long-term risk of major adverse cardiovascular events (MACEs) in older patients with non-ST-elevation acute coronary syndrome (NSTEACS) undergoing invasive treatment. METHODS: Patients aged ≥75 years with NSTEACS undergoing an invasive strategy were included in the multicentre prospective study (NCT01933581). Montreal Cognitive Assessment was used to evaluate cognitive status at baseline (scores ≥26 classified as normal, <26 as cognitive impairment). Long-term follow-up data were obtained from electronic patient care records. The primary endpoint was MACE as a composite of all-cause deaths, reinfarction, stroke/transient ischaemic attack, urgent revascularisation and significant bleeding. RESULTS: 239 patients with baseline cognitive assessment completed long-term follow-up. Median age was 80.9 years (IQR 78.2-83.9 years) and 62.3% were male. On 5-year follow-up, there was no significant difference in the occurrence of MACE between the cognitively impaired group and the normal cognition group (p=0.155). Cognition status was not associated with MACE (HR 1.37 (95% CI 0.96 to 1.95); p=0.082). However, there was significantly more deaths (p=0.005) in those with cognitive impairment. Kaplan-Meier survival analysis (log-rank p=0.003) and Cox regression analysis (aHR 1.85 (95% CI 1.11 to 3.08); p=0.018) revealed increased risk of all-cause mortality, even after adjusting for frailty and GRACE (Global Registry of Acute Coronary Events) score. CONCLUSION: Cognitive impairment in older patients with NSTEACS undergoing an invasive strategy was associated with long-term all-cause mortality. Routine cognitive screening may aid risk stratification and further studies are needed to identify how this should influence management strategies and individual decision-making in this patient group. TRIAL REGISTRATION NUMBER: NCT01933581.

[Percutaneous revascularization in non-ST-elevation acute coronary syndromes: complete or incomplete?] / Rivascolarizzazione percutanea nelle sindromi coronariche acute senza sopraslivellamento del tratto ST: completa o incompleta?

Non-ST-elevation myocardial infarction with multivessel coronary disease is increasing in patients presenting with acute coronary syndrome (ACS) and it is associated with a high rate of mortality. Complete revascularization may reduce major adverse cardiac events in patients with ACS. However, the preferred revascularization strategies (complete vs incomplete) of non-culprit lesions in this setting, as well as the correct timing of revascularization are still matters of debate. This is mostly related to the heterogeneity of patients with this clinical presentation, who are often older and affected by multiple comorbidities. The present review aims to evaluate this topic highlighting the pros and cons of complete revascularization according to anatomical or functional and imaging evaluation and based on timing and patient's clinical phenotype.

Tailoring antiplatelet therapy in older patients with coronary artery disease.

The older population represents a unique subset of patients due to a higher rate of comorbidities and risk factors, which can lead to a higher rate of ischemic and bleeding events. As a result, older adults are mainly underrepresented or excluded from randomized trials. Although the advancement in the percutaneous coronary intervention field with the development of new technologies, techniques, and potent antiplatelet therapy led to a reduction of ischemic risk, there is still a concern regarding bleeding hazards. Apart from the global utilization of less invasive trans-radial approach and proton pump inhibitors to reduce bleeding risk, proper tailoring of antiplatelet therapy in the older person is imperative. So far, several antiplatelet drugs have been introduced in different clinical scenarios, with dual antiplatelet therapy (combination of acetylsalicylic acid and P2Y12 inhibitor) recommended after percutaneous coronary intervention. The decision on the choice of antiplatelet drug and the DAPT duration is challenging and should be based on the relationship between ischemia and bleeding with the purpose of reducing ischemic events but not at the expense of increased bleeding complications. This is particularly important in the older population, where the evidence is obscure. The main objective of this review is to summarize the available evidence on contemporary antiplatelet therapy and different approaches of de-escalation strategies in older patients after percutaneous coronary intervention.

What is the context?The older population represents a unique subset of patients due to a higher rate of comorbidities, risk factors, and unfavorable prognostic features, which can lead to a higher rate of ischemic and bleeding events. They are either excluded or underrepresented in most randomized clinical trials, which is why guidelines recommendation should be taken cautiously. Thus, the decision on the choice of antiplatelet therapy and its duration after percutaneous coronary intervention in older adults is challenging and should be tailored to a particular patient to avoid bleeding complications but not at the expense of increased ischemic events.What is new?In this review, we summarize all available evidence on contemporary antiplatelet therapy and different approaches of de-escalation strategies in older patients after percutaneous coronary intervention. In particular, several recommended approaches in patients with high bleeding risk, are thoroughly discussed in this review: De-escalation strategies with discontinuation of one antiplatelet drugDe-escalation strategy with switching between P2Y12 inhibitorsDe-escalation strategy based on dose reductionFinally, based on the current knowledge on factors contributing to high bleeding risk and the aforementioned antiplatelet modification approaches, in this review, we propose antiplatelet algorithm after percutaneous coronary intervention in older adults.What is the impact?The review provides comprehensive knowledge on antiplatelet therapy in older population and may help in tailoring antiplatelet therapy in this unique subset of patients.

Differences in treatment and clinical outcomes in patients aged ≥75 years compared with those aged ≤74 years following acute coronary syndromes: a prospective multicentre study.

OBJECTIVE: This study describes the differences in treatment and clinical outcomes in patients aged ≥75 years compared with those aged ≤74 years presenting with acute coronary syndrome (ACS) and undergoing invasive management. METHODS: A large-scale cohort study of patients with ST-elevation/non-ST-elevation myocardial infarction (MI)/unstable angina underwent coronary angiography (January 2015-December 2019). Patients were classified as older (≥75 years) and younger (≤74 years). Regression analysis was used to yield adjusted risks of mortality for older versus younger patients (adjusted for history of heart failure, hypercholesterolaemia, peripheral vascular disease, chronic obstructive pulmonary disease, ischaemic heart disease, presence of ST-elevation MI on presenting ECG, female sex and cardiogenic shock at presentation). RESULTS: In total, 11 763 patients were diagnosed with ACS, of which 39% were aged ≥75 years. Percutaneous coronary intervention was performed in fewer older patients than younger patients (81.2% vs 86.2%, p<0.001). At discharge, older patients were prescribed less secondary-prevention medications than younger patients. Median follow-up was 4.57 years. Older patients had a greater risk of in-hospital mortality than younger patients (adjusted OR (aOR) 2.12, 95% CI 1.62 to 2.78, p<0.001). Older patients diagnosed with ST-elevation MI had greater adjusted odds of dying in-hospital (aOR 2.47, 95% CI 1.79 to 3.41, p<0.001). Older age was not an independent prognostic factor of mortality at 1 year (adjusted HR (aHR) 0.95, 95% CI 0.82 to 1.09, p=0.460) and at longer term (aHR 0.98, 95% CI 0.87 to 1.10, p=0.684). CONCLUSIONS: Older patients are discharged with less secondary prevention. Patients aged ≥75 years are more likely to die in-hospital than younger patients.

[Ischemia with non-obstructive coronary artery disease: state-of-the-art review]. / L'ischemia miocardica in assenza di coronaropatia ostruttiva: stato dell'arte.

Chest pain affects more than 100 million people globally, however up to 70% of patients undergoing invasive angiography do not have obstructive coronary artery disease and ischemia with non-obstructive coronary artery disease (INOCA) is often a cause of the clinical picture. The symptoms reported by INOCA patients are very heterogeneous and often misdiagnosed as non-cardiac leading to under-diagnosis/investigation and under-treatment. The underlying pathophysiological mechanisms of INOCA are multiple and include coronary vasospasm and microvascular dysfunction. Most importantly, this condition must not be considered benign: compared to asymptomatic individuals, INOCA patients present an increased incidence of cardiovascular events, rehospitalizations, as well as impaired quality of life, with increasing costs for healthcare systems. The aims of this review are to describe the pathophysiological and clinical characteristics of INOCA and to provide guidance to the medical community on the diagnostic approaches and management of INOCA, also via a series of clinical case reports.

[Epicardial adipose tissue: a novel cardiovascular risk factor]. / Tessuto adiposo epicardico quale nuovo fattore di rischio cardiovascolare.

Epicardial adipose tissue (EAT) has various metabolic functions aiming at heart protection. When abnormal, it is related to atherosclerotic plaque development and adverse cardiovascular outcome. Additionally, in recent years, several studies have demonstrated its role in other settings such as atrial fibrillation and heart failure with preserved ejection fraction. Future studies should aim to assess diagnostic role of EAT and the effect of medical therapy on EAT volume and attenuation.

Coronary Computed Tomography Angiography: Beyond Obstructive Coronary Artery Disease.

Nowadays, coronary computed tomography angiography (CCTA) has a role of paramount importance in the diagnostic algorithm of ischemic heart disease (IHD), both in stable coronary artery disease (CAD) and acute chest pain. Alongside the quantification of obstructive coronary artery disease, the recent technologic developments in CCTA provide additional relevant information that can be considered as "novel markers" for risk stratification in different settings, including ischemic heart disease, atrial fibrillation, and myocardial inflammation. These markers include: (i) epicardial adipose tissue (EAT), associated with plaque development and the occurrence of arrhythmias; (ii) late iodine enhancement (LIE), which allows the identification of myocardial fibrosis; and (iii) plaque characterization, which provides data about plaque vulnerability. In the precision medicine era, these emerging markers should be integrated into CCTA evaluation to allow for the bespoke interventional and pharmacological management of each patient.