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Objectives The authors explored the development and validation of machine-learning models for augmenting the echocardiographic grading of aortic stenosis (AS) severity. Background In AS, symptoms and adverse events develop secondarily to valvular obstruction and left ventricular decompensation. The current echocardiographic grading of AS severity focuses on the valve and is limited by diagnostic uncertainty. Methods Using echocardiography (ECHO) measurements (ECHO cohort, n = 1,052), we performed patient similarity analysis to derive high-severity and low-severity phenogroups of AS. We subsequently developed a supervised machine-learning classifier and validated its performance with independent markers of disease severity obtained using computed tomography (CT) (CT cohort, n = 752) and cardiovascular magnetic resonance (CMR) imaging (CMR cohort, n = 160). The classifier’s prognostic value was further validated using clinical outcomes (aortic valve replacement [AVR] and death) observed in the ECHO and CMR cohorts. Results In 1,964 patients from the 3 multi-institutional cohorts, 1,346 (68%) subjects had either nonsevere or discordant AS severity. Machine learning identified 1,117 (57%) patients as having high-severity and 847 (43%) as having low-severity AS. High-severity patients in CT and CMR cohorts had higher valve calcium scores and left ventricular mass and fibrosis, respectively than the low-severity group. In the ECHO cohort, progression to AVR and progression to death in patients who did not receive AVR was faster in the high-severity group. Compared with the conventional classification of disease severity, machine-learning–based severity classification improved discrimination (integrated discrimination improvement: 0.07; 95% confidence interval: 0.02 to 0.12) and reclassification (net reclassification improvement: 0.17; 95% confidence interval: 0.11 to 0.23) for the outcome of AVR at 5 years. For both ECHO and CMR cohorts, we observed prognostic value of the machine-learning classifications for subgroups with asymptomatic, nonsevere or discordant AS. Conclusions Machine learning can integrate ECHO measurements to augment the classification of disease severity in most patients with AS, with major potential to optimize the timing of AVR.

BACKGROUND: The extent to which health care systems have adapted to the COVID-19 pandemic to provide necessary cardiac diagnostic services is unknown.OBJECTIVES: The aim of this study was to determine the impact of the pandemic on cardiac testing practices, volumes and types of diagnostic services, and perceived psychological stress to health care providers worldwide.METHODS: The International Atomic Energy Agency conducted a worldwide survey assessing alterations from baseline in cardiovascular diagnostic care at the pandemic's onset and 1 year later. Multivariable regression was used to determine factors associated with procedure volume recovery.RESULTS: Surveys were submitted from 669 centers in 107 countries. Worldwide reduction in cardiac procedure volumes of 64% from March 2019 to April 2020 recovered by April 2021 in high- and upper middle-income countries (recovery rates of 108% and 99%) but remained depressed in lower middle- and low-income countries (46% and 30% recovery). Although stress testing was used 12% less frequently in 2021 than in 2019, coronary computed tomographic angiography was used 14% more, a trend also seen for other advanced cardiac imaging modalities (positron emission tomography and magnetic resonance; 22%-25% increases). Pandemic-related psychological stress was estimated to have affected nearly 40% of staff, impacting patient care at 78% of sites. In multivariable regression, only lower-income status and physicians' psychological stress were significant in predicting recovery of cardiac testing.CONCLUSIONS: Cardiac diagnostic testing has yet to recover to prepandemic levels in lower-income countries. Worldwide, the decrease in standard stress testing is offset by greater use of advanced cardiac imaging modalities. Pandemic-related psychological stress among providers is widespread and associated with poor recovery of cardiac testing.

Η κλοπιδογρέλη είναι ένα ευρέως χρησιμοποιούμενο αντιαιμοπεταλιακό φάρμακο για τη δευτερογενή πρόληψη αθηροθρομβωτικών επεισοδίων, σε συνδυασμό με ασπιρίνη ή ως μονοθεραπεία. Το κλινικό όφελος της κλοιδογρέλης έχει καθιερωθεί με μια πληθώρα μεγάλων κλινικών μελετών, καθώς και στην παγκόσμια κλινική πρακτική. Όλη αυτή η γνώση και η εμπειρία έχουν ληφθεί χρησιμοποιώντας το πρωτότυπο σκεύασμα της όξινης θειϊκής κλοπιδογρέλης (CHS-Plavix® / Iscover®). Μετά τη λήξη των φαρμακευτικών διπλωμάτων ευρεσιτεχνίας της τον Μάιο του 2012, η κλοπιδογρέλη έχει καταστεί γενόσημηκαι έτσι διάφορα εμπορικά σκευάσματα έχουν αναπτυχθεί και εγκριθεί για χρήση σε όλο τον κόσμο, συμπεριλαμβανομένης της Ευρώπης και των ΗΠΑ,για τη δευτερογενή πρόληψη των αθηροθρομβωτικών επεισοδίων. Σε αυτά περιλαμβάνονται η κλοπιδογρέλη βάσης, η κλοπδογρέλη resinate, ηυδροχλωρική κλοπιδογρέλη και η βεσυλική κλοπιδογρέλη (CB). Κατά την ανάπτυξη μιας νέας γενόσημης μορφής, είναι σημαντικό να συμμορφώνονταιμε τη διαδικασία παρασκευής και να χρησιμοποιούνται τα ίδια έκδοχα όπως και στο αρχικό άλας, προκειμένου να ελαχιστοποιηθούν τα προβλήματα σταθερότητας. Συγκεκριμένα, κατά τη διάρκεια της φάσης ανάπτυξης μιας από του στόματος στερεής μορφής, αρκετές φυσικοχημικές δοκιμές προ κα ιμετά διαμόρφωσης του σκευάσματος διεξάγονται προκειμένου να επιτευχθεί ένα υψηλής ποιότητας γενόσημο προϊόν που είναι ισάξιο με το αρχικό πρωτότυπο σκεύασμα από την άποψη της αποτελεσματικότητας και της ασφάλειας . Κατά συνέπεια, ένα γενόσημο προϊόν πρέπει να παρουσιάζει ένα προφίλ διάλυσης in vitro, παρόμοιο ή επικαλυπτόμενο εκείνου του αρχικού προϊόντος, προκειμένου να εξασφαλισθεί ένα πετυχημένο προφίλ βιοϊσοδυναμίας του προϊόντος. Ωστόσο, σύμφωνα με το βιοφαρμακευτικό σύστημα ταξινόμησης, η κλοπιδογρέλη είναι ένα προϊόν Class II και η in vitroδιάλυση δεν αρκεί για να αποδείξει ότι είναι ισάξια με το πρωτότυπο σκεύασμα. Έτσι, τα γενόσημα δισκία κλοπιδογρέλης θα πρέπει ναυποβάλλονται σε μελέτη βιοϊσοδυναμίας σε σύγκριση με το πρωτότυπο σκεύασμα. Επιπλέον, είναι κρίσιμης σημασίας να αποδειχθεί ότι αυτά ταπαρασκευάσματα έχουν παρόμοια φαρμακοδυναμική δραστικότητα στηναναστολή της δραστικότητας των αιμοπεταλίων και επίσης είναι κλινικά βιοϊσοδύναμα με το αρχικό άλας από την άποψη της αποτελεσματικότητας και της ασφάλειας. Σε αυτό το πλαίσιο, θα πρέπει να τονιστεί ότι σε αντίθεση με άλλα γενικά καρδιαγγειακά φάρμακα, όπως οι στατίνες ή τααντιυπερτασικά, για τα οποία μικρές διαφορές στην βιολογική αποτελεσματικότητά τους θα ήταν απίθανο να έχουν οποιαδήποτε διακριτόκλινικό αποτέλεσμα, μια μικρή μείωση στη φαρμακοδυναμική ισχύ της κλοπιδογρέλης θα μπορούσε να οδηγήσει σε σοβαρές ισχαιμικές θρομβωτικές επιπλοκές, ιδιαίτερα σε καταστάσεις όπου η θεραπευτική αποτελεσματικότητα είναι κρίσιμη, όπως αμέσως μετά από μια διαδερμική στεφανιαία παρέμβαση. Η ανάγκη για την αξιολόγηση της θεραπευτικής αποτελεσματικότητας ενός γενόσημου άλατος κλοπιδογρέλης υποστηρίζεται περαιτέρω από τη σημαντική ετερογένεια μεταξύ των υφιστάμενων γενόσημων σκευασμάτων κλοπιδογρέλης, όσον αφορά το περιεχόμενο της κλοπιδογρέλης, το προφίλ καθαρότητας, τις ιδιότητες διάλυσης και σταθερότητας, ακόμη και αν αυτές αφορούν το ίδιο το άλας. Έως σήμερα έχει διεξαχθεί μια σειρά από μικρές και συχνά χαμηλής ισχύος μελέτες που συγκρίνουν είτε φαρμακοδυναμικά είτε κλινικά καταληκτικά σημεία σε ασθενείς που λαμβάνουν γενόσημα έναντι της πρωτότυπης κλοπιδογρέλης. Μεταξύ αυτών πολύ λίγες είναι οι μελέτες που χρησιμοποιούν μείζονα καταληκτικά συμβάντα και παρακολούθηση ασθενών για περισσότερο από 3 μήνες, ενώ πολλές δοκιμές διεξήχθησαν σε υγιείς εθελοντές. Η ερευνητική μας ομάδα είχε δημοσιεύσει δύο μελέτες οι οποίες κατέληξαν στο συμπέρασμα ότι υπήρξε φαρμακοδυναμική βιοϊσοδυναμία μεταξύ του γενόσημου σκευάσματος CB σε σχέση με εκείνο του πρωτότυπου σκευάσματος CHS σε ασθενείς με 1 και 6 μήνες παρακολούθησης μετά από οξύ στεφανιαίο σύνδρομο. ΣΚΟΠΟΣ: O σκοπός της παρούσας μελέτης ήταν να συγκριθεί η κλινική αποτελεσματικότητα και ασφάλεια του σκευάσματος CB σε σχέση με εκείνητης πρωτότυπης CHS, που χορηγήθηκαν για 12 μήνες σε ένα σχετικά μεγάλο αριθμό ασθενών που μπορούν να λάβουν κλοπιδογρέλη σύμφωνα με τις ενδείξεις και τις κατευθυντήριες οδηγίες. Η ενδιάμεση ανάλυση αυτής της μελέτης έγινε στους 6 μήνες παρακολούθησης. ΜΕΘΟΔΟΙ: Διενεργήθηκε μια τυχαιοποιημένη προοπτική 2-βραχίονων, πολυκεντρική, ανοικτή, φάσης 4 κλινική μελέτη, που ονομάστηκε Salts of Clopidogrel: Investigation to EN sure Clinical Equivalence (SCIENCE). Κατά τη διάρκεια της μελέτης αυτής 1864 διαδοχικοί ασθενείς ελέγχθηκαν και 1800 καταγράφηκαν στη μελέτη και τυχαιοποιήθηκαν σε CHS ή CB. Πρωτεύον καταληκτικό σημείο αποτελεσματικότητας ήταν το σύνθετο του εμφράγματος του μυοκαρδίου, ΑΕΕ ή θανάτου από αγγειακά αίτια, και πρωτεύον καταληκτικό σημείο ασφάλειας ήταν η συχνότητα των αιμορραγικών επεισοδίων, όπως ορίζεται από τα αιμορραγικά κριτήρια Bleeding Academic Research Consortium (BARC) ΑΠΟΤΕΛΕΣΜΑΤΑ: Στους 6 μήνες παρακολούθησης δεν παρατηρήθηκαν διαφορές μεταξύ των CB(n=759) και CHS (n=798) στο πρωτεύον καταληκτικό σημείο αποτελεσματικότητας (OR, 0.80; 95% CI, 0.37 to 1.71; p=0.57). Ποσοστά αιμορραγίας BARC-1, -2, -3a και -5b ήταν παρόμοια μεταξύ των δύο ομάδων της μελέτης, ενώ δεν παρατηρήθηκαν αιμορραγικά συμβάντα BARC-3b, -3c,-4 και -5a είτε στη CHS είτε στη CB ομάδα. Στους 12 μήνες παρακολούθησης, δεν παρατηρήθηκαν διαφορές μεταξύ των CB και CHS στα πρωτεύοντα καταληκτικά σημεία αποτελεσματικότητας και ασφάλειας (προσαρμοσμένο ποσοστό πιθανότητας για ηλικία, φύλο, ιστορικό διαδερμικής στεφανιαίας αγγειοπλαστικής [OR], 0.70; 95% διάστημα εμπιστοσύνης [CI], 0.41-1.21 καιOR, 0.81; 95% CI, 0.51-1.29 αντίστοιχα). Αναλύσεις αποτελεσματικότητας και ασφάλειας σε υποομάδες οι οποίες καθορίζονταν σύμφωνα με την ειδική διάγνωση κατέληξαν στο ότι δεν υπήρχε διαφορά μεταξύ CHS και CB. ΣΥΜΠΕΡΑΣΜΑ: Η παρούσα κλινική μελέτη κατέληξε στο συμπέρασμα ότι η κλινική αποτελεσματικότητα του άλατος της CB που χορηγείται για 12 μήνες σε διάφορες κατηγορίες ασθενών που μπορούν να λάβουν κλοπιδογρέλη είναι παρόμοια με εκείνη του πρωτότυπου άλατος της CHS. Επιπλέον και τα δυο άλατα κλοπιδογρέλης επέδειξαν παρόμοιο προφίλ ασφάλειας. Η ενδιάμεση ανάλυση αυτής της μελέτης που διεξήχθη στους 6 μήνες παρακολούθησης έδειξε επίσης ότι δεν υπήρχαν διαφορές στα κλινικά πρωτεύοντα και δευτερεύοντα καταληκτικά σημεία αοτελεσματικότητας και ασφάλειας μεταξύ CB και CHS. Σύμφωνα με τα δεδομένα μας αυτή είναι η μεγαλύτερη κλινική μελέτη που πραγματοποιήθηκε μέχρι σήμερα από την άποψη τουμεγέθους του πληθυσμού, τη διάρκεια της μελέτης και τις υπο ομάδες ασθενών,με στόχο να συγκριθεί η αποτελεσματικότητα και η ασφάλεια ενός γενόσημου άλατος κλοπιδογρέλης με το πρωτότυπο σκεύασμα κλοπιδογρέλης στη δευτερογενή πρόληψη των αθηροθρομβωτικών επεισοδίων. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE trial; ClinicalTrials.gov Identifier: NCT02126982). Ευχαριστίες (Χορηγίες/ Οικονομική ενίσχυση):Η μελέτη αυτή χρηματοδοτήθηκε εν μέρει από την Ευρωπαϊκή Ένωση και μέσω του Επιχειρησιακού Προγράμματος «Ανταγωνιστικότητα και Επιχειρηματικότητα» του Εθνικού Στρατηγικού Πλαισίου Αναφοράς (ΕΣΠΑ)–Ερευνητικό Πρόγραμμα Χρηματοδότησης: Συνεργασία 2009. Δράση Ι. Συνεταιρισμός μικρής και μεσαίας κλίμακας (κωδικός έργου: 09ΣΥΝ-12-827) και από την επιτροπή ερευνών μέσω του ειδικού λογαριασμού κονδυλίων έρευνας (ΕΛΚΕ) του Πανεπιστημίου Ιωαννίνων. Η μελέτη αυτή επίσης χρηματοδοτήθηκε εν μέρει από την ELPEN (Ελλάδα), κατασκευάστρια εταιρεία του σκευάσματος της βεσυλικής κλοπιδογρέλης (Clovelen®) που χρησιμοποιήθηκε στην παρούσα μελέτη. Ωστόσο, ο χορηγός δεν είχε καμία συμμετοχή στο σχεδιασμό και τη διεξαγωγή της μελέτης, κατά τη συλλογή, διαχείριση, ανάλυση και ερμηνεία των δεδομένων ή στην προετοιμασία, διόρθωση, υποβολή και έγκριση των δημοσιευμένων άρθρων.

Stress echocardiography (SE) is a well-established and valid technique, widely-used for the diagnostic evaluation of patients with ischemic and non-ischemic cardiac diseases. This statement of the Echocardiography Working Group of the Hellenic Society of Cardiology summarizes the consensus of the writing group regarding the applications of SE, based on the expertise of their members and on a critical review of current medical literature. The main objectives of the consensus document include a comprehensive review of SE methodology and training, focusing on the preparation, the protocols used and the analysis of the SE images and an updated, evidence-based knowledge about SE applications on ischemic and non-ischemic heart diseases, such as in cardiomyopathies, heart failure and valvular heart disease.

Despite medical advancements, the prognosis of patients with heart failure remains poor. While echocardiography and cardiac magnetic resonance imaging remain at the forefront of diagnosing and monitoring patients with heart failure, cardiac computed tomography (CT) has largely been considered to have a limited role. With the advancements in scanner design, technology, and computer processing power, cardiac CT is now emerging as a valuable adjunct to clinicians managing patients with heart failure. In the current manuscript, we review the current applications of cardiac CT to patients with heart failure and also the emerging areas of research where its clinical utility is likely to extend into the realm of treatment, procedural planning, and advanced heart failure therapy implementation.

Learning objectives Coronary computed tomographic angiography (CTA) is now established as a clinically valuable non-invasive anatomical test for the detection and exclusion of significant coronary disease. A number of prospective multicentre trials have shown coronary CTA to be an ideal test for the exclusion and detection of coronary disease using invasive angiography as the reference.1–3 Despite this, owing to its relatively low positive predictive value of 48% and inability to determine functional significance,1 its use in international guidelines has generally been restricted to patients with chest pain at a low-intermediate risk of having coronary artery disease (CAD).4 For patients at an intermediate risk of CAD, functional testing is generally indicated, and for high-risk patients, invasive coronary angiography (ICA) remains the recommended diagnostic test. Although this strategy is designed to determine whether a patient’s symptoms are attributable to CAD, and specifically myocardial ischaemia, recent studies indicate that this approach has important flaws. In a study of almost 400 000 patients, Patel et al showed that up to 62% of the patients who underwent ICA in the USA were subsequently found to have no significant obstructive disease. Furthermore, of those patients with a positive stress test, approximately two-thirds had no obstructive disease and, conversely, 28% of the patients with a negative stress …

In this report, we present a 42-year-old woman without structural heart disease who underwent an implantable loop recorder implantation for recurrent syncopal episodes during the past 12 years. Four hours after implantation, the patient suffered sudden loss of consciousness while sitting on her bed in the ward. Interestingly, interrogation of the device revealed an episode of advanced atrioventricular block with a very prolonged ventricular asystole of 25 sec. We also provide a concise overview of the literature regarding the implantable loop recorder use in recurrent unexplained syncope as well as regarding idiopathic advanced atrioventricular block.

BACKGROUND: For two decades, bright-blood late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been considered the reference standard for the non-invasive assessment of myocardial viability. While bright-blood LGE can clearly distinguish areas of myocardial infarction from viable myocardium, it often suffers from poor scar-to-blood contrast, making subendocardial scar difficult to detect. Recently, we proposed a novel dark-blood LGE approach that increases scar-to-blood contrast and thereby improves subendocardial scar conspicuity. In the present study we sought to assess the clinical value of this novel approach in a large patient cohort with various non-congenital ischemic and non-ischemic cardiomyopathies on both 1.5 T and 3 T CMR scanners of different vendors.METHODS: Three hundred consecutive patients referred for clinical CMR were randomly assigned to a 1.5 T or 3 T scanner. An entire short-axis stack and multiple long-axis views were acquired using conventional phase sensitive inversion recovery (PSIR) LGE with TI set to null myocardium (bright-blood) and proposed PSIR LGE with TI set to null blood (dark-blood), in a randomized order. The bright-blood LGE and dark-blood LGE images were separated, anonymized, and interpreted in a random order at different time points by one of five independent observers. Each case was analyzed for the type of scar, per-segment transmurality, papillary muscle enhancement, overall image quality, observer confidence, and presence of right ventricular scar and intraventricular thrombus.RESULTS: Dark-blood LGE detected significantly more cases with ischemic scar compared to conventional bright-blood LGE (97 vs 89, p = 0.008), on both 1.5 T and 3 T, and led to a significantly increased total scar burden (3.3 ± 2.4 vs 3.0 ± 2.3 standard AHA segments, p = 0.015). Overall image quality significantly improved using dark-blood LGE compared to bright-blood LGE (81.3% vs 74.0% of all segments were of highest diagnostic quality, p = 0.006). Furthermore, dark-blood LGE led to significantly higher observer confidence (confident in 84.2% vs 78.4%, p = 0.033).CONCLUSIONS: The improved detection of ischemic scar makes the proposed dark-blood LGE method a valuable diagnostic tool in the non-invasive assessment of myocardial scar. The applicability in routine clinical practice is further strengthened, as the present approach, in contrast to other recently proposed dark- and black-blood LGE techniques, is readily available without the need for scanner adjustments, extensive optimizations, or additional training.

In the current manuscript, we report an unusual case of a young 18-year-old woman who survived an out-of-hospital cardiac arrest secondary to Bland-White-Garland syndrome. Her transthoracic echocardiogram showed an abnormal color Doppler flow-pattern within the myocardium indicative of coronary fistulous flow that prompted further evaluation with coronary CT angiography, which confirmed the diagnosis. Our case serves not only as a reminder to consider coronary artery anomalies as a cause of sudden cardiac death in young individuals but also as a prompt to investigate unusual echocardiographic findings with alternative imaging when the diagnosis may not be initially clear.

Background: In the present clinical trial, we compared the efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulfate (CHS) salt in patients eligible to receive clopidogrel. Methods: A prospective 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n = 1864) were screened and 1800 were enrolled in the trial and randomized to CHS or CB. Primary efficacy end point was the composite of myocardial infarction, stroke, or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium criteria. Results: At 12-month follow-up, no differences were observed between CB (n = 759) and CHS (n = 798) in primary efficacy and safety end points (age, sex, history of percutaneous coronary intervention adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.21 and OR, 0.81; 95% CI, 0.51-1.29, respectively) between CHS and CB. Analyses of efficacy and safety in subgroups that were defined according to the qualifying diagnosis revealed that there was no difference between CHS and CB. Conclusion: The efficacy and safety of CB administered for 12 months for the secondary prevention of atherothrombotic events are similar to that of CHS. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE trial; ClinicalTrials.gov Identifier:NCT02126982).

Platelet adhesion and aggregation are key functions leading to thrombus formation. The effect of aspirin, clopidogrel, and ticagrelor on platelet aggregation has been well established, however, there is limited data on the effect of these drugs on platelet adhesion. We therefore evaluated the effect of these drugs on platelet adhesion in acute coronary syndrome (ACS) patients. Citrated blood was collected from 50 ACS patients loaded with 325 mg of aspirin (baseline) and at 5 days after the administration of aspirin 100 mg/day and clopidogrel (600 mg loading dose, 75 mg/day) (n = 26) or ticagrelor (180 mg loading dose, 90 mg × 2/day) (n = 24). High on-treatment platelet reactivity (HTPR) to clopidogrel was estimated by vasodilator stimulated phosphoprotein (VASP) phosphorylation assay. Platelet adhesion to collagen was studied for 6 min under high shear stress and was evaluated using the time to platelet recruitment (TPR), the perimeter and average area of each adherent object, number of adherent objects, and the total percent of surface coverage (SC%). Six ACS patients exhibited HTPR to clopidogrel and excluded from the platelet adhesion assays. TPR and SC% values were similar among patient groups at baseline and controls. However, all other adhesion parameters were different in ACS patients, indicating the formation of more aggregates in regard to controls. At 5 days post-treatment with either clopidogrel or ticagrelor, the TPR values were increased and the SC% values were reduced to a similar extent compared with baseline. However, significant differences were observed in the ticagrelor group in the perimeter, number of adherent objects, and the average area of each adherent object indicating a more potent inhibition of adherence-induced platelet aggregation than clopidogrel. In conclusion, aspirin does not affect platelet adherence to collagen, whereas clopidogrel and ticagrelor inhibit to a similar extent dynamic platelet adhesion at 5 days post-treatment in ACS patients. However, ticagrelor exhibits a greater inhibitory effect on reducing adhesion-induced platelet aggregation.

Obesity is a worldwide health problem with epidemic proportions that has been associated with atrial fibrillation (AF). Even though the underlying pathophysiological mechanisms have not been completely elucidated, several experimental and clinical studies implicate obesity in the initiation and perpetuation of AF. Of note, hypertension, diabetes mellitus, metabolic syndrome, coronary artery disease, and obstructive sleep apnea, represent clinical correlates between obesity and AF. In addition, ventricular adaptation, diastolic dysfunction, and epicardial adipose tissue appear to be implicated in atrial electrical and structural remodeling, thereby promoting the arrhythmia in obese subjects. The present article provides a concise overview of the association between obesity and AF, and highlights the underlying pathophysiological mechanisms.

Chronic obstructive pulmonary disease (COPD) is independently associated with an increased burden of cardiovascular disease. Besides coronary artery disease (CAD) and congestive heart failure (CHF), specific electrocardiographic (ECG) abnormalities and cardiac arrhythmias seem to have a significant impact on cardiovascular prognosis of COPD patients. Disturbances of heart rhythm include premature atrial contractions (PACs), premature ventricular contractions (PVCs), atrial fibrillation (AF), atrial flutter (AFL), multifocal atrial tachycardia (MAT), and ventricular tachycardia (VT). Of note, the identification of ECG abnormalities and the evaluation of the arrhythmic risk may have significant implications in the management and outcome of patients with COPD. This article provides a concise overview of the available data regarding ECG abnormalities and arrhythmias in these patients, including an elaborated description of the underlying arrhythmogenic mechanisms. The clinical impact and prognostic significance of ECG abnormalities and arrhythmias in COPD as well as the appropriate antiarrhythmic therapy and interventions in this setting are also discussed.

Objectives The primary aim of this study was to quantify the dimensions and geometry of the mitral valve complex in patients with dilated cardiomyopathy and significant mitral regurgitation. The secondary aim was to evaluate the validity of an automated segmentation algorithm for assessment of the mitral valve compared to manual assessment on computed tomography. Background Transcatheter mitral valve replacement (TMVR) is an evolving technique which relies heavily on the lengthy evaluation of cardiac computed tomography (CT) datasets. Limited data is available on the dimensions and geometry of the mitral valve in pathological states throughout the cardiac cycle, which may have implications for TMVR device design, screening of suitable candidates and annular sizing prior to TMVR. Methods A retrospective study of 15 of patients with dilated cardiomyopathy who had undergone full multiphase ECG gated cardiac CT. A comprehensive evaluation of mitral valve geometry was performed at 10 phases of the cardiac cycle using the recommended D-shaped mitral valve annulus (MA) segmentation model using manual and automated CT interpretation platforms. Mitral annular dimensions and geometries were compared between manual and automated methods. Results Mitral valve dimensions in patients with dilated cardiomyopathy were similar to previously reported values (MAarea Diastole: 12.22 ± 1.90 cm2), with dynamic changes in size and geometry between systole and diastole of up to 5%. The distance from the centre of the MA to the left ventricular apex demonstrated moderate agreement between automated and manual methods (ρc = 0.90) with other measurements demonstrating poor agreement between the two methods (ρc = 0.75–0.86). Conclusions Variability of mitral valve annulus measurements are small during the cardiac cycle. Novel automated algorithms to determine cardiac cycle variations in mitral valve geometry may offer improved segmentation accuracy as well as improved CT interpretation times.

Background— Computed tomography aortic valve calcium scoring (CT-AVC) holds promise for the assessment of patients with aortic stenosis (AS). We sought to establish the clinical utility of CT-AVC in an international multicenter cohort of patients. Methods and Results— Patients with AS who underwent ECG-gated CT-AVC within 3 months of echocardiography were entered into an international, multicenter, observational registry. Optimal CT-AVC thresholds for diagnosing severe AS were determined in patients with concordant echocardiographic assessments, before being used to arbitrate disease severity in those with discordant measurements. In patients with long-term follow-up, we assessed whether CT-AVC thresholds predicted aortic valve replacement and death. In 918 patients from 8 centers (age, 77±10 years; 60% men; peak velocity, 3.88±0.90 m/s), 708 (77%) patients had concordant echocardiographic assessments, in whom CT-AVC provided excellent discrimination for severe AS (C statistic: women 0.92, men 0.89). Our optimal sex-specific CT-AVC thresholds (women 1377 Agatston unit and men 2062 Agatston unit) were nearly identical to those previously reported (women 1274 Agatston unit and men 2065 Agatston unit). Clinical outcomes were available in 215 patients (follow-up 1029 [126–2251] days). Sex-specific CT-AVC thresholds independently predicted aortic valve replacement and death (hazard ratio, 3.90 [95% confidence interval, 2.19–6.78]; P P =0.010). Conclusions— Sex-specific CT-AVC thresholds accurately identify severe AS and provide powerful prognostic information. These findings support their integration into routine clinical practice. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT01358513, NCT02132026, NCT00338676, NCT00647088, NCT01679431.

Background: Triflusal has demonstrated an efficacy similar to aspirin in the prevention of vascular events in patients with acute myocardial infarction (ΜΙ) and ischaemic stroke but with less bleeding events. Objective: We performed a randomised, multicentre, phase 4 clinical trial to compare the clinical efficacy and safety of triflusal versus aspirin, administered for 12 months in patients eligible to receive a cyclooxygenase-1 (COX-1) inhibitor. Methods: Patients with stable coronary artery disease or with a history of non-cardioembolic ischaemic stroke were randomly assigned to receive either triflusal 300 mg twice or 600 mg once daily or aspirin 100 mg once daily for 12 months. The primary efficacy endpoint was the composite of: (a) ΜΙ, (b) stroke (ischaemic or haemorrhagic), or, (c) death from vascular causes for the entire follow-up period. The primary safety endpoints were the rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. Results: At 12-month follow-up, an equivalent result was revealed between the triflusal (n=559) and aspirin (n=560) in primary efficacy endpoint. Specifically, the combined efficacy outcome rate (i.e. MI, stroke or death from vascular causes) difference was equal to -1.3% (95% confidence interval -1.1 to 3.5) and lied within the a-priori defined equivalence interval (p Conclusion: The efficacy of triflusal in the secondary prevention of vascular events is similar to aspirin when administered for 12 months. Importantly, triflusal significantly reduced the incidence of ΜΙ and showed a better safety profile compared with aspirin. : (ASpirin versus Triflusal for Event Reduction In Atherothrombosis Secondary prevention, ASTERIAS trial; Clinical Trials.gov Identifier: NCT02616497).

A 61-year-old man with type II diabetes mellitus was referred with breathlessness on exertion. On auscultation, there was a continuous ejection systolic murmur on the left upper sternal border. Transthoracic echocardiography showed a dilated vessel in aortic wall in the parasternal long axis view () and a spherical lesion in the apical 4-chamber view (). A coronary computed tomographic angiographic (CTCA) study revealed a dilated and ectatic right coronary artery (RCA). It arose from the ascending aorta at the 12 [...]

There is considerable interest in transcatheter prosthetic valve treatment for mitral valve disease in high-risk individuals. Although the presence of mitral annular calcium (MAC) may provide an anchoring zone for such devices, results to date have been modest with reported technical failure rates approaching 30% in specialist centers. This in part relates to the risk of left ventricular outflow tract obstruction and device dislodgment but also to the lack of specific imaging guidelines to plan for such procedures. We present the use of finite element analysis and computer simulation based on cardiac CT in three patients with severe MAC in whom transcatheter devices were considered. In the first two cases, the computer simulations were performed after the clinical procedure and were concordant with the clinical outcome. For the third case, computer simulation was performed prior to the clinical procedure. This indicated unsuitability for transcatheter device deployment and a subsequent medical management was adopted. Overall, our initial results suggest that computer simulation may have the potential to improve patient selection for transcatheter mitral valve replacement in the presence of significant MAC.

Iatrogenic acute aortic dissection during percutaneous coronary intervention is an extremely rare but critical complication. Although sealing the entry point with a coronary stent is an option to treat localized dissections, more extensive cases may require surgical intervention. We present a case of Type A aortic dissection that occurred during an angioplasty of a chronically occluded right coronary artery. Despite the extent of the dissection, a 'watch-and-wait' strategy was chosen, and repeated imaging a few days later revealed that the aorta had been remodelled to its normal anatomy.

Background Few data exist about the implementation of contemporary oral antiplatelet treatment guidelines in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods GReek AntiPlatelet rEgistry (GRAPE), initiated on January 2012, is a prospective, observational, multicenter cohort study focusing on contemporary use of P2Y12 inhibitors. In 1434 patients we evaluated appropriateness of P2Y12 selection initially and at discharge by applying an eligibility-assessing algorithm based on P2Y12 inhibitors' contraindications/specific warnings and precautions. Results Appropriate, less preferable and inappropriate P2Y12 inhibitor selections were made initially in 45.8%, 47.2% and 6.6% and at discharge in 64.1%, 29.2% and 6.6% of patients, respectively. The selection of clopidogrel was most commonly less preferable, both initially (69.7%) and at discharge (75.6%). Appropriate selection of newer agents was high initially (79.2%–82.8%), with further increase as selection at discharge (89.4%–89.8%). Inappropriate selection of the newer agents was 17.2%–20.8% initially, decreasing to 10.2%–10.6% at discharge. Conditions and co-medications related to increased bleeding risk, presentation with ST elevation myocardial infarction and the absence of reperfusion within the first 24h were the most powerful predictors of appropriate P2Y12 selection initially, whereas age ≥75years, conditions and co-medications related to increased bleeding risk and regional trends mostly affected appropriate P2Y12 selection at discharge. Conclusions In GRAPE, adherence with the recently released guidelines on oral antiplatelet therapy was satisfactory. Clopidogrel was most commonly used as a less preferable selection, while prasugrel or ticagrelor selection was mostly appropriate. Certain factors may predict initial and at discharge guideline implementation. Clinical Trial Registration -clinicaltrials.gov Identifier: NCT01774955 http://clinicaltrials.gov/.

Ischemic heart disease and cerebrovascular disease remain major health problems with associated mortality and quality-of-life consequences. Antiplatelet agents, including thienopyridines and the new P2Y12 inhibitors, have been shown to improve survival in the secondary prevention setting. We review the available evidence on the effectiveness and safety of previous established as well as novel antithrombotic agents in the secondary prevention of cardiovascular disease with a special focus on cerebrovascular disease.

Obstructive prosthetic valve thrombosis (PVT) is a rare but severe complication that usually occurs in the presence of suboptimal anticoagulation. Although fluoroscopy is commonly used to detect abnormal leaflet motion as a surrogate marker for PVT, its inability to directly visualize adjacent tissue and valve physiology leaves it susceptible to miss clinically important PVT. In this manuscript, we report the case of a 54-year-old woman with a mechanical mitral valve who was admitted to our institute with exertional dyspnea. Although valve fluoroscopy was normal, subsequent 3D echocardiography and ECG-gated multiphase computed tomography confirmed the presence of PVT that was subsequently treated successfully with surgical replacement. Our case demonstrates the utility of multimodality imaging in establishing PVT in patients with abnormal prosthetic valve physiology and progressive symptoms.

The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. In this study we compared the antiplatelet effectiveness of a generic clopidogrel salt, clopidogrel besylate (CB), with the original CHS in patients with an ACS.Ninety-six ACS patients were randomized to receive a 600-mg loading dose of either CHS (n = 45) or CB (n = 51), followed by 75 mg/day. Sixty-eight patients underwent a percutaneous coronary intervention (PCI), whereas 28 were treated conservatively. Platelet aggregatory response, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression and platelet-leucocyte conjugates were determined before clopidogrel loading (baseline), as well as at 5 days and at 1 month afterwards.No difference in the clopidogrel response variability was observed between patients receiving CHS or CB either at 5 days or at 1 month of follow-up. Similarly, no difference in the inhibition of platelet aggregation, P-selectin expression or in the platelet-leucocyte conjugates was observed between CHS and CB group during the follow-up.There is no overall significant difference in the antiplatelet efficacy between CB and CHS during their administration in ACS patients for up to 1 month after the episode.

The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. We compared the antiplatelet effectiveness of long-term administration of the original CHS with a generic clopidogrel besylate (CB) salt formulation in 86 patients with a history of an ACS. At 1 month after the episode, patients receiving 75 mg/d CHS were randomized to continue with CHS (n = 41) or to switch to 75 mg/d CB (n = 45). Platelet aggregation, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression, and platelet–leucocyte conjugates were determined before randomization and at 6 months afterward. No difference in any platelet parameter studied was observed between the 2 groups either before randomization or after 6 months of treatment with CHS or CB. We conclude that there is no difference in the antiplatelet efficacy between CB and CHS during long-term administration in patients with a history of an ACS.

Saccharomyces boulardii has been and continues to be extensively used as a probiotic, with only rare associations with fungemia. This study evaluated the virulence of this yeast when given as a probiotic, and its role in preventing gastrointestinal (GI) colonization by Candida . Adult male Crl:CD1 (ICR) BR mice were given S. boulardii orally in three different doses or normal saline for 14 days. Stool cultures were performed at the time of discontinuation of yeast administration, as well as 1 and 2 weeks later. Gut colonization was proportional to the given dose but lasted only 1 week and no dissemination of the yeast was detected. S. boulardii was also given for 2 and 4 weeks to mice fed chow containing Candida albicans . S. boulardii in the gut did not affect Candida GI colonization. These fi ndings suggest that oral administration of S. boulardii induces a substantial but short term increase of this yeast in the intestinal lumen and administration of the probiotic does not prevent subsequent GI colonization by C. albicans .

Background: The aim of the present interim analysis was to compare the clinical efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulphate (CHS) salt in patient groups eligible to receive clopidogrel. Methods: A 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n=1,864) were screened and 1,800 were enrolled in the trial and randomized to CHS (n=759) or CB (n=798). Primary efficacy end point was the composite of myocardial infarction, stroke or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. Results: At 6-months follow-up no differences were observed between CB and CHS in primary efficacy end point (OR, 0.80; 95% CI, 0.37 to 1.71; p=0.57). Rates of BARC-1,-2,-3a and -5b bleeding were similar between the two study groups whereas no bleeding events according to BARC-3b, -3c, -4 and -5a were observed in either CHS or CB group. Conclusion: The clinical efficacy and safety of the generic CB is similar to that of the innovator CHS salt, thus, it can be routinely used in the secondary prevention of atherothrombotic events for a period of at least 6 months. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE study Clinical Trials.gov Identifier: NCT02126982).

Atrial fibrillation is the most common arrhythmia in athletes and may be associated with endurance sport practice. Atrial ectopic beats, chronic systemic inflammation, autonomic system alterations, anatomic adaptation, myocardial injury and illicit drugs seem to be implicated in the increased prevalence of atrial fibrillation in athletes, but clear evidence is lacking. Treatment of the arrhythmia is a challenging issue, as atrial fibrillation may impair athletic performances and deteriorate athletes' quality of life. This review focuses on the epidemiology, possible pathophysiological mechanisms, and management of atrial fibrillation in athletes.

Diabetes mellitus (DM) represents one of the most important risk factors for atrial fibrillation (AF) while AF is a strong and independent marker of overall mortality and cardiovascular morbidity in diabetic patients. Autonomic, electrical, electromechanical, and structural remodeling, including oxidative stress, connexin remodeling and glycemic fluctuations seem to be implicated in AF pathophysiology in the setting of DM. The present review highlights the association between DM and AF, provides a comprehensive overview of the responsible pathophysiological mechanisms and briefly discusses potential upstream therapies for DM-related atrial remodeling.

The prevalence of contraindications/special warnings and precautions (CON/SWP) for clopidogrel, prasugrel and ticagrelor use is not adequately studied and might affect P2Y12 inhibitor choice in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).In the context of the GReek AntiPlatelet rEgistry (GRAPE) a detailed recording of CON/SWP for use of clopidogrel, prasugrel and ticagrelor was done for 1,280 consecutive, moderate-high-risk ACS patients undergoing PCI. At least 1 CON for use of clopidogrel, prasugrel and ticagrelor was present in 5 (0.4%), 49 (3.8%) and 12 patients (0.9%), respectively. Prevalence of at least 1 CON/SWP to clopidogrel (45.8%) was less frequent compared to prasugrel (49.1%) or ticagrelor (49.1%; P=0.02 and P=0.04, respectively), while 34% of patients had at least 1 CON/SWP to all the 3 P2Y12 inhibitors. At discharge, 482 (38.6%), 301 (24.1%) and 464 patients (37.2%) received clopidogrel, prasugrel and ticagrelor, respectively. Age ≥75 years, co-medication related to increased bleeding risk, and history of asthma/chronic obstructive pulmonary disease favored clopidogrel vs. prasugrel or ticagrelor use as discharge medication, while geographic region also affected this choice (C-statistic, 0.81; 95% CI: 0.78-0.83).In patients with ACS undergoing PCI the prevalence of CON to antiplatelet agents is low, whereas that of SWP is high. Certain SWP, along with regional trends may affect the choice of newer P2Y12 inhibitors vs. clopidogrel.

Purpose: Data on in-hospital bleeding events with the concurrent use of clopidogrel, prasugrel and ticagrelor in real-life practice are lacking. Methods: In the context of GReek AntiPlatelet rEgistry (GRAPE), a prospective, observational, multicenter cohort study conducted in in 8 PCI-capable hospitals in Greece, we investigated in-hospital bleeding events (Bleeding Academic Research Consortium -BARC classification) in ACS patients undergoing percutaneous coronary intervention (PCI). Results: Between January and December 2012, 1280 patients were included in analysis (82.8% men, 22.7% diabetics, 53.5% admitted with ST elevation myocardial infarction (STEMI), with a mean age of 61.8±12.4 years). Overall, in-hospital bleeding BARC type 1, 2 3a and 3b occurred in 54 (4.2%), 31 (2.4%), 21 (1.6%) and 5 (0.4%) patients respectively. No fatal bleeding event occurred. In the subgroup of patients who were initially treated either with clopidogrel (N=478), prasugrel (N=92) or ticagrelor (N=228) without switching thereafter, multivariate analysis (backward logistic regression) revealed age≥75 years and recent/recurrent gastrointestinal (GI) bleeding as predictive factors of in-hospital bleeding BARC of any type (OR=2.14, 1.21-3.80 95% CIs, p=0.009 and OR=6.48, 1.13-37.2 95% CIs, p=0.04 respectively). In 215 propensity-matched pairs of patients, rate of in-hospital bleeding BARC of any type did not differ significantly between clopidogrel vs prasugrel or ticagrelor -treated patients (3.7% vs 7.9%, p=0.098). Conclusions: In a real-world PCI-treated ACS population, older age and previous GI bleeding are associated with an increased risk of low to moderate severity in-hospital bleeding events. A trend towards more bleeding with the newer agents is apparent.