Publications by authors named "Giulio Conte"

130 Publications

A Primary Prevention Clinical Risk Score Model for Patients With Brugada Syndrome (BRUGADA-RISK).

JACC Clin Electrophysiol 2021 Feb 28;7(2):210-222. Epub 2020 Oct 28.

The Barts Heart Centre, Barts Health NHS Trust, London, United Kingdom. Electronic address:

Objectives: The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS).

Background: Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence.

Methods: A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation.

Results: A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 ± 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country.

Conclusions: This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverter-defibrillator prescription.
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http://dx.doi.org/10.1016/j.jacep.2020.08.032DOI Listing
February 2021

Adjusted Unit Value Transfer as a Tool for Raising Awareness on Ecosystem Services Provided by Constructed Wetlands for Water Pollution Control: An Italian Case Study.

Int J Environ Res Public Health 2021 Feb 5;18(4). Epub 2021 Feb 5.

IRIDRA SRL, Via La Marmora 51, 50121 Florence, Italy.

Constructed wetlands (CWs) are nature-based solutions (NBS) for water pollution control that can also be designed to be multipurpose in terms of additional ecosystem services (ESs), such as biodiversity support and social benefits. Awareness about additional ESs of CWs can be raised with value transfer (VT) methods for ESs monetization, in particular, the simplified adjusted unit VT method. A multi-criteria analysis (MCA) was performed to compare grey and green infrastructure alternatives for the management of a combined sewer overflow in the Buccinasco town (Italy), in which the criteria related to ESs were monetized with an adjusted VT method (B£ST software). The results highlighted the potential interest in the implementation of the green infrastructure in a new urban park, due to the activation of additional ESs of interest, such as health and recreational aspects. The results were also confirmed by a sensitivity analysis, which simulated the variation of preferences among different stakeholder groups (e.g., citizens, environmentalists). In conclusion, this work provided a transparent methodology to support decisions regarding green and grey infrastructure, allowing to evaluate additional ESs from the beginning of the decision stage with low cost and efforts.
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http://dx.doi.org/10.3390/ijerph18041531DOI Listing
February 2021

Worldwide Survey of COVID-19 Associated Arrhythmias.

Circ Arrhythm Electrophysiol 2021 Feb 7. Epub 2021 Feb 7.

Department of Medicine, Division of Cardiology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY.

- COVID-19 has led to over 1 million deaths worldwide and has been associated with cardiac complications including cardiac arrhythmias. The incidence and pathophysiology of these manifestations remain elusive. In this worldwide survey of patients hospitalized with COVID-19 who developed cardiac arrhythmias, we describe clinical characteristics associated with various arrhythmias, as well as global differences in modulations of routine electrophysiology practice during the pandemic. - We conducted a retrospective analysis of patients hospitalized with COVID-19 infection worldwide with and without incident cardiac arrhythmias. Patients with documented atrial fibrillation (AF), atrial flutter (AFL), supraventricular tachycardia (SVT), non-sustained or sustained ventricular tachycardia (VT), ventricular fibrillation (VF), atrioventricular block (AVB), or marked sinus bradycardia (HR<40bpm) were classified as having arrhythmia. De-identified data was provided by each institution and analyzed. - Data was collected for 4,526 patients across 4 continents and 12 countries, 827 of whom had an arrhythmia. Cardiac comorbidities were common in patients with arrhythmia: 69% had hypertension, 42% diabetes mellitus, 30% had heart failure and 24% coronary artery disease. Most had no prior history of arrhythmia. Of those who did develop an arrhythmia, the majority (81.8%) developed atrial arrhythmias, 20.7% developed ventricular arrhythmias, and 22.6% had bradyarrhythmia. Regional differences suggested a lower incidence of AF in Asia compared to other continents (34% vs. 63%). Most patients in in North America and Europe received hydroxychloroquine, though the frequency of hydroxychloroquine therapy was constant across arrhythmia types. Forty-three percent of patients who developed arrhythmia were mechanically ventilated and 51% survived to hospital discharge. Many institutions reported drastic decreases in electrophysiology procedures performed. - Cardiac arrhythmias are common and associated with high morbidity and mortality among patients hospitalized with COVID-19 infection. There were significant regional variations in the types of arrhythmias and treatment approaches.
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http://dx.doi.org/10.1161/CIRCEP.120.009458DOI Listing
February 2021

Short P-Wave Duration is a Marker of Higher Rate of Atrial Fibrillation Recurrences after Pulmonary Vein Isolation: New Insights into the Pathophysiological Mechanisms Through Computer Simulations.

J Am Heart Assoc 2021 Jan 7;10(2):e018572. Epub 2021 Jan 7.

Division of Cardiology Cardiocentro Ticino Lugano Switzerland.

Background Short ECG P-wave duration has recently been demonstrated to be associated with higher risk of atrial fibrillation (AF). The aim of this study was to assess the rate of AF recurrence after pulmonary vein isolation in patients with a short P wave, and to mechanistically elucidate the observation by computer modeling. Methods and Results A total of 282 consecutive patients undergoing a first single-pulmonary vein isolation procedure for paroxysmal or persistent AF were included. Computational models studied the effect of adenosine and sodium conductance on action potential duration and P-wave duration (PWD). About 16% of the patients had a PWD of 110 ms or shorter (median PWD 126 ms, interquartile range, 115 ms-138 ms; range, 71 ms-180 ms). At Cox regression, PWD was significantly associated with AF recurrence (=0.012). Patients with a PWD <110 ms (hazard ratio [HR], 2.20; 95% CI, 1.24-3.88; =0.007) and patients with a PWD ≥140 (HR, 1.87, 95% CI, 1.06-3.30; =0.031) had a nearly 2-fold increase in risk with respect to the other group. In the computational model, adenosine yielded a significant reduction of action potential duration 90 (52%) and PWD (7%). An increased sodium conductance (up to 200%) was robustly accompanied by an increase in conduction velocity (26%), a reduction in action potential duration 90 (28%), and PWD (22%). Conclusions One out of 5 patients referred for pulmonary vein isolation has a short PWD which was associated with a higher rate of AF after the index procedure. Computer simulations suggest that shortening of atrial action potential duration leading to a faster atrial conduction may be the cause of this clinical observation.
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http://dx.doi.org/10.1161/JAHA.120.018572DOI Listing
January 2021

Diagnosis, family screening, and treatment of inherited arrhythmogenic diseases in Europe: results of the European Heart Rhythm Association Survey.

Europace 2020 12;22(12):1904-1910

ERN GUARDHEART.

The spectrum of inherited arrhythmogenic diseases (IADs) includes disorders without overt structural abnormalities (i.e. primary inherited arrhythmia syndromes) and structural heart diseases (i.e. arrhythmogenic ventricular cardiomyopathy, hypertrophic cardiomyopathy). The aim of this European Heart Rhythm Association (EHRA) survey was to evaluate current clinical practice and adherence to 2015 European Society of Cardiology Guidelines regarding the management of patients with IADs. A 24-item centre-based online questionnaire was presented to the EHRA Research Network Centres and the European Cardiac Arrhythmia Genetics Focus Group members. There were 46 responses from 20 different countries. The survey revealed that 37% of centres did not have any dedicated unit focusing on patients with IADs. Provocative drug challenges were widely used to rule-out Brugada syndrome (BrS) (91% of centres), while they were used in a minority of centres during the diagnostic assessment of long-QT syndrome (11%), early repolarization syndrome (12%), or catecholaminergic polymorphic ventricular tachycardia (18%). While all centres advised family clinical screening with electrocardiograms for all first-degree family members of patients with IADs, genetic testing was advised in family members of probands with positive genetic testing by 33% of centres. Sudden cardiac death risk stratification was straightforward and in line with current guidelines for hypertrophic cardiomyopathy, while it was controversial for other diseases (i.e. BrS). Finally, indications for ventricular mapping and ablation procedures in BrS were variable and not in agreement with current guidelines in up to 54% of centres.
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http://dx.doi.org/10.1093/europace/euaa223DOI Listing
December 2020

Left Atrial Appendage Electrical Isolation Reduces Atrial Fibrillation Recurrences: A Simulation Study.

Circ Arrhythm Electrophysiol 2021 Jan 24;14(1):e009230. Epub 2020 Dec 24.

Center for Computational Medicine in Cardiology, Institute of Computational Science, Università della Svizzera italiana, Lugano, Switzerland (A.G., S.P., G.C., R.K., A.A.).

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http://dx.doi.org/10.1161/CIRCEP.120.009230DOI Listing
January 2021

Editorial: Sudden Cardiac Death and Channelopathies.

Front Cardiovasc Med 2020 25;7:605834. Epub 2020 Nov 25.

Heart Rhythm Management Center, Brussels, Belgium.

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http://dx.doi.org/10.3389/fcvm.2020.605834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723825PMC
November 2020

Challenges in activation of remote monitoring in patients with cardiac rhythm devices during the coronavirus (COVID-19) pandemic.

Int J Cardiol 2020 Dec 2. Epub 2020 Dec 2.

Division of Cardiology, Cardiocentro Ticino, Lugano, Switzerland.

Background: Remote monitoring (RM) technology embedded in cardiac rhythm devices permits continuous monitoring of device function, and recording of selected cardiac physiological parameters and cardiac arrhythmias and may be of utmost utility during Coronavirus (COVID-19) pandemic, when in-person office visit for regular follow-up were postponed. However, patients not alredy followed-up via RM represent a challenging group of patients to be managed during the lockdown.

Methods: We reviewed patient files scheduled for an outpatient visit between January 1, 2020 and May 11th, 2020 to assess the proportion of patients in whom RM activation was possible without office visit, and compared them to those scheduled for visit before the lockdown.

Results: During COVID-19 pandemic, RM activation was feasible in a minority of patients (7.8% of patients) expected at outpatient clinic for a follow-up visit and device check-up. This was possible in a good proportion of complex implantable devices such as cardiac resynchronization therapy and implantable cardioverter defibrillator but only in a minority of patients with a pacemaker the RM function could be activated during the period of restricted access to hospital.

Conclusions: Our experience strongly suggest to consider the systematic activation of RM function at the time of implantation or - by default programming - in all cardiac rhythm management devices.
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http://dx.doi.org/10.1016/j.ijcard.2020.11.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709476PMC
December 2020

Reconstruction of three-dimensional biventricular activation based on the 12-lead electrocardiogram via patient-specific modelling.

Europace 2020 Nov 26. Epub 2020 Nov 26.

Center for Computational Medicine in Cardiology, Institute of Computational Science, Università della Svizzera italiana, Via Giuseppe Buffi 13, CH-6904 Lugano, Switzerland.

Aims: Non-invasive imaging of electrical activation requires high-density body surface potential mapping. The nine electrodes of the 12-lead electrocardiogram (ECG) are insufficient for a reliable reconstruction with standard inverse methods. Patient-specific modelling may offer an alternative route to physiologically constraint the reconstruction. The aim of the study was to assess the feasibility of reconstructing the fully 3D electrical activation map of the ventricles from the 12-lead ECG and cardiovascular magnetic resonance (CMR).

Methods And Results: Ventricular activation was estimated by iteratively optimizing the parameters (conduction velocity and sites of earliest activation) of a patient-specific model to fit the simulated to the recorded ECG. Chest and cardiac anatomy of 11 patients (QRS duration 126-180 ms, documented scar in two) were segmented from CMR images. Scar presence was assessed by magnetic resonance (MR) contrast enhancement. Activation sequences were modelled with a physiologically based propagation model and ECGs with lead field theory. Validation was performed by comparing reconstructed activation maps with those acquired by invasive electroanatomical mapping of coronary sinus/veins (CS) and right ventricular (RV) and left ventricular (LV) endocardium. The QRS complex was correctly reproduced by the model (Pearson's correlation r = 0.923). Reconstructions accurately located the earliest and latest activated LV regions (median barycentre distance 8.2 mm, IQR 8.8 mm). Correlation of simulated with recorded activation time was very good at LV endocardium (r = 0.83) and good at CS (r = 0.68) and RV endocardium (r = 0.58).

Conclusion: Non-invasive assessment of biventricular 3D activation using the 12-lead ECG and MR imaging is feasible. Potential applications include patient-specific modelling and pre-/per-procedural evaluation of ventricular activation.
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http://dx.doi.org/10.1093/europace/euaa330DOI Listing
November 2020

Impact of contact force sensing technology on outcome of catheter ablation of idiopathic pre-mature ventricular contractions originating from the outflow tracts.

Europace 2020 Nov 18. Epub 2020 Nov 18.

Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland.

Aims: Catheter ablation of frequent idiopathic pre-mature ventricular contractions (PVC) is increasingly performed. While potential benefits of contact force (CF)-sensing technology for atrial fibrillation ablation have been assessed in several studies, the impact of CF-sensing on ventricular arrhythmia ablation remains unknown. This study aimed to compare outcomes of idiopathic outflow tract PVC ablation when using standard ablation catheters as opposed to CF-sensing catheters.

Methods And Results: In a retrospective multi-centre study, unselected patients undergoing catheter ablation of idiopathic outflow tract PVCs between 2013 and 2016 were enrolled. All procedures were performed using irrigated-tip ablation catheters and a 3D electro-anatomical mapping system. Sustained ablation success was defined as a  ≥80% reduction of pre-procedural PVC burden determined by 24 h Holter ECG during follow-up. Overall, 218 patients were enrolled (median age 52 years, 51% males). Baseline and procedural data were similar in the standard ablation (24%) and the CF-sensing group (76%). Overall, the median PVC burden decreased from 21% (IQR 10-30%) before ablation to 0.2% (IQR 0-3.0%) after a median follow-up of 2.3 months (IQR 1.4-3.9 months). The rates of both acute (91% vs. 91%, P = 0.94) and sustained success (79% vs. 74%, P = 0.44) were similar in the standard ablation and the CF-sensing groups. No differences were observed in subgroups according to arrhythmia origin from the RVOT (65%) or LVOT (35%). Complications were rare (1.8%) and evenly distributed between the two groups.

Conclusion: The use of CF-sensing technology is not associated with increased success rate nor decreased complication rate in idiopathic outflow tract PVC ablation.
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http://dx.doi.org/10.1093/europace/euaa315DOI Listing
November 2020

Idiopathic ventricular fibrillation: the ongoing quest for diagnostic refinement.

Europace 2020 Oct 10. Epub 2020 Oct 10.

Department of Cardiovascular Medicine (Clinician-Investigator Training Program), Mayo Clinic, Rochester, MN, USA.

Prior to the recognition of distinct clinical entities, such as Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and long QT syndrome, all sudden cardiac arrest (SCA) survivors with ventricular fibrillation (VF) and apparently structurally normal hearts were labelled as idiopathic ventricular fibrillation (IVF). Over the last three decades, the definition of IVF has changed substantially, mostly as result of the identification of the spectrum of SCA-predisposing genetic heart diseases (GHDs), and the molecular evidence, by post-mortem genetic analysis (aka, the molecular autopsy), of cardiac channelopathies as the pathogenic basis for up to 35% of unexplained cases of sudden cardiac death (SCD) in the young. The evolution of the definition of IVF over time has led to a progressively greater awareness of the need for an extensive diagnostic assessment in unexplained SCA survivors. Nevertheless, GHDs are still underdiagnosed among SCA survivors, due to the underuse of pharmacological challenges (i.e. sodium channel blocker test), misrecognition of electrocardiogram (ECG) abnormalities/patterns (i.e. early repolarization pattern or exercise-induced ventricular bigeminy) or errors in the measurement of ECG parameters (e.g. the heart-rate corrected QT interval). In this review, we discuss the epidemiology, diagnostic approaches, and the controversies related to role of the genetic background in unexplained SCA survivors with a default diagnosis of IVF.
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http://dx.doi.org/10.1093/europace/euaa211DOI Listing
October 2020

A factor score reflecting cognitive functioning in patients from the Swiss Atrial Fibrillation Cohort Study (Swiss-AF).

PLoS One 2020 9;15(10):e0240167. Epub 2020 Oct 9.

Cardiology Division, Department of Medicine, University Hospital Basel, Basel, Switzerland.

Background: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is considered as risk factor for the development of mild cognitive impairment (MCI) and dementia. However, dynamics of cognitive functions are subtle, and neurocognitive assessments largely differ in detecting these changes. We aimed to develop and evaluate a score which represents the common aspects of the cognitive functions measured by validated tests (i.e., "general cognitive construct"), while reducing overlap between tests and be more sensitive to identify changes in overall cognitive functioning.

Methods: We developed the CoCo (cognitive construct) score to reflect the cognitive performance obtained by all items of four neurocognitive assessments (Montreal Cognitive Assessment (MoCA); Trail Making Test; Semantic Fluency, animals; Digital Symbol Substitution Test). The sample comprised 2,415 AF patients from the Swiss Atrial Fibrillation Cohort Study (Swiss-AF), 87% aged at least 65 years. Psychometric statistics were calculated for two cognitive measures based on (i) the full set of items from the neurocognitive test battery administered in the Swiss-AF study (i.e., CoCo item set) and (ii) the items from the widely used MoCA test. For the CoCo item set, a factor score was derived based on a principal component analysis, and its measurement properties were analyzed.

Results: Both the MoCA item set and the full neurocognitive test battery revealed good psychometric properties, especially the full battery. A one-factor model with good model fit and performance across time and groups was identified and used to generate the CoCo score, reflecting for each patient the common cognitive skill performance measured across the full neurocognitive test battery. The CoCo score showed larger effect sizes compared to the MoCA score in relation to relevant clinical variables.

Conclusion: The derived factor score allows summarizing AF patients' cognitive performance as a single score. Using this score in the Swiss-AF project increases measurement sensitivity and decreases the number of statistical tests needed, which will be helpful in future studies addressing how AF affects the risk of developing cognitive impairment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240167PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546506PMC
December 2020

HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for telehealth and arrhythmia monitoring during and after a pandemic.

J Arrhythm 2020 Jun 25. Epub 2020 Jun 25.

Society Washington US.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started in the city of Wuhan late in 2019. Within a few months, the disease spread toward all parts of the world and was declared a pandemic on March 11, 2020. The current health care dilemma worldwide is how to sustain the capacity for quality services not only for those suffering from COVID-19 but also for non-COVID-19 patients, all while protecting physicians, nurses, and other allied health care workers.
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http://dx.doi.org/10.1002/joa3.12389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361598PMC
June 2020

High-density mapping in patients undergoing ablation of atrial fibrillation with the fourth-generation cryoballoon and the new spiral mapping catheter.

Europace 2020 11;22(11):1653-1658

Division of Cardiology, Cardiocentro Ticino, Lugano, Switzerland.

Aims: To assess the value of high-density mapping (HDM) in revealing undetected incomplete pulmonary vein isolation (PVI) after the fourth-generation cryoballoon (CB4G) ablation compared to the previous cryoballoon's versions.

Methods And Results: Consecutive patients with paroxysmal or early-persistent atrial fibrillation (AF) undergoing CB ablation as the index procedure, assisted by HDM, were retrospectively included in this study. A total of 68 patients (52 males; mean age: 60 ± 12 years, 58 paroxysmal AF) were included, and a total of 272 veins were mapped. Fourth-generation cryoballoon with the new spiral mapping catheter (SMC) was used in 35 patients (51%). Time to PVI was determined in 102/132 (77%) and in 112/140 (80%) veins during second-generation cryoballoon/third-generation cryoballoon (CB2G/CB3G) and CB4G ablation, respectively (P = 0.66). There was a statistically significant difference in terms of discrepancy rate between the SMC and the mini-basket catheter in PV detection after CB4G and CB2G/CB3G ablation(1.4% vs. 7.6%; P = 0.01). A total of 57 patients (84%) remained free of symptomatic AF during a mean follow-up of 9.8 ± 4.6 months.

Conclusion: High-density mapping after cryoballoon ablation using CB4G and the new SMC identifies incomplete PVI, not detected by the new SMC, in a significantly lower proportion of veins compared to HDM performed after the other generation CB ablation.
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http://dx.doi.org/10.1093/europace/euaa160DOI Listing
November 2020

Contemporary management of patients with syncope in clinical practice: an EHRA physician-based survey.

Europace 2020 06;22(6):980-987

School of Medicine, University of Belgrade, Cardiology Clinic, Clinical Center of Serbia Visegradska 26, Belgrade 11000, Serbia.

Syncope is a heterogeneous syndrome encompassing a large spectrum of mechanisms and outcomes. The European Society of Cardiology published an update of the Syncope Guidelines in 2018. The aim of the present survey was to capture contemporary management of syncope and guideline implementation among European physicians. A 23-item questionnaire was presented to 2588 European Heart Rhythm Association (EHRA) members from 32 European countries. The response rate was 48%, but only complete responses (n = 161) were included in this study. The questionnaire contained specific items regarding syncope facilities, diagnostic definitions, diagnostic tools, follow-up, and therapy. The survey revealed that many respondents did not have syncope units (88%) or dedicated management algorithms (44%) at their institutions, and 45% of the respondents reported syncope-related hospitalization rates >25%, whereas most (95%) employed close monitoring and hospitalization in syncope patients with structural heart disease. Carotid sinus massage, autonomic testing, and tilt-table testing were inconsistently used. Indications were heterogeneous for implanted loop recorders (79% considered them for recurrent syncope in high-risk patients) or electrophysiological studies (67% considered them in bifascicular block and inconclusive non-invasive testing). Non-pharmacological therapy was consistently considered by 68% of respondents; however, there was important variation regarding the choice of drug and device therapy. While revealing an increased awareness of syncope and good practice, our study identified important unmet needs regarding the optimal management of syncope and variable syncope guideline implementation.
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http://dx.doi.org/10.1093/europace/euaa085DOI Listing
June 2020

Development of Chitosan/Mannitol Microparticles as Delivery System for the Oral Administration of a Spirulina Bioactive Peptide Extract.

Molecules 2020 Apr 29;25(9). Epub 2020 Apr 29.

Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano (SA), Italy.

contains several compounds showing nutritional and therapeutic benefits. Recently, a series of peptides able to reduce the blood pressure level and to enhance the endothelial vasorelaxation was isolated from the hydrolyzed highly water-soluble extract (HSE). However, HSE shows critical organoleptic characteristics also having poor intestinal permeability, limiting absorption when orally delivered. This research aims to overcome the critical issues through the encapsulation of HSE in Chitosan/Mannitol-(CM)-based microparticles by spray drying. The produced powders (CM-HSE) showed good process yield (≈70%) and encapsulation efficiency (≈100%) also having good derived flow properties as well as stability up to six months storage. The microparticles constituting the spray-dried powder resulted in an amorphous micrometric state (d ≈ 14 µm) able to retain dark colour and unpleasant smell of raw HSE. Moreover, the in vitro permeation study by Franz cell indicated that the engineered microparticles are able to enhance the permeation of HSE through an intestinal biomimetic barrier (551.13 μg/cm CM-HSE vs. 315.46 μg/cm HSE at 270 min).
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http://dx.doi.org/10.3390/molecules25092086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248919PMC
April 2020

Response to "Electrocardiographic sexual differences in patients with atrial fibrillation".

Int J Cardiol 2020 06;308:50-51

Center for Computational Modeling in Cardiology, Switzerland; Cardiocentro Ticino, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2020.03.016DOI Listing
June 2020

Brugada syndrome: A comprehensive review of pathophysiological mechanisms and risk stratification strategies.

Int J Cardiol Heart Vasc 2020 Feb 21;26:100468. Epub 2020 Jan 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, PR China.

Brugada syndrome (BrS) is an inherited ion channel channelopathy predisposing to ventricular arrhythmias and sudden cardiac death. Originally believed to be predominantly associated with mutations in SCN5A encoding for the cardiac sodium channel, mutations of 18 genes other than SCN5A have been implicated in the pathogenesis of BrS to date. Diagnosis is based on the presence of a spontaneous or drug-induced coved-type ST segment elevation. The predominant electrophysiological mechanism underlying BrS remains disputed, commonly revolving around the three main hypotheses based on abnormal repolarization, depolarization or current-load match. Evidence from computational modelling, pre-clinical and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening ventricular arrhythmic events. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers. Current treatment options include pharmacological therapy to reduce the occurrence of arrhythmic events or to abort these episodes, and interventions such as implantable cardioverter-defibrillator insertion or radiofrequency ablation of abnormal arrhythmic substrate.
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http://dx.doi.org/10.1016/j.ijcha.2020.100468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974766PMC
February 2020

Sex-related electrocardiographic differences in patients with different types of atrial fibrillation: Results from the SWISS-AF study.

Int J Cardiol 2020 05 3;307:63-70. Epub 2020 Jan 3.

Center for Computational Modeling in Cardiology, Switzerland; Cardiocentro Ticino, Switzerland. Electronic address:

Background: Sex-related electrocardiographic differences are a well-known phenomenon, but not their expression in patients with atrial fibrillation (AF). In this study we aim to assess the presence of significant sex-related differences in ECG features, with particular attention to P-wave parameters, of a large cohort of patients affected by different types of AF.

Methods: A 5-min resting 16-lead ECG was evaluated for 1119 AF patients in sinus rhythm. The durations of the main ECG waves and intervals were measured for both atrial and ventricular activity. Moreover, the beat-to-beat P-wave variability was computed for lead II and for the first principal component (PC1) computed across the 16 leads. The percentage of variance explained by PC1 was computed.

Results: Males compared to females showed significantly longer RR interval (1.02 ± 0.16 s vs 0.97 ± 0.15 s, p < .001), PQ interval (191 ± 34 ms vs 183 ± 35 ms, p = .008), QRS duration (105 ± 17 ms vs 98 ± 13 ms, p = .021), significantly lower percentage of variance explained by PC1 and P-wave variability. Males with paroxysmal AF compared to females with paroxysmal AF had significantly longer RR interval (1.01 ± 0.17 s vs 0.96 ± 0.14 s, p < .001), shorter QTc (388 ± 27 ms vs 402 ± 27 ms, p < .001), lower P-wave variability in PC1. Males with persistent AF compared to females with persistent AF had significantly shorter QTc interval (396 ± 30 ms vs 407 ± 26 ms, p = .019), longer PQ interval (194 ± 35 ms vs 182 ± 30 ms, p = .037), higher V1 terminal force (2.1 ± 1.2 mV*ms vs 1.8 ± 1 mV*ms, p = .007), lower percentage of variance explained by PC1.

Conclusions: AF patients present with several sex-related ECG differences. Consequently, sex should be taken into account when developing ECG algorithms identifying patients at risk for AF progression.
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http://dx.doi.org/10.1016/j.ijcard.2019.12.053DOI Listing
May 2020

The influence of scar on the spatio-temporal relationship between electrical and mechanical activation in heart failure patients.

Europace 2020 05;22(5):777-786

Center for Computational Medicine in Cardiology, Università della Svizzera italiana, Via G. Buffi 13, CH-6900 Lugano, Switzerland.

Aims: The aim of this study was to determine the relationship between electrical and mechanical activation in heart failure (HF) patients and whether electromechanical coupling is affected by scar.

Methods And Results: Seventy HF patients referred for cardiac resynchronization therapy or biological therapy underwent endocardial anatomo-electromechanical mapping (AEMM) and delayed-enhancement magnetic resonance (CMR) scans. Area strain and activation times were derived from AEMM data, allowing to correlate mechanical and electrical activation in time and space with unprecedented accuracy. Special attention was paid to the effect of presence of CMR-evidenced scar. Patients were divided into a scar (n = 43) and a non-scar group (n-27). Correlation between time of electrical and mechanical activation was stronger in the non-scar compared to the scar group [R = 0.84 (0.72-0.89) vs. 0.74 (0.52-0.88), respectively; P = 0.01]. The overlap between latest electrical and mechanical activation areas was larger in the absence than in presence of scar [72% (54-81) vs. 56% (36-73), respectively; P = 0.02], with smaller distance between the centroids of the two regions [10.7 (4.9-17.4) vs. 20.3 (6.9-29.4) % of left ventricular radius, P = 0.02].

Conclusion: Scar decreases the association between electrical and mechanical activation, even when scar is remote from late activated regions.
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http://dx.doi.org/10.1093/europace/euz346DOI Listing
May 2020

Acute fluctuating neurological deficits after pulmonary vein isolation: unmasking a rare complication due to spontaneous spinal subdural bleeding: a case report.

Eur Heart J Case Rep 2019 Sep 5;3(3):ytz109. Epub 2019 Jul 5.

Department of Cardiology, Fondazione Cardiocentro Ticino, Via Tesserete 48, CH-6900 Lugano, Switzerland.

Background: Pulmonary vein isolation (PVI) is becoming the therapy of choice for symptomatic paroxysmal drug-refractory atrial fibrillation (AF). The most frequently reported complications are vascular complications (1.4%). Bleeding complications of the central nervous system have rarely been described. We report a case of spontaneous spinal bleed after PVI.

Case Summary: A 68-year-old woman with a 2-year history of highly symptomatic paroxysmal AF (EHRA 3) was referred for a PVI redo procedure. A high-density mapping showed pulmonary vein reconnection of all pulmonary veins successfully isolated by radiofrequency ablation. During the entire procedure, the patient had sinus rhythm with an ACT around 300 s. No intraprocedural and peri-procedural complications occurred. Four hours after haemostasis, the anticoagulation clotting time (ACT) was 110 s and rivaroxaban (20 mg) was reinitiated. In the following hours, the patient developed fluctuating neurological lower limb symptoms. A lumbar magnetic resonance imaging showed a subdural spinal haematic collection with an associated epidural component from L3 to S2 exerting compression over the dural sheath. A conservative treatment approach was adopted with progressive recovery of sensorial and motor deficits. After 5 months, the patient still presented residual lower limb motor deficits necessitating the support of a walking stick.

Discussion: We describe the first case of a spontaneous spinal bleeding following PVI. Given the gradual diffusion of PVI to treat AF in more clinically complex patients with a larger range of comorbidities, particular consideration should be given to seek predisposing bleeding factors in order to assess the risk for neurological complications.
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http://dx.doi.org/10.1093/ehjcr/ytz109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764566PMC
September 2019

Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry.

Europace 2019 Nov;21(11):1670-1677

Electrophysiology Unit, Department of Cardiology, Fondazione Cardiocentro Ticino, via Tesserete 48, Lugano, Switzerland.

Aims : To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs).

Methods And Results: Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18-0.92; P = 0.03].

Conclusion : Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences.
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http://dx.doi.org/10.1093/europace/euz221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826207PMC
November 2019

CPVT: Arrhythmogenesis, Therapeutic Management, and Future Perspectives. A Brief Review of the Literature.

Front Cardiovasc Med 2019 12;6:92. Epub 2019 Jul 12.

Heart Rhythm Management Centre, Vrije University, Brussels, Belgium.

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a primary electrical disease characterized by a normal resting electrocardiogram and induction of malignant arrhythmias during adrenergic stress leading to syncope or sudden cardiac death (SCD). CPVT is caused by mutations in the cardiac ryanodine receptor (RyR2) or in the sarcoplasmic reticulum protein calsequestrin 2 genes (). The RyR2 mutations are responsible for the autosomal dominant form of CPVT, while mutations are rare and account for the recessive form. These mutations cause a substantial inballance in the homeostasis of intracellular calcium resulting in polymorphic ventricular tachycardia through triggered activity. Beta blockers were for years the cornerstone of therapy in these patients. Sodium channel blockers, especially flecainide, have an additive role in those not responding in beta blockade. Implantation of defibrillators needs a meticulous evaluation since inappropriate shocks may lead to electrical storm. Finally, cardiac sympathetic denervation might also be an alternative therapeutic option. Early identification and risk stratification is of major importance in patients with CPVT. The aim of the present review is to present the arrhythmogenic mechanisms of the disease, the current therapies applied and potential future perspectives.
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http://dx.doi.org/10.3389/fcvm.2019.00092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644488PMC
July 2019

Ethnic differences in patients with Brugada syndrome and arrhythmic events: New insights from Survey on Arrhythmic Events in Brugada Syndrome.

Heart Rhythm 2019 10 5;16(10):1468-1474. Epub 2019 Jul 5.

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Heart Institute, Hadassah University Hospital, Jerusalem, Israel. Electronic address:

Background: There is limited information on ethnic differences between patients with Brugada syndrome (BrS) and arrhythmic events (AEs).

Objective: The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between white and Asian patients with BrS and AEs.

Methods: The Survey on Arrhythmic Events in Brugada Syndrome is a multicenter survey from Western and Asian countries, gathering 678 patients with BrS and first documented AE. After excluding patients with other (n = 14 [2.1%]) or unknown (n = 30 [4.4%]) ethnicity, 364 (53.7%) whites and 270 (39.8%) Asians comprised the study group.

Results: There was no difference in AE age onset (41.3 ± 16.1 years in whites vs 43.3 ± 12.3 years in Asians; P = .285). Higher proportions of whites were observed in pediatric and elderly populations. Asians were predominantly men (98.1% vs 85.7% in whites; P < .001) and frequently presented with aborted cardiac arrest (71.1% vs 56%; P < .001). Asians tended to display more spontaneous type 1 BrS-ECG pattern (71.5% vs 64.3%; P = .068). A family history of sudden cardiac death was noted more in whites (29.1% vs 11.5%; P < .001), with a higher rate of SCN5A mutation carriers (40.1% vs 13.2% in Asians; P < .001), as well as more fever-related AEs (8.5% vs 2.9%; P = .011). No difference was observed between the 2 groups regarding history of syncope and ventricular arrhythmia inducibility.

Conclusion: There are important differences between Asian and white patients with BrS. Asian patients present almost exclusively as male adults, more often with aborted cardiac arrest and spontaneous type 1 BrS-ECG. However, they have less family history of sudden cardiac death and markedly lower SCN5A mutation rates. The striking difference in SCN5A mutation rates should be tested in future studies.
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http://dx.doi.org/10.1016/j.hrthm.2019.07.003DOI Listing
October 2019

Usefulness of Genetic Testing in Sudden Cardiac Arrest Survivors With or Without Previous Clinical Evidence of Heart Disease.

Am J Cardiol 2019 06 18;123(12):2031-2038. Epub 2019 Mar 18.

Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address:

Genetic testing in survivors of sudden cardiac arrest (SCA) with a suspicious cardiac phenotype is considered clinically useful, whereas its value in the absence of phenotype is disputed. We aimed to evaluate the clinical utility of genetic testing in survivors of SCA with or without cardiac phenotype. Sixty unrelated SCA survivors (median age: 34 [interquartile range 20 to 43] years, 82% male) without coronary artery disease were included: 24 (40%) with detectable cardiac phenotype (Ph(+)SCA) after the SCA event and 36 (60%) with no clear cardiac phenotype (Ph(-)SCA). The targeted exome sequencing was performed using the TruSight-One Sequencing Panel (Illumina). Variants in 185 clinically relevant cardiac genes with minor allele frequency <1% were analyzed. A total of 32 pathogenic or likely pathogenic variants were found in 27 (45%) patients: 17 (71%) in the Ph(+)SCA group and 10 (28%) in the Ph(-)SCA group. Sixteen (67%) Ph(+)SCA patients hosted mutations congruent with the suspected phenotype, in which 12 (50%) were cardiomyopathies and 4 (17%) channelopathies. In Ph(-)SCA cases, 6 (17%) carried a mutation in cardiac ion channel genes that could explain the event. The additional 4 (11%) mutations in this group, could not explain the phenotype and require additional studies. In conclusion, cardiac genetic testing was positive in nearly 2/3 patients of the Ph(+)SCA group and in 1/6 of the Ph(-)SCA group. The test was useful in both groups to identify or confirm an inherited heart disease, with an important impact on the patient care and first-degree relatives at risk.
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http://dx.doi.org/10.1016/j.amjcard.2019.02.061DOI Listing
June 2019

Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome.

J Am Coll Cardiol 2019 04;73(14):1756-1765

Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Background: Information on young patients with Brugada syndrome (BrS) and arrhythmic events (AEs) is limited.

Objectives: The purpose of this study was to describe their characteristics and management as well as risk factors for AE recurrence.

Methods: A total of 57 patients (age ≤20 years), all with BrS and AEs, were divided into pediatric (age ≤12 years; n = 26) and adolescents (age 13 to 20 years; n = 31).

Results: Patients' median age at time of first AE was 14 years, with a majority of males (74%), Caucasians (70%), and probands (79%) who presented as aborted cardiac arrest (84%). A significant proportion of patients (28%) exhibited fever-related AE. Family history of sudden cardiac death (SCD), prior syncope, spontaneous type 1 Brugada electrocardiogram (ECG), inducible ventricular fibrillation at electrophysiological study, and SCN5A mutations were present in 26%, 49%, 65%, 28%, and 58% of patients, respectively. The pediatric group differed from the adolescents, with a greater proportion of females, Caucasians, fever-related AEs, and spontaneous type-1 ECG. During follow-up, 68% of pediatric and 64% of adolescents had recurrent AE, with median time of 9.9 and 27.0 months, respectively. Approximately one-third of recurrent AEs occurred on quinidine therapy, and among the pediatric group, 60% of recurrent AEs were fever-related. Risk factors for recurrent AE included sinus node dysfunction, atrial arrhythmias, intraventricular conduction delay, or large S-wave on ECG lead I in the pediatric group and the presence of SCN5A mutation among adolescents.

Conclusions: Young BrS patients with AE represent a very arrhythmogenic group. Current management after first arrhythmia episode is associated with high recurrence rate. Alternative therapies, besides defibrillator implantation, should be considered.
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http://dx.doi.org/10.1016/j.jacc.2019.01.048DOI Listing
April 2019