Publications by authors named "Nikolaos Fragakis"

57 Publications

A Patient-Oriented App (ThessHF) to Improve Self-Care Quality in Heart Failure: From Evidence-Based Design to Pilot Study.

JMIR Mhealth Uhealth 2021 Apr 13;9(4):e24271. Epub 2021 Apr 13.

Cardiovascular Prevention and Digital Cardiology Lab, Third Cardiology Department, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Background: Heart failure (HF) remains a major public health challenge, while HF self-care is particularly challenging. Mobile health (mHealth)-based interventions taking advantage of smartphone technology have shown particular promise in increasing the quality of self-care among these patients, and in turn improving the outcomes of their disease.

Objective: The objective of this study was to co-develop with physicians, patients with HF, and their caregivers a patient-oriented mHealth app, perform usability assessment, and investigate its effect on the quality of life of patients with HF and rate of hospitalizations in a pilot study.

Methods: The development of an mHealth app (The Hellenic Educational Self-care and Support Heart Failure app [ThessHF app]) was evidence based, including features based on previous clinically tested mHealth interventions and selected by a panel of HF expert physicians and discussed with patients with HF. At the end of alpha development, the app was rated by mHealth experts with the Mobile Application Rating Scale (MARS). The beta version was tested by patients with HF, who rated its design and content by means of the Post-Study System Usability Questionnaire (PSSUQ). Subsequently, a prospective pilot study (THESS-HF [THe Effect of a Specialized Smartphone app on Heart Failure patients' quality of self-care, quality of life and hospitalization rate]) was performed to investigate the effect of app use on patients with HF over a 3-month follow-up period. The primary endpoint was patients' quality of life, which was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 5-level EQ-5D version (EQ-5D-5L). The secondary endpoints were the European Heart Failure Self-care Behavior Scale (EHFScBS) score and the hospitalization rate.

Results: A systematic review of mHealth-based HF interventions and expert panel suggestions yielded 18 separate app features, most of which were incorporated into the ThessHF app. A total of 14 patients and 5 mHealth experts evaluated the app. The results demonstrated a very good user experience (overall PSSUQ score 2.37 [SD 0.63], where 1 is the best, and a median MARS score of 4.55/5). Finally, 30 patients (male: n=26, 87%) participated in the THESS-HF pilot study (mean age 68.7 [SD 12.4] years). A significant increase in the quality of self-care was noted according to the EHFScBS, which increased by 4.4% (SD 7.2%) (P=.002). The mean quality of life increased nonsignificantly after 3 months according to both KCCQ (mean increase 5.8 [SD 15] points, P=.054) and EQ-5D-5L (mean increase 5.6% [SD 15.6%], P=.06) scores. The hospitalization rate for the follow-up duration was 3%.

Conclusions: The need for telehealth services and remote self-care management in HF is of vital importance, especially in periods such as the COVID-19 pandemic. We developed a user-friendly mHealth app to promote remote self-care support in HF. In this pilot study, the use of the ThessHF app was associated with an increase in the quality of self-care. A future multicenter study will investigate the effect of the app use on long-term outcomes in patients with HF.
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http://dx.doi.org/10.2196/24271DOI Listing
April 2021

Echo(e)s of an invasion. A rare pericardial synovial sarcoma.

Hellenic J Cardiol 2021 Apr 8. Epub 2021 Apr 8.

Third Cardiology Department, Hippokrateion University Hospital, Medical School, Aristotle University Thessaloniki, Thessaloniki, Greece.

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http://dx.doi.org/10.1016/j.hjc.2021.03.010DOI Listing
April 2021

Bolus Intravenous Procainamide in Patients with Frequent Ventricular Ectopics during Cardiac Magnetic Resonance Scanning: A Way to Ensure High Quality Imaging.

Diagnostics (Basel) 2021 Jan 27;11(2). Epub 2021 Jan 27.

First Department of Cardiology, AHEPA Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 546 36 Thessaloniki, Greece.

Acquiring high-quality cardiac magnetic resonance (CMR) images in patients with frequent ventricular arrhythmias remains a challenge. We examined the safety and efficacy of procainamide when administered on the scanner table prior to CMR scanning to suppress ventricular ectopy and acquire high-quality images. Fifty consecutive patients (age 53.0 [42.0-58.0]; 52% female, left ventricular ejection fraction 55 ± 9%) were scanned in a 1.5 T scanner using a standard cardiac protocol. Procainamide was administered at intermittent intravenous bolus doses of 50 mg every minute until suppression of the ectopics or a maximum dose of 10 mg/kg. The average dose of procainamide was 567 ± 197 mg. Procainamide successfully suppressed premature ventricular contractions (PVCs) in 82% of patients, resulting in high-quality images. The baseline blood pressure (BP) was mildly reduced (mean change systolic BP -12 ± 9 mmHg; diastolic BP -4 ± 9 mmHg), while the baseline heart rate (HR) remained relatively unchanged (mean HR change -1 ± 6 bpm). None of the patients developed proarrhythmic changes. Bolus intravenous administration of procainamide prior to CMR scanning is a safe and effective alternative approach for suppressing PVCs and acquiring high-quality images in patients with frequent PVCs and normal or only mildly reduced systolic function.
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http://dx.doi.org/10.3390/diagnostics11020178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911068PMC
January 2021

Trends in ablation procedures in Greece over the 2008-2018 period: Results from the Hellenic Cardiology Society Ablation Registry.

Hellenic J Cardiol 2021 Jan-Feb;62(1):48-54. Epub 2020 Sep 19.

First Department of Cardiology, Hippokration University Hospital, National and Kapodistian University of Athens, Athens, Greece.

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.
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http://dx.doi.org/10.1016/j.hjc.2020.09.005DOI Listing
September 2020

Excessive Supraventricular Ectopic Activity and Adverse Cardiovascular Outcomes: a Systematic Review and Meta-analysis.

Curr Atheroscler Rep 2020 05 21;22(4):14. Epub 2020 May 21.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, 300211, People's Republic of China.

Purpose Of Review: Excessive supraventricular ectopic activity (ESVEA), in the form of frequent premature atrial contractions (PACs) and runs of PACs, is commonly observed in clinical practice and is frequently considered to be benign. Yet, recent studies have demonstrated a link between ESVEA and adverse cardiovascular outcomes. The aim of this meta-analysis was to examine the association between ESVEA and the risk of atrial fibrillation (AF), stroke, and mortality.

Recent Findings: A systematic search was performed in PubMed, EMBASE, and the Cochrane Library up to December 2017 to identify studies assessing adverse cardiovascular outcomes in patients with ESVEA, recorded on ambulatory electrocardiography. ESVEA was defined as a burden of PACs > 30 PACs/h or any runs of ≥20 PACs. The risk estimates for EVSEA and each clinical endpoint were pooled and analyzed separately.

Results: Five studies comprising 7545 participants were included in this meta-analysis. The pooled analysis showed that ESVEA doubled the risk of AF (HR 2.19, 95% CI 1.70-2.82). ESVEA was also associated with a higher incidence of stroke (HR 2.23, 95% CI 1.24-4.02). Finally, ESVEA was associated with higher all-cause mortality (HR 1.61, 95% CI 1.25-2.07). Our meta-analysis found that ESVEA is closely associated with AF, stroke, and all-cause mortality. Further studies are required to examine the implication of therapeutic strategies in patients with ESVEA, in order to prevent potential subsequent adverse cardiovascular outcomes.
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http://dx.doi.org/10.1007/s11883-020-0832-4DOI Listing
May 2020

Left atrial strain, intervendor variability, and atrial fibrillation recurrence after catheter ablation: A systematic review and meta-analysis.

Hellenic J Cardiol 2020 May - Jun;61(3):154-164. Epub 2020 Apr 20.

Third Cardiology Department, Hippokration University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address:

The aim of this systematic review and meta-analysis is to investigate the capacity of preinterventional left atrial strain (LAS) to predict AF recurrence (AFR) after catheter ablation by using all relative published data. Intervendor variability regarding different ultrasound stations and strain analysis software suites was taken into consideration. The research was performed according to PRISMA guidelines. The Cochrane database, MEDLINE, and EMBASE were searched for studies assessing echocardiography LAS prior to catheter ablation of AF cases. The systematic research yielded 10 studies (2 retrospective and 8 prospective, 880 patients in total). LAS differed significantly between the patients with AFR and those with no AF recurrence (nAFR) during the follow-up period (LAS: 17.5 ± 8.7% vs. LAS: 24.1 ± 9.5%, p < 0.00001). A pooled cutoff value of 21.9% for LAS was extracted for the prediction of ablation success. Regarding intervendor variability, subgroup analyses were able to be performed for studies using GE and TomTec software. The difference in LAS and LAS remained significant (p < 0.00001 and p < 0.0001 for TomTec and GE, respectively), while significant intervendor difference in absolute strain values was also detected (p < 0.0001 for both AFR and nAFR groups). LAS prior to catheter ablation is consistently lower in patients who experience AF recurrence. Its incorporation in clinical practice would assist physicians detect patients who require closer follow-up. Intervendor variability appears to be considerable and steps must be taken to document it thoroughly and mitigate it if possible.
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http://dx.doi.org/10.1016/j.hjc.2020.04.008DOI Listing
April 2020

Clinical characteristics and long-term clinical course of patients with Brugada syndrome without previous cardiac arrest: a multiparametric risk stratification approach.

Europace 2019 12;21(12):1911-1918

Second Department of Cardiology, Laboratory of Invasive Cardiac Electrophysiology, "Evangelismos" General Hospital of Athens, Ispilantou 45-47, 10676, Athens, Greece.

Aims: Risk stratification in Brugada syndrome (BrS) still represents an unsettled issue. In this multicentre study, we aimed to evaluate the clinical characteristics and the long-term clinical course of patients with BrS.

Methods And Results: A total of 111 consecutive patients (86 males; aged 45.3 ± 13.3 years) diagnosed with BrS were included and followed-up in a prospective fashion. Thirty-seven patients (33.3%) were symptomatic at enrolment (arrhythmic syncope). An electrophysiological study (EPS) was performed in 59 patients (53.2%), and ventricular arrhythmias were induced in 32 (54.2%). A cardioverter defibrillator was implanted in 34 cases (30.6%). During a mean follow-up period of 4.6 ± 3.5 years, appropriate device therapies occurred in seven patients. Event-free survival analysis (log-rank test) showed that spontaneous type-1 electrocardiogram pattern (P = 0.008), symptoms at presentation (syncope) (P = 0.012), family history of sudden cardiac death (P < 0.001), positive EPS (P = 0.024), fragmented QRS (P = 0.004), and QRS duration in lead V2 > 113 ms (P < 0.001) are predictors of future arrhythmic events. Event rates were 0%, 4%, and 60% among patients with 0-1 risk factor, 2-3 risk factors, and 4-5 risk factors, respectively (P < 0.001). Current multiparametric score models exhibit an excellent negative predictive value and perform well in risk stratification of BrS patients.

Conclusions: Multiparametric models including common risk factors appear to provide better risk stratification of BrS patients than single factors alone.
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http://dx.doi.org/10.1093/europace/euz288DOI Listing
December 2019

Iron deficiency as therapeutic target in heart failure: a translational approach.

Heart Fail Rev 2020 03;25(2):173-182

3rd Department of Cardiology Hippocration Hospital, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54 352, Thessaloniki, Greece.

Heart failure (HF) is a potentially debilitating condition, with a prognosis comparable to many forms of cancer. It is often complicated by anemia and iron deficiency (ID), which have been shown to even further harm patients' functional status and hospitalization risk. Iron is a cellular micronutrient that is essential for oxygen uptake and transportation, as well as mitochondrial energy production. Iron is crucially involved in electrochemical stability, maintenance of structure, and contractility of cardiomyocytes. There is mounting evidence that ID indeed hampers the homeostasis of these properties. Animal model and stem cell research has verified these findings on the cellular level, while clinical trials that treat ID in HF patients have shown promising results in improving real patient outcomes, as electromechanically compromised cardiomyocytes translate to HF exacerbations and arrhythmias in patients. In this article, we review our current knowledge on the role of iron in cardiac muscle cells, the contribution of ID to anemia and HF pathophysiology and the capacity of IV iron therapy to ameliorate the patients' arrhythmogenic profile, quality of life, and prognosis.
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http://dx.doi.org/10.1007/s10741-019-09815-zDOI Listing
March 2020

Arrhythmic risk stratification in post-myocardial infarction patients with preserved ejection fraction: the PRESERVE EF study.

Eur Heart J 2019 09;40(35):2940-2949

First Department of Cardiology, National and Kapodistrian University of Athens, Hippokrateion Hospital, 114 Vasilissis Sofias avenue, Athens, Attica, Greece.

Aims: Sudden cardiac death (SCD) annual incidence is 0.6-1% in post-myocardial infarction (MI) patients with left ventricular ejection fraction (LVEF)≥40%. No recommendations for implantable cardioverter-defibrillator (ICD) use exist in this population.

Methods And Results: We introduced a combined non-invasive/invasive risk stratification approach in post-MI ischaemia-free patients, with LVEF ≥ 40%, in a multicentre, prospective, observational cohort study. Patients with at least one positive electrocardiographic non-invasive risk factor (NIRF): premature ventricular complexes, non-sustained ventricular tachycardia, late potentials, prolonged QTc, increased T-wave alternans, reduced heart rate variability, abnormal deceleration capacity with abnormal turbulence, were referred for programmed ventricular stimulation (PVS), with ICDs offered to those inducible. The primary endpoint was the occurrence of a major arrhythmic event (MAE), namely sustained ventricular tachycardia/fibrillation, appropriate ICD activation or SCD. We screened and included 575 consecutive patients (mean age 57 years, LVEF 50.8%). Of them, 204 (35.5%) had at least one positive NIRF. Forty-one of 152 patients undergoing PVS (27-7.1% of total sample) were inducible. Thirty-seven (90.2%) of them received an ICD. Mean follow-up was 32 months and no SCDs were observed, while 9 ICDs (1.57% of total screened population) were appropriately activated. None patient without NIRFs or with NIRFs but negative PVS met the primary endpoint. The algorithm yielded the following: sensitivity 100%, specificity 93.8%, positive predictive value 22%, and negative predictive value 100%.

Conclusion: The two-step approach of the PRESERVE EF study detects a subpopulation of post-MI patients with preserved LVEF at risk for MAEs that can be effectively addressed with an ICD.

Clinicaltrials.gov Identifier: NCT02124018.
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http://dx.doi.org/10.1093/eurheartj/ehz260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748724PMC
September 2019

Impact of Radiofrequency Ablation and Antiarrhythmic Medications on the Quality of Life of Patients with Supraventricular Tachycardias: Preliminary Validation of the Greek Version of the Umea22 (U22) Questionnaire.

Biomed Res Int 2018 9;2018:3059478. Epub 2018 Oct 9.

Third Department of Cardiology, Hippokration General Hospital, Aristotle University Medical School, 49 Konstantinoupoleos Road, 54642 Thessaloniki, Greece.

Objective: This study aims to (i) translate, culturally adapt, and preliminarily validate the arrhythmia-specific Umea22 (U22) questionnaire and (ii) assess the impact of radiofrequency (RF) ablation and medical treatment on the quality of life of patients with supraventricular tachycardias (SVTs).

Methods: A total of 140 patients with atrioventricular nodal re-entry tachycardia (AVNRT) and atrioventricular re-entry tachycardia (AVRT) were enrolled in the study. Of these, 100 patients underwent RF ablation (group A) and 40 patients were managed with antiarrhythmic medications (group B). Health-related quality of life (HRQoL) was assessed for both groups using the Short Form-36 Health Survey (SF-36) and the arrhythmia-specific Umea22 (U22) questionnaire at baseline and 3-month follow-up. Exploratory and confirmatory factor analyses were performed to assess the validity of the U22 questionnaire. Univariate comparisons of HRQoL scores between study timepoints and multivariate regression analyses adjusting for baseline confounders were conducted.

Results: The factor analysis of the U22 questionnaire yielded a six-factor model ("burden of spells"; "heart contractility"; "character of spells"; "general/non-specific feeling"; "other specific somatic symptoms"; "fear") with acceptable fit results. Patients of group A showed significant improvement in all SF-36 and U22 scores at 3 months' follow-up compared to baseline (all p<0.05). Patients of group B presented deterioration of the total SF-36 score (p=0.001) and improvement of certain U22 measures, namely, well-being (p=0.004), heartbeat speed, and intensity during arrhythmia spells (p<0.0001 for both measures) at 3 months' follow-up, compared to baseline. Employment status, male sex, and urban residence emerged as important predictors.

Conclusion: The Greek version of the U22 questionnaire is a valid tool to assess SVT-related symptoms. RF ablation appears to exert more pronounced beneficial outcomes on HRQoL of patients with SVTs compared to medical treatment. Prompt referral of patients with SVTs to specialist centers may favorably affect their quality of life and should be encouraged.
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http://dx.doi.org/10.1155/2018/3059478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198555PMC
February 2019

Electrocardiographic conduction and repolarization markers associated with sudden cardiac death: moving along the electrocardiography waveform.

Minerva Cardioangiol 2019 Apr 26;67(2):131-144. Epub 2018 Sep 26.

Faculty of Medicine, Newcastle University, Newcastle Upon Tyne, UK -

The QT interval along with its heart rate corrected form (QTc) are well-established ECG markers that have been found to be associated with malignant ventricular arrhythmogenesis. However, extensive preclinical and clinical investigations over the years have allowed for novel clinical ECG markers to be generated as predictors of arrhythmogenesis and sudden cardiac death. Repolarization markers include the older QTc, QT dispersion and newer Tpeak - Tend intervals, (Tpeak - Tend) / QT ratios, T-wave alternans (TWA), microvolt TWA and T-wave area dispersion. Meanwhile, conduction markers dissecting the QRS complex, such as QRS dispersion (QRSD) and fragmented QRS, were also found to correlate conduction velocity and unidirectional block with re-entrant substrates in various cardiac conditions. Both repolarization and conduction parameters can be combined into the excitation wavelength (λ). A surrogate marker for λ is the index of Cardiac Electrophysiological Balance (iCEB: QT / QRSd). Other markers based on conduction-repolarization are [QRSD x (Tpeak-Tend) / QRSd] and [QRSD x (Tpeak-Tend) / (QRSd x QT)]. Advancement in technology permitted sophisticated electrophysiological analyses such as principal component analysis and periodic repolarization dynamics to further improve risk stratification. This was closely followed by other novel indices including ventricular ectopic QRS interval, the f99 index and EntropyXQT, which integrates mathematical and physical calculations for determining the risk markers. Though proven to be effective in limited patient cohorts, more clinical studies across different cardiac pathologies are required to confirm their validity. As such, this review seeks to encapsulate the development of old and new ECG markers along with their associated utility and shortcomings in clinical practice.
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http://dx.doi.org/10.23736/S0026-4725.18.04775-8DOI Listing
April 2019

Inflammation and atrial fibrillation: A comprehensive review.

J Arrhythm 2018 Aug 4;34(4):394-401. Epub 2018 Jun 4.

Department of Cardiology Tianjin Institute of Cardiology Second Hospital of Tianjin Medical University Tianjin China.

Atrial fibrillation (AF) has different underlying substrates. Atrial remodeling involves electrophysiological and structural abnormalities that promote the development and perpetuation of AF. Experimental and clinical data indicate that inflammation is implicated in the pathophysiology of atrial remodeling. The mechanistic links between atrial remodeling and inflammation are complex while diverse underlying diseases and conditions may affect these pathways. Inflammatory markers have also been associated with AF development, recurrence, perpetuation, total AF burden as well as with thromboembolic complications. The development of specific anti-inflammatory interventions in this setting seems to be challenging and complicated. Several agents with pleiotropic properties, including anti-inflammatory, have been tested in experimental and clinical settings with variable results. This updated review provides a concise overview of all available data regarding the role of inflammation in AF including the predictive role of inflammatory markers. Also, current knowledge and future directions on anti-inflammatory strategies are critically discussed.
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http://dx.doi.org/10.1002/joa3.12077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111477PMC
August 2018

Oxidative stress and atrial fibrillation: an update.

Free Radic Res 2018 Dec 10;52(11-12):1199-1209. Epub 2018 Sep 10.

f Department of Cardiology , Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University , Tianjin , P. R. China.

Atrial remodelling involves electrophysiological and structural abnormalities that promote the development and perpetuation of atrial fibrillation. Experimental and clinical data indicate that oxidative stress is implicated in the pathophysiology of atrial remodelling. The mechanistic links between atrial remodelling and oxidative stress are complex with several underlying diseases and conditions may affect these pathways. Therefore, the development of antioxidant interventions in this setting remains difficult. Besides classical antioxidant compounds, several agents with pleiotropic effects, including anti-inflammatory and antioxidant, have been tested in experimental and clinical settings with variable results. Strategies applying conventional antioxidants in specific situations such as postoperative atrial fibrillation show beneficial effects, especially the two-step regimen of antioxidants combination. Of note, there are limited data on the development of strategies that target specific sources of reactive oxygen species implicated in atrial remodelling. Lifestyle, diet, and risk factors modification is a complementary promising approach. This updated review provides a concise and critical overview of all available data regarding oxidative stress and its modulation in atrial fibrillation. Future directions on this exciting field are also discussed.
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http://dx.doi.org/10.1080/10715762.2018.1500696DOI Listing
December 2018

Left atrial deformation as a potent predictor for paroxysmal atrial fibrillation in patients with end-stage renal disease.

Int J Cardiovasc Imaging 2018 Sep 21;34(9):1393-1401. Epub 2018 Apr 21.

3rd Cardiology Department, Hippokrateio University Hospital, Aristotle University of Thessaloniki, Konstantinoupoleos 43 Str, 54643, Thessaloniki, Greece.

It is widely known that various factors contribute to left atrial (LA) mechanical dysfunction in patients with end stage renal disease (ESRD). However, the connection between atrial dysfunction and arrhythmic events such as paroxysmal atrial fibrillation (PAF), in this group of patients, remains unclear. The purpose of our study was to evaluate prospectively the association between LA deformation indices and PAF in ESRD patients. 79 patients (41 men, mean age 57 ± 17) with ESRD and preserved left ventricular systolic function comprised the study population. All patients underwent a baseline comprehensive echocardiography study and were followed for a mean period of 16 ± 5 months. PAF episodes, first and the following events, were reported. LA longitudinal strain reflecting LA reservoir function and LA longitudinal strain rate reflecting LA pump function were specifically evaluated as LA deformation indices of interest, using 2D speckle tracking echocardiography. At the end of follow up period nine patients died. 15 of the rest 70 reported one or more episodes of PAF. LA indexed volumes were significantly higher in patients with PAF (32 ± 26 vs. 21.5 ± 9 ml/m, p = 0.002), mean LA strain was significantly reduced (17 ± 7 vs. 27 ± 9%, p < 0.001) as well as mean LA stain rate (- 1.19 ± 0.5 vs. - 1.95 ± 0.5 1/s, p < 0.001). Multivariate analysis showed that LA strain rate when adjusted with age together with PAF history remained the single most significant echocardiographic parameter for PAF prediction. Impaired LA strain and LA strain rate are associated with PAF in ESRD patients. LA strain rate might be a better independent predictor of PAF, compared to standard echocardiographic indices. Further prospective studies are needed to validate its relevance in routine clinical practice.
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http://dx.doi.org/10.1007/s10554-018-1353-xDOI Listing
September 2018

Mahaim Accessory Pathways.

Arrhythm Electrophysiol Rev 2017 12;6(4):222

Assistant Professor of Cardiology, Aristotle University of Thessaloniki, Thessaloniki, Greece.

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http://dx.doi.org/10.15420/aer.2017.6.4:L1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739894PMC
December 2017

Electrophysiological markers predicting impeding AV-block during ablation of atrioventricular nodal reentry tachycardia.

Pacing Clin Electrophysiol 2018 01 28;41(1):7-13. Epub 2017 Dec 28.

Third Department of Cardiology, Hippokration Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Background: Radiofrequency (RF) ablation of the slow pathway (SP) in atrioventricular nodal reentry tachycardia (AVNRT) is occasionally complicated with atrioventricular block (AVB) often predicted by junctional beats (JB) with loss of ventriculo-atrial (VA) conduction.

Methods: We analyzed retrospectively 153 patients undergoing ablation of SP for typical AVNRT. Patients were divided into two age groups: 127 ≤ 70 years and 26 > 70 years. We analyzed the interval between the atrial electrogram in the His-bundle position and the distal ablation catheter [A(H)-A(RFd)] and between the distal ablation catheter and the proximal coronary sinus catheter [A(RFd)-A(CS)] before RF applications with and without JB. We evaluated if these intervals can be used as predictors of JB incidence and also of JB with loss of VA conduction. We also assessed if age influences the risk of loss of VA conduction.

Results: The A(H)-A(RFd) and A(RFd)-A(CS) intervals were significantly shorter in RF applications causing JB than those without JB (33 ± 11 ms vs 39 ± 9 ms, P < 0.001, 14 ± 9 ms vs 20 ± 7 ms, P < 0.001, respectively). The A(H)-A(RFd) and A(RFd)-A(CS) intervals were also significantly shorter in RFs causing JB with VA block than those with VA conduction (29 ± 11 ms vs 35 ± 11 ms, P < 0.001, 8 ± 8 ms vs 17 ± 8 ms, P < 0.001, respectively). Patients > 70 years had shorter intervals (36 ± 11 ms vs 29 ± 8 ms, P  =  0.012, 17 ± 8 ms vs 13 ± 7 ms, P  =  0.027, respectively), while VA block was more common in this age group.

Conclusions: The A(H)-A(RFd) and A(RFd)-A(CS) intervals can be used as markers for predicting JB occurrence as well as impending AVB. JB with loss of VA conduction occur more often in older patients possibly due to a higher position of SP.
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http://dx.doi.org/10.1111/pace.13245DOI Listing
January 2018

Intraventricular conduction disturbances: are we just looking at the tip of the iceberg?

Hellenic J Cardiol 2017 May - Jun;58(3):202-203. Epub 2017 Aug 23.

Third Department of Cardiology, Hippokration Hospital, Aristotle University Medical School, Thessaloniki, Greece. Electronic address:

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http://dx.doi.org/10.1016/j.hjc.2017.08.006DOI Listing
November 2017

Electrical storm in a patient with Duchenne muscular dystrophy cardiomyopathy triggered by abrupt β-blocker interruption.

Ann Noninvasive Electrocardiol 2017 Nov 15;22(6). Epub 2017 Jun 15.

Third Department of Cardiology, Hippokration Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

We present a case of a young man with Duchenne muscular dystrophy cardiomyopathy (DMDC) having an implantable cardioverter defibrillator for secondary prevention, who presented with electrical storm shortly after β-blocker interruption. The patient was stabilized and remained free of ventricular arrhythmias soon after reinitiating b-adrenoreceptor antagonists. The present case highlights the importance of sympathetic blockage in patients with DMDC due to existing pathophysiology of excess diastolic Ca leak from sarcoplasmic reticulum as a result of ryanodine receptor dysfunction.
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http://dx.doi.org/10.1111/anec.12477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931609PMC
November 2017

Meta-Analysis of the Usefulness of Change in QRS Width to Predict Response to Cardiac Resynchronization Therapy.

Am J Cardiol 2016 Nov 13;118(9):1368-1373. Epub 2016 Aug 13.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People's Republic of China. Electronic address:

The existing data regarding the role of QRS duration (QRSd) change on cardiac resynchronization therapy (CRT) response show some inconsistent results. We conducted a meta-analysis of data obtained from observational studies to examine the impact of QRS change after CRT device implantation on the clinical and/or echocardiographic response. We searched the PubMed and EMBASE databases for relevant studies published before January 2016. Twenty-seven studies were retrieved for detailed evaluation of which 12 studies with a total population of 1,545 patients met our eligibility criteria. The analysis demonstrated that QRSd narrowing was a positive predictor of response to CRT (mean difference [MD] = -19.24 ms, 95% CI = -24.00 to -14.48 ms, p <0.00001). This effect was consistent in the studies using clinical criteria (MD = -19.91 ms, 95% CI = -27.20 to -12.62 ms, p <0.00001) and in those that used echocardiographic criteria (MD = -19.51 ms, 95% CI = -25.78 to -13.25 ms, p <0.00001). The heterogeneity test showed moderate differences among the individual studies (I = 42%). Subgroup analysis showed that QRSd change was more pronounced in studies having a follow-up ≤6 months. We did not find significant differences in studies measuring postimplantation QRSd after a certain follow-up period compared with studies measuring QRSd immediately after CRT device implantation. Further studies should clarify the exact timing of QRSd assessments during follow-up. In conclusion, QRSd shortening after CRT device implantation is associated with a favorable clinical and echocardiographic response.
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http://dx.doi.org/10.1016/j.amjcard.2016.07.070DOI Listing
November 2016

Role of ranolazine in the prevention and treatment of atrial fibrillation: A meta-analysis of randomized clinical trials.

Heart Rhythm 2017 01 13;14(1):3-11. Epub 2016 Oct 13.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, People's Republic of China. Electronic address:

Background: Randomized controlled trials (RCTs) on the use of ranolazine (RN) for prevention and cardioversion of atrial fibrillation (AF) have yielded conflicting results.

Objective: The purpose of this study was to conduct a meta-analysis of RCTs to examine the potential role of RN in the prevention and cardioversion of AF.

Methods: PubMed and EMBASE were searched until June 2016. Of 484 initially identified studies, 8 RCTs were finally analyzed.

Results: The analysis of RCTs showed that RN significantly reduced the incidence of AF compared to the control group in various clinical settings, such as after cardiac surgery, in acute coronary syndromes, and post-electrical cardioversion of AF (relative risk [RR] 0.67, 95% confidence interval [CI] 0.52-0.87, Z = 3.06, P = .002). Furthermore, a higher conversion rate of AF from the combined use of RN and amiodarone compared to amiodarone alone (RR 1.23, 95% CI 1.08-1.40, Z = 3.07, P = .002) was clear, with conversion time significantly shorter in RN plus amiodarone compared to the amiodarone group (weighted mean difference [WMD] = -10.38 hours, 95% CI -18.18 to -2.57, Z = 2.61, P = .009).

Conclusion: Our meta-analysis suggests that RN may be effective in AF prevention, whereas it potentiates and accelerates the conversion effect of amiodarone of recent-onset AF. Larger RCTs with long-term follow-up in diverse clinical settings are needed to further clarify the impact of RN on AF therapy.
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http://dx.doi.org/10.1016/j.hrthm.2016.10.008DOI Listing
January 2017

P-wave alternans in a patient with hyponatremia.

Hellenic J Cardiol 2016 May - Jun;57(3):188-190. Epub 2016 Jun 25.

Third Department of Cardiology, Hippokrateion Hospital, Aristotle University Medical School, 49 Konstantinoupoleos Str., 54642 Thessaloniki, Greece. Electronic address:

We describe an unusual electrocardiographic (ECG) case of an alternating P-wave configuration that spares other ECG components. Hyponatremia due to chronic indapamide use was proposed as a plausible cause of this ECG phenomenon because its correction led to the recovery of a steady P-wave morphology.
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http://dx.doi.org/10.1016/j.hjc.2015.12.001DOI Listing
June 2017

Successful catheter ablation of an incessant ventricular tachycardia originating from the posterior papillary muscle in a structurally normal right ventricle.

Hellenic J Cardiol 2016 Aug 20. Epub 2016 Aug 20.

Third Department of Cardiology, Hippokrateion Hospital, Aristotle University-Medical School, Thessaloniki, Greece.

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http://dx.doi.org/10.1016/j.hjc.2016.05.007DOI Listing
August 2016

Ranolazine as a novel therapy for pulmonary arterial hypertension.

Int J Cardiol 2016 Nov 22;223:860-862. Epub 2016 Aug 22.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2016.08.330DOI Listing
November 2016

Association Between rs2200733 Polymorphism on Chromosome 4q25 and Atrial Fibrillation in a Greek Population.

Hellenic J Cardiol 2015 May-Jun;56(3):224-9

Department of General Biology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Introduction: Atrial fibrillation (AF) is a common arrhythmia with evidence of genetic susceptibility. The rs2200733 single-nucleotide polymorphism (SNP) in a non-coding region on chromosome 4q25 has been associated with AF. The purpose of this case-control study was to examine the possible association of the rs2200733 polymorphism with AF in the Greek population.

Methods: A total of 295 individuals, 167 AF patients and 128 controls, were genotyped for the presence of the rs2200733 polymorphism using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLPs) method.

Results: The T/T genotype and the T allele were detected more frequently in patients with AF compared to controls (13.2% vs. 2.3%, p=0.001, and 29.6% vs. 17.9%, p=0.001), suggesting that the rs2200733 polymorphism increases susceptibility to AF in the Greek population. In a multivariate stepwise analysis that included many conventional precipitating factors for AF, T/T genotype and left atrium (LA) diameter were the only independent predictors of AF (OR 1.74, 95% CI: 1.40-2.98, p=0.005, and OR 2.88, 95% CI: 1.835.62, p<0.001, respectively). A trend of association was observed between the T/T genotype and lone AF (p=0.08).

Conclusions: Our results suggest that SNP rs2200733 confers a significant risk of AF in the Greek population, providing further support to the previously reported association between AF and rs2200733 polymorphism on chromosome 4q25.
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March 2016

A case of coronary-cameral fistulae involving all three major coronary arteries.

Circulation 2015 Mar;131(12):e380-1

From Third Cardiology Department, Hippokration Hospital, Aristotle University Medical School, Thessaloniki, Greece (N.F.); Department of Cardiology, Athens Euroclinic, Athens, Greece (E.G., D.G.K.); and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (D.G.K.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.114.013936DOI Listing
March 2015

The use of adenosine and adenosine triphosphate testing in the diagnosis, risk stratification and management of patients with syncope: current evidence and future perspectives.

Int J Cardiol 2015 Mar 30;183:267-73. Epub 2015 Jan 30.

Department of Arrhythmology, Maria Cecilia Hospital, Cotignola, Italy.

Syncope is a significant source of cardiovascular-related morbidity yet the etiology is frequently obscure and the identification of patients at highest risk is challenging. Adenosine (AD) and adenosine triphosphate (ATP) administrations have been suggested as potentially useful non-invasive tools in the diagnostic workup of patients with neurally-mediated or bradycardia-related syncope. It has been postulated that both compounds by modulating the autonomic innervation in the heart and exerting negative chronotropic and dromotropic effects in the conduction system, may unmask the mechanism of syncope. However, the clinical implications derived from the efficacy of both tests in the investigation of syncope remain unclear mainly due to inconclusive and occasionally contradictory results of published studies. This review article summarizes recent and past information in the use of ATP and AD in the investigation of syncope with emphasis on clinical trials. We present the current level of evidence for the use of these agents in clinical practice, identify areas where further research is warranted and highlight the future perspectives of these agents as complements to an accurate risk-stratification of patients with syncope.
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http://dx.doi.org/10.1016/j.ijcard.2015.01.089DOI Listing
March 2015

Improving cardiac resynchronization therapy response with multipoint left ventricular pacing: Twelve-month follow-up study.

Heart Rhythm 2015 Jun 9;12(6):1250-8. Epub 2015 Feb 9.

Department of Arrhythmology, Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy.

Background: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], St. Jude Medical) improves acute LV function and LV reverse remodeling at 3 months.

Objective: The purpose of this study was to test the hypothesis that MPP can also improve LV function at 12 months.

Methods: Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were randomized to receive pressure-volume (PV) loop optimized biventricular pacing with either conventional cardiac resynchronization therapy (CONV) or MPP. CRT response was defined by a reduction in end-systolic volume (ESV) ≥15% relative to BASELINE as determined by a blinded observer and alive status.

Results: Forty-four patients (New York Heart Association class III, ejection fraction [EF] 29% ± 6%, QRS 152 ± 17 ms) were enrolled and randomized to either CONV (N = 22) or MPP (N = 22). During the observation period, 2 patients died of noncardiac causes and 2 patients were lost to follow-up. After 12 months, 12 of 21 patients (57%) in the CONV group and 16 of 21 patients (76%) in the MPP group were classified as CRT responders (P = .33). ESV reduction and EF increase relative to BASELINE were significantly greater with MPP than with CONV (ESV: median -25%, interquartile range [IQR] [-39% to -20%] vs median -18%, IQR [-25% to -2%], P = .03; EF: median +15%, IQR [8% to 20%] vs median +5%, IQR [-1% to 8%], P <.001).

Conclusion: Sustaining the trend observed 3 months postimplant, PV loop-guided multipoint LV pacing resulted in greater LV reverse remodeling and increased LV function at 12 months compared to PV loop-guided conventional CRT.
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http://dx.doi.org/10.1016/j.hrthm.2015.02.008DOI Listing
June 2015

Ranolazine as a promising treatment option for atrial fibrillation: electrophysiologic mechanisms, experimental evidence, and clinical implications.

Pacing Clin Electrophysiol 2014 Oct 19;37(10):1412-20. Epub 2014 Aug 19.

Third Department of Cardiology, Hippokrateion Hospital, Aristotle University Medical School, Thessaloniki, Greece.

Currently available agents for pharmacologic management of atrial fibrillation (AF) are limited by their suboptimal efficacy and nonnegligible proarrhythmic risk. Ranolazine (RN) is a novel antianginal agent with increasingly appreciated antiarrhythmic properties that can suppress ventricular and supraventricular arrhythmias including AF. In this review, we describe the electrophysiological properties of RN, focusing on atrial-selective inhibition of a number of ion channels implicated in the development of AF, particularly the sodium current. We further summarize evidence from experimental studies that demonstrate a potent AF-suppressing effect of RN, alone or in combination with other antiarrhythmic drugs. Of clinical relevance, we present growing evidence from preliminary clinical investigations indicating the safety and efficacy of RN for prevention and treatment of AF in various clinical settings including prevention of AF in patients with acute coronary syndromes, prevention and conversion of postoperative AF after surgical coronary revascularization, sinus rhythm maintenance in drug-resistant recurrent AF, and facilitating of electrical or pharmacological cardioversion in cardioversion-resistant patients. While current experimental and clinical evidence points to RN as a potentially promising agent for suppression of AF, well-designed, large-scale trials will be required before RN can be considered for pharmacological treatment of AF in clinical practice.
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http://dx.doi.org/10.1111/pace.12486DOI Listing
October 2014

Endurance Sport Activity and Risk of Atrial Fibrillation - Epidemiology, Proposed Mechanisms and Management.

Arrhythm Electrophysiol Rev 2014 May 30;3(1):15-9. Epub 2014 May 30.

Department of Arrhythmology, Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy.

There is evidence for a higher prevalence of atrial fibrillation (AF) in athletes engaged in long-term endurance sports training compared with the general population. Although atrial anatomic adaptations, alterations in autonomic nervous system, chronic systemic inflammation and fibrosis have been proposed as potential mechanisms, they remain speculative. Medical therapy with long-term antiarrhythmic agents or 'pill in the pocket' medications is hampered by limitations, such as sports eligibility and interference with exercise tolerance. AF ablation represents a valid therapeutic option with results similar to these achieved in other patients. Nevertheless, further clinical trials are needed to confirm whether endurance sport practice affects the maintenance of sinus rhythm following catheter ablation of AF.
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http://dx.doi.org/10.15420/aer.2011.3.1.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711509PMC
May 2014