bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac hereditary diseases: genetic insights from a single center 15-year experience
Authors: Porretta A P , Pavlidou D , Atallah Gonzalez M I , Unger S , Monney P , Pruvot E , Superti-Furga A 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
In the last decades, the implementation of high-throughput next-generation (NGS) technologies has profoundly changed the landscape of human genome sequencing. However, the molecular diagnosis in cardiac hereditary diseases is still hampered by the incomplete penetrance, variable expressivity, and genetic heterogeneity of the diseases.

Objective
We report our 15-year experience on a cohort of consecutive patients (pts) with suspicion of cardiac hereditary disease referred to the specialized cardiogenetic outpatient clinic of our center.

Methods
We retrospectively reviewed DNA sequencing results of pts referred to our center from July 1st 2007 through December 31st 2021, who were tested with NGS technologies for suspected cardiac hereditary diseases including channelopathies, inherited cardiomyopathies and unexplained sudden cardiac death.

Results
Among the 488 tested pts, the most frequent clinical indication were presymptomatic screening (37.3%) for a known familial variant, followed by suspected arrhythmic syndrome (28.3%) and hereditary cardiomyopathy (26.8%). A likely pathogenic/pathogenic variant was found in 198 pts for an overall diagnostic yield of 40.6% and of 23.6% considering only index cases. The rate of identified mutation-carriers was higher among pts with cardiomyopathy (45.8%) than among pts with inherited arrhythmic syndromes (37%). Panel A and B display variant distribution in arrhythmic syndromes and cardiomyopathies respectively. In particular, the highest diagnostic yield was observed among pts with suspected hypertrophic cardiomyopathy (60.7%) and catecholaminergic polymorphic ventricular tachycardia (50%), followed by congenital long QT syndrome (48.6%). The pathogenic variants were mainly identified in genes with definitive scientific evidence of causal association with the disease.

Conclusions
The 15-year experience of our specialized cardiogenetic outpatient clinic has demonstrated the pivotal role of genetic analysis for the diagnostic confirmation and, hence for the therapeutic management of pts with suspected cardiac hereditary disease.
Familial cardiolaminopathy due to a previously undescribed LMNA gene mutation
Authors: Ibarra R , Laso Bayas J L , Zambrano A K 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Cardiolaminopathies are rare genetic alterations, which present diverse mechanical and electrical alterations.

OBJECTIVE
To present a family carrying an LMNA gene mutation that although not described manifest clinical and electrocardiographic characteristics of the disease.

Methods
We present the case of two sisters and one brother, aged 65, 57 and 51 years, respectively. At the beginning of their fourth decade, all of them debuted with atrial flutter associated with second and third degree atrioventricular block. Two of them (one or the sisters and the brother) underwent ablation of isthmus-dependent atrial flutter. However, in both, the flutter recurred and no new interventional treatment was further offered. The male subject received a pacemaker implant for treatment of AV block; some years later, he presented a cerebrovascular event and subsequently a recurrence, both while in oral anticoagulation and, actually remains with moderate motor deficit and dysarthria. The youngest woman suffered an embolic cerebrovascular event when she was 50 y/o; she remained asymptomatic in relation to the rhythm disorder and refused a pacemaker. The oldest sister who is asymptomatic, received a pacemaker when she was 45 y/o and now is anticoagulated. By echocardiography, all siblings presented left ejection fraction in between 40 and 50% with decreased strain values and normal left ventricular geometry.

Results
Recently in our country it is possible to carry out a genetic test, for which the three were subjected to it. In this family, the genetic testing was done using a comercial kit for 172 genes. The result was a Frameshift Indels (non misense) mutation NM_170707.3 c.1526del p.(Pro509LeufsTer39) Exon:9/12, in all three. The caveat is that this LMNA gene mutation has not been previously described. In light of these results, the youngest woman with total AV block and sequelae of cerebrovascular disease and mild left ventricular dysfunction, received an implantable cardiac defibrillator (ICD) implant for primary prevention of sudden death and her siblings are undergoing an upgrade to ICD.

Conclusion
The mutation found in this family is unique and for the first time reported in the LMNA gene in the world. Genetic diagnosis is limited in our country, which makes it difficult to determine this type of pathology. However, given the clinical presentation of an electrical disorder in all the siblings of a family, in this particular case, it was mandatory to perform this test. These results allow us to better understand the prognosis and intervene appropriately to prevent sudden death, even though there is no treatment to avoid the progression of the disease.
Positive Ajmaline provocation test for Brugada syndrome: acute and long-term outcomes
Authors: Sabbag A , Tomer O , Ozkartal T , Ollitrault P , Laredo M , Tovia-Brodie O , Amoroso G , Gandjbakhch E , Conte G , Milman A 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Diagnosis of Brugada Syndrome (BrS) is established either by a observing a spontaneous Type 1 Brugada pattern on ECG or by unmasking Type 1 pattern with a drug challenge using a sodium channel blocker in suspected individuals. There are no clear indications on when to apply the Ajmaline provocation test and how to manage positive case. Data regarding the long-term outcome of this population is limited. The present study was designed to evaluate the incidence and identify predictors of arrhythmic events among subjects with Ajmaline induced Brugada ECG.

Objectives
To evaluate the long-term outcomes of subjects diagnosed with drug induced Brugada ECG.

Methods
A multicenter international consecutive cohort including all cases of positive Ajmaline provocation test from 5 large electrophysiology centers form Israel, France, and Switzerland

Results
A total of 130 patients were recruited, the majority were males (70.8%) and Caucasian (97.7%). In our cohort the most frequent indication for performing an ajmaline test was a family history of BrS or sudden cardiac death (43.1%), then a suspicious ECG (38.5%), syncope (16.1%) and 3 with ventricular fibrillation (VF) (2.3%). The common infusion protocols used were 1mg/kg over 5 minutes (56%) and 1mg/kg over 10 minutes (26%). In all centers ajmaline infusion was stopped when type 1 Brugada pattern was observed. No adverse events occurred during the studies. All patients received instructions regarding the avoidance of arrhythmic triggers (specific drugs, alcohol and reduction of fever). During a median follow up time of 36 (7.5-66.9) months, 9 syncope occurred, 15 ICD (3 for secondary prevention because of VF as initial presentation) and 29 ILRs were implanted. No VF or deaths occurred in any of the study groups.

Conclusion
In the present study of consecutive patients with a positive Ajmaline provocation test, there were no adverse outcomes during a median follow up of 3 years, irrespective of the indication for the test. Our results, indicating a low risk, are in agreement with the current ESC guidelines limiting the diagnosis of Brugada syndrome. Further research is warranted to test whether these patients maybe be managed safely solely by education to avoid arrhythmic triggers.
Electroanatomical voltage mapping with a force-sensing technology catheter for diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Authors: Rossi V A , Lunk D , Mohsen M , Akdis D , Costa S , Gasperetti A , Duru F , Brunckhorst C B , Saguner A M 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Invasive three-dimensional electroanatomical mapping (EAM) can be helpful to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC). Contact force sensing catheters (CFSC) represent the gold standard to verify adequate tissue contact during EAM. However, normal reference values for right ventricular (RV) EAM as well as substrate characterization in patients with ARVC using CFSC have not been systematically investigated, which was the aim of this prospective study.

Methods
EAM of the RV during sinus rhythm was performed with the Thermocool SmartTouch catheter via a long sheath in the CARTO3 system in 11 patients with definite ARVC and 5 age- and gender-matched control subjects without structural heart disease. Only points with a mean contact force of ≥4G were analyzed. To account for differences due to RV anatomy, it was divided into 5 segments: RV outflow tract (RVOT), septum, free wall, sub-tricuspid region and apex. Endocardial bipolar and unipolar voltages, signal characteristics and signal duration were analyzed. The impact of catheter orientation on endocardial signals was also assessed.

Results
A median of 227 (IQR:120-364) endocardial RV points were analyzed. Median bipolar voltage in healthy controls was 3.8mV (range 3.6-4.6, IQR 2.7-5.4), with lower values in the RVOT and higher values in the RV septum. ARVC patients showed significantly lower bipolar voltages as compared to controls (repeated measures ANOVA; between-subjects effect: F=6.443,p=0.024), showing significantly lower bipolar voltage values in the sub-tricuspid region (1.8±1.9vs.4.6±2.9mV,p=0.031) and in the RV apex (2.9±1.4vs.7.2±5.2mV,p=0.024), Figure 1c. Bipolar voltage values in all RV regions yielded a high sensitivity and specificity for ARVC diagnosis (AUC62-78%,p&lt;0.001 for all), with the highest performance for the sub-tricuspid region (AUC78%,95%CI0.75-0.81,p&lt;0.001). A bipolar voltage value &lt;1.5mV in the sub-tricuspid region yielded a sensitivity of 98% and a specificity of 53% for ARVC diagnosis (Figure 1a-b, showing the typical RV free wall "C-scar" in ARVC and normal values for the RV apex in less advanced disease stages). A positive correlation between bipolar voltage values and an orthogonal catheter orientation (46°-90°: r=0.106,p&lt;0.001) as well as a higher catheter contact force (r=0.054,p=0.008), and a negative correlation between bipolar voltage values and QRS duration (r=-0.370,p&lt;0.001) was found.

Conclusions
For the first time a systematic analysis of RV endocardial low voltage areas in ARVC patients as compared to controls by using CFSC was performed, and confirmed that RV voltages are generally lower in ARVC as compared to controls, with the sub-tricuspid area showing the lowest values and highest discriminatory power vs controls.
Diagnostic gain of cardiac MR in patients with premature ventricular complexes and structurally normal hearts on echocardiography
Authors: Ahmed T , Aagaard-Nilsen S , Anfinsen O G , Hegbom F , Holm T , Bosse G , Edvardsen T , Kongsgaard E , Dejgaard L A , Korseberg Stokke M 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): KG Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway

Background
An important part of the diagnostic evaluation of patients with premature ventricular complexes (PVCs) is to identify underlying cardiac disease. The majority of these patients referred to catheter ablation have PVCs with inferior axis and left bundle branch block morphology (I-LBBB). Although this is the most common morphology in patients with idiopathic PVCs, cardiac magnetic resonance (CMR) is recommended to exclude potential other underlying pathology. However, the diagnostic gain of CMR in patients with I-LBBB PVCs is uncertain.

Purpose
The purpose of this study was to explore the prevalence of cardiac abnormalities identified by CMR in patients with I-LBBB PVCs evaluated for catheter ablation without signs of underlying cardiac disease from resting ECG, stress test, or echocardiography.

Methods
We retrospectively collected data from consecutive patients with I-LBBB PVCs evaluated for catheter ablation at our tertiary referral centre from 2011 to 2022. We included patients with normal ECG and stress test, and no evidence of functional or structural heart disease by echocardiography. We categorized CMR examinations as normal or as having signs of functional or structural abnormalities.

Results
We identified a total of 63 patients with I-LBBB PVCs evaluated for catheter ablation, with no signs of underlying conditions from sinus rhythm ECG, stress test or echocardiography. All were studied by CMR at our institution. The median age was 49 years (IQR 36-61), and 39 were females (62 %). The maximum PVC burden recorded in each patient prior to referral was 20 % (IQR 11-29.5). Left ventricular (LV) ejection fraction by echocardiography was 56±4 %. CMR was normal in 52 patients (83 %), while functional or structural abnormalities were detected in 11 patients (17 %). These abnormalities comprised reduced LV systolic function (2 patients), dilated right ventricle (2 patients), dilated LV (1 patient), ventricular septal defect (2 patients), non-compaction cardiomyopathy (1 patient), mitral annular disjunction (2 patients), tricuspidal annular disjunction (1 patient), and myocardial fibrosis by late contrast enhancement (3 patients).

Conclusions
In patients with I-LBBB PVCs evaluated for catheter ablation, and with no signs of underlying pathology from standard diagnostic work-up, CMR detected abnormalities in 17 %. These results support the routine use of CMR in the evaluation of patients with I-LBBB PVCs referred for catheter ablation.
Predictive value of left and right atrial strain for the detection of atrial fibrillation in patients with cryptogenic stroke and implant of loop recorder
Authors: Arabia G , Cersosimo A , Cerini M , Salghetti F , Falco R , Calvi E , Dell'aquila A , Bontempi L , Mitacchione G , Magdi M , Curnis A 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Structural and functional remodeling of left and right atrium (LA-RA) are predictors of the risk of hospitalization and mortality. These are chronic and complex processes, dependent on an adaptive response implemented by the atrial myocytes against stressors of an electrical, mechanical and metabolic nature. Atrial fibrillation (AF) is the most common condition associated with remodeling of both atria, of which it can be cause and effect at the same time: atrial enlargement, interstitial fibrosis and myocardial distension. Often the first manifestation of AF is cryptogenic stroke (CS) which is associated with a high rate of recurrence and adverse long-term follow-up outcomes, mainly due to its unknown etiology often leading to secondary prevention ineffective. Asymptomatic (AF) may play an important pathophysiological role to detect CS. Evidence has demonstrated the efficacy of AF ablation in restoring the structure of the LA and, consequently, in favoring the maintenance of sinus rhythm. However, little is known regarding the evaluation of RA remodeling and its variation over time in patients with FA.

Aim of the study
Evaluate the relationship between echocardiographic parameters of LA and RA function, and the occurrence of AF revealed by continuous ECG monitoring through insertable cardiac monitors (ICM) implant in a cohort of patients with CS

Methods
Single-center retrospective study. A total of 204 patients who suffered from cryptogenic stroke underwent ICM between May 2013 and July 2022. All detected AF episodes lasting more than 30 seconds were considered, according to Guidelines. All patients underwent to Transthoracic Echocardiography (TTE) to study on LA and RA function, including both standard and longitudinal strain-derived parameters. Transesophageal Echocardiography (TEE) was also performed to exclude embolic sources.

Results
During a median follow-up period of 15.3 months (interquartile range, 7.4 / 23.5), continuous ECG monitoring revealed AF in 96 patients (47.0%). Many echocardiographic parameters, such as LA maximum and minimal volume were significantly associated with the occurrence of AF, suggesting the worst atrial function in the AF group. Furthermore, multivariable regression analysis revealed that peak atrial contraction strain of both atria were independently associated with AF (p &lt; 0.001,respectively).

Conclusion
In patients with cryptogenic CS, LA and RA strain analysis are strong and independent predictors of the occurrence of AF despite clinical and morpho-functional echocardiographic parameters.
Clinical evaluation of the new 12-lead ECG noninvasive epi-endocardial mapping technology
Authors: Chmelevsky M , Zubarev S , Khamzin S , Dokuchaev A , Bazhutina A , Sinitca A , Budanova M , Auricchio A 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: Private company. Main funding source(s): XSpline S.p.a.

Aim
Noninvasive electrocardiographic mapping systems may require multichannel (150-250) ECG body surface recordings which is a huge limitation for the adoption into clinical practice. However, most of the currently available noninvasive mapping systems accurately represent epicardial activation. Over the last few years, various technical solutions have been implemented to increase the accuracy of ECG forward-inverse calculations including machine learning algorithms. We developed a novel 12-lead ECG-based, fully automated system for noninvasive full transmural (epi-endocardial) mapping. The aim of this study was to evaluate accuracy of this system in heart failure patients with typical LBBB.

Methods
Eight consecutive patients (median age: 65; 25-75% range 59-64; 5 male) with typical LBBB QRS morphology (QRS duration 146–224 ms), scheduled for CRT implantation underwent a cardiac CT scan and 12-lead ECG recording, followed by detailed bi-ventricular endocardial electroanatomical contact mapping (EAM). A median of 258 (181-576) local electrograms in LV and 86 (70-139) in RV were collected during EAM. Cardiac CT data were semiautomatically processed using a Unet-like neural network to obtain meshes containing the heart (each chamber with both endocardial and epicardial contour as well as coronary sinus and its branches), lungs and torso using different segmentation module. Noninvasive epi-endocardial activation maps were calculated using state-of-the-art mathematical models including machine learning methods. These data were compared with EAM from the invasive mapping system using Spearman correlation (r), mean absolute error (MAE) and relative distance metrics.

Results
All early and latest activation patterns were correctly identified (see figure). The average correlation (r) of endocardial activation maps was 0.92 for all cases (min-max: 0.82-0.96). MAE was rather small (9-15 mm) when the non-invasive late activation zone nearly matches the CARTO data (average distance error 14 mm). Overall, the QRS complex was correctly reproduced by our method in all cases (r = 0.96).

Conclusions
This study shows that new mapping technique can accurately reconstruct endocardial electrical activation maps based on 12-lead ECG and cardiac CT scan. The approach may be very useful in pre-procedural planning of device implantation and catheter ablation. Larger validation studies are however needed for confirming method accuracy at epicardial site.
Atrial stimulation protocols to test inducibility of atrial fibrillation
Authors: Fischer P , Wintrich J , Pavlicek V , Boehm M , Mahfoud F , Ukena C 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
The electrophysiological inducibility of atrial fibrillation (AF) after pulmonary vein isolation (PVI) has been identified as a predictor of future AF recurrence. Stimulation protocols have not been sufficiently studied prospectively with respect to their reliability for inducing AF.

Methods and results
We conducted a prospective monocentric randomized clinical trial to evaluate different standardized electrical stimulation protocols on their potential to induce AF. Patients with symptomatic AF presenting in sinus rhythm scheduled for PVI were enrolled. The primary outcome was induction of AF. A total of 30 patients (age=62±2 years, 17% female, 13% persistent AF, left atrial systolic volume (LASV) 93±5 ml) were enrolled and randomized. To one of three different stimulation protocols performed at the beginning of PVI. Atrial fibrillation was induced in 4 out of 10 patients (40%) with fixed cycle length stimulation followed by up to 3 extrastimuli (protocol A), 6 out of 10 patients (60%) with burst stimulation (protocol B) and 9 out of 10 patients (90%) with fixed stimulation using the shortest cycle length with 1:1 atrial capture (protocol C), respectively. Time from start of stimulation to inducibility of AF was significantly lower in protocol C vs. protocol B and A (29±10 sec vs 40±14 sec vs 366±71 sec; p&lt;0.0001). Isoprenaline was used in 10% in protocol A, 40% in protocol B and 80% protocol C. Overall, there were no significant differences concerning age (61±3 vs. 63±4 years; p=0.74), LASV (93±6 vs. 94±8 ml; p=0.98) or other parameters between patients with inducible and non-inducible AF.

Conclusion
With systematic stimulation protocols AF can be induced in up to 90%. Further studies are warranted to assess the specifity of these stimulations.