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Objective In 2008, the radiofrequency ablation (RFA) procedures registry of the Hellenic Society of Cardiology was created. This online database allowed electrophysiologists around the country to input data for all performed ablation procedures. The aim of this study is to provide a thorough report and interpretation of the data submitted to the registry between 2008 and 2018. Methods In 2008, a total of 27 centers/medical teams in 24 hospitals were licensed to perform RFA in Greece. By 2018, the number had risen to 31. Each center was tasked with inserting their own data into the registry, which included patient demographics (anonymized), type of procedure and technique, complications, and outcomes. Results A total of 18587 procedures in 17900 patients were recorded in the period of 2008-2018. By 2018, slightly more than 70% of procedures were performed in 7 high-volume centers (>100 cases/year). The most common procedure since 2014 was atrial fibrillation ablation, followed by atrioventricular nodal reentry tachycardia ablation. Complication rates were low, and success rates remained high, whereas the 6-month relapse rates declined steadily. Conclusion This online RFA registry has proved that ablation procedures in Greece have reached a very high standard, with results and complication rates comparable to European and American standards. Ablation procedures for atrial fibrillation are increasing constantly, with it being the most common intervention over the last 6-year period, although the absolute number of procedures still remains low, compared to other European countries.

Soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) has been shown to have both pro- and anti-apoptotic activities and is associated to better prognosis in heart failure. The aim of this study was to determine the transcardiac concentration gradient of sTRAIL and inflammatory biomarkers after AF cardioversion and assess their relation to AF recurrence.We measured transcardiac gradients (coronary sinus concentration minus aortic root concentration) of sTRAIL, C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with non-valvular AF after electrical cardioversion. Six-month AF recurrence was the study endpoint.There were no differences in sTRAIL and hsCRP concentrations in peripheral venous blood between patients with and without AF recurrence (p=0.066 and 0.149, respectively), while IL-6 was higher in patients with recurrence (p=0.032). Only sTRAIL showed a significant transcardiac gradient [3 pg/mL (IQR 1-4 pg/mL); p=0.01]. sTRAIL gradient was 4 pg/mL (IQR 3-5 pg/mL) in patients without recurrence versus -1 pg/mL (IQR -2-1 pg/mL) in those with recurrence (p0.001). IL-6 (p=0.281) and hsCRP (p=0.979) aortic concentrations were not significantly different from coronary sinus concentrations. In multivariate analysis, sTRAIL transcardiac gradient (beta -0.81, p=0.004) remained a negative predictor of AF recurrence.This study demonstrates the existence of a significant transcardiac sTRAIL concentration gradient in patients with non-valvular AF, inversely associated to AF recurrence. These results suggest production of sTRAIL by the heart and a protective role against substrate-altering processes in AF-prone atria. This could have implications for TRAIL-targeting therapies currently under development.

Objectives The aim of the present study was to assess the efficacy of remote ischemic post-conditioning (RIPC) by repeated intermittent balloon inflations in preventing acute kidney injury (AKI) in patients with a non–ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). Background AKI complicating PCI is associated with increased morbidity and mortality. Remote ischemic preconditioning, using cycles of upper limb ischemia-reperfusion as a conditioning stimulus, has been recently shown to prevent AKI in patients undergoing elective coronary angiography. Methods Eligible patients were randomized to receive RIPC by cycles of inflation and deflation of the stent balloon during PCI or a sham procedure (control patients). The primary endpoint was AKI, defined as an increase of ≥0.5 mg/dl or ≥25% in serum creatinine within 96 h from PCI. The 30-day rate of death or re-hospitalization for any cause was one of the secondary endpoints. Results A total of 225 patients were included (median age, 68 years; 36% female). The AKI rate in the RIPC group was 12.4% versus 29.5% in the control group (p = 0.002; odds ratio: 0.34; 95% confidence interval: 0.16 to 0.71). The number needed to treat to avoid 1 case of AKI was 6 (95% confidence interval: 3.6 to 15.2). The 30-day rate of death or re-hospitalization for any cause was 22.3% in the control group versus 12.4% in RIPC patients (p = 0.05). Conclusions RIPC by serial balloon inflations and deflations during PCI was found to confer protection against AKI in patients with a non–ST-segment elevation myocardial infarction undergoing PCI. The reduction in the rate of AKI translated into a clear trend (of borderline significance) toward better 30-day clinical outcome.

Objectives This study sought to test the hypothesis that colchicine treatment after percutaneous coronary intervention (PCI) can lead to a decrease in in-stent restenosis (ISR). Background ISR rates are particularly high in certain patient subsets, including diabetic patients, especially when a bare-metal stent (BMS) is used. Pharmacological interventions to decrease ISR could be of clinical relevance. Methods Diabetic patients with contraindication to a drug-eluting stent, undergoing PCI with a BMS, were randomized to receive colchicine 0.5 mg twice daily or placebo for 6 months. Restenosis and neointima formation were studied with angiography and intravascular ultrasound 6 months after the index PCI. Results A total of 196 patients (63.6 ± 7.0 years of age, 128 male) were available for analysis. The angiographic ISR rate was 16% in the colchicine group and 33% in the control group (p = 0.007; odds ratio: 0.38, 95% confidence interval: 0.18 to 0.79). The number needed to treat to avoid 1 case of angiographic ISR was 6 (95% confidence interval: 3.4 to 18.7). The results were similar for IVUS-defined ISR (odds ratio: 0.42; 95% confidence interval: 0.22 to 0.81; number needed to treat = 5). Lumen area loss was 1.6 mm2 (interquartile range: 1.0 to 2.9 mm2) in colchicine-treated patients and 2.9 mm2 (interquartile range: 1.4 to 4.8 mm2) in the control group (p = 0.002). Treatment-related adverse events were largely limited to gastrointestinal symptoms. Conclusions Colchicine is associated with less neointimal hyperplasia and a decreased ISR rate when administered to diabetic patients after PCI with a BMS. This observation may prove useful in patients undergoing PCI in whom implantation of a drug-eluting stent is contraindicated or undesirable.

The introduction of biochemical biomarkers in the evaluation of patients with cardiovascular disease has led to practice-changing advancements in the way these patients are diagnosed and managed. Measurements of cardiac troponins or brain-type natriuretic peptide (BNP) and its precursor, N-terminal brain-type natriuretic peptide (NT-proBNP), have become indispensable in the evaluation of patients with acute coronary syndromes and heart failure, respectively, constituting an integral part of the diagnostic algorithm and risk stratification of these conditions. Copeptin, a glycopeptide, part of the prehormone molecule of the antidiuretic hormone - or arginine-vasopressin - has shown considerable promise in this field. There is evidence that copeptin might be useful as a diagnostic or prognostic biomarker and risk-stratifier in a range of cardiovascular disease conditions. The main clinical scenarios where copeptin has been studied as a biomarker are: early rule-out of myocardial infarction in patients with acute chest pain, diagnosis of heart failure in patients with acute dyspnea and determining the prognosis of destabilized or chronic stable heart failure. The present review is aimed at providing concise information about the molecular structure and biosynthesis of copeptin, the available medical chemistry methods of quantification, and the potential clinical uses of this molecule in patients with heart disease.

Objectives The aim of this study was to test the hypothesis that moderate procedural sedation can reduce the incidence of radial artery spasm. Background Transradial access for left heart catheterization and percutaneous coronary intervention is increasingly used for emergent and elective procedures, in lieu of the femoral approach. However, increased rates of access site crossover have been reported, with radial artery spasm being a major contributor to this effect. Methods Patients undergoing elective transradial percutaneous coronary intervention were prospectively randomized to receive fentanyl and midazolam during the procedure or no treatment (control subjects). The primary endpoint was angiographically confirmed radial artery spasm. Patient discomfort was quantified with a visual analogue scale. Results Two thousand thirteen patients (age 64.5 ± 8.4 years) were randomized. Spasm occurred in 2.6% of the treatment group versus 8.3% of control subjects (p Conclusions Routine administration of relatively low doses of an opioid/benzodiazepine combination during transradial interventional procedures is associated with a substantial reduction in the rate of spasm, the need for access site crossover, and the procedure-related level of patient discomfort.

Catheter ablation for rhythm control in atrial fibrillation has been recognized as an established treatment. Patients with atrial fibrillation suffer from an increased risk of thromboembolic events. Long-term stroke risk and mortality have been shown to be reduced after catheter ablation, still the procedure per se is associated with an additive peri-procedural thromboembolic risk. Maintenance of the thrombotic - bleeding equilibrium in such patients during interventional procedures is compelling. Lack of data from randomized studies along with the recent introduction of novel oral anticoagulants in clinical practice has resulted in a wide variance of antithrombotic treatment approaches. Procedural interruption of anticoagulants, switching of anticoagulation scheme (i.e. from novel oral anticoagulants to vitamin K antagonists), bridging with heparin, timing of re-initiation of therapy and/or utilization of novel oral anticoagulants have all been points of dispute. In the present review we present the available data regarding optimal peri-procedural anticoagulation strategies in patients undergoing catheter ablation for atrial fibrillation.

Objectives The purpose of the present study was to test the potential of colchicine, an agent with potent anti-inflammatory action, to reduce atrial fibrillation (AF) recurrence after pulmonary vein isolation in patients with paroxysmal AF. Background Proinflammatory processes induced by AF ablation therapy have been implicated in postablation arrhythmia recurrence. Methods Patients with paroxysmal AF who received radiofrequency ablation treatment were randomized to a 3-month course of colchicine 0.5 mg twice daily or placebo. C-reactive protein (CRP) and interleukin (IL)-6 levels were measured on day 1 and on day 4 of treatment. Results In the 3-month follow-up, recurrence of AF was observed in 27 (33.5%) of 80 patients of the placebo group versus 13 (16%) of 81 patients who received colchicine (odds ratio: 0.38, 95% confidence interval: 0.18 to 0.80). Gastrointestinal side-effects were the most common symptom among patients receiving active treatment. Diarrhea was reported in 7 patients in the colchicine group (8.6%) versus 1 in the placebo group (1.3%, p = 0.03). Colchicine led to higher reductions in CRP and IL-6 levels: the median difference of CRP and IL-6 levels between days 4 and 1 was −0.46 mg/l (interquartile range: −0.78 to 0.08 mg/l) and −0.10 mg/l (−0.30 to 0.10 pg/ml), respectively, in the placebo group versus −1.18 mg/l (−2.35 to −0.46 mg/l) and −0.50 pg/ml (−1.15 to −0.10 pg/ml) in the colchicine group (p Conclusions Colchicine is an effective and safe treatment for prevention of early AF recurrences after pulmonary vein isolation in the absence of antiarrhythmic drug treatment. This effect seems to be associated strongly with a significant decrease in inflammatory mediators, including IL-6 and CRP.

Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, is the third most common cause of vascular death after myocardial infarction and stroke. Clinicians are often summoned to make challenging decisions for the prevention and treatment of high risk patients with an unpredicted outcome, often relying on data that are less than definitive. During the last decades, heparins (unfractionated and low molecular weight heparins) as well as vitamin K antagonists, such as warfarin, and indirect Xa inhibitors, such as fontaparinux, are the cornerstone for the prevention and treatment of patients with venous thromboembolism. However, the traditionally used anticoagulants have several drawbacks that may limit their efficacy and use in every day clinical practise. The newly developed oral anticoagulants, belonging to the categories of direct thrombin inhibitors (DTIs) and direct Xa inhibitors, have emerged as promising agents with remarkable efficacy, concentrating many parameters of an ideal anticoagulant. Rivaroxaban, dabigatran and apixaban are the most studied agents, while a plethora of others are investigated in clinical trials of different phases and are expected to reach the market in the following years. The purpose of this review is to summarize the so far acquired knowledge on these agents, to report briefly some of their pharmacodynamic and pharmacokinetic properties and to focus on their role in the treatment and prevention of venous thromboembolism.

Objective: Hypertension may lead to left ventricular hypertrophy, fibrosis and degeneration of the conduction system. Our aim was to study the association of hypertrophy with certain arrhythmias such as complete atrioventricular block (AVB) and symptomatic sick sinus syndrome (SSS) that require implantation of permanent pacemaker. Methods: We studied 130 patients that had been given a pacemaker because of complete AVB, 130 patients that had been given a pacemaker because of symptomatic SSS and 45 patients without cardiac conduction disturbances. In order to estimate left ventricular hypertrophy, indexes of relative wall thickness (RWT) and left ventricular mass (LVM) were evaluated by echocardiography. Results: We observed significant association between complete AVB and abnormal values of echocardiographic indexes. Conclusions: Our results lend further support to the hypothesis that complete AVB is associated with left ventricular hypertrophy. This hypothesis is enhanced by the observation that the majority of patients with complete AVB were hypertensive.

a Cardiology Department and Cardiac Catheterization Laboratory, Athens General Hospital “G. Gennimatas”, Athens, Greece b 1st Department of Cardiology, University of Athens Medical School, Hippokrateion Hospital, Athens, Greece c Department of Cardiology, University of Patras Medical School, Patras, Greece d Cardiac Catheterization Laboratory, Yale-New Haven Hospital, Yale School of Medicine, New Haven, CT, USA

coronary intervention on bifurcation lesions Spyridon Deftereos , Georgios Giannopoulos , Dimitris Tousoulis ⁎, Konstantinos Raisakis , Andreas Kaoukis , Charalambos Kossyvakis , Vasiliki Panagopoulou , Olga Ntzouvara , Aggeliki Mavrogianni , Nikolaos Michelakakis , Konstantinos Toutouzas , Vlasios Pyrgakis , Georgios Bobotis , Michael W. Cleman , Christodoulos Stefanadis b a Department of Cardiology, Athens General Hospital “G. Gennimatas”, Athens, Greece b 1st Department of Cardiology, Hippokrateion Hospital, University of Athens Medical School, Athens, Greece c 2nd Department of Cardiology, “G. Papageorgiou” Hospital, Thessaloniki, Greece d Cardiac Catheterization Laboratory, Yale-New Haven Hospital, Yale School of Medicine, New Haven, CT, USA

The aim of this study was to test the hypothesis that moderate procedural sedation can reduce the incidence of radial artery spasm.Transradial access for left heart catheterization and percutaneous coronary intervention is increasingly used for emergent and elective procedures, in lieu of the femoral approach. However, increased rates of access site crossover have been reported, with radial artery spasm being a major contributor to this effect.Patients undergoing elective transradial percutaneous coronary intervention were prospectively randomized to receive fentanyl and midazolam during the procedure or no treatment (control subjects). The primary endpoint was angiographically confirmed radial artery spasm. Patient discomfort was quantified with a visual analogue scale.Two thousand thirteen patients (age 64.5 ± 8.4 years) were randomized. Spasm occurred in 2.6% of the treatment group versus 8.3% of control subjects (p0.001; odds ratio [OR]: 0.29). The number needed to treat to avoid 1 case of spasm was 18 (95% confidence interval [CI]: 12.9 to 26.6). The access site crossover rate was 34% lower in the treatment group: 9.9% versus 15.0% (OR: 0.62; 95% CI: 0.48 to 0.82). Patient discomfort visual analogue scale score was 18.8 ± 12.5 in the treatment group versus 27.4 ± 17.4 in control subjects (p0.001). No significant differences were observed in the 30-day rate of death or repeat hospital stay for any cause: 4.6% versus 4.5% (OR: 1.02; 95% CI: 0.67 to 1.56).Routine administration of relatively low doses of an opioid/benzodiazepine combination during transradial interventional procedures is associated with a substantial reduction in the rate of spasm, the need for access site crossover, and the procedure-related level of patient discomfort.

Objectives: Soluble tumor necrosis factor-related apoptosis inducing ligand (sTRAIL) has been shown to exert protective action against atherosclerosis. The aim of this study was to investigate potential associations of coronary sTRAIL levels with indices of in-stent neointimal hyperplasia. Methods: 67 patients who underwent percutaneous coronary intervention with drug-eluting stent were followed up at approximately 12 months with determination of coronary sTRAIL concentration, angiography and intravascular ultrasound evaluation of the stent sites. Results: Mean sTRAIL concentration was 72.2 ± 2.8 pg/ml. sTRAIL was negatively correlated to indices of neointimal hyperplasia and positively correlated to in-stent minimum lumen area (p < 0.001). Neointimal obstruction and maximal in-stent cross-sectional neointima burden in patients in the upper sTRAIL quartile were 3.8 ± 1.2 and 12.6 ± 3.3%, respectively, versus 14.0 ± 0.7 and 49.8 ± 2.7% in the lower quartile (p < 0.001 for both). sTRAIL levels were significantly lower in patients with binary restenosis (48.7 ± 3.0 vs. 75.2 ± 2.9 pg/ml; p < 0.001). In the multivariate analysis, sTRAIL was an independent predictor of neointimal hyperplasia. Conclusion: This study demonstrates a negative association of sTRAIL to in-stent neointima formation. The potential pathophysiologic substrate of this effect implicates modulation of apoptosis in various cell types. These observations should prompt further evaluation of the link between sTRAIL and in-stent restenosis.

Thrombosis plays a key role in the pathophysiology of acute coronary syndromes (ACS). The management of patients with ACS includes interventional procedures and use of antithrombotic agents acutely, and dual antiplatelet therapy (aspirin and a P2Y12 receptor antagonist) for secondary prevention. However, patients with recent ACS remain at a substantial residual risk for recurrent ischemic events or death. The idea of follow-up treatment with an oral anticoagulant on top of standard therapy seems promising. Warfarin was the first oral anticoagulant thoroughly investigated in this direction, but the widespread long-term use of warfarin in ACS has been limited by challenges associated with pharmacodynamic/pharmacokinetic deficiencies of the drug and the risk of bleeding. Novel oral anticoagulants, such as direct thrombin inhibitors (DTIs) and FXa inhibitors overcome the downsides of VKAs. Ximelagatran was the first DTI, investigated and proven to be effective in prevention of recurrent ischemic events in ACS patients, but the drug association with hepatotoxicity prompted its withdrawal. Dabigatran etexilate, apixaban, darexaban (YM150) and TAK-442 were studied in phase II dose-escalation trials in order to determine the balance between clinical effectiveness and bleeding risk in daily use with dual antiplatelet therapy, with both positive and negative results. Rivaroxaban is the only agent that completed a phase III trial, showing reduction in recurrent ischemic events rate and death from cardiovascular causes as well as all-cause death. This review summarizes the data from completed and ongoing clinical trials of the new oral anticoagulants in patients with ACS.

Intracardiac echocardiography (ICE) offers the ability to image the left atrium in order to reconstruct a three-dimensional model that can be integrated with electroanatomic data to guide pulmonary vein isolation. We report a case series representing the first-in-Greece experience with the CartoSound module.Patients with paroxysmal or persistent atrial fibrillation (AF) referred for pulmonary vein isolation were included in this case-series. The SoundStar ICE catheter was used to trace left atrial and pulmonary vein contours from the right atrium, the right ventricular outflow tract and the coronary sinus.Eight patients (age 66.3 ± 1.6 years) are presented in this case-series report. Six of them (75%) had paroxysmal AF and the rest were in persistent AF for less than one year. The time for ICE imaging and left atrium three-dimensional reconstruction decreased from a median of 20.5 minutes (interquartile range 19.3-23.3) for the chronologically first four cases to a median of 16.5 minutes (interquartile range 14.517.0) for the chronologically last four cases (p=0.02). The procedure was completed in all cases. No significant periprocedural complications were encountered. Acute success, with restoration of sinus rhythm, was achieved in both patients with persistent AF. Seven of the eight patients (87.5%) were AF-free in 48-hour Holter recordings one week after the procedure.ICE integration into three-dimensional electroanatomic reconstruction of the left atrium provides reliable guidance for pulmonary vein isolation. It appears that this modality is a sound alternative to magnetic resonance and computed tomography image data registration, although randomized comparisons are lacking.

Placement of an electrode catheter in the coronary sinus (CS) through the jugular or subclavian vein, as part of electrophysiology (EP) procedures, increases patient discomfort and the possibility of adverse events. We studied the hypothesis that peripheral venous access for CS cannulation, as part of EP procedures, is feasible and can reduce patient discomfort, eliminating central venous access-associated risks. Consecutive patients submitted to EP procedures were randomly assigned to peripheral or central venous access for CS cannulation. If after 30 min from initial needle insertion the CS was still not catheterized, the attempt was considered unsuccessful. Patient level of discomfort was assessed with a visual analog scale (VAS). Success rate was 90% in the peripheral versus 95% in the central venous access group (p = 1.00). No complications related to venous access were observed in the peripheral venous access group, whereas one case of pneumothorax and one case of extensive hematoma in the anterior cervical area were recorded in the central venous access group. Patients submitted to central vein catheterization reported higher VAS scores, 46.8 ± 16.3 versus 36.8 ± 12.9 (p = 0.04). No significant difference was observed in fluoroscopy time needed for CS cannulation (51.1 ± 9.2 s versus 51.4 ± 7.9 s; p = 0.71) between the two groups. This small, randomized study indicates that peripheral venous access for CS catheter placement during EP procedures is feasible, with equivalent success rate to the central venous access approach, and associated with lower levels of self-reported patient discomfort.

The transfemoral approach (TFA) has been the mainstay for arterial access during percutaneous coronary intervention (PCI) in the setting of acute ST-segment elevation myocardial infarction (STEMI). However, the transradial approach (TRA) has been shown to be an equally effective and possibly safer way of performing primary PCI (pPCI).The study population included 98 serially recruited patients who underwent pPCI in our institution. All patients were clinically followed during their hospital stay (6.4 ± 3.1 days).In the 98 patients included in the study, 65 procedures (66.3%) were completed via TRA, whereas the remaining 33 procedures (33.7%) used TFA. Door-to-balloon time was similar (57 ± 19 min vs. 54 ± 15 min, p=ns). Patients in the TRA group were mobilized sooner (28 ± 9 hours vs. 36 ± 13 hours, p0.05). Hospital stay was significantly shorter in the TRA group (6.0 ± 3.2 days vs. 7.1 ± 2.8 days, p0.05). TRA and TFA did not differ significantly as to the incidence of death, non-fatal myocardial infarction or subacute stent thrombosis, but major access-related vascular complications were significantly more frequent in the TFA group (2% vs. 15%, p0.01). Cerebrovascular events did not differ between TRA and TFA.Compared to TFA, TRA seems to be associated with a lower incidence of bleeding complications, as well as earlier mobilization and discharge from hospital. It is conceivable that TRA could become the first choice in the treatment of STEMI patients in the near future, while TFA is kept as an alternative.

A 62-year-old woman was referred for evaluation of recent-onset dyspnoea at rest and a newly found systolic heart murmur, heard best at the apex of the heart. The patient's history was notable for surgical mitral valve replacement 3 years ago, due to severe mitral regurgitation (myxomatous degeneration of the mitral valve). The transthoracic echocardiogram gave the impression of a mitral regurgitant jet, but the acoustic shadow of the prosthesis did not allow adequate evaluation of the regurgitation. A transoesophageal echocardiogram was performed showing a normally functioning mitral prosthesis, with a small periprosthetic leak (Figure 1, upper panel), disproportionate to the patient's symptoms and marked signs of haemolysis. An intracardiac ultrasound study revealed a large paravalvular regurgitant jet, indicating significant periprosthetic regurgitation (Figure 1, lower panel). Intracardiac echocardiography is increasingly being used to guide percutaneous interventions and electrophysiological procedures. The present case suggests a potentially useful widening of the range of intracardiac ultrasound clinical applications, out of the realm of device-closure interventions and electrophysiological procedures. It appears that intracardiac echocardiography could become a second-line alternative to transoesophageal echocardiography, especially in patients with contraindication to the latter.