Use of Sodium–Glucose Cotransporter 2 (SGLT-2) Inhibitors Beyond Diabetes: On the Verge of a Paradigm Shift?

The sodium–glucose co-transporter 2 (SGLT2) inhibitors have proven effective in glycemia control in patients with type 2 diabetes (T2D) by increasing urinary glucose excretion. However, the beneficial effects of SGLT2 inhibition extend beyond glycemic control, with new studies demonstrating beneficial effects that lead to improved cardiovascular (CV) (cardioprotection) and renal outcomes (renoprotection) in patients with T2D. Pivotal CV outcomes trials have demonstrated a 27-35% reduction in heart failure (HF) hospitalizations in patients with T2D. Importantly, a variety of pleiotropic effects of these new agents have been identified that include, but are not limited to, anti-atherosclerotic, anti-inflammatory, and anti-oxidant effects, decreased vascular stiffness and improved endothelial function, weight loss, reduction in sympathetic activity and in cardiac arrhythmogenesis. Ongoing studies are investigating these actions in patients with and without diabetes. Such results, if positive, may lead to a paradigm shift in the management of CV, renal and even other diseases beyond diabetes. Rhythmos 2020;15(1):67-71

Hybrid Heart Failure Treatment

A case of refractory heart failure (HF) is presented in a 64-year-old gentleman with ischemic cardiomyopathy and severe left ventricular dysfunction, who availed himself of currently available hybrid HF treatment, like optimal medical treatment, electrical and interventional therapies comprising drugs, an implantable cardiac resynchronization therapy defibrillator (CRT-D) effected via alternate route (middle cardiac vein) for left ventricular lead placement combined with percutaneous mitral valve therapy (MitraClip) that prolonged his life to ~10 years. Rhythmos 2021; 16(1):99-101

Eggshell Calcification of the Heart

   A case of a patient with extensive egg-shell calcification of the pericardium is presented without signs of constriction. This was imaged by fluoroscopy during an ablation procedure performed for persistent atrial fibrillation.  Rhythmos 2022; 17(1):105-106

Cardiology News / Recent Literature Review / Last Quarter 2019

HCS Working Groups: Thessaloniki, 20-22/2/2020 ACC Meeting: Chicago, IL, USA, 28-30/3/2020 EHRA Meeting: Vienna, 29-31/3/2020 HRS Meeting: San Diego, 6-9/5/2020 EuroPCR: Paris, 19-22/5/2020 ESC Meeting: Amsterdam, 29/8-2/9/2020 Childhood Secondhand Smoke Exposure Predicts Increased Risk for Adulthood Atrial Fibrillation (AF) After Adjustment for AF Risk Factors A study analyzed Framingham Offspring cohort participants with parents in the Original cohort with known smoking status during the offspring’s childhood, evaluated every 2-8 years and being under routine surveillance for incident AF. Of 2,816 Offspring cohort participants with at least 1 parent in the Original cohort, 82% were exposed to parental smoking. For every pack/day increase in parental smoking, there was an 18% increase in offspring AF incidence (adjusted hazard ratio - HR: 1.18; p=0.04). Additionally, parental smoking was a risk factor for offspring smoking (adjusted odds ratio - OR: 1.34; p<0.001). Offspring smoking mediated 17% of the relationship between parental smoking and offspring AF (Groh CA et al, J Am Coll Cardiol 2019; 74:1658-64). When Left Untreated, Severe Aortic Stenosis (AS) is Associated With Poor Long-Term Survival / But Also Moderate AS Confers Poor Survival Rates Among 16,129 (6.7%), 3,315 (1.4%), and 6,383 (2.6%) patients had mild, moderate, and severe AS, respectively, on an adjusted basis (vs. no AS; 5-year mortality 19%), patients with mild to severe AS had an increasing risk of long-term mortality (adjusted hazard ratio: 1.44-2.09; p<0.001 for all comparisons). The 5-year mortality was 56% and 67%, respectively, in those with moderate AS (mean gradient 20.0-39.0 mmHg/peak velocity 3.0-3.9 m/s) and severe AS (≥40 mmHg, ≥4 m/s, or AV area<1 cm2 in low-flow, low-gradient severe AS). A markedly increased risk of death from all causes (5-year mortality >50%) and CV disease was evident from a mean AV gradient >20 mmHg (moderate AS) after adjusting for age, sex, LV systolic or diastolic dysfunction, and aortic regurgitation (Strange G et al, J Am Coll Cardiol 2019; 74:1851-63). Premature (Age≤45 Years) Acute or Stable Obstructive Coronary Artery Disease (CAD) is an Aggressive Disease Despite the Currently Recommended Prevention Measures, With High Rates of Recurrent Events and Mortality Among 880 patients with premature CAD, aged 40.1 ± 5.7 years, mainly men, smokers, with a family history of CAD or hypercholesterolemia, at baseline presentation, 91% underwent coronary revascularization, predominantly for acute MI (79%). Over 20 years, one-third (n = 264) of patients presented with a total of 399 ischemic events, and 36% had at least a second recurrent event. MI was the most frequent first recurrent event (n=131 of 264), mostly related to new coronary lesions (17% vs 8%; p=0.01; hazard ratio - HR: 1.45 for new vs initial culprit lesion). All-cause death (n=55; 6.3%) occurred at 8.4 years (median time). Ethnic origin (sub-Saharan African vs. Caucasian, adjusted HR - adjHR: 1.95; p=0.02), inflammatory disease (adjHR: 1.58; p=0.03), and persistent smoking (adjHR: 2.32; p<0.01) were the strongest correlates of a first recurrent event. When considering all recurrent events, the same factors and Asian ethnicity predicted poor outcome, but persistent smoking had the greatest impact on prognosis (Collet J-P et al, J Am Coll Cardiol 2019; 74:1868-78)... (excerpt

Cardiology News / Recent Literature Review / Last Quarter 2019

HCS Working Groups: Thessaloniki, 20-22/2/2020 ACC Meeting: Chicago, IL, USA, 28-30/3/2020 EHRA Meeting: Vienna, 29-31/3/2020 HRS Meeting: San Diego, 6-9/5/2020 EuroPCR: Paris, 19-22/5/2020 ESC Meeting: Amsterdam, 29/8-2/9/2020 Childhood Secondhand Smoke Exposure Predicts Increased Risk for Adulthood Atrial Fibrillation (AF) After Adjustment for AF Risk Factors A study analyzed Framingham Offspring cohort participants with parents in the Original cohort with known smoking status during the offspring’s childhood, evaluated every 2-8 years and being under routine surveillance for incident AF. Of 2,816 Offspring cohort participants with at least 1 parent in the Original cohort, 82% were exposed to parental smoking. For every pack/day increase in parental smoking, there was an 18% increase in offspring AF incidence (adjusted hazard ratio - HR: 1.18; p=0.04). Additionally, parental smoking was a risk factor for offspring smoking (adjusted odds ratio - OR: 1.34; p<0.001). Offspring smoking mediated 17% of the relationship between parental smoking and offspring AF (Groh CA et al, J Am Coll Cardiol 2019; 74:1658-64). When Left Untreated, Severe Aortic Stenosis (AS) is Associated With Poor Long-Term Survival / But Also Moderate AS Confers Poor Survival Rates Among 16,129 (6.7%), 3,315 (1.4%), and 6,383 (2.6%) patients had mild, moderate, and severe AS, respectively, on an adjusted basis (vs. no AS; 5-year mortality 19%), patients with mild to severe AS had an increasing risk of long-term mortality (adjusted hazard ratio: 1.44-2.09; p<0.001 for all comparisons). The 5-year mortality was 56% and 67%, respectively, in those with moderate AS (mean gradient 20.0-39.0 mmHg/peak velocity 3.0-3.9 m/s) and severe AS (≥40 mmHg, ≥4 m/s, or AV area<1 cm2 in low-flow, low-gradient severe AS). A markedly increased risk of death from all causes (5-year mortality >50%) and CV disease was evident from a mean AV gradient >20 mmHg (moderate AS) after adjusting for age, sex, LV systolic or diastolic dysfunction, and aortic regurgitation (Strange G et al, J Am Coll Cardiol 2019; 74:1851-63). Premature (Age≤45 Years) Acute or Stable Obstructive Coronary Artery Disease (CAD) is an Aggressive Disease Despite the Currently Recommended Prevention Measures, With High Rates of Recurrent Events and Mortality Among 880 patients with premature CAD, aged 40.1 ± 5.7 years, mainly men, smokers, with a family history of CAD or hypercholesterolemia, at baseline presentation, 91% underwent coronary revascularization, predominantly for acute MI (79%). Over 20 years, one-third (n = 264) of patients presented with a total of 399 ischemic events, and 36% had at least a second recurrent event. MI was the most frequent first recurrent event (n=131 of 264), mostly related to new coronary lesions (17% vs 8%; p=0.01; hazard ratio - HR: 1.45 for new vs initial culprit lesion). All-cause death (n=55; 6.3%) occurred at 8.4 years (median time). Ethnic origin (sub-Saharan African vs. Caucasian, adjusted HR - adjHR: 1.95; p=0.02), inflammatory disease (adjHR: 1.58; p=0.03), and persistent smoking (adjHR: 2.32; p<0.01) were the strongest correlates of a first recurrent event. When considering all recurrent events, the same factors and Asian ethnicity predicted poor outcome, but persistent smoking had the greatest impact on prognosis (Collet J-P et al, J Am Coll Cardiol 2019; 74:1868-78)... (excerpt

Στοχαστική ανάλυση και βέλτιστος σχεδιασμός κατασκευών υποκείμενων σε θραύση

232 σ.Η παρούσα διατριβή ασχολείται με τη στοχαστική ανάλυση και το βέλτιστο σχεδιασμό κατασκευών που υπόκεινται σε θραύση, σε ένα ενοποιημένο πλαίσιο βασισμένο στις σύγχρονες αριθμητικές τεχνικές προσομοίωσης των φαινομένων θραύσης που προφέρουν τα εμπλουτισμένα πεπερασμένα στοιχεία. Η διαμόρφωση του πλαισίου αυτού, γίνεται εφικτή αφενός στη βάση της μεθόδου των στοχαστικών πεπερασμένων στοιχείων, αφετέρου εντός ενός σύγχρονου περιβάλλοντος βελτιστοποίησης με τη χρήση μεταευρετικών αλγορίθμων αναζήτησης (metaheuristic search algorithms). Στο πρώτο μέρος της διατριβής, προτείνεται η σύζευξη της μεθόδου των στοχαστικών πεπερασμένων στοιχείων και της διαδοχικής γραμμικής ανάλυσης (sequentially linear analysis), παρέχοντας λύσεις στα μη-γραμμικά στατικά προβλήματα κατασκευών από υλικά που χαρακτηρίζονται από χαλάρωση, των οποίων οι ιδιότητες είναι τυχαία κατανεμημένες εντός της δομής τους. Η αβεβαιότητα που χαρακτηρίζει τις ιδιότητες του υλικού, ποσοτικοποιείται με τη χρήση της θεωρίας των στοχαστικών συναρτήσεων (διαδικασίες/πεδία) και η μεταβλητότητα στην απόκριση των κατασκευών υπολογίζεται με τη μέθοδο της άμεσης προσομοίωσης Monte Carlo. Επιπλέον, εξετάζονται η επίδραση της μεταβολής της κάθε τυχαίας παραμέτρου, η κατανομή της συνάρτησης πιθανότητας, ο συντελεστής διακύμανσης καθώς και το μήκος συσχέτισης των στοχαστικών πεδίων. Η ανάλυση δύο κατασκευών αναφοράς έδειξε ότι οι καμπύλες φορτίου-μετατόπισης και η πιθανότητα αστοχίας επηρεάζονται έντονα από τα στατιστικά χαρακτηριστικά των στοχαστικών πεδίων. Στο δεύτερο μέρος της διατριβής, η μέθοδος των εκτεταμένων πεπερασμένων στοιχείων (extended finite element method) συνιστά ένα κατάλληλο πλαίσιο για την προσομοίωση της διαδικασίας θραύσης σε κατασκευές υποκείμενες σε κόπωση. Προτείνεται μια ανάλυση αξιοπιστίας με στόχο την διερεύνηση της σχέσης μεταξύ των γεωμετρικών χαρακτηριστικών των κατασκευών και της διάρκειας ζωής αυτών. Κατά τη διαδικασία βέλτιστου σχεδιασμού λαμβάνονται υπόψη, η τυχαιότητα στη θέση της αρχικής ατέλειας και η αβεβαιότητα στις ιδιότητες του υλικού των κατασκευών με την εισαγωγή συγκεκριμένων πιθανοτικών περιορισμών στην διατύπωση των προβλημάτων βελτιστοποίησης. Προκειμένου να επιλεχθεί ο κατάλληλος μεταευρετικός αλγόριθμος για την επίλυση των προβλημάτων βελτιστοποίησης, διεξήχθη ανάλυση ευαισθησίας τεσσάρων αλγορίθμων βασισμένων στη εξελικτική διαδικασία (evolutionary algorithms). Το πεδίο εφαρμογής των προτεινόμενων διατυπώσεων διερευνάται με δύο χαρακτηριστικά αριθμητικά παραδείγματα. Αποδεικνύεται ότι με τις κατάλληλες αλλαγές στη γεωμετρία των κατασκευών, η διάρκεια ζωής τους μπορεί να ενισχυθεί σημαντικά και ακολουθεί σύγκριση των βέλτιστων γεωμετρικών μορφών που προκύπτουν για τα επιθυμητά επίπεδα διάρκειας ζωής. Η επιλογή ως προς την θέση της αρχικής ατέλειας και ο προσανατολισμός αυτής βρέθηκαν επίσης να έχουν σημαντική επίδραση στις βέλτιστες γεωμετρικές μορφές.The present thesis deals with a unified framework for stochastic analysis and optimum design of structures subjected to fracture developed in the ambit of modern numerical techniques for crack growth simulation mainly based on enriched finite elements methods. This has been done within the context of the stochastic finite element method as well as within a modern optimization environment implementing metaheuristic search algorithms. In the first part of this thesis, the stochastic finite element method is presented within the framework of the sequentially linear analysis (SLA) scheme, providing solutions to stochastic nonlinear static problems for structures made with softening materials whose properties are randomly distributed in the structure, but also giving specific information on the probability of failure. The uncertainty characterizing the material properties, is quantified by using the theory of stochastic functions (processes/fields). The response variability of the structures is computed by means of the direct Monte Carlo simulation. Furthermore, the influence of the variation of each random parameter, the probability distribution, coefficient of variation and correlation length of the stochastic fields are examined. The analysis of two benchmark structures has shown that the load-displacement curves and the probability of failure are strongly affected by the statistical characteristics of the stochastic fields. This extension of SLA to the stochastic framework offers an efficient means to perform parametric investigations of the fracture behavior of structures in the case of variable material properties. In the second part of this thesis, the extended finite element method which consists an appropriate framework for the simulation of the fracture process in structural members caused by fatigue, is incorporated into a shape optimization environment. A reliability analysis combined with a structural shape design optimization formulation is proposed where probabilistic constraints are considered in the formulation of the design optimization problem. Shape design optimization problems are formulated aiming at investigating the relation between structural geometry and service life in the design process. Randomness on the crack initialization along with the uncertainty on the material properties are also examined. A sensitivity analysis of four optimization algorithms based on evolution process is conducted in order to identify the best algorithm for solving the structural shape optimization problem. The applicability and potential of the formulations presented are demonstrated with two characteristic numerical examples. It is shown that with proper shape changes, the service life of structural members subjected to fatigue loads can be enhanced significantly. Comparisons with optimized shapes found for targeted service life are also addressed, while the choice of initial imperfection position and orientation was found to have a significant effect on the optimal shapes.Μανώλης Σ. Γεωργιουδάκη

Measuring the effects of political unrest on the tourist industry : the case of Cyprus

The objective of this paper is to determine how political events, such as the Turkish Invasion of Cyprus, the Lebanese Conflict and the Gulf War, affected the growth of tourism in Cyprus. The paper, by using four regression models, proves that political instabilities in Cyprus and/or neighboring countries had detrimental effect on the tourism of Cyprus.peer-reviewe

Micro RNAs: a Revolutionary Discovery in Biology

MicroRNAs (miRNAs) are endogenous, single-stranded, short, noncoding ribonucleic acids (RNAs), which can bind to their target messenger RNAs (mRNAs), leading to the inhibition of translation or degradation of the mRNA. Only recently have scientists discovered the important role that miRNAs play in gene regulation. To date, more than 700 miRNAs have been identified from the human genome. Malfunctioning miRNAs have been implicated in a number of diseases, due to their regulatory functions in transcription, signal transduction, cell cycle regulation, proliferation, cell growth and metabolism, cell apoptosis, and neurogenesis. Absence of miRNAs or their mutations, detected by genetic analysis, has been associated with a broad spectrum of disease processes, such as various cancers and autoimmune, cardiovascular, infectious, metabolic, neurodegenerative, skin, and psychiatric diseases. The large progress made in understanding miRNAs also points to their great potential as new biomarkers in the diagnosis and early detection of various diseases, as well as their promising role in future therapeutics