Firat Duru - Academia.edu (original) (raw)

Papers by Firat Duru

Europace, Jun 1, 2016

To assess heart rhythm disturbances (HRD) rate and structure in children with single ventricle (S... more To assess heart rhythm disturbances (HRD) rate and structure in children with single ventricle (SV) at the stages of defect hemodynamic correction. Methods: 70 patients with CHD with SV that were performed total cavopulmonary connection (TCPC) with extracardiac conduit were examined. All the patients were performed ECG and Holter monitoring. To integrate data, all the patients were divided into 8 groups: 1-sinus rhythm; 2-non-sinus rhythm (atrial rate, nodal rhythm, AV-dissociation); 3-bradyarrhythmia (sinus and atrial bradycardia); 4-sinus tachycardia; 5-supraventricular tachycardias (SVT) (paroxysmal and incessant); 6-extrasystole (supraventricular and ventricular); 7-atrioventricular block (AVB) of I-II deg.; 8-AV block, III deg. Results: Only one patient had 2 SVT paroxysms, broken cordarone bolus dosing, in early postoperative period at the first stage. At the second stage (Glenn operation) HRD was recorded in 14 (20%) pts, in 7 (10%) of them during admission. Non-sinus rhythm (86%) predominated in HRD structure. At the third stage (TCPC) recent HRD was recorded in 36 (51.4%) pts. After TCPC recent HRD was registered in 23 (32.9%) pts, in 13 of them HRD was preserved, and in 34 (48.6%) it was not recorded. Arrhythmias, connected with sinus node dysfunction (bradyarrhythmias, SVT, non-sinus rhythm), predominate in HRD structure in 43.9%. The negative correlation between Sat O2 in capillary blood and arrhythmias frequency was disclosed after TCPC, p ¼ 0,02. The older patient at TCPC and lower SV contractile function after it, the oftener arrhythmias, connected with sinus node dysfunction, appeared (p ¼ 0,04). Conclusions: HRD appeared in patients with extracardiac Fontan at any stage of hemodynamic correction. Arrhythmias, connected with sinus node dysfunction, predominated in frequency of occurrence. Low Sat, low SV contractile function and the age of TCPC made their own contributions into HRD appearance after Fontan.

International Journal of Molecular Sciences

Aims: Some gene variants in the sodium channels, as well as calcium channels, have been associate... more Aims: Some gene variants in the sodium channels, as well as calcium channels, have been associated with Brugada syndrome (BrS). However, the investigation of the human cellular phenotype and the use of drugs for BrS in presence of variant in the calcium channel subunit is still lacking. Objectives: The objective of this study was to establish a cellular model of BrS in the presence of a CACNB2 variant of uncertain significance (c.425C > T/p.S142F) using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and test drug effects using this model. Methods and results: This study recruited cells from a patient with Brugada syndrome (BrS) and recurrent ventricular fibrillation carrying a missense variant in CACNB2 as well as from three healthy independent persons. These cells (hiPSC-CMs) generated from skin biopsies of healthy persons and the BrS patient (BrS-hiPSC-CMs) as well as CRISPR/Cas9 corrected cells (isogenic control, site-variant corrected) were used for th...

Aims The treatment with the wearable cardioverter defibrillator (WCD) may protect against sudden ... more Aims The treatment with the wearable cardioverter defibrillator (WCD) may protect against sudden cardiac death (SCD) as a bridging therapy until a cardioverter-defibrillator may be implanted. We analyzed in a multicenter setting a consecutive patient cohort wearing WCD to explore gender differences. Methods and results We analyzed 708 consecutive patients, 579 from whom were males and 129 females (age, 60.5±14 vs. 61.6±17 years old; p=0.44). All patients were divided into age quartiles for analysis. While the rate of ischemic cardiomyopathy (ICM) as a cause of prescription of WCD was significantly higher in males as compared to females (42.7% vs. 26.4%; p=0.001), females received it more frequently due to non-ischemic cardiomyopathy (NICM) (55.8% vs. 42.7%); p=0.009). The wear time of WCD was equivalent in both groups (21.1±4.3 hours/days in males vs. 21.5±4.4 hours/days in females; p=0.27; and 62.6±44.3 days in males vs. 56.5±39 days in females; p=0.15). Mortality was comparable in...

Objective—To assess diVerences in psychosocial adaptation, quality of life, and incidence of aVec... more Objective—To assess diVerences in psychosocial adaptation, quality of life, and incidence of aVective disorders between patients with pacemakers and those with implantable cardioverterdefibrillators (ICDs). Design—Patients aged 40–70 years who underwent a first pectoral implantation of a pacemaker or an ICD system were studied. All subjects were asked to complete the hospital anxiety and depression scale (HAD), the short form general health survey (SF-36), and a specially designed device related questionnaire. Data analysis was performed for three patient groups: pacemaker (n = 76), ICD patients who received therapeutic shocks (n = 45), and ICD patients who did not receive shocks (n = 31). Results—There were no diVerences between the three patient groups in HAD scores or in any of the SF-36 subscales or summary ratings. Probable depressive disorder (depression score > 10) was observed in 5.2%, 6.5%, and 6.6%, and probable anxiety disorder (anxiety score > 10) in 13.1%, 9.7%, 1...

Sensors, 2021

Background: The wearable cardioverter–defibrillator (WCD) has a built-in accelerometer, which all... more Background: The wearable cardioverter–defibrillator (WCD) has a built-in accelerometer, which allows tracking of patients’ physical activity by remote monitoring. It is unclear whether WCD-measured physical activity, step count, and heart rate correlate with established tools for the assessment of cardiopulmonary fitness such as the 6-min walk test (6MWT). Objective: To correlate measurements of patient physical activity through the WCD with a supervised 6MWT during in-patient cardiac rehabilitation (CR) and to allow their use as surrogate parameters of cardiopulmonary fitness in an out-patient setting. Methods: Consecutive patients with a history of WCD use treated at our center and an in-patient CR following an index hospitalization were included. Baseline characteristics, measurements of WCD accelerometer (median daily step count, median daily activity level), median daily heart rate, and clinically supervised 6MWT at admission and discharge of CR were obtained. Results: Forty-on...

EP Europace, 2020

Aims The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 pat... more Aims The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 patients undergoing hydroxychloroquine (HCQ) therapy in different clinical settings. Methods and results COVID-19 patients at seven institutions receiving HCQ therapy from whom a baseline and at least one ECG at 48+ h were available were enrolled in the study. QT/QTc prolongation, QT-associated and QT-independent arrhythmic events, arrhythmic mortality, and overall mortality during HCQ therapy were assessed. A total of 649 COVID-19 patients (61.9 ± 18.7 years, 46.1% males) were enrolled. HCQ therapy was administrated as a home therapy regimen in 126 (19.4%) patients, and as an in-hospital-treatment to 495 (76.3%) hospitalized and 28 (4.3%) intensive care unit (ICU) patients. At 36–72 and at 96+ h after the first HCQ dose, 358 and 404 ECGs were obtained, respectively. A significant QT/QTc interval prolongation was observed (P < 0.001), but the magnitude of the increase was modest [+13 (9–...

Journal of Clinical Medicine, 2021

Background: The wearable cardioverter defibrillator (WCD) uses surface electrodes to detect arrhy... more Background: The wearable cardioverter defibrillator (WCD) uses surface electrodes to detect arrhythmia before initiating a treatment sequence. However, it is also prone to inappropriate detection due to artefacts. Objective: The aim of this study is to assess the alarm burden in patients and its impact on clinical outcomes. Methods: Patients from the nationwide Swiss WCD Registry were included. Clinical characteristics and data were obtained from the WCDs. Arrhythmia recordings ≥30 s in length were analysed and categorized as VT/VF, atrial fibrillation (AF), supraventricular tachycardia (SVT) or artefact. Results: A total of 10653 device alarms were documented in 324 of 456 patients (71.1%) over a mean WCD wear-time of 2.0 ± 1.6 months. Episode duration was 30 s or more in 2996 alarms (28.2%). One hundred and eleven (3.7%) were VT/VF episodes. The remaining recordings were inappropriate detections (2736 (91%) due to artefacts; 117 (3.7%) AF; 48 (1.6%) SVT). Two-hundred and seven pat...

EP Europace, 2020

Aims Radiofrequency catheter ablation (RFCA) represents an effective option for idiopathic premat... more Aims Radiofrequency catheter ablation (RFCA) represents an effective option for idiopathic premature ventricular contractions (PVCs) treatment. Ablation Index (AI) is a novel ablation marker incorporating RF power, contact force, and time of delivery into a single weighted formula. Data regarding AI-guided PVCs RFCA are currently lacking. Aim of the study was to compare AI-guided and standard RFCA outcomes in patients with PVCs originating from the right ventricle outflow tract (RVOT). Methods and results Consecutive patients undergoing AI-guided RFCA of RVOT idiopathic PVCs were prospectively enrolled. Radiofrequency catheter ablation was performed following per-protocol target cut-offs of AI, depending on targeted area (RVOT free wall AI cut-off: 590; RVOT septum AI cut-off: 610). A multi-centre cohort of propensity-matched (age, sex, ejection fraction, and PVC site) patients undergoing standard PVCs RFCA was used as a comparator. Sixty AI-guided patients (44.2 ± 18.0 years old, 5...

Swiss Medical Weekly, 2019

INTRODUCTION: The wearable cardioverter-defibrillator (WCD) has established itself in treatment o... more INTRODUCTION: The wearable cardioverter-defibrillator (WCD) has established itself in treatment of potentially lifethreatening ventricular arrhythmias, when implantation of an implantable cardioverter-defibrillator (ICD) is not warranted. Careful patient selection for this therapy is crucial, but unfortunately very little information from randomised controlled trials is available to guide clinical decision-making. Consequently, data from real-world patient registries play a more important role in this context. CONCLUSION: The WCD is safe and effective in terminating malignant ventricular arrhythmias. A substantial subgroup of patients, however, discontinued WCD use prematurely because of comfort issues. This subset of patients deserves further attention in clinical practice to ensure therapy adherence.

BMC Cardiovascular Disorders, 2019

The American Journal of Cardiology, 2019

Genetic testing in survivors of sudden cardiac arrest (SCA) with a suspicious cardiac phenotype i... more 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.

European heart journal, Jan 17, 2018

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by right ventricular myoc... more Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by right ventricular myocardial replacement and life-threatening ventricular arrhythmias. Desmosomal gene mutations are sometimes identified, but clinical and genetic diagnosis remains challenging. Desmosomal skin disorders can be caused by desmosomal gene mutations or autoantibodies. We sought to determine if anti-desmosome antibodies are present in subjects with ARVC. We evaluated ARVC subjects and controls for antibodies to cardiac desmosomal cadherin proteins. Desmoglein-2 (DSG2), desmocollin-2, and N-cadherin proteins on western blots were exposed to sera, in primary and validation cohorts of subjects and controls, as well as the naturally occurring Boxer dog model of ARVC. We identified anti-DSG2 antibodies in 12/12 and 25/25 definite ARVC cohorts and 7/8 borderline subjects. Antibody was absent in 11/12, faint in 1/12, and absent in 20/20 of two control cohorts. Anti-DSG2 antibodies were present in 10/10 ...

European heart journal cardiovascular Imaging, May 26, 2017

Right ventricular outflow tract (RVOT) dilation is one of the echocardiographic criteria in the 2... more Right ventricular outflow tract (RVOT) dilation is one of the echocardiographic criteria in the 2010 revised Task Force Criteria (TFC) of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). However, studies comparing cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) suggest a lower diagnostic accuracy of TTE due to its operator dependence and limited reproducibility. The goal of this study was to compare the 2010 TFC measures of RVOT dilation with three alternative measures for improving the echocardiographic assessment of RVOT in patients with ARVC/D. In this multicentre study, CMR and TTE were performed in 38 patients with a definite, borderline, or possible ARVC/D diagnosis and in 10 healthy controls. Besides the echocardiographic RVOT measurements listed by the 2010 TFC, we assessed three additional end-diastolic RVOT diameters. These included the RVOT diameter defined by the parasternal long axis M-mode of the aortic sinus portion (RVOT3)...

The American journal of medicine, Jan 14, 2015

Patients with congenital left ventricular aneurysms and diverticula may present with arrhythmia. ... more Patients with congenital left ventricular aneurysms and diverticula may present with arrhythmia. The incidence of ventricular arrhythmias and the clinical outcome of these patients have not been reported to date. Among 250 consecutive patients with congenital left ventricular aneurysms and diverticula detected by echocardiography, the clinical outcome of patients who presented with ventricular arrhythmias or associated symptoms was investigated. Of 250 patients with congenital left ventricular aneurysms and diverticula, 30 had ventricular arrhythmias or syncope at initial presentation. During a follow-up of 85 months, spontaneous ventricular tachycardia occurred in 17 of these patients (57%). Ventricular tachycardia was sustained in 13, with a monomorphic pattern in 9 patients. In 82% (11 patients), ventricular tachycardia was inducible during electrophysiologic testing. In 7 patients a sustained monomorphic ventricular tachycardia with a right bundle branch block pattern similar to...

Circulation Journal, 2015

or.jp infiltration of the atria to a different extent than in the ventricles. 7 AF in ARVD is a v... more or.jp infiltration of the atria to a different extent than in the ventricles. 7 AF in ARVD is a very interesting topic, and future basic and clinical research is obviously necessary to better delineate and understand the various aspects of atrial arrhythmias in this challenging disease.

Pacing and Clinical Electrophysiology, 2008

European Heart Journal, 2011

Short QT syndrome (SQTS) is a genetically determined ion-channel disorder, which may cause malign... more Short QT syndrome (SQTS) is a genetically determined ion-channel disorder, which may cause malignant tachyarrhythmias and sudden cardiac death. Thus far, mutations in five different genes encoding potassium and calcium channel subunits have been reported. We present, for the first time, a novel loss-of-function mutation coding for an L-type calcium channel subunit. Methods and results The electrocardiogram of the affected member of a single family revealed a QT interval of 317 ms (QTc 329 ms) with tall, narrow, and symmetrical T-waves. Invasive electrophysiological testing showed short ventricular refractory periods and increased vulnerability to induce ventricular fibrillation. DNA screening of the patient identified no mutation in previously known SQTS genes; however, a new variant at a heterozygous state was identified in the CACNA2D1 gene (nucleotide c.2264G. C; amino acid p.Ser755Thr), coding for the Ca v a 2 d-1 subunit of the Ltype calcium channel. The pathogenic role of the p.Ser755Thr variant of the CACNA2D1 gene was analysed by using co-expression of the two other L-type calcium channel subunits, Ca v 1.2a1 and Ca v b 2b , in HEK-293 cells. Barium currents (I Ba) were recorded in these cells under voltage-clamp conditions using the whole-cell configuration. Co-expression of the p.Ser755Thr Ca v a 2 d-1 subunit strongly reduced the I Ba by more than 70% when compared with the co-expression of the wild-type (WT) variant. Protein expression of the three subunits was verified by performing western blots of total lysates and cell membrane fractions of HEK-293 cells. The p.Ser755Thr variant of the Ca v a 2 d-1 subunit was expressed at a similar level compared with the WT subunit in both fractions. Since the mutant Ca v a 2 d-1 subunit did not modify the expression of the pore-forming subunit of the L-type calcium channel, Ca v 1.2a1, it suggests that single channel biophysical properties of the L-type channel are altered by this variant. Conclusion In the present study, we report the first pathogenic mutation in the CACNA2D1 gene in humans, which causes a new variant of SQTS. It remains to be determined whether mutations in this gene lead to other manifestations of the Jwave syndrome.

European Heart Journal, 2012

Europace, Jun 1, 2016

To assess heart rhythm disturbances (HRD) rate and structure in children with single ventricle (S... more To assess heart rhythm disturbances (HRD) rate and structure in children with single ventricle (SV) at the stages of defect hemodynamic correction. Methods: 70 patients with CHD with SV that were performed total cavopulmonary connection (TCPC) with extracardiac conduit were examined. All the patients were performed ECG and Holter monitoring. To integrate data, all the patients were divided into 8 groups: 1-sinus rhythm; 2-non-sinus rhythm (atrial rate, nodal rhythm, AV-dissociation); 3-bradyarrhythmia (sinus and atrial bradycardia); 4-sinus tachycardia; 5-supraventricular tachycardias (SVT) (paroxysmal and incessant); 6-extrasystole (supraventricular and ventricular); 7-atrioventricular block (AVB) of I-II deg.; 8-AV block, III deg. Results: Only one patient had 2 SVT paroxysms, broken cordarone bolus dosing, in early postoperative period at the first stage. At the second stage (Glenn operation) HRD was recorded in 14 (20%) pts, in 7 (10%) of them during admission. Non-sinus rhythm (86%) predominated in HRD structure. At the third stage (TCPC) recent HRD was recorded in 36 (51.4%) pts. After TCPC recent HRD was registered in 23 (32.9%) pts, in 13 of them HRD was preserved, and in 34 (48.6%) it was not recorded. Arrhythmias, connected with sinus node dysfunction (bradyarrhythmias, SVT, non-sinus rhythm), predominate in HRD structure in 43.9%. The negative correlation between Sat O2 in capillary blood and arrhythmias frequency was disclosed after TCPC, p ¼ 0,02. The older patient at TCPC and lower SV contractile function after it, the oftener arrhythmias, connected with sinus node dysfunction, appeared (p ¼ 0,04). Conclusions: HRD appeared in patients with extracardiac Fontan at any stage of hemodynamic correction. Arrhythmias, connected with sinus node dysfunction, predominated in frequency of occurrence. Low Sat, low SV contractile function and the age of TCPC made their own contributions into HRD appearance after Fontan.

International Journal of Molecular Sciences

Aims: Some gene variants in the sodium channels, as well as calcium channels, have been associate... more Aims: Some gene variants in the sodium channels, as well as calcium channels, have been associated with Brugada syndrome (BrS). However, the investigation of the human cellular phenotype and the use of drugs for BrS in presence of variant in the calcium channel subunit is still lacking. Objectives: The objective of this study was to establish a cellular model of BrS in the presence of a CACNB2 variant of uncertain significance (c.425C > T/p.S142F) using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and test drug effects using this model. Methods and results: This study recruited cells from a patient with Brugada syndrome (BrS) and recurrent ventricular fibrillation carrying a missense variant in CACNB2 as well as from three healthy independent persons. These cells (hiPSC-CMs) generated from skin biopsies of healthy persons and the BrS patient (BrS-hiPSC-CMs) as well as CRISPR/Cas9 corrected cells (isogenic control, site-variant corrected) were used for th...

Aims The treatment with the wearable cardioverter defibrillator (WCD) may protect against sudden ... more Aims The treatment with the wearable cardioverter defibrillator (WCD) may protect against sudden cardiac death (SCD) as a bridging therapy until a cardioverter-defibrillator may be implanted. We analyzed in a multicenter setting a consecutive patient cohort wearing WCD to explore gender differences. Methods and results We analyzed 708 consecutive patients, 579 from whom were males and 129 females (age, 60.5±14 vs. 61.6±17 years old; p=0.44). All patients were divided into age quartiles for analysis. While the rate of ischemic cardiomyopathy (ICM) as a cause of prescription of WCD was significantly higher in males as compared to females (42.7% vs. 26.4%; p=0.001), females received it more frequently due to non-ischemic cardiomyopathy (NICM) (55.8% vs. 42.7%); p=0.009). The wear time of WCD was equivalent in both groups (21.1±4.3 hours/days in males vs. 21.5±4.4 hours/days in females; p=0.27; and 62.6±44.3 days in males vs. 56.5±39 days in females; p=0.15). Mortality was comparable in...

Objective—To assess diVerences in psychosocial adaptation, quality of life, and incidence of aVec... more Objective—To assess diVerences in psychosocial adaptation, quality of life, and incidence of aVective disorders between patients with pacemakers and those with implantable cardioverterdefibrillators (ICDs). Design—Patients aged 40–70 years who underwent a first pectoral implantation of a pacemaker or an ICD system were studied. All subjects were asked to complete the hospital anxiety and depression scale (HAD), the short form general health survey (SF-36), and a specially designed device related questionnaire. Data analysis was performed for three patient groups: pacemaker (n = 76), ICD patients who received therapeutic shocks (n = 45), and ICD patients who did not receive shocks (n = 31). Results—There were no diVerences between the three patient groups in HAD scores or in any of the SF-36 subscales or summary ratings. Probable depressive disorder (depression score > 10) was observed in 5.2%, 6.5%, and 6.6%, and probable anxiety disorder (anxiety score > 10) in 13.1%, 9.7%, 1...

Sensors, 2021

Background: The wearable cardioverter–defibrillator (WCD) has a built-in accelerometer, which all... more Background: The wearable cardioverter–defibrillator (WCD) has a built-in accelerometer, which allows tracking of patients’ physical activity by remote monitoring. It is unclear whether WCD-measured physical activity, step count, and heart rate correlate with established tools for the assessment of cardiopulmonary fitness such as the 6-min walk test (6MWT). Objective: To correlate measurements of patient physical activity through the WCD with a supervised 6MWT during in-patient cardiac rehabilitation (CR) and to allow their use as surrogate parameters of cardiopulmonary fitness in an out-patient setting. Methods: Consecutive patients with a history of WCD use treated at our center and an in-patient CR following an index hospitalization were included. Baseline characteristics, measurements of WCD accelerometer (median daily step count, median daily activity level), median daily heart rate, and clinically supervised 6MWT at admission and discharge of CR were obtained. Results: Forty-on...

EP Europace, 2020

Aims The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 pat... more Aims The aim of the study was to describe ECG modifications and arrhythmic events in COVID-19 patients undergoing hydroxychloroquine (HCQ) therapy in different clinical settings. Methods and results COVID-19 patients at seven institutions receiving HCQ therapy from whom a baseline and at least one ECG at 48+ h were available were enrolled in the study. QT/QTc prolongation, QT-associated and QT-independent arrhythmic events, arrhythmic mortality, and overall mortality during HCQ therapy were assessed. A total of 649 COVID-19 patients (61.9 ± 18.7 years, 46.1% males) were enrolled. HCQ therapy was administrated as a home therapy regimen in 126 (19.4%) patients, and as an in-hospital-treatment to 495 (76.3%) hospitalized and 28 (4.3%) intensive care unit (ICU) patients. At 36–72 and at 96+ h after the first HCQ dose, 358 and 404 ECGs were obtained, respectively. A significant QT/QTc interval prolongation was observed (P < 0.001), but the magnitude of the increase was modest [+13 (9–...

Journal of Clinical Medicine, 2021

Background: The wearable cardioverter defibrillator (WCD) uses surface electrodes to detect arrhy... more Background: The wearable cardioverter defibrillator (WCD) uses surface electrodes to detect arrhythmia before initiating a treatment sequence. However, it is also prone to inappropriate detection due to artefacts. Objective: The aim of this study is to assess the alarm burden in patients and its impact on clinical outcomes. Methods: Patients from the nationwide Swiss WCD Registry were included. Clinical characteristics and data were obtained from the WCDs. Arrhythmia recordings ≥30 s in length were analysed and categorized as VT/VF, atrial fibrillation (AF), supraventricular tachycardia (SVT) or artefact. Results: A total of 10653 device alarms were documented in 324 of 456 patients (71.1%) over a mean WCD wear-time of 2.0 ± 1.6 months. Episode duration was 30 s or more in 2996 alarms (28.2%). One hundred and eleven (3.7%) were VT/VF episodes. The remaining recordings were inappropriate detections (2736 (91%) due to artefacts; 117 (3.7%) AF; 48 (1.6%) SVT). Two-hundred and seven pat...

EP Europace, 2020

Aims Radiofrequency catheter ablation (RFCA) represents an effective option for idiopathic premat... more Aims Radiofrequency catheter ablation (RFCA) represents an effective option for idiopathic premature ventricular contractions (PVCs) treatment. Ablation Index (AI) is a novel ablation marker incorporating RF power, contact force, and time of delivery into a single weighted formula. Data regarding AI-guided PVCs RFCA are currently lacking. Aim of the study was to compare AI-guided and standard RFCA outcomes in patients with PVCs originating from the right ventricle outflow tract (RVOT). Methods and results Consecutive patients undergoing AI-guided RFCA of RVOT idiopathic PVCs were prospectively enrolled. Radiofrequency catheter ablation was performed following per-protocol target cut-offs of AI, depending on targeted area (RVOT free wall AI cut-off: 590; RVOT septum AI cut-off: 610). A multi-centre cohort of propensity-matched (age, sex, ejection fraction, and PVC site) patients undergoing standard PVCs RFCA was used as a comparator. Sixty AI-guided patients (44.2 ± 18.0 years old, 5...

Swiss Medical Weekly, 2019

INTRODUCTION: The wearable cardioverter-defibrillator (WCD) has established itself in treatment o... more INTRODUCTION: The wearable cardioverter-defibrillator (WCD) has established itself in treatment of potentially lifethreatening ventricular arrhythmias, when implantation of an implantable cardioverter-defibrillator (ICD) is not warranted. Careful patient selection for this therapy is crucial, but unfortunately very little information from randomised controlled trials is available to guide clinical decision-making. Consequently, data from real-world patient registries play a more important role in this context. CONCLUSION: The WCD is safe and effective in terminating malignant ventricular arrhythmias. A substantial subgroup of patients, however, discontinued WCD use prematurely because of comfort issues. This subset of patients deserves further attention in clinical practice to ensure therapy adherence.

BMC Cardiovascular Disorders, 2019

The American Journal of Cardiology, 2019

Genetic testing in survivors of sudden cardiac arrest (SCA) with a suspicious cardiac phenotype i... more 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.

European heart journal, Jan 17, 2018

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by right ventricular myoc... more Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by right ventricular myocardial replacement and life-threatening ventricular arrhythmias. Desmosomal gene mutations are sometimes identified, but clinical and genetic diagnosis remains challenging. Desmosomal skin disorders can be caused by desmosomal gene mutations or autoantibodies. We sought to determine if anti-desmosome antibodies are present in subjects with ARVC. We evaluated ARVC subjects and controls for antibodies to cardiac desmosomal cadherin proteins. Desmoglein-2 (DSG2), desmocollin-2, and N-cadherin proteins on western blots were exposed to sera, in primary and validation cohorts of subjects and controls, as well as the naturally occurring Boxer dog model of ARVC. We identified anti-DSG2 antibodies in 12/12 and 25/25 definite ARVC cohorts and 7/8 borderline subjects. Antibody was absent in 11/12, faint in 1/12, and absent in 20/20 of two control cohorts. Anti-DSG2 antibodies were present in 10/10 ...

European heart journal cardiovascular Imaging, May 26, 2017

Right ventricular outflow tract (RVOT) dilation is one of the echocardiographic criteria in the 2... more Right ventricular outflow tract (RVOT) dilation is one of the echocardiographic criteria in the 2010 revised Task Force Criteria (TFC) of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). However, studies comparing cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) suggest a lower diagnostic accuracy of TTE due to its operator dependence and limited reproducibility. The goal of this study was to compare the 2010 TFC measures of RVOT dilation with three alternative measures for improving the echocardiographic assessment of RVOT in patients with ARVC/D. In this multicentre study, CMR and TTE were performed in 38 patients with a definite, borderline, or possible ARVC/D diagnosis and in 10 healthy controls. Besides the echocardiographic RVOT measurements listed by the 2010 TFC, we assessed three additional end-diastolic RVOT diameters. These included the RVOT diameter defined by the parasternal long axis M-mode of the aortic sinus portion (RVOT3)...

The American journal of medicine, Jan 14, 2015

Patients with congenital left ventricular aneurysms and diverticula may present with arrhythmia. ... more Patients with congenital left ventricular aneurysms and diverticula may present with arrhythmia. The incidence of ventricular arrhythmias and the clinical outcome of these patients have not been reported to date. Among 250 consecutive patients with congenital left ventricular aneurysms and diverticula detected by echocardiography, the clinical outcome of patients who presented with ventricular arrhythmias or associated symptoms was investigated. Of 250 patients with congenital left ventricular aneurysms and diverticula, 30 had ventricular arrhythmias or syncope at initial presentation. During a follow-up of 85 months, spontaneous ventricular tachycardia occurred in 17 of these patients (57%). Ventricular tachycardia was sustained in 13, with a monomorphic pattern in 9 patients. In 82% (11 patients), ventricular tachycardia was inducible during electrophysiologic testing. In 7 patients a sustained monomorphic ventricular tachycardia with a right bundle branch block pattern similar to...

Circulation Journal, 2015

or.jp infiltration of the atria to a different extent than in the ventricles. 7 AF in ARVD is a v... more or.jp infiltration of the atria to a different extent than in the ventricles. 7 AF in ARVD is a very interesting topic, and future basic and clinical research is obviously necessary to better delineate and understand the various aspects of atrial arrhythmias in this challenging disease.

Pacing and Clinical Electrophysiology, 2008

European Heart Journal, 2011

Short QT syndrome (SQTS) is a genetically determined ion-channel disorder, which may cause malign... more Short QT syndrome (SQTS) is a genetically determined ion-channel disorder, which may cause malignant tachyarrhythmias and sudden cardiac death. Thus far, mutations in five different genes encoding potassium and calcium channel subunits have been reported. We present, for the first time, a novel loss-of-function mutation coding for an L-type calcium channel subunit. Methods and results The electrocardiogram of the affected member of a single family revealed a QT interval of 317 ms (QTc 329 ms) with tall, narrow, and symmetrical T-waves. Invasive electrophysiological testing showed short ventricular refractory periods and increased vulnerability to induce ventricular fibrillation. DNA screening of the patient identified no mutation in previously known SQTS genes; however, a new variant at a heterozygous state was identified in the CACNA2D1 gene (nucleotide c.2264G. C; amino acid p.Ser755Thr), coding for the Ca v a 2 d-1 subunit of the Ltype calcium channel. The pathogenic role of the p.Ser755Thr variant of the CACNA2D1 gene was analysed by using co-expression of the two other L-type calcium channel subunits, Ca v 1.2a1 and Ca v b 2b , in HEK-293 cells. Barium currents (I Ba) were recorded in these cells under voltage-clamp conditions using the whole-cell configuration. Co-expression of the p.Ser755Thr Ca v a 2 d-1 subunit strongly reduced the I Ba by more than 70% when compared with the co-expression of the wild-type (WT) variant. Protein expression of the three subunits was verified by performing western blots of total lysates and cell membrane fractions of HEK-293 cells. The p.Ser755Thr variant of the Ca v a 2 d-1 subunit was expressed at a similar level compared with the WT subunit in both fractions. Since the mutant Ca v a 2 d-1 subunit did not modify the expression of the pore-forming subunit of the L-type calcium channel, Ca v 1.2a1, it suggests that single channel biophysical properties of the L-type channel are altered by this variant. Conclusion In the present study, we report the first pathogenic mutation in the CACNA2D1 gene in humans, which causes a new variant of SQTS. It remains to be determined whether mutations in this gene lead to other manifestations of the Jwave syndrome.

European Heart Journal, 2012