Embolic strokes of undetermined source: a clinical consensus statement of the ESC Council on Stroke, the European Association of Cardiovascular Imaging and the European Heart Rhythm Association of the ESC.

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.

PSYChosomatic Medicine in ONcologIc and Cardiac Disease (PSYCHONIC) Study-A Retrospective and Prospective Observational Research Protocol.

Psychosocial factors play an important role in non-communicable diseases (NCDs). This observational study is primarily aimed at assessing the relationship of psychological characteristics of patients with the outcomes of different NCDs, and to assess short-term psychotherapy (STP) efficacy in the real world. Methods: One hundred and forty patients with recent acute myocardial infarction, Takotsubo syndrome, or non-metastatic breast cancer and a control group of 140 age and sex-matched healthy subjects, will be enrolled. All subjects will be administered psychometric tests, quality of life tests, a specific body perception questionnaire, a dream questionnaire, and a projective test, the Six Drawing test at baseline and follow-up. All subjects with medical conditions will be asked to freely choose between an ontopsychological STP along with standard medical therapy and, whenever indicated, rehabilitation therapy or medical therapy plus rehabilitation alone. The study endpoints will be to evaluate: the relationship of the psychological characteristics of enrolled subjects with the outcomes of different NCDs, predictors of the choice of psychotherapy, and the efficacy of ontopsychological intervention on psychological and medical outcomes. Conclusion: This study will generate data on distinctive psychological characteristics of patients suffering from different CDs and their relationship with medical outcomes, as well as explore the efficacy of ontopsychological STP in these patients in the real world. (Number of registration: NCT03437642).

Long-term benefits and risks in patients after persistent foramen ovale closure: a contemporary approach to guide clinical decision making.

Persistent foramen ovale (PFO) is a congenital heart disease which represents 80% of atrial septal defects. It is a remnant of fetal circulation that functions in postnatal conditions as a transient interatrial right­to­­left shunt of variable magnitude. Persistent foramen ovale may be implicated in the pathogenesis of several medical conditions, such as cryptogenic stroke, cryptogenic left circulation thromboembolism, migraine syndromes, and decompression sickness. The most frequent indication for PFO closure remains PFO­associated left circulation thromboembolism. In select patients, PFO closure reduces stroke recurrence in comparison with medical therapy after more than 3 years of follow­up on average, especially in patients with a high risk of recurrence. While in PFO­associated left circulation embolism, there is now conclusive evidence on the growing benefit of PFO closure in long­term follow­up, in many other clinical conditions, the degree of certainty of the results is deceiving. In this paper, we will review the benefits and risks that one can expect in the long term after percutaneous PFO closure in various clinical scenarios in order to facilitate therapeutic decision making.

European position paper on the management of patients with patent foramen ovale. Part II - Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions.

Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

European position paper on the management of patients with patent foramen ovale. Part II - Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions.

Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

Recent Advances in Systems and Network Medicine: Meeting Report from the First International Conference in Systems and Network Medicine.

The First International Conference in Systems and Network Medicine gathered together 200 global thought leaders, scientists, clinicians, academicians, industry and government experts, medical and graduate students, postdoctoral scholars and policymakers. Held at Georgetown University Conference Center in Washington D.C. on September 11-13, 2019, the event featured a day of pre-conference lectures and hands-on bioinformatic computational workshops followed by two days of deep and diverse scientific talks, panel discussions with eminent thought leaders, and scientific poster presentations. Topics ranged from: Systems and Network Medicine in Clinical Practice; the role of -omics technologies in Health Care; the role of Education and Ethics in Clinical Practice, Systems Thinking, and Rare Diseases; and the role of Artificial Intelligence in Medicine. The conference served as a unique nexus for interdisciplinary discovery and dialogue and fostered formation of new insights and possibilities for health care systems advances.

EULAR points to consider for the use of big data in rheumatic and musculoskeletal diseases.

BACKGROUND: Tremendous opportunities for health research have been unlocked by the recent expansion of big data and artificial intelligence. However, this is an emergent area where recommendations for optimal use and implementation are needed. The objective of these European League Against Rheumatism (EULAR) points to consider is to guide the collection, analysis and use of big data in rheumatic and musculoskeletal disorders (RMDs). METHODS: A multidisciplinary task force of 14 international experts was assembled with expertise from a range of disciplines including computer science and artificial intelligence. Based on a literature review of the current status of big data in RMDs and in other fields of medicine, points to consider were formulated. Levels of evidence and strengths of recommendations were allocated and mean levels of agreement of the task force members were calculated. RESULTS: Three overarching principles and 10 points to consider were formulated. The overarching principles address ethical and general principles for dealing with big data in RMDs. The points to consider cover aspects of data sources and data collection, privacy by design, data platforms, data sharing and data analyses, in particular through artificial intelligence and machine learning. Furthermore, the points to consider state that big data is a moving field in need of adequate reporting of methods and benchmarking, careful data interpretation and implementation in clinical practice. CONCLUSION: These EULAR points to consider discuss essential issues and provide a framework for the use of big data in RMDs.

Current status of use of big data and artificial intelligence in RMDs: a systematic literature review informing EULAR recommendations.

Objective: To assess the current use of big data and artificial intelligence (AI) in the field of rheumatic and musculoskeletal diseases (RMDs). Methods: A systematic literature review was performed in PubMed MEDLINE in November 2018, with key words referring to big data, AI and RMDs. All original reports published in English were analysed. A mirror literature review was also performed outside of RMDs on the same number of articles. The number of data analysed, data sources and statistical methods used (traditional statistics, AI or both) were collected. The analysis compared findings within and beyond the field of RMDs. Results: Of 567 articles relating to RMDs, 55 met the inclusion criteria and were analysed, as well as 55 articles in other medical fields. The mean number of data points was 746 million (range 2000-5 billion) in RMDs, and 9.1 billion (range 100 000-200 billion) outside of RMDs. Data sources were varied: in RMDs, 26 (47%) were clinical, 8 (15%) biological and 16 (29%) radiological. Both traditional and AI methods were used to analyse big data (respectively, 10 (18%) and 45 (82%) in RMDs and 8 (15%) and 47 (85%) out of RMDs). Machine learning represented 97% of AI methods in RMDs and among these methods, the most represented was artificial neural network (20/44 articles in RMDs). Conclusions: Big data sources and types are varied within the field of RMDs, and methods used to analyse big data were heterogeneous. These findings will inform a European League Against Rheumatism taskforce on big data in RMDs.

[What's new in the management of patients with patent foramen ovale?] / Cosa c'è di nuovo nelle indicazioni alla chiusura del forame ovale pervio?

Patent foramen ovale (PFO) is associated with a number of clinical syndromes in which it plays variable roles that, often, cannot be accurately determined. This situation creates conflicting data and controversial studies. However, in 2017 and 2018, four randomized clinical trials have been published, allowing for the clarification of certain issues pertaining to cryptogenic stroke. Shortly after this, 8 European scientific societies collaborated to publish the first official international position paper on PFO and cryptogenic stroke, based upon best-available evidence. In the current report, the main positions are presented, relating to PFO diagnosis, general management, and therapeutic choices. Generally speaking, given the complexity of PFO roles, an interdisciplinary and personalized approach was chosen, especially taking into consideration patient involvement at all stages of management. This approach is not suitably addressed by standard guidelines, but can be accommodated in a position statement like this. For this reason, it was possible to offer an approach capable of aiding clinicians to make rational, patient-shared decisions, even when the available evidence is either weak or scarce.

Insertable cardiac monitor detection of silent atrial fibrillation in candidates for percutaneous patent foramen ovale closure.

AIM: An underlying atrial vulnerability or a preexisting misdiagnosed atrial fibrillation in some patients who are candidates for patent foramen ovale (PFO) closure may lead to an unnecessary percutaneous intervention. The aim of this work was to define paroxysmal atrial fibrillation rate, through a 6-month insertable loop-recorder monitoring, in patients over 55 years old with cryptogenic stroke and PFO. METHODS: PFO closure criteria: significant right-to-left shunt and at least one high-risk feature (permanent right-to-left shunt, atrial septal aneurysm, prominent Eustachian valve, recurrent brain ischemia, previous deep vein thrombosis, thrombophilia). Insertable cardiac monitoring criteria: previous cryptogenic stroke, more than 55 years and at least one atrial fibrillation risk factor (heart failure, hypertension, age older than 65 years, diabetes, atrial runs, left atrium dilatation, left ventricle hypertrophy, pulmonary disease, thyroid disease, obesity). Atrial fibrillation detection threshold: arrhythmia duration longer than 5 min. RESULTS: From January 2008 to March 2017, 195 patients underwent to loop-recorder monitoring. A total of 70 (36%) patients were candidates for PFO closure. The 6-month silent atrial fibrillation rate was 11.4%. In the arrhythmia-free cohort, 28 patients (45.2%) underwent percutaneous foramen ovale closure (group A) and 34 (54.8%) were medically treated (group B). Atrial fibrillation detection rate was 14.3% in group A and 0% in group B. The 36-month atrial fibrillation-free survival was 76%. CONCLUSION: An occult preexisting atrial fibrillation may lead to unnecessary percutaneous foramen ovale closure in a significant proportion of patients. A 6-month loop-recorder monitoring may improve the patient oriented decision-making.

Short-TErm Psychotherapy IN Acute Myocardial Infarction (STEP-IN-AMI) Trial: Final Results.

PURPOSE: The purpose of this research was to assess whether short-term psychotherapy enhances long-term clinical outcomes in patients with a recent acute myocardial infarction (AMI). METHODS: Patients ≤70 years old were randomized within 1 week of their AMI to short-term ontopsychological psychotherapy plus routine medical therapy vs routine medical therapy only. The primary composite outcome was defined as the combined incidence of new cardiovascular events (re-infarction, death, stroke, revascularization, life-threatening ventricular arrhythmias, and the recurrence of clinically significant angina) and clinically significant new comorbidities. Secondary outcome measures were: rates for individual components of the primary composite outcome; the rate of re-hospitalization for cardiovascular problems; and New York Heart Association functional class. RESULTS: Ninety-four patients were analyzed, translating into 425 patient-years. The 2 treatment groups were similar across baseline characteristics. At 5-year follow-up, psychotherapy patients had a lower incidence of primary outcome, relative to controls (77/223 vs 98/202 patient-years, respectively; P = .035; absolute risk reduction = 19%, number needed to treat = 8); this benefit was attributable to the lower incidence of new comorbidities and clinically significant angina in the psychotherapy group. Gains in the primary outcome, relative to controls, among psychotherapy patients occurred in the first year and subsequently remained stable over the following 4 years. CONCLUSIONS: Adding short-term ontopsychological psychotherapy to routine secondary prevention of myocardial infarction improves clinical outcomes overall up to 5 years post AMI. Studying time trends may aid in better targeting of psychological interventions during follow-up. Larger studies remain necessary to confirm these results. TRIAL REGISTRATION: www.ClinicalTrial.gov NCT00769366.

European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism.

The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published. This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO. In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales. Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism. For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials. This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence.

Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018.

The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at www.eso-karolinska.org and http://eso-stroke.org) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.

ANMCO/AIAC/SICI-GISE/SIC/SICCH Consensus Document: percutaneous occlusion of the left atrial appendage in non-valvular atrial fibrillation patients: indications, patient selection, staff skills, organisation, and training.

Atrial fibrillation (AF) is the most common arrhythmia and its prevalence is increasing due to the progressive aging of the population. About 20% of strokes are attributable to AF and AF patients are at five-fold increased risk of stroke. The mainstay of treatment of AF is the prevention of thromboembolic complications with oral anticoagulation therapy. Drug treatment for many years has been based on the use of vitamin K antagonists, but recently newer and safer molecules have been introduced (dabigatran etexilate, rivaroxaban, apixaban, and edoxaban). Despite these advances, many patients still do not receive adequate anticoagulation therapy because of contraindications (relative and absolute) to this treatment. Over the last decade, percutaneous closure of left atrial appendage, main site of thrombus formation during AF, proved effective in reducing thromboembolic complications, thus offering a valid medical treatment especially in patients at increased bleeding risk. The aim of this consensus document is to review the main aspects of left atrial appendage occlusion (selection and multidisciplinary assessment of patients, currently available methods and devices, requirements for centres and operators, associated therapies and follow-up modalities) having as a ground the significant evolution of techniques and the available relevant clinical data.

Residual SYNTAX score following coronary artery bypass grafting.

Objectives: To quantify residual coronary artery disease measured using the SYNTAX score (SS) and its relation to outcomes after coronary artery bypass grafting (CABG). Methods: We conducted a retrospective analysis on a consecutive series of 1608 patients [mean age 68 years, standard deviation (SD): 7, F:M, 242:1366] undergoing first-time isolated CABG from 2004 to 2015. The baseline SS was retrospectively determined from preoperative angiograms, and the residual SS (rSS) was measured during assessment of the actual operative report for each patient after CABG. Patients were then stratified according to tercile cut points of low (rSS low 0-11, N = 537), intermediate (rSS mid >11-18.5, N = 539) and high residual SS (rSS high >18.5, N = 532). The Cox regression model was used to investigate the impact of rSS on major adverse cardiac and cerebrovascular events (MACCE) at 1 year. Results: The mean preoperative SS was 26.6 (SD: 9.4) (range 10.1-53), and the residual SS after CABG was 15.3 (SD: 8.4) (range 0-34) ( P < 0.001 versus preoperative). At 1 year, cumulative incidence of MACCE in the low rSS was 1.5% ( N = 8/537), 4.5% ( N = 24/539) in the intermediate and 8.8% ( N = 47/532) in the high rSS group. Kaplan-Meier analysis showed a statistically significant difference of MACCE-free survival between the three groups (log-rank test, P < 0.001). The estimated MACCE-free survival rate at 1 year was 98.1% [standard error (SE): 1.6] for the rSS low , 95.5% (SE: 1.9) for the rSS mid , and 90.5% (SE: 1.3) for the rSS high group, respectively. After multivariable adjustment, the rSS high group was independently associated with a higher incidence of MACCE at 1 year (hazard ratio 1.92, 95% confidence interval 1.21-3.23) compared to the rSS low group. Conclusions: These unanticipated findings suggest that a residual SS may be a useful tool for risk stratification of patients undergoing isolated first-time CABG. Our study may set the stage for further investigations addressing this important clinical question.

[ANMCO/AIAC/SICI-GISE/SIC/SICCH Consensus document: Percutaneous left atrial appendage occlusion in patients with nonvalvular atrial fibrillation: indications, patient selection, competences, organization, and operator training]. / Documento di consenso ANMCO/AIAC/SICI-GISE/SIC/SICCH: Chiusura percutanea dell'auricola sinistra in pazienti con fibrillazione atriale non valvolare: indicazioni, selezione del paziente, competenze e organizzazione e formazione degli operatori.

Atrial fibrillation (AF) is the most common arrhythmia and its prevalence is increasing due to the progressive aging of the population. About 20% of strokes are attributable to AF and AF patients are at 5-fold increased risk of stroke. The mainstay of treatment of AF is the prevention of thromboembolic complications with oral anticoagulation therapy. Drug treatment for many years has been based on the use of vitamin K antagonists, but recently newer and safer molecules have been introduced (dabigatran etexilate, rivaroxaban, apixaban and edoxaban). Despite these advances, many patients still do not receive adequate anticoagulation therapy because of contraindications (relative and absolute) to this treatment. Over the last decade, percutaneous closure of left atrial appendage, main site of thrombus formation during AF, proved effective in reducing thromboembolic complications, thus offering a valid medical treatment especially in patients at increased bleeding risk. The aim of this consensus document is to review the main aspects of left atrial appendage occlusion (selection and multidisciplinary assessment of patients, currently available methods and devices, requirements for centers and operators, associated therapies and follow-up modalities) having as a ground the significant evolution of techniques and the available relevant clinical data.

A prognostic index for risk stratification for acute heart failure and death in subjects with ischemic cardiomyopathy and cardiac defibrillator.

To propose a clinical prognostic index for death and heart failure in patients with ischemic cardiomyopathy implanted with an ICD. This prospective study included 192 consecutive patients (age 68 ± 10) recruited from 2004 to 2009 and implanted with an ICD for MADIT II criteria. All patients performed 24-h ambulatory blood pressure monitoring after discharge and common haematological samples. The prognostic index (PI) was built according to the formula: 120 - age + mean 24 h systolic blood pressure--(creatinine 9 10). Other variables were assessed: EF, haemoglobin concentration, mean 24 h heart rate and diastolic blood pressure, sodium level, pacing mode and diabetes. Non-arrhythmic cardiac death and new hospitalizations for heart failure during 1-year follow-up were the combined end point. A total of 48 events (25%) occurred during the follow-up: 7 cardiac deaths and 41 hospitalizations for acute heart failure. Cox proportional hazards model showed that PI was the only predictor of events (HR = 0.96; CI 95% 0.944­0.976, p < 0.0001). ROC curve showed that PI best cut-off was 144, with AUC 0.79, p < 0.0001; sensitivity 77%, specificity 74%, positive predictive value 50%, negative predictive value 90%. PI was predictive of events in a clinical setting where EF had no predictive value. PI works according to the rule ''the lower the worse''. The high negative predictive value (90%) of PI allows to identify subjects at lower risk for death and heart failure. PI can be a practical tool to stratify risk in ischemic cardiomyopathy.