Δείκτες οστεοβλαστικής μετατροπής στη στένωση αορτικής βαλβίδας εκφυλιστικής αιτιολογίας, σε ανθρώπινο και ζωικό ιστό κονίκλου

Εισαγωγή: Η ασβεστοποιός αορτική στένωση έχει μια συνεχώς αυξανόμενη επίπτωση, ενώ αποτελεί έναν κύριο αιτιολογικό αλλά και προγνωστικό παράγοντα οξέων καρδιαγγειακών συμβαμάτων. Παρά το μεγάλο κοινωνικοοικονομικό κόστος, το κόστος των υπηρεσιών υγείας και τις εκτεταμένες ερευνητικές προσπάθειες, οι θεραπευτικές στρατηγικές παραμένουν ακόμα ανεπαρκείς. Σκοπός: Σκοπός της παρούσας εργασίας είναι η ανάδειξη της οστεοβλαστικής μεταπλασίας του ιστού ως κύριο παθοφυσιολογικά υπεύθυνο φαινόμενο για την αορτική στένωση, χρησιμοποιώντας το ζωικό μοντέλο του κονίκλου. Υλικό και μέθοδος: Το ζωικό μοντέλο αποτελείται από αρσενικούς κονίκλους Νέας Ζηλανδίας, βάρους 4-5 κιλών, οι οποία τυχαιοποιήθηκαν να λαμβάνουν είτε κανονική τροφή είτε τροφή εμπλουτισμένη με 1% χοληστερόλη και 3500 I.U. βιταμίνης D2 ανά κιλό βάρους σώματος. Τα ζώα χωρίστηκαν σε 3 ομάδες 1:1 ελέγχου- πειραματικά και ακολούθως θυσιάστηκαν ως εξής: α) στις 2 εβδομάδες, β) στις 4 εβδομάδες και γ) στις 7 εβδομάδες. Αποτελέσματα: Οι κόνικλοι που λάμβαναν τροφή εμπλουτισμένη με χοληστερόλη και βιταμίνη D2, παρουσιάζουν επιτάχυνση της ασβεστοποιού αορτικής στένωσης. Οι δείκτες που το μοντέλο μας προσπαθεί να προσδιορίσει -η οστική μορφογενετική πρωτεΐνη-2 (BMP-2), η οστεοποντίνη, η οστική σιαλοπρωτεΐνη και η ιστική μη-ειδική αλκαλική φωσφατάση- φαίνεται ότι έχουν σημαντικό ρόλο στην εξέλιξη της ασβεστοποιού αορτικής νόσου. Συμπέρασμα: Η πρόοδος της εκφυλιστικής στένωσης της αορτικής βαλβίδας είναι μια ενεργός διεργασία όπου ενεργό ρόλο διαδραματίζει η φλεγμονή και προσαβεστοποιοί δείκτες.Introduction: The calcifying aortic stenosis has an ever-increasing incidence, while it is a major causal and prognostic factor of acute cardiovascular events. Despite the high socio-economic costs, the cost of health services and the extensive research efforts, treatment strategies are still insufficient. Aim: The aim of the present study is to highlight the osteoblastic tissue metaplasia as the main pathophysiological responsible mechanism for aortic stenosis, using the animal model of the rabbit. Material and method: The animal model consists of male New Zealand rabbits, weighing 4-5 kg, who were randomly assigned to receive either normal food or food fortified with 1% cholesterol and 3500 I.U. Vitamin D2 per kilogram of body weight. The animals were divided into 3 groups of 1: 1 control-experimental and then sacrificed as follows: a) at 2 weeks, b) at 4 weeks and c) at 7 weeks. Results: Rabbits fed a diet rich in cholesterol and vitamin D2 showed an acceleration of calcifying aortic stenosis. The markers that our model is trying to identify - bone morphogenetic protein-2 (BMP-2), osteopontin, bone sialoprotein and tissue non-specific alkaline phosphatase - seem to play an important role in the development of aortic calcifying disease. Conclusion: The progression of degenerative stenosis of the aortic valve is an active process where inflammation and calcification mechanisms play an active role

ST-elevation myocardial infarction in a 39-year-old patient with "normal" coronary arteries as a thrombotic complication of COVID-19.

We report the case of a 39-year-old male without traditional risk factors for coronary artery disease (CAD), i.e. smoking, hypercholesterolemia, hypertension, diabetes mellitus, familial history of premature CAD, admitted with anterior ST-segment elevation myocardial infarction and concurrent coronavirus disease-2019 infection. Coronary angiography showed high intracoronary thrombus burden and thrombotic occlusion of the proximal segment of left anterior descending artery, while optical coherence tomography revealed intact endothelium after thromboaspiration. LEARNING OBJECTIVE: : Coronavirus disease-2019 (COVID-19) may predispose to thrombotic complications in both the venous and the arterial circulation. ST-segment elevation myocardial infarction (STEMI), rarely, may be the main clinical presentation of COVID-19. STEMI in patients with concurrent COVID-19 may be caused by thrombotic coronary occlusion even in the setting of "normal" coronary arteries

Rationale and design of a prospective, observational, multicentre study on the safety and efficacy of apixaban for the prevention of thromboembolism in adults with congenital heart disease and atrial arrhythmias: the PROTECT-AR study

Introduction The risk for stroke in adults with congenital heart disease (ACHD) is increased, especially in the setting of commonly ensuing atrial arrhythmias (AA), namely atrial fibrillation, atrial flutter or intra-atrial re-entrant tachycardia. Data are limited regarding treatment with non-vitamin K oral anticoagulants in long-term studies involving patients with ACHD and AA.Methods and analysis PReventiOn of ThromboEmbolism in Adults with Congenital HearΤ disease and Atrial aRrhythmias is a prospective, multicenter, single-arm, non-interventional cohort study designed to investigate the safety and efficacy of apixaban for the prevention of thromboembolism in ACHD with AA in a ‘real-world’ setting. Eligible patients will be evaluated by the means of available registries and clinical counter. The study aims to accumulate approximately 500 patient-years of exposure to apixaban as part of routine care. Enrolment will take place at four ACHD centres in Greece. The first patient was enrolled in July 2019. The primary efficacy endpoint is a composite of stroke, systemic or pulmonary embolism and intracardiac thrombosis. The primary safety endpoint is major bleeding, according to the International Society on Thrombosis and Haemostasis bleeding criteria.Ethics and dissemination The study protocol has been approved by the institutional review board/independent ethics committee at each site prior to study commencement. All patients will provide written informed consent. Results will be disseminated at scientific meetings and published in peer-reviewed journals.Trial registration number NCT03854149; Pre-results

The Adult Congenital Heart Disease Anatomic and Physiological Classification: Associations with Clinical Outcomes in Patients with Atrial Arrhythmias

The implications of the adult congenital heart disease anatomic and physiological classification (AP-ACHD) for risk assessment have not been adequately studied. A retrospective cohort study was conducted using data from an ongoing national, multicentre registry of patients with ACHD and atrial arrhythmias (AA) receiving apixaban (PROTECT-AR study, NCT03854149). At enrollment, patients were stratified according to Anatomic class (AnatC, range I to III) and physiological stage (PhyS, range B to D). A follow-up was conducted between May 2019 and September 2021. The primary outcome was a composite of death from any cause, any major thromboembolic event, major or clinically relevant non-major bleeding, or hospitalization. Cox proportional-hazards regression modeling was used to evaluate the risks for the outcome among AP-ACHD classes. Over a median 20-month follow-up period, 47 of 157 (29.9%) ACHD patients with AA experienced the composite outcome. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for the outcome in PhyS C and PhyS D were 1.79 (95% CI 0.69 to 4.67) and 8.15 (95% CI 1.52 to 43.59), respectively, as compared with PhyS B. The corresponding aHRs in AnatC II and AnatC III were 1.12 (95% CI 0.37 to 3.41) and 1.06 (95% CI 0.24 to 4.63), respectively, as compared with AnatC I. In conclusion, the PhyS component of the AP-ACHD classification was an independent predictor of net adverse clinical events among ACHD patients with AA

Association of Health Status Metrics with Clinical Outcomes in Patients with Adult Congenital Heart Disease and Atrial Arrhythmias

The prognostic value of health status metrics in patients with adult congenital heart disease (ACHD) and atrial arrhythmias is unclear. In this retrospective cohort study of an ongoing national, multicenter registry (PROTECT-AR, NCT03854149), ACHD patients with atrial arrhythmias on apixaban are included. At baseline, health metrics were assessed using the physical component summary (PCS), the mental component summary (MCS) of the Short-Form-36 (SF-36) Health Survey, and the modified European Heart Rhythm Association (mEHRA) score. Patients were divided into groups according to their SF-36 PCS and MCS scores, using the normalized population mean of 50 on the PCS and MCS as a threshold. The primary outcome was the composite of mortality from any cause, major thromboembolic events, major/clinically relevant non-major bleedings, or hospitalizations. Multivariable Cox-regression analyses using clinically relevant parameters (age greater than 60 years, anatomic complexity, ejection fraction of the systemic ventricle, and CHA₂DS₂-VASc and HAS-BLED scores) were performed to examine the association of health metrics with the composite outcome. Over a median follow-up period of 20 months, the composite outcome occurred in 50 of 158 (32%) patients. The risk of the outcome was significantly higher in patients with SF-36 PCS ≤ 50 compared with those with PCS > 50 (adjusted hazard ratio (aHR), 1.98; 95% confidence interval [CI], 1.02–3.84; p = 0.04) after adjusting for possible confounders. The SF-36 MCS ≤ 50 was not associated with the outcome. The mEHRA score was incrementally associated with a higher risk of the composite outcome (aHR = 1.44 per 1 unit increase in score; 95% CI, 1.03–2.00; p = 0.03) in multivariable analysis. In ACHD patients with atrial arrhythmias, the SF-36 PCS ≤ 50 and mEHRA scores predicted an increased risk of adverse events