Faculty of Medicine

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Sex and gender differences in coronary pathophysiology and ischaemic heart disease
(Oxford University Press (OUP), 2026-01-23)
Manfrini, Olivia
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Tousoulis, Dimitris
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Antoniades, Charalambos
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Badimon, Lina
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Bugiardini, Raffaele
Ischaemic heart disease shows important differences between men and women, requiring an understanding of sex and gender dissimilarities to improve outcomes. This Scientific Statement provides an updated review of the current knowledge from risk factors to prognosis. It discusses the unequal impact of certain traditional risk factors between men and women, along with additional factors, such as hormonal changes and treatments (including those for transgender people and cancer), pregnancy-related complications, and autoimmune diseases, which contribute to the sex-specific risk profiles. Moreover, it outlines functional and structural sex differences in the pathophysiology (e.g. coronary atheroma plaques and burden, coronary dissection, vasospasm, and microvascular disease) with women being more prone to microvascular disease and endothelial dysfunction, while paradoxically experiencing less severe myocardial ischaemia at similar levels of coronary stenosis. The document further addresses the evaluation of diagnostic tools, which often have a male-centric bias, resulting in underdiagnosis in women who also tend to receive less guideline-recommended treatment. Additionally, women can have different responses and side effects to various preventive and therapeutic treatments, potentially contributing to the worse prognosis documented in acute coronary syndromes with obstructive coronary artery disease, particularly at a young age. Considering all these sex and gender differences and the low enrolment of women in randomized controlled trials, questions arise regarding the optimal treatment for women. Addressing sex differences requires conducting sex-specific research to close the knowledge gap. Overall, the Scientific Statement highlights all relevant sex- and gender-specific dissimilarities to advance clinical practice and identify directions for future research to improve guideline recommendations for equitable care.
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EAPCI Core Curriculum for Percutaneous Cardiovascular Interventions (2020): Committee for Education and Training European Association of Percutaneous Cardiovascular Interventions (EAPCI). A branch of the European Society of Cardiology
(The Official Journal of EuroPCR and the European Association of Percutaneous Cardiovascular Interventions, 2020-07-07)
Van Belle, Eric
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Teles, Rui C
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Pyxaras, Stylianos A
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Johnson, Thomas William
The proposed 2020 Core Curriculum for Percutaneous Cardiovascular Interventions aims to provide an updated European consensus that defines the level of experience and knowledge in the field of Percutaneous Cardiovascular Intervention (PCI). It promotes homogenous education and training programmes among countries, and is the cornerstone of the new EAPCI certification, designed to support the recognition of competencies at the European level and the free movement of certified specialists in the European Community. It is based on a thorough review of the ESC guidelines and of the EAPCI Textbook in Percutaneous Interventional Cardiovascular Medicine. The structure of the current Core Curriculum evolved from previous EAPCI Core Curriuclum and from the "2013 core curriculum of the general cardiologist" to follow the current ESC recommendations for Core Curriculums. In most subject areas, there was a wide - if not unanimous - consensus among the task force members on the training required for the interventional cardiologist of the future. The document recommends that acquisition of competence in Interventional Cardiology requires at least 2 years of postgraduate training, in addition to 4 years devoted to cardiology. The first part of the curriculum covers general aspects of training and is followed by a comprehensive description of the specific components in 54 chapters. Each of the chapters includes statements of the objectives, and is further subdivided into the required knowledge, skills, behaviours, and attitudes.
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Perivascular adipose tissue as a source of therapeutic targets and clinical biomarkers
(Oxford Academic, 2023-08-21)
Antoniades, Charalambos
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Tousoulis, Dimitris
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Fleming, Ingrid
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Duncker, Dirk J
Obesity is a modifiable cardiovascular risk factor, but adipose tissue (AT) depots in humans are anatomically, histologically, and functionally heterogeneous. For example, visceral AT is a pro-atherogenic secretory AT depot, while subcutaneous AT represents a more classical energy storage depot. Perivascular adipose tissue (PVAT) regulates vascular biology via paracrine cross-talk signals. In this position paper, the state-of-the-art knowledge of various AT depots is reviewed providing a consensus definition of PVAT around the coronary arteries, as the AT surrounding the artery up to a distance from its outer wall equal to the luminal diameter of the artery. Special focus is given to the interactions between PVAT and the vascular wall that render PVAT a potential therapeutic target in cardiovascular diseases. This Clinical Consensus Statement also discusses the role of PVAT as a clinically relevant source of diagnostic and prognostic biomarkers of vascular function, which may guide precision medicine in atherosclerosis, hypertension, heart failure, and other cardiovascular diseases. In this article, its role as a 'biosensor' of vascular inflammation is highlighted with description of recent imaging technologies that visualize PVAT in clinical practice, allowing non-invasive quantification of coronary inflammation and the related residual cardiovascular inflammatory risk, guiding deployment of therapeutic interventions. Finally, the current and future clinical applicability of artificial intelligence and machine learning technologies is reviewed that integrate PVAT information into prognostic models to provide clinically meaningful information in primary and secondary prevention.
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Mechanisms, therapeutic implications, and methodological challenges of gut microbiota and cardiovascular diseases: a position paper by the ESC Working Group on Coronary Pathophysiology and Microcirculation
(Oxford Journals, 2022-12-29)
Tousoulis, Dimitris
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Guzik, Tomasz
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Padro, Teresa
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Duncker, Dirk J
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De Luca, Giuseppe
The human gut microbiota is the microbial ecosystem in the small and large intestines of humans. It has been naturally preserved and evolved to play an important role in the function of the gastrointestinal tract and the physiology of its host, protecting from pathogen colonization, and participating in vitamin synthesis, the functions of the immune system, as well as glucose homeostasis and lipid metabolism, among others. Mounting evidence from animal and human studies indicates that the composition and metabolic profiles of the gut microbiota are linked to the pathogenesis of cardiovascular disease, particularly arterial hypertension, atherosclerosis, and heart failure. In this review article, we provide an overview of the function of the human gut microbiota, summarize, and critically address the evidence linking compositional and functional alterations of the gut microbiota with atherosclerosis and coronary artery disease and discuss the potential of strategies for therapeutically targeting the gut microbiota through various interventions.
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Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA)
(Oxford University Press (OUP), 2021-09-16)
Cenko, Edina
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Badimon, Lina
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Bugiardini, Raffaele
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Claeys, Marc J
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De Luca, Giuseppe
The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between SARS-CoV-2 and ACE2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as "post-acute COVID-19" may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance.
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Impact of SARS-CoV-2 positivity on clinical outcome among STEMI patients undergoing mechanical reperfusion: Insights from the ISACS STEMI COVID 19 registry
(Elsevier BV, 2021-07-20)
De Luca, Giuseppe
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Debel, Niels
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Cercek, Miha
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Jensen, Lisette Okkels
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Background and aims SARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Methods We selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1 until April 30, 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure. Results Our population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p < 0.001). Despite similar pre and postprocedural TIMI flow, we observed a trend in higher use of GP IIb-IIIa inhibitors and significantly higher use of thrombectomy in the SARS-CoV-2 positive patients. SARS-CoV-2 positivity was associated with a remarkably higher in hospital mortality (29 % vs 5.5 %, p < 0.001), definite in-stent thrombosis (8.1 % vs 1.6 %, p = 0.004) and heart failure (22.6 % vs 10.6 %, p = 0.001) that was confirmed after adjustment for confounding factors. Conclusions Our study showed that among STEMI patients, SARS-CoV-2 positivity is associated with larger thrombus burden, a remarkably higher mortality but also higher rates of in-stent thrombosis and heart failure.
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ESC Working Group on Coronary Pathophysiology and Microcirculation position paper on 'coronary microvascular dysfunction in cardiovascular disease'
(Oxford University Press (OUP), 2020-03-01)
Padro, Teresa
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Manfrini, Olivia
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Bugiardini, Raffaele
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Canty, John
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Cenko, Edina
Although myocardial ischaemia usually manifests as a consequence of atherosclerosis-dependent obstructive epicardial coronary artery disease, a significant percentage of patients suffer ischaemic events in the absence of epicardial coronary artery obstruction. Experimental and clinical evidence highlight the abnormalities of the coronary microcirculation as a main cause of myocardial ischaemia in patients with 'normal or near normal' coronary arteries on angiography. Coronary microvascular disturbances have been associated with early stages of atherosclerosis even prior to any angiographic evidence of epicardial coronary stenosis, as well as to other cardiac pathologies such as myocardial hypertrophy and heart failure. The main objectives of the manuscript are (i) to provide updated evidence in our current understanding of the pathophysiological consequences of microvascular dysfunction in the heart; (ii) to report on the current knowledge on the relevance of cardiovascular risk factors and comorbid conditions for microcirculatory dysfunction; and (iii) to evidence the relevance of the clinical consequences of microvascular dysfunction. Highlighting the clinical importance of coronary microvascular dysfunction will open the field for research and the development of novel strategies for intervention will encourage early detection of subclinical disease and will help in the stratification of cardiovascular risk in agreement with the new concept of precision medicine.
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Impact of COVID-19 Pandemic on Mechanical Reperfusion for Patients With STEMI
(Elsevier, 2020-11-17)
De Luca, Giuseppe
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Verdoia, Monica
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Cercek, Miha
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Jensen, Lisette Okkels
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The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality.
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Impact of COVID-19 pandemic and diabetes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry
(Springer Science and Business Media LLC, 2020-12-18)
De Luca, Giuseppe
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Cercek, Miha
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Jensen, Lisette Okkels
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Calmac, Lucian
It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes-ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19.

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